Urethral carcinoma after skin substitution urethral reconstruction.

Urethral cancer after urethral reconstruction is an under-recognized, uncommon disease associated with significant morbidity and mortality. The survival rates of patients with carcinoma of the bulbar urethra are as low as 20%-30%. Stricture recurrence and unrecognized malignant changes present prior to reconstruction are major risk factors for urethral cancer. Skin substitution urethroplasty is subjected to higher rates of recurrence, which lends to the potential for carcinogenesis. We present a case of a 59-year-old male who underwent multi-stage skin substitution urethroplasty who developed urethral carcinoma 20 years later.

Development and validation of a PD-L1/PD-1/CD8 axis-based classifier to predict cancer survival of upper tract urothelial carcinoma after radical nephroureterectomy.

The expression status of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1) and the infiltration of CD8+ T cells in tumor tissues are considered to be related to immunotherapy efficacy and patient prognosis. The purpose of this study is to clarify the prognostic value of the PD-L1/PD-1/CD8 axis, and to develop and validate a comprehensive scoring system based on multiple immune variables to predict cancer survival of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). The immunohistochemical method was used to detect the expression of PD-L1, PD-1, and CD8 in cancer tissues of UTUC patients after RNU. Then, an immunoscore was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression model in the training cohort (n = 120), and it was verified in the validation cohort (n = 54). We found that infiltration of PD-L1+ immune cells (ICs), stromal PD-1+ tumor-infiltrating lymphocytes (TILs), and intratumoral CD8+ TILs was associated with poor overall survival (OS). The immunoscore based on the three immune variables further divided the patients into low- and high-risk groups, and there was a significant difference in the survival rate. A nomogram was constructed by combining tumor-node-metastasis (TNM) stage and immunoscore, and the area under the curve of the receiver-operating characteristic (ROC) (0.78) for predicting 5-year mortality was better than that of the TNM stage (0.70) and immunoscore (0.76). Our results show that the PD-L1/PD-1/CD8 axis-based classifier have potential clinical application to predict cancer survival of UTUC patients after RNU.

Comportamiento de las infecciones del sistema genitourinario en el Hospital Universitario "Comandante Faustino Pérez Hernández". Matanzas. 2014-2019 / Behavior of the genitourinary system infections in the University Hospital "Comandante Faustino Perez Hernandez". 2014-2019

RESUMEN Introducción: durante mucho tiempo los términos infección y sepsis han sido utilizados en forma alternativa, la tendencia actual es referirse al término infección como proceso bacteriano dependiente del germen. Objetivo: caracterizar el comportamiento de las infecciones urológicas en el servicio de urología del Hospital Universitario Comandante "Faustino Pérez Hernández", Matanzas. Materiales y métodos: se realizó un estudio observacional, descriptivo y transversal, a los pacientes atendidos en el servicio de urología del hospital Faustino Pérez, mediante el método de pesquisaje activo en el periodo comprendido desde enero de 2014 hasta diciembre de 2019. Resultados: se comprobó que la mayor parte de la población sometida a estudio es adulta mayor, predominando el sexo masculino. Entre las patologías crónicas asociadas a infecciones se encuentran la diabetes mellitus, la insuficiencia renal crónica, las inmunodeficiencias. El uso de catéteres se presentó en más de un 64% de los pacientes con infecciones. La echerichia coli fue el germen de mayor incidencia seguido de la klepsiella, pseudomonas. Conclusiones: la hiperplasia benigna de próstata, las litiasis, estenosis uretrales y los tumores uroteliales y prostático, son las principales causas obstructivas asociadas a infecciones. Un grupo importante de los pacientes operados presentaron infección del sitio quirúrgico. La sensibilidad bacteriana ante los antibióticos mostró mayor sensibilidad a meropenem, aztreonam y amikacina (AU).

Summary Introduction: the terms infection and sepsis have being alternatively used during many years; the current tendency is referring to the term infection as a germ- dependent bacterial process. Objective: to characterize the behavior of urologic infections in urological service of the University Hospital "Comandante Faustino Perez Hernandez". Materials and methods: an observational, descriptive, cross-sectional research has been made to the patients who have attended the urology service of the University Hospital "Comandante Faustino Perez Hernandez", using the method of active screening in the period from January 2014 until December 2019. Results: it was proved that the biggest part of the studied population is elder adult people, predominating the male sex. Diabetes mellitus, chronic renal failure, immunodeficiency were found among the chronic diseases associated to infections. The use of catheters was present in more than 64% of patients. Echerichia coli was the germ with highest incidence, followed by Klepsiella, andPseudomonas. Conclusions: benign prostatic hyperplasia, lithiasis, urethral stenosis, prostatic and urothelial tumors are the main obstructive causes associated to infections. An important group of patients who underwent surgery presented infections at the surgical site. Bacteria showed higher sensitivity to antibiotics like meropenem, aztreonam and amikacin (AU).

Villous Adenoma Arising in the Urethra of a Female with Bladder Augmentation History: A Case Report and Review of the Literature.

Villous adenomas (VAs) in the female urethra are rare with only seven cases in the English literature to our knowledge. In patients with bladder augmentation cystoplasty, the neoplasia development risk increases and most of these develop in the neobladder or anastomosis line. Only two cases of VA developing from the native bladder mucosa have been reported. Physical examination of a 76-year-old female who had a history of augmentation cystoplasty revealed a caruncula-like structure protruding from the urethral meatus. The urinary USG showed that the lesion had no relation with the bladder. The lesion was excised. Microscopically, it consisted of villous structures covered with pseudostratified intestinal type epithelium. Low-grade dysplasia was present in the epithelium but high-grade dysplasia or in-situ/invasive carcinoma was not observed. Immunohistochemical study showed positivity for CK7, CK20, EMA, CEA and CDX2. The case was reported as VA of the urethra. We presented the first VA case arising in the urethra of a female patient with intestinal bladder augmentation. Excision is curative for pure VAs. Transformation to carcinoma or recurrence has not been reported. However, in one third of the cases, a malignant tumor may accompany the lesion. Therefore, all excision material should be examined carefully. Routine endoscopic follow-up should be performed in cases with bladder augmentation.

[Urethral sarcoma 14 years after brachytherapy of the prostate gland]. / Urethrasarkom 14 Jahre nach Prostata-Brachytherapie.

We report a case of an 83-year-old male patient with the rare diagnosis of a urethral sarcoma.

Oncogenic Addiction to ERBB2 Signaling Predicts Response to Trastuzumab in Urothelial Cancer.

Urothelial carcinoma (UC) is a common and frequently lethal cancer. Despite the presence of genomic alterations creating dependency on particular signaling pathways, the use of targeted therapies in advanced and metastatic UC has been limited. We performed an integrated analysis of whole-exome and RNA sequencing of primary and metastatic tumors in a patient with platinum-resistant UC. We found a strikingly high ERBB2 mRNA expression and enrichment of downstream oncogenic ERBB2 signaling in this patient's tumors compared with tumors from an unselected group of patients with UC (N=17). This patient had an exceptional sustained response to trastuzumab. Our findings show that oncogenic addiction to ERBB2 signaling potentially predicts response to ERBB2-directed therapy of UC.

Primary Small Cell Neuroendocrine Tumor Within a Urethral Diverticulum.

BACKGROUND: Primary small cell neuroendocrine carcinoma of the urinary tract is a very rare cancer, accounting for fewer than 0.5% of urinary tract tumors. These are aggressive neoplasms with high rates of metastases. Urethral diverticula can be found in up to 6% of women. CASE: A 31-year-old woman presented with a clear vaginal discharge and an anterior vaginal wall mass that was thought to be a recurrent cyst. After surgical dissection, she was noted to have a urethral diverticulum with a solid nodule at the base. Final pathology showed a high-grade small cell neuroendocrine carcinoma. CONCLUSION: Malignancy in a urethral diverticulum can occur in young patients. Clinicians should be aware of this possibility when choosing to manage urethral lesions expectantly.

Primary urethral squamous cell carcinoma: a unique manifestation of a penile tumor.

This case report describes a unique manifestation of a primary urethral squamous cell carcinoma (SCC) as the underlying pathology in an 80-year-old male patient who underwent partial penectomy due to an enlarging penile mass. Persistent pain in the right knee was discovered to be a pathologic fracture using magnetic resonance imaging. Computed tomography-guided biopsy confirmed metastatic SCC. Whole-body positron emission tomography revealed systemic dissemination to multiple sites. Orthopedic knee replacement was performed in combination with local radiotherapy. Palliative chemotherapy was rejected due to poor performance status. Primary urethral SCC is rare and an uncommon cause of advanced penile cancer. These findings could be of great interest to clinicians for two reasons. First, a tumor's appearance can be misleading. Consequently, histological work-up in accordance with clinical guidelines is necessary for accurate diagnosis. Second, a more comprehensive investigation is required when clinical symptoms persist despite the use of conventional treatment. Our case is an instance in which persistent pain masked the presence of downstream metastasis. We believe that these aforementioned points are of significant clinical importance and present a salient learning opportunity.

Nuclear Factor-κB Promotes Urothelial Tumorigenesis and Cancer Progression via Cooperation with Androgen Receptor Signaling.

We investigated the role of NF-κB in the development and progression of urothelial cancer as well as cross-talk between NF-κB and androgen receptor (AR) signals in urothelial cells. Immunohistochemistry in surgical specimens showed that the expression levels of NF-κB/p65 (P = 0.015)/phospho-NF-κB/p65 (P < 0.001) were significantly elevated in bladder tumors, compared with those in nonneoplastic urothelial tissues. The rates of phospho-NF-κB/p65 positivity were also significantly higher in high-grade (P = 0.015)/muscle-invasive (P = 0.033) tumors than in lower grade/non-muscle-invasive tumors. Additionally, patients with phospho-NF-κB/p65-positive muscle-invasive bladder cancer had significantly higher risks of disease progression (P < 0.001) and cancer-specific mortality (P = 0.002). In immortalized human normal urothelial SVHUC cells stably expressing AR, NF-κB activators and inhibitors accelerated and prevented, respectively, their neoplastic transformation induced by a chemical carcinogen 3-methylcholanthrene. Bladder tumors were identified in 56% (mock), 89% (betulinic acid), and 22% (parthenolide) of N-butyl-N-(4-hydroxybutyl)nitrosamine-treated male C57BL/6 mice at 22 weeks of age. NF-κB activators and inhibitors also significantly induced and reduced, respectively, cell proliferation/migration/invasion of AR-positive bladder cancer lines, but not AR-knockdown or AR-negative lines, and their growth in xenograft-bearing mice. In both nonneoplastic and neoplastic urothelial cells, NF-κB activators/inhibitors upregulated/downregulated, respectively, AR expression, whereas AR overexpression was associated with increases in the expression levels of NF-κB/p65 and phospho-NF-κB/p65. Thus, NF-κB appeared to be activated in bladder cancer, which was associated with tumor progression. NF-κB activators/inhibitors were also found to modulate tumorigenesis and tumor outgrowth in AR-activated urothelial cells. Accordingly, NF-κB inhibition, together with AR inactivation, has the potential of being an effective chemopreventive and/or therapeutic approach for urothelial carcinoma. Mol Cancer Ther; 17(6); 1303-14. ©2018 AACR.

Association between selected dietary scores and the risk of urothelial cell carcinoma: A prospective cohort study.

Studies investigating the association of food and nutrient consumption with the risk of urothelial cell carcinoma (UCC) have produced mixed results. We used three common dietary scores, the Mediterranean Diet Score (MDS), the Alternate Healthy Eating Index 2010 (AHEI-2010) and the Dietary Inflammatory Index (DII) to assess the evidence of an association between diet and the risk of UCC. Over a median follow-up time of 21.3 years, 379 incident UCC cases were diagnosed. Dietary scores were calculated using data from a 121-item food frequency questionnaire administered at baseline. We used Cox models to compute hazard ratios (HR) for the association between dietary scores (per one standard deviation) and UCC risk. In order to reflect overall adherence to a healthy diet, a metascore was constructed by summing the quintiles of each of the three scores. None of the dietary scores was associated with the risk of UCC overall. A healthier diet was found to be inversely associated with the risk of invasive (MDS: HR = 0.86, 95% CI: 0.74-1.00, metascore: HR = 0.84, 95% CI: 0.71-0.98), but not superficial disease (heterogeneity between subtypes p = 0.04 and p = 0.03, respectively). Results were consistent but weaker for the DII and the AHEI-2010. We found some evidence of effect modification by smoking, in particular for the metascore (Current: HR = 0.77, 95% CI: 0.58-1.01, Former: HR = 0.77, 95% CI: 0.64-0.92, Never: HR = 1.01, 95% CI: 0.81-1.26, p for heterogeneity = 0.05). A healthy diet may be protective against the risk of invasive, but not superficial, UCC. Promoting healthy dietary habits may help lower the risk of invasive UCC, especially for current and former smokers.

Is there an association between polypropylene midurethral slings and malignancy?

OBJECTIVE: To examine any association between polypropylene mesh used in midurethral slings and malignancy in humans. Macroporous, monofilament polypropylene midurethral slings have been established as a safe and effective treatment for stress urinary incontinence. However, despite long-term studies supporting the efficacy and safety of midurethral slings, there have been concerns regarding the general risks of using mesh in transvaginal surgery. In addition, concerns have recently been raised about synthetic midurethral slings and a possible link with malignancy. Therefore, the goal of this work was to further assess any association between polypropylene mesh slings and malignancy. MATERIALS AND METHODS: All sling procedures performed at our institution from 2004 to 2013 were retrospectively reviewed. From within this group, the International Classification of Disease codes for urethral cancer, vaginal cancer, and bladder cancer were reviewed. RESULTS: From 2004-2013, 2545 procedures were performed. Of these, 2361 (96.3%) underwent polypropylene midurethral sling placement. Average follow-up after sling placement was 42.0 ± 38.6 months, with follow-up extending up to 122.3 months. The rate of bladder cancer after the sling procedure was 1 of 2361 (0.0%), with the same rate of vaginal cancer. No sarcomas were noted. CONCLUSION: Overall, the rate of malignancy after polypropylene mesh midurethral sling placement in our series was 0.0% (2 of 2361). With a mean follow-up of almost 4 years and follow-up extending up to a maximum of 122.3 months, our series does not support any association between the polypropylene mesh used for midurethral slings and the development of malignancy in humans.

Current controversies regarding oncologic risk associated with polypropylene midurethral slings.

Midurethral synthetic slings are the gold standard treatment for stress urinary incontinence. However, recent concerns have been raised regarding a possible association between synthetic midurethral slings and malignancy. The aim of this editorial was to examine the data behind these concerns. After a review of the data, no evidence was found to suggest that polypropylene midurethral slings are associated with a risk of malignancy.ᅟ

Neonatal urethral polyps associated with Beckwith-Wiedemann syndrome.

We report the first case of Beckwith-Wiedemann syndrome without urinary obstruction, but with a congenital urethral polyp as a tumor protruding from the external urinary meatus. The present case suggests a possible relation between Beckwith-Wiedemann and the onset of fibroepithelial polyps in the reno-urinary system during the neonatal period.

Nephrogenic adenoma in a urethral diverticulum.

Nephrogenic adenoma (NA) is a rare benign metaplastic lesion of the urothelial tract that arises as a response to injury and chronic inflammation. Although the most common site for NA is the bladder, it can occur in any part of urinary tract lined by urothelium. NA can mimic minor variants of urothelial cancer, clear cell adenocarcinoma, and prostate adenocarcinoma, making a combination of histologic examination and immunohistochemistry essential for diagnosis. We hereby report a rare case of nephrogenic adenoma arising in a urethral diverticulum.

[A case of clear cell adenocarcinoma arising from a female urethral diverticulum].

A 49-year-old female was followed up at the gynecology clinic after conization for cervical cancer and underwent routine cervical smear, which revealed a cluster of adenocarcinoma cells. Positron emission tomography-computed tomography (PET-CT) showed increased FDG uptake around the proximal urethra. Urethroscopy showed a tumor arising from the urethral diverticulum, and it was revealed to be clear cell adenocarcinoma by cold-cup biopsy. Then, she was referred to our hospital for the treatment of the urethral cancer arising from the urethral diverticulum. MRI showed the urethral diverticulum at circumference of the urethra and a tumor projecting into its lumen. The patient underwent urethrectomy together with resection of the diverticulum tumor and cutaneous vesicostomy. Pathological examination demonstrated pT2, clear cell adenocarcinoma of the urethra. The patient had no local recurrence or metastasis 5 months after the surgery.

[Malignant degeneration in a urethral diverticulum: an uncommon complication in a common condition]. / Divertículo uretral con degeneración maligna: una complicación infrecuente en una dolencia frecuente.

Acquired urethral diverticula are relatively common in women. They are usually asymptomatic but they can lead to complications; infection and stones are the most common complications. Malignant degeneration with the development of a malignant tumor in the diverticulum is a rare complication that must be taken into account. Few cases of malignant tumors in urethral diverticula have been reported. We present the case of a woman diagnosed with a malignant tumor in a urethral diverticulum. We review the imaging findings for urethral diverticula and the complications that can arise in this condition.

A leiomyoma presenting as an exophytic periurethral mass: a case report and review of the literature.

Periurethral masses in females are rarely observed, although they can occur anywhere along the genitourinary tract. They may be detected on physical examination or present with symptoms such as vaginal swelling, bladder outlet obstruction, vaginal bleeding, hematuria, or urinary tract infection. We report a sexually inactive, 27-year-old woman with an exophytic, fimbria-like periurethral mass. The benign nature of the lesion was suspected on the basis of the findings of magnetic resonance imaging. Surgical enucleation was performed. The microscopic examination revealed a urethral leiomyoma. Immunohistochemical study confirmed a leiomyoma with positive staining for smooth muscle actin and negative staining for S-100.