Nasopharyngeal cyst in an adolescent boy: differential diagnosis - embryological and anatomical considerations.

In the current article, we present a case of an adolescent boy with a nasopharyngeal cyst that induced nasal and Eustachian tube obstruction. Nasopharyngeal cysts can be found incidentally during imaging examinations such as MRI; however, a symptomatic nasopharyngeal cyst is a rare finding in the paediatric population. The cyst was treated successfully by marsupialisation, and the histological diagnosis revealed an adenoidal retention cyst. The differential diagnosis of a nasopharyngeal cyst is always challenging since developmental cysts such as Rathke's pouch cysts, Torwaldt's and branchial cleft cysts may be encountered at the nasopharynx. The current article also intends to present the diagnostic and therapeutic approach to a nasopharyngeal cyst, emphasising anatomical and embryological considerations that address its differential diagnosis.

Embryological, anatomical and clinical considerations on pleuroperitoneal communication.

The pleural and peritoneal cavity share many related features due to their common celomic origin. Normally these two spaces are completely separated with the development of the diaphragm. Defects in diaphragm morphogenesis may result in congenital diaphragmatic hernias, which is the most known form of communication between the pleural and peritoneal cavity. However, in several cases, findings of pleuroperitoneal communication (PPC) have been described in adults through an apparently intact diaphragm. In this comprehensive review we systematically evaluate clinical scenarios of this form of "unexpected" PPC as reported in the literature and focus on the possible mechanisms involved.

Radical Prostatectomy and Anatomical Controversies: The Urethral Sphincter and the Elusive Continence Mechanisms.

Prostate cancer incidence is rising [...].

DNA Damage Repair Pathways in Prostate Cancer: A Narrative Review of Molecular Mechanisms, Emerging Biomarkers and Therapeutic Targets in Precision Oncology.

Prostate cancer (PCa) has a distinct molecular signature, including characteristic chromosomal translocations, gene deletions and defective DNA damage repair mechanisms. One crucial pathway involved is homologous recombination deficiency (HRD) and it is found in almost 20% of metastatic castrate-resistant PCa (mCRPC). Inherited/germline mutations are associated with a hereditary predisposition to early PCa development and aggressive behavior. BRCA2, ATM and CHECK2 are the most frequently HRD-mutated genes. BRCA2-mutated tumors have unfavorable clinical and pathological characteristics, such as intraductal carcinoma. PARP inhibitors, due to the induction of synthetic lethality, have been therapeutically approved for mCRPC with HRD alterations. Mutations are detected in metastatic tissue, while a liquid biopsy is utilized during follow-up, recognizing acquired resistance mechanisms. The mismatch repair (MMR) pathway is another DNA repair mechanism implicated in carcinogenesis, although only 5% of metastatic PCa is affected. It is associated with aggressive disease. PD-1 inhibitors have been used in MMR-deficient tumors; thus, the MMR status should be tested in all metastatic PCa cases. A surrogate marker of defective DNA repair mechanisms is the tumor mutational burden. PDL-1 expression and intratumoral lymphocytes have ambivalent predictive value. Few experimental molecules have been so far proposed as potential biomarkers. Future research may further elucidate the role of DNA damage pathways in PCa, revealing new therapeutic targets and predictive biomarkers.

Lateral semicircular canal dilatation in a patient with congenital hearing loss due to α-tectorin mutation: microanatomical considerations.

The tectorial membrane is crucial in the physiology of the auditory neuroepithelium. Mutations in one of its functional molecules, α-tectorin, lead to autosomal dominant and recessive congenital mid-frequency, non-syndromic hearing loss.Typically, α-tectorin mutations are not accompanied by any morphological abnormalities of the labyrinth. For the first time, we present a case of a toddler boy with congenital hearing loss due to TECTA gene mutation and concomitant bilateral dilation of the lateral semicircular canals.The expression of glycoproteins, like α-tectorin, varies between the distinct labyrinth acellular membranes. Various mutations in the TECTA gene may affect additional glycoproteins that share a high percentage of sequence similarity at the amino acid level with α-tectorin. The mutated glycoproteins differ in the hydration level of their side chains of glycosaminoglycans. Hydration level could affect the mass of the ampullary cupula of the lateral semicircular canal leading to its dilation during embryogenesis.

Use of Thiel-embalmed cadavers in urology training and their ability to retain real-life anatomy: a systematic review.

BACKGROUND: Thiel-embalmed cadavers (TeCs) have been proposed as an alternative and probably safer method of surgical training, compared to formalin-embalmed cadavers. We aimed to perform a systematic review on the use of TeCs in urology training and their ability to represent real-life anatomy. METHODS: PubMed, SCOPUS and Cochrane databases were searched for articles with purpose to explore the use of TeCs in urology training, without date restrictions, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From each paper, we evaluated the type of procedure, the number of participants, the type of study, the educational outcomes and their level, according to Kirkpatrick hierarchy. RESULTS: Of the 225 records initially retrieved, eight articles were eventually included. All studies evaluated participants' perceptions about the procedure. Overall, urology trainees and specialists have positively commented on the educational value of TeCs, which have been also found able to adequately mimic real-life conditions. In all the eight studies, trainees stated that tissue quality of TeCs was adequately realistic and considered TeCs as a useful surgical training tool. CONCLUSION: Although the use of TeCs in urology training has so far been limited, their value as a surgical training tool has been positively perceived. These outcomes suggest that TeCs may also enhance urology trainees' surgical skills and may encourage their implementation as a simulation tool in urology training.

Epithelial-to-Mesenchymal Transition in Metastasis: Focus on Laryngeal Carcinoma.

In epithelial neoplasms, such as laryngeal carcinoma, the survival indexes deteriorate abruptly when the tumor becomes metastatic. A molecular phenomenon that normally appears during embryogenesis, epithelial-to-mesenchymal transition (EMT), is reactivated at the initial stage of metastasis when tumor cells invade the adjacent stroma. The hallmarks of this phenomenon are the abolishment of the epithelial and acquisition of mesenchymal traits by tumor cells which enhance their migratory capacity. EMT signaling is mediated by complex molecular pathways that regulate the expression of crucial molecules contributing to the tumor's metastatic potential. Effectors of EMT include loss of adhesion, cytoskeleton remodeling, evasion of apoptosis and immune surveillance, upregulation of metalloproteinases, neovascularization, acquisition of stem-cell properties, and the activation of tumor stroma. However, the current approach to EMT involves a holistic model that incorporates the acquisition of potentials beyond mesenchymal transition. As EMT is inevitably associated with a reverse mesenchymal-to-epithelial transition (MET), a model of partial EMT is currently accepted, signifying the cell plasticity associated with invasion and metastasis. In this review, we identify the cumulative evidence which suggests that various aspects of EMT theory apply to laryngeal carcinoma, a tumor of significant morbidity and mortality, introducing novel molecular targets with prognostic and therapeutic potential.

The Eustachian Tube Dysfunction in Children: Anatomical Considerations and Current Trends in Invasive Therapeutic Approaches.

The eustachian tube (ET) has a crucial role in the physiology of the middle ear. Thus, any condition that renders the tube dysfunctional is directly implicated with middle ear pathophysiology, like in the case of acute otitis media and otitis media with effusion. Children are more vulnerable to pathologies of the middle ear, primarily due to the immature development of their eustachian tubes. Otitis media with effusion, apart from being a burden for hearing, with direct consequences for speech development, may also be implicated in cholesteatoma formation. Medical therapy is not practically effective for the treatment of effusion. Moreover, the established surgical approaches, like grommets and adenoidectomy, deal only indirectly with the problem since they are not addressing the dysfunctional ET itself. An emerging interventional approach that intends to restore the function of the tube is the transnasal balloon dilation of the cartilaginous part of the ET. Growing international experience indicates that this promising technique is safe and effective. In the current review, we aim to provide background information on the anatomy, physiology, and pathophysiology of the ET and to present the progress of the balloon dilation technique with emphasis on pediatric patients.

Cell Plasticity and Prostate Cancer: The Role of Epithelial-Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance.

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial-mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell-cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

Clinical implications of the anatomical position of the urethra meatus in women with recurrent post-coital cystitis: a case-control study.

INTRODUCTION AND HYPOTHESIS: Recurrent post-coital urinary infection (rUTI)-usually cystitis-is a common entity among otherwise healthy young women. However, little is known about the possible influence of genital anatomical variations. Only a shorter urethral meatus-anus distance has been described as a risk factor. The aim of this study was to evaluate our hypothesis that a shorter urethra-vagina distance is involved in the etiology of post-coital urinary infection. METHODS: In this prospective case-control study, 61 young women aged between 18 and 40 years with an acute post-coital UTI and a history of intercourse-related rUTI were consecutively recruited between January 2013 and February 2018. Fifty-six age-matched, sexually active women with no history of UTI served as controls. Perineal measurements included the distances between the clitoris-urethra (C-U), urethra-vagina (U-V), urethra-anus (U-A) and perineum. Demographic and sexual behavior characteristics and the morphology of the urethral meatus were also noted. Univariate analysis compared variables between groups. ROC analysis was used to define the efficiency of perineal measurements in predicting outcome. Odds ratios and 95% confidence intervals for UTI-predisposing variables were estimated using logistic regression analysis. RESULTS: The U-V and U-A distance was shorter in patients compared with controls [median (interquatile range): 16 mm (14-18) vs. 21 mm (19-23) and 51 mm (47-53) vs. 59 mm (55-62), respectively, p < 0.001]. The U-V performed better in ROC analysis than the U-A distance (AUC 0.952 vs. 0.875, p = 0.023). The only statistically significant parameters in multivariate analysis influencing UTI were BMI (OR: 0.702; 0.510-0.967, p = 0.030) and U-V (OR: 0.297; 0.161-0.549, p < 0.001). CONCLUSIONS: Our results indicate an association between shorter urethra-vagina distance and post-coital rUTIs.

Meatal stenosis after surgical correction of short frenulum: Is the "pull-and-burn" method the way to go?

BACKGROUND AND OBJECTIVES: The surgical correction of a short frenulum includes several procedures that vary in complexity of the technique and the use of stitches, lasers, or skin grafts. However, little is known about the effect of these procedures on meatal stenosis. A possible association of frenular artery trauma during circumcision and subsequent meatal stenosis has raised concerns regarding the importance of frenulum preservation. We hereby report our experience over 15 years of applying the "pull-and-burn" method for short frenulum correction. PATIENTS AND METHODS: A total of 236 patients underwent the "pull-and-burn" procedure for short frenulum under local anesthesia on an outpatient basis between November 2002 and November 2017. The method is suture free and involves tearing the frenulum superficially and vertically by the aid of a low-power, high-frequency hyfrecator, avoiding the underlying frenular vessels. Patients were advised for a regular follow-up visit at 2-3 months postoperatively and were reviewed for symptoms and signs suggestive of meatal stenosis. RESULTS: Follow-up files were available for 228 patients (96.6%). No symptoms suggestive of meatal stenosis (dysuria and stream pattern abnormalities) were reported by any patient. Examination of the urethral meatus revealed normal appearance, with no signs of edema or scarring in all the 228 patients. CONCLUSIONS: The "pull-and-burn" method is a simple and safe procedure for the correction of short frenulum that respects anatomically the delicate vasculature of the frenular area, resulting in the preservation of the integrity of the urethral meatus.

The expression of p-mTOR and COUP-TFII correlates with increased lymphangiogenesis and lymph node metastasis in prostate adenocarcinoma.

BACKGROUND: Mammalian target of rapamycin (mTOR) is a central regulator of major cellular processes such as growth and proliferation. Deregulated mTOR signaling is implicated in a wide spectrum of human malignancies including prostate cancer. The aim of this study is to address the role of phosphorylated mTOR (p-mTOR) in prostate adenocarcinoma-induced lymphangiogenesis and lymph node metastasis as well as to investigate its relationship with chicken ovalbumin upstream promoter transcriptional factor 2 (COUP-TFII) and the vascular endothelial growth factors A/C (VEGF A/C). METHODS: We analyzed 92 paraffin embedded specimens from patients with prostate cancer who underwent radical prostatectomy with pelvic lymph node (LN) dissection. Twenty-four of these men were pathologically assessed to have regional LN metastasis (pN1 group) and 68 with negative lymph nodes (pN0 group). Lymph vessel density was measured using anti-D2-40 and anti-LYVE-1 antibodies. The expression of p-mTOR, COUP-TFII, and VEGF A/C was also evaluated by immunohistochemistry. RESULTS: Specimens from pN1 group exhibited higher cytoplasmic p-mTOR expression compared to pN0 specimens. Mean vessel densities assessed by COUP-TFII and D2-40 were increased in pN1 tumors and positively associated with higher p-mTOR expression. Interestingly, increased expression of p-mTOR was positively associated with COUP-TFII expression in cancer cells and elevated immunoreactivity for both VEGF A and C, which in turn exhibited higher expression in pN1 group. CONCLUSIONS: Our findings suggest that increased p-mTOR and COUP-TFII expression are implicated in human prostate adenocarcinoma-induced lymphangiogenesis and LN metastasis.

The aberrant urethral meatus as a possible aetiological factor of recurrent post-coital urinary infections in young women.

Recurrent urinary tract infections (rUTI) in women is a common cause of morbidity worldwide. In young women recurrent cystitis associated with sexual intercourse is quite common; however not all sexually active women will suffer a post-coital UTI episode. A variety of possible predisposing factors has been described, including behavioral risk patterns, genetic factors and increased virulence of certain subtypes of uropathogens. It has long been regarded that anatomical anomalies are rare in this setting of rUTIs. The shorter distance of the urethra to the anus has been the only anatomical risk factor described that is marginally significant in predisposing women for rUTIs. We hereby present a hypothesis that focuses on the shorter distance of the urethral meatus to the vaginal opening as the mainstay of sexually-induced rUTIs. In this theory of "functional hypospadias", the low misplacement of the urethral opening allows for easier advancement of pathogen-laden mucous by penile thrust and increased friction during intercourse. Our hypothesis suggests that a shorter distance of the urethral meatus to the vaginal opening (and not the anus itself) is an anatomical risk factor for recurrent post-coital cystitis. Verification of this hypothesis might lead to a more patient-oriented approach by alerting clinicians in looking for an aberrant meatus and save the patient from unnecessary imaging and endoscopic examinations often used in these cases. Moreover it may also aid the patient in understanding her anatomy and modify behavioral risk practices.

The role of the endothelin axis in promoting epithelial to mesenchymal transition and lymph node metastasis in prostate adenocarcinoma.

INTRODUCTION: Aberrant activation of endothelin (ET) axis has been identified as a key player in tumor growth and metastasis in several tumor types. However, little is known about the possible interaction of the ET with epithelial to mesenchymal transition (EMT), a process that transforms tumor cells in a motile, resistant to apoptosis phenotype prone to invasion and metastasis. The aim of this study was to investigate the activation of the ET axis in prostate adenocarcinoma and examine possible associations with EMT markers, lymph node (LN) metastasis, and other clinicopathological parameters. MATERIALS AND METHODS: We immunohistochemically evaluated the expression of ET-1 and its receptors A and B (ET-A, ET-B) in 64 N0 and 23 N1 prostate adenocarcinoma cases. EMT markers E-cadherin, N-cadherin, and ß-catenin and the transcriptional factor SNAIL were evaluated. We examined possible correlations of ET pathway members with EMT markers, LN status, Gleason grade, and T stage. RESULTS: Our results revealed increased expression of ET-1 and ET-A (but not ET-B) in prostate carcinoma; both ET-1 and ET-A were associated with lymph metastasis and T stage but not with Gleason grade. We observed E-cadherin and ß-catenin decrease/relocalization and increased N-cadherin expression. SNAIL also showed increased expression in tumor tissue and was associated with LN metastasis (Mann-Whitney test, P = 0.0032). Expression of ET-1 and ET-A correlated well with SNAIL expression (Spearman r, P = 0.0002 and P = 0.0176, respectively). CONCLUSIONS: These findings indicate that activation of the ET pathway may induce EMT through SNAIL activation and correlates with increased metastatic potential.

The efficacy and safety of topical EMLA cream application for minor surgery of the adult penis.

BACKGROUND AND OBJECTIVES: A variety of surgical procedures of the penis can be performed under local anesthesia. We evaluated the efficacy and safety of EMLA cream anesthetic in such procedures. MATERIALS AND METHODS: In total 330 adult patients were subjected to minor penile surgery including: Complete circumcision (73), short frenulum plasty (168), meatotomy (14), fulguration of penile warts (56) and fulguration of urethral (meatal) warts (19). The level of anesthesia obtained by EMLA cream application along with any adverse effects was recorded. RESULTS: The use of EMLA on mucosal lesions provided excellent level of local anesthesia in almost all patients (245/246, 99.5%). Anesthesia of skin lesions was in part influenced by the site of application. Circumcision patients showed the lowest efficacy of the EMLA cream as the majority (~80%) required some form of further anesthesia until the completion of the procedure. No significant adverse effects were noted. A transient erythema was present in almost all mucosal applications. CONCLUSIONS: The topical anesthetic EMLA cream is a useful, efficient and safe tool for minor surgical procedures of the penis at the office setting, with the exception of circumcision, where an additional type of anesthesia is likely to be necessary. Side effects can be kept to a minimum when the suggested doses are respected (especially at mucosal application) and the time allowed for action is carefully tailored to the site of application and the type of procedure.

Increased expression of endothelin-1 and its receptors in varicocele: an immunohistochemical study.

We hypothesized that diminished endothelin 1 (ET-1) expression at the spermatic vein wall level might be responsible for the development of varicocele. However, immunohistochemical evaluation of spermatic and control vein samples from 55 patients with varicocele showed overexpression of ET-1 and its receptors ETA and ETB in varicose veins.

Male dyspareunia due to short frenulum: the suture-free, "pull and burn" method.

INTRODUCTION: The presence of a short frenulum is a common cause for dyspareunia in males, often resulting in painful intercourse and trauma to the frenulum. Most of the described techniques use sutures that may sever the frenular artery and lead to meatal stenosis or leave skin tags that create a poor cosmetic result. AIM: The aim of this study is to describe the "pull and burn" method for the correction of a short frenulum with respect to the anatomy of the glans penis. METHODS: The procedure was performed on 127 young adults presenting with dyspareunia due to short frenulum. Local anesthesia was achieved by application of eutectic mixture of local anesthetic (EMLA) for 15-20 minutes. The point of maximum tension was cut by diathermy and a controlled vertical tear was made on the frenulum by applying gentle but firm retraction on the glans. Minor bleeding was sealed with diathermy. Personal hygiene was advised and no local antiseptics or antibiotics were further used. MAIN OUTCOME MEASURES: Achievement of adequate anesthesia with EMLA cream, use of sutures, complications of the procedure, and final cosmetic and functional result. RESULTS: The application of EMLA for 15-20 minutes was sufficient for local anesthesia. Only one patient with very thick frenulum required further lignocaine infiltration. No sutures were applied except in two cases (1.6%), in which a wide and thick frenulum required approximation of the tear edges for a better cosmesis. At 3 months follow up, no inflammation or meatal stenosis were noted. One patient required further release of a scarry frenulum. Functional and cosmetic results were excellent in all cases. CONCLUSION: The "pull and burn" method is an easy, bloodless, and sutureless procedure for the correction of a short frenulum. Local anesthesia with EMLA is satisfactory, the procedure respects the glans anatomy, and preserves the frenular artery, achieving an excellent functional and cosmetic result.

Clinical correlation of prostatic lithiasis with chronic pelvic pain syndromes in young adults.

OBJECTIVE: To investigate the incidence, morphology and clinical presentation of prostatic calculi in a selected population of young adults and to examine any possible correlation with chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS). METHODS: A population of 1374 young adults was screened with ultrasound imaging of the prostate and 101 cases with prostatic lithiasis were selected. Patients were divided in two groups, according to the type of prostatic calculi (type A: small, multiple or type B: larger, coarser calculi). Further evaluation included history and physical examination, recording of lower urinary tract symptoms and the Meares-Stamey test. RESULTS: Calculi were type A in 71.3% and type B in 28.7% of cases. Localization (central/periurethral) was not correlated with other parameters. Age was closely related to calculus burden ( p =0.034 ). Type B calculi were more often associated with symptoms and chronic prostatitis/CPPS (chi(2)-test, p=0.007 and 0.018 respectively). CONCLUSIONS: Small, multiple calcifications are a normal, often incidental ultrasonographic finding in the prostate and represent a result of age rather than a pathologic entity. However, larger prostatic calculi may be related to underlying inflammation and require further evaluation and possibly, treatment.

The use of the tissue adhesive enbucrilate (histoacryl) in the treatment of symptomatic nephroptosis.

PURPOSE: To evaluate the use of the tissue adhesive enbucrilate in the treatment of symptomatic nephroptosis. MATERIALS AND METHODS: We performed adhesive nephropexy in 9 patients who presented with well-documented symptomatic nephroptosis that was demonstrated with intravenous pyelography and/or radionuclide renogram studies. The ptotic kidney was fixed on the psoas muscle using 0.5 ml of enbucrilate (Histoacryl). RESULTS: Adhesive nephropexy was successful in all 9 patients. Average operative time was 37 min. Postoperative opioid analgesia duration and hospital stay were limited (mean 2 and 4.4 days, respectively). Most patients returned to normal activity within 2 weeks (mean 14.2 days). Mean follow-up was 25 months and showed postoperatively a good anatomical result in radiographic studies as well as significant pain alleviation (mean 1 vs. 7 preoperatively, on a 10-point scale, p < 0.005 Wilcoxon rank test). CONCLUSIONS: The tissue adhesive enbucrilate seems to be a safe, efficient agent to obtain good results in a simple, quick approach in the surgical treatment of symptomatic nephroptosis.