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

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 expression of vascular endothelial growth factor-C correlates with lymphatic microvessel density and lymph node metastasis in prostate carcinoma: An immunohistochemical study

Aim: To evaluate the expression of two different lymphatic vascular density (LVD) markers (D2-40 and LYVE-1) and a lymphangiogenic cytokine (Vascular Endothelial Growth Factor-C, [VEGF-C]) in prostate carcinoma and to investigate their relationship with the lymph node status. Settings and Design: Archival material study of 92 non-consecutive radical prostatectomy specimens. Materials and Methods: The mean LVD was assessed immunohistochemically in 24 prostate carcinoma specimens from patients with clinically localized disease, who were found to have nodal metastasis (pN1), and was compared with 68 pN0 cases. Furthermore, the mean LVD, VEGF-C expression, and lymphatic invasion were examined in relation to lymph node involvement. Results: Peritumoral (but not intratumoral) mean LVD assessed by D2-40 was higher in pN1 tumors (P = 0.015). LYVE-1 expression was limited and not associated with lymph node status. The VEGF-C expression was higher in the N1 cases and also correlated with the increased mean LVD in both the peri- and intratumoral compartments. Lymphatic invasion was strongly associated with nodal metastasis and higher VEGF-C expression. Conclusions: Our results indicate that increased peritumoral (but not intratumoral) LVD in the tumor specimen is associated with lymph node metastasis. Increased expression of VEGF-C is associated with higher LVD (in both intratumoral and peritumoral compartments) and with positive lymph node status, indicating a possible dual role in both lymphangiogenesis and lymphatic vessel invasion

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 β-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 β-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

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