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Total Penectomy for Recurrent Chordoma of the Corpus Cavernosum.

ABSTRACT: Chordomas are rare low malignant neoplasm arising from remnants of the notochord with predilection site of the clivus or the os sacrum. Standard therapy is radical excision and adjuvant radiation. Due to invasive growth and adjacent to vital structures resection is often incomplete, and therefore, local recurrence is frequent. First, to the best knowledge of our authors, we present a 70-year-old man with a recurrent chordoma infiltrating the corpus cavernosum. Asymptomatic recurrence was diagnosed by magnet resonance imaging according to the standard follow-up. Our interdisciplinary tumor board recommended surgical resection. We performed a total penectomy and perineal urethrostomy to achieve negative resection margins and preserve best quality of life for the patient.

SUBMITTER: Eismann L

PROVIDER: S-EPMC7040421 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Total Penectomy for Recurrent Chordoma of the Corpus Cavernosum.

Eismann Lennert L Kess Sabine S Stief Christian G CG Strittmatter Frank F

Case reports in urology 20200213

Chordomas are rare low malignant neoplasm arising from remnants of the notochord with predilection site of the clivus or the os sacrum. Standard therapy is radical excision and adjuvant radiation. Due to invasive growth and adjacent to vital structures resection is often incomplete, and therefore, local recurrence is frequent. First, to the best knowledge of our authors, we present a 70-year-old man with a recurrent chordoma infiltrating the corpus cavernosum. Asymptomatic recurrence was diagnos ...[more]

PMID: 32099713

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Project description:Purpose: Molecular mechanisms of penile corpus cavernosum aging and male age-related erectile dysfunction (ED) remain unclear. Here we profiled young and old rat penile corpus cavernousm by single-cell RNA sequencing (scRNA-seq). Methods:To map the single-cell transcriptomic landscape of penile corpus cavernosum during aging, we performed uniform manifold approximation and projection (UMAP), differential gene expression analysis (DGEs), pseudotime analysis and single-cell entropy algorithm to dissect cellular composition and transcriptional heterogeneity. For validation analysis, we further performed immunofluorescence studies on key molecules involved during penile corpus cavernosum aging. Results: After stringent filtering,transcriptomes of 14,879 single cells (8,557 young and 6,322 old) derived from penile corpus cavernosum of 5 young (3 months) and 5 old (23 months) rats were analyzed subsequently. Clustering analysis of cell-type specific gene expression identified 19 cell types, such as smooth muscle cells, endothelial cells, fibroblasts,myofibroblasts and immune cells.Transcriptomic analyses revealed that transcriptional alterations across all cell types exhibited distinct properties rather than universally consistent. DGEs analysis demonstrated that genes related to extracellular matrix organization were highly expressed. Among these cell types, fibroblasts showed apparent heterogeneities. By performing pseudotime and single-cell entropy analysis on fibroblasts, we observed the age-associated decrease of entropy, and aged fibroblasts were found to adopt senescent secretory phenotype, as evidenced by the high expression of genes associated with the senescence-associated secretory phenotype (SASP). Since eliminating senescent cells or SASP were demonstrated to improve health and life span, we further investigated the distinct senescence-related gene expression signatures across all cell types during aging. Conclusions: We plotted a cellular atlas of penile corpus cavernosum, and revealed the molecular alterations of aging cells, especially fibroblasts. Our work will deepen the understanding of the heterogeneity among certain cell types during penile corpus cavernosum aging and provide novel entry points for the age-associated ED treatment.

Project description:BackgroundAging is an important risk factor for erectile dysfunction (ED). Both calorie restriction (CR) and physical exercise (PE) have been established as a non-medical method for the improvement of detrimental changes in aging. It is well documented that both CR and PE influence on sympathetic and parasympathetic systems; however, there are few studies on non-adrenergic non-cholinergic pathways. This study aims to investigate the NO-mediated mechanisms of CR and PE on corpus cavernosum in aged rats.Materials and Methods3 and 15 month-old rats were divided into five experimental groups: young rats fed ad libitum (Y-C), aged rats fed ad libitum (O-S), aged rats with CR (O-CR), aged rats with PE (O-PE), and aged rats with CR and PE (O-CR-PE). CR was applied to animals as a 40% reduction of daily food intake for 6 weeks. PE was moderate swimming at 30 min at 3 days/week. The effects of CR and PE were evaluated by histologic, biologic, and in-vitro tissue bath studies.ResultsThe outcomes in CR and PE groups (characterized by decreased nitrosative damage together with increased antioxidant capacity) were improved in comparison to the O-S. Apoptotic biomarkers were also lower and both endothelial and smooth muscle cell’ functions were preserved too. There was no statistical difference between apoptosis, antioxidant capacity, and nitrosative damage parameters. Contractile responses to phenylephrine and relaxation responses to carbachol were: O-CR > O-PE > O-CR-PE. In these groups, NOS protein levels determined by western-blot were: eNOS: O-CR = O-CR + PE > O-PE; iNOS: O-CR = O-PE > O-CR-PE; nNOS: O-PE > O-CR-PE > O-CR.ConclusionIn our study, both CR and PE prevented age-related changes in the corpus cavernosum of rats. Reducing nitrosative damage in the neurovascular structure was the main mechanism. CR and exercise restored the endothelial and smooth muscle cells in corpus cavernosum by decreasing apoptosis. The mechanism of enhancing functional response in corpus cavernosum with CR was the improvement of endothelial function via eNOS activation however it involves increases in the NO-cGMP signaling pathway by an endothelium-independent mechanism with PE. This might be a direct stimulation of smooth muscle cells by NO, which released from the cavernous nerve endings via nNOS activation.

Project description:BackgroundThe mechanism of erectile dysfunction (ED) caused by a low androgen level is still not clear.AimTo explore the influence of the low testosterone state on G protein-coupled receptor kinase interactor 1 (GIT1) and its contact to erectile function.MethodsThirty male Sprague-Dawley rats aged 8 weeks were distributed at random into 5 groups: control (sham operated), castration, testosterone supplement after castration, castration + vacant lentiviral transfection, and castration + lentiviral transfection. The testis and epididymis were removed through a scrotal incision to develop castrated rats. Four weeks after castration, a lentivirus carrying the GIT1 gene was injected into the middle of rat penile corpus cavernosum. One week after transfection, maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), serum testosterone, nitric oxide, GIT1, endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), p-eNOS/eNOS, and the interaction between eNOS and GIT1 were assessed in the rats.OutcomesThe levels of GIT1 in the penile cavernous tissue of castrated rats are significantly lower than that of controls.ResultsGIT1 was expressed in the cytoplasm and cell membrane of vascular endothelial cells and smooth muscle cells in rat penile tissue. In comparison with normal rats, the castrated rats showed lower levels of GIT1 expression, GIT1 and eNOS interaction, p-eNOS/eNOS, nitric oxide, and ICPmax/MAP (P < .01). Overexpression of GIT1 can intensively enhance the expression level of GIT1, the interaction between GIT1 and eNOS, p-eNOS/eNOS, nitric oxide, and ICPmax/MAP in rats (P < .01).Clinical translationModulating the interaction between eNOS and GIT1 might be a novel method of treating ED caused by a low androgen level.Strengths and limitationsThe impact of GIT1 phosphorylation on the activity of eNOS and its possible mechanisms affecting erectile function require further study.ConclusionA low testosterone state inhibits erectile function in rats by reducing the expression of GIT1 and the protein interaction between GIT1 and eNOS.

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Total Penectomy for Recurrent Chordoma of the Corpus Cavernosum.

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Total Penectomy for Recurrent Chordoma of the Corpus Cavernosum.

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