Anatomic considerations of inflatable penile prosthetics: lessons gleaned from surgical body donor workshops.

Surgical implantation of an inflatable penile prosthesis (IPP) remains the gold-standard treatment for severe erectile dysfunction. The ideal surgical technique requires a thorough understanding of the relevant anatomy. This includes anatomic considerations related to, but not limited to, dissection and exposure of penoscrotal fasciae and tissues, corporal configuration, and abdominal structures. Insights obtained from pre-dissected anatomic specimens can obviate urethral injury, nerve damage, corporal perforation, inappropriate sizing, crossover, or implant malposition. We present penile implant-specific anatomic dissections and topographic landmarks identified over the last decade in the course of surgical training programs provided for IPP implantation.

The surgical anatomy of a (robot-assisted) minimally invasive transcervical esophagectomy.

BACKGROUND: Transcervical esophagectomy allows for esophagectomy through transcervical access and bypasses the thoracic cavity, thereby eliminating single lung ventilation. A challenging surgical approach demands thorough understanding of the encountered anatomy. This study aims to provide a comprehensive overview of surgical anatomy encountered during the (robot-assisted) minimally invasive transcervical esophagectomy (RACE and MICE). METHODS: To assess the surgical anatomy of the lower neck and mediastinum, MR images were made of a body donor after, which it was sliced at 24-µm intervals with a cryomacrotome. Images were made every 3 slices resulting in 3.200 images of which a digital 3D multiplanar reconstruction was made. For macroscopic verification, microscopic slices were made and stained every 5 mm (Mallory-Cason). Schematic drawings were made of the 3D reconstruction to demonstrate the course of essential anatomical structures in the operation field and identify anatomical landmarks. RESULTS: Surgical anatomy 'boxes' of three levels (superior thoracic aperture, upper mediastinum, subcarinal) were created. Four landmarks were identified: (i) the course of the thoracic duct in the mediastinum; (ii) the course of the left recurrent laryngeal nerve; (iii) the crossing of the azygos vein right and dorsal of the esophagus; and (iv) the position of the aortic arch, the pulmonary arteries, and veins. CONCLUSIONS: The presented 3D reconstruction of unmanipulated human anatomy and schematic 3D 'boxes' provide a comprehensive overview of the surgical anatomy during the RACE or MICE. Our findings provide a useful tool to aid surgeons in learning the complex anatomy of the mediastinum and the exploration of new surgical approaches such as the RACE or MICE.

Internal anal sphincter nerves - a macroanatomical and microscopic description of the extrinsic autonomic nerve supply of the internal anal sphincter.

AIM: The internal anal sphincter (IAS) contributes substantially to anorectal functions. While its autonomic nerve supply has been studied at the microscopic level, little information is available concerning the macroscopic topography of extrinsic nerve fibres. This study was designed to identify neural connections between the pelvic plexus and the IAS, provide a detailed topographical description, and give histological proof of autonomic nerve tissue. METHODS: Macroscopic dissection of pelvic autonomic nerves was performed under magnification in seven (five male, two female) hemipelvises obtained from body donors (67-92 years). Candidate structures were investigated by histological and immunohistochemical staining protocols to visualize nerve tissue. RESULTS: Nerve fibres could be traced from the anteroinferior edge of the pelvic plexus to the anorectal junction running along the neurovascular bundle anterolaterally to the rectum and posterolaterally to the prostate/vagina. Nerve fibres penetrated the longitudinal rectal muscle layer just above the fusion with the levator ani muscle (conjoint longitudinal muscle) and entered the intersphincteric space to reach the IAS. Histological and immunohistochemical findings confirmed the presence of nerve tissue. CONCLUSIONS: Autonomic nerve fibres supplying the IAS emerge from the pelvic plexus and are distinct to nerves entering the rectum via the lateral pedicles. Thus, they should be classified as IAS nerves. The identification and precise topographical location described provides a basis for nerve-sparing rectal resection procedures and helps to prevent postoperative functional anorectal disorders.

Can we use peripheral tissue biopsies to diagnose Parkinson's disease? A review of the literature.

Phosphorylated α-synuclein (phosαSYN) containing inclusions in neurons (Lewy bodies, LB) and nerve terminals (Lewy neurites, LN), the pathological hallmark of Parkinson's disease (PD), are not confined to the central nervous system, but have also been reported in peripheral tissues. However, the usefulness of αSYN/phosαSYN detection in tissues accessible to biopsies as a reliable biomarker for prodromal PD remains unclear. A systematic review of studies using biopsies of skin, olfactory and gastrointestinal (GI) tissues was conducted to evaluate the sensitivity and specificity of both αSYN and phosαSYN staining in PD patients. Data analysis was hampered by the diversity of the methods used, e.g. choice of biopsy sites, tissue processing, staining protocols and evaluation of the findings. Tissue obtained from GI tract/salivary glands (13 post-mortem, 13 in vivo studies) yielded the highest overall sensitivity and specificity compared to skin (three post-mortem, eight in vivo studies) and olfactory mucosa/bulb (six post-mortem studies, one in vivo study). In contrast to phosαSYN, αSYN was more consistently detectable in peripheral tissues of healthy controls. GI tract/salivary glands appear to be the most promising candidate tissue for peripheral biopsy-taking. phosαSYN is considered as the marker of choice to delineate pathological aggregates from normal αSYN regularly found in peripheral neural tissues. However, the sensitivity and specificity of phosαSYN are not yet acceptable for using phosαSYN as a reliable peripheral biomarker for PD in clinical routine. Further refinement regarding the interpretation of the peripheral αSYN/phosαSYN burden and the phenotypical definition of peripheral LB/LN is needed to optimize screening methods for prodromal PD.

[Interdisciplinary Diagnosis and Treatment of Deep Infiltrating Endometriosis]. / Interdisziplinäre Diagnostik und Therapie der tief infiltrierenden Endometriose.

Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the interdisciplinary approach to the treatment of deep infiltrating endometriosis. Endometriosis has been defined as the presence of endometrial glands and stroma outside the internal epithelial lining of the cavum uteri. As a consequence, endometriosis can cause a wide range of symptoms such as chronic pelvic pain, subfertility, dysmenorrhea, deep dyspareunia, cyclical bowel or bladder symptoms (e.g., dyschezia, bloating, constipation, rectal bleeding, diarrhoea and hematuria), abnormal menstrual bleeding, chronic fatigue or low back pain. Approx. 50 % of teenagers and up to 32 % of women of reproductive age, operated for chronic pelvic pain or dysmenorrhoea, suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, a causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The correct treatment for each patient should take into account the severity of the disease and whether the patient desires to have children. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 and > 60 % and is very much dependent on the integrated management and surgical skills of the respective hospital. Consequently, to optimise the individual patient's treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should, especially in the case of deep infiltrating endometriosis, be undertaken in appropriate centres.

Comparison of intraoperative flat panel imaging and postoperative plain radiography for the detection of intraarticular screw displacement in volar distal radius plate ostheosynthesis.

OBJECTIVES: To investigate if intraoperative 3D flat panel imaging improves the detection of radiocarpal intraarticular screw misplacement (RCSM) in comparison to standard postoperative x-ray. METHODS: In a study on cadaver specimens, we evaluated the sensitivity and specificity to detect RCSM using X-ray, intraoperative 3D-fluoroscopy as well as the digital volume tomography. The gold standard reference was computed tomography. RESULTS: Sensitivity for the detection of RCSM for X-ray was 58% and specificity 88%. For DVT, the sensitivity to detect RCSM was 88% and the specificity 53%. For 3D-fluoroscopy, the sensitivity for RCSM was 68% and specificity 95%. When combining the methods, the best performance was found, when combining the two intraoperative imaging methods, with a resulting sensitivity of 88% and a specificity of 73%. CONCLUSIONS: Intraoperative 3D fluoroscopy and digital volume tomography appear to be at least as sensitive and specific to detect RCSM than the regular postoperative radiography in two planes. However, especially discrete screw misplacements can be missed with either method. LEVEL OF EVIDENCE: Level IV. Diagnostic device study.

SNAP-25 is abundantly expressed in enteric neuronal networks and upregulated by the neurotrophic factor GDNF.

Control of intestinal motility requires an intact enteric neurotransmission. Synaptosomal-associated protein 25 (SNAP-25) is an essential component of the synaptic vesicle fusion machinery. The aim of the study was to investigate the localization and expression of SNAP-25 in the human intestine and cultured enteric neurons and to assess its regulation by the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF). SNAP-25 expression and distribution were analyzed in GDNF-stimulated enteric nerve cell cultures, and synaptic vesicles were evaluated by scanning and transmission electron microscopy. Human colonic specimens were processed for site-specific SNAP-25 gene expression analysis and SNAP-25 immunohistochemistry including dual-labeling with the pan-neuronal marker PGP 9.5. Additionally, gene expression levels and distributional patterns of SNAP-25 were analyzed in colonic specimens of patients with diverticular disease (DD). GDNF-treated enteric nerve cell cultures showed abundant expression of SNAP-25 and exhibited granular staining corresponding to synaptic vesicles. SNAP-25 gene expression was detected in all colonic layers and isolated myenteric ganglia. SNAP-25 co-localized with PGP 9.5 in submucosal and myenteric ganglia and intramuscular nerve fibers. In patients with DD, both SNAP-25 mRNA expression and immunoreactive profiles were decreased compared to controls. GDNF-induced growth and differentiation of cultured enteric neurons is paralleled by increased expression of SNAP-25 and formation of synaptic vesicles reflecting enhanced synaptogenesis. The expression of SNAP-25 within the human enteric nervous system and its downregulation in DD suggest an essential role in enteric neurotransmission and render SNAP-25 as a marker for impaired synaptic plasticity in enteric neuropathies underlying intestinal motility disorders.

[Anatomy and pathogenesis of diverticular disease]. / Anatomie und Pathogenese der Divertikelkrankheit.

BACKGROUND: Although diverticular disease is one of the most frequent gastrointestinal disorders the pathogenesis is not yet sufficiently clarified. OBJECTIVES: The aim is to define the anatomy and pathogenesis of diverticular disease considering the risk factors and description of structural and functional alterations of the bowel wall. METHODS: This article gives an appraisal of the literature, presentation and evaluation of classical etiological factors, analysis and discussion of novel pathogenetic concepts. RESULTS: Colonic diverticulosis is defined as an acquired out-pouching of multiple and initially asymptomatic pseudodiverticula through muscular gaps in the colon wall. Diverticular disease is characterized by diverticular bleeding and/or inflammatory processes (diverticulitis) with corresponding complications (e.g. abscess formation, fistula, covered and open perforation, peritonitis and stenosis). Risk factors for diverticular disease include increasing age, genetic predisposition, congenital connective tissue diseases, low fiber diet, high meat consumption and pronounced overweight. Alterations of connective tissue cause a weakening of preformed exit sites of diverticula and rigidity of the bowel wall with reduced flexibility. It is assumed that intestinal innervation disorders and structural alterations of the musculature induce abnormal contractile patterns with increased intraluminal pressure, thereby promoting the development of diverticula. Moreover, an increased release of pain-mediating neurotransmitters is considered to be responsible for persistent pain in chronic diverticular disease. CONCLUSIONS: According to the present data the pathogenesis of diverticular disease cannot be attributed to a single factor but should be considered as a multifactorial event.

GDNF induces synaptic vesicle markers in enteric neurons.

Regulation of intestinal motility depends on an intact synaptic vesicle apparatus. Thus, we investigated the expression of the synaptic vesicle markers synaptophysin and synaptobrevin in the human enteric nervous system (ENS) and their regulation by glial cell line-derived neurotrophic factor (GDNF) in cultured enteric neurons. Full-thickness specimens of the human colon were assessed for expression of synaptophysin and synaptobrevin and neuronal localization was assessed by dual-label immunocytochemistry with PGP 9.5. Effects of GDNF on both synaptic markers were monitored in enteric nerve cell cultures and the presence of varicosities was determined by applying electron microscopy to the cultures. Human colonic specimens showed immunoreactivity for synaptophysin and synaptobrevin in both myenteric and submucosal ganglia as well as in nerve fibers. Both synaptic vesicle markers co-localized with the neuronal marker PGP 9.5 and exhibited granular accumulation patterns in the human and rat ENS. In cultured rat myenteric neurons GDNF treatment promoted expression of both synaptic vesicle markers and the formation of neuronal varicosities. The regulation of synaptophysin and synaptobrevin in enteric neurons by GDNF argues for the induction of functional neuronal networks in culture characterized by an increase of synaptogenesis.

Site-specific gene expression and localization of growth factor ligand receptors RET, GFRα1 and GFRα2 in human adult colon.

Two of the glial-cell-line-derived neurotrophic factor (GDNF) family ligands (GFLs), namely GDNF and neurturin (NRTN), are essential neurotropic factors for enteric nerve cells. Signal transduction is mediated by a receptor complex composed of GDNF family receptor alpha 1 (GFRα1) for GDNF or GFRα2 for NRTN, together with the tyrosine kinase receptor RET (rearranged during transfection). As both factors and their receptors are crucial for enteric neuron survival, we assess the site-specific gene expression of these GFLs and their corresponding receptors in human adult colon. Full-thickness colonic specimens were obtained after partial colectomy for non-obstructing colorectal carcinoma. Samples were processed for immunohistochemistry and co-localization studies. Site-specific gene expression was determined by real-time quantitative polymerase chain reaction in enteric ganglia and in circular and longitudinal muscle harvested by microdissection. Protein expression of the receptors was mainly localized in the myenteric and submucosal plexus. Dual-label immunohistochemistry with PGP 9.5 as a pan-neuronal marker detected immunoreactivity of the receptors in neuronal somata and ganglionic neuropil. RET immunoreactivity co-localized with neuronal GFRα1 and GFRα2 signals. The dominant source of receptor mRNA expression was in myenteric ganglia, whereas both GFLs showed higher expression in smooth muscle layers. The distribution and expression pattern of GDNF and NRTN and their corresponding receptors in the human adult enteric nervous system indicate a role of both GFLs not only in development but also in the maintenance of neurons in adulthood. The data also provide a basis for the assessment of disturbed signaling components of the GDNF and NRTN system in enteric neuropathies underlying disorders of gastrointestinal motility.

Expression and function of the Transforming Growth Factor-b system in the human and rat enteric nervous system.

BACKGROUND: Transforming growth factor-betas (TGF-bs) are pleiotropic growth factors exerting neurotrophic functions upon various neuronal populations of the central nervous system. In contrast, the role of TGF-b isoforms in the enteric nervous system (ENS) is largely unknown. We therefore analyzed the gene expression pattern of the TGF-b system in the human colon and in rat myenteric plexus, and smooth muscle cell cultures and determined the effect of TGF-b isoforms on neuronal differentiation. METHODS: Human colonic samples as well as cultured rat myenteric plexus, and smooth muscle cells were assessed for mRNA expression levels of the TGF-b system (TGF-b1-3, TbR-1-3) by qPCR. The colonic wall was separated into mucosa and tunica muscularis and enteric ganglia were isolated by laser microdissection (LMD) to allow site-specific gene expression analysis. Effects of TGF-b isoforms on neurite outgrowth and branching pattern of cultured myenteric neurons were monitored. KEY RESULTS: mRNA expression of the TGF-b system was detected in all compartments of the human colonic wall as well as in LMD-isolated myenteric ganglia. Cultured myenteric neurons and smooth muscle cells of rat intestine also showed mRNA expression of all ligands and receptors. Transforming growth factor-b2 treatment increased neurite length and branching pattern in cultured myenteric neurons. CONCLUSIONS & INFERENCES: The TGF-b system is abundantly expressed in the human and rat ENS arguing for an auto-/paracrine function of this system on enteric neurons. Transforming growth factor-b2 promotes neuronal differentiation and plasticity characterizing this molecule as a relevant neurotrophic factor for the ENS.

Quantitation of cellular components of the enteric nervous system in the normal human gastrointestinal tract--report on behalf of the Gastro 2009 International Working Group.

BACKGROUND: Patients with gastrointestinal neuromuscular diseases may undergo operative procedures that yield tissue appropriate to diagnosis of underlying neuromuscular pathology. Critical to accurate diagnosis is the determination of limits of normality based on the study of control human tissues. Although robust diagnostic criteria exist for many qualitative alterations in the neuromuscular apparatus, these do not include quantitative values due to lack of adequate control data. PURPOSE: The aim of this report was to summarize all relevant available published quantitative data for elements of the human enteric nervous system (neuronal cell bodies, glial cells, and nerve fibers) from the perspective of the practicing pathologist. Forty studies meeting inclusion criteria were systematically reviewed with data tabulated in detail and discussed in the context of methodological variations and limitations. The results reveal a lack of concordance between observations of different investigators resulting in data insufficient to produce robust normal ranges. This diversity highlights the need to standardize the way pathologists collect, process, and quantitate neuronal and glial elements in enteric neuropathologic samples, as suggested by recent international guidelines on gastrointestinal neuromuscular pathology.

Laser microdissection as a new tool to investigate site-specific gene expression in enteric ganglia of the human intestine.

BACKGROUND: Myenteric ganglia are key-structures for the control of intestinal motility and their mRNA expression profiles might be altered under pathological conditions. A drawback of conventional RT-PCR from full-thickness specimens is that gene expression analysis is based on heterogeneously composed tissues. To overcome this problem, laser microdissection combined with real-time RT-PCR can be used to detect and quantify low levels of gene expression in isolated enteric ganglia. METHODS: Fresh unfixed full-thickness specimens of sigmoid colon were obtained from patients (n = 8) with diseases unrelated to intestinal motility disorders. 10 microm cryo-sections were mounted on membrane-coated slides and ultra-rapidly stained with toluidine blue. Myenteric ganglia were isolated by laser microdissection and catapulting for mRNA isolation. Real-time RT-PCR was performed for selected growth factors, neurotransmitter receptors and specific cell type markers. KEY RESULTS: Collection of 0.5 mm(2) of ganglionic tissue was sufficient to obtain positive RT-PCR results. Collection of 4 mm(2) resulted in ct-values allowing a reliable quantitative comparison of gene expression levels. mRNA analysis revealed that neurotrophic growth factor, neurotrophin-3, serotonin receptor 3A, PGP 9.5 and S100 beta are specifically expressed in myenteric ganglia of the human colon. CONCLUSIONS & INFERENCES: Laser microdissection combined with real-time RT-PCR is a novel technique to reliably detect and quantify site-specific expression of low-abundance mRNAs (e.g. growth factors, neurotransmitter receptors) related to the human enteric nervous system. This technical approach expands the spectrum of available tools to characterize enteric neuropathologies underlying human gastrointestinal motility disorders at the molecular biological level.

Expression of estrogen receptors in the hypothalamo-pituitary-ovarian axis in middle-aged rats after re-instatement of estrus cyclicity.

During reproductive aging female rats enter an anovulatory state of persistent estrus (PE). In an animal model of reinstatement of estrus cyclicity in middle-aged PE rats we injected the animals with progesterone (0.5 mg progesterone/kg body weight) at 12:00 for 4 days whereas control animals received corn oil injections. After the last injection animals were analyzed at 13:00 and 17:00. Young regular cycling rats served as positive controls and were assessed at 13:00 and 17:00 on proestrus. Progesterone treatment of middle-aged PE rats led to occurrence of luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin surges in a subset of animals that were denoted as responders. Responding middle-aged rats displayed a reduction of ER-beta mRNA in the preoptic area which was similar to the effect in young rats. Within the mediobasal hypothalamus, only young rats showed a decline of ER-alpha mRNA expression. A decrease of ER-alpha mRNA levels in the pituitary was observed in progesterone-responsive rats and in young animals. ER-beta mRNA expression was reduced in young regular cycling rats. ER-beta mRNA levels in the ovary were reduced following progesterone treatment in PE rats and in young rats. Taken together our data show that cyclic administration of progesterone reinstates ovulatory cycles in intact aging females which have already lost their ability to display spontaneous cyclicity. This treatment leads to the occurrence of preovulatory LH, FSH and prolactin surges which are accompanied by differential modulation of ERs in the hypothalamus, the pituitary and the ovary.