Abnormalities of neuromuscular anatomy in diverticular disease

The pathogenesis of diverticular disease is still poorly understood and considered to be multifactorial. Whereas classical pathogenetic concepts have focused on risk factors including increasing age, low-fiber diet and connective tissue disorders, novel concepts take into account that patients with diverticular disease exhibit disturbed intestinal motility patterns (that may result in functional obstruction and painful sensations) therefore postulating an underlying enteric neuro-/myopathy. Recent studies including quantitative evaluations of the enteric nervous system (ENS) in diverticular disease yielded hypoganglionic conditions of both myenteric and submucosal plexus as well as a nerve tissue remodeling in chronic diverticular disease. The disturbed neuromuscular communication was proven by demonstrating alterations in several enteric neurotransmitter systems, exemplified for the cholinergic, serotonergic, nitrergic system as well as for vasointestinal peptide, galanin and tachykinins. Novel lines of evidence have added the involvement of neurotrophic factors such as glial cell line-derived neurotrophic factor which is supposed to regulate ENS development and maintenance and which is downregulated in patients with diverticular disease. Consistent with the hypothesis of an enteric myopathy, deficits in smooth muscle integrity and composition such as hypertrophy, fibrotic transformation and gene expression deficits could be delineated. Taken together, the structural and functional findings on alterations of the ENS and the enteric musculature in diverticular disease provide evidence to strengthen the hypothesis that an enteric neuro-/myopathy may contribute to the development of colonic diverticula and the generation of symptoms in the course of the disease

Review: Pelvic nerves - from anatomy and physiology to clinical applications

A prerequisite for nerve-sparing pelvic surgery is a thorough understanding of the topographic anatomy of the fine and intricate pelvic nerve networks, and their connections to the central nervous system. Insights into the functions of pelvic nerves will help to interpret disease symptoms correctly and improve treatment. In this article, we review the anatomy and physiology of autonomic pelvic nerves, including their topography and putative functions. The aim is to achieve a better understanding of the mechanisms of pelvic pain and functional disorders, as well as improve their diagnosis and treatment. The information will also serve as a basis for counseling patients with chronic illnesses. A profound understanding of pelvic neuroanatomy will permit complex surgery in the pelvis without relevant nerve injury

Morphologic Basis for Developing Diverticular Disease, Diverticulitis, and Diverticular Bleeding

Diverticula of the colon are pseudodiverticula defined by multiple outpouchings of the mucosal and submucosal layers penetrating through weak spots of the muscle coat along intramural blood vessels. A complete prolapse consists of a diverticular opening, a narrowed neck, and a thinned diverticular dome underneath the serosal covering. The susceptibility of diverticula to inflammation is explained by local ischemia, translocation of pathogens due to retained stool, stercoral trauma by fecaliths, and microperforations. Local inflammation may lead to phlegmonous diverticulitis, paracolic/mesocolic abscess, bowel perforation, peritonitis, fistula formation, and stenotic strictures. Diverticular bleeding is due to an asymmetric rupture of distended vasa recta at the diverticular dome and not primarily linked to inflammation. Structural and functional changes of the bowel wall in diverticular disease comprise: i) Altered amount, composition, and metabolism of connective tissue; ii) Enteric myopathy with muscular thickening, deranged architecture, and altered myofilament composition; iii) Enteric neuropathy with hypoganglionosis, neurotransmitter imbalance, deficiency of neurotrophic factors and nerve fiber remodeling; and iv) Disturbed intestinal motility both in vivo (increased intraluminal pressure, motility index, high-amplitude propagated contractions) and in vitro (altered spontaneous and pharmacologically triggered contractility). Besides established etiologic factors, recent studies suggest that novel pathophysiologic concepts should be considered in the pathogenesis of diverticular disease

Embryological Development and Topographic Anatomy of Pelvic Compartments-Surgical Relevance for Pelvic Lymphonodectomy

Background The oncological outcome of surgery for the treatment of pelvic malignancies can be improved by performing pelvic lymphonodectomy. However, the extent and regions of lymph node harvest are debated and require profound knowledge of anatomy in order to avoid collateral damage. Methods The embryological development and topographic anatomy of pelvic compartments in relation to pelvic lymphonodectomy for rectal, uterine, and prostate cancer are reviewed. Based on pre-dissected anatomical specimens, lymph node regions and drainage routes of the posterior and urogenital pelvic compartments are described in both genders. Anatomical landmarks are highlighted to identify structures at risk of injury during pelvic lymphonodectomy. Results The ontogenesis of urogenital and anorectal compartments and their lymphatic supply are key factors for adequate lymphonodectomy, and have led to compartment-based surgical resection strategies. However, pelvic lymphonodectomy bears the risk of injury to somatic and autonomic nerves, vessels, and organs, depending on the regions and extent of surgery. Conclusion Embryologically defined, compartment-based resection of pelvic malignancies and their lymphatic drainage routes are based on clearly delineated anatomical landmarks, which permit template-oriented pelvic lymphonodectomy. Comprehensive knowledge of pelvic anatomy, the exchange of surgical concepts between specialties, and minimally invasive techniques will optimize pelvic lymphonodectomy and reduce complications

Less invasive causal treatment of ejaculatory duct obstruction by balloon dilation: a case report, literature review and suggestion of a CT- or MRI-guided intervention

Uni- or bilateral ejaculatory duct obstruction (EDO) is a rare but correctable cause of infertility, chronic pelvic pain and postejaculatory pain

Impaired Expression of Neuregulin 1 and Nicotinic Acetylcholine Receptor β4 Subunit in Diverticular Disease

Neuregulin 1 (NRG1) regulates the expression of the nicotinic acetylcholine receptor (nAChR) and is suggested to promote the survival and maintenance of the enteric nervous system (ENS), since deficiency of its corresponding receptor complex ErbB2/ErbB3 leads to postnatal colonic aganglionosis. As diverticular disease (DD) is associated with intestinal hypoganglionosis, the NRG1-ErbB2/ErbB3 system and the nAChR were studied in patients with DD and controls. Samples of tunica muscularis of the sigmoid colon from patients with DD (n = 8) and controls (n = 11) were assessed for mRNA expression of NRG1, ErbB2, and ErbB3 and the nAChR subunits α3, α5, α7, β2, and β4. Site-specific gene expression levels of the NRG1-ErbB2/3 system were determined in myenteric ganglia harvested by laser microdissection (LMD). Localization studies were performed by immunohistochemistry for the NRG1-ErbB2/3 system and nAChR subunit β4. Rat enteric nerve cell cultures were stimulated with NRG1 or glial-cell line derived neurotrophic factor (GDNF) for 6 days and mRNA expression of the aforementioned nAchR was measured. NRG1, ErbB3, and nAChR subunit β4 expression was significantly down-regulated in both the tunica muscularis and myenteric ganglia of patients with DD compared to controls, whereas mRNA expression of ErbB3 and nAChR subunits β2, α3, α5, and α7 remained unaltered. NRG1, ErbB3, and nAChR subunit β4 immunoreactive signals were reduced in neuronal somata and the neuropil of myenteric ganglia from patients with DD compared to control. nAChR subunit β4 exhibited also weaker immunoreactive signals in the tunica muscularis of patients with DD. NRG1 treatment but not GDNF treatment of enteric nerve cell cultures significantly enhanced mRNA expression of nAchR β4. The down-regulation of NRG1 and ErbB3 in myenteric ganglia of patients with DD supports the hypothesis that intestinal hypoganglionosis observed in DD may be attributed to a lack of neurotrophic factors. Regulation of nAChR subunit β4 by NRG1 and decreased nAChR β4 in patients with DD provide evidence that a lack of NRG1 may affect the composition of enteric neurotransmitter receptor subunits thus contributing to the intestinal motility disorders previously reported in DD

Distribution Pattern of the Superior and Inferior Labial Arteries: Impact for Safe Upper and Lower Lip Augmentation Procedures

Background: Understanding the precise position and course of the superior and inferior labial arteries within the upper lip and the lower lip is crucial for safe and complication-free applications of volumizing materials. Methods: One hundred ninety-three anatomical head specimens (56.5 percent female cadavers) of Caucasian ethnicity were investigated in this large multicenter anatomical study. In total, six 3-cm-long vertical incisions were performed on each lip (midline and 1 cm medial to the angles of the mouth) to identify the position of the superior and inferior labial arteries in relation to the orbicularis oris muscle. Results: Three different positions of the superior and inferior labial arteries were identified: submucosal (i.e., between the oral mucosa and the orbicularis oris muscle in 78.1 percent of the cases), intramuscular (i.e., between the superficial and deep layers of the orbicularis oris muscle in 17.5 percent of the cases), and subcutaneous (i.e., between the skin and the orbicularis oris muscle in 2.1 percent of the cases). The variability in changing the respective position along the labial course was 29 percent for the total upper and 32 percent for the total lower lip. The midline location was identified in both the upper and lower lips to be the most variable. Conclusions: Based on the results of this investigation, a safer location for the application of volumizing material is the subcutaneous plane in the paramedian location of both the upper lip and the lower lip. Care has to be taken when aiming to inject in the midline, as the artery can be identified more frequently in superficial positions

Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia/reperfusion injury: Implication from an isolated perfused rat small intestine model

Background Intestinal ischemia/reperfusion (I/R)-injury often results in sepsis and organ failure and is of major importance in the clinic. A potential strategy to reduce I/R-injury is the application of ischemic preconditioning (IPC) during which repeated, brief episodes of I/R are applied. The aim of this study was to evaluate physiological and cellular effects of intestinal I/R-injury and to compare the influence of in-vivo IPC (iIPC) with ex-vivo IPC (eIPC), in which blood derived factors and nerval regulations are excluded. Results I/R-injury decreased intestinal galactose uptake (iIPC group: p<0.001), increased vascular perfusion pressure (iIPC group: p<0.001; eIPC group: p<0.01) and attenuated venous flow (iIPC group: p<0.05) while lactate-to-pyruvate ratio (iIPC group, eIPC group: p<0.001), luminal flow (iIPC group: p<0.001; eIPC group: p<0.05), goblet cell ratio (iIPC group, eIPC group: p<0.001) and apoptosis (iIPC group, eIPC group: p<0.05) were all increased. Application of iIPC prior to I/R increased vascular galactose uptake (P<0.05) while eIPC had no significant impact on parameters of I/R-injury. On cellular level, I/R-injury resulted in a reduction of the phosphorylation of several MAPK signaling molecules. Application of iIPC prior to I/R increased phosphorylation of JNK2 and p38δ while eIPC enhanced CREB and GSK-3α/β phosphorylation. Conclusion Intestinal I/R-injury is associated with major physiological and cellular changes. However, the overall influence of the two different IPC strategies on the acute phase of intestinal I/R-injury is rather limited

Laser-capture microdissection for layer-specific analysis of enteric ganglia

The enteric nervous system (ENS) is the division of the autonomic nervous system that innervates the gastrointestinal (GI) tract and controls central intestinal functions such as peristalsis and fluid movement. Enteric nerve cell bodies (neurons and glia) are predominantly organized in ganglionated networks that are present along the entire length of the GI tract in multiple tissue layers. Most cell bodies are organized in the myenteric plexus allocated between the longitudinal and the circular muscle layers or in the submucosal plexus between muscle tissue and mucosa. The site-specific characteristics of these enteric nerve cells have traditionally been analyzed via imaging techniques. Laser-capture microdissection (LCM) offers the prospect of site-specifically analyzing the gene expression profiles of these different subpopulations. This protocol addresses critical aspects of handling intestinal tissue for ENS dissection, such as the optimal quick-staining procedure, suitable laser settings, and limits of tissue material required to successfully dissect and analyze tissue layers for gene expression