BACKGROUND/AIMS: Previous studies from Korea have described chronic intestinal pseudo-obstruction (CIPO) patients with transition zone (TZ) in the colon. In this study, we evaluated the pathological characteristics and their association with long-term outcomes in Korean colonic pseudo-obstruction (CPO) patients with TZ. METHODS: We enrolled 39 CPO patients who were refractory to medical treatment and underwent colectomy between November 1989 and April 2016 (median age at symptoms onset: 45 [interquartile range, 29–57] years, males 46.2%). The TZ was defined as a colonic segment connecting a proximally dilated and distally non-dilated segment. Detailed pathologic analysis was performed. RESULTS: Among the 39 patients, 37 (94.9%) presented with TZ and 2 (5.1%) showed no definitive TZ. Median ganglion cell density in the TZ adjusted for the colonic circumference was significantly decreased compared to that in proximal dilated and distal non-dilated segments in TZ (+) patients (9.2 vs 254.3 and 150.5, P < 0.001). Among the TZ (+) patients, 6 showed additional pathologic findings including eosinophilic ganglionitis (n = 2), ulcers with combined cytomegalovirus infection (n = 2), diffuse ischemic changes (n = 1), and heterotropic myenteric plexus (n = 1). During follow-up (median, 61 months), 32 (82.1%) TZ (+) patients recovered without symptom recurrence after surgery. The presence of pathological features other than hypoganglionosis was an independent predictor of symptom recurrence after surgery (P = 0.046). CONCLUSIONS: Hypoganglionosis can be identified in the TZ of most Korean CPO patients. Detection of other pathological features in addition to TZ-associated hypoganglionosis was associated with poor post-operative outcomes.
Cell Count ; Colectomy ; Colon ; Colonic Pseudo-Obstruction ; Cytomegalovirus Infections ; Eosinophils ; Follow-Up Studies ; Ganglion Cysts ; Humans ; Intestinal Pseudo-Obstruction ; Korea ; Male ; Myenteric Plexus ; Pathology ; Recurrence ; Ulcer

Achalasia is a motility disorder of the esophagus that is characterized by loss of ganglionic neurons within the myenteric plexus of the lower esophageal sphincter (LES) resulting in failure of the LES to relax. Clinically this disorder presents with simultaneous dysphagia to solids and liquids, and if left untreated, leads to esophageal dilation, which can give rise to many adverse consequences. Extrinsic compression of respiratory structures is one such consequence, and rarely, cases of tracheal compression secondary to achalasia have been reported. However, cases of extrinsic bronchial compression are yet rarer. Here, we present a case series comprised of two patients with achalasia who presented with extrinsic bronchial compression by a dilated esophagus secondary to achalasia.
Airway Obstruction ; Cardia ; Deglutition Disorders ; Esophageal Achalasia ; Esophageal Motility Disorders ; Esophageal Sphincter, Lower ; Esophagus ; Ganglion Cysts ; Humans ; Myenteric Plexus ; Neurons

KBG syndrome is an autosomal dominant syndrome presenting with macrodontia, distinctive facial features, skeletal anomalies, and neurological problems caused by mutations in the ankyrin repeat domain 11 (ANKRD11) gene. The diagnosis of KBG is difficult in very young infants as the characteristic macrodontia and typical facial features are not obvious. The youngest patient diagnosed to date was almost one year of age. We here describe a 2-month-old Korean boy with distinctive craniofacial features but without any evidence of macrodontia due to his very early age. He also had a congenital megacolon without ganglion cells in the rectum. A de novo deletion of exons 5–9 of the ANKRD11 gene was identified in this patient by exome sequencing and real-time genomic polymerase chain reaction. As ANKRD11 is involved in the development of myenteric plexus, a bowel movement disorder including a congenital megacolon is not surprising in a patient with KBG syndrome and has possibly been overlooked in past cases.
Ankyrin Repeat ; Diagnosis ; Exome ; Exons ; Ganglion Cysts ; Hirschsprung Disease ; Humans ; Infant ; Male ; Movement Disorders ; Myenteric Plexus ; Polymerase Chain Reaction ; Rectum

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a common disease characterized by intestinal dysmotility, the mechanism of which remains elusive. We aim to determine whether the high-affinity choline transporter 1 (CHT1), a determinant of cholinergic signaling capacity, modulates intestinal motility associated with stress-induced IBS. METHODS: A rat IBS model was established using chronic water avoidance stress (WAS). Colonic pathological alterations were evaluated histologically and intestinal motility was assessed by intestinal transit time and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response to colorectal distension. RT-PCR, western blotting, and immunostaining were performed to identify colonic CHT1 expression. Contractility of colonic muscle strips was measured using isometric transducers. enzyme-linked immunosorbent assay was used to measure acetylcholine (ACh). We examined the effects of MKC-231, a choline uptake enhancer, on colonic motility. RESULTS: After 10 days of WAS, intestinal transit time was decreased and fecal water content increased. Visceromotor response magnitude in WAS rats in response to colorectal distension was significantly enhanced. Protein and mRNA CHT1 levels in the colon were markedly elevated after WAS. The density of CHT1-positive intramuscular interstitial cells of Cajal and myenteric plexus neurons in WAS rats was higher than in controls. Ammonium pyrrolidine dithiocarbamate partly reversed CHT1 upregulation and alleviated colonic hypermotility in WAS rats. Pharmacological enhancement of CHT1 activity by MKC-231 enhanced colonic motility in control rats via upregulation of CHT1 and elevation of ACh production. CONCLUSION: Upregulation of CHT1 in intramuscular interstitial cells of Cajal and myenteric plexus neurons is implicated in chronic stress-induced colonic hypermotility by modulation of ACh synthesis via nuclear factor-kappa B signaling.
Acetylcholine ; Ammonium Compounds ; Animals ; Blotting, Western ; Choline ; Colon ; Enzyme-Linked Immunosorbent Assay ; Gastrointestinal Motility ; Interstitial Cells of Cajal ; Irritable Bowel Syndrome ; Models, Animal ; Myenteric Plexus ; Neurons ; Rats ; RNA, Messenger ; Transducers ; Up-Regulation ; Water

Laryngopharyngeal reflux disease (LPRD) is common in laryngologic practice. In Korea, up to 1 out of every 5 patients who visit otorhinolaryngology clinic is supposed to have LPRD with symptoms and physical findings. Major symptoms of LPRD include hoarseness, cough, reflux symptom and mild dysphagia. Even though LPRD is common, its diagnosis may be difficult, because its symptoms are nonspecific and the laryngeal findings are not always associated with symptom severity. In Recent study, 66.4% of Patient who has LPRD also associated with esophageal motility disorders. Esophageal achalasia is a disease of unknown etiology characterized by an absence of peristalsis in the body of esophagus and nonrelaxing hypertension of the lower esophageal sphincter. Common cause is loss of ganglion cells in Auerbachs plexus. The classic triad of symptoms in achalasia includes dysphagia, regurgitation and weight loss. LPRD and esophageal achalasia have similar symptoms but have different treatment of choice. The Differentiation diagnosis of theses disease is important and should be established by history, radiologic examination and endoscopic examination. We recently assessed a 59-year-old female patient who complained of an epigastric pain, dysphagia and chronic cough. LPRD was initially diagnosed on Laryngoscopic examination and Reflux Symptom Index, but patient was not relieved of any symptoms after treatment of Proton Pump Inhibitor for 3 months. After high resolution manometry, esophageal achalasia was finally diagnosed. We report this case regarding the diagnosis and treatment with review of literatures because we have to think about esophageal motility disorders as a differential diagnosis in laryngology.
Cough ; Deglutition Disorders ; Diagnosis ; Diagnosis, Differential ; Esophageal Achalasia* ; Esophageal Motility Disorders ; Esophageal Sphincter, Lower ; Esophagus ; Female ; Ganglion Cysts ; Hoarseness ; Humans ; Hypertension ; Korea ; Laryngopharyngeal Reflux* ; Manometry ; Middle Aged ; Myenteric Plexus ; Otolaryngology ; Peristalsis ; Proton Pumps ; Weight Loss

Eosinophilic myenteric ganglionitis is a disorder characterized by infiltration of the Auerbach myenteric plexus by eosinophils. As a cause of chronic intestinal pseudo-obstruction (CIPO), eosinophilic myenteric ganglionitis has been rarely reported and the majority of the reported cases in the literature were children. We experienced a case of eosinophilic myenteric ganglionitis associated with CIPO in a 53-year-old female patient. Histologic examination of the resected descending colon showed moderate eosinophilic infiltrates with hypogangliosis in the myenteric plexus. Immunohistochemical study revealed increased number of CD4-positive lymphocytes and stronger but scantier glial fibillary acid protein expression in the inflamed myenteric plexus.
CD4-Positive T-Lymphocytes ; Child ; Colon, Descending ; Eosinophils* ; Female ; Ganglion Cysts* ; Humans ; Intestinal Pseudo-Obstruction ; Middle Aged ; Myenteric Plexus

BACKGROUND/AIMS: Neuronal degeneration and changes in interstitial cells of Cajal (ICCs) are important mechanisms of age-related constipation. This study aims to compare the distribution of ICCs and neuronal nitric oxide synthase (nNOS) with regard to age-related changes between the ascending colon (AC) and descending colon (DC) in 6-, 31-, and 74-week old and 2-year old male Fischer-344 rats. METHODS: The amount of fecal pellet and the bead expulsion times were measured. Fat proportion in the muscle layer of the colon was analyzed by hematoxylin and eosin staining. Proto-oncogene receptor tyrosine kinase (KIT) and neuronal nitric oxide synthase (nNOS) expression were analyzed with Western blotting and immunohistochemistry. Isovolumetric contractile measurements and electrical field stimulation were used to assess smooth muscle contractility. RESULTS: Colon transit and bead expulsion slowed with senescence. Fat in the muscle layer accumulated with age in the AC, but not in the DC. The proportion of KIT-immunoreactive ICCs in the submucosal and myenteric plexus was higher in the DC than in the AC, and it declined with age, especially in the AC. In contrast, the proportion of NOS-immunoreactive neurons in the myenteric plexus was higher in the AC than in the DC, and both decreased in older rats. Nitric oxide levels declined with age in the DC. Muscle strip experiments showed that the inhibitory response mediated by nitric oxide in the circular direction of the DC was reduced in 2-year old rats. CONCLUSION: The AC and DC differ in their distribution of ICCs and nNOS, and age-related loss of nitrergic neurons more severely affects the DC than the AC.
Aging* ; Animals ; Blotting, Western ; Colon ; Colon, Ascending ; Colon, Descending* ; Constipation ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Immunohistochemistry ; Interstitial Cells of Cajal* ; Male ; Muscle, Smooth ; Myenteric Plexus ; Neurons* ; Nitrergic Neurons ; Nitric Oxide Synthase Type I ; Nitric Oxide* ; Protein-Tyrosine Kinases ; Proto-Oncogenes ; Rats ; Rats, Inbred F344*

BACKGROUND/AIMS: Myenteric plexus interstitial cells of Cajal (ICC-MY) are involved in the generation of gut pacemaker activity and neuronal communication. We performed patch clamp on ICC-MY in situ to observe the changes of pacemaker activity in response to neural modulations. METHODS: A fresh longitudinal muscle with myenteric plexus (LMMP) from mouse jejunum was prepared. ICC-MY and ganglion neurons embedded in the layer of longitudinal muscles were targeted by patch clamping in whole-cell configuration in a model of current or voltage clamp. Neurogenic modulators were applied to evaluate their effects on ICC pacemaker activity. RESULTS: In situ ICC-MY showed spontaneous and rhythmical voltage oscillations with a frequency of 27.2 ± 3.9 cycles/min, amplitude of 32.6 ± 6.3 mV, and resting membrane potential of −62.2 ± 2.8 mV. In situ neurons showed electrically evocable action potential in single or multiple spikes. Pacemaker activity was modulated by neuronal activators through receiving a neuronal input. Application of tetrodotoxin depolarized pacemaker potentials in a dose dependent manner, and decreased the amplitude at tetrodotoxin 0.3 μM for about 40 ± 10%; capsaicin (1 μM) ameliorated ICC-MY K+ current for about 49 ± 14.8%; and, nitric oxide hyperpolarized pacemaker potential and decreased the amplitude and frequency. CONCLUSIONS: The in situ preparation patch clamp study further demonstrates that the pacemaker activity is an intrinsic property of ICC. The neurogenic activators change and shape pacemaker potential and activity in situ. LMMP preparation in situ patch clamp provides an ideal platform to study the functional innervation of the ICC and the enteric neural system, thereby, for evaluating the neural regulation of pacemaker activity, especially in disorder models.
Action Potentials ; Animals ; Capsaicin ; Constriction ; Enteric Nervous System ; Ganglion Cysts ; Interstitial Cells of Cajal ; Jejunum* ; Membrane Potentials ; Mice* ; Muscles ; Myenteric Plexus* ; Neurons ; Nitric Oxide ; Tetrodotoxin

BACKGROUND/AIMS: Neurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. METHODS: The effects of neurotensin with concentrations ranging from 0.1-100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin. RESULTS: Low concentration of neurotensin (0.1-1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction—relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. CONCLUSIONS: Neurotensin (0.1-1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions.
Absorption ; Animals ; Baths ; Colon* ; In Vitro Techniques ; Interstitial Cells of Cajal ; Lidocaine ; Myenteric Plexus ; Neural Conduction ; Neurotensin* ; Peristalsis ; Rats* ; Receptors, Neurotensin ; Video Recording

BACKGROUND/AIMS: Physical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. METHODS: The rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. RESULTS: The intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase- and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). CONCLUSIONS: These morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea.
Animals ; Carbon ; Choline ; Choline O-Acetyltransferase ; Diarrhea* ; Enteric Nervous System ; Fluorescence ; Ganglia ; Gastrointestinal Motility ; Gastrointestinal Tract ; Ileum ; Intestine, Small* ; Irritable Bowel Syndrome* ; Models, Animal* ; Myenteric Plexus ; Neurons* ; Nitric Oxide ; Nitric Oxide Synthase ; Rats* ; Stress, Psychological ; Submucous Plexus ; Vasoactive Intestinal Peptide