title: Molecular and Cellular Characteristics of the Colonic Pseudo-obstruction in Patients With Intractable Constipation.
abstract: OBJECTIVE
  Chronic intestinal pseudo-obstruction (CIPO) is a disorder characterized by recurrent symptoms suggestive of obstruction such as abdominal pain, proximal distension with extremely suppressed motility in the absence of lumen-occluding lesion, whose etiology/ pathophysiology is poorly understood. In this study we investigated a functionally obstructive lesion that could underlie symptoms of CIPO.
  
  
  METHODS
  We studied colons surgically removed from 13 patients exhibiting clinical/pathological features of pseudo-obstruction but were unresponsive to standard medical treatments. The colons were characterized morphologically, functionally and molecularly, which were compared between regions and to 28 region-matched controls obtained from colon cancer patients.
  
  
  RESULTS
  The colons with pseudo-obstruction exhibited persistent luminal distension proximally, where the smooth muscle was hypertrophied with changes in the cell phenotypes. Distinct luminal narrowing was observed near the distal end of the dilated region, close to the splenic flexure, previously referred to as the "transition zone (TZ)" between the dilated and non-dilated loops. Circular muscles from the TZ responded less to depolarization and cholinergic stimulation, which was associated with downregulation of L-type calcium channel expression. Smooth muscle contractile protein was also downregulated. Myenteric ganglia and neuronal nitric oxide synthase (nNOS) positive cells were deficient, more severely in the TZ region. Interstitial cells of Cajal was relatively less affected.
  
  
  CONCLUSIONS
  The TZ may be the principal site of functional obstruction, leading to proximal distension and smooth muscle hypertrophy, in which partial nNOS depletion could play a key role. The neuromuscular abnormalities probably synergistically contributed to the extremely suppressed motility observed in the colonic pseudo-obstruction.
authors.affiliation: Department of Gastroenterology, Asan Digestive Disease Research Institute, Seoul, Korea.
authors.forename: Yoon Suh
authors.initials: YS
authors.lastname: Do
authors.affiliation: Department of Gastroenterology, Asan Digestive Disease Research Institute, Seoul, Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Myung
authors.affiliation: Department of Pharmacology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kwak
authors.affiliation: Department of Pharmacology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Soohan
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Enoch
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Song
authors.affiliation: Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Yu
authors.affiliation: Department of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Department of Pharmacology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Lee
keywords: Colon; Hypoganglionosis; Intestinal Pseudo-obstruction; Nitric oxide; Smooth muscle