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Chronic intestinal pseudoobstruction (CIPO) is a group of disorders characterized by repeated episodes of symptoms and signs of obstruction without a mechanical cause (1–4). CIPO is thought to be the result of a motility disorder of the gastrointestinal tract and can be broadly divided into myopathic, in which the primary defect is at the level of the smooth muscle cell, and neuropathic, in which the primary defect is at the level of the enteric nervous system (1–4). CIPO is further divided into familial and sporadic types. Sporadic CIPO may be the result of connective tissue diseases, general neurologic diseases, infections, drugs, and tumors (1–4). A subset of CIPO, idiopathic CIPO, is thought to result from a defective neuronal myenteric network (1). Full-thickness biopsies from patients with idiopathic CIPO may show neuronal damage, but many times the biopsies are unrevealing (1). A role for interstitial cells of Cajal (ICC) in coordinating intestinal motility has become more apparent in recent years (5–10). ICC are found throughout the gastrointestinal tract interspersed within the circular and longitudinal muscle layers and also form a dense network at the level of the neuronal myenteric plexus in the stomach, small intestine, and colon, and a second network at the level of the deep muscular plexus in the small intestine and at the submucosal plexus in the large intestine (11–13). This report describes a patient with CIPO with an intact enteric nervous system and a normal distribution of ICC within the muscle layers but with absent ICC networks in the myenteric and submucosal regions.The Institutional Review Board of the Mayo Clinic approved procurement of human tissue. Normal control tissue (n = 4, descending and sigmoid colon) was obtained as surgical waste. Two of the control samples were from a 23-year-old woman and a 30-year-old man who underwent surgery for nonobstructive colon cancer. The other two samples were sigmoid colon from subjects aged 9 and 13 years with diverting colostomies for rectovaginal fistulae. The tissue of the control subjects and the patient was collected in the operating room and immediately frozen at −70°C until studied. No differences were noted between the adolescent and adult colonic tissue. The findings in the descending and sigmoid colon were similar, and figures shown are all from the sigmoid colon. Colonic samples were fixed with 4% buffered paraformaldehyde solution at 4°C for 4 hours to 16 hours, rinsed several times for 1 hour with 0.1 mol/L phosphate-buffered saline (PBS) at 4°C, and then immersed overnight at 4°C in PBS containing 30% sucrose. Tissues were next placed in optimal cutting temperature (OCT) embedding medium (Miles, Elkhart, IN, U.S.A.) and snap-frozen in isopentane at −40°C to −50°C. Cryostat sections (12 μm thick) were cut, mounted on gelatin-chrome alum-coated glass slides, and air-dried at room temperature before processing for immunohistochemistry and histochemistry.Immunoreactivity for nerves was studied by the indirect immunofluorescence method using antibodies for protein gene product (PGP 9.5; Biogenesis, Poole, U.K.), substance P (SP; Chemicon, Temecula, CA, U.S.A.), and vasoactive intestinal peptide (VIP; Santa Cruz Biotech, Santa Cruz, CA, U.S.A.). Tissues were rinsed several times with PBS, incubated in PBS containing 10% nonimmune donkey serum (NDS) and 0.3% Triton X-100 for 1 hour, and then incubated with antiserum diluted 1:800 (PGP 9.5), 1:400 (SP), or 1:200 (VIP) in 5% NDS overnight at 4°C in a moist chamber. Sections were rinsed in PBS and then incubated with CY3- or fluorescein-conjugated donkey antirabbit or donkey antigoat immunoglobulin G (IgG; Chemicon) diluted 1:100 in 2.5% NDS for 2 hours at 4°C in a moist chamber.