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Background: The treatment of ulcerative colitis (UC) is based on conventional therapies (aminosalicylates, corticosteroids, and immunosuppressants) and when these are ineffective, biologic drugs. However, in a substantial portion of patients undergoing treatment with biologic agents there is primary or secondary loss of response. Thus, new therapeutic options are been actively explored; among these, there is interest in the Janus kinase (JAK) inhibitors, small molecules that can be administered orally., Methods: We carried out an extensive literature search concerning the effects of JAK inhibitors for the treatment of patients with UC., Results: Tofacitinib is the drug more extensively studied in this setting, and it was recently approved in Europe for the treatment of moderate to severe UC. The available data suggest that this drug can be effective in obtaining clinical and endoscopic remission in UC patients unresponsive to other treatments, even in those previously treated with biologic drugs. In addition, the drug was able to improve significantly the quality of life of these patients. There are still few data available for the treatment of UC with other JAK inhibitors., Conclusions: The JAK inhibitors, in particular tofacitinib, are a new class of orally administered drugs effective for the treatment of UC. However, more studies are needed to ascertain the safety of tofacitinib in the long term and whether other compounds of this class may be equally effective.

Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients.

Background: Achalasia is a primary esophageal motor disorder characterized by degenerative changes of the myenteric plexus. The pathophysiologic abnormalities may be the final result of several intermeshing mechanisms, and more than one single factor may cause the motor abnormalities., Aims: To report our experience in investigating the myenteric plexus of achalasia patients undergoing esophagomyotomy., Patients and Methods: Tissue samples from 12 patients undergoing Heller myotomy for achalasia were evaluated and compared with esophageal tissue specimens from 7 controls. Enteric neurons and interstitial cells of Cajal (ICC) were assessed by immunohistochemical methods, and the presence of vasoactive intestinal polypeptide ergic fibers and of CD3 lymphocytes. The possible presence of herpesvirus was also assessed by immunohistochemistry, whereas that of papillomavirus was assessed by in-situ hybridization., Results: Compared with controls, achalasia patients displayed a significant decrease of both enteric neurons and ICC. Immunoreactivity for vasoactive intestinal polypeptide was completely absent in each patient. CD3 staining disclosed myenteric plexitis in 5 (42%) patients; no control patient had plexitis. All patients were completely negative for the presence of both herpes simplex virus and human papillomavirus., Conclusions: The enteric nervous system of the lower esophageal sphincter area is impaired in patients with "idiopathic achalasia," and the abnormalities involve ICC and neurons in many patients. The triggering factors for these abnormalities are, however, still unknown.

Chronic granulomatous disease (CGD) is a primary phagocytic disorder characterized by greatly increased susceptibility to severe bacterial and fungal infections. Patients with CGD may have gastrointestinal manifestations, commonly colitis, usually mimicking Crohn disease. We report an adult case, the second in literature, of CGD with severe colitis displaying histologic features of ulcerative colitis. The patient had a prompt improvement (continuing up to more than 5 y of follow-up) of the clinical picture after ileostomy and fecal diversion.

Background: Although histology is considered the gold standard for the diagnosis of celiac disease, the early stages (latent or potential) of this disease are difficult to diagnose, because of the negativity of laboratory tests and the lack of villous atrophy. Thus, markers of early disease are needed., Aims: We investigated the possibility to detect latent or potential celiac disease by means of TCRgamma clonality assay in intraepithelial T cells in patients with suspected disease, negative laboratory tests, and an increased number of intraepithelial lymphocytes., Patients and Methods: Duodenal biopsies were obtained from 35 patients with nonspecific duodenitis (controls), 13 latent or potential celiac disease subjects, 28 well-defined celiac patients, and 8 celiac patients in gluten-free diet. Histologic and immunohistochemical quantification of intraepithelial lymphocytes, as well as TCRgamma clonality assay, were carried out in all subjects by means of standard techniques., Results: Intraepithelial lymphocytes and TCRgamma clonality were significantly increased in potential and defined celiac patients with respect to the controls, even though the increase in TCRgamma clonality was lesser with respect to that of intraepithelial lymphocytes. No significant differences were found concerning this variable between the potential and defined celiac subjects., Conclusions: TCRgamma clonality does not represent a marker of early disease. However, it might be useful to help in distinguishing celiac disease from other causes of nonspecific duodenitis.

The hypertensive lower esophageal sphincter is an infrequent primary esophageal motor disorder characterized by elevated mean lower esophageal sphincter pressure (greater than or equal to 3 SD from that of controls), sphincter relaxations greater than 75%, and normal peristaltic activity in the esophageal body. This disorder is frequently associated with the nutcracker esophagus. We report our clinical and manometric experience with the isolated hypertensive lower esophageal sphincter (i.e., unassociated with other motor disorders), which constituted 2.7% of all patients who complained of dysphagia or chest pain referred for manometry during the period from October 1982 to February 1991.