Hand-assisted laparoscopic subtotal colectomy with cecorectal anastomosis for chronic idiopathic colonic pseudo-obstruction: report of a case

Chronic idiopathic colonic pseudo-obstruction (CICP) is characterized by the chronic disturbance of colonic motility without mechanical obstruction, any underlying disease or medication. Currently, there are no established medical treatments for CICP. A 62-year-old female who had undergone right hemicolectomy for splenic flexure syndrome caused by idiopathic megacolon was referred to our hospital with relapse, experiencing palpitation and abdominal fullness. She was diagnosed with CICP according to findings of marked dilation of the colon without mechanical obstruction, dilation of other parts of the gastrointestinal tract, or underlying disease. The dilated colon was surgically removed by hand-assisted laparoscopic subtotal colectomy, followed by cecorectal anastomosis. Histopathologically, there was no degeneration or lack of ganglion cells in Auerbach\u27s plexus. The patient has experienced no severe symptoms after undergoing the present operation

Mutations in RAD21 disrupt regulation of apob in patients with chronic intestinal pseudo-obstruction

Background Aims Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. Methods We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. Results We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. Conclusions Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons. © 2015 by the AGA Institute

Immediate vs. deferred switching from a boosted protease inhibitor (PI/r) based regimen to a Dolutegravir (DTG) based regimen in virologically suppressed patients with high cardiovascular risk or Age ≥50 years: final 96 weeks results of NEAT 022 study

Background Both immediate and deferred switching from a ritonavir-boosted protease inhibitor (PI/r)–based regimen to a dolutegravir (DTG)–based regimen may improve lipid profile. Methods European Network for AIDS Treatment 022 Study (NEAT022) is a European, open-label, randomized trial. Human immunodeficiency virus (HIV)–infected adults aged ≥50 years or with a Framingham score ≥10% were eligible if HIV RNA was <50 copies/mL. Patients were randomized to switch from PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D). Week 96 endpoints were proportion of patients with HIV RNA <50 copies/mL, percentage change of lipid fractions, and adverse events (AEs). Results Four hundred fifteen patients were randomized: 205 to DTG-I and 210 DTG-D. The primary objective of noninferiority at week 48 was met. At week 96, treatment success rate was 92.2% in the DTG-I arm and 87% in the DTG-D arm (difference, 5.2% [95% confidence interval, –.6% to 11%]). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AEs or treatment-modifying AEs. Total cholesterol and other lipid fractions (except high-density lipoprotein) significantly (P < .001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Conclusions Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV-infected patients ≥50 years old or with a Framingham score ≥10% was highly efficacious and well tolerated, and improved the lipid profile

Unsolved problems in the management of patients with gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease is a common problem that brings large numbers of patients to physicians every day. It lowers the quality of life of affected individuals and exposes them to potentially dangerous complications. An increasing awareness exists among patients, doctors and authorities about the relevance of this pathological condition. Despite an improved understanding of many aspects of gastro-oesophageal reflux disease, clinical management of several cases is still unsatisfactory. Atypical cases with extra-oesophageal manifestations often defy diagnosis. Even typical symptoms are often misunderstood and considered to be part of the poorly defined area of dyspepsia by both patients and doctors. As a consequence, management remains uncertain for too many cases. If correctly diagnosed, gastro-oesophageal reflux disease can be efficaciously treated with proton pump inhibitors (PPIs). Although standard doses of PPIs can heal mucosal lesions and provide symptom relief in the vast majority of oesophagitis patients, non-oesophagitis symptomatic individuals and those with extra-oesophageal manifestations may fail to respond to similar regimens. Antireflux surgery is a possible alternative to PPI therapy, but it is hampered by complications in a substantial percentage of cases and by sporadic casualties even when performed by experienced surgeons. The high prevalence of gastro-oesophageal reflux disease in the general population and the relatively high management costs should prompt any doctor to seek the best possible therapeutic approach

Widespread eradication of Helicobacter pylori: a debate

Background. Helicobacter pylori eradication is recommended currently only in peptic ulcer patients. The accumulating evidence of a possible pathogenetic role of the germ in other pathological conditions, such as mucosa-associated lymphoid tissue lymphomas and (possibly) also functional dyspepsia and gastric cancer, creates increasing pressure in favor of an expansion of such indication. However, at present, cultural and practical considerations should discourage widespread screening and eradication programs. Methods. The basis for our study is a critical review of the literature. Results. The lack of a sound pathophysiological basis linking H. pylori infection to both dyspeptic symptom perception and gastric cancer risk sharply contrasts with the numerical and clinical relevance of these pathological conditions. Screening tests are not sufficiently cheap, easy, and reliable to be applicable on a large scale. Also, eradication therapies may provide suboptimal therapeutic effects and excessive side effects if applied by physicians who are not prepared culturally. Conclusions. Improvement of pathophysiological, diagnostic, and therapeutic knowledge must be achieved before eradication programs can be proposed on a large scale

Dyspeptic symptoms and gastric emptying in the irritable bowel syndrome

OBJECTIVES: Irritable bowel syndrome (IBS) and dyspepsia often overlap. Delayed gastric emptying has been reported in IBS patients, although conflicting results exist. Whether overlapping dyspepsia correlates with gastric emptying abnormalities in IBS patients has not been clarified. This study aimed to evaluate gastric emptying of solids and its relationship with dyspeptic symptoms in IBS patients. METHODS: A total of 146 IBS outpatients seen in a referral center were evaluated for dyspeptic symptoms using a validated questionnaire. Gastric emptying of solids was evaluated scintigraphically in all patients and in 50 healthy controls. RESULTS: Overlapping dyspepsia was diagnosed in 96 (66%) IBS patients. On average, gastric emptying rates were lower in IBS patients (mean ± SEM, 33% ± 1%/h) compared with controls (40% ± 2%/h; p &lt; 0.01). Specifically, gastric emptying was delayed in IBS patients with overlapping dyspepsia (31% ± 1%/h; p &lt; 0.01), whereas IBS patients without dyspeptic complaints showed gastric emptying rates (37% ± 2%/h) that were similar to those of healthy controls (40% ± 2%/h). Relevant postprandial fullness (OR = 4.7, 95% CI = 1.8-12.5) and relevant nausea (OR = 3.3, 95% CI 1.2-9.3) were independently associated with delayed gastric emptying. CONCLUSIONS: IBS patients without overlapping dyspepsia have normal gastric emptying of solids. A significant association exists in IBS patients between delayed gastric emptying and overlapping relevant postprandial fullness and nausea

Fiber and macrogol in the therapy of chronic constipation.

Chronic constipation is a common condition in the general population. Although the majority of affected individuals do not seek medical consultation and search for remedies for their condition in the pharmacy or herbal shops, the actual health burden caused by this condition is extremely high. Many laxatives are available, but patients are often dissatisfied with the therapies adopted, whether prescribed by a doctor or self prescribed, and this leads to further social and health burdens. All of the available guidelines promote initiating the therapy of any type of constipation by ensuring an adequate intake of dietary fiber and water. However, high amounts of insoluble vegetable fiber such as those normally contained in fruits and vegetables, can lead to a further worsening of the digestive symptoms typical of chronic constipation, such as bloating and distension and pain. Better results can be obtained with soluble fibers, such as psyllium. Among the various available laxatives, polyethylene glycol (PEG), or macrogol, is the product which has been most studied and has produced the best results with the least number of side effects. This is an inert not absorbable molecule that, diluted in water, forms an isotonic solution that prevents part of the water from being absorbed, thus increasing the volume of the intestinal contents, reducing the consistency and facilitating transport and evacuation. The combination of psyllium and PEG could combine the advantages of fiber and isotonic solutions and represent an important therapeutic option for patients suffering from chronic constipation

Predictors of gastroparesis in out-patients with secondary and idiopathic upper gastrointestinal symptoms

Copyright © 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Science Ltd. All rights reserved.BACKGROUND:Delayed gastric emptying occurs frequently in patients with upper gastrointestinal symptoms associated with functional or organic diseases. AIMS:To evaluate whether: (i) the prevalence of delayed gastric emptying is influenced by the presence of organic disease; (ii) demographic or clinical factors predict modestly or markedly (gastroparesis) delayed emptying. PATIENTS:A total of 327 consecutive out-patients with upper gastrointestinal symptoms. METHODS:Routine diagnostic work-up and evaluation of demographic factors, gastrointestinal symptom evaluation and scintigraphic gastric emptying of solids were performed. RESULTS:Organic diseases were detected in 227/327 (65%) patients: 33% had delayed emptying and 20% gastroparesis. Female gender (OR: 2.1; 95% C.I.: 1.3-3.4). overweight (0.5; 0.3-0.9), relevant postprandial fullness (1.8; 1.1-3.2) and relevant epigastric bloating (1.8; 1.1-2.9), but not the presence of organic diseases, were associated with delayed emptying. Female gender (3.9; 1.3-11.9) and relevant postprandial fullness (4.1; 1.7-10.2) were associated with gastroparesis. CONCLUSIONS:(i) There is a high prevalence of delayed gastric emptying and gastroparesis in out-patients with upper gastrointestinal symptoms, which is not influenced by the presence of organic disease; (ii) female gender, low body weight, relevant fullness and bloating are associated with delayed emptying; female gender and relevant postprandial fullness predict gastroparesis.V. Stanghellinia, C. Tosetti, M. Horowitz, R. De Giorgio, G. Barbara, R. Cogliandro, L. Cogliandro , R. Corinaldes

Review article: Helicobacter pylori, mucosal inflammation and symptom perception - New insights into an old hypothesis

The role of Helicobacter pylori and the accompanying mucosal inflammatory response in functional dyspepsia is still undefined. Human and animal studies have clearly demonstrated a link between intestinal mucosal inflammation and changes in sensory-motor function. Growing clinical and basic evidence supports the concept that a similar paradigm may occur in H. pylori-related dyspepsia. The infection may both induce gastric dysmotility and trigger neuroplastic changes in the afferent neural pathways leading to visceral hyperalgesia. A reduction of central antinociceptive control systems may also play a pathophysiological role. H. pylori eradication has provided disappointing results in terms of improvement of symptoms. This may reflect the long-term recovery of neuroplastic changes occurring in the afferent nervous system or, alternatively, the incomplete resolution of gastritis and the persistent production of inflammatory mediators by resident cells in the muscularis externa. The identification of these mechanisms may provide a better understanding of the pathophysiology of H. pylori-related dyspepsia and prompt innovative therapeutic approaches