Centrally Mediated Disorders of Gastrointestinal Pain.

Centrally Mediated Abdominal Pain Syndrome (CAPS), formerly known as Functional Abdominal Pain Syndrome, can be distinguished from other functional GI disorders by its strong central component and relative independence from motility disturbances. CAPS is a result of central sensitization with disinhibition of pain signals rather than increased peripheral afferent excitability. A newly described condition, Narcotic Bowel Syndrome (NBS)/Opioid-Induced GI Hyperalgesia, is characterized by the paradoxical development of or increases in abdominal pain associated with continuous or increasing dosages of opioids. Patients only have relief when opioids are withdrawn. We define both conditions in the context of epidemiology, pathophysiology, clinical evaluation and treatment, emphasizing the importance of a physician-patient relationship in all aspects of care.

End-stage renal disease is associated with worse outcomes in hospitalized patients with peptic ulcer bleeding.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk of peptic ulcer bleeding (PUB). To our knowledge, there are no population-based studies of the impact of ESRD on PUB. OBJECTIVE: To determine nationwide impact of ESRD on outcomes of hospitalized patients with PUB. DESIGN: Cross-sectional study. SETTING: Hospitals from a 2008 Nationwide Inpatient Sample. PATIENTS: We used the International Classification of Diseases, the 9th Revision, Clinical Modification codes to identify patients who had a primary discharge diagnosis of PUB. MAIN OUTCOME MEASUREMENT: In-hospital mortality, length of stay, and hospitalization charges. INTERVENTIONS: Comparison of PUB outcomes in patients with and without ESRD. RESULTS: Of a total of 102,525 discharged patients with PUB, 3272 had a diagnosis of both PUB and ESRD, whereas 99,253 had a diagnosis of PUB alone without ESRD. The mortality of ESRD patients with PUB was significantly higher than that of the control group without ESRD (4.8% vs 1.9%, P < .0001). On multivariate analysis, patients with PUB and ESRD had greater mortality than patients admitted to the hospital with PUB alone (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI], 1.3-3.4), were more likely to undergo surgery (aOR 1.4; 95% CI, 1.2-1.7), and had a longer hospital stay (aOR 2.1; 95% CI, 1.2-2.9). These patients also incurred higher hospitalization charges ($54,668 vs $32,869, P < .01) compared with patients with PUB alone. LIMITATIONS: Administrative data set. CONCLUSIONS: ESRD is associated with a significant health care burden in hospitalized patients with PUB. The presence of ESRD contributes to a higher mortality rate, longer hospital stay, and increased need for surgery.

What factors are associated with the difficult-to-sedate endoscopy patient?

BACKGROUND: Difficult sedation during endoscopy results in inadequate examinations and aborted procedures. We hypothesized that gender, alcohol abuse, physical/sexual abuse, and anxiety are predictors of difficult-to-sedate endoscopy patients. METHODS: This is a prospective cohort study. At the time of enrollment, subjects completed the following three validated questionnaires: state-trait anxiety inventory, self-report version of alcohol use disorder inventory, and Drossman questionnaire for physical/sexual abuse. Conscious sedation was administered for the endoscopic procedures at the discretion of the endoscopist and was graded in accordance with the Richmond agitation sedation scale (RASS). Subjects' perceptions of sedation were documented on a four-point Likert scale 24 h after their procedure. RESULTS: One-hundred and forty-three (79 %) of the 180 subjects enrolled completed the study. On the basis of the RASS score, 56 (39 %) subjects were found to be difficult to sedate of which only five were dissatisfied with their sedation experience. State (n = 39; p = 0.003) and trait (n = 41; p = 0.008) anxiety and chronic psychotropic use (p = 0.040) were associated with difficult sedation. No association was found between difficult sedation and gender (p = 0.77), alcohol abuse (p = 0.11), sexual abuse (p = 0.15), physical abuse (p = 0.72), chronic opioid use (p = 0.16), or benzodiazepines (BDZ) use (p = 0.10). CONCLUSION: Pre-procedural state or trait anxiety is associated with difficult sedation during endoscopy. In this study neither alcohol abuse nor chronic opiate/BDZ use was associated with difficult sedation.

Diagnostic approach to chronic constipation in adults.

Constipation is traditionally defined as three or fewer bowel movements per week. Risk factors for constipation include female sex, older age, inactivity, low caloric intake, low-fiber diet, low income, low educational level, and taking a large number of medications. Chronic constipation is classified as functional (primary) or secondary. Functional constipation can be divided into normal transit, slow transit, or outlet constipation. Possible causes of secondary chronic constipation include medication use, as well as medical conditions, such as hypothyroidism or irritable bowel syndrome. Frail older patients may present with nonspecific symptoms of constipation, such as delirium, anorexia, and functional decline. The evaluation of constipation includes a history and physical examination to rule out alarm signs and symptoms. These include evidence of bleeding, unintended weight loss, iron deficiency anemia, acute onset constipation in older patients, and rectal prolapse. Patients with one or more alarm signs or symptoms require prompt evaluation. Referral to a subspecialist for additional evaluation and diagnostic testing may be warranted.

Risk of adverse clinical outcomes with concomitant use of clopidogrel and proton pump inhibitors following percutaneous coronary intervention.

BACKGROUND: Recent studies have suggested that proton pump inhibitors (PPIs) attenuate the benefits of clopidogrel. The clinical relevance of this interaction in patients who have undergone percutaneous coronary intervention (PCI) is unknown. We hypothesized that post-PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used. AIMS: To determine whether post-PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used. METHODS: We reviewed the medical records of all the patients discharged on clopidogrel who underwent PCI from January 2003 to August 2004. The primary outcome studied was a major adverse cardiovascular event (MACE), which was defined as a composite of death, myocardial infarction, and target vessel failure. RESULTS: Of the 315 post-PCI patients who were discharged on clopidogrel, 72 were discharged on PPI. During a mean follow-up period of 50 months, patients discharged on concomitant clopidogrel-PPI therapy had a MACE rate of 56% (vs. 38% in the clopidogrel alone group) (P = 0.025) and had 95% excess risk of MACE. CONCLUSION: Concomitant use of clopidogrel and PPI in post-PCI patients is associated with a higher risk of MACE. This suggests that PPIs may attenuate clopidogrel's beneficial antiplatelet effect, which is crucial after PCI. Prospective randomized studies are warranted to provide definitive evidence for this interaction.

Fecal incontinence in an inpatient population: a not uncommon finding.

The prevalence of fecal incontinence (FI) in hospitalized patients was determined, as well as the frequency with which physicians query about FI. Using a standardized questionnaire, subjects admitted to general medicine services at three university hospitals were questioned about FI. Investigators also reviewed the subjects' charts to determine if presence or absence of FI was documented. One hundred ninety-nine patients were enrolled, and 46% (92/199) reported ongoing FI. Advanced age, looser stools, symptoms of fecal urgency, urinary incontinence, and history of forceps delivery were found to be potential predictors of FI. Only 6% (6/92) with FI had documentation of FI in the medical chart and only 3% (6/199) of the entire sample were queried about FI. Fecal incontinence is an extremely common condition in hospitalized patients. Physician history-taking is severely deficient in this area. Methods to improve FI detection in the hospitalized patient population need to be developed.

Carcinosarcoma of the colon: a rare cause of colovesical fistula.

Carcinosarcomas are relatively rare tumors composed of both carcinomatous and sarcomatous components. The most common sites involved by this tumor are the head and neck, respiratory tract, uterus, ovaries, and fallopian tubes. Within the gastrointestinal tract this tumor most often occurs in the esophagus, followed by the stomach. Carcinosarcomas are very aggressive tumors associated with a poor prognosis. The first case of carcinosarcoma of the colon was reported in 1986. The case reported here is the only one involving an associated colovesical fistula.

Isolated tuberculosis of the pancreas: a case report.

CONTEXT: Pancreatic tuberculosis is a rare entity. Only a few cases have been reported in the medical literature. We hereby describe a case of pancreatic tuberculosis in an immunocompromized individual. CASE REPORT: A fifty-year-old African-American gentleman with history of HIV non-compliant on anti-retroviral therapy presented with epigastric pain for five weeks duration. CT scan of abdomen showed large necrotic node on the posterior aspect of the head of pancreas and multiple cystic masses adjacent to the pancreas. Acid fast bacilli were found on staining of CT guided biopsy of the node. Cultures grew Mycobacterium tuberculosis. Anti-tubercular therapy was initiated and resulted in gradual resolution of symptoms. CONCLUSION: Pancreatic tuberculosis is rare and is frequently confused with pancreatic cancer on clinical presentation as well as on imaging studies. Since it is a curable disease, accurate diagnosis is paramount CT or ultrasound guided biopsy is cornerstone of diagnosis. Endoscopic ultrasound is now increasingly being used for obtaining tissue for diagnosis. Anti-tubercular therapy is curative in majority of the cases.

Pancreatic plasmacytoma presenting as variceal hemorrhage: life threatening complication of a rare entity.

CONTEXT: Pancreatic plasmacytoma is a rare entity and presents with features of mass lesion of pancreas. CASE REPORT: We present an interesting case of pancreatic plasmacytoma with life threatening gastrointestinal bleeding secondary to isolated gastric varices. CONCLUSION: This case highlights the importance of considering it in differential diagnosis of patients with anemia, recurrent pancreatitis or jaundice and isolated gastric varices, prompting a CT scan to evaluate for any pancreatic mass lesions.

Mirtazapine for Refractory Gastroparesis.

Gastroparesis is a chronic condition of delayed gastric emptying in the absence of mechanical outlet obstruction. We report a 47-year-old African American woman with diabetic gastroparesis who presented with intractable nausea, vomiting, and decreased oral intake with electrolyte disturbances. The patient's symptoms were difficult to control with antiemetic and conventional prokinetic agents, and she was started on mirtazapine 15 mg nightly. She experienced an almost complete symptom relief and was able to tolerate solid food within 24-48 hours. We highlight the role of mirtazapine, a 5-HT1a agonist, as an effective therapy for refractory gastroparesis.

Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use, health-related quality of life, safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP. METHODS: A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1 mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS). RESULTS: Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p = .0181) or for IBS-D (p = .0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported. CONCLUSIONS: Alosetron 1 mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP.

Cyclic vomiting and compulsive bathing with chronic cannabis abuse.

Cannabis is commonly recognized for its antiemetic properties. However, chronic cannabis use can lead to paroxysmal vomiting. In some patients this vomiting can take on a pattern identical to cyclic vomiting syndrome. Interestingly cyclic vomiting syndrome has been associated with compulsive bathing which patients report can relieve their intense feelings of nausea and lessen their vomiting intensity. We report a case of a patient with chronic cannabis use who developed symptoms similar to cyclic vomiting syndrome who also engaged in compulsive bathing behavior as observed by members of the medical and nursing staff. The patient reported that frequent hot showers would prevent him from vomiting and also relieve his concomitant abdominal pain. Previous hospitalizations at our hospital for the same complaint also noted similar showering behavior. During the hospital stay, the patient agreed to engage in a outpatient drug rehabilitation program which he subsequently completed. Abstinence from cannabis use caused the patients vomiting symptoms and abdominal pain to disappear completely. Likewise, his compulsive showering behavior also ceased. Other investigators have reported similar findings in patients with cyclic vomiting syndrome who initially used cannabis to treat their vomiting episodes but subsequently found that it contributed to their vomiting. Our patient has lead us to conclude that in patients seen for chronic severe vomiting and abdominal pain which has no obvious structural or chemical etiology and which is accompanied by compulsive showering and/or bathing behavior a diagnosis of cyclic vomiting syndrome with concomitant cannabis abuse needs to be considered.

Ischemic duodenal ulcer, an unusual presentation of sickle cell disease.

Sickle cell disease is caused by molecular abnormalities in the formation of hemoglobin, leading to pain crisis from recurrent vascular occlusion by sickled hemoglobin. Impaired flow in the microvasculature can lead to ischemia, tissue infarction and ulceration. Abdominal pain, a common complaint in sickle cell disease, can be due to an uncommon etiology, ischemic duodenal ulceration. This is due to primary mucosal infarction caused by sickling, leading to poor healing of infarcted areas. Prompt endoscopic and/or urgent surgical intervention should be considered, particularly if anticoagulation is an issue, as proton pump inhibitor use is ineffective in healing this type of ulcer.

[The Latin-American Consensus on Chronic Constipation]. / Consenso Latinoamericano de Estreñimiento Crónico.

The Latin-American Consensus on Chronic Constipation aimed to establish guidelines to improve the identification, diagnosis and treatment of this disorder in the region. Two coordinators and an honorary coordinator established the process and the topics to be discussed, based on a systematic review of the literature published in the previous 10 years, since 1995. Seventeen members participated with the support of their local gastroenterology societies. The members reviewed the different subjects based on the levels of evidence and grades of recommendation; the topics were then discussed in a plenary session. A written report was drafted and the coordinators prepared the final declarations to be submitted to a vote by all the members in October 2006. The consensus concluded that chronic constipation has an estimated prevalence of 5-21% in the region, with a female-to-male ratio of 3:1. Among individuals with constipation, 75% use some type of medication, with more than 50% using home remedies. A diagnosis based on Rome Criteria was recommended and diagnostic testing only in persons older than 50 years or with alarm symptoms. The use of barium enema as an initial investigation was recommended only in countries with a high prevalence of idiopathic megacolon or Chagas' disease. Recommendations on treatment included an increase in dietary fiber of up to 25-30 g/day (grade C). No evidence was found to recommend measures such as exercise, increased water intake, or frequent visits to the toilet. Fiber supplements such as Psyllium received a grade B and pharmacological treatments such as tegaserod and polyethylene glycol, both grade A. There was insufficient evidence to recommend lactulose, but the consensus did not disadvise its use when necessary. Complementary investigations such as colonic transit followed by anorectal manometry and defecography were only recommended to rule out colonic inertia and/or obstructive defecation in patients not responding to treatment. Biofeedback was recommended (grade B) for those with pelvic dyssynergia.

Activation of type-2 chloride channels: a novel therapeutic target for the treatment of chronic constipation.

Chronic constipation affects up to 27% of the population and negatively impacts health-related quality-of-life. Prescription medications targeting chronic constipation currently include polyethylene glycol, lactulose and tegaserod, a serotonin type 4 receptor partial agonist. The most recent addition is lubiprostone (Amitiza), a type-2 chloride channel (ClC-2) activator which is a member of a new class of compounds known as prostones. Lubiprostone is a bicyclic fatty acid that acts locally on ClC-2 channels located in the apical membrane of intestinal epithelial cells. This stimulation of chloride secretion induces the passive movement of sodium and water into the intestinal lumen, yielding a net increase in isotonic fluid, which results in improved bowel function. In double-blind, placebo-controlled clinical trials, lubiprostone increased the number of spontaneous bowel movements compared with placebo and was generally well tolerated. The predominant adverse effects were nausea and diarrhea. Lubiprostone represents a new therapeutic class of compounds for the treatment of chronic constipation and will be the focus of this review.

The use of antidepressants in functional gastrointestinal disorders: new uses for old drugs.

Since their introduction 50 years ago, antidepressants have been used in a wide variety of settings involving gastrointestinal (GI) disease. In the 1950s, antidepressants were shown to have some efficacy for the treatment of peptic ulcer disease. This is most likely due to their antihistaminic and anticholinergic effects. Since then, more efficacious and more disease-specific treatments have become available. In the last 20 years, antidepressants have been increasingly used for the treatment of functional gastrointestinal disorders such as irritable bowel syndrome, noncardiac chest pain, and other functional GI disorders. This article will review the rationale for the use of antidepressant drugs for the treatment of functional GI disorders. The role of psychiatric comorbidity in functional GI disorders, the impact of antidepressants on GI motility and visceral sensation, and the ability of these agents to produce improvements in the global well-being and overall quality of life will be reviewed. Finally, guidelines for prescribing and barriers to a patient's acceptance of these agents will be discussed.

Antidepressants in the treatment of irritable bowel syndrome and visceral pain syndromes.

Irritable bowel syndrome (IBS) is characterized by abdominal pain associated with disordered defecation, which may include urgency and altered stool frequency. Visceral pain syndromes, including IBS, may be effectively treated by a variety of therapies that modulate the interactions between the central and enteric nervous systems. Clinical observations and preliminary data suggest that antidepressants may be efficacious for the treatment of these syndromes. The tricyclic antidepressants (TCAs) have been utilized most extensively in this area, but there is a need for more rigorous efficacy data. Serotonin, an important neurotransmitter in both the central and enteric nervous systems, modifies both motility and sensation in the gut. Recognition of the importance of serotonin in digestive motility and sensation has sparked interest in the use of agents that modify serotonergic transmission in visceral pain syndromes. Pharmacological therapeutics that modulate the biological amines (serotonin, norepinephrine, dopamine and catecholamines) both peripherally and within the central nervous system may offer more effective therapies for these disorders. The selective serotonin reuptake inhibitors are commonly used in clinical practice, but more rigorous, controlled studies are needed to determine their effects beyond the treatment of psychiatric comorbidity. The newer generation antidepressants may provide additional insight into the pathophysiology of the brain-gut interactions and their relationship to functional bowel disorders, providing new therapeutic interventions.