Durability and Decay of Treatment Benefit of Cognitive Behavioral Therapy for Irritable Bowel Syndrome: 12-Month Follow-Up.

BACKGROUND: There is a need for safe and effective IBS treatments that provide immediate and sustained improvement of IBS symptoms, particularly among more severe patients. The aim was to assess long-term clinical response of cognitive behavioral therapy (CBT) with reference to IBS education. METHODS: A total of 436 Rome III-diagnosed IBS patients (80% F, M age = 41 years) were randomized to: 4 session home-based CBT (minimal contact (MC-CBT)), 10 session clinic-based CBT (standard (S-CBT)), or 4 session IBS education (EDU). Follow-up occurred at 2 weeks and 3, 6, 9, and 12 months following treatment completion. Treatment response was based a priori on the Clinical Global Improvement Scale (global IBS symptom improvement) and IBS Symptom Severity Scale (IBS-SSS). RESULTS: Post-treatment CGI gains were generally maintained by MC-CBT patients at quarterly intervals through 12-month follow-up with negligible decay. For MC-CBT and S-CBT, 39 and 33% of respondents maintained treatment response at every follow-up assessment. The corresponding percent for EDU was 19%, which was significantly lower (p < 0.05) than for the CBT groups. On the IBS-SSS, therapeutic gains also showed a pattern of maintenance with trends towards increased efficacy over time in all conditions, with the mean unit reductions between baseline and follows-up being approximately -76 at immediate and approximately -94 at 12 months (-50 = clinically significant). CONCLUSIONS: For treatment-refractory IBS patients, home- and clinic-based CBT resulted in substantial and enduring relief of multiple IBS symptoms that generally extended to 12-month post treatment.

Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome.

BACKGROUND & AIMS: There is an urgent need for safe treatments for irritable bowel syndrome (IBS) that relieve treatment-refractory symptoms and their societal and economic burden. Cognitive behavior therapy (CBT) is an effective treatment that has not been broadly adopted into routine clinical practice. We performed a randomized controlled trial to assess clinical responses to home-based CBT compared with clinic-based CBT and patient education. METHODS: We performed a prospective study of 436 patients with IBS, based on Rome III criteria, at 2 tertiary centers from August 23, 2010, through October 21, 2016. Subjects (41.4 ± 14.8 years old; 80% women) were randomly assigned to groups that received the following: standard-CBT (S-CBT, n = 146, comprising 10 weekly, 60-minute sessions that emphasized the provision of information about brain-gut interactions; self-monitoring of symptoms, their triggers, and consequences; muscle relaxation; worry control; flexible problem solving; and relapse prevention training), or 4 sessions of primarily home-based CBT requiring minimal therapist contact (MC-CBT, n = 145), in which patients received home-study materials covering the same procedures as S-CBT), or 4 sessions of IBS education (EDU, n = 145) that provided support and information about IBS and the role of lifestyle factors such as stress, diet, and exercise. The primary outcome was global improvement of IBS symptoms, based on the IBS-version of the Clinical Global Impressions-Improvement Scale. Ratings were performed by patients and board-certified gastroenterologists blinded to treatment allocation. Efficacy data were collected 2 weeks, 3 months, and 6 months after treatment completion. RESULTS: A higher proportion of patients receiving MC-CBT reported moderate to substantial improvement in gastrointestinal symptoms 2 weeks after treatment (61.0% based on ratings by patients and 55.7% based on ratings by gastroenterologists) than those receiving EDU (43.5% based on ratings patients and 40.4% based on ratings by gastroenterologists) (P < .05). Gastrointestinal symptom improvement, rated by gastroenterologists, 6 months after the end of treatment also differed significantly between the MC-CBT (58.4%) and EDU groups (44.8%) (P = .05). Formal equivalence testing applied across multiple contrasts indicated that MC-CBT is at least as effective as S-CBT in improving IBS symptoms. Patients tended to be more satisfied with CBT vs EDU (P < .05) based on immediate posttreatment responses to the Client Satisfaction Questionnaire. Symptom improvement was not significantly related to concomitant use of medications. CONCLUSIONS: In a randomized controlled trial, we found that a primarily home-based version of CBT produced significant and sustained gastrointestinal symptom improvement for patients with IBS compared with education. Clinicaltrials.gov no.: NCT00738920.

(Can't Get No) Patient Satisfaction: The Predictive Power of Demographic, GI, and Psychological Factors in IBS Patients.

GOALS: The goal of this study is to assess: (1) the relative contribution of patient factors to satisfaction ratings in irritable bowel syndrome (IBS) patients and (2) the relationship between patient satisfaction (PS) and the number of diagnostic tests patients underwent prior to receiving IBS diagnosis. BACKGROUND: Although PS is regarded as an important indicator of quality of care, little is known about its determinants. STUDY: A total of 448 Rome III-diagnosed patients (M age=41 y; 79% F), whose GI symptoms were at least moderate in severity completed patient-reported outcome measures as part of pretreatment evaluation of an NIH-funded clinical trial. PS was measured with the 11-point Hospital Consumer Assessment of Healthcare Providers and Systems global rating scale modified to assess for IBS treatments. A series of multiple regression analyses were conducted for demographic, IBS-specific, general physical health, and psychological predictors before running a final model of significant predictors from each domain. RESULTS: The final regression model was significant, F6,419=6.34, P<0.001, R=0.08, with race, insurance, number of diagnostic tests, and lower neuroticism predicting PS. Medical tests were rendered nonsignificant when history of seeking care from a gastroenterologist was introduced into the equation. CONCLUSIONS: Contrary to hypotheses, neither the IBS symptom severity nor quality of life impairment predicted PS. Patient factors such as a neurotic personality style and sociodemographic profile had a significant but modest impact on PS. Pattern of regression analyses suggests that patients may turn to their gastroenterologist for testing for reassurance, which may in the long-term fuel demand for more testing.

Detection of drug effects on gastric emptying and contractility using a wireless motility capsule.

BACKGROUND: A wireless motility capsule is a new method for ambulatory assessment of transit times and motility throughout the gastrointestinal tract. The objective of this study was to evaluate the ability of a wireless motility capsule to detect drug effects on gastric emptying time (GET) and gastric contractility. METHODS: 15 healthy adults were administered in random order saline, erythromycin IV 150 mg, or morphine IV 0.05 mg/kg BW. Subjects ate a standard meal after each infusion, and subsequently ingested the motility capsule. Data were recorded for 8 hours, and the results were analyzed using the manufacturer's software. RESULTS: GET was significantly faster after erythromycin than either saline or morphine. Morphine tended to delay emptying of the capsule compared to saline. There was a trend toward a greater frequency of gastric contractions with erythromycin and a reduced frequency of gastric contractions with morphine that did not reach statistical significance. CONCLUSIONS: A wireless motility capsule successfully detected acceleration of gastric emptying induced by erythromycin, and retardation of gastric motility caused by morphine. These results indicate that a wireless motility capsule is a promising technique to assess pharmacologic effects on gastric transit and contractility and aid in development of drugs for gastric motor disorders.

Negative aspects of close relationships are more strongly associated than supportive personal relationships with illness burden of irritable bowel syndrome.

OBJECTIVE: This study assessed the relative magnitude of associations between IBS outcomes and different aspects of social relationships (social support, negative interactions). METHOD: Subjects included 235 Rome III diagnosed IBS patients (M age=41yrs, F=78%) without comorbid GI disease. Subjects completed a testing battery that included the Interpersonal Support Evaluation List (Social Support or SS), Negative Interaction (NI) Scale, IBS Symptom Severity Scale (IBS-SSS), IBS-QOL, BSI Depression, STAI Trait Anxiety, SOMS-7 (somatization), Perceived Stress Scale, and a medical comorbidity checklist. RESULTS: After controlling for demographic variables, both SS and NI were significantly correlated with all of the clinical variables (SS r's=.20 to .36; NI r's=.17 to .53, respectively; ps<.05) save for IBS symptom severity (IBS-SSS). NI, but not SS, was positively correlated with IBS-SSS. After performing r-to-z transformations on the correlation coefficients and then comparing z-scores, the correlation between perceived stress, and NI was significantly stronger than with SS. There was no significant difference between the strength of correlations between NI and SS for depression, somatization, trait anxiety, and IBSQOL. A hierarchical linear regression identified both SS and NI as significant predictors of IBS-QOL. CONCLUSIONS: Different aspects of social relationships - support and negative interactions - are associated with multiple aspects of IBS experience (e.g. stress, QOL impairment). Negative social relationships marked by conflict and adverse exchanges are more consistently and strongly related to IBS outcomes than social support.

Type, rather than number, of mental and physical comorbidities increases the severity of symptoms in patients with irritable bowel syndrome.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) has significant mental and physical comorbidities. However, little is known about the day-to-day burden these comorbidities place on quality of life (QOL), physical and mental function, distress, and symptoms of patients. METHODS: We collected cross-sectional data from 175 patients with IBS, which was diagnosed on the basis of Rome III criteria (median age, 41 years; 78% women), who were referred to 2 specialty care clinics. Patients completed psychiatric interviews, a physical comorbidity checklist, the IBS Symptom Severity Scale, the IBS-QOL instrument, the Brief Symptom Inventory, the abdominal pain intensity scale, and the Short Form-12 Health Survey. RESULTS: Patients with IBS reported an average of 5 comorbidities (1 mental, 4 physical). Subjects with more comorbidities reported worse QOL after adjusting for confounding variables. Multiple linear regression analyses indicated that comorbidity type was more consistently and strongly associated with illness burden indicators than disease counts. Of 10,296 possible physical-mental comorbidity pairs, 6 of the 10 most frequent dyads involved specific conditions (generalized anxiety, depression, back pain, agoraphobia, tension headache, and insomnia). These combinations were consistently associated with greater illness and symptom burdens (QOL, mental and physical function, distress, more severe symptoms of IBS, and pain). CONCLUSIONS: Comorbidities are common among patients with IBS. They are associated with distress and reduced QOL. Specific comorbidities are associated with more severe symptoms of IBS.

Development of the nephrotic syndrome during treatment of Crohn's disease with adalimumab.

We report a patient with Crohn's disease who presented with renal insufficiency and the nephrotic syndrome after initiating therapy with adalimumab. Renal biopsy showed stages 2 to 3 membranous glomerulonephritis, and immunostaining showed glomerular deposition of immunoglobulin G and C3. The patient's serum creatinine decreased after discontinuation of adalimumab, and treatment with prednisone and mycophenolic acid reversed his proteinuria. The pathogenesis of glomerular disease induced by antitumor necrosis factor antibodies is uncertain, and the potential roles of the generation of autoantibodies, development of antiadalimumab antibodies, and the interaction of adalimumab with glomerular tumor necrosis factor are discussed.

Outcomes of percutaneous endoscopic gastrostomy tube placement using a T-fastener gastropexy device in head and neck and esophageal cancer patients.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tube placement by the pull technique in head, neck, and esophageal cancer patients has a high complication rate, particularly in infections, and a small risk of tumor implantation. The T-fastener gastropexy technique uses a transabdominal approach to place the PEG device. OBJECTIVES: The objective of this study was to review the clinical outcomes and complications related to endoscopic PEG placement with the T-fastener gastropexy technique in patients with head, neck, and esophageal cancers. METHODS: This study was a retrospective review of all patients with head, neck, and esophageal cancers with PEG placement from January 1998 to June 2008. Clinical data including patient's age, gender, type and stage of cancer, date of PEG placement and removal, and reason for PEG removal was recorded. RESULTS: The study group consisted of a total of 356 patients of which 244 were male and 112 were female with a mean age of 63.3 years. There were 276 patients with head and neck cancer, 75 patients with esophageal cancer, and 5 with gastro-esophageal junction cancer. Staging data was available for 326 patients of which 56 (17.1%) had early stage disease (stage 1 and 2) and 270 patients (82.9%) had late stage (3 and 4) disease. None of these patients received antibiotic prophylaxis prior to PEG placement. Cellulitis around the PEG site occurred in 8.4% of cases and an abscess in 3.7% of cases. Only 4 (1.2%) infectious complications were within the first 30 days of PEG placement, and there were no intraoperative deaths or cases of tumor implantation. CONCLUSIONS: In the authors' experience, the T-fastener gastropexy technique for PEG placement in head, neck, and esophageal cancer patients carried a low overall complication rate and compared favorably with the results of pull method reported in the literature.

Clinical outcomes of using a conservative approach of late esophageal stent placement in palliation of malignant dysphagia.

BACKGROUND: Esophageal stents have been used as first-line treatment for palliation of malignant dysphagia, but this is associated with significant complications. The present study evaluated clinical outcomes and survival in patients with malignant dysphagia with esophageal stent placement who did not respond to prior chemoradiation or endoscopic modalities. PATIENTS AND METHODS: Patients with esophageal cancer, who had esophageal stents, were retrospectively reviewed from the electronic medical records. The patient demographics, type of stent placed, dysphagia scores, stent-related complications, and survival were recorded. RESULTS: Thirty-five patients with esophageal cancer received a total of 41 stents. There were 25 males and 10 females with mean age of 69.8 years. Twenty-two patients had esophageal adenocarcinoma, ten patients had squamous cell carcinoma, and three had poorly differentiated tumor. Esophageal malignancy was early stage (I, II) in 10 patients and advanced (III, IV) in 24 patients. Three patients had upper esophageal involvement, eight patients had mid-esophageal involvement; distal esophageal malignancy was present in 24 patients with 10 patients having gastroesophageal junction involvement. Six patients presented with tracheoesophageal fistula. Nine patients had prior esophagectomy. Thirty-three patients had chemoradiation, and 32 patients had other endoscopic therapies previously. Twelve of the 35 (33%) patients developed stent-related complications; nine patients had dysphagia due to various causes; one patient each developed aspiration, intractable hiccups, and intractable vomiting after stent placement, respectively. Nine patients underwent a repeat esophagogastroduodenoscopy. Development of stent-related complications was not significantly associated with poor survival. CONCLUSIONS: The clinical outcomes for patients with esophageal stent placement for malignant dysphagia after chemoradiation and other endoscopic treatments is not worse than that reported in patients where esophageal stent placement was used as first-line treatment.

Do stool form and frequency correlate with whole-gut and colonic transit? Results from a multicenter study in constipated individuals and healthy controls.

OBJECTIVES: Despite a lack of supportive data, stool form and stool frequency are often used as clinical surrogates for gut transit in constipated patients. The aim of this study was to assess the correlation between stool characteristics (form and frequency) and gut transit in constipated and healthy adults. METHODS: A post hoc analysis was performed on 110 subjects (46 chronic constipation) from nine US sites recording stool form (Bristol Stool Scale) and frequency during simultaneous assessment of whole-gut and colonic transit by wireless motility capsule (WMC) and radio-opaque marker (ROM) tests. Stool form and frequency were correlated with transit times using Spearman's rank correlation. Accuracy of stool form in predicting delayed transit was assessed by receiver operating characteristic analysis. RESULTS: In the constipated adults (42 females, 4 males), moderate correlations were found between stool form and whole-gut transit measured by WMC (r=-0.61, P<0.0001) or ROM (-0.45, P=0.0016), as well as colonic transit measured by WMC (-0.62, P<0.0001). A Bristol stool form value <3 predicted delayed whole-gut transit with a sensitivity of 85% and specificity of 82% and delayed colonic transit with a sensitivity of 82% and specificity of 83%. No correlation between stool form and measured transit was found in healthy adults, regardless of gender. No correlation was found between stool frequency and measured transit in constipated or healthy adults. The correlation between stool frequency and measured transit remained poor in constipated adults with <3 bowel movements per week. CONCLUSIONS: Stool form predicts delayed vs. normal transit in adults. However, only a moderate correlation exists between stool form and measured whole-gut or colonic transit time in constipated adults. In contrast, stool frequency is a poor surrogate for transit, even in those with reduced stool frequency.

Heightened colon motor activity measured by a wireless capsule in patients with constipation: relation to colon transit and IBS.

Relationships of regional colonic motility to transit in health, constipation, and constipation-predominant irritable bowel syndrome (C-IBS) are poorly characterized. This study aimed to 1) characterize regional differences in colon pressure, 2) relate motor differences in constipation to colon transit, and 3) quantify the role of IBS in altered contractility with constipation. Colon pH and pressure were measured by wireless capsules in 53 healthy and 36 constipated subjects. Numbers of contractions >25 mmHg and areas under curves (AUC) were calculated for colon transit quartiles by time. Constipation was classified as normal transit (<59 h), moderate slow transit (STC) (59-100 h), and severe STC (>100 h). Twelve out of 36 constipated subjects had C-IBS; 24 had functional constipation. Numbers of contractions and AUCs increased from the first to the fourth quartile in health (P < 0.0001). Mean numbers of contractions in constipated subjects were similar to controls. Mean AUCs with normal transit (P = 0.01) and moderate STC (P = 0.004) but not severe STC (P = NS) were higher than healthy subjects. IBS was associated with greater mean numbers of contractions (P = 0.05) and AUCs (P = 0.0006) vs. controls independent of transit. Numbers of contractions increased from the first to fourth quartiles in moderate STC, C-IBS, and functional constipation; AUCs increased from the first to fourth quartiles in all groups (all P < 0.05). In conclusion, colon pressure activity is greater distally than proximally in health. Constipated patients with normal or moderately delayed transit show increased motor activity that is partly explained by IBS. These findings emphasize differential effects on transit and motility in different constipation subtypes.

Investigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation.

BACKGROUND & AIMS: Colonic transit time (CTT) traditionally is assessed with radiopaque markers (ROMs), which requires radiation and is hindered by lack of standardization and compliance. We assessed regional and CTT with the SmartPill (SmartPill Corporation, Buffalo, NY), a new wireless pH and pressure recording capsule, in constipated and healthy subjects and compared this with ROM. METHODS: Seventy-eight constipated (Rome II) and 87 healthy subjects ingested a 260-kcal meal, a ROM capsule, and the SmartPill. Subjects wore a data receiver and kept daily stool diaries for 5 days. SmartPill recordings assessed CTT, whole-gut transit time (WGTT), small-bowel transit time, and gastric emptying time. Abdominal radiographs on days 2 and 5 assessed ROM transit. Sensitivity/specificity and receiver operating characteristics (ROCs) of each technique and utility were compared. RESULTS: Gastric emptying time, CTT, and WGTT were slower (P < .01) in constipated subjects than controls. CTT was slower in women than men (P = .02). Day 2 and day 5 ROM transits were slower (P < .001) in constipated subjects. Correlation of the SmartPill CTT with ROMs expelled on day 2/day 5 was r = 0.74/r = 0.69 in constipation, and r = 0.70/r = 0.40 in controls, respectively. The diagnostic accuracy of the SmartPill CTT to predict constipation from ROC was 0.73, with a specificity of 0.95. These were comparable with those of day 5 ROM (ROC, 0.71; specificity, 0.95). CONCLUSIONS: The SmartPill is a novel ambulatory technique of assessing regional (gastric, small bowel, colonic) and WGTT without radiation. It reveals hitherto unrecognized gender differences and upper-gut dysfunction in constipation. It correlates well with ROM and offers a standardized method of discriminating normal from slow colonic transit.

Vitamin D's role in cell proliferation and differentiation.

Vitamin D has pleiotropic effects that go beyond its traditional role in calcium homeostasis. Hundreds of genes with vitamin D receptor response elements directly or indirectly influence cell cycling and proliferation, differentiation, and apoptosis. Vitamin D compounds also have effects on cell function that are nongenomic. The noncalcemic actions of vitamin D influence normal and pathological cell growth, carcinogenesis, immune function, and cardiovascular physiology. This review examines many of the various mechanisms by which vitamin D alters cellular growth and differentiation and explores cell-specific factors that influence responsiveness to vitamin D.

Differences in intragastric pH in diabetic vs. idiopathic gastroparesis: relation to degree of gastric retention.

Evidence suggests that distinct mechanisms underlie diabetic and idiopathic gastroparesis. Differences in gastric acid in gastroparesis of different etiologies and varying degrees of gastric stasis are uninvestigated. We tested the hypotheses that 1) gastric pH profiles show differential alteration in diabetic vs. idiopathic gastroparesis and 2) abnormal pH profiles relate to the severity of gastric stasis. Sixty-four healthy control subjects and 44 gastroparesis patients (20 diabetic, 24 idiopathic) swallowed wireless transmitting capsules and then consumed (99m)Tc-sulfur colloid-labeled meals for gastric scintigraphy. Gastric pH from the capsule was recorded every 5 s. Basal pH was higher in diabetic (3.64 +/- 0.41) vs. control subjects (1.90 +/- 0.18) and idiopathic subjects (2.41 +/- 0.42; P < 0.05). Meals evoked initial pH increases that were greater in diabetic (4.98 +/- 0.32) than idiopathic patients (3.89 +/- 0.39; P = 0.03) but not control subjects (4.48 +/- 0.14). pH nadirs prior to gastric capsule evacuation were higher in diabetic patients (1.50 +/- 0.23) than control subjects (0.58 +/- 0.11; P = 0.003). Four-hour gastric retention was similar in diabetic (18.3 +/- 0.5%) and idiopathic (19.4 +/- 0.5%) patients but higher than control subjects (2.2 +/- 0.5%; P < 0.001). Compared with control subjects, those with moderate-severe stasis (>20% retention at 4 h) had higher basal (3.91 +/- 0.55) and nadir pH (2.23 +/- 0.42) values (P < 0.05). In subgroup analyses, both diabetic and idiopathic patients with moderate-severe gastroparesis exhibited increased pH parameters vs. those with mild gastroparesis. In conclusion, diabetic patients with gastroparesis exhibit reduced gastric acid, an effect more pronounced in those with severely delayed gastric emptying. Idiopathic gastroparetic subjects exhibit nearly normal acid profiles, although those with severely delayed emptying show reduced acid vs. those with mild delays. Thus both etiology and degree of gastric stasis determine gastric acidity in gastroparesis.

Extended octreotide suppression test to determine hormone responsiveness of multiple type I gastric carcinoid tumors.

A 70-year-old man was found to have at least 12 type I gastric carcinoids and microcarcinoidosis. We performed an extended octreotide suppression test to determine if the tumors were gastrin-dependent and would likely regress after antrectomy. He was given an octreotide infusion at 12.5-25 mcg/h for 86 hr followed by depot octreotide 20 mg intramuscularly every four weeks for eight months. Fasting serum gastrin and chromogranin A levels were measured, and endoscopy with biopsies was performed before and after the infusion and at five months and eight months. Total RNA was extracted for quantitation of histidine decarboxylase mRNA using real-time PCR. Fasting serum gastrin decreased from 306 pg/ml pretreatment to 31 pg/ml at the end of infusion and 115 pg/ml at eight months. Chromogranin A decreased from four to six times the upper limit of normal to normal. Tissue histidine decarboxylase mRNA decreased 50-fold. At eight months, only a few diminutive nodules were present on endoscopy. These results demonstrated that the carcinoid tumors in this patient were under neuroendocrine control and were expected to respond to antrectomy.

Colonic squamous cell carcinoma in ulcerative colitis: Report of a case and review of the literature.

Squamous cell carcinoma (SCC) is a rare neoplasm in the colorectum. A case of SCC rising from an area of squamous metaplasia in the rectum is presented in a patient with long-standing ulcerative colitis and perianal warts. This is the first report in the literature describing the evolution of squamous metaplasia in the colonic mucosa into invasive carcinoma over time. Related literature on colorectal SCC and squamous metaplasia, and their relationships with inflammatory bowel disease and human papilloma virus, is reviewed.