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ABSTRACT: To formally study age of diagnosis of papillary thyroid cancer (PTC) in inflammatory bowel disease (IBD) patients and evaluate the prevalence of PTC in IBD patients compared to a control population.
We were interested in testing the hypothesis that patients with IBD are more likely to be diagnosed with PTC than a control population. A retrospective cohort analysis was performed using the University of Pennsylvania Health System's electronic database. Outpatients from 1998-2009 were included in the search, and patients in the cohort were selected based on ICD-9 codes. Inclusion criteria included the diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) and the concurrent diagnosis of thyroid cancer in comparison to a control population. Using these methods 912 patients with CD and 1774 with UC were compared to 1638 diverticulitis and 19 447 asthma controls. Statistics were performed using corrected chi-square analysis. The primary outcome for this study was the diagnosis of PTC. Approval to conduct this study was obtained by the Institutional Review Board at the University of Pennsylvania.
The mean age was 47.5 years (range: 18-102 years) and 66% patients were female. An analysis of variance model was used to compare the age of PTC diagnosis between the CD, UC, asthma and diverticulitis groups, and a statistically significant difference in age at PTC diagnosis was noted across all groups ( = 6.35, df = 3, = 0.0006). The age of PTC diagnosis in CD patients was statistically significantly lower than UC, asthma, and diverticulitis patients (average PTC diagnosis age for CD 25, UC 49, asthma 45, diverticulitis 63). After covarying for sex and age in 2009, the difference in age at PTC diagnosis remained statistically significant ( = 4.13, df = 3, = 0.0089). A total of 86 patients were diagnosed with PTC. Nine patients (0.5%) with UC were diagnosed with PTC. Patients with UC were not shown to be more likely to develop PTC [odds ratio (OR): 1.544, 95%CI 0.767-3.108] compared to asthma controls. Four patients (0.4%) with CD were diagnosed with PTC. Patients with CD were not shown to be more likely to develop PTC (OR: 1.334, 95%CI 0.485-3.672) compared to a control population with asthma. Nine patients (0.5%) with a history of diverticulitis were diagnosed with PTC. Patients with diverticulitis were not shown to be more likely to develop PTC (OR: 1.673, 95%CI 0.831-3.368) compared to asthma controls. Patients with CD or UC were not less likely to develop PTC compared to those with diverticulitis (CD OR: 0.80, 95%CI 0.25-2.60; UC OR: 0.92, 95%CI 0.37-2.33). None of the patients used immunosuppressant medications prior to the diagnosis of PTC (azathioprine, 6-mercaptopurine, and methotrexate).
There is a significant difference in age of diagnosis of PTC in patients with CD compared to patients with UC and the control populations studied.
World Journal of Gastroenterology 02/2013; 19(7):1079-84. · 2.47 Impact Factor
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ABSTRACT: BACKGROUND: The immunosuppressive potential of anti-tumor necrosis factor (TNF) in exacerbating chronic hepatitis C virus (HCV) infection has been a major concern. We aim to critically analyze the impact of anti-TNF on the course of chronic HCV infection in patients with concurrent inflammatory bowel disease (IBD) and HCV infection. MATERIALS AND METHODS: Patients with diagnosis of IBD and HCV were identified retrospectively through the University of Pennsylvania Health System electronic database. Data assessed included demographics, duration of IBD and HCV infection, HCV RNA levels, HCV genotype, liver histology, hepatic biochemical tests (HBT) and IBD disease activity index. RESULTS: A total of 4,274 IBD and 3,523 HCV patients were identified from 10/1998 to 05/2010. Thirty-seven patients had concurrent HCV infection and IBD, of which 23 patients were eligible (61 % CD; 39 % UC). Five patients (22 %) received anti-TNF therapy (infliximab). Two patients received pegylated interferon and ribavirin (both were non-responders). Overall, three patients had clinical remission and one patient had clinical response to infliximab. When compared to baseline, one patient had HBT improvement, three patients remained stable and one patient had HBT elevation, which was likely due to progressive liver disease in view of HIV co-infection. CONCLUSION: This represents the first critical analysis assessing the impact of anti-TNF therapy on the course of chronic HCV in IBD patients. Concurrent HCV infection in IBD patients is uncommon. Treatment of IBD with infliximab in HCV patients did not result in flares in hepatic biochemical tests while there was an improvement in the IBD disease activity score.
Digestive Diseases and Sciences 11/2012; · 2.12 Impact Factor
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ABSTRACT: Many clinical factors predict the aggressive course of CD. Younger age at initial diagnosis, the presence of perianal lesions, ileal involvement, smoking, and the need for therapy with corticosteroids are the major predictors of disabling disease or change of behavior to a more aggressive disease. On the other hand, treatment with azathioprine and biologic agents and colonic localization of disease are the major factors that are predictive of less aggressive CD course. The problem we face with determining the factors that increase the risk of disabling disease is that there is no standardized and consistent definition of disabling or aggressive disease. Only two studies analyzed predictors using the same definition of aggressive disease. Only Beaugerie and colleagues developed the score predictive of disabling disease based on three independent factors associated with disabling course that were present at the time of initial diagnosis of CD (requirement of corticosteroids, age less than 40 years, and presence of perianal disease). This score ranged from 0 to 3 points based on the presence of given parameters. The positive predictive value was 0.91 and 0.93 in patients having two or three risk factors, 0.61 for no factors present, and 0.67 for one factor present. In order to determine factors predictive of disabling CD there is a need to establish consistent definition of disabling disease with subsequent future studies on large group of patients to validate such definition and determine factors that may predict the aggressive course.
Gastroenterology clinics of North America 06/2012; 41(2):443-62. · 2.56 Impact Factor
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ABSTRACT: Crohn’s disease (CD) is a chronic inflammatory disorder characterized by focal, asymmetric, transmural inflammation of any
part of the luminal gastrointestinal tract of uncertain etiology and an unpredictable course. The available treatment options
include aminosalicylates, budesonide and systemic corticosteroids, antibiotics, immunomodulators,methotrexate and anti-TNF
agents. This review discusses recent developments in the treatment of CD and provides a comprehensive update on management
of patients with CD based on the data from randomized controlled trials. Pique
Key wordsCrohn’s disease–Mesalamine–Corticosteroids–Budesonide–Azathioprine–6-mercaptopurine–Anti-TNF antibodies–Infliximab–Adalimumab–Certolizumab pegol–Natalizumab
Current Gastroenterology Reports 04/2012; 13(5):465-474.
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Digestive Diseases and Sciences 03/2012; 57(6):1435-8. · 2.12 Impact Factor
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ABSTRACT: Crohn's disease (CD) is a chronic inflammatory disorder characterized by focal, asymmetric, transmural inflammation of any part of the luminal gastrointestinal tract of uncertain etiology and an unpredictable course. The available treatment options include aminosalicylates, budesonide and systemic corticosteroids, antibiotics, immunomodulators,methotrexate and anti-TNF agents. This review discusses recent developments in the treatment of CD and provides a comprehensive update on management of patients with CD based on the data from randomized controlled trials.
Current Gastroenterology Reports 07/2011; 13(5):465-74.
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ABSTRACT: The aim of this article is to review current evidence-based approaches to treatment of ulcerative colitis and Crohn's disease.
The primary goal of treatment is to induce and to maintain remission in a safe and efficacious fashion. The 5-aminosalicylic acid (5-ASA) agents and oral steroids remain the first-line approach for the treatment of ulcerative colitis and Crohn's disease. The 'step-up' approach includes the use of immunomodulators [azathioprine (AZA), or 6-mercaptopurine (6-MP)] and newer biologic agents (infliximab, adalimumab, and natalizumab). The 'step-down' approach can also be considered individually on the basis of the severity of Crohn's disease.
Current treatment regimens still involve medications with well known efficacy and safety profiles and progress to more potent treatments such as immunomodulators and biologic agents. Adverse events of potent treatment with biologics and immunomodulators have been recognized. In some cases, aggressive approaches with the use of more potent agents as first-line therapy has been proposed, but they are still not considered a routine approach.
Current opinion in gastroenterology 07/2011; 27(4):346-57. · 4.33 Impact Factor
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ABSTRACT: Conventional corticosteroids, such as prednisone, should be used as a therapy to induce remission in patients with mild to
moderately active ulcerative colitis with inadequate response or intolerance to 5-ASA, or in patients presenting with moderate
to severe UC. Patients with ulcerative proctitis may benefit from combined treatment with rectal enema formulations of beclomethasone
dipropionate and 5-ASA. Rectal formulations of topical budesonide might be a promising treatment in patients with left-side
colitis. Corticosteroids are not effective in maintaining remission in ulcerative colitis. Intravenous corticosteroids are
indicated in patients not responding to oral corticosteroids or in those with severe activity of disease. Crohn’s disease
Controlled ileal-release formulations of topical budesonide should be used in patients with mild to moderate ileocecal Crohn’s
disease. Conventional corticosteroids are recommended in patients with moderate to severe CD regardless of disease location
or in those with ileocecal CD with no response to budesonide. Corticosteroids are not recommended in patients presenting with
perianal fistulas. Systemic corticosteroids are not effective as maintenance therapy of CD. Budesonide 6 mg daily is effective
and safe in maintaining medically induced remission in CD but the duration of remission is limited only up to 6 months while
on therapy. Intravenous corticosteroids are indicated in patients not responding to oral corticosteroids or in those with
severe activity of disease.
KeywordsInflammatory bowel disease-Crohn’s disease-Ulcerative colitis-Corticosteroids-Controlled ileal release-Enema-Prednisone-Prednisolone-Budesonide-Hydrocortisone-Beclomethasone dipropionate-Adrenocorticotropic hormone
03/2011: pages 73-92;
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The American Journal of Gastroenterology 10/2010; 105(10):2299-301. · 7.28 Impact Factor
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ABSTRACT: Mesalamine has been the first-line of therapy in patients with inflammatory bowel disease (IBD) since the 1960s. This article serves as a review of the different 5-aminosalicylic acid compounds, release formulations, use and dosing in the treatment of IBD, in particular ulcerative colitis.
Gastroenterology clinics of North America 09/2010; 39(3):559-99. · 2.56 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and represents an international public health concern as one of the most deadly cancers worldwide. The main etiology of HCC is chronic infection with hepatitis B and hepatitis C viruses. However, there are other important factors that contribute to the international burden of HCC. Among these are obesity, diabetes, non-alcoholic steatohepatitis and dietary exposures. Emerging evidence suggests that the etiology of many cases of HCC is in fact multifactorial, encompassing infectious etiologies, comorbid conditions and environmental exposures. Clarification of relevant non-viral causes of HCC will aid in preventative efforts to curb the rising incidence of this disease.
World Journal of Gastroenterology 08/2010; 16(29):3603-15. · 2.47 Impact Factor
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ABSTRACT: Crohn's disease (CD) is an idiopathic chronic inflammatory disorder of the digestive tract, which is incurable. Present therapeutic guidelines follow a sequential step-up approach that focuses on treating acute disease or 'inducing clinical remission' and subsequently aims to 'maintain clinical response'. In view of the chronic relapsing-remitting disabling disease course, new treatment approaches have been sought with the ultimate end point of disease course modification and mucosal healing. A recent preliminary study from D'Haens et al. has provided evidence suggesting that reversing the treatment paradigm from a 'step-up' to a 'top-down' approach may positively alter the natural course of this illness. Their findings indicate that early use of biologic therapy, in combination with immunomodulators, resulted in remission occuring more rapidly than the conventional 'step-up' treatment, with a longer time period to relapse, a decreased need for treatment with corticosteroids, a faster reduction in clinical symptoms, rapid decline in biochemical inflammatory markers (C-reactive protein) and improved endoscopic mucosal healing. These results, supported by previous studies on infliximab use, may hold a promising outcome of fewer stricturing complications, hospitalizations and surgeries for patients with CD. However, we need to better define the timing and candidates for the 'top-down' approach as we are still uncertain about the safety data and the long-term benefits if biologic agents are given as routine maintenance treatment, since most of the trials in CD have been short term, and approximately 30% of patients might have been overtreated. Future clinical trials will be crucial in answering these questions.
Expert review of gastroenterology & hepatology 04/2010; 4(2):167-80.
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ABSTRACT: The aim of this study was to assess and compare reflux frequency during prolonged multichannel intraluminal impedance and pH monitoring with special attention to the 2-hour postprandial interval after the major meal in patients on or off proton pump inhibitor (PPI) therapy.
We retrospectively analyzed multichannel intraluminal impedance and pH studies performed in 110 patients monitored on (n=70) or off PPI (n=40) to assess number of acid and nonacid reflux episodes per hour (RE/h).
Patients on PPI had significantly higher mean number of nonacid than acid RE/h during the total monitoring and 2-hour postprandially (pp). The mean number of nonacid RE/h was significantly higher during 2-hour pp than the total monitoring period (4.5 vs. 1.7). Patients off PPI had significantly higher mean number of acid than nonacid RE/h only during the total monitoring. The total number of RE/h was significantly higher during 2-hour pp than the total monitoring (5.1 vs. 2.3). Patients on PPI had significantly higher mean number of nonacid RE/h whereas patients off PPI had significantly higher mean number of acid RE/h throughout total monitoring and 2-hour pp. Number of RE/h was numerically (2.3 vs. 1.7) but not statistically greater off PPI than on PPI during total monitoring.
The total number of reflux episodes increases during the postprandial period irrespective of PPI therapy. Maximal rate of reflux episodes occurs during the postprandial period and is the same whether taking PPI or not.
Journal of clinical gastroenterology 05/2009; 43(9):816-20. · 2.21 Impact Factor
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ABSTRACT: There is limited information on medications with promotility effects on the esophagus. Studies in healthy volunteers have shown the potential role of the direct cholinergic agonist bethanechol and the serotonin receptor agonist buspirone in improving esophageal motility. It has been also shown that an acetylcholinesterase inhibitor, the short-acting drug edrophonium administered intravenously caused a greater increase in the esophageal contraction amplitude and duration than bethanechol. Edrophonium cannot be used as a promotility therapy owing to short duration of action and lack of oral administration. The use of another acetylcholinesterase inhibitor pyridostygmine with longer duration of action has not been studied. The aim of the study was to evaluate the effect of oral pyridostygmine (60 mg), buspirone (20 mg), and bethanechol (25 mg) on esophageal function assessed by combined multichannel intraluminal impedance-esophageal manometry.
Ten healthy volunteers were enrolled in a double blind randomized 3-period crossover study. Multichannel intraluminal impedance-esophageal manometry recorded esophageal pressures and bolus transit data during 6 liquid and 6 viscous swallows at baseline and 20, 40, and 60 minutes after the randomized oral administration of each drug.
Blinded analysis found significant increases in mean distal esophageal amplitude for liquid swallows from baseline to 60 minutes postdosing after pyridostygmine (87.6 vs. 118.0 mm Hg, P<0.001), buspirone (85.1 vs. 101.9 mm Hg, P<0.05), and bethanechol (87.6 vs. 118.8 mm Hg, P<0.01). Only pyridostygmine showed a significant decrease in mean distal onset velocity for liquid swallows at 60 minutes postdosing (3.4 vs. 2.3 cm/s, P<0.01) and increase in total bolus transit time at 60 minutes postdosing (7.9 vs. 9.3 s, P<0.05). All 3 agents significantly increased mean lower esophageal sphincter residual pressure for liquid swallows at 20, 40, and 60 minutes postdosing. Increased lower esophageal sphincter resting pressure was not significant. Similar results were found with viscous swallows.
Oral pyridostygmine, buspirone, and bethanechol enhance esophageal motility with pyridostygmine appearing to have the greatest effect. A potential effect on improving esophageal function and symptoms in patients requires further study.
Journal of clinical gastroenterology 12/2008; 43(3):253-60. · 2.21 Impact Factor
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ABSTRACT: Combined multichannel intraluminal impedance and manometry provides simultaneous evaluation of bolus transit and pressure changes within the esophagus. The aim of this study was to analyze and to compare distal esophageal impedance values between healthy volunteers and patients with normal and abnormal esophageal manometry.
We analyzed multichannel intraluminal impedance and manometry studies in 130 individuals (79 women, mean age 53 y, age range 17 to 85 y). There were 20 healthy volunteers and 20 patients with normal manometry. Patients with abnormal manometry were separated into nutcracker esophagus (n=20), distal esophageal spasm (n=20), ineffective esophageal motility (IEM, n=20), achalasia (n=20), and scleroderma esophagus (n=10). Manometric and MII parameters were assessed during 10 liquid and 10 viscous swallows. MII findings included esophageal impedance values and number of complete and incomplete bolus transits (CBTs). Esophageal impedance values from 2 distal impedance measuring segments (5 and 10-cm above lower esophageal sphincter) were assessed over a 2 to 3 seconds interval before the first liquid and the first viscous swallow, and 2 to 3 seconds after the tenth viscous swallow. The average values of esophageal impedance measured at 5 and 10-cm above lower esophageal sphincter (distal esophageal impedance) were calculated before liquid [distal baseline impedance (DBI)] and after 10 liquid swallows [distal liquid impedance (DLI)] and after 10 viscous swallows [distal viscous impedance (DVI)]. The correlations between DLI and DVI and number of CBT for liquid and viscous as well as distal esophageal amplitude (DEA) for liquid and viscous were also assessed using Pearson correlation coefficient.
Patients with achalasia or scleroderma esophagus had significantly lower DBI, DLI, and DVI than healthy volunteers, patients with normal manometry, nutcracker esophagus, or distal esophageal spasm. Patients with IEM had significantly lower DBI, DLI, and DVI than healthy volunteers or patients with nutcracker esophagus. Patients with IEM had significantly lower DLI and DVI than patients with normal manometry and significantly higher DVI than patients with achalasia. Overall, there was a significant correlation between DLI and CBTs during 10 liquid swallows (r=0.7, P<0.0001), DVI and CBTs during 10 viscous swallows (r=0.6, P<0.0001), DLI and DEA during 10 liquid swallows (r=0.5, P<0.0001), and DVI and DEA during 10 viscous swallows (r=0.5, P<0.0001).
Our results suggest that evaluation of distal esophageal impedance may assist in recognition and diagnosis of esophageal motility abnormalities.
Journal of clinical gastroenterology 09/2008; 42(7):776-81. · 2.21 Impact Factor
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ABSTRACT: Noninvasive approaches in the diagnosis and monitoring of fibrosis are still evolving. Transient elastography is an inexpensive, rapid, and relatively accurate form of noninvasive monitoring, especially in severe fibrosis It is a nascent technology, however, and there is no clear indication that elastography is better than biopsy for less severe fibrosis. With improved resolution and longer term data, it may become a vital supplement. The combined use of transient elastography and biochemical markers seems to be the most promising noninvasive technique.
Clinics in Liver Disease 09/2008; 12(3):557-71, viii. · 3.18 Impact Factor
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ABSTRACT: Primary liver cancer is the sixth most common cancer in the world and the third most common cause of death attributable to cancer. Most primary liver cancers are hepatocellular carcinoma (HCC), accounting for 85% to 90% of cases. There is a trend of growing incidence of HCC in the United States. One of the most important risk factors for developing HCC is chronic hepatitis C virus (HCV) infection. Although several studies suggested the preventive effect of interferon from developing HCC in HCV-infected individuals, these findings need to be validated in large prospective and randomized trials.
Clinics in Liver Disease 09/2008; 12(3):661-74, x. · 3.18 Impact Factor
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ABSTRACT: Ineffective esophageal motility (IEM) has been defined by the presence of > or = 30% liquid swallows with contraction amplitude < 30 mmHg (ineffective swallows) in the distal esophagus ("old" IEM). A recent study with combined multichannel intraluminal impedance and manometry (MII-EM) raised the question whether the manometric diagnosis of IEM should be based on a new definition: > or = 50% ineffective liquid swallows ("new" IEM). The aim of this study was to evaluate the association between the number of ineffective liquid swallows and symptoms and bolus transit in patients with "new" or "old" IEM who underwent MII-EM studies using 10 liquid and 10 viscous swallows.
There were 150 patients with "old" IEM included in the study. The patients diagnosed with "old" IEM (N = 150) (group A) were compared with those who retained a manometric diagnosis of IEM by the new definition (N = 101) (group B). The patients who did not retain their manometric diagnosis of IEM by the new definition (N = 49) (group C) were compared with group B. IEM was characterized as mild (normal bolus transit for both liquid and viscous swallows), moderate (abnormal bolus transit either for liquid or viscous swallows), or severe (abnormal bolus transit for both liquid and viscous swallows).
There was no statistical difference in frequency of mild, moderate, or severe IEM and frequency of symptoms between group A and B. Group C had a significantly higher frequency of mild IEM and significantly lower frequency of severe IEM than group B. Heartburn (25.7%vs 10.2%, P= 0.03) and dysphagia (24.8%vs 12.3%, P= 0.08) showed a trend towards a greater frequency in group B than in group C.
Our study indicates that IEM with > or = 50% ineffective liquid swallows is frequently associated with bolus transit abnormalities and esophageal symptoms. Our results underscore the rationale for using the new definition of IEM.
The American Journal of Gastroenterology 03/2008; 103(3):699-704. · 7.28 Impact Factor
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ABSTRACT: Esophageal function testing with combined multichannel intraluminal impedance and manometry (MII-EM) is performed using ten 5-ml liquid and viscous swallows. Diagnosis of bolus transit abnormalities identified by impedance is based on both liquid and viscous swallows. Manometric diagnosis is based solely on liquid swallows. The aim of this study was to establish the normal values for manometry performed with a viscous bolus.
MII-EM studies performed in 80 healthy volunteers were analyzed. The analyzed manometric parameters included contraction amplitude and duration, distal onset velocity and lower esophageal sphincter (LES) residual pressure.
Mean distal esophageal amplitude (DEA) (mmHg) for liquid swallows was 104 (+/-44) and for viscous swallows 102 (+/-51). Viscous versus liquid swallows were characterized by higher contraction amplitudes at 10 cm above the LES, slower distal onset velocities and higher LES residual pressures. Duration of contractions was similar between liquid and viscous swallows. Upper normal limits for viscous swallows were: 204 mmHg for DEA (mean+/-2 SDs); 6 ineffective and 1 simultaneous swallows and 11.7 mmHg for LES residual pressure (95th percentile).
Based on our results, the following values should be considered normal for manometry performed with viscous swallows: <or= 60% ineffective contractions, <or= 10% simultaneous contractions and DEA <204 mmHg, LES residual pressure <or= 11.7 mmHg.
Scandinavian Journal of Gastroenterology 02/2008; 43(2):155-60. · 2.02 Impact Factor
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ABSTRACT: Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer. It was widely believed that dysplastic lesions are invisible on colonoscopy and can only be detected by random biopsies, as 95% of dysplastic lesions occur in flat colonic mucosa indistinct from surrounding tissue. The aim of this study was to determine whether dysplasia is visible during routine surveillance colonoscopy by evaluating only patients who had dysplasia without overt carcinoma.
The medical records, endoscopy and pathology databases were systematically reviewed between 1997 and 2004 at the University of Pennsylvania Health System. Patients with inflammatory bowel disease and dysplasia were identified and their medical charts reviewed.
Of the 113 patients with colonic dysplasia confirmed by pathology at our center, 102 (90%) had UC. Forty-nine of the 102 (48%) patients with UC underwent colonoscopic evaluation prior to dysplasia detection. This group was selected as our study cohort. Overall, 72 macroscopic abnormalities were detected at 49 colonoscopies, including 55 polypoid lesions, 12 areas of ulceration, 3 areas of nodularity, 1 irregular hemicircumferential lesion and 1 area of stricture. Overall, 58 dysplastic sites were detected; 51 were macroscopically visible (87.9%) and 7 were macroscopically invisible (12.1%).
Most of the dysplasia in UC is endoscopically visible, but further prospective evaluation of a large number of patients is needed to validate the current observations. Our findings have the potential to modify current recommendations for surveillance biopsies in UC if validated by prospective studies.
Scandinavian journal of gastroenterology 02/2008; 43(6):698-703. · 2.08 Impact Factor
