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Chiarello MM, Pepe G, Fico V, Bianchi V, Tropeano G, Altieri G, Brisinda G. Therapeutic strategies in Crohn's disease in an emergency surgical setting. World J Gastroenterol 2022; 28:1902-1921. [PMID: 35664965 PMCID: PMC9150057 DOI: 10.3748/wjg.v28.i18.1902] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/28/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Crohn's disease (CD) remains a chronic, incurable disorder that presents unique challenges to the surgeon. Multiple factors must be considered to allow development of an appropriate treatment plan. Medical therapy often precedes or complements the surgical management. The indications for operative management of CD include acute and chronic disease complications and failed medical therapy. Elective surgery comes into play when patients are refractory to medical treatment if they have an obstructive phenotype. Toxic colitis, acute obstruction, perforation, acute abscess, or massive hemorrhage represent indications for emergency surgery. These patients are generally in critical conditions and present with intra-abdominal sepsis and a preoperative status of immunosuppression and malnutrition that exposes them to a higher risk of complications and mortality. A multidisciplinary team including surgeons, gastroenterologists, radiologists, nutritional support services, and enterostomal therapists are required for optimal patient care and decision making. Management of each emergency should be individualized based on patient age, disease type and duration, and patient goals of care. Moreover, the recurrent nature of disease mandates that we continue searching for innovative medical therapies and operative techniques that reduce the need to repeat surgical operations. In this review, we aimed to discuss the acute complications of CD and their treatment.
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Affiliation(s)
- Maria Michela Chiarello
- Department of Surgery, San Giovanni in Fiore Hospital, Azienda Sanitaria Provinciale di Cosenza, Cosenza 87100, Italy
| | - Gilda Pepe
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Valeria Fico
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Valentina Bianchi
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Giuseppe Tropeano
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Gaia Altieri
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Giuseppe Brisinda
- Department of Surgery, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Medical and Surgical Science, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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2
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Dotimas J, Das M, Martin D. Cutaneous T-cell lymphoma in the setting of anti-tumor necrosis factor and immunomodulator therapy: A case report and literature review. SAGE Open Med Case Rep 2020; 8:2050313X20937223. [PMID: 32655868 PMCID: PMC7328350 DOI: 10.1177/2050313x20937223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 05/31/2020] [Indexed: 01/23/2023] Open
Abstract
Immunosuppressive therapy is well recognized as increasing the risk of lymphoma. Mycosis fungoides is a rare cutaneous form of T-cell lymphoma with a largely unknown etiology and not typically associated with immunosuppression. In this article, we describe our encounter with a 24-year-old male with Crohn’s disease in remission on immunotherapy, specifically dual therapy with azathioprine and infliximab, presenting with a facial rash found to be consistent with mycosis fungoides on biopsy. The patient’s rash resolved with treatment of topical steroids. In addition, the decision was made to discontinue his azathioprine to minimize his risks of developing future malignancies.
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Affiliation(s)
- James Dotimas
- The University of Illinois College of Medicine at Peoria, Peoria, IL, USA
| | - Manjusha Das
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The University of Illinois College of Medicine at Peoria, Peoria, IL, USA
| | - Daniel Martin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The University of Illinois College of Medicine at Peoria, Peoria, IL, USA
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3
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Obando C, Ding Z, Muser E, Vaidya N, Qiang W, Sun X, Wang H, Mallampati R, Xie L. Persistence, Dose Titration, and Health Care Resource Utilization Among Crohn's Disease Patients Treated With Ustekinumab: A Real-World Analysis in the United States. Adv Ther 2020; 37:2127-2143. [PMID: 32193810 PMCID: PMC7467496 DOI: 10.1007/s12325-020-01276-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. This real-world study evaluated persistence, dose titration, health care resource utilization (HCRU) and associated costs, and medication use among CD patients treated with ustekinumab (UST) in several pooled US commercial database populations. METHODS CD patients aged ≥ 18 years with medical or pharmacy claims for UST were selected from pooled data from 3 large, national commercial databases. The first observed medical or pharmacy claim for UST was the index date. Patients were required to have had ≥ 1 medical claim with a CD diagnosis during the 12 months prior to the index date and continuous health plan enrollment for a minimum of 12 months prior to and 12 months after the index date. Comparisons of outcomes during the baseline and follow-up periods were conducted using inferential statistical tests. RESULTS A total of 214 eligible UST patients were selected. The majority (74.8%) were biologic experienced (mean age: 41 years), and 83.6% remained treatment persistent during the 12-month post-index period. Among discontinuers, 25.7% restarted UST, and 8.6% switched from UST in the 12-month observation period. The mean treatment duration was 329 days. Most patients (77%) used the recommended UST dose, as defined as being within a 20% dose variation from label (90 mg/8 weeks ± 20%), 17.9% experienced dose escalation, and 5.1% experienced dose reduction. Post-index immunomodulator and corticosteroid use reduced by 20% and 28%, respectively, as compared with pre-index use among CD patients using UST. Annual all-cause ER visits and inpatient stays decreased by 20.5% and 30.3%, respectively, with similar downward trends for annual CD-related HCRU. CONCLUSIONS The majority of CD patients prescribed UST were biologic experienced, and persistence was high over the 1-year follow-up. UST treatment initiation was associated with reductions in ER visits, inpatient stays, and steroid and other medication use.
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Affiliation(s)
- Camilo Obando
- Real World Value & Evidence, Janssen Scientific Affairs LLC, Horsham, PA, USA
| | - Zhijie Ding
- Real World Value & Evidence, Janssen Scientific Affairs LLC, Horsham, PA, USA
| | - Erik Muser
- Real World Value & Evidence, Janssen Scientific Affairs LLC, Horsham, PA, USA.
| | - Neel Vaidya
- Health Economics and Outcomes Research, STATinMED Research, Ann Arbor, MI, USA
| | - Wenqin Qiang
- Health Economics and Outcomes Research, STATinMED Research, Ann Arbor, MI, USA
| | - Xiaoxi Sun
- Health Economics and Outcomes Research, STATinMED Research, Ann Arbor, MI, USA
| | - Huiqi Wang
- Health Economics and Outcomes Research, STATinMED Research, Ann Arbor, MI, USA
| | - Rajesh Mallampati
- Health Economics and Outcomes Research, STATinMED Research, Ann Arbor, MI, USA
| | - Lin Xie
- Health Economics and Outcomes Research, STATinMED Research, Ann Arbor, MI, USA
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4
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Estruch JJ, Barken D, Bennett N, Krawiec DK, Ogilvie GK, Powers BE, Polansky BJ, Sueda MT. Evaluation of novel serological markers and autoantibodies in dogs with inflammatory bowel disease. J Vet Intern Med 2020; 34:1177-1186. [PMID: 32282988 PMCID: PMC7255684 DOI: 10.1111/jvim.15761] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 03/13/2020] [Indexed: 12/13/2022] Open
Abstract
Background The use of serological markers to diagnose inflammatory bowel disease (IBD) in humans is well‐established. Because of the frequency of IBD in dogs and resources required for its diagnosis with current methods, new approaches are desired. Objective The goal is to evaluate novel serologic markers to differentiate clinical cohorts in dogs with gastrointestinal (GI) disease and assess their potential to develop a serum‐based IBD diagnostic test. Animals Seventy dogs diagnosed with biopsy‐confirmed IBD, 23 dogs with non‐IBD predominantly acute GI diseases, and 58 normal dogs. Methods Prospective control study. ELISA methods were developed to detect autoantibodies to polymorphonuclear leukocytes (APMNA) and calprotectin (ACNA), antibodies against gliadins (AGA), microbial outer membrane porin C (ACA), and flagellins (AFA) isolated from diseased dogs based on clinical and histopathological scoring. Results IBD dogs displayed a 39%‐76% prevalence of seropositivity against selected serologic markers that markedly decreased to 0%‐13% in non‐IBD and normal dogs. ROC analysis showed statistical significance in differentiating the cohorts, with seropositivity against OmpC being the highest single performance marker. The combination of markers such as OmpC and APMNA reached specificities of 93%‐99% and 79%‐98% and sensitivities of 76%‐97% and 66%‐86% when comparing IBD versus normal cohorts and non‐IBD cohorts, respectively. Conclusion and Clinical Importance Seropositivity of canine immunoglobulins A against selected serologic markers in dogs appears promising in the detection and differentiation of IBD versus other acute GI conditions. Among them, antibody reactivity to Escherichia coli OmpC and canine autoantibodies against polymorphonuclear leukocytes displayed the highest single marker discriminating performance.
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Affiliation(s)
- Juan J Estruch
- Vetica Labs, Inc., 3525 Del Mar Heights Rd. Suite 106, San Diego, California, United States
| | - Derren Barken
- BaseChange Bioinformatics, 7465 Mission Gorge Road Suite #120, San Diego, California, United States
| | - Nicole Bennett
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
| | - Donald K Krawiec
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
| | - Gregory K Ogilvie
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
| | - Barbara E Powers
- CSU, Diagnostic Laboratories, 300 West Drake, Fort Collins, Colorado, United States
| | - Benjamin J Polansky
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
| | - Michael T Sueda
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
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5
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Gwon Y, Mo M, Chen MH, Chi Z, Li J, Xia AH, Ibrahim JG. Network meta-regression for ordinal outcomes: Applications in comparing Crohn's disease treatments. Stat Med 2020; 39:10.1002/sim.8518. [PMID: 32166784 PMCID: PMC7727029 DOI: 10.1002/sim.8518] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 02/08/2020] [Accepted: 02/14/2020] [Indexed: 12/22/2022]
Abstract
Crohn's disease (CD) is a life-long condition associated with recurrent relapses characterized by abdominal pain, weight loss, anemia, and persistent diarrhea. In the US, there are approximately 780 000 CD patients and 33 000 new cases added each year. In this article, we propose a new network meta-regression approach for modeling ordinal outcomes in order to assess the efficacy of treatments for CD. Specifically, we develop regression models based on aggregate covariates for the underlying cut points of the ordinal outcomes as well as for the variances of the random effects to capture heterogeneity across trials. Our proposed models are particularly useful for indirect comparisons of multiple treatments that have not been compared head-to-head within the network meta-analysis framework. Moreover, we introduce Pearson residuals and construct an invariant test statistic to evaluate goodness-of-fit in the setting of ordinal outcome data. A detailed case study demonstrating the usefulness of the proposed methodology is carried out using aggregate ordinal outcome data from 16 clinical trials for treating CD.
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Affiliation(s)
- Yeongjin Gwon
- Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - May Mo
- Amgen Inc., Thousand Oaks, California, USA
| | - Ming-Hui Chen
- Department of Statistics, University of Connecticut, Storrs, Connecticut, USA
| | - Zhiyi Chi
- Department of Statistics, University of Connecticut, Storrs, Connecticut, USA
| | - Juan Li
- Lily Biotechnology Center, Eli Lily and Company, San Diego, California, USA
| | - Amy H. Xia
- Amgen Inc., Thousand Oaks, California, USA
| | - Joseph G. Ibrahim
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Iheozor‐Ejiofor Z, Gordon M, Clegg A, Freeman SC, Gjuladin‐Hellon T, MacDonald JK, Akobeng AK. Interventions for maintenance of surgically induced remission in Crohn's disease: a network meta-analysis. Cochrane Database Syst Rev 2019; 9:CD013210. [PMID: 31513295 PMCID: PMC6741529 DOI: 10.1002/14651858.cd013210.pub2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic disease of the gut. About 75% of people with CD undergo surgery at least once in their lifetime to induce remission. However, as there is no known cure for the disease, patients usually experience a recurrence even after surgery. Different interventions are routinely used in maintaining postsurgical remission. There is currently no consensus on which treatment is the most effective. OBJECTIVES To assess the effects and harms of interventions for the maintenance of surgically induced remission in Crohn's disease and rank the treatments in order of effectiveness. SEARCH METHODS We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, and Embase from inception to 15 January 2019. We also searched reference lists of relevant articles, abstracts from major gastroenterology meetings, ClinicalTrials.gov, and the WHO ICTRP. There was no restriction on language, date, or publication status. SELECTION CRITERIA We considered for inclusion randomised controlled trials (RCTs) that compared different interventions used for maintaining surgically induced remission in people with CD who were in postsurgical remission. Participants had to have received maintenance treatment for at least three months. We excluded studies assessing enteral diet, diet manipulation, herbal medicine, and nutritional supplementation. DATA COLLECTION AND ANALYSIS Two review authors independently selected relevant studies, extracted data, and assessed the risk of bias. Any disagreements were resolved by discussion or by arbitration of a third review author when necessary. We conducted a network meta-analysis (NMA) using a Bayesian approach through Markov Chain Monte Carlo (MCMC) simulation. For the pairwise comparisons carried out in Review Manager 5, we calculated risk ratios (RR) with their corresponding 95% confidence intervals (95% CI). For the NMA, we presented hazard ratios (HR) with corresponding 95% credible intervals (95% CrI) and reported ranking probabilities for each intervention. For the NMA, we focused on three main outcomes: clinical relapse, endoscopic relapse, and withdrawals due to adverse events. Data were insufficient to assess time to relapse and histologic relapse. Adverse events and serious adverse events were not sufficiently or objectively reported to permit an NMA. We used CINeMA (Confidence in Network Meta-Analysis) methods to evaluate our confidence in the findings within networks, and GRADE for entire networks. MAIN RESULTS We included 35 RCTs (3249 participants) in the review. The average age of study participants ranged between 33.6 and 38.8 years. Risk of bias was high in 18 studies, low in four studies, and unclear in 13 studies. Of the 35 included RCTs, 26 studies (2581 participants; 9 interventions) were considered eligible for inclusion in the NMA. The interventions studied included 5-aminosalicylic acid (5-ASA), adalimumab, antibiotics, budesonide, infliximab, probiotics, purine analogues, sulfasalazine, and a combination of sulfasalazine and prednisolone. This resulted in 30 direct contrasts, which informed 102 mixed-treatment contrasts.The evidence for the clinical relapse network (21 studies; 2245 participants) and endoscopic relapse (12 studies; 1128 participants) were of low certainty while the evidence for withdrawal due to adverse events (15 studies; 1498 participants) was of very low certainty. This assessment was due to high risk of bias in most of the studies, inconsistency, and imprecision across networks. We mainly judged individual contrasts as of low or very low certainty, except 5-ASA versus placebo, the evidence for which was judged as of moderate certainty.We ranked the treatments based on effectiveness and the certainty of the evidence. For clinical relapse, the five most highly ranked treatments were adalimumab, infliximab, budesonide, 5-ASA, and purine analogues. We found some evidence that adalimumab (HR 0.11, 95% Crl 0.02 to 0.33; low-certainty evidence) and 5-ASA may reduce the probability of clinical relapse compared to placebo (HR 0.69, 95% Crl 0.53 to 0.87; moderate-certainty evidence). However, budesonide may not be effective in preventing clinical relapse (HR 0.66, 95% CrI 0.27 to 1.34; low-certainty evidence). We are less confident about the effectiveness of infliximab (HR 0.36, 95% CrI 0.02 to 1.74; very low-certainty evidence) and purine analogues (HR 0.75, 95% CrI 0.55 to 1.00; low-certainty evidence). It was unclear whether the other interventions reduced the probability of a clinical relapse, as the certainty of the evidence was very low.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing endoscopic relapse. Whilst there might be some evidence of prevention of endoscopic relapse with adalimumab (HR 0.10, 95% CrI 0.01 to 0.32; low-certainty evidence), no other intervention studied appeared to be effective.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing withdrawal due to adverse events. Withdrawal due to adverse events appeared to be least likely with sulfasalazine (HR 1.96, 95% Crl 0.00 to 8.90; very low-certainty evidence) and most likely with antibiotics (HR 53.92, 95% Crl 0.43 to 259.80; very low-certainty evidence). When considering the network as a whole, two adverse events leading to study withdrawal (i.e. pancreatitis and leukopenia) occurred in more than 1% of participants treated with an intervention. Pancreatitis occurred in 2.8% (11/399) of purine analogue participants compared to 0.17% (2/1210) of all other groups studied. Leukopenia occurred in 2.5% (10/399) of purine analogue participants compared to 0.08% (1/1210) of all other groups studied. AUTHORS' CONCLUSIONS Due to low-certainty evidence in the networks, we are unable to draw conclusions on which treatment is most effective for preventing clinical relapse and endoscopic relapse. Evidence on the safety of the interventions was inconclusive, however cases of pancreatitis and leukopenia from purine analogues were evident in the studies. Larger trials are needed to further understand the effect of the interventions on endoscopic relapse.
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Affiliation(s)
| | - Morris Gordon
- University of Central LancashireSchool of MedicineHarrington BuildingPrestonLancashireUK
| | - Andrew Clegg
- University of Central LancashireFaculty of Health and WellbeingBrook BuildingVictoria StreetPrestonLancashireUKPR1 2HE
| | - Suzanne C Freeman
- University of LeicesterDepartment of Health SciencesUniversity RoadLeicesterUKLE1 7RH
| | - Teuta Gjuladin‐Hellon
- University of Central LancashireSchool of MedicineHarrington BuildingPrestonLancashireUK
| | - John K MacDonald
- University of Western OntarioDepartment of MedicineLondonONCanada
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7
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Gjuladin‐Hellon T, Iheozor‐Ejiofor Z, Gordon M, Akobeng AK. Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease. Cochrane Database Syst Rev 2019; 8:CD010233. [PMID: 31425621 PMCID: PMC6699648 DOI: 10.1002/14651858.cd010233.pub3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic relapsing inflammatory condition and maintenance of remission is a major issue as many patients fail to achieve remission with medical management and require surgical interventions. Purine analogues such as azathioprine (AZA) and 6-mercaptopurine (6-MP) have been used to maintain surgically-induced remission in CD, but the effectiveness, tolerability and safety of these agents remains controversial. OBJECTIVES To assess the efficacy and safety of purine analogues (AZA and 6-MP) for maintenance of surgically-induced remission in CD. SEARCH METHODS We searched PubMed, MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 26 July 2018 (and from inception to 31 July 2019). In addition, we searched reference lists of all included studies and relevant reviews, conference proceedings and trials registers. SELECTION CRITERIA Randomised controlled trials (RCTs) with a duration of at least three months that enrolled adults and children with surgically-induced remission of CD and compared AZA or 6-MP to no treatment, placebo or any other active intervention were considered for inclusion. DATA COLLECTION AND ANALYSIS Two authors independently assessed trial eligibility, extracted data, assessed the risk of bias and assessed the certainty of the evidence using GRADE. The primary outcome was clinical relapse. Secondary outcomes included endoscopic relapse, radiologic and surgical relapse, adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs and health-related quality of life. MAIN RESULTS Ten RCTs with a total of 928 participants were included. Study participants were adults recruited from university clinics and gastroenterology hospitals who received interventions post-surgery for a duration between 12 to 36 months. Most study participants were recruited less than three months after surgery in all except one study where participants were recruited between 6 to 24 months post-surgery. One study was rated as low risk of bias, six studies were rated high risk of bias and three were rated unclear risk of bias.There was moderate certainty evidence that purine analogues are more efficient for preventing clinical relapse than placebo. At 12 to 36 months, 51% (109/215) of AZA/6-MP participants relapsed compared to 64% (124/193) of placebo participants (RR 0.79; 95% CI 0.67 to 0.92; 408 participants; 3 studies; I² = 0%; moderate certainty evidence). The certainty of the evidence regarding the efficacy of AZA or 6-MP for maintaining postoperative clinical remission compared to 5-ASA compounds was low. At 12 to 24 months , 64% (113/177) of purine analogue participants relapsed compared to 59% (101/170) of 5-ASA participants (RR 1.05; 95% CI 0.89 to 1.24; 347 participants; 4 studies; I² = 8%; low certainty evidence). The certainty of evidence that purine analogues are inferior for preventing postsurgical clinical relapse compared to tumour necrosis factor alpha agents (anti-TNF-α) was very low. At 12 to 24 months, 43% (29/67) of AZA participants relapsed compared to 14% (10/72) of anti-TNF-α participants (RR 2.89; 95% CI 1.50 to 5.57; 139 participants; 3 studies; I² = 0%; very low certainty evidence).The effect of purine analogues compounds on AEs compared to placebo or any active treatment was uncertain, as the quality of evidence ranged from very low to low. After 12 to 24 months, 14% (12/87) of purine analogue participants experienced an AE compared to 10% (8/81) of placebo participants (RR 1.36; 95% CI 0.57 to 3.27; 168 participants; 2 studies; I² = 0%; low certainty evidence). The effect of purine analogues on AEs compared to 5-ASA agents was uncertain. After 12 to 24 months, 41% (73/176) of purine analogue participants had an AE compared to 47% (81/171) of 5-ASA participants (RR 0.89; 95% CI 0.74 to 1.07; 346 participants; 4 studies; I² = 15%; low certainty evidence). The effect of purine analogues on AEs in comparison to anti TNF-α agents was uncertain. At 12 to 24 months, 57% (32/56) of AZA participants had an AE compared to 51% (31/61) of anti-TNF-α participants (RR 1.13; 95% CI 0.83 to 1.53; 117 participants; 2 studies; I² = 0%; low certainty evidence). Purine analogue participants were more like than 5-ASA participants to have a SAE (RR 3.39, 95% CI 1.26 to 9.13, 311 participants; 3 studies; I² = 9%; very low certainty evidence), or to withdraw due to an AE (RR 2.21, 95% CI 1.28 to 3.81; 425 participants; 5 studies; I² = 0%; low certainty evidence). Commonly reported AEs across all studies included leucopenia, arthralgia, abdominal pain or severe epigastric intolerance, elevated liver enzymes, nausea and vomiting, pancreatitis, anaemia, nasopharyngitis and flatulence. AUTHORS' CONCLUSIONS Moderate certainty evidence suggests that AZA and 6-MP may be superior to placebo for maintenance of surgically-induced remission in participants with CD. There was no clear difference in the number of clinical relapses when purine analogues were compared with 5-ASA agents, however this is based on low certainty evidence. There was very low certainty evidence that AZA and 6-MP are more likely to result in more serious adverse events (SAEs) and withdrawals due to an AE (low certainty) when compared to 5-ASA agents. Very low certainty evidence suggests that purine analogues may be inferior to anti-TNF-α agents, however, no firm conclusions can be drawn. Further research investigating the efficacy and safety of AZA and 6-MP in comparison to other active medications in surgically-induced remission of CD is warranted.
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Affiliation(s)
| | | | - Morris Gordon
- University of Central LancashireSchool of MedicinePrestonLancashireUKPR1 7BH
- Blackpool Victoria HospitalFamilies DivisionBlackpoolUK
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8
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Nyitray AG, Peng F, Day RS, Carvalho Da Silva RJ, Baggio ML, Salmerón J, Quiterio M, Abrahamsen M, Lazcano-Ponce E, Villa LL, Giuliano AR. The association between body mass index and anal canal human papillomavirus prevalence and persistence: the HIM study. Hum Vaccin Immunother 2019; 15:1911-1919. [PMID: 30897017 DOI: 10.1080/21645515.2019.1593083] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background: While receptive anal sex is an established risk factor for anal human papillomavirus (HPV) infection and squamous cell carcinoma of the anus (SCCA), people with anal HPV infection and SCCA commonly report no lifetime receptive anal sex suggesting other factors may also increase risk for anal HPV infection and persistence. Given potential associations between obesity and conditions that may cause perianal or anal canal lesions, we hypothesized that body mass index (BMI) was associated with HPV infection. Methods: Genotyping for 36 HPV types was conducted on anal canal specimens from men, ages 18-70, from Brazil, Mexico, and the USA. Eligibility included no history of genital warts or HIV. Evaluable specimens were collected from 328 men having sex with men (MSM) and 1348 men having sex with women (MSW) who reported no lifetime receptive anal sex. Prevalence of anal HPV infection and six-month persistence by BMI were estimated in addition to adjusted prevalence ratios for the association between BMI and HPV infection. Results: Among MSW, obese men had a higher prevalence of HPV-16 in the anal canal (3.1%), compared to normal weight men (1.3%) although 95% CI overlapped. Among MSM, prevalence of HPV decreased with increasing BMI. A similar pattern was observed for persistence. After adjustment for confounders, obese MSW had 2.4 times higher odds of HPV-16 compared to normal weight men. Conclusions: BMI may be positively associated with anal HPV (especially HPV-16) among MSW and negatively associated with anal HPV among MSM which supports continued universal HPV vaccination programs.
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Affiliation(s)
- Alan G Nyitray
- a Clinical Cancer Center and Center for AIDS Intervention Research, Medical College of Wisconsin , Milwaukee , WI , USA
| | - Fen Peng
- b Department of Clinical Research, Medtronic, Inc , Northridge , CA , USA
| | - Rena S Day
- c Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center School of Public Health at Houston , Houston , TX , USA
| | | | - Maria Luiza Baggio
- e Centro de Investigação Translacional em Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , Brazil
| | - Jorge Salmerón
- f Research Center on Policies, Population, and Health, Faculty of Medicine, National Autonomous University of Mexico , Mexico City , Mexico.,g Center for Population Health Research, National Institute of Public Health , Cuernavaca , Morelos , Mexico
| | - Manuel Quiterio
- g Center for Population Health Research, National Institute of Public Health , Cuernavaca , Morelos , Mexico
| | - Martha Abrahamsen
- h Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center and Research Institute , Tampa , FL , USA
| | - Eduardo Lazcano-Ponce
- g Center for Population Health Research, National Institute of Public Health , Cuernavaca , Morelos , Mexico
| | - Luisa L Villa
- i Faculdade de Medicina, Universidade de São Paulo Department of Radiology and Oncology, Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo , Brazil
| | - Anna R Giuliano
- h Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center and Research Institute , Tampa , FL , USA
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9
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Chiba M, Tanaka Y, Ono I. Early intestinal obstruction after infliximab therapy in Crohn's disease. AUTOPSY AND CASE REPORTS 2019; 9:e2018068. [PMID: 30863735 PMCID: PMC6394366 DOI: 10.4322/acr.2018.068] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 11/11/2018] [Indexed: 12/18/2022] Open
Abstract
There is scarce knowledge on early intestinal obstruction in Crohn’s disease (CD) after infliximab treatment. Therefore, we describe two cases of early intestinal obstruction in a series of 46 CD patients treated with infliximab. Both our two cases were 21-year-old men with newly diagnosed CD who were diagnosed with perianal disease 2 years previously. They were suffering from diarrhea and abdominal pain, but there were no symptoms indicating bowel obstruction. Radiographic studies revealed stenotic sites in the terminal ileum in both cases. In both cases, infliximab 300 mg was infused, after which their abnormal laboratory data as well as symptoms such as diarrhea and abdominal pain clearly improved. However, on the 11th or 13th day post-treatment, they presented abdominal distension with air-fluid levels on imaging studies. Ileocolonic resection was performed in both cases. Early intestinal obstruction after infliximab therapy is characterized by initial improvement of the symptoms and the laboratory data, which is soon followed by clinical deterioration. This outcome indicates that infliximab is so swiftly effective that the healing process tapers the stenotic site, resulting in bowel obstruction. Thus, although unpleasant and severe, the obstruction cannot be considered as a side effect but rather a consequence of infliximab’s efficacy. CD patients with intestinal stricture, particularly the penetrating type with stricture, should be well informed about the risk of developing intestinal obstruction after infliximab therapy and the eventual need for surgical intervention.
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Affiliation(s)
- Mitsuro Chiba
- Akita City Hospital, Division of Gastroenterology. Akita City, Japan
| | - Yuichi Tanaka
- Nakadori General Hospital, Division of Surgery. Akita City, Japan
| | - Iwao Ono
- Nakadori General Hospital, Division of Pathology. Akita City, Japan
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10
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Alegbeleye BJ. Crohn's disease in a developing African mission hospital: a case report. J Med Case Rep 2019; 13:80. [PMID: 30846003 PMCID: PMC6407268 DOI: 10.1186/s13256-019-1971-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 01/03/2019] [Indexed: 12/31/2022] Open
Abstract
Background A case is reported of innocuous intestinal obstruction requiring surgical intervention that was confirmed to be Crohn’s disease histopathologically in a resource-constrained rural mission hospital in Cameroon. Case presentation A 70-year man of Kumbo origin from Northwest region of Cameroon with a history of crampy right lower-quadrant abdominal pain, non-bloody, non-mucoid diarrhea alternating with constipation presented to my institution. Abdominal examination of the patient revealed an ill-defined mass in the right iliac fossa and visible peristalsis. An abdominal computed tomographic scan and barium enema study confirmed a complex ascending colonic and cecal tumor. The patient underwent exploratory laparotomy. The intraoperative finding was a huge complex inflammatory mass involving the cecum, terminal ileum, and sigmoid colon. He subsequently had sigmoidectomy with end–to-end sigmoidorectal anastomosis and a cecal resection, and the proximal ascending colon was exteriorized because end mucoid fistula and terminal ileostomy were performed. The histopathological diagnosis confirmed Crohn’s disease. The patient subsequently received five courses of adjuvant chemotherapy consisting of azathioprine, methotrexate, mesalamine, and methylprednisolone. He had complete disease remission and subsequently had closure of ileostomy with satisfactory postoperative status. The most recent follow-up abdominal computed tomographic scan and colonoscopy revealed disease-free status. The patient is also currently receiving a maintenance dose of rectal mesalamine and oral omeprazole treatment. He has been followed every 2 months in the surgical outpatient clinic over the last 16 months with satisfactory clinical outcome. Conclusions Crohn’s disease is uncommon in Africa, and this entity is encountered sparingly. The signs and symptoms of Crohn’s disease overlap with many other abdominal disorders, such as tuberculosis, ulcerative colitis, irritable bowel syndrome, and others. Several publications in the literature describe that it is difficult to make an accurate diagnosis of this disease, despite the fact that many diagnostic armamentaria are available to suggest its presence. Most of the patients with Crohn’s disease are treated conservatively, and a few may require surgical intervention, especially those presenting with complications such as intestinal obstruction, perforations, and abscess as well as fistula formations, as seen in this index patient. Crohn’s disease is considered by many to be a very rare disease in Africa. It is interesting to know that Crohn’s disease, which affects mainly young adults, may debut at any age. The rarity and clinical curiosity of this entity suggested reporting of my patient’s case. Evidence-based up-to-date information on Crohn’s disease is also documented.
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Affiliation(s)
- Bamidele Johnson Alegbeleye
- Department of Surgery, St Elizabeth Catholic General Hospital, Shisong, P.O Box 8, Kumbo - Nso, Bui Division, Northwestern Region, Cameroon.
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11
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Sagami S, Kobayashi T, Kikkawa N, Umeda S, Nakano M, Toyonaga T, Okabayashi S, Ozaki R, Hibi T. Combination of colonoscopy and magnetic resonance enterography is more useful for clinical decision making than colonoscopy alone in patients with complicated Crohn's disease. PLoS One 2019; 14:e0212404. [PMID: 30785943 PMCID: PMC6382266 DOI: 10.1371/journal.pone.0212404] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 01/25/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIMS The small bowel is affected in more than half of patients with Crohn's disease (CD) at the time of diagnosis, and small bowel involvement has a negative impact on the long-term outcome. Many patients reportedly have active lesions in the small intestine even in patients in clinical remission. This study was performed to compare findings of magnetic resonance enterography (MRE) and ileocolonoscopy. METHODS A single-center retrospective study was conducted in 50 patients (60 imaging series) with CD, for whom MRE was additionally performed during the bowel preparation for subsequent ileocolonoscopy. Endoscopic remission was defined as a Simple Endoscopic Score for CD (SES-CD) of <5. MRE remission was defined as a Magnetic Resonance Index of Activity (MaRIA) score of <50. The time to treatment escalation was assessed by the log-rank test. RESULTS Importantly, 7 of 29 patients (24.1%) with endoscopic remission had a MaRIA score of ≥50. Both SES-CD and MaRIA correlated with the need for treatment escalation (P = 0.025, P = 0.009, respectively). MRE predicted the need for treatment escalation even in patients with endoscopic remission. Although no correlation was present between SES-CD and MaRIA score in patients with structuring/penetrating disease, or insufficient ileal insertion (<10cm), a high MaRIA score still correlated with the need for treatment escalation in stricturing or penetrating disease (P = 0.0306). CONCLUSIONS The MaRIA score predicts the need for treatment escalation even in patients with endoscopic remission, indicating that addition of MRE to conventional ileocolonoscopy alone can be a useful, noninvasive tool for monitoring CD especially in stricturing or penetrating disease.
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Affiliation(s)
- Shintaro Sagami
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
- * E-mail:
| | - Nao Kikkawa
- Department of Radiology, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
| | - Satoko Umeda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Masaru Nakano
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
| | - Takahiko Toyonaga
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
| | - Shinji Okabayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
| | - Ryo Ozaki
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan
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12
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Chiba M, Tsuji T, Nakane K, Tsuda S, Ishii H, Ohno H, Watanabe K, Ito M, Komatsu M, Sugawara T. Induction with Infliximab and a Plant-Based Diet as First-Line (IPF) Therapy for Crohn Disease: A Single-Group Trial. Perm J 2018; 21:17-009. [PMID: 29035182 DOI: 10.7812/tpp/17-009] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Approximately 30% of patients with Crohn disease (CD) are unresponsive to biologics. No previous study has focused on a plant-based diet in an induction phase of CD treatment. OBJECTIVE To investigate the remission rate of infliximab combined with a plant-based diet as first-line (IPF) therapy for CD. METHODS This was a prospective single-group trial conducted at tertiary hospitals. Subjects included consecutive adults with a new diagnosis (n = 26), children with a new diagnosis (n = 11), and relapsing adults (n = 9) with CD who were naïve to treatment with biologics. Patients were admitted and administered a standard induction therapy with infliximab (5 mg/kg; 3 infusions at 0, 2, and 6 weeks). Additionally, they received a lacto-ovo-semivegetarian diet. The primary end point was remission, defined as the disappearance of active CD symptoms at week 6. Secondary end points were Crohn Disease Activity Index (CDAI) score, C-reactive protein (CRP) concentration, and mucosal healing. RESULTS Two adults with a new diagnosis were withdrawn from the treatment protocol because of intestinal obstruction. The remission rates by the intention-to-treat and per-protocol analyses were 96% (44/46) and 100% (44/44), respectively. Mean CDAI score (314) on admission decreased to 63 at week 6 (p < 0.0001). Mean CRP level on admission (5.3 mg/dL) decreased to 0.2 (p < 0.0001). Mucosal healing was achieved in 46% (19/41) of cases. CONCLUSION IPF therapy can induce remission in most patients with CD who are naïve to biologics regardless of age or whether they have a new diagnosis or relapse.
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Affiliation(s)
- Mitsuro Chiba
- Chief of the Inflammatory Bowel Disease Section at Akita City Hospital in Japan.
| | - Tsuyotoshi Tsuji
- Chief of the Gastrointestinal Endoscopy Section at Akita City Hospital in Japan.
| | - Kunio Nakane
- Chief of the Gastroenterology Division at Akita City Hospital in Japan.
| | - Satoko Tsuda
- Gastroenterologist at Akita City Hospital in Japan.
| | - Hajime Ishii
- Gastroenterologist at Akita City Hospital in Japan.
| | - Hideo Ohno
- Gastroenterologist at Akita City Hospital in Japan.
| | | | - Mai Ito
- Gastroenterologist at Akita City Hospital in Japan.
| | - Masafumi Komatsu
- Gastroenterologist and the Director of Akita City Hospital, in Japan.
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13
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Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, Kato J, Kobayashi K, Kobayashi K, Koganei K, Kunisaki R, Motoya S, Nagahori M, Nakase H, Omata F, Saruta M, Watanabe T, Tanaka T, Kanai T, Noguchi Y, Takahashi KI, Watanabe K, Hibi T, Suzuki Y, Watanabe M, Sugano K, Shimosegawa T. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol 2018; 53:305-353. [PMID: 29429045 PMCID: PMC5847182 DOI: 10.1007/s00535-018-1439-1] [Citation(s) in RCA: 365] [Impact Index Per Article: 52.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 01/23/2018] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn's disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.
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Affiliation(s)
- Katsuyoshi Matsuoka
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Taku Kobayashi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Fumiaki Ueno
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Ofuna Central Hospital, 6-2-24 Ofuna, Kamakura-shi, Kanagawa, 247-0056, Japan.
| | - Toshiyuki Matsui
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Fumihito Hirai
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Nagamu Inoue
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Jun Kato
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kenji Kobayashi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kiyonori Kobayashi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazutaka Koganei
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Reiko Kunisaki
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Satoshi Motoya
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masakazu Nagahori
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroshi Nakase
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Fumio Omata
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masayuki Saruta
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Toshiaki Watanabe
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Toshiaki Tanaka
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takanori Kanai
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshinori Noguchi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Ken-Ichi Takahashi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kenji Watanabe
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Toshifumi Hibi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yasuo Suzuki
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Mamoru Watanabe
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kentaro Sugano
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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14
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Comparison of Concomitant Mesalamine and Immunomodulator Therapy and Immunomodulator Monotherapy for Crohn's Disease. Gastroenterol Res Pract 2018; 2018:4826973. [PMID: 29576767 PMCID: PMC5822780 DOI: 10.1155/2018/4826973] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 05/03/2017] [Indexed: 12/18/2022] Open
Abstract
Background Although immunomodulators are increasingly used in Crohn's disease (CD), a significant number of gastroenterologists still use 5-aminosalicylate (5-ASA) in combination with azathioprine (AZA) or 6-mercaptopurine (6-MP); there is limited evidence regarding the benefit of concomitant 5-ASA with AZA/6-MP compared with AZA/6-MP monotherapy for the treatment of CD. Study Design A total of 106 patients who received AZA/6-MP for more than 3 months between January 1991 and May 2014 were identified retrospectively. Each patient was matched with 3 randomly selected controls who were treated with concomitant therapy during the same period. Results The cumulative probabilities of steroid use at 5 and 10 years were 24.9% and 75.8% in the 5-ASA + AZA/6-MP group and 31.2% and 87.8% in the AZA/6-MP group, respectively (P = 0.187). The cumulative probabilities of anti-TNF use, resectional surgery, and disease-related hospitalization were comparable between the groups. The younger age and the use of lower doses of immunomodulators were associated with higher requirement of rescue therapy. Conclusions This study did not demonstrate that the concomitant use of 5-ASA with AZA/6-MP showed the proof or effect in terms of steroid requirements, anti-TNF use, resectional surgery, or disease-related hospitalization compared with that of AZA/6-MP alone.
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15
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Kang J, Chung WH, Lim TJ, Lim S, Nam YD. Complete genome sequence of the Bifidobacterium animalis subspecies lactis BL3, preventive probiotics for acute colitis and colon cancer. New Microbes New Infect 2017; 19:34-37. [PMID: 28702200 PMCID: PMC5485758 DOI: 10.1016/j.nmni.2017.05.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 05/11/2017] [Indexed: 01/10/2023] Open
Abstract
We report the genome sequence of Bifidobacterium animalis subspecies lactis BL3, which has preventive properties on acute colitis and colon cancer. The genome of BL3, which was isolated from Korean faeces, consisted of a 1 944 323 bp size single chromosome, and its G+C content was 60.5%. Genome comparison against the closest Bifidobacterium animalis strain revealed that BL3 had particularly different regions of four areas encoding flavin-nucleotide-binding protein, transposase, multidrug ABC transporter and ATP binding protein.
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Affiliation(s)
- J Kang
- Research Group of Gut Microbiome, Korea Food Research Institute, Sungnam, Republic of Korea.,Department of Food Biotechnology, Korea University of Science and Technology, Daejeon, Republic of Korea
| | - W-H Chung
- Research Group of Gut Microbiome, Korea Food Research Institute, Sungnam, Republic of Korea
| | - T-J Lim
- Research and Development Center, Cell Biotech Co. Ltd., Gimpo, Republic of Korea
| | - S Lim
- Research and Development Center, Cell Biotech Co. Ltd., Gimpo, Republic of Korea
| | - Y-D Nam
- Research Group of Gut Microbiome, Korea Food Research Institute, Sungnam, Republic of Korea.,Department of Food Biotechnology, Korea University of Science and Technology, Daejeon, Republic of Korea
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16
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Chan HCH, Ng SC. Emerging biologics in inflammatory bowel disease. J Gastroenterol 2017; 52:141-150. [PMID: 27832357 DOI: 10.1007/s00535-016-1283-0] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 10/27/2016] [Indexed: 02/04/2023]
Abstract
Early biologic therapy is recommended in patients with inflammatory bowel disease and poor prognostic factors and in those refractory to conventional medications. Anti-tumor necrosis factor (anti-TNF) agents are the most commonly used biologic agents. However, some patients may not have an initial response to anti-TNF therapy, and one-third will develop loss of response over time. Anti-TNF drugs can also be associated with side effects. In addition, the use of biologics is currently limited by their cost, especially in developing countries. A number of new therapeutic targets, including novel small molecules, and cellular therapy are available or under investigation. These novel molecules include oral Janus kinase (JAK) inhibitor (tofacitinib), interleukin inhibitor (ustekinumab), oral SMAD7 antisense oligonucleotide (mongersen), and anti-integrin inhibitors (vedolizumab). Here, we review the mechanisms of action, the efficacy, and the safety data of these novel agents. Biological products that are highly similar to reference biologic products whose patents have expired-also known as "biosimilars"-can be produced at lower cost with similar efficacy, and are also available for the treatment of IBD. We review the efficacy data for such agents as well.
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Affiliation(s)
- Heyson Chi-Hey Chan
- Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
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17
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Park JJ, Yang SK, Ye BD, Kim JW, Park DI, Yoon H, Im JP, Lee KM, Yoon SN, Lee H. Second Korean guidelines for the management of Crohn's disease. Intest Res 2017; 15:38-67. [PMID: 28239314 PMCID: PMC5323307 DOI: 10.5217/ir.2017.15.1.38] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 01/15/2017] [Accepted: 01/16/2017] [Indexed: 02/07/2023] Open
Abstract
Crohn's disease (CD) is a chronic, progressive, and disabling inflammatory bowel disease (IBD) with an uncertain etiopathogenesis. CD can involve any site of the gastrointestinal tract from the mouth to the anus, and is associated with serious complications, such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower compared with those in Western countries, but they have been rapidly increasing during the recent decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies have been applied for the treatment of this disease. Concerning CD management, there have been substantial discrepancies among clinicians according to their personal experience and preference. To suggest recommendable approaches to the diverse problems of CD and to minimize the variations in treatment among physicians, guidelines for the management of CD were first published in 2012 by the IBD Study Group of the Korean Association for the Study of Intestinal Diseases. These are the revised guidelines based on updated evidence, accumulated since 2012. These guidelines were developed by using mainly adaptation methods, and encompass induction and maintenance treatment of CD, treatment based on disease location, treatment of CD complications, including stricture and fistula, surgical treatment, and prevention of postoperative recurrence. These are the second Korean guidelines for the management of CD and will be continuously revised as new evidence is collected.
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Affiliation(s)
- Jae Jun Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Wook Kim
- Department of Internal Medicine, Inje University College of Medicine Ilsan Paik Hospital, Goyang, Korea
| | - Dong Il Park
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jong Pil Im
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kang Moon Lee
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Suwon, Korea
| | - Sang Nam Yoon
- Department of Surgery, Hallym University College of Medicine, Chuncheon, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
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18
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Chung SH, Lee HW, Kim SW, Park SJ, Hong SP, Kim TI, Kim WH, Cheon JH. Usefulness of Measuring Serum Procalcitonin Levels in Patients with Inflammatory Bowel Disease. Gut Liver 2016; 10:574-580. [PMID: 26780089 PMCID: PMC4933418 DOI: 10.5009/gnl15209] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 07/07/2015] [Accepted: 08/07/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIMS The relationships between serum procalcitonin, inflammatory bowel disease (IBD) and intestinal Behçet's disease (BD) have not been completely determined. We aimed to evaluate the usefulness of measuring serum procalcitonin levels to assess disease activity and infection stage in patients with IBD and intestinal BD. METHODS We retrospectively analyzed clinical data from 129 patients with IBD and intestinal BD for whom serum procalcitonin and C-reactive protein (CRP) levels were measured between January 2006 and February 2013. RESULTS The median serum procalcitonin levels in the IBD and intestinal BD with septic shock or sepsis (n=8), with localized infection (n=76), and without infection (n=45) were 3.46 ng/mL (range, 0.17 to 63.66 ng/mL), 0.22 ng/mL (range, 0.05 to 140.18 ng/mL), and 0.07 ng/mL (range, 0.00 to 31.50 ng/mL), respectively (p=0.001). The serum CRP levels in the IBD and intestinal BD patients did not differ according to the infection stage. Variations in serum procalcitonin levels were not observed in the IBD and intestinal BD patients with different disease activities. CONCLUSIONS Serum procalcitonin levels may not be affected by IBD and intestinal BD activity itself, although they may be affected by concomitant infection. Serum procalcitonin measurements could be more useful than CRP in determining the infection stage that reflects the severity of infection in IBD and intestinal BD patients.
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Affiliation(s)
- Sook Hee Chung
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Hye Won Lee
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Seung Won Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Soo Jung Park
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Sung Pil Hong
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Tae Il Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Won Ho Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
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Lim W, Wang Y, MacDonald JK, Hanauer S. Aminosalicylates for induction of remission or response in Crohn's disease. Cochrane Database Syst Rev 2016; 7:CD008870. [PMID: 27372735 PMCID: PMC6457996 DOI: 10.1002/14651858.cd008870.pub2] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Randomized trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in these patients. OBJECTIVES To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease. SEARCH METHODS We searched PubMed, EMBASE, MEDLINE and the Cochrane Central Library from inception to June 2015 to identify relevant studies. There were no language restrictions. We also searched reference lists from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2015) of the American Gastroenterological Association and American College of Gastroenterology. SELECTION CRITERIA Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included. DATA COLLECTION AND ANALYSIS Data extraction and assessment of methodological quality was independently performed by the investigators and any disagreement was resolved by discussion and consensus. We assessed methodological quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Secondary outcomes included mean Crohn's disease activity index (CDAI) scores, adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes we calculated the pooled risk ratio (RR) and corresponding 95% confidence interval (CI) using a random-effects model. For continuous outcomes we calculated the mean difference (MD) and 95% CI using a random-effects model. Sensitivity analyses based on a fixed-effect model and duration of therapy were conducted where appropriate. MAIN RESULTS Twenty studies (2367 patients) were included. Two studies were judged to be at high risk of bias due to lack of blinding. Eight studies were judged to be at high risk of bias due to incomplete outcomes data (high drop-out rates) and potential selective reporting. The other 10 studies were judged to be at low risk of bias. A non-significant trend in favour of sulfasalazine over placebo for inducing remission was observed, with benefit confined mainly to patients with Crohn's colitis. Forty-five per cent (63/141) of sulfasalazine patients entered remission at 17-18 weeks compared to 29% (43/148) of placebo patients (RR 1.38, 95% CI 1.00 to 1.89, 2 studies). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (106 events). There was no difference between sulfasalazine and placebo in adverse event outcomes. Sulfasalazine was significantly less effective than corticosteroids and inferior to combination therapy with corticosteroids (RR 0.64, 95% CI 0.47 to 0.86, 1 study, 110 patients). Forty-three per cent (55/128) of sulfasalazine patients entered remission at 17 to 18 weeks compared to 60% (79/132) of corticosteroid patients (RR 0.68, 95% CI 0.51 to 0.91; 2 studies, 260 patients). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (134 events). Sulfasalazine patients experienced significantly fewer adverse events than corticosteroid patients (RR 0.43, 95% CI 0.22 to 0.82; 1 study, 159 patients). There was no difference between sulfasalazine and corticosteroids in serious adverse events or withdrawal due to adverse events. Olsalazine was less effective than placebo in a single trial (RR 0.36, 95% CI 0.18 to 0.71; 91 patients). Low dose mesalamine (1 to 2 g/day) was not superior to placebo for induction of remission. Twenty-three per cent (43/185) of low dose mesalamine patients entered remission at week 6 compared to 15% (18/117) of placebo patients (RR = 1.46, 95% CI 0.89 to 2.40; n = 302). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to risk of bias (incomplete outcome data) and sparse data (61 events). There was no difference between low dose mesalamine and placebo in the proportion of patients who had adverse events (RR 1.33, 95% CI 0.91 to 1.96; 3 studies, 342 patients) or withdrew due to adverse events (RR 1.21, 95% CI 0.75 to 1.95; 3 studies, 342 patients). High dose controlled-release mesalamine (4 g/day) was not superior to placebo, inducing a clinically non significant reduction in CDAI (MD -19.8 points, 95% CI -46.2 to 6.7; 3 studies, 615 patients), and was also inferior to budesonide (RR 0.56, 95% CI 0.40 to 0.78; 1 study, 182 patients, GRADE = low). While high dose delayed-release mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02, 95% CI 0.75 to 5.45; 1 study, 38 patients, GRADE = very low), no significant difference in efficacy was found when compared to conventional corticosteroids (RR 1.04, 95% CI 0.79 to 1.36; 3 studies, 178 patients, GRADE = moderate) or budesonide (RR 0.89, 95% CI 0.76 to 1.05; 1 study, 307 patients, GRADE = moderate). However, these trials were limited by risk of bias (incomplete outcome data) and sparse data (small numbers of events). There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. Adverse events that were commonly reported included headache, nausea, vomiting, abdominal pain and diarrhea. AUTHORS' CONCLUSIONS Sulfasalazine is only modestly effective with a trend towards benefit over placebo and is inferior to corticosteroids for the treatment of mildly to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3.2 to 4 g/day) is not more effective than placebo for inducing response or remission. However, trials assessing the efficacy of high dose mesalamine (4 to 4.5 g/day) compared to budesonide yielded conflicting results and firm conclusions cannot be made. Future large randomized controlled trials are needed to provide definitive evidence on the efficacy of aminosalicylates in active Crohn's disease.
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Affiliation(s)
- Wee‐Chian Lim
- Tan Tock Seng HospitalDepartment of Gastroenterology and Hepatology11 Jalan Tan Tock SengSingaporeSingaporeS 308433
| | - Yongjun Wang
- University of Western OntarioSchulich School of Medicine & DentistryLondonONCanada
| | - John K MacDonald
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanadaN6A 5B6
- University of Western OntarioDepartment of MedicineLondonONCanada
| | - Stephen Hanauer
- Northwestern University Feinberg School of Medicine676 N St ClairSuite 1400ChicagoILUSA60611
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20
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Lee HW, Chung SH, Moon CM, Che X, Kim SW, Park SJ, Hong SP, Kim TI, Kim WH, Cheon JH. The Correlation of Serum IL-12B Expression With Disease Activity in Patients With Inflammatory Bowel Disease. Medicine (Baltimore) 2016; 95:e3772. [PMID: 27281077 PMCID: PMC4907655 DOI: 10.1097/md.0000000000003772] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2016] [Revised: 04/23/2016] [Accepted: 04/29/2016] [Indexed: 02/07/2023] Open
Abstract
Genetic variants in IL12B, encoding the p40 subunit common in interleukin-12 (IL-12) and interleukin-23, were identified as the susceptibility loci for inflammatory bowel disease (IBD). This study aimed to identify the correlation of serum IL-12B expression with disease activity in patients with IBD and evaluate the possibility of IL-12B as a biomarker for assessing inflammatory status in IBD.A total of 102 patients with IBD, including 38, 32, and 32 patients with Crohn's disease (CD), ulcerative colitis (UC), and intestinal Behçet's disease (intestinal BD), respectively, were included. The clinical and laboratory data from the patients were collected at the time of serum IL-12B measurement. Serum IL-12B levels were measured using an enzyme-linked immunosorbent assay.The median IL-12B levels in patients with CD, UC, and intestinal BD were significantly higher than those in controls (1.87, 2.74, and 2.73 pg/mL, respectively, vs. 1.42 pg/mL, all P <0.05). IL-12B concentrations were associated with disease activity in patients with UC and intestinal BD but not in those with CD. IL-12B levels were increased with increasing disease activity in patients with UC (P <0.001). Likewise, patients with active intestinal BD had higher IL-12B levels than those without active disease (P = 0.008). IL-12B levels were correlated with the endoscopic disease activity of UC (P = 0.002) and intestinal BD (P = 0.001) but not that of CD.Serum IL-12B levels were significantly correlated with clinical and endoscopic disease activity in patients with UC and intestinal BD, suggesting its potential use as a biomarker for assessing disease activity in these patients.
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Affiliation(s)
- Hye Won Lee
- From the Department of Internal Medicine (HWL, SWK, SJP, SPH, TIK, WHK, JHC), Institute of Gastroenterology, Yonsei University College of Medicine, Seoul; Department of Internal Medicine (SHC), Ajou University College of Medicine, Suwon; Department of Internal Medicine (CMM), School of Medicine, Ewha Womans University, Seoul, Republic of Korea; and Brain Korea 21 Plus Project for Medical Science (XC), Yonsei University
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Wu KC, Ran ZH, Gao X, Chen M, Zhong J, Sheng JQ, Kamm MA, Travis S, Wallace K, Mostafa NM, Shapiro M, Li Y, Thakkar RB, Robinson AM. Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn's disease. Intest Res 2016; 14:152-63. [PMID: 27175116 PMCID: PMC4863049 DOI: 10.5217/ir.2016.14.2.152] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 03/15/2016] [Accepted: 03/15/2016] [Indexed: 12/11/2022] Open
Abstract
Background/Aims This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD). Methods Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220–450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8–26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored. Results Mean adalimumab serum concentrations during the induction phase were 13.9–18.1 µg/mL (160/80 mg group) and 7.5−9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups. Conclusions Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported.
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Affiliation(s)
- Kai-Chun Wu
- Xijing Hospital of the Fourth Military Medical University, Xi'an, China
| | - Zhi Hua Ran
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiang Gao
- The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Zhong
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jian-Qiu Sheng
- The Military General Hospital of Beijing, PLA, Beijing, China
| | - Michael A Kamm
- St. Vincent's Hospital and University of Melbourne, Melbourne, Australia.; Imperial College, London, UK
| | | | | | | | | | - Yao Li
- AbbVie, North Chicago, Illinois, USA
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Handler M, Dotan I, Klausner JM, Yanai H, Neeman E, Tulchinsky H. Clinical recurrence and re-resection rates after extensive vs. segmental colectomy in Crohn's colitis: a retrospective cohort study. Tech Coloproctol 2016; 20:287-292. [PMID: 26886936 DOI: 10.1007/s10151-016-1440-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Accepted: 01/23/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND The aim of the present study was to document long-term clinical recurrence and re-resection rates of segmental and extended colectomy in patients with Crohn's colitis and to identify risk factors causing recurrence. METHODS Records of patients with isolated colonic Crohn's disease who underwent colectomy between 1995 and 2013 and were followed at our medical center were identified. Data on age at diagnosis, gender, smoking, disease location at diagnosis, perianal and rectal disease, indication for surgery, preoperative disease duration, type of operation, primary anastomosis at first operation, length of resected specimen, recurrence of symptoms, postoperative medication, reoperation, and total follow-up time were retrieved. RESULTS Thirty-five suitable patients (18 segmental colectomy, 17 extensive colectomy; 17 males; mean age at operation 36.6 years) were identified. Mean age at primary operation was 36 years. The mean preoperative disease duration was 121 months. Postoperative medical treatment was needed in 10 (56 %) patients undergoing segmental colectomy and in 16 (94 %) of those undergoing extensive colectomy (p = 0.01). There was longer reoperation-free survival in the segmental colectomy patient group (p = 0.02) and also a trend toward longer symptom-free survival compared to the extensive colectomy patient group (p = 0.105). There was no correlation between the length of resected bowel and recurrence. Patients operated on at a younger age did not have a higher rate of recurrence of symptoms. Shorter disease duration, smoking, and male gender were risk factors for clinical recurrence. CONCLUSIONS Segmental resection with primary anastomosis can be safely performed in patients with limited Crohn's colitis with reasonable clinical recurrence rates.
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Affiliation(s)
- M Handler
- Colorectal Unit, Division of Surgery, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv Medical Center, Tel-Aviv University, 6 Weizman Street, 6423906, Tel-Aviv, Israel
| | - I Dotan
- IBD Center, Department of Gastroenterology and Liver Diseases, Tel-Aviv Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - J M Klausner
- Colorectal Unit, Division of Surgery, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv Medical Center, Tel-Aviv University, 6 Weizman Street, 6423906, Tel-Aviv, Israel
| | - H Yanai
- IBD Center, Department of Gastroenterology and Liver Diseases, Tel-Aviv Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - E Neeman
- Colorectal Unit, Division of Surgery, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv Medical Center, Tel-Aviv University, 6 Weizman Street, 6423906, Tel-Aviv, Israel
| | - H Tulchinsky
- Colorectal Unit, Division of Surgery, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv Medical Center, Tel-Aviv University, 6 Weizman Street, 6423906, Tel-Aviv, Israel.
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Chang S, Malter L, Hudesman D. Disease monitoring in inflammatory bowel disease. World J Gastroenterol 2015; 21:11246-11259. [PMID: 26523100 PMCID: PMC4616202 DOI: 10.3748/wjg.v21.i40.11246] [Citation(s) in RCA: 126] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2015] [Revised: 07/26/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
The optimal method for monitoring quiescent disease in patients with Crohn’s disease (CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive, costly, and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease (IBD), but the most widely adopted biomarkers are C-reactive protein (CRP) and fecal calprotectin (FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing, traditionally used for colorectal cancer screening, is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers, clinical status, and endoscopic evaluation, the best treatment decisions can be made for the patient with IBD.
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Sumi R, Nakajima K, Iijima H, Wasa M, Shinzaki S, Nezu R, Inoue Y, Ito T. Influence of nutritional status on the therapeutic effect of infliximab in patients with Crohn's disease. Surg Today 2015; 46:922-9. [PMID: 26438200 DOI: 10.1007/s00595-015-1257-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 09/02/2015] [Indexed: 12/21/2022]
Abstract
PURPOSE Crohn's disease (CD) is a refractory inflammatory bowel disease of unknown etiology, frequently complicated by malnutrition. It is thought that the delayed wound healing associated with this malnutrition in CD patients might adversely affect the therapeutic benefits of infliximab (IFX). Therefore, we investigated the effects of nutritional status on IFX treatment. METHODS We assessed nutritional status and CD activity when IFX therapy was initiated and following the third dose, 6 weeks later. Nutritional status was assessed using the body mass index (BMI) and nutritional risk index (NRI), whereas CD activity was assessed using the CD activity index (CDAI). RESULTS All patients with a BMI ≥ 18.5 kg/m(2) at the time of IFX therapy met the effective criteria for the CDAI, and IFX treatment was considered responsive in these patients. Furthermore, IFX treatment was responsive, with a high level of effectiveness, in all five subjects (31.3 %) with NRI scores of 97.5 and above with no risk of malnutrition (p = 0.037). CONCLUSIONS Our results suggest that nutritional status does influence the therapeutic effect of IFX in CD patients. The response rate to IFX treatment thus could be improved by optimizing the nutritional status. We recommend comprehensive nutritional assessment and intervention prior to IFX treatment schedules.
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Affiliation(s)
- Ryoko Sumi
- Division of Nutrition and Medical Engineering, Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.,Department of Integrative Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kiyokazu Nakajima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2, E-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Hideki Iijima
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Masafumi Wasa
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Shinichiro Shinzaki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Riichiro Nezu
- Nishinomiya Municipal Central Hospital, Hyogo, Japan
| | - Yoshifumi Inoue
- Division of Nutrition and Medical Engineering, Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan
| | - Toshinori Ito
- Department of Integrative Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.,Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2, E-2, Yamadaoka, Suita, Osaka, 565-0871, Japan
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Pellino G, Selvaggi F, Ghezzi G, Corona D, Riegler G, Delaini GG. A think tank of the Italian society of colorectal surgery (SICCR) on the surgical treatment of inflammatory bowel disease using the Delphi method: Crohn's disease. Tech Coloproctol 2015; 19:639-651. [PMID: 26403232 DOI: 10.1007/s10151-015-1368-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Accepted: 07/08/2015] [Indexed: 12/18/2022]
Abstract
The management of Crohn's disease (CD) requires extensive expertise. Many treatment options are available, and surgery still plays a crucial role. In recent years, many medical societies have provided surgeons and gastroenterologists dealing with CD with authoritative guidelines. However, a certain degree of variation can be observed in these papers, and application of guidelines in clinical practice should be improved. The Italian society of colorectal surgery (SICCR) promoted the project reported here, which consists of a think tank of Italian colorectal surgeons to address the surgical aspects of CD management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of CD. The management of CD is, by necessity, patient-tailored, and it is based on clinical data and surgeon's preference, but the committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.
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Affiliation(s)
- G Pellino
- Colorectal Surgery Unit, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Piazza Miraglia, 2, 80138, Naples, Italy
| | - F Selvaggi
- Colorectal Surgery Unit, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Piazza Miraglia, 2, 80138, Naples, Italy.
| | - G Ghezzi
- Department of General and Hepatobiliary Surgery, Policlinico "G.B. Rossi", University of Verona, Verona, Italy
| | - D Corona
- Department of General and Hepatobiliary Surgery, Policlinico "G.B. Rossi", University of Verona, Verona, Italy
| | - G Riegler
- Gastroenterology Unit, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Piazza Miraglia, 2, 80138, Naples, Italy
| | - G G Delaini
- Department of Surgery, "Pederzoli" Hospital, Peschiera del Garda, Verona, Italy
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Mondal P, Trigun SK. Bacopa monnieri Extract (CDRI-08) Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2015; 2015:535013. [PMID: 26413124 PMCID: PMC4564645 DOI: 10.1155/2015/535013] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Revised: 02/09/2015] [Accepted: 02/09/2015] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells. Bacopa monnieri (BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE.
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Affiliation(s)
- Papia Mondal
- Biochemistry Section, Department of Zoology, Banaras Hindu University, Varanasi 221005, India
| | - Surendra Kumar Trigun
- Biochemistry Section, Department of Zoology, Banaras Hindu University, Varanasi 221005, India
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Gordon M, Taylor K, Akobeng AK, Thomas AG. Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease. Cochrane Database Syst Rev 2014; 2014:CD010233. [PMID: 25081347 PMCID: PMC6486089 DOI: 10.1002/14651858.cd010233.pub2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic relapsing inflammatory condition. Many patients fail to achieve remission with medical management and require surgical interventions. Purine analogues have been used to maintain surgically-induced remission in CD, but the effectiveness of these agents is unclear. OBJECTIVES The objectives were to evaluate the efficacy and safety of purine analogues for maintenance of surgically-induced remission in CD. SEARCH METHODS We searched the following databases from inception to 30 April 2014: PubMed, MEDLINE, EMBASE, CENTRAL, and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register). We also searched the reference lists of all included studies, and contacted personal sources and drug companies to identify additional studies. The searches were not limited by language. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared purine analogues to placebo or another intervention, with treatment durations of at least six months were considered for inclusion. Participants were patients of any age with CD in remission following surgery. DATA COLLECTION AND ANALYSIS Two authors independently assessed trial eligibility and extracted data. Methodological quality was assessed using the Cochrane risk of bias tool. The primary outcome measures were clinical and endoscopic relapse as defined by the primary studies. Secondary outcomes included adverse events, withdrawal due to adverse events and serious adverse events. Data were analysed on an intention-to-treat basis where patients with missing final outcomes were assumed to have relapsed. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes. The Chi(2) and I(2) statistics were used to assess heterogeneity. The overall quality of the evidence supporting the primary outcomes and selected secondary outcomes was assessed using the GRADE criteria. MAIN RESULTS Seven RCTs (n = 584 patients) were included in the review. Three studies compared azathioprine to 5-aminosalicylic acid (5-ASA). One small study compared azathioprine to both 5-ASA and adalimumab. One study compared azathioprine to placebo and another study compared 6-mercaptopurine to 5-ASA and placebo. One small study compared azathioprine to infliximab. Three studies were judged to be at low risk of bias. Four studies were judged to be at high risk of bias due to blinding. The study (n = 22) comparing azathioprine to infliximab found that the effects on the proportion of patients who had a clinical (RR 2.00, 95% CI 0.21 to 18.98) or endoscopic relapse (RR 4.40, 95% CI 0.59 to 3.07) were uncertain. One study (n = 33) found decreased clinical (RR 5.18, 95% CI 1.35 to 19.83) and endoscopic relapse (RR 10.35, 95% CI 1.50 to 71.32) rates favouring adalimumab over azathioprine. A pooled analysis of two studies (n = 168 patients) showed decreased clinical relapse rates at one or two years favouring purine analogues over placebo. Forty-eight per cent of patients in the purine analogue group experienced a clinical relapse compared to 63% of placebo patients (RR 0.74, 95% CI 0.58 to 0.94). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to high risk of bias (one study was single-blind) and sparse data (93 events). One study (87 patients) found a reduction in endoscopic relapse rates favouring 6-mercaptopurine over placebo. Seventeen per cent of 6-mercaptopurine patients had an endoscopic relapse at two years compared to 42% of placebo patients (RR 0.40, 95% CI 0.19 to 0.83). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to very sparse data (25 events). A pooled analysis of five studies (n = 425 patients) showed no difference in clinical relapse rates at one or two years between purine analogues and 5-ASA agents. Sixty-three per cent of patients in the purine analogues group experienced a clinical relapse compared to 54% of 5-ASA patients (RR 1.15, 95% CI 0.99 to 1.34). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to high risk of bias (two open-label studies), sparse data (249 events) and moderate heterogeneity (I(2) = 45%). There was no difference in endoscopic relapse at 12 months between azathioprine and 5-ASA (RR 0.78, 95% CI 0.52 to 1.17; 1 study, 35 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was very low due to high risk of bias (open-label study) and very sparse data (26 events). There was a reduction in endoscopic relapse at 24 months favouring 6-mercaptopurine over 5-ASA patients. Seventeen per cent of 6-mercaptopurine patients had an endoscopic relapse compared to 48% of 5-ASA patients (RR 0.36, 95% CI 0.18 to 0.72; 1 study, 91 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to very sparse data (29 events). Adverse events that required withdrawal were more common in the purine analogue group compared to 5-ASA. Twenty per cent of patients in the purine analogue group withdrew due to adverse events compared to 10% of 5-ASA patients (RR 2.07, 95% CI 1.26 to 3.39; 5 studies, 423 patients).The results for withdrawal due to adverse events between purine analogues and placebo or for other comparisons were uncertain. Commonly reported adverse events across all studies included leucopenia, arthralgia, abdominal pain or severe epigastric intolerance, elevated liver enzymes, nausea and vomiting, pancreatitis, anaemia, exacerbation of Crohn's disease, nasopharyngitis, and flatulence. AUTHORS' CONCLUSIONS Purine analogues may be superior to placebo for maintenance of surgically-induced remission in patients with CD, although this is based on two small studies. The results for efficacy outcomes between purine analogues and 5-ASA agents were uncertain. However, patients taking purine analogues were more likely than 5-ASA patients to discontinue therapy due to adverse events. No firm conclusions can be drawn from the two small studies that compared azathioprine to infliximab or adalimumab. Adalimumab may be superior to azathioprine but further research is needed to confirm these results. Further research investigating the efficacy and safety of azathioprine and 6-mercaptopurine in comparison to other active medications in patients with surgically-induced remission of CD is warranted.
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Affiliation(s)
| | - Kelly Taylor
- North Manchester General HospitalDepartment of PaediatricsCrumpsallUK
| | | | - Adrian G Thomas
- Royal Manchester Children's HospitalOxford RoadManchesterUKM13 9WL
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Sasaki T, Kunisaki R, Kinoshita H, Kimura H, Kodera T, Nozawa A, Hanzawa A, Shibata N, Yonezawa H, Miyajima E, Morita S, Fujii S, Numata K, Tanaka K, Tanaka M, Maeda S. Doppler ultrasound findings correlate with tissue vascularity and inflammation in surgical pathology specimens from patients with small intestinal Crohn's disease. BMC Res Notes 2014; 7:363. [PMID: 24927748 PMCID: PMC4080771 DOI: 10.1186/1756-0500-7-363] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Accepted: 05/26/2014] [Indexed: 12/14/2022] Open
Abstract
Background Crohn’s disease (CD) is routinely evaluated using clinical symptoms, laboratory variables, and the CD activity index (CDAI). However, clinical parameters are often nonspecific and do not precisely reflect the actual activity of CD small-intestinal lesions. The purposes of this prospective study were to compare color Doppler ultrasound (US) findings with histological findings from surgically resected specimens and confirm the hypothesis that color Doppler US can distinguish tissue inflammation and fibrosis. Methods Among 1764 consecutive patients who underwent color Doppler US examinations, 10 patients with CD (12 small-intestinal CD lesions) who underwent US examinations before elective small-intestine resection were evaluated in the present study. Areas of thickened intestinal walls were evaluated in terms of blood flow using color Doppler US imaging. The blood flow was semiquantitatively classified as “hyper-flow” and “hypo-flow” according to the Limberg score. Resected lesions were macroscopically and histopathologically processed. Inflammatory cell infiltration, fibrosis and vascularity were evaluated by myeloperoxidase (granulocytes), CD163 (macrophages), CD79a (B cells), CD3 (T cells), Masson’s trichrome (fibrosis), and factor VIII staining (vascular walls). All histopathological images were entered into virtual slide equipment and quantified using a quantitative microscopy integrated system (TissueMorph™). Results There were no significant differences in disease features or laboratory findings between “hypo-flow” lesions (n = 4) and “hyper-flow” lesions (n = 8). Histopathologically, “hyper-flow” lesions showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T cells, and CD79a B cells (p = 0.043), than did “hypo-flow” lesions. There was no apparent association between the blood flow and CDAI. Conclusions In this study, active CD lesions were macroscopically visible in surgical specimens of patients with increased blood flow on preoperative color Doppler US imaging. Additionally, these CD lesions exhibited significantly greater vascularity and numbers of inflammatory leukocytes microscopically. Color Doppler US may predict tissue inflammation and fibrosis in small-intenstinal CD lesions.
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Affiliation(s)
| | - Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan.
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Ueno F, Matsui T, Matsumoto T, Matsuoka K, Watanabe M, Hibi T. Evidence-based clinical practice guidelines for Crohn's disease, integrated with formal consensus of experts in Japan. J Gastroenterol 2013; 48:31-72. [PMID: 23090001 PMCID: PMC3541931 DOI: 10.1007/s00535-012-0673-1] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2012] [Accepted: 08/16/2012] [Indexed: 02/04/2023]
Abstract
Crohn's disease is a disorder of unknown etiology and complicated pathogenesis. A substantial amount of evidence has accumulated recently and has been applied to clinical practice. The present guidelines were developed based on recent evidence and the formal consensus of experts relevant to this disease. Here we provide an overview of these guidelines, as follows. Target disease: Crohn's disease Users: Clinical practitioners in internal medicine, surgery, gastroenterology, and general practice Purpose: To provide appropriate clinical indicators to practitioners Scope of clinical indicators: Concept of Crohn's disease, epidemiology, classifications, diagnosis, treatment, follow up, and special situations Intervention: Diagnosis (interview, physical examination, clinical laboratory tests, imaging, and pathology) and treatment (lifestyle guidance, drug therapy, nutritional therapy, surgery, etc.) Outcome assessment: Attenuation of symptoms, induction and maintenance of remission, imaging findings, quality of life (QOL), prevention of complications and harm of therapy Methods for developing these guidelines: Described in the text Basis of recommendations: Integration of evidence level and consensus of experts Cost-benefit analysis: Not implemented Evaluation of effectiveness: Yet to be confirmed Status of guidelines: Updated version of the first Guidelines published in 2010 Publication sources: Printed publication available and electronic information in preparation Patient information: Not available Date of publication: October 2011 These guidelines were intended primarily to be used by practitioners in Japan, and the goal of these guidelines is to improve the outcomes of patients with Crohn's disease.
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Affiliation(s)
| | - Toshiyuki Matsui
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Takayuki Matsumoto
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Katsuyoshi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshifumi Hibi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
| | - On Behalf of the Guidelines Project Group of the Research Group of Intractable Inflammatory Bowel Disease subsidized by the Ministry of Health, Labour and Welfare of Japan and the Guidelines Committee of the Japanese Society of Gastroenterology
- Ofuna Chuo Hospital, Kanagawa, Japan
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi Shinjuku, Tokyo, 160-8582 Japan
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
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Cortesi R, Ravani L, Menegatti E, Esposito E, Ronconi F. Eudragit(®) microparticles for the release of budesonide: a comparative study. Indian J Pharm Sci 2012; 74:415-21. [PMID: 23716869 PMCID: PMC3660867 DOI: 10.4103/0250-474x.108416] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Revised: 10/02/2012] [Accepted: 10/10/2012] [Indexed: 01/19/2023] Open
Abstract
This study compares the behaviour of budesonide-containing microparticles made of Eudragit(®)RS or Eudragit(®)RS/Eudragit(®)RL 70:30 (w/w) prepared either by solvent evaporation or spray-drying technique. The loading efficiency of budesonide within microparticles was about 72% for microparticles prepared by solvent evaporation and around 78% for spray-dried microparticles. Thermal analyses were assessed to collect information about the structural stability of budesonide within the polymeric microspheres. The in vitro release was performed using simulating gastric (fasted state simulated gastric fluid) and intestinal (fasted state simulated intestinal fluid) fluids as the receiving solutions. After 3 h the drug release from Eudragit(®)RS/Eudragit(®)RL microparticles was about 6-fold higher than that obtained in the case of monopolymer microparticles. Using fasted state simulated intestinal fluid the drug was released between 4 and 30% in both types of preparations. Eudragit(®)RS microparticles showed a better protection of the drug from gastric acidity than those of Eudragit(®)RS/Eudragit(®)RL allowing us to propose Eudragit(®)RS microparticles as a hypothetical system of colon specific controlled delivery.
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Affiliation(s)
- Rita Cortesi
- Department of Life Sciences and Biotechnology, University of Ferrara, 44121-Ferrara, Italy
| | - Laura Ravani
- Department of Life Sciences and Biotechnology, University of Ferrara, 44121-Ferrara, Italy
| | - Enea Menegatti
- Department of Life Sciences and Biotechnology, University of Ferrara, 44121-Ferrara, Italy
| | - Elisabetta Esposito
- Department of Life Sciences and Biotechnology, University of Ferrara, 44121-Ferrara, Italy
| | - F. Ronconi
- Department of Physics, University of Ferrara, 44121-Ferrara, Italy
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31
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Gupta M, Goyal S, Goyal R. Crohn's disease presenting as acute abdomen: Report of two cases. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2012; 3:209-11. [PMID: 22540094 PMCID: PMC3336915 DOI: 10.4297/najms.2011.3209] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Context: Crohn's Disease may involve any part of GI tract leading to inflammation of all the layers of the affected bowel. The symptoms may mimc other intestinal pathologies and at times diagnosis remains a dilemma. Mostly medical therapy remains the mainstay of treatment. However surgical intervention is warranted in cases presenting with acute abdomen.
Case Report: We present two such cases of acute abdomen admitted in our hospital and diagnosed as case of intestinal obstruction. Exploratory laparotomy was performed in both cases and diseased resected segments were confirmed as Crohn's Disease on histopathology. Conclusion: Crohn's Disease should be kept as a differential diagnosis in patients presenting with acute abdomen especially with a long history of vague abdominal complaints.
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Affiliation(s)
- Mahesh Gupta
- Department of Surgery, M.M. Institute Of Medical Sciences And Research, Mullana, (Distt - Ambala), Haryana, India
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32
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Systems analysis of inflammatory bowel disease based on comprehensive gene information. BMC MEDICAL GENETICS 2012; 13:25. [PMID: 22480395 PMCID: PMC3368714 DOI: 10.1186/1471-2350-13-25] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2011] [Accepted: 04/05/2012] [Indexed: 12/19/2022]
Abstract
Background The rise of systems biology and availability of highly curated gene and molecular information resources has promoted a comprehensive approach to study disease as the cumulative deleterious function of a collection of individual genes and networks of molecules acting in concert. These "human disease networks" (HDN) have revealed novel candidate genes and pharmaceutical targets for many diseases and identified fundamental HDN features conserved across diseases. A network-based analysis is particularly vital for a study on polygenic diseases where many interactions between molecules should be simultaneously examined and elucidated. We employ a new knowledge driven HDN gene and molecular database systems approach to analyze Inflammatory Bowel Disease (IBD), whose pathogenesis remains largely unknown. Methods and Results Based on drug indications for IBD, we determined sibling diseases of mild and severe states of IBD. Approximately 1,000 genes associated with the sibling diseases were retrieved from four databases. After ranking the genes by the frequency of records in the databases, we obtained 250 and 253 genes highly associated with the mild and severe IBD states, respectively. We then calculated functional similarities of these genes with known drug targets and examined and presented their interactions as PPI networks. Conclusions The results demonstrate that this knowledge-based systems approach, predicated on functionally similar genes important to sibling diseases is an effective method to identify important components of the IBD human disease network. Our approach elucidates a previously unknown biological distinction between mild and severe IBD states.
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Gionchetti P, Calabrese C, Tambasco R, Brugnera R, Straforini G, Liguori G, Fornarini GS, Riso D, Campieri M, Rizzello F. Role of conventional therapies in the era of biological treatment in Crohn’s disease. World J Gastroenterol 2011; 17:1797-806. [PMID: 21528051 PMCID: PMC3080713 DOI: 10.3748/wjg.v17.i14.1797] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2010] [Revised: 07/12/2010] [Accepted: 07/19/2010] [Indexed: 02/06/2023] Open
Abstract
Outstanding progress regarding the pathophysiology of Crohn’s disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized, placebo-controlled trials, and meta-analyses when available, that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD, modifying the treatment goals. However, the large majority of patients with CD will be managed through conventional therapy, even if they are a prelude to biological therapy.
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Abstract
Crohn's disease represents a challenging operative dilemma. The nature of the disease increases the technical complexity of operations, their morbidity, and the likelihood of multiple operations. In this setting, the advantages of laparoscopic surgery, including shorter hospital stays, less adhesion formation, fewer wound complications, and faster recovery of bowel function, are particularly beneficial to the patient. Patients with Crohn's disease requiring operations in the elective and semi-elective setting can all be approached initially laparoscopically. The surgeon's skill set should include extensive experience in advanced laparoscopic bowel surgery as well as open management of Crohn's disease and its complications. Strict adherence to the basic tenet of bowel preservation is imperative. The operations most commonly performed for Crohn's disease include diagnostic laparoscopy, stricturoplasty, small bowel resection, ileocolic resection, colectomy, repair of fistulae, and gastrojejunostomy for bypass of gastric or duodenal disease. Postoperative management includes resumption of steroids, typically without the need for "stress-dosing," bowel rest for a short period, and pain control, which is also less than that experienced with a laparotomy.
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Affiliation(s)
- Murali N Naidu
- Division of Laparoscopic Surgery, Mount Sinai School of Medicine, New York, NY 10029, USA
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35
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Westbrook AM, Szakmary A, Schiestl RH. Mechanisms of intestinal inflammation and development of associated cancers: lessons learned from mouse models. Mutat Res 2010; 705:40-59. [PMID: 20298806 PMCID: PMC2878867 DOI: 10.1016/j.mrrev.2010.03.001] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2009] [Revised: 02/21/2010] [Accepted: 03/08/2010] [Indexed: 12/15/2022]
Abstract
Chronic inflammation is strongly associated with approximately 1/5th of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With regards to extraintestinal manifestations such as lymphoma, however, more suitable models are required to further investigate the complex and heterogeneous mechanisms that may be at play.
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Affiliation(s)
- Aya M. Westbrook
- Molecular Toxicology Interdepartmental Program, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095
- Department of Pathology and Lab Medicine, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095
| | - Akos Szakmary
- Institute for Cancer Research, Medical University of Vienna, Austria
| | - Robert H. Schiestl
- Molecular Toxicology Interdepartmental Program, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095
- Department of Pathology and Lab Medicine, UCLA School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, CA 90095
- Institute for Cancer Research, Medical University of Vienna, Austria
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Lee JS, Park SY, Thapa D, Choi MK, Chung IM, Park YJ, Yong CS, Choi HG, Kim JA. Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-alpha production and its signaling. Exp Mol Med 2010; 42:143-54. [PMID: 20054232 DOI: 10.3858/emm.2010.42.2.016] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 micg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.
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Affiliation(s)
- Jong Suk Lee
- College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea
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37
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Abstract
Crohn's disease (CD) is a chronic relapsing and remitting disorder of the gastrointestinal tract with no known cure. The inflammation that drives the disease can lead to debilitating symptoms and a number of complications that may lead to surgery. The introduction of biologic therapy a decade ago has offered a new option for patients failing conventional therapy. Over time, biologic therapy has also led to the desire to achieve treatment goals beyond the control of symptoms. In order to achieve short-term and long-term goals with these new agents, it is important to review how these therapies may be optimized for the best results.
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Affiliation(s)
- Remo Panaccione
- Director, Inflammatory Bowel Disease Clinic, Assistant Professor of Medicine, University of Calgary, Rm. 6D32, TRW Building, 3280 Hospital Drive NW, Calgary, Alberta T2N 4N1
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38
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Eren F, Akkiprik M, Atuğ O, Sönmez O, Tahan G, Ozdemir F, Hamzaoğlu HO, Celikel CA, Imeryüz N, Avşar E, Ozer A. R72P polymorphism of TP53 in ulcerative colitis patients is associated with the incidence of colectomy, use of steroids and the presence of a positive family history. Pathol Oncol Res 2010; 16:563-8. [PMID: 20309662 DOI: 10.1007/s12253-010-9255-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2009] [Accepted: 02/24/2010] [Indexed: 12/14/2022]
Abstract
P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR = 3.03; 95%CI = 1.91-2.40; p = 0.003), but only modest association with UC (OR = 1.61; 95%CI = 0.98-2.65; p = 0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR = 8.0; 95%CI = 1.68-38.08, p = 0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR = 17.77; 95%CI = 0.98-323.34, p = 0.012) and steroid use (OR = 10.14; 95%CI = 2.63-39.12, p = 0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.
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Affiliation(s)
- Fatih Eren
- School of Medicine, Department of Medical Biology, Marmara University, Tibbiye Cad, No 49, Haydarpasa, 34668 Istanbul, Turkey
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Kim ES, Kim WH. Inflammatory bowel disease in Korea: epidemiological, genomic, clinical, and therapeutic characteristics. Gut Liver 2010; 4:1-14. [PMID: 20479907 PMCID: PMC2871616 DOI: 10.5009/gnl.2010.4.1.1] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2009] [Accepted: 10/04/2009] [Indexed: 12/16/2022] Open
Abstract
Inflammatory bowel disease (IBD) describes chronic inflammatory disease of the intestines and has a variable course; Crohn's disease and ulcerative colitis comprise the two main forms of the condition. Although IBD occurs worldwide, its epidemiologic and clinical characteristics vary depending upon the geographic location and the ethnicity of the population. Identifying the characteristic features of IBD in populations living in different geographical locations and with different ethnicities may provide significant clues about its etiology and pathophysiology, which in turn may be helpful in the development of more appropriate treatment strategies for IBD for these different populations. Therefore, it is important for each country and region to evaluate critically the epidemiology, genomics, and clinical characteristics of IBD among its own population. We have performed a critical review of the recent data in Korea, and describe herein the current epidemiologic and genotypic status, as well as the clinical manifestations and therapeutic responses of IBD that are unique to Korean patients.
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Affiliation(s)
- Eun Soo Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Won Ho Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Iacucci M, de Silva S, Ghosh S. Mesalazine in inflammatory bowel disease: a trendy topic once again? CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2010; 24:127-33. [PMID: 20151072 PMCID: PMC2852235 DOI: 10.1155/2010/586092] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2009] [Accepted: 03/21/2009] [Indexed: 12/19/2022]
Abstract
5-aminosalicylic acid (5-ASA) preparations (eg, mesalazine, mesalamine) are well-established preparations used in the management of inflammatory bowel disease. These drugs are most useful for the treatment of mild to moderate flares of ulcerative colitis and, especially, for maintenance of remission. Although most gastroenterologists are very familiar with these drugs, the interest in these drugs has undergone a resurgence, with new preparations offering convenience and high dosage, while preserving their customary safety. New dosage regimens are likely to become standard practice in the near future. There is also considerable interest in chemoprevention of colorectal cancer in the context of inflammatory bowel disease, and the role of long-term maintenance therapy with 5-ASAs in achieving such chemoprevention. A mechanism of action for such chemoprevention has been provided by the agonism of the peroxisome proliferator-activated receptor-gamma by 5-ASA, which unifies its efficacy as an anti-inflammatory and chemopreventive agent. In the future, even more effective agents based on 5-ASA are expected, based on more powerful agonism of peroxisome proliferator-activated receptor-gamma; 5-ASA preparations have become 'trendy' again.
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Affiliation(s)
- Marietta Iacucci
- Gastrointestinal Unit, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Shanika de Silva
- Division of Gastroenterology, University of Calgary, Calgary, Alberta
| | - Subrata Ghosh
- Division of Gastroenterology, University of Calgary, Calgary, Alberta
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Sahasranaman S, Howard D, Roy S. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol 2008; 64:753-67. [PMID: 18506437 DOI: 10.1007/s00228-008-0478-6] [Citation(s) in RCA: 265] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2007] [Accepted: 02/20/2008] [Indexed: 02/07/2023]
Abstract
The thiopurine drugs-azathioprine (AZA), 6-mercaptopurine (6-MP), and thioguanine-are widely used to treat malignancies, rheumatic diseases, dermatologic conditions, inflammatory bowel disease, and solid organ transplant rejection. However, thiopurine drugs have a relatively narrow therapeutic index and are capable of causing life-threatening toxicity, most often myelosuppression. Thiopurine S-methyltransferase (TPMT; EC 2.1.1.67), an enzyme that catalyzes S-methylation of these drugs, exhibits a genetic polymorphism in 10% of Caucasians, with 1/300 individuals having complete deficiency. Patients with intermediate or deficient TPMT activity are at risk for excessive toxicity after receiving standard doses of thiopurine medications. This report reviews the recent advances in the knowledge of the mechanism of action as well as the molecular basis and interethnic variations of TPMT and inosine triphosphate pyrophosphatase (ITPase; EC 3.6.1.19), another enzyme implicated in thiopurine toxicity. In addition, an update on pharmacokinetics, metabolism, drug-drug interactions, safety, and tolerability of thiopurine drugs is provided.
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Affiliation(s)
- Srikumar Sahasranaman
- Drug Metabolism and Pharmacokinetics, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA
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Self-management for people with inflammatory bowel disease. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2008; 22:281-7. [PMID: 18354757 DOI: 10.1155/2008/428967] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
In North America and the United Kingdom, we are in the age of self-management. Many patients with chronic diseases are ready to participate in the therapeutic decision-making process, and join their physicians in a co-management model. It is particularly useful to consider this concept at a time when physician shortages and waiting times are on the front page every day, with no immediate prospect of relief. Conditions such as diabetes, asthma, chronic obstructive pulmonary disease, recurrent urinary tract infections and others lend themselves to this paradigm of medical care for the informed patient. The present paper reviews some of the literature on self-management for the patient with inflammatory bowel disease (IBD), and provides a framework for the use of self-management in the IBD population, with emphasis on the concept of a patient passport, and the use of e-mail, supported by an e-mail contract, as proposed by the Canadian Medical Protective Association. Examples of specific management strategies are provided for several different IBD scenarios. Eliminating the need for some office visits has clear environmental and economical benefits. Potential negative consequences of this form of patient care are also discussed.
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Abstract
The clinical course of Crohn's disease (CD) is characterized by unpredictable phases of disease activity and quiescence. The majority of CD patients experience mild to moderate disease or are in clinical remission over significant periods during the course of their disease. These patients can be treated conservatively with 5-aminosalicylates or budesonide depending on the disease location. Those patients with more severe forms of the disease who require corticosteroids should be treated more aggressively with early introduction of immunomodulator and/or biologic therapy, which may help to prevent the complications associated with CD. It has been suggested that therapies directed at mucosal healing may favorably modify the natural history of CD. As newer, more effective medications become available and new therapeutic approaches are introduced (top-down therapy), mucosal healing, and not solely clinical remission, may well become the preferred treatment objective.
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Affiliation(s)
- Paul A. Feldman
- Division of Gastroenterology, Leonard Miller School of Medicine/University of Miami, Mount Sinai Medical Center, Miami Florida
| | - Daniel Wolfson
- Division of Gastroenterology, Leonard Miller School of Medicine/University of Miami, Mount Sinai Medical Center, Miami Florida
| | - Jamie S. Barkin
- Division of Gastroenterology, Leonard Miller School of Medicine/University of Miami, Mount Sinai Medical Center, Miami Florida
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Caviglia R, Ribolsi M, Rizzi M, Emerenziani S, Annunziata ML, Cicala M. Maintenance of remission with infliximab in inflammatory bowel disease: efficacy and safety long-term follow-up. World J Gastroenterol 2007; 13:5238-5244. [PMID: 17876895 PMCID: PMC4171306 DOI: 10.3748/wjg.v13.i39.5238] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2007] [Revised: 08/08/2007] [Accepted: 09/24/2007] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the safety and efficacy of a long-term therapy with infliximab in Crohn's disease (CD) and ulcerative colitis (UC) patients retrospectively. METHODS The medical charts of 50 patients (40 CD and 10 UC), who received after a loading dose of 3 infliximab infusions scheduled re-treatments every 8 wk as a maintenance protocol, were reviewed. RESULTS Median (range) duration of treatment was 27 (4-64) mo in CD patients and 24.5 (6-46) mo in UC patients. Overall, 32 (80%) CD and 9 (90%) UC patients showed a sustained clinical response or remission throughout the maintenance period. Three CD patients shortened the interval between infusions. Eight (20%) CD patients and 1 UC patient underwent surgery for flare up of disease. Nine out of 29 CD and 4 out of 9 UC patients, who discontinued infliximab scheduled treatment, are still relapse-free after a median of 16 (5-30) and 6.5 (4-16) mo following the last infusion, respectively. Ten CD patients (25%) and 1 UC patient required concomitant steroid therapy during maintenance period, compared to 30 (75%) and 9 (90%) patients at enrollment. Of the 50 patients, 16 (32%) experienced at least 1 adverse event and 3 patients (6%) were diagnosed with cancer during maintenance treatment. CONCLUSION Scheduled infliximab strategy is effective in maintaining long-term clinical remission both in CD and UC and determines a marked steroid sparing effect. Long-lasting remission was observed following infliximab withdrawal.
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Affiliation(s)
- Renato Caviglia
- University Campus Bio-Medico, Department of Digestive Disease, Via E Longoni, Rome, Italy.
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Kristinsson JO, Hopman WPM, Oyen WJG, Drenth JPH. Gastroparesis in patients with inactive Crohn's disease: a case series. BMC Gastroenterol 2007; 7:11. [PMID: 17376243 PMCID: PMC1838914 DOI: 10.1186/1471-230x-7-11] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2006] [Accepted: 03/21/2007] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Few studies have described patients with foregut dysmotility in inflammatory bowel disease. The aim of this case series was to evaluate clinical characteristics of 5 patients with inflammatory bowel disease and symptoms and signs of upper gut dysmotility. CASE PRESENTATIONS We describe a series of four patients with Crohn's disease and one with indeterminate colitis who presented with severe symptoms and signs of gastroparesis. We reviewed medical records of all cases. Gastric emptying of a solid meal was assessed by scintigraphy. Small bowel enteroclysis, gastroduodenoscopy and colonoscopy with biopsies were performed to estimate the activity of the disease and to exclude organic obstruction. None of the patients had any signs of active inflammation or stricture. All of the patients had markedly delayed gastric emptying with a mean t 1/2 of 234 minutes (range 110-380 minutes; normal values 54-94 minutes). CONCLUSION Clinicians should consider impaired gastric emptying when evaluating patients with Crohn's disease and severe symptoms of upper gut dysmotility, which cannot be attributed to active inflammation or organic obstruction of the digestive tract. Symptoms in these patients are refractory to various therapeutic interventions including tube feeding and gastric surgery.
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Affiliation(s)
- Jón O Kristinsson
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Wim PM Hopman
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Wim JG Oyen
- Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Joost PH Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
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Dinesen L, Travis S. Targeting nanomedicines in the treatment of Crohn's disease: focus on certolizumab pegol (CDP870). Int J Nanomedicine 2007; 2:39-47. [PMID: 17722511 PMCID: PMC2673818 DOI: 10.2147/nano.2007.2.1.39] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
A variety of targets for therapeutic intervention are based upon advances in understanding of the immunopathogenesis of Crohn's disease. Crohn's disease is initiated by an innate immune response, which eventuates in a T-cell driven process, characterized by a T-helper cell 1 type cytokine profile. Several new treatments now focus on suppressing T-cell differentiation or T-cell inflammation. Since inflammatory bowel disease (IBD) represents a state of dysregulated inflammation, drugs that augment the anti-inflammatory response have the potential to downregulate inflammation and thereby hopefully modify the disease. Tumour necrosis factor (TNF) is a major target of research and clinical investigation. TNF has proinflammatory effects in the intestinal mucosa and is a pivotal cytokine in the inflammatory cascade. Certolizumab pegol (CDP870) is a PEGylated, Fab' fragment of a humanized anti-TNF-alpha monoclonal antibody. PEGylation increases the half-life, reduces the requirement for frequent dosing, and possibly reduces antigenicity as well. Certolizumab has been shown in Phase III trials to achieve and maintain clinical response and remission in Crohn's disease patients. It improves the quality of life. Certolizumab pegol will be indicated for moderately to severely active Crohn's disease, but it is not yet licensed in Europe or the US. It is not possible to construct an algorithm for treatment, but when compared with infliximab the two principal advantages are likely to be lower immunogenicity (as shown by anti-drug antibodies, absence of infusion reactions, and low rate of antinuclear antibodies), and a subcutaneous route of administration. These two factors may be sufficient to promote it up the pecking order of anti-TNF agents.
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Affiliation(s)
- Lotte Dinesen
- Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
| | - Simon Travis
- Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
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Abstract
Crohn’s disease (CD) is a multifactorial disorder of unknown cause. Outstanding progress regarding the pathophysiology of CD has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD over the last years. However, many drugs have not been approved by regulatory authorities due to lack of efficacy or severe side effects. Therefore, well-known drugs, including 5-ASA, systemic or topical corticosteroids, and immunosuppressants such as azathioprine, are still the mainstay of CD therapy. Importantly, biologicals such as infliximab have shown to be efficacious in problematic settings such as fistulizing or steroid-dependent CD. This review is intended to give practical guidelines to clinicians for the conventional treatment of CD. We concentrated on the results of randomized, placebo-controlled trials and meta-analyses, when available, that provide the highest degree of evidence. We provide evidence-based treatment algorithms whenever possible. However, many clinical situations have not been answered by controlled clinical trials and it is important to fill these gaps through expert opinions. We hope that this review offers a useful tool for clinicians in the challenging treatment of CD.
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Affiliation(s)
- Carsten Büning
- Department of Gastroenterology, Hepatology & Endocrinology, Charité Campus Mitte, Universitätsmedizin Berlin, Schumannstrasse 20/21, Berlin 10117, Germany.
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Abstract
There is no medical or surgical treatment that provides a permanent cure for Crohn's disease (CD). However, an evolving understanding of the pathogenesis of CD has provided clinicians with a diversity of medical treatment options for the disease. The goal of therapy is to induce and maintain clinical remission. The efficacy of immune-modifying agents such as azathioprine/6-mercaptopurine and infliximab have supported a paradigm shift in CD treatment in which maintenance agents are introduced earlier in the disease course. At the same time, it is imperative to balance the efficacy, safety, and tolerability of medical therapy. Given the variable and relapsing clinical course of CD, the physician and patient should ideally develop an ongoing relationship that allows for individualization of treatment regimens, monitoring of response and side effects, and modification of the therapeutic strategy in the absence of improvement.
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Affiliation(s)
- Shamina Dhillon
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA.
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Abstract
Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. This complex interplay of genetic, microbial and environmental factors culminates in a sustained activation of the mucosal immune and non-immune response, probably facilitated by defects in the intestinal epithelial barrier and mucosal immune system, resulting in active inflammation and tissue destruction. Under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory (tumour necrosis factor [TNF]-alpha, interferon [IFN]-gamma, interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may, therefore, be a logical target for IBD therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, T-helper cell (T(h))-1 polarisation, T-cell activation or nuclear factor (NF)-kappaB, and other miscellaneous therapies are being evaluated as potential therapies for IBD. In this context, infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulising Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP 571, certolizumab pegol (CDP 870), etanercept, onercept and adalimumab. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and selective blockade of these adhesion molecules is a novel and promising strategy to treat Crohn's disease. Therapeutic agents that inhibit leukocyte trafficking include natalizumab, MLN-02 and alicaforsen (ISIS 2302). Other agents being investigated for the treatment of Crohn's disease include inhibitors of T-cell activation, peroxisome proliferator-activated receptors, proinflammatory cytokine receptors and T(h)1 polarisation, and growth hormone and growth factors. Agents being investigated for treatment of ulcerative colitis include many of those mentioned for Crohn's disease. More controlled clinical trials are currently being conducted, exploring the safety and efficacy of old and new biologic agents, and the search certainly will open new and exciting perspectives on the development of therapies for IBD.
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Affiliation(s)
- Sandro Ardizzone
- Chair of Gastroenterology, L. Sacco University Hospital, Milan, Italy
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Greenwald DA, Brandt LJ. Inflammatory Bowel Disease After Age 60. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2003; 6:213-225. [PMID: 12744821 DOI: 10.1007/s11938-003-0003-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
New-onset idiopathic inflammatory bowel disease (IBD) is not uncommon among the elderly, although more common are colonic infection, ischemia, or neoplasia, all of which may mimic IBD. Although the clinical presentation of IBD in the elderly often resembles that of younger subjects, atypical manifestations are common and may lead to difficulty in diagnosis. Much progress has been made in both medical and surgical therapy for IBD, but such therapy poses additional challenges in the elderly, who are more likely to experience adverse effects of medications or complications of surgery. The elderly generally have a favorable outcome to both medical and surgical therapy for IBD. Although concern about possible untoward effects of therapy is warranted, treatment should not be withheld because of fear of complications.
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Affiliation(s)
- David A. Greenwald
- Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA.
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