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Hematopoietic stem cell transplantation for non-malignant gastrointestinal diseases

World Journal of Gastroenterology 2014年第46期20卷 17368-17375页

作者： Abdulbaqi Al-toma Petula Nijeboer Gerd Bouma Otto Visser chris jj mulder Department of Internal Medicine and Gastroenterology 3430 EM NieuwegeinThe Netherlands Department of Gastroenterology VU University Medical Centre1005 MB AmsterdamThe Netherlands Department of Hematology VU University Medical Centre1005 MB AmsterdamThe Netherlands

Both, autologous and allogeneic hematopoietic stem cell transplantation (HSCT) can be used to cure or ameliorate a variety of malignant and non-malignant diseases. The rationale behind this strategy is based on the concept of immunoablation using high-dose chemotherapy, with subsequent regeneration of naive T-lymphocytes derived from reinfused hematopoietic progenitor cells. In addition, the use of HSCT allows for the administration of high-dose chemotherapy (whether or not combined with immunomodulating agents such as antithymocyte globulin) resulting in a prompt remission in therapy-refractory patients. This review gives an update of the major areas of successful uses of HSCT in non-malignant gastrointestinal disorders. A Medline search has been conducted and all relevant published data were analyzed. HSCT has been proved successful in treating refractory Crohn’s disease (CD). Patients with refractory celiac disease type II and a high risk of developing enteropathy associated T-cell lymphoma have shown promising improvement. Data concerning HSCT and mesenchymal SCT in end-stage chronic liver diseases are encouraging. In refractory autoimmune gastrointestinal diseases high-dose chemotherapy followed by HSCT seems feasible and safe and might result in long-term improvement of disease activity. Mesenchymal SCT for a selected group of CD is promising and may represent a significant therapeutic alternative in treating fistulas in CD.

关键词： Hematopoietic stem cell transplantation Mesenchymal stem cells Non-malignant gastrointestinal diseases Celiac disease Refractory celiac disease Lymphoma Crohn’ s Ulcerative colitis Cirrhosis

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Efficacy of thioguanine treatment in inflammatory bowel disease: A systematic review

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World Journal of Gastroenterology 2016年第40期22卷 9012-9021页

作者： Berrie Meijer chris jj mulder Godefridus J Peters Adriaan A van Bodegraven Nanne KH de Boer Department of Gastroenterology and Hepatology VU University Medical Center Department of Medical Oncology VU University Medical Center Department of Gastroenterology Geriatrics Internal and Intensive Care Medicine (Co-MIK) Zuyderland Medical Center

AIM To critically assess the available literature regarding the efficacy of thioguanine treatment in inflammatory bowel disease(IBD) patients, irrespective of the(hepato-) toxicity *** A systematic literature search of the MEDLINE database using Pub Med was performed using the keywords "thioguanine", "6-TG", "thioguanine", "inflammatory bowel disease", "IBD", "Crohn's disease", "Ulcerative colitis" and "effectiveness" in order to identify relevant articles published in English starting from 2000. Reference lists of the included articles were crosschecked for missing articles. Reviewed manuscripts concerning the effectiveness of thioguanine treatment in IBD were reviewed by the authors and the data were extracted. Data were subsequently analyzed with descriptive statistics. Due to the lack of standardized outcomes, a formal meta-analysis was not *** A total of 11 applicable studies were found that involved the effectiveness of thioguanine therapy in IBD. Eight studies were conducted in a prospectivemanner, in the remaining three studies, data was collected retrospectively. In total, 353 IBD-patients(225 patients with Crohn's disease, 119 with ulcerative colitis and nine with unclassified IBD) with prior azathioprine/mercaptopurine resistance and/or intolerance(n = 321) or de novo thioguanine administration(n = 32) were included for analysis, of which 228(65%) had clinical improvement on thioguanine therapy, based on standard IBD questionnaires, biochemical parameters or global physician assessments. Short-term results were based on 268 treatment years(median follow-up 9 mo, range 3-22 mo) with a median daily dose of 20 mg(range 10-80 mg). Discontinuation, mostly due to adverse events, was reported in 72 patients(20%). CONCLUSION The efficacy of thioguanine therapy in IBD patients intolerant to conventional thiopurine therapy is observed in 65%, with short term adverse events in 20% of patients.

关键词： Thiopurines Thioguanine Inflammatory bowel disease Crohn’s disease Ulcerative colitis

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Indications for 5-aminosalicylate in inflammatory bowel disease:Is the body of evidence complete?

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World Journal of Gastroenterology 2006年第38期12卷 6115-6123页

作者： Ad A van Bodegraven chris jj mulder Section of Inflammatory Bowel Diseases VU University medical centre Amsterdam The Netherlands Department of Gastroenterology VU University medical centre Amsterdam The Netherlands

Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and con- comitant drug pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)-related co- lonic carcinoma has not yet been completely elucidated. Therapeutic success of mesalazine may be optimized by a combination of high dose and low frequency of dos- age to improve compliance. Therefore, due to its supe- rior safety profile and pharmacokinetic characteristics, mesalazine is preferable to sulphasalazine. This paper reviews the literature concerning mechanisms of action, indications and off-label use, pharmacokinetic properties and formulations, therapeutic efficacy, compliance, pae- diatric indications, chemoprevention, and safety issues and adverse event profile of mesalazine treatment versus sulphasalazine. It also highlights these controversies in order to clarify the potential benefits of mesalazines in IBD therapy and evidence for its use.

关键词： Mesalazine Sulphasalazine Review Ulcerative colitis Crohn's disease Treatment Chemoprevention Pregnancy Adverse events

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Auto immune hepatitis

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World Journal of Gastroenterology 2016年第19期22卷 4651-4661页

作者： nicole mf van gerven ynto s de boer chris jj mulder carin mj van nieuwkerk gerd bouma department of gastroenterology and hepatology vu university medical centre1081 HV Amsterdam The Netherlands

To provide an update of the latest trends in epidemiology, clinical course, diagnostics, complications and treatment of auto immune hepatitis(AIH). A search ofthe MEDLINE database was performed using the search terms: "auto immune hepatitis", "clinical presentation", "symptoms", "signs", "diagnosis", "auto antibodies", "laboratory values", "serology", "histopathology", " h i s t o l o g y ", " g e n e t i c s ", "HLA g e n e s ", "non-HLA genes", "environment", "epidemiology", "prevalence", "incidence", "demographics", "complications", "HCC", "PBC", "PSC", "corticosteroid", "therapy", "treatment", "alternative treatment". English-language full-text articles and abstracts were considered. Articles included reviews, meta-analysis, prospective retrospective studies. No publication date restrictions were applied. AIH is an immune meditated progressive inflammatory liver disease that predominantly affects middle-aged females but may affect people of all ages. The clinical spectrum of AIH is wide, ranging from absent or mild symptoms to fulminant hepatic failure. The aetiology of AIH is still unknown, but is believed to occur as the consequence of an aberrant immune response towards an un-known trigger in a genetically susceptible host. In the absence of a gold standard, diagnosis is based on the combination of clinical, biochemical and histopathological criteria. Immunosuppressive treatment has been the cornerstone of treatment since the earliest description of the disease in 1950 by Waldenstr?m. Such treatment is often successful at inducing remission and generally leads to normal life expectancy. Nevertheless, there remain significant areas of unmet aetiological a clinical needs including fundamental insight in disease pathogenesis, optimal therapy, duration of treatment and treatment alternatives in those patients unresponsive to standard treatment regimens.

关键词： Auto immune hepatitis Diagnosis Liver Epidemiology Treatment

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Anal plugs and retrograde colonic irrigation are helpful in fecal incontinence or constipation

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World Journal of Gastroenterology 2007年第22期13卷 3101-3105页

作者： Marcel Cazemier Richelle JF Felt-Bersma chris jj mulder Department of Gastroenterology and Hepatology VU University Medical Center Postbus 7057 1007 MB Amsterdam The Netherlands

AIM： To evaluate the feasibility, clinical effect and predicting factors for favorable outcome of treatment with anal plugs in fecal incontinence and retrograde colonic irrigation （RCI） in patients with fecal incontinence or constipation.METHODS： Patients who received treatment with an anal plug or RCI between 1980 and 2005 were investigated with a questionnaire.RESULTS： Of the 201 patients （93 adults, 108 children）, 101 （50%） responded. Adults： anal plugs （8）, five stopped immediately, one stopped after 20 mo and two used it for 12-15 too. RCl （40, 28 fecal incontinence, 12 constipation）, 63% are still using it （mean 8.5 years）, 88% was satisfied. Younger adults （〈 40 years） were more satisfied with RCI （94 % vs 65%, P = 0.05）. Children： anal plugs （7）, 5 used it on demand for an average of 2.5 years with satisfactory results, one stopped immediately and one after 5 years. RCI （26 fecal incontinence, 22 constipation）, 90% are still using it （mean time 6.8 years） and felt satisfied. Children tend to be more satisfied （P = 0.001）. Besides age, no predictive factors for success were found. There was no difference in the outcome between patients with fecal incontinence or constipation.CONCLUSION： RCI is more often applied than anal plugs and is helpful in patients with fecal incontinence or constipation, especially for younger patients. Anal plugs can be used incidentally for fecal incontinence, especially in children.

关键词： Fecal incontinence Constipation Retrograde colonic irrigation Anal plug

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Referral for anorectal function evaluation is indicated in 65% and beneficial in 92% of patients

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World Journal of Gastroenterology 2008年第2期14卷 272-277页

作者： Maria M Szojda Erik Tanis chris jj mulder Richelle JF Felt-Bersma Department of Gastroenterology and Hepatology VU University Medical Centre PO Box 7057 1007 MB Amsterdam The Netherlands

AIM: To determine the indicated referrals to a tertiary centre for patients with anorectal symptoms, the effect of the advised treatment and the discomfort of the ***: In a retrospective study, patients referred for anorectal function evaluation (AFE) between May 2004 and October 2006 were sent a questionnaire, as were the doctors who referred them. AFE consisted of anal manometry, rectal compliance measurement and anal endosonography. An indicated referral was defined as needing AFE to establish a diagnosis with clinical consequence (fecal incontinence without diarrhea, 3rd degree anal sphincter rupture, congenital anorectal disorder, inflammatory bowel disease with anorectal complaints and preoperative in patients for re-anastomosis or enterostoma, anal fissure, fistula or constipation). Anal ultrasound is always indicated in patients with fistula, anal manometry and rectal compliance when impaired continence reserve is suspected. The therapeutic effect was noted as improvement, no improvement but reassurance, and ***: From the 216 patients referred, 167 (78%) returned the questionnaire. The referrals were indicated in 65%. Of these, 80% followed the proposed advice. Improvement was achieved in 35% and a reassurance in 57% of the patients, no difference existed between patient groups. On a VAS scale (1 to 10) symptoms improved from 4.0 to 7.2. Most patients reported no or little discomfort with AFE. CONCLUSION: Referral for AFE was indicated in 65%. Beneficial effect was seen in 92%: 35% improved and 57% was reassured. Advice was followed in 80%. Better instruction about indication for AFE referral is warranted.

关键词： Anorectal function evaluation Fecal incontinence Anal endosonography Anal manometry

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Nonalcoholic fatty liver disease: An overview of current insights in pathogenesis, diagnosis and treatment

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World Journal of Gastroenterology 2008年第16期14卷 2474-2486页

作者： Tim CMA Schreuder Bart J Verwer Carin MJ van Nieuwkerk chris jj mulder Department of Gastroenterology and Hepatology VU University Medical Center

Estimates of people suffering from overweight (one billion) and obesity (300 million) are increasing. The accumulation of triglycerides in the liver, in the absence of excess alcohol intake, has been described in the early sixties. It was not until 1980, however, that Ludwig et al named this condition nonalcoholic steatohepatitis (NASH). Subsequently, nonalcoholic fatty liver disease (NAFLD) has been used as a general name for conditions ranging from simple steatosis through steatohepatitis to end-stage liver disease (cirrhosis). Many studies have demonstrated the significant correlation with obesity and insulin resistance. Other studies have revealed a signifi- cant correlation between hepatic steatosis, cardiovascu- lar disease and increased intima-media thickness. WHO estimated that at least two million patients will develop cirrhosis due to hepatic steatosis in the years to come. Longitudinal cohort studies have demonstrated that those patients with cirrhosis have a similar risk to devel- op hepatocellular carcinoma as those with other causes of cirrhosis. Taken all together, NAFLD has become the third most important indication for liver transplantation. There- fore, training programmes in internal medicine, gastroen- terology and hepatology should stress the importance of diagnosing this entity and treat properly those at risk for developing complications of portal hypertension and con- comittant cardiovascular disease. This review will focus on the clinical characteristics, pathophysiology, imaging tech- niques and the readily available therapeutic options.

关键词： Non-alcoholic fatty liver disease Non-alcoholicsteatohepatitis Insulin resistance Liver Obesity Steatosis

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Small bowel capsule endoscopy in 2007:Indications,risks and limitations

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World Journal of Gastroenterology 2007年第46期13卷 6140-6149页

作者： Emanuele Rondonotti Federica Villa chris jj mulder Maarten AJM Jacobs Roberto de Franchis Università degli Studi di Milano IRCCS Fondazione PoliclinicoMangiagalliRegina Elena.UnitàOperativa di Gastroenterologia 3 via Pace 9Milano 20122Italy VU University Medical Centre Department of Gastroenterology and HepatologyBoelelaan 11171081 HV AmsterdamThe Nederlands Universitàdegli Studi di Milano IRCCS Fondazione PoliclinicoMangiagalliRegina Elena.UnitàOperativa di Gastroenterologia 3 via Pace 9Milano 20122Italy

Capsule endoscopy has revoluzionized the study of the small bowel by providing a reliable method to evaluate, endoscopically, the entire small bowel. In the last six years several papers have been published exploring the possible role of this examination in different clinical conditions. At the present time capsule endoscopy is generally recommended as a third examination, after negative bidirectional endoscopy, in patients with obscure gastrointestinal bleeding. A growing body of evidence suggests also an important role for this examination in other clinical conditions such as Crohn＇s disease, celiac disease, small bowel polyposis syndromes or small bowel tumors. The main complication of this examination is the retention of the device at the site of a previously unknown small bowel stricture. However there are also some other open issues mainly due to technical limitations of this tool （which is not driven from remote control, is unable to take biopsies, to insufflate air, to suck fluids or debris and sometimes to correctly size and locate lesions）.The recently developed double balloon enteroscope, owing to its capability to explore a large part of the small bowel and to take targeted biopsies, although being invasive and time consuming, can overcome some limitations of capsule endoscopy. At the present time, in the majority of clinical conditions （i.e. obscure GI bleeding）, the winning strategy seems to be to couple these two techniques to explore the small bowel in a painless, safe and complete way （with capsule endoscopy） and to define and treat the lesions identified （with double balloon enteroscopy）.

关键词： Capsule endoscopy Double balloon

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Surgery in (pre)malignant celiac disease

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World Journal of Gastroenterology 2015年第43期21卷 12403-12409页

作者： Jolanda MW van de Water Petula Nijeboer Laura R de Baaij Jessy Zegers Gerd Bouma Otto J Visser Donald L van der Peet chris jj mulder Wilhelmus JHJ Meijerink Department of Gastroenterology and Hepatology Coeliac Center AmsterdamVU University Medical Center Department of Haematology Coeliac Center AmsterdamVU University Medical Center Department of Surgery Coeliac Center Amsterdam VU University Medical Center

AIM: To report the outcome of surgery in patients with(pre)malignant conditions of celiac disease(CD) and the impact on ***: A total of 40 patients with(pre)malignant conditions of CD,ulcerative jejunitis(n = 5) and enteropathy associated T-cell lymphoma(EATL)(n = 35),who underwent surgery between 2002 and 2013 were retrospectively evaluated. Data on indications,operative procedure,post-operative morbidity and mortali ty,adjuvant therapy and overal l survival(OS) were collected. Eleven patients with EATL who underwent chemotherapy without resection were included as a control group for survival analysis. Patients were followed-up every three months during the first year and at 6-mo intervals ***: Mean age at resection was 62 years. The majority of patients(63%) underwent elective laparotomy. Functional stenosis(n = 1 3) and perforation(n = 12) were the major indications for surgery. In 70% of patients radical resection wasperformed. Early postoperative complications,mainly due to leakage or sepsis,occurred in 14/40(35%) of patients. Eight patients required reoperation. More patients who underwent resection in the acute setting(n = 3,20%) died compared to patients treated in the elective setting. With a median follow-up of 20 mo,seven patients(18%) required reoperation due to long-term complications. Significantly more patients who underwent acute surgery could not be treated with adjuvant chemotherapy. Patients who first underwent surgical resection showed significantly better OS than patients who received chemotherapy without ***: Although the complication rate is high,the preferred first step of treatment in(pre)malignant CD consists of local resection as early as possible to improve survival.

关键词： Enteropathy associated T-cell lymphoma Ulcerative

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Gastroenterology in developing countries:Issues and advances

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World Journal of Gastroenterology 2009年第23期15卷 2839-2854页

作者： Kate L Mandeville Justus Krabshuis Nimzing Gwamzhi Ladep chris jj mulder Eamonn MM Quigley Shahid A Khan Centre for Infectious Diseases Epidemiology Department of Primary Care and Population Sciences University College London Hampstead Campus Royal Free Hospital London NW3 2PF United Kingdom Highland Data Les Charleix 24390 Tourtoirac Dordogne France Department of Medicine University of Jos and Jos University Teaching Hospital Jos Plateau State P.M.B. 2076 Nigeria Department of Gastroenterology VU University Medical Center Amsterdam 1081 HV Holland World Gastroenterology Organisation and Department of Medicine National University of Ireland Cork University Hospital Clinical Sciences Building Wilton Cork Ireland Department of Hepatology and Gastro-enterology Faculty of Medicine Imperial College London St Mary's Campus London W2 1NY United Kingdom

Developing countries shoulder a considerable burden of gastroenterological disease. Infectious diseases in particular cause enormous morbidity and mortality. Diseases which afflict both western and developing countries are often seen in more florid forms in poorer countries. Innovative techniques continuously improve and update gastroenterological practice. However, advances in diagnosis and treatment which are commonplace in the West, have yet to reach many developing countries. Clinical guidelines, based on these advances and collated in resource-rich environments, lose their relevance outside these settings. In this two-part review, we first highlight the global burden of gastroenterological disease in three major areas： diarrhoeal diseases, hepatitis B, and Helicobacter pylori. Recent progress in their management is explored, with consideration of future solutions. The second part of the review focuses on the delivery of clinical services in developing countries. Inadequate numbers of healthcare workers hamper efforts to combat gastroenterological disease. Reasons for this shortage are examined, along with possibilities for increased specialist training. Endoscopy services, the mainstay of gastroenterology in the West, are in their infancy in many developing countries. The challenges faced by those se^ing up a service are illustrated by the example of a Nigerian endoscopy unit. Finally, we highlight the limited scope of many clinical guidelines produced in western countries. Guidelines which take account of resource limitations in the form of ＂cascades＂ are advocated in order to make these guidelines truly global. Recognition of the different working conditions facing practitioners worldwide is an important step towards narrowing the gap between gastroenterology in rich and poor countries.

关键词： Helicobacter pylori Developing countries Gastrointestinal diseases Health care delivery Practice guidelines

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