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1.
Scand J Gastroenterol ; 55(8): 1002-1004, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32634343

ABSTRACT

A stenosing tumour in the throat region is a common indication for percutaneous endoscopic gastrostomy (PEG), which may be used for enteral nutrition in palliative cases or placed prior to curative treatment (surgery, radiotherapy and/or chemotherapy) and removed when the patient has recovered and has a reliable and adequate oral intake. Major complications related to PEG are rare, but their treatment poses a challenge. We are presenting a case of the transmission of metastasis to the gastrostomy site in a patient with pharynx cancer after percutaneous endoscopic gastrostomy.


Subject(s)
Gastrostomy , Head and Neck Neoplasms , Neoplasm Metastasis , Pharyngeal Neoplasms , Enteral Nutrition , Humans , Pharyngeal Neoplasms/pathology
2.
J Bacteriol ; 201(21)2019 11 01.
Article in English | MEDLINE | ID: mdl-31405919

ABSTRACT

Colonic spirochetosis, diagnosed based on the striking appearance in histological sections, still has an obscure clinical relevance, and only a few bacterial isolates from this condition have been characterized to date. In a randomized, population-based study in Stockholm, Sweden, 745 healthy individuals underwent colonoscopy with biopsy sampling. Of these individuals, 17 (2.3%) had colonic spirochetosis, which was associated with eosinophilic infiltration and a 3-fold-increased risk for irritable bowel syndrome (IBS). We aimed to culture the bacteria and perform whole-genome sequencing of the isolates from this unique representative population sample. From 14 out of 17 individuals with spirochetosis we successfully isolated, cultured, and performed whole-genome sequencing of in total 17 isolates, including the Brachyspira aalborgi type strain, 513A. Also, 16S analysis of the mucosa-associated microbiota was performed in the cases and nonspirochetosis controls. We found one isolate to be of the species Brachyspira pilosicoli; all remaining isolates were of the species Brachyspira aalborgi Besides displaying extensive genetic heterogeneity, the isolates harbored several mucin-degrading enzymes and other virulence-associated genes that could confer a pathogenic potential in the human colon. We also showed that 16S amplicon sequencing using standard primers for human microbiota studies failed to detect Brachyspira due to primer incompatibility.IMPORTANCE This is the first report of whole-genome analysis of clinical isolates from individuals with colonic spirochetosis. This characterization provides new opportunities in understanding the physiology and potentials of these bacteria that densely colonize the gut in the individuals infected. The observation that standard 16S amplicon primers fail to detect colonic spirochetosis may have major implications for studies searching for associations between members of the microbiota and clinical conditions such as irritable bowel syndrome (IBS) and should be taken into consideration in project design and interpretation of gastrointestinal tract microbiota in population-based and clinical settings.


Subject(s)
Brachyspira/isolation & purification , Colon/microbiology , Spirochaetales Infections/microbiology , Brachyspira/genetics , Genomics/methods , Humans , Microbiota/genetics , RNA, Ribosomal, 16S/genetics
4.
J Crohns Colitis ; 12(10): 1200-1209, 2018 11 09.
Article in English | MEDLINE | ID: mdl-29659773

ABSTRACT

Background and Aims: The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease, we aimed to assess whether the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function. Methods: Ileal biopsies from 15 twin pairs discordant for Crohn's disease [monozygotic n = 9, dizygotic n = 6] and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to 51Chromium [Cr]-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins. Results: Healthy co-twins and affected twins displayed increased 51Cr-EDTA permeability at 120 min, both with acetylsalicylic acid [p < 0.001] and without [p < 0.001] when compared with controls. A significant increase in 51Cr-EDTA flux was already seen at 20 min in healthy monozygotic co-twins compared with controls [p≤0.05] when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins [p < 0.05] and affected twins [p < 0.05] compared with external controls, while ELISA only showed lower tricellulin in Crohn's disease twins [p < 0.05]. Conclusion: Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation, rather than representing a primary defect.


Subject(s)
Aspirin/pharmacokinetics , Chromium Radioisotopes/pharmacokinetics , Claudin-5/genetics , Crohn Disease , Edetic Acid/pharmacokinetics , Escherichia coli K12/metabolism , Ileum , MARVEL Domain Containing 2 Protein/genetics , Adult , Chelating Agents/pharmacology , Crohn Disease/genetics , Crohn Disease/pathology , Diagnostic Techniques, Radioisotope , Female , Genetic Predisposition to Disease , Humans , Ileum/metabolism , Ileum/pathology , Male , Middle Aged , Permeability , Tight Junctions/genetics , Tight Junctions/metabolism , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics
5.
Scand J Gastroenterol ; 53(4): 410-416, 2018 04.
Article in English | MEDLINE | ID: mdl-29546806

ABSTRACT

OBJECTIVES: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn's disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature. METHODS: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed. RESULTS: We identified 31 patients with onset of MC after a median (range) of 20 (2-52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients. CONCLUSIONS: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.


Subject(s)
Colitis, Collagenous/epidemiology , Colitis, Lymphocytic/epidemiology , Colitis, Ulcerative/complications , Crohn Disease/complications , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Retrospective Studies , Sweden , Young Adult
7.
Lakartidningen ; 1142017 05 15.
Article in Swedish | MEDLINE | ID: mdl-28510242

ABSTRACT

Endoscopic surveillance after colorectal polypectomy These guidelines for endoscopic surveillance after colorectal polypectomy are based on the recommendations published by European Society of Gastrointestinal Endoscopy (ESGE) in 2013. A precondition for the guidelines is that patients have undergone a high-quality colonoscopy, including complete removal and histopathological evaluation of all detected neoplastic lesions. Current research has made it possible to stratify patients into a low-risk and a high-risk group in terms of metachronous cancer. Low-risk group patients (1-2 tubular adenomas <10 mm in size) are recommended a surveillance colonoscopy 10 years after the index colonoscopy if the patient is less than 50 years old, otherwise not. High-risk group patients (adenomas with villous histology or high grade dysplasia or ≥10 mm in size, or ≥ 3 adenomas), should undergo a repetition colonoscopy 3 years after the index colonoscopy. If high-risk adenomas are detected at first or subsequent surveillance colonoscopy, a 3-year repetition of the next endoscopic examination is recommended. If a high-risk patient has no high-risk adenomas at the first surveillance colonoscopy, a 5-year period is recommended until the second surveillance colonoscopy. ESGE recommends termination of the follow-up at 80 years of age although individualised recommendations should consider general health and co-morbidity of the patients as well as findings at previous colonoscopies.


Subject(s)
Adenoma , Colonoscopy , Colorectal Neoplasms , Practice Guidelines as Topic , Adenoma/diagnosis , Adenoma/prevention & control , Adenomatous Polyps/surgery , Aged , Aged, 80 and over , Colonic Polyps/surgery , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Early Detection of Cancer/methods , Humans , Middle Aged , Risk Factors
8.
Endosc Int Open ; 4(8): E901-11, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27540581

ABSTRACT

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis associated inflammatory bowel disease (PSC-IBD) is characterized by a high risk of colorectal dysplasia. Surveillance colonoscopies with random biopsies have doubtful power for dysplasia detection. Our aim was to prospectively investigate the feasibility and efficacy of pCLE in surveillance colonoscopies in patients with PSC-IBD. PATIENTS AND METHODS: Sixty-nine patients with PSC-IBD underwent colonoscopy in 2 steps. On the way from rectum to cecum, the mucosa was inspected with high definition endoscopy (HDE) and random biopsies were taken according to the standard routine. On the way from cecum to rectum, fluorescein-enhanced pCLE and chromoendoscopy were performed. Regions where random biopsies had been taken, as well as visible lesions, were examined with pCLE and targeted biopsies were taken of lesions suspicious for dysplasia. Two investigators, blinded to histology and endoscopy results, analyzed all pCLE videos off-line. RESULTS: Nineteen biopsies obtained in 13 patients (17 targeted biopsies, 2 random biopsies) revealed the presence of low-grade dysplasia. Thirteen lesions with dysplasia were endoscopically visible but by using pCLE-targeted biopsies, additional endoscopically invisible dysplasias in 4 biopsies obtained from 3 patients were detected. The sensitivity, specificity, and accuracy of pCLE in predicting dysplasia were respectively 89 % (95 % CI: 65 - 98), 96 % (95 % CI: 94 - 97), and 96 % (95 % CI: 94 - 97). pCLE showed a good performance for differentiating neoplastic from non-neoplastic mucosa with negative predictive value of 99 %. CONCLUSIONS: pCLE in PSC-IBD surveillance is feasible and may be a good complement to HDE. Future research should aim at elucidating whether real-time pCLE is applicable in PSC-IBD surveillance.

9.
Scand J Gastroenterol ; 51(5): 556-62, 2016.
Article in English | MEDLINE | ID: mdl-26679722

ABSTRACT

OBJECTIVE: Microscopic colitis is a common cause of chronic diarrhoea in the Scandinavian countries. This report comprises demographic data, clinical and endoscopic features, and occurrence of coeliac and inflammatory bowel disease (IBD) in a large urban cohort of patients with lymphocytic colitis (LC) and collagenous colitis (CC). MATERIALS AND METHODS: A total of 795 patients with microscopic colitis from two hospitals in Stockholm were included. Medical records were reviewed and clinical data, including endoscopic and histological findings, were compiled. RESULTS: Forty-three percent had CC (female:male ratio 3.7:1) and 57% had LC (female:male ratio 2.7:1). The mean age at diagnosis of CC was 63 years and of LC was 59 years (p = 0.005). Clinical features were similar in both entities, but the intensity of symptoms differed. Watery diarrhoea was reported in 55% in CC patients versus in 43% in LC patients (p = 0.0014), and nocturnal diarrhoea in 28% versus 18% (p = 0.002). Subtle endoscopic mucosal findings were reported in 37% of the CC patients and in 25% of the LC patients (p = 0.0011). Colorectal adenomatous polyps were found in 5.3% of all patients. Coeliac disease occurred in 6% and IBD occurred in 2.1% of all patients. CONCLUSIONS: Clinical features of LC and CC are similar but not identical. CC seems to be a more severe type of bowel inflammation and LC tends to occur earlier in life. Both forms might indeed feature endoscopic findings despite the designation 'microscopic'. Our study confirms the strong association with coeliac disease.


Subject(s)
Colitis, Microscopic/diagnosis , Colonoscopy/methods , Diarrhea/etiology , Intestinal Mucosa/pathology , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Biopsy , Chronic Disease , Colitis, Collagenous/complications , Colitis, Collagenous/diagnosis , Colitis, Collagenous/epidemiology , Colitis, Lymphocytic/complications , Colitis, Lymphocytic/diagnosis , Colitis, Lymphocytic/epidemiology , Colitis, Microscopic/complications , Colitis, Microscopic/epidemiology , Diagnosis, Differential , Diarrhea/diagnosis , Diarrhea/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Lymphocyte Count , Male , Middle Aged , Retrospective Studies , Sweden/epidemiology , Young Adult
10.
Gut ; 65(1): 47-56, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25425655

ABSTRACT

OBJECTIVE: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. DESIGN: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. RESULTS: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. CONCLUSIONS: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. TRIAL REGISTRATION NUMBERS: http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Budesonide/administration & dosage , Colitis, Collagenous/drug therapy , Maintenance Chemotherapy/methods , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Budesonide/therapeutic use , Double-Blind Method , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
11.
Hum Pathol ; 46(2): 277-83, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25540866

ABSTRACT

Irritable bowel syndrome (IBS) is a functional disorder defined by symptoms in the absence of overt pathology. Colonic spirochetosis (CS), defined by histologic observation of spirochetal strains of Brachyspira in colonic biopsies, is uncommon and considered of doubtful significance. We aimed to determine the prevalence of CS in the general population, identify subtle colon pathologies, and evaluate a link with symptoms of IBS. Colonoscopy was performed in 745 subjects (aged 19-70 years, mean age 51 years, 43% male) with biopsies (ileum and 4 colonic sites) from a random population sample, Stockholm, Sweden, who completed a validated questionnaire of gastrointestinal symptoms; IBS was identified by Rome III criteria. CS was identified by histology and immunohistochemistry. In a general population, 17 individuals (2.28%; 95% confidence interval, 1.2%-3.5%) were diagnosed as having CS by histology; 6 (35%) had IBS. CS was always present in the sigmoid colon, but only 14 rectal biopsies. Eosinophils were increased in colon biopsies in CS cases versus controls, in the transverse (P = .02), sigmoid colon (P = .001), and rectum (P = .0005) with subepithelial eosinophil clusters (P = .053). Lymphoid follicles (at any site) were present in 13 CS (P = .0003). There was a 3-fold increased risk of IBS in CS (odds ratio, 3.59; 95% confidence interval, 1.27-10.11; P = .015). Polyps and diverticular disease were similar in CS cases and controls. The prevalence of CS in a general population is 2% and associated with nonconstipating IBS. Colonic eosinophilia with lymphoid follicles may signify the presence of CS.


Subject(s)
Colon/pathology , Eosinophilia/epidemiology , Irritable Bowel Syndrome/epidemiology , Rectum/pathology , Adult , Aged , Biopsy , Colonoscopy/methods , Female , Humans , Irritable Bowel Syndrome/diagnosis , Male , Middle Aged , Prevalence , Sweden/epidemiology , Young Adult
12.
Radiol Res Pract ; 2012: 415616, 2012.
Article in English | MEDLINE | ID: mdl-22550583

ABSTRACT

Background. Somatostatin receptors (SSTRs) are over-expressed in several tumors making it possible for imaging with labelled SSTR. A previous study showed feasibility to image oesophageal cancer with SSTR analogue (99m)Tc-depreotide. Purpose. (1) To investigate expression of the SSTRs in different types of esophageal carcinoma and (2) to correlate such an expression with (99m)Tc-depreotide uptake in these lesions. Material and Methods. Total 28 patients (17 with esophageal cancer and 11 with Barrett's esophagus) were examined with (99m)Tc-depreotide scintigraphy. The SSTR2A, SSTR2B, SSTR3, and SSTR5 were analyzed immunohistochemically in the lesion samples. Results. Among the patients with adenocarcinoma 10/11 expressed different amounts of SSTRs, while SSTRs were absent in 5/6 patients with Squamous cell carcinoma (Sqcc). There was no correlation neither between the (99m)Tc-depreotide uptake and the amount of SSTRs nor between the amount of SSTRs and differentiation grade of the tumor. Conclusions. (1) SSTRs are expressed in esophageal carcinoma and more abundantly so in adenocancer specimens; (2) in vivo (99m)Tc-depreotide uptake does not obviously correlate with the immunohistochemically detection of SSTRs of different subtypes in esophageal carcinoma.

13.
Dis Colon Rectum ; 54(11): 1392-7, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21979184

ABSTRACT

BACKGROUND: Almost 10% of all patients with primary sclerosing cholangitis receive a diagnosis of Crohn's disease. Clinical characteristics and the risk of colon cancer or dysplasia in Crohn's disease and primary sclerosing cholangitis are less well examined than in ulcerative colitis. OBJECTIVE: This study aimed to describe the clinical characteristics and risk of colorectal dysplasia and cancer in Crohn's disease in patients with primary sclerosing cholangitis. DESIGN: This is a cohort study of all patients diagnosed with primary sclerosing cholangitis and colorectal Crohn's disease at Karolinska University Hospital, Huddinge, 1978 to 2006. Each patient was matched for age and the onset of Crohn's disease to 2 controls with colorectal Crohn's disease without liver disease. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Twenty-eight patients (61% male) with primary sclerosing cholangitis and Crohn's disease and 46 patients (50% male) with Crohn's disease alone were studied. Clinical and endoscopic data were retrieved from medical records. Colonic biopsies from patients with primary sclerosing cholangitis were re-reviewed. MAIN OUTCOME MEASURES: The primary outcome measured was the proportion of patients developing colorectal cancer. RESULTS: Colorectal cancer or dysplasia developed in 9 patients with primary sclerosing cholangitis and in 3 controls. Patients with primary sclerosing cholangitis were more likely to develop colorectal dysplasia or cancer than controls (OR 6.78; 95% CI (1.65-27.9); P = .016). In patients with primary sclerosing cholangitis compared with controls, perianal fistulas occurred in 3% vs 33% (P = .003), bowel strictures occurred in 7% vs 30% (P = .03), and bowel surgery was performed in 18% vs 46% (P = .01). Histological granulomas were seen in 29% of the patients with primary sclerosing cholangitis compared with 43% in controls (P = not significant). LIMITATIONS: This study was limited by its retrospective nature and the limited cohort. CONCLUSIONS: Primary sclerosing cholangitis is a risk factor for the development of colorectal cancer and dysplasia in Crohn's disease. Obstructing disease and perianal fistulas are rare in primary sclerosing cholangitis and less common than in colonic Crohn's disease without liver disease.


Subject(s)
Cholangitis, Sclerosing/pathology , Colitis/pathology , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Crohn Disease/pathology , Precancerous Conditions/pathology , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/mortality , Cohort Studies , Colitis/complications , Colitis/mortality , Crohn Disease/complications , Crohn Disease/mortality , Disease-Free Survival , Endoscopy , Female , Humans , Male , Middle Aged , Precancerous Conditions/complications , Precancerous Conditions/mortality , Young Adult
14.
Inflamm Bowel Dis ; 17(5): 1101-7, 2011 May.
Article in English | MEDLINE | ID: mdl-20853434

ABSTRACT

BACKGROUND: There is uncertainty about how patients with Crohn's colitis should be monitored for colorectal cancer (CRC). By analogy to ulcerative colitis, regular colonoscopy with biopsies for dysplasia has been used. We describe the occurrence of dysplasia and DNA aneuploidy in a cohort of patients with Crohn's colitis. METHODS: In all, 245 patients with extensive colitis (225 with a firm diagnosis of Crohn's disease, and 20 diagnosed as indeterminate colitis) at Stockholm Söder Hospital and Karolinska University Hospital, Huddinge were included. They were followed with regular colonoscopies with biopsies both for dysplasia and DNA aneuploidy. The cumulative occurrence of DNA aneuploidy and dysplasia was estimated using Kaplan-Meier curves. Time sequences and interactions between DNA aneuploidy, dysplasia, and CRC were studied using Cox regression analysis, adjusted for age, sex, and age at diagnosis. RESULTS: During a median follow-up time of 9.2 person-years, DNA aneuploidy was found in 53 patients (22%), with 10 patients having multifocal aneuploidy and high S-phase values. Dysplasia was found in 42 patients (17%), 10 having multifocal dysplasia. Relative risk (RR) of dysplasia given DNA aneuploidy was 5.3 (95% confidence interval [CI] 2.3-12). RR of CRC given dysplasia was 10 (95% CI 2-50), and RR of CRC given aneuploidy was 1.5 (95% CI 0.3-9.3). CONCLUSIONS: Dysplasia and DNA aneuploidy including S-phase analysis may complement stratification of patients with Crohn's


Subject(s)
Colitis/epidemiology , Colitis/genetics , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Crohn Disease/epidemiology , Crohn Disease/genetics , Adolescent , Adult , Aged , Aneuploidy , Biopsy , Child , Child, Preschool , Cohort Studies , Colitis/pathology , Colonoscopy , Colorectal Neoplasms/pathology , Crohn Disease/pathology , Female , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Precancerous Conditions/epidemiology , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Retrospective Studies , Risk Factors , Young Adult
15.
J Clin Apher ; 25(5): 287-93, 2010.
Article in English | MEDLINE | ID: mdl-20806415

ABSTRACT

Cellsorba™ is a medical device for leukocytapheresis (LCAP) treatment of ulcerative colitis (UC). Cellsorba™ EX Global type has been developed from Cellsorba E for intended use with ACD-A as anticoagulant. We evaluated safety and efficacy of the modified Cellsorba using ACD-A in a pilot trial comprising patients with active UC, despite receiving 5-ASA. A total of 10 LCAP treatments/patients were administered. Safety assessment focused on clinical signs and symptoms, hematological variables, as well as levels of bradykinin and IL-6. Efficacy was determined using the Mayo clinical/endoscopic scoring index as well histological assessment of biopsies. Additional aim was to evaluate the impact of apheresis system lines and filter on selected regulatory molecules. All six subjects completed the trial without any serious adverse events. WBC, platelet counts, and levels of bradykinin and IL-6 were not significantly affected. The median Mayo score decreased from 8.0 to 3.5 at week 8 (and to 2 at week 16 for the responders). Four patients were responders, of whom two patients went into remission. Median histological scores decreased from 3.5 to 2.0 in these four patients. Concentration of LL-37 increased within the apheresis system lines. LCAP with Cellsorba EX using ACD-A as anticoagulant was found to be a safe and well-tolerated procedure in patients with active UC. The positive impact on efficacy parameters merits further evaluation in a controlled fashion.


Subject(s)
Anticoagulants/therapeutic use , Citric Acid/therapeutic use , Colitis, Ulcerative/therapy , Glucose/analogs & derivatives , Leukapheresis/instrumentation , Adolescent , Adult , Antimicrobial Cationic Peptides/blood , CD30 Ligand/blood , Female , Glucose/therapeutic use , Humans , Male , Middle Aged , Pilot Projects , Safety , Cathelicidins
17.
Am J Gastroenterol ; 104(3): 679-85, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19209166

ABSTRACT

OBJECTIVES: Collagenous colitis is increasingly recognized as a common diarrheal disorder of inflammatory origin. Intestinal inflammation is generally associated with increased mucosal permeability, but little is known about barrier function in microscopic colitis. Our aim was to investigate the mucosal barrier to nonpathogenic bacteria in collagenous colitis. METHODS: The study included 33 individuals, 25 with collagenous colitis (14 in clinical remission, 11 with active disease, and 8 of these again after 6 weeks budesonide treatment) and 8 control patients. Bowel movements were registered for 1 week. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (I(sc)), transepithelial resistance (TER), and transmucosal passage of chemically killed Escherichia coli K12. RESULTS: Bacterial uptake was increased in patients in remission, 1.6 U (1.1-3.0) and in those with active disease, 4.6 U (2.5-5.8; median (IQR)), compared to controls, 0.7 U (0.1-1.1; P=0.004 and P-0.001, respectively). Active disease also had significant decrease in transepithelial resistance (TER) after 120 min, -9.7 Omega cm(2) ((-13)-(-4.3)), compared to controls, -5.2 Omega cm(2) ((-7.2)-(-3.1)), P-0.03; or patients in remission, -4.8 Omega cm(2) ((-8.0)-(-1.2)), P=0.04. Budesonide decreased median stool frequency to 1.9 (1.3-2.2) compared to 3.8 (3.7-4.2) before treatment (P=0.01), but bacterial uptake was still increased after budesonide 2.9 U (1.5-3.8), (P=0.006 compared to controls), and there were no significant changes in histology. CONCLUSIONS: Collagenous colitis presents with significantly increased uptake and altered mucosal reactivity to nonpathogenic bacteria. Budesonide induces clinical remission and restores mucosal reactivity but does not abolish the increased bacterial uptake. An underlying barrier dysfunction may explain the frequent and rapid relapses in CC.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Budesonide/therapeutic use , Colitis, Collagenous/microbiology , Escherichia coli K12/physiology , Intestinal Mucosa/microbiology , Aged , Colitis, Collagenous/drug therapy , Colitis, Collagenous/pathology , Colitis, Collagenous/physiopathology , Electric Impedance , Female , Humans , In Vitro Techniques , Intestinal Mucosa/pathology , Intestinal Mucosa/physiopathology , Male , Recurrence
18.
Scand J Gastroenterol ; 44(4): 441-5, 2009.
Article in English | MEDLINE | ID: mdl-19110988

ABSTRACT

OBJECTIVE: In 10-15% of patients with colorectal inflammatory bowel disease it is not possible to determine whether they have Crohn's disease or ulcerative colitis and they are therefore classified as having inflammatory bowel disease unclassified (IBDU) (formerly referred to as "indeterminate colitis"). The aim of this study was to determine whether upper endoscopy with biopsies could be a useful tool for diagnosing patients with colorectal inflammatory disease. MATERIAL AND METHODS: Fifty-two patients (14 colorectal Crohn's disease, 19 ulcerative colitis, 6 IBDU, 8 microscopic colitis and 5 without IBD) were examined by upper endoscopy. Biopsies from gastric and duodenal mucosa were examined histologically and the frequency of focal cryptitides was estimated. Helicobacter pylori-positive patients were excluded. RESULTS: Focal cryptitides (sometimes called focally enhanced gastritis) were found in 8/14 of patients with Crohn's disease, 4/19 patients with ulcerative colitis, 2/6 patients with IBDU, 2/8 of patients with microscopic colitis and in 2/5 patients without IBD. CONCLUSIONS: Focal cryptitides are more commonly found in gastric and/or duodenal mucosa in patients with colorectal Crohn's disease than in other patients. Upper endoscopy with mucosal biopsies contributes towards a diagnosis in patients with colitis.


Subject(s)
Colitis, Ulcerative/pathology , Crohn Disease/pathology , Duodenum/pathology , Endoscopy, Gastrointestinal , Gastric Mucosa/pathology , Intestinal Mucosa/pathology , Adult , Aged , Biopsy , Colitis, Ulcerative/complications , Crohn Disease/complications , Dyspepsia/etiology , Dyspepsia/pathology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Young Adult
19.
Gastroenterology ; 134(7): 1869-81; quiz 2153-4, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18466904

ABSTRACT

BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) and the irritable bowel syndrome (IBS) are heterogeneous disorders of the gastrointestinal tract and can profoundly affect the quality of life. Because many of the symptoms of IBD are similar to those of IBS, the former may be misdiagnosed. In addition, the 2 major forms of IBD, ulcerative colitis (UC) and Crohn's disease (CD), have overlapping nonspecific, pathologic features leading to difficulties in assessing colonic inflammation and hence the term IBD unclassified has been proposed. The aim of this study was to identify and assess the utility of a certain set of marker genes that could help to distinguish IBS from IBD, and further to discriminate between UC and CD. METHODS: Subtractive suppression hybridization was used to identify IBD-specific genes in colonic mucosal biopsy specimens. In quantitative polymerase chain reaction experiments, the differential expressions of identified genes then were analyzed using a classification algorithm and the possible clinical value of these marker genes was evaluated in a total of 301 patients in 3 stepwise studies. RESULTS: Seven marker genes were identified as differentially expressed in IBD, making it possible to discriminate between patients suffering from UC, CD, or IBS with area under the receiver-operating characteristic curves ranging from 0.915 to 0.999 (P < .0001) using the clinical diagnosis as gold standard. CONCLUSIONS: Expression profiling of relevant marker genes in colonic biopsy specimens from patients with IBD/IBS-like symptoms may enable swift and reliable determination of diagnosis, ultimately improving disease management.


Subject(s)
Colitis, Ulcerative/genetics , Crohn Disease/genetics , Gene Expression Profiling , Genetic Markers , Genetic Testing , Irritable Bowel Syndrome/genetics , Adult , Aged , Aged, 80 and over , Algorithms , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/pathology , Colon/chemistry , Colon/pathology , Crohn Disease/diagnosis , Crohn Disease/pathology , DNA, Complementary/analysis , Diagnosis, Differential , Female , Gene Expression Profiling/methods , Genetic Predisposition to Disease , Genotype , Humans , Intestinal Mucosa/chemistry , Intestinal Mucosa/pathology , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/pathology , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Phenotype , Pilot Projects , Predictive Value of Tests , Prospective Studies , RNA/analysis , ROC Curve , Reproducibility of Results , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction
20.
Cancer Epidemiol Biomarkers Prev ; 14(2): 512-20, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15734980

ABSTRACT

BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has increased worldwide in recent decades. Diet could influence NHL risk by modulating the immune system, although evidence is limited. We did a population-based case-control study to determine whether differences in diet were associated with NHL risk. METHODS: A total of 597 NHL cases and 467 population controls in Sweden completed a semiquantitative food frequency questionnaire evaluating their dietary habits 2 years before the interview. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for associations between food intake and risk of NHL. RESULTS: High consumption of dairy products and fried red meat was associated with increased risk of NHL. The OR of NHL for individuals in the highest quartile compared with the lowest quartile of dairy intake was 1.5 (95% CI, 1.1-2.2; P(trend) = 0.003). The OR for the highest versus lowest quartile of fried red meat intake was 1.5 (95% CI, 1.0-2.1; P(trend) = 0.02). In contrast, high consumption of fruits and vegetables was associated with reduced risk of NHL, particularly follicular lymphoma, among women but not men. Compared with the lowest quartile of vegetable intake, the OR of follicular lymphoma among women in the highest quartile of vegetable intake was 0.3 (95% CI, 0.1-0.7; P(trend) = 0.002). CONCLUSIONS: The positive associations of NHL risk with dairy products and fried red meat and the inverse association with fruits and vegetables suggest that diet affects NHL risk and could explain the increase of some histopathogic subtypes.


Subject(s)
Diet , Lymphoma, Non-Hodgkin/epidemiology , Case-Control Studies , Diet Surveys , Female , Food , Humans , Logistic Models , Male , Middle Aged , Risk Factors , Sweden/epidemiology
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