Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn's Disease.

BACKGROUND & AIMS: Patients with perianal fistulizing Crohn's disease have a poor prognosis because these lesions do not heal well. We evaluated the effects of local administration of bone marrow-derived mesenchymal stromal cells (MSCs) to these patients from healthy donors in a double-blind, placebo-controlled study. METHODS: Twenty-one patients with refractory perianal fistulizing Crohn's disease were randomly assigned to groups given injections of 1 × 10(7) (n = 5, group 1), 3 × 10(7) (n = 5, group 2), or 9 × 10(7) (n = 5, group 3) MSCs, or placebo (solution with no cells, n = 6), into the wall of curettaged fistula, around the trimmed and closed internal opening. The primary outcome, fistula healing, was determined by physical examination 6, 12, and 24 weeks later; healing was defined as absence of discharge and <2 cm of fluid collection-the latter determined by magnetic resonance imaging at week 12. All procedures were performed at Leiden University Medical Center, The Netherlands, from June 2012 through July 2014. RESULTS: No adverse events were associated with local injection of any dose of MSCs. Healing at week 6 was observed in 3 patients in group 1 (60.0%), 4 patients in group 2 (80.0%), and 1 patient in group 3 (20.0%), vs 1 patient in the placebo group (16.7%) (P = .08 for group 2 vs placebo). At week 12, healing was observed in 2 patients in group 1 (40.0%), 4 patients in group 2 (80.0%), and 1 patient in group 3 (20.0%), vs 2 patients in the placebo group (33.3%); these effects were maintained until week 24 and even increased to 4 (80.0%) in group 1. At week six, 4 of 9 individual fistulas had healed in group 1 (44.4%), 6 of 7 had healed in group 2 (85.7%), and 2 of 7 had healed in group 3 (28.6%) vs 2 of 9 (22.2%) in the placebo group (P = .04 for group 2 vs placebo). At week twelve, 3 of 9 individual fistulas had healed in group 1 (33.3%), 6 of 7 had healed in group 2 (85.7%), 2 of 7 had healed in group 3 (28.6%), and 3 of 9 had healed in the placebo group (33.3%). These effects were stable through week 24 and even increased to 6 of 9 (66.7%) in group 1 (P = .06 group 2 vs placebo, weeks 12 and 24). CONCLUSIONS: Local administration of allogeneic MSCs was not associated with severe adverse events in patients with perianal fistulizing Crohn's disease. Injection of 3 × 10(7) MSCs appeared to promote healing of perianal fistulas. ClinicalTrials.gov ID NCT01144962.

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

OBJECTIVE: The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). DESIGN: After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in the Netherlands. Patients with previous small-bowel surgery were excluded. After bowel preparation, VCE was performed. The videos were read by two independent investigators. If significant lesions were detected, an endoscopic procedure was subsequently performed to obtain histology and, if possible, remove the lesion. RESULTS: In total, 200 patients (mean age 50 years (range 35-69), M/F 88/112), with proven mutations were included. These concerned MLH1 (n = 50), MSH2 (n = 68), MSH6 (n = 76), PMS2 (n = 3) and Epcam (n = 3) mutation carriers. In 95% of the procedures, caecal visualisation was achieved. Small-bowel neoplasia was detected in two patients: one adenocarcinoma (TisN0Mx) and one adenoma, both located in the duodenum. In another patient, a duodenal cancer (T2N0Mx) was diagnosed 7 months after a negative VCE. This was considered a lesion missed by VCE. All three neoplastic lesions were within reach of a conventional gastroduodenoscope. All patients with neoplasia were men, over 50 years of age and without a family history of small-bowel cancer. CONCLUSIONS: The prevalence of small-bowel neoplasia in asymptomatic patients with LS was 1.5%. All neoplastic lesions were located in the duodenum and within reach of conventional gastroduodenoscopy. Although VCE has the potential to detect these neoplastic lesions, small-bowel neoplasia may be missed. TRIAL REGISTRATION NUMBER: NCT00898768.

[Important rise in antibiotic resistance rates inHelicobacter pyloriin the Netherlands]. / Verontrustende toename van antibioticaresistentie bijHelicobacter pylori.

OBJECTIVE: Description of the changing patterns of antibiotic resistance in Helicobacter pylori infection in the Netherlands. DESIGN: Retrospective database study using the Dutch infectious disease surveillance information system-antibiotic resistance (ISIS-AR). METHOD: In the ISIS-AR database antibiotic resistance data are reported by 46 microbiologic laboratories in the Netherlands. For the present study, data from 16 centres were used with a 10 year period of reporting H. pylori resistance data, from 1 January 2010 till 1 January 2020, for amoxycillin, levofloxacin, claritrhromycin, tetracyclin and metronidazole. RESULTS: In 2019 Antimicrobial resistance rates in the Netherlands were 1% for tetracycline, 5% for amoxycillin, 23%% for levofloxacin, 46% for metronidazole and 47% for clarithromycin. The combined resistance rate for clarithromycin and metronidazole was 29%. Significantly higher resistance rates were found in female patients for amoxycillin (8% vs 1%), clarithromycin (53% vs 38%) and metronidazole (52% vs 38%). From 2010 to 2019, a significant rise in resistance rates was found for amoxycillin (0% - 5%), clarithromycin (7% - 40%), metronidazole (14% - 45%) and for the clarithromycin and metronidazole combination (2% - 29%). CONCLUSION: There was an important rise in antibiotic resistance rates in H. pylori in the Netherlands. For optimal H. pylori treatment bismuth-based therapies should become available again in the Netherlands. Treatment of H. pylori should be based on the individual antibiotic resistance profile and be in concordance with the principles of antibiotic stewardship. Guidelines for treatment of H. pylori in the Netherlands should be adapted and have a better correlation with International guidelines and best practices.

EUS-guided fiducial marker placement for radiotherapy in rectal cancer: feasibility of two placement strategies and four fiducial types.

Background and study aims To facilitate image guidance during radiotherapy of rectal cancer, we investigated the feasibility of fiducial marker placement. This study aimed to evaluate technical success rate and safety of two endoscopic ultrasound (EUS)-guided placement strategies and four fiducial types for rectal cancer patients. Patients and methods This prospective multicenter study included 20 participants who were scheduled to undergo rectal cancer treatment with neoadjuvant short-course radiotherapy or chemoradiation. EUS-guided endoscopy was used for fiducial placement at the tumor site (n = 10) or in the mesorectal fat and in the tumor (n = 10). Four fiducial types were used (Visicoil 0.75 mm, Visicoil 0.50 mm, Cook, Gold Anchor). The endpoints were technical success rate and retention of fiducials, the latter of which was evaluated on cone-beam computed tomography scans during the first five radiotherapy fractions. Results A total of 64 fiducials were placed in 20 patients. For each fiducial type, at least three fiducials were successfully placed in all patients. Technical failure consisted of fiducial blockage within the needle (n = 2) and ejection of two preloaded fiducials at once (n = 4). No serious adverse events were reported. In three patients, one of the fiducials was misplaced without clinical consequences; two in the prostate and one in the intraperitoneal cavity. After a median time of 17 days after placement (range 7 - 47 days), a total of 42/64 (66 %) fiducials were still present (24/44 intratumoral vs. 18/20 mesorectal fiducials, P  = 0.009). Conclusions Placement of fiducials in rectal cancer patients is feasible, however, retention rates for intratumoral fiducials were lower (55 %) than for mesorectal fiducials (90 %).

Standardization of mesenchymal stromal cell therapy for perianal fistulizing Crohn's disease.

BACKGROUND: Local administration of mesenchymal stromal cells (MSCs) into the fistula tract seems to improve patient outcome in perianal fistulas due to Crohn's disease (CD). In this paper we propose a standardized and validated protocol for the local administration of MSCs for CD perianal fistulas to be able to reliably assess efficacy. MATERIALS AND METHODS: A working group consisting of gastroenterologists and surgeons with expertise in the treatment of perianal CD developed a consensus perianal fistula treatment protocol for local MSC treatment of perianal fistulizing CD. The treatment protocol was validated during a trial of allogeneic bone marrow-derived MSCs for the treatment of refractory perianal Crohn's fistulas. RESULTS: Localization and classification of perianal fistulas with MRI and rectoscopy is of crucial importance prior to surgical intervention with local therapy administration. Examination under anesthesia is necessary to incise and drain abscesses when present. Optimization of medical treatment when active luminal CD is present, is the first step before embarking on surgery and local therapy administration. In addition, strictures preventing the surgeon from adequately performing the surgical procedure have to be endoscopically dilated. Curettage of the fistula tract has an important role as long-standing CD perianal fistulas close poorly without removal of their epithelial lining. To diminish bacterial contamination of the fistula, the internal opening has to be closed. The origin of the fistula is the internal opening, therefore, efficacy of MSCs is presumably the highest when they are injected into the tissue around the internal opening. CONCLUSION: In this article, we propose a standardized method of local MSC administration for perianal fistulizing CD. The use of this standardized and validated protocol for the administration of local treatment of CD perianal fistulas will allow reliable comparison of the efficacy of local therapies in future.

High Growth Rate of Pancreatic Ductal Adenocarcinoma in CDKN2A-p16-Leiden Mutation Carriers.

CDKN2A-p16-Leiden mutation carriers have a 20% to 25% risk of developing pancreatic ductal adenocarcinoma (PDAC). Better understanding of the natural course of PDAC might allow the surveillance protocol to be improved. The aims of the study were to evaluate the role of cystic precursor lesions in the development of PDAC and to assess the growth rate. In 2000, a surveillance program was initiated, consisting of annual MRI in carriers of a CDKN2A-p16-Leiden mutation. The study cohort included 204 (42% male) patients. Cystic precursor lesions were found in 52 (25%) of 204 mutation carriers. Five (9.7%) of 52 mutation carriers with cystic lesions and 8 (7.0%) of 114 mutation carriers without cystic lesions developed PDAC (P = 0.56). Three of 6 patients with a cystic lesion of ≥10 mm developed PDAC. The median size of all incident PDAC detected between 9 and 12 months since the previous normal MRI was 15 mm, suggesting an annual growth rate of about 15 mm/year. In conclusion, our findings show that patients with and without a cystic lesions have a similar risk of PDAC. However, cystic precursor lesions between 10 and 20 mm increase the risk of PDAC substantially. In view of the large size of the screen-detected tumors, a shorter interval of screening might be recommended for all patients. Cancer Prev Res; 11(9); 551-6. ©2018 AACR.

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study).

BACKGROUND: Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. METHODS/DESIGN: Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. DISCUSSION: The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46462267.

Dilemmas in the management of screen-detected lesions in patients at high risk for pancreatic cancer.

In 3-5 % of all cases of pancreatic ductal adenocarcinoma (PDAC), hereditary factors influence etiology. While surveillance of high-risk individuals may improve the prognosis, this study describes two very different outcomes in patients with screen-detected lesions. In 2000, a surveillance program of carriers of a CDKN2A/p16-Leiden-mutation consisting of annual MRI was initiated. Patients with a suspected pancreatic lesion undergo CT-scan and Endoscopic Ultrasound, and surgery is offered when a lesion is confirmed. In 2015, two patients with a screen-detected solid lesion were identified. In both patients, lesions were visible on MRI and CT scan, while the EUS was unremarkable. Surgical resection of the head of the pancreas resulted in nearly fatal complications in the first patient. This patient was shown to have a benign lesion. In contrast, timely identification of an early cancer in the second patient was accompanied by an uneventful postoperative course. These cases underline the risks inherent to a PDAC prevention program. All patients should be fully informed about the possible outcomes before joining a surveillance program.

Toward optical guidance during endoscopic ultrasound-guided fine needle aspirations of pancreatic masses using single fiber reflectance spectroscopy: a feasibility study.

Endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) of pancreatic masses suffer from sample errors and low-negative predictive values. Fiber-optic spectroscopy in the visible to near-infrared wavelength spectrum can noninvasively extract physiological parameters from tissue and has the potential to guide the sampling process and reduce sample errors. We assessed the feasibility of single fiber (SF) reflectance spectroscopy measurements during EUS-FNA of pancreatic masses and its ability to distinguish benign from malignant pancreatic tissue. A single optical fiber was placed inside a 19-gauge biopsy needle during EUS-FNA and at least three reflectance measurements were taken prior to FNA. Spectroscopy measurements did not cause any related adverse events and prolonged procedure time with ? 5 ?? min . An accurate correlation between spectroscopy measurements and cytology could be made in nine patients (three benign and six malignant). The oxygen saturation and bilirubin concentration were significantly higher in benign tissue compared with malignant tissue (55% versus 21%, p = 0.038 ; 166 ?? ? mol / L versus 17 ?? ? mol / L , p = 0.039 , respectively). To conclude, incorporation of SF spectroscopy during EUS-FNA was feasible, safe, and relatively quick to perform. The optical properties of benign and malignant pancreatic tissue are different, implying that SF spectroscopy can potentially guide the FNA sampling.

Incidence of small bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

BACKGROUND AND STUDY AIMS: Lynch syndrome (LS) patients have an increased risk of small bowel cancer. The question is whether surveillance will lead to early detection of (pre)malignant lesions. We recently reported on prevalence of small bowel neoplasia (SBN) in LS patients as assessed by video capsule endoscopy (VCE). The aim of this prospective study was to determine the incidence of SBN. PATIENTS AND METHODS: Asymptomatic LS patients who underwent a VCE were invited to undergo a second VCE procedure 2 years later. If abnormalities or polypoid lesions larger than 1 cm were detected, subsequent endoscopic procedures were performed. RESULTS: A total of 155 (78 %) of the initial 200 patients underwent a second VCE procedure after a mean of 2.2 (range 1 - 6) years. In 17 of the 155 (11 %) patients possibly significant lesions were detected, which required further investigation by means of gastroduodenoscopy (n = 8) or balloon-assisted endoscopy (n = 9). These procedures revealed no SBN. CONCLUSION: No SBN was found after 2 years. Surveillance of the small bowel by VCE does not seem to be warranted in asymptomatic LS patients.

Back/joint pain, illness perceptions and coping are important predictors of quality of life and work productivity in patients with inflammatory bowel disease: a 12-month longitudinal study.

BACKGROUND AND AIMS: Back and joint pain are the most common extraintestinal symptoms reported by patients with inflammatory bowel disease (IBD). We assessed the impact of back/joint pain, illness perceptions, and coping on quality of life (QOL) and work productivity in patients with IBD. METHODS: Our cohort included 155 IBD patients with and 100 without arthropathy. Arthropathy was defined as daily back pain for ≥3 months and/or peripheral joint pain and/or joint swelling over the last year. At baseline and at 12 months, patients completed questionnaires on the extent of back/joint pain, IBD disease activity, illness perceptions, coping, QOL, and work productivity. The impact of back/joint pain, illness perceptions and coping on QOL and work productivity was determined, using linear mixed models. RESULTS: In total, 204 IBD patients (72% Crohn's disease, 40% male, mean age 44 ± 14 years) completed questionnaires at both time points. At both time points, IBD patients with back/joint pain reported a significantly lower QOL and work productivity compared with IBD patients without back/joint pain. Predictors of low QOL were back/joint pain (ß = -1.04, 95% confidence interval [CI] -1.40, -0.68), stronger beliefs about the illness consequences (ß = -0.39, 95% CI -0.59, -0.18) and emotional impact of IBD (ß = -0.47, 95% CI -0.66, -0.28), and the coping strategy 'decreasing activity' (ß = -0.26, 95% CI -0.48, -0.03). Predictors of work productivity were back/joint pain (ß = 0.22, 95% CI 0.07, 0.37) and illness consequences (ß = 0.14, 95% CI 0.06, 0.22). CONCLUSION: Back/joint pain, illness perceptions, and coping are significant predictors of QOL and work productivity, after controlling for disease activity.

Randomized Comparison of Surveillance Intervals in Familial Colorectal Cancer.

PURPOSE: Colonoscopic surveillance is recommended for individuals with familial colorectal cancer (CRC). However, the appropriate screening interval has not yet been determined. The aim of this randomized trial was to compare a 3-year with a 6-year screening interval. PATIENTS AND METHODS: Individuals between ages 45 and 65 years with one first-degree relative with CRC age < 50 years or two first-degree relatives with CRC were selected. Patients with zero to two adenomas at baseline were randomly assigned to one of two groups: group A (colonoscopy at 6 years) or group B (colonoscopy at 3 and 6 years). The primary outcome measure was advanced adenomatous polyps (AAPs). Risk factors studied included sex, age, type of family history, and baseline endoscopic findings. RESULTS: A total of 528 patients were randomly assigned (group A, n = 262; group B, n = 266). Intention-to-treat analysis showed no significant difference in the proportion of patients with AAPs at the first follow-up examination at 6 years in group A (6.9%) versus 3 years in group B (3.5%). Also, the proportion of patients with AAPs at the final follow-up examination at 6 years in group A (6.9%) versus 6 years in group B (3.4%) was not significantly different. Only AAPs at baseline was a significant predictor for the presence of AAPs at first follow-up. After correction for the difference in AAPs at baseline, differences between the groups in the rate of AAPs at first follow-up and at the final examination were statistically significant. CONCLUSION: In view of the relatively low rate of AAPs at 6 years and the absence of CRC in group A, we consider a 6-year surveillance interval appropriate. A surveillance interval of 3 years might be considered in patients with AAPs and patients with ≥ three adenomas.

Classification, epidemiology and aetiology.

Intestinal failure and its most important cause, short-bowel syndrome (SBS), are rare clinical entities leading to a vast complex of symptoms and complications with significant morbidity and mortality. Both conditions occur as the result of a massive reduction in enteral nutrient absorptive capacity. Disease manifestation is based on aetiological and anatomical characteristics such as remaining intestinal length and the presence of a functionally intact colon. Congenital and perinatal conditions, for example, intestinal atresia, necrotizing enterocolitis (NEC) and intestinal volvulus are the most important causes in children. The aetiology in adults is based on diseases inducing loss of intestinal function or loss of intestinal surface area after extensive surgical resections. The most frequent causes are mesenteric infarction, radiation enteritis and Crohn's disease. Knowledge of the epidemiology of intestinal failure and SBS is limited, being mainly based on the extrapolated figures of home parenteral nutrition centres and single-centre studies. At present, the incidence of SBS is estimated to be 2-5 per million.

Improving the outcome of fistulising Crohn's disease.

Fistulas are a frequent manifestation of Crohn's disease (CD) and can result in considerable morbidity. Approximately 35% of all patients with CD will experience one fistula episode during their disease course of which 54% is perianal. The major symptoms of patients with perianal fistulas are constant anal pain, the formation of painful swellings around the anus and continuous discharge of pus and/or blood from the external fistula opening. The exact aetiology of perianal fistulas in CD patients remains unclear, but it is thought that a penetrating ulcer in the rectal mucosa caused by active CD forms an abnormal passage between the epithelial lining of the rectum and the perianal skin. Genetic, microbiological and immunological factors seem to play important roles in this process. Although the incidence of perianal fistulas in patients with CD is quite high, an effective treatment is not yet discovered. In this review all available medical and surgical therapies are discussed and new treatment options and research targets will be highlighted.

Influence of combination therapy with immune modulators on anti-TNF trough levels and antibodies in patients with IBD.

BACKGROUND: It is important to identify factors that can reduce the incidence of immunogenicity against anti-tumor necrosis factor medication in patients with inflammatory bowel disease. The objective of our study was to evaluate the influence of cotreatment with immune modulators (IMs) on trough levels (TLs) and antidrug antibodies. METHODS: The records of all patients with inflammatory bowel disease at the Leiden University Medical Center who received either adalimumab or infliximab (IFX) in the year 2011 and/or 2012 (n = 352) were retrospectively evaluated about the assessment of TL and antibodies and use of IM. RESULTS: Two hundred seventeen patients were included (108 patients IFX; 109 patients adalimumab). Mean TL in the IFX group was higher in the combination therapy group compared with the monotherapy group, 4.6 versus 7.5 µg/mL, P = 0.04. In the adalimumab group, the difference was not significant. In patients with IFX monotherapy, the incidence of antibody formation was higher compared with patients with combination therapy (29.8% versus 5.7%, P = 0.001). IFX patients with a suboptimal dose of IM had a higher TL compared with patients who had an optimal dose, P = 0.02. The incidence of antibody formation was lower in IFX patients who immediately started with IMs compared with patients who did not (33.3% versus 66.7%, P = 0.04). CONCLUSIONS: The influence of combination therapy with IM on TL and antibodies to anti-tumor necrosis factor medication was significant for IFX-treated patients. Patients who started combination therapy immediately developed antibodies less often than patients who started later with concomitant medication.

Value-based healthcare in Lynch syndrome.

Lynch syndrome (LS), one of the most frequent forms of hereditary colorectal cancer (CRC), is caused by a defect in one of the mismatch repair (MMR) genes. Carriers of MMR defects have a strongly increased risk of developing CRC and endometrial cancer. Over the last few years, value-based healthcare has been introduced as an approach to the cost-effective delivery of measurable patient value over complete cycles of care. This requires all involved stakeholders to formulate and validate 'patient value' for Lynch syndrome, as well as to identify targets and associated costs. The aim of this study was to develop a value-based care model for Lynch syndrome that can determine patient value and associated costs, and to design a coordinated care pathway from existing guidelines. All specialists in our hospital involved in the management of LS patients evaluated the care delivered to these patients at their department and formulated outcome measures relevant to patient value. Patients were then invited to complete a questionnaire that assessed the importance of these measures on a scale of 1-10. Six high-value outcomes were identified: (1) prevention of cancer or detection of early stage cancer (2) rapid results from MMR gene mutation testing (3) rapid investigation of the colon and uterus (4) no/little pain during colonoscopy and gynaecologic examination/biopsy (5) the offer of psychological help and (6) registration with the Dutch Lynch syndrome registry. A total of 38 (59 %) out of 62 patients completed the questionnaire. The relevance of all outcomes was confirmed by the patients and mean scores varied from 7.2 to 9.9. Patients underscored the relevance of both proper patient education and the efficiency of surveillance during their care cycle. Value-based care delivery for Lynch syndrome includes the implementation of six parameters related to prevention and early detection of cancer, a short cycle time and registration to ensure continuation of care. Estimated costs are 3320 for the first cycle of care ( 3550 including gynaecologic surveillance) and approximately 720 per subsequent annual cycle ( 950 including gynaecologic surveillance).

Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels.

BACKGROUND: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. AIM: This study was performed to investigate whether H. pylori-affected gastric mucosal MMP-2 and MMP-9 levels are reversible by successful treatment of the infection. PATIENTS AND METHODS: Fifty-eight patients with H. pylori-associated gastritis were treated with a combination regimen of acid inhibitory therapy and antibiotics for 14 days. The levels and isoforms of MMP-2 and MMP-9 were measured by semiquantitative gelatin-zymography, bioactivity assay and enzyme-linked immunosorbent assay in gastric mucosal biopsy homogenates. RESULTS: Latent, active, and total MMP-9 levels decreased consistently and significantly by successful H. pylori eradication, in antrum as well as corpus mucosa, compared with those prior to treatment, irrespective of the therapy regimen used. The elevated levels remained unchanged, however, when treatment failed. MMP-2 levels did not show major alterations after H. pylori therapy. CONCLUSION: Elevated MMP-9 levels in H. pylori-infected gastric mucosa are reversible by eradication of the infection. No major changes in mucosal MMP-2 levels were observed by H. pylori eradication.