CLINICAL AND ENDOSCOPIC HEALING AFTER INFLIXIMAB TREATMENT IN PATIENTS WITH CROHN's DISEASE

Background: Intestinal mucosal lesions in Crohn's disease were endoscopically evaluated before and after giving infliximab, and the usefulness of this treatment was investigated. Patients and methods: The present study included 12 patients with active Crohn's disease who could undergo colonoscopy before and after giving infliximab. (i) The treatment assessment consisted of evaluations of short‐term and long‐term therapeutic effects. The clinical evaluation was conducted using the Crohn's disease activity index (CDAI). The results of the clinical evaluation were compared with those of the colonoscopic evaluation. (ii) The endoscopic evaluation findings were divided into polyposis, ulcer and stenosis, and the area ranging from the rectum to the terminal ileum. The scores for the findings at seven sites were totaled. In the short‐term therapeutic effect, characteristics of ulcer morphology and background factors were investigated endoscopically. Results: (i) The efficacy rate was 92% clinically and 67% endoscopically in the evaluation of short‐term therapeutic effects. The efficacy rate was 86% clinically and 86% endoscopically in the evaluation of long‐term therapeutic effects. (ii) On the endoscopic evaluation, the ulcer score was significantly (P = 0.03) improved after giving infliximab, while there was no remarkable change in the polyposis score and the stenosis score tended to worsen. On the evaluation of therapeutic effects based on ulcer morphology, infliximab was endoscopically effective in patients with longitudinal ulcers. On the evaluation of therapeutic effects based on background factors, the treatment was effective in patients given a combination of infliximab and immunosuppressants. Conclusion: The ulcerative lesions were found to be markedly improved, but the intestinal stenosis tended to worsen, after giving infliximab. It is necessary that the severity of intestinal stenosis be adequately understood before giving infliximab. Giving immunosuppressants should be used for combined treatment.     

ENDOSCOPIC FINDINGS OF ENTEROPATHY‐TYPE T‐CELL LYMPHOMA BY DOUBLE‐BALLOON ENTEROSCOPY AND CAPSULE ENDOSCOPY

Enteropathy‐type T‐cell lymphoma (ETL) is a rare primary intestinal disorder, particularly in Japan, and there have been few reports on the endoscopic findings of the disease. Here we report detailed endoscopic findings of ETL based on double‐balloon enteroscopy and capsule endoscopy. Double‐balloon enteroscopy and capsule endoscopy may be useful tools for diagnosing and monitoring the effects of therapy in patients with ETL.     

EFFICACY OF AZATHIOPRINE IN MILD OR MODERATE RELAPSE IN CROHN'S DISEASE: CLINICAL AND ENDOSCOPIC EVALUATION

Aim: The present study was aimed at evaluating the efficacy of azathioprine (AZA) in patients with active and relapsing Crohn's disease (CD) and the usefulness of endoscopy in this evaluation. Methods: The 53 patients with active CD treated with AZA at our hospital were subjected to the following retrospective analysis: (i) evaluation of the clinical efficacy of AZA through comparison of the Crohn's disease activity index (CDAI); (ii) analysis of the relationship of the clinical efficacy to the difference in the mean corpuscular volume (MCV); (iii) evaluation of mucosal healing through analysis of the scores of the endoscopic findings in 16 patients; and (iv) analysis of the relapse rate. Results: (i) Among the 53 patients, treatment was rated as having induced complete remission in 22.6%, as being effective in 41.5%, and as being ineffective in 13.3% of patients. The treatment was discontinued in 22.6% of patients. (ii) The post‐treatment MCV was significantly increased after treatment. (iii) When the ulcer score estimated after treatment was compared with that before the start of treatment, a significant improvement of the score was noted. (iv) When the non‐relapse rate after AZA therapy was calculated in the 41 patients followed up for 12 months, it was 84.8%. Conclusion: AZA was shown to cause endoscopic mucosal healing as well as clinical efficacy. In the present study, it was inferred that the efficacy of AZA therapy in CD patients is manifested clinically first and that mucosal healing is an effect that occurs later.     

Response of cutaneous Crohn’s disease to infliximab and methotrexate

Cutaneous or metastatic Crohn's disease is a rare complication of Crohn's disease and is frequently refractory to medical treatment. A case of metastatic Crohn's disease affecting first the abdominal wall and subsequently both submammary folds is reported. These extraintestinal manifestations occurred many years after proctocolectomy. The activity of cutaneous disease was associated with a chronic active fistulizing disease. Skin manifestations were resistant to treatment with steroids, antibiotics and azathioprine. Repetitive treatment with infliximab led to significant improvement of both cutaneous and fistulous disease. However, disease relapsed and even progressed after a period of 6 weeks following each infliximab treatment. Only the introduction of methotrexate, together with repetitive administration of infliximab, allowed maintenance of the patient in remission.     

Continuing low incidence of Crohn’s disease in Northwest Greece

AIM OF STUDY: The largest population-based study for inflammatory bowel disease in Northwest Greece. MATERIALS AND METHODS: A retrospective survey for the years 1982-1997. RESULTS: Of 400 patients, 334 had ulcerative colitis, 43 Crohn's disease and 23 indeterminate colitis. CONCLUSIONS: Crohn's disease still remains rare in Northwest Greece.     

Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn’s disease

Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn’s disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.     

USEFULNESS OF DOUBLE BALLOON ENTEROSCOPY AND VIDEO CAPSULE ENDOSCOPY FOR THE DIAGNOSIS AND MANAGEMENT OF PRIMARY FOLLICULAR LYMPHOMA OF THE GASTROINTESTINAL TRACT IN ITS EARLY STAGES

Aim: The aim of this study is to evaluate the usefulness of double balloon enteroscopy (DBE) and video capsule endoscopy (VCE) in patients with primary follicular lymphoma (FL) of the gastrointestinal (GI) tract. Furthermore, we estimate the effectiveness of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) including rituximab for them. Methods: Thirteen consecutive patients who were diagnosed of having FL in the duodenum between July 2005 and September 2008 were studied. All patients were given the conventional staging examinations, including total enteroscopy using DBE and/or VCE procedures. Chemotherapy was performed after written informed consent. Response assessment was performed every 6‐12 months. The median follow‐up period was 30.2 months. Results: FL was diagnosed in each patient as low grade (grade 1, n = 7; 2, n = 6) and, in all but 4 patients, localized lymphoma (stage I, n = 8; II₁, n = 1; II₂, n = 4). DBE revealed multifocal lesions in the jejunum in 10 of the patients, and in the ileum in 6. VCE showed similar findings in the jejunum in the recent 2 patients. Eleven of 13 patients finally received chemotherapy, and all of them achieved complete regression. They showed no evidence of recurrence after that. Conclusion: Total examination of the small intestine using DBE should be performed before treatment to choose a suitable treatment procedure for primary FL of the GI tract. On the other hand, VCE is useful for screening and following the small intestine in the patients with it. Chemotherapy is effective to achieve complete regression of primary FL of the GI tract.     

Successful treatment with topical mesalazine for a patient with intractable crohn’s colitis

A 32‐year‐old woman was admitted to our hospital for intractable Crohn’s disease. Crohn’s colitis was diagnosed at another hospital in August 1999. She had been successfully treated with oral mesalazine and an elemental diet. In March 2000, she had been admitted to the previous hospital for her third flare up of symptoms. She responded to oral mesalazine administration and total parenteral nutrition, but bowel symptoms were exacerbated and C‐reactive protein level was elevated after a polymeric diet was started. Prednisolone 30 mg/day was started in addition to total parenteral nutrition, but hematochezia and elevated serum C‐reactive protein level persisted, and she was referred to our hospital. She had about four bowel movements per day with fresh bleeding at the time of admission. Total parenteral nutrition and oral mesalazine were continued. The dose of oral prednisolone was increased from 15 mg/day to 40 mg/day. However, the frequency of bowel movements did not decrease and C‐reactive protein level continued to exceed 1.5 mg/day. Mesalazine enemas were begun on 23 January 2001, and were effective in improving hematochezia and serum C‐reactive protein. Both radiologic and endoscopic examinations revealed remarkable improvement.     

Wireless capsule video endoscopy compared to barium follow-through and computerised tomography in patients with suspected Crohn’s disease—final report

BACKGROUND: Wireless capsule endoscopy is a superior diagnostic tool to barium small bowel follow-through and enteroscopy in diagnosing patients with occult blood loss. AIM: To compare capsule endoscopy with barium follow-through and entero-computerised tomography in patients with suspected Crohn's disease. SUBJECTS AND METHODS: Thirty-five patients with suspected Crohn's disease underwent the three examinations. The radiologist and gastroenterologist were blinded to each other's results. In cases of discrepancy, colonoscopy and ileoscopy were performed. RESULTS: Thirty-five patients (22 males), mean age 28.4 years, were included. Eighty-eight percent had abdominal pain, 83% had diarrhoea and 69% had weight loss. The diagnostic yield of capsule endoscopy was 77% versus 23% and 20% of barium and computerised tomography examinations, respectively (P < 0.05). The capsule detected all of the lesions diagnosed by barium follow-through and entero-computerised tomography. CONCLUSIONS: Capsule endoscopy is a superior and more sensitive diagnostic tool than barium follow-through and entero-computerised tomography in patients with suspected Crohn's disease.     

Comparison between methotrexate and azathioprine in the treatment of chronic active Crohn’s disease: a randomised, investigator-blind study

BACKGROUND AND AIMS: The efficacy of azathioprine in the treatment of chronic active Crohn's disease is well established. However, this drug has a long onset of action. Methotrexate has also been shown to be effective in chronic active Crohn's disease. The aim of this study was to evaluate the efficacy and safety of methotrexate in comparison with azathioprine, and to establish whether methotrexate has a shorter onset of action in this setting. METHODS: Patients with chronic active Crohn's disease were admitted to this investigator-blind study. Chronicity was defined as the need for steroid therapy of > or = 10 mg/day for at least 4 months during the preceding 12 months, with at least one attempt to discontinue treatment. The disease had to be clinically active at entry, with a Crohn's Disease Activity Index of > or = 200. Six patients treated with azathioprine and methotrexate, respectively, were found to have enterocutaneous and perianal fistulas. At entry, all patients received prednisolone (40 mg once a day) which was tapered over a period of 12 weeks unless their clinical condition deteriorated. All patients were randomised to receive i.v. methotrexate 25 mg/week, or oral azathioprine 2 mg/kg per day, for a 6-month follow-up period. After the first 3 months, methotrexate was switched to oral administration maintaining the same dose. The primary efficacy outcome considered was the proportion of patients entering first remission after 3 and 6 months of therapy. Clinical remission was defined as the lack of need for steroid treatment and a Crohn's Disease Activity Index score of < or = 150 points at each scheduled visit. RESULTS: In the 54 patients (26 F, 28 M, mean age 34 years, range 18-60) randomly assigned to methotrexate (n=27) or azathioprine (n=27), no statistically significant difference was found between the two treatment regimens with respect to remission rate after 3 (methotrexate 44%, azathioprine 33%, p=0.28, (95% CI, 0.369-0.147), and 6 months (methotrexate 56%, azathioprine 63%, p=0.39, 95% CI, 0.187-0.335), respectively. Six patients withdrew from therapy due to adverse events: 3/27 (11%) in methotrexate and 3/27 (11%) in azathioprine. Drug-related adverse events (asthenia, nausea and vomiting) that did not require withdrawal from therapy were more frequent in the methotrexate group (azathioprine: 2/27 (7%); methotrexate: 12/27 (44%), p=0.00009). The frequency of these adverse events was comparable during the intravenous or oral administration of the drug. CONCLUSIONS: This study confirms that methotrexate is effective in inducing remission in patients with chronic active Crohn's disease, therapeutic efficacy being comparable, but not faster, than that of azathioprine.     

ENDOSCOPIC BALLOON DILATATION USING DOUBLE‐BALLOON ENDOSCOPY IS A USEFUL AND SAFE TREATMENT FOR SMALL INTESTINAL STRICTURES IN CROHN'S DISEASE

Background: Endoscopic balloon dilatation (EBD) is a therapeutic option for intestinal strictures of Crohn's disease (CD). Double‐balloon endoscopy (DBE) enables EBD to be performed even for deep‐situated strictures of the small intestine. The aim of this study was to clarify the efficacy and safety of EBD using DBE for small bowel strictures in patients with CD. Patients and Methods: The subjects comprised 25 patients with CD who underwent EBD using DBE for small intestinal strictures for which a colonoscope or gastrointestinal scope could not be inserted. All subjects had obstructive symptoms due to strictures that were confirmed using small intestinal enteroclysis. They were observed for at least 6 months after the initial EBD. The short‐term success rate of EBD using DBE, the complication rate and the long‐term outcome were investigated. Results: This procedure was successful with regard to short‐term dilatation in 18 of the 25 CD patients (72%). Long strictures measuring more than 3 cm were seen in six out of seven (85.7%) of the unsuccessful EBD cases, compared with two out of 18 (11.1%) of the successful EBD cases (P = 0.001). Complications were encountered in two of the 25 patients (8%). The cumulative surgery‐free rate for all the subjects was 83% and 72% at 6 and 12 months, respectively. Conclusion: EBD using DBE is a useful and safe procedure for small intestinal short strictures in CD patients. We conclude that this procedure is a therapeutic option that should be attempted before resorting to surgical therapy.     

Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease

BACKGROUND: Infliximab has recently emerged as an efficacious agent for patients with severe Crohn's disease. There are only few studies on the use of infliximab in children with Crohn's disease: most of them are retrospective and deal only with the clinical response to the drug. AIM: We aimed at assessing the efficacy of infliximab in children and adolescents with severe Crohn's disease recruited consecutively and followed up prospectively at a single centre. Clinical response, intestinal inflammation and growth pattern were evaluated. PATIENTS: Eighteen patients entered into the trial (median age: 13 years, range: 6-18). They were referred because of severe symptoms with unsatisfactory response to conventional drugs. METHODS: All patients received a baseline schedule of three intravenous infusions of infliximab (0, 2 and 6 weeks), 5 mg/kg. Paediatric Crohn's Disease Activity Index, nutritional and activity serum variables, and ileocolonoscopy (with histology) were evaluated before and 8 weeks after beginning the therapy. All patients had long-term administration of azathioprine (2 mg/kg per day). After the baseline schedule, eight patients had a retreatment infusion of infliximab (5 mg/kg) every 8 weeks. Weight and height Z scores were measured before starting the baseline infusion programme and after 6 months. RESULTS: After 8 weeks of therapy, there was a dramatic improvement in Paediatric Crohn's Disease Activity Index, in nutritional and activity blood parameters, as well as in endoscopic and histological scores; 10 patients had a clinical remission (Paediatric Crohn's Disease Activity Index < or = 10), 12 patients had an inflammatory remission (decrease in both endoscopic and histological scores for > or = 50% as compared to baseline values). In all patients corticosteroids were stopped within 4 weeks after beginning infliximab therapy. After 6 months of therapy, Paediatric Crohn's Disease Activity Index was markedly lower than the pre-treatment value; however, it was significantly lower in patients on retreatment than in those who received only three infusions of infliximab. Furthermore, a significant increase in both weight and height Z scores was observed 6 months after beginning of the baseline infusion programme. Moreover, weight and height gain was significantly higher in patients on retreatment rather than in those treated only with three baseline infusions of infliximab. Mild infusion reactions controlled by slowing infusion rate were observed in four patients. No delayed hypersensitivity-like reactions were seen. CONCLUSIONS: In children with severe Crohn's disease, infliximab is a safe and valuable treatment in inducing remission, in healing inflammatory lesions of the gut, as documented by endoscopy and histology, and in promoting growth. Retreatment infusions of infliximab may be suggested in childhood-onset Crohn's disease to maintain remission and reverse growth failure.     

Safety and efficacy of capsule endoscopy for patients with newly diagnosed Crohn’s disease: A multicenter retrospective study

Crohn’s disease (CD) is a chronic inflammatory disease that develops at a young age and frequently leads to intestinal resection. Capsule endoscopy (CE) can directly and non-invasively inspect the entire small bowel mucosa. We suspected that CE could be a good diagnostic tool for detecting CD in young patients. The aim of this study was to investigate the safety and efficacy of CE in patients with newly diagnosed CD and to evaluate the CE findings, especially in the upper small bowel of young patients. We retrospectively investigated 32 patients with newly diagnosed CD from 5 institutions. Patient characteristics, clinical course, and characteristics of CE findings were analyzed. The total small intestine observation rate was 93%, and the retention rate was 3% (1/32). No abnormality was identified by ileocolonoscopy in 46% (15/32), and transition of small bowel lesions (TSL) was found in 35% (12/34) of the patients. The frequency of longitudinal ulcers and cobblestones in the upper small intestine was significantly higher in younger patients (≤20 years). Moreover, positive findings in the upper small intestine were predominantly observed in younger patients (≤20 years). CE for patients with newly diagnosed CD was safe and useful, especially for the detection of upper small bowel lesions in young patients.     

冠心病、高血压病患者脉压、C-反应蛋白和同型半胱氨酸相关性分析

目的探讨脉压(PP)、C-反应蛋白(CRP)、同型半胱氨酸(Hcy)与冠心病、高血压病(EH)的关系.方法回顾性分析150例曾接受冠状动脉造影的患者,测量血压,检测血清CRP、Hcy浓度及其他生化指标,比较冠心病组和非冠心病组中PP、CRP、Hcy的差异.结果150例患者中,冠心病79例,非冠心病71例,冠心病组、非冠心病组PP分别为(6246±1417)mmHg、(4702±1201)mmHg(P＜001);血清CRP浓度分别为(12.03±707)mg/L、(483±626)mg/L(P＜001);血清Hcy浓度分别为(3042±1660)mol/L、(1662±11.39)mol./L(P＜001).同样高血压病患者与非高血压病患者的PP、CRP、Hcy差异有显著性,高血压病患者高于非高血压病患者.结论PP、CRP、Hcy与冠心病、高血压病相关,参与了冠心病、高血压病的发生和发展.     

DIAGNOSIS OF BARRETT’S ESOPHAGUS AND ESOPHAGEAL NEOPLASIA: EAST MEETS WEST

Barrett’s esophagus has traditionally been considered to be a predominantly ‘Western world’ neoplastic condition. However, over the years, Asian countries are beginning to diagnose increasing numbers of patients with gastroesophageal reflux disease, columnar metaplasia at the gastroesophageal junction, Barrett’s esophagus, and esophageal adenocarcinoma. Hence, the controversies regarding screening for and surveillance of Barrett’s esophagus and esophageal adenocarcinoma have become more widely relevant to gastroenterologists around the world. Emerging concepts related to esophageal cancer prevention and early detection include the screening for Barrett’s esophagus using wireless videocapsule endoscopy, and chromoendoscopy, enhanced high resolution endoscopy. There is also interest in improving surveillance for esophageal neoplasia using novel imaging techniques, such as high resolution and high magnification endoscopy, narrow‐band imaging, autofluorescence imaging, and endocytoscopy/endomicroscopy. The enhanced detection of Barrett’s esophagus and esophageal neoplasia become even more clinically relevant because of accumulating data on the safety and effectiveness of mucosal ablative techniques (such as photodynamic therapy, argon plasma coagulation, low pressure cryotherapy) and endoscopic mucosal resection. This article summarizes the latest developments related to Barrett’s esophagus that are of interest to endoscopists from the East or West.     

Amyloid‐β neurotoxicity in organotypic culture is attenuated by melatonin: involvement of GSK‐3β, tau and neuroinflammation

Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by accumulation of extracellular deposits of amyloid‐β (Aβ) peptide in brain regions that are important for memory and cognition. The buildup of Aβ aggregates in the AD is followed by the formation of intracellular neurofibrillary tangles and activation of neuroinflammatory reactions. The present study investigated whether melatonin possesses a neuroprotective effect against Aβ‐induced toxicity. For this purpose, organotypic hippocampal slices were cultured and exposed to 25 μm of Aβ_25–35 in the absence or in the presence of melatonin (25, 50, or 100 μm ). In addition, the authors have investigated the involvement of GSK‐3β, tau protein, astroglial, and microglial activation, and cytokine levels in the melatonin protection against Aβ‐induced neurotoxicity. Melatonin prevented the cell damage in hippocampus induced by the exposure to Aβ_25–35. In addition, melatonin significantly reduced the activation of GSK‐3β, the phosphorylation of tau protein, the glial activation and the Aβ‐induced increase of TNF‐α and IL‐6 levels. On the basis of these findings, we speculate that melatonin may provide an effective therapeutic strategy for AD, by attenuating Aβ‐induced phosphorylation of tau protein, and preventing GSK‐3β activation and neuroinflammation.