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Endoscopy is currently the gold standard for the diagnosis of inflammatory bowel disease (IBD). The presence of macroscopic lesions along with the microscopic detection of inflammatory infiltration in the terminal ileum often leads the gastroenterologist to the diagnosis of Crohn’s disease (CD). However, some of these cases could be, in fact, an infection caused byYersiniaspp., accompanied or not with CD, which could be easily diagnosed with the identification of serum antibodies againstYersiniaouter protein antigens (YOP antigens). Since Yersiniosis is considered to be an uncommon situation, food and water are not usually checked for the possibility of contamination byYersinia. Therefore, it is reasonable to assume that the true prevalence ofYersiniainfection in patients with terminal ileitis is probably underestimated. In this article, we review the most important data regarding the various aspects ofYersiniainfection with special focus on its pathophysiology and diagnosis. We recommend testing for serum antibodies against YOP antigens in all patients with an endoscopic and histological image of terminal ileitis in order to identify Yersiniosis in conjunction or not with terminal ileum CD.

Enteral nutrition seems to play a significant role in the treatment of both adults and children with active Crohn’s disease, and to a lesser degree in the treatment of patients with active ulcerative colitis. The inclusion of some special factors in the enteral nutrition formulas might increase the rate of the efficacy. Actually, enteral nutrition enriched in Transforming Growth Factor-β reduced the activity index and maintained remission in patients with Crohn’s disease. In addition, a number of experimental animal studies have shown that colostrum exerts a significantly positive result. Probiotics of a special type and a certain dosage could also reduce the inflammatory process in patients with active ulcerative colitis. Therefore, the addition of these factors in an enteral nutrition formula might increase its effectiveness. Although the use of these formulas is not supported by large clinical trials, it could be argued that their administration in selected cases as an exclusive diet or in combination with the drugs used in patients with inflammatory bowel disease could benefit the patient. In this review, the authors provide an update on the role of enteral nutrition, supplemented with Transforming Growth Factor-β, colostrum, and probiotics in patients with inflammatory bowel disease.

Highlights • Entero-vesical fistulas (EVFs) represent an uncommon complication of Crohn’s disease. • EVFs affects mostly men patients. • Conservative treatment improves symptoms but is associated with low rate of healing. • Surgical approach is usually necessary, establishing long-term remission., Background Entero-vesical fistula (EVF) is an abnormal link between the enteric lumen and the urinary bladder. Crohn's disease (CD) represents, nowadays, the most common cause in the formation of this fistula. Materials and methods The aim of this study was to describe the diagnostic and treating modalities applied in nine patients with CD and EVFs, the clinical/epidemiological features of this clinical entity and to perform a systemic review of the literature, concerning the diagnosis and treatment of this complication. Results The medical records of eight men and one woman (mean age 42 ± 12 years) with EVFs were analyzed. The terminal ileum and the ileocecal region were affected in three and six cases, respectively. The most common symptoms were pneumaturia, fecaluria, fever, urinary urgency and abdominal pain. The diagnosis was suspected by abdominal CT scan and by indirect findings of bladder infection in cystoscopy. MRI with concurrent cystography set the diagnosis in three patients. Colonoscopy was not helpful. Conservative treatment, including administration of antibiotics and immunosuppressive agents in all patients and anti-TNF-a agent (infliximab) in six patients, was ineffective. Surgical treatment was applied in seven cases (77.8%), including fistula repair in all patients, drainage of coexistent intraabdominal abscess in two, small bowel resection in four and ileocecectomy in two cases. Conclusion EFVs are uncommon but potentially dangerous complications of CD. Abdominal CT scan and cystoscopy are the most commonly used diagnostic modalities. Surgical treatment seems to be unavoidable in most cases, although medical treatment could also benefit a small cohort of patients.

Biliary obstruction is common in pancreatobiliary malignancies and has a negative impact on the patient’s quality of life, postoperative complications, and survival rates. Particularly in the last decade, there has been enormous progress regarding the diagnostic and therapeutic options in patients with malignant biliary obstruction. Endoscopy has given a new insight in this direction and novel techniques have been developed for the better characterization and treatment of malignant strictures. We herein summarize the available data on the different endoscopic techniques, and clarify their role in the diagnosis and treatment of malignant biliary obstructive disease. Finally, we propose an algorithm that can facilitate management decisions in these patients.

We describe a rare case of a young patient with Crohn’s disease, who accidentally was found to have developed renal cell carcinoma while on treatment with anti-TNF-α biologic agent. The patient was submitted to laparoscopic resection of the tumor. Up to December 2019 he is in perfect condition without receiving any kind of antineoplastic treatment. Clinicians should bear in mind this clinical combination in patients with Crohn’s disease under treatment with biologic anti-TNF-α agents. Because the exact influence of anti-TNF-α biologic agents is largely unclear for now, the continuation of treatment might be a possible option.

Background/Aim. Treatment with growth factors could be beneficial in both inflammatory bowel disease and experimental colitis. The aim of this study was to investigate the effect of Colony Stimulating Factor (CSF), and Recombinant Human (rHu) Granulocyte Stimulating Factor (GSF) in experimental colitis in rats. Methods. Experimental colitis was induced in 62 male Wistar rats, divided into 9 groups, using 2,4,6-trinitrobenzensulfonic acid (TNBS). Group 1: Ten rats with colitis without treatment (control group). Euthanasia after 15 days. Group 2: Ten animals with colitis without treatment (control group). Euthanasia after 30 days. Group 3: Six animals with colitis. Immediate treatment with CSF. Euthanasia after 19 days. Group 4: Six animals with colitis. Treatment started 7 days after the induction of colitis. Animals were kept for 19 days. Group 5: Six animals with colitis. Treatment started 2 weeks after the induction of colitis. Group 6: Six animals with colitis, the same as in group 3. Treatment with GSF. Group 7: Six animals with colitis, the same as in group 4. Treatment with GSF. Group 8. Six animals with colitis, the same as in group 5. Treatment with GSF. Group 9: Six animals with colitis. Immediate treatment with prednisolone. Euthanasia after 15 days. Results. CSF and GSF administration significantly improved the histological score (P<0.05) and reduced malondialdehyde contents (P<0.05), compared to control groups in all animals. CSF was superior to GSF and to prednisolone. Conclusion. Administration of both CSF and GSF could significantly improve the histological score and oxidative stress in experimental colitis in rats.

In recent years, the role of primary care physicians (PCPs) in the diagnosis and management of gastrointestinal disorders, including screening for colorectal cancer (CRC), has been recognized as very important. The available data indicate that PCPs are not adequately following CRC screening guidelines because a number of factors have been identified as significant barriers to the proper application of CRC screening guidelines. These factors include lack of time, patient reluctance, and challenges related to scheduling colonoscopy. Further positive engagement of PCPs with CRC screening is required to overcome these barriers and reach acceptable levels in screening rates. To meet the expectations of modern medicine, PCPs should not only be able to recommend occult blood testing or colonoscopy but also, under certain conditions, able to perform colonoscopy. In this review, the authors aim to provide the current knowledge of the role of PCPs in increasing the rate and successfully implementing a screening program for CRC by applying the relevant international guidelines.

We report a patient with an exceptionally rare combination of synchronous pancreatic and rectal cancer diagnosed within a 4 months’ interval. A 69-year-old female was evaluated for continuous epigastric pain and anorexia over the last three months. The tumor was classified as non-operable, as infiltration of large vessels was detected. The patient responded well to chemo/radiotherapy. However, infiltration of the large vessels was persisted. Four months later the patient started complaining of tenesmus and bloody stools. A digital rectal examination revealed the presence of a mass starting 7-8cm from the anal margin. Sigmoidoscopy showed a mass protruding into the bowel lumen. The patient died 16 months after the diagnosis of pancreatic cancer and 12 months after the diagnosis of rectal cancer. We suggest that clinicians should be aware about the possibility of the existence of multiple primary tumors in the same patient and subsequently to optimize their investigational plans.

Oxidative stress is present in patients with Inflammatory Bowel Disease (IBD), and natural supplements with antioxidant properties have been investigated as a non-pharmacological approach. The objective of the present study was to assess the effects of a natural Pistacia lentiscus (PL) supplement on oxidative stress biomarkers and to characterise the plasma-free amino acid (AA) profiles of patients with active IBD (Crohn&rsquo, s disease (CD) N = 40, ulcerative colitis (UC) N = 20). The activity was determined according to 5 &le, Harvey Bradshaw Index &le, 16 or 2 &le, Partial Mayo Score &le, 6. This is a randomised, double-blind, placebo-controlled clinical trial. IBD patients (N = 60) were randomly allocated to PL (2.8 g/day) or to placebo for 3 months being under no treatment (N = 21) or under stable medical treatment (mesalamine N = 24, azathioprine N = 14, and corticosteroids N = 23) that was either single medication (N = 22) or combined medication (N = 17). Plasma oxidised, low-density lipoprotein (oxLDL), total serum oxidisability, and serum uric acid were evaluated at baseline and follow-up. OxLDL/LDL and oxLDL/High-Density Lipoprotein (HDL) ratios were calculated. The plasma-free AA profile was determined by applying a gas chromatography/mass spectrometry analysis. oxLDL (p = 0.031), oxLDL/HDL (p = 0.020), and oxLDL/LDL (p = 0.005) decreased significantly in the intervention group. The mean change differed significantly in CD between groups for oxLDL/LDL (p = 0.01), and, in the total sample, both oxLDL/LDL (p = 0.015) and oxLDL/HDL (p = 0.044) differed significantly. Several changes were reported in AA levels. PL ameliorated a decrease in plasma-free AAs seen in patients with UC taking placebo. In conclusion, this intervention resulted in favourable changes in oxidative stress biomarkers in active IBD.

Background/aims The aim of this study was to investigate the influence of a synbiotic preparation (a mixture of six probiotics and a prebiotic) on aberrant crypt foci (ACF) formation, dysplasia, inflammation, and colitis-like lesions in experimental colon cancer in rats. Materials and methods Sixty male rats were categorized into three groups of 20 animals each. Group A was administered 1,2-dimethylydrazine, 15 mg/kg body weight (BW), once a week for 2 weeks. Group B was administered 1,2-dimethylydrazine at the same dose plus synbiotic, started after the second dose of carcinogen and lasted for 5 weeks. Group C was administered synbiotic plus carcinogen from the beginning of the experiment and lasted for 7 weeks. Animals were killed at the end of week 7. Results At the end of the experiment, the animals that received carcinogen plus the synbiotic had 100%, whereas the animals that received only carcinogen has 70% survival. Animals of groups B and C had significantly lower percentage of inflammation, colitis-like lesions, and ACF dysplasia than animals of group A, whereas those of group C had the least pathological lesions. Conclusion Synbiotics seem to protect against the appearance of preneoplastic colon lesions in rats. The results of this experimental study suggest that treatment with a synbiotic preparation exerts significant antimutagenic properties against the development of preneoplastic lesions in rats.

Colonoscopy represents a very important diagnostic modality for screening for colorectal cancer, because it has the ability to both detect and effectively remove pro-malignant and malignant lesions. It is recommended by almost all international and national gastroenterology and cancer societies, as an initial screening modality or, following a positive fecal occult blood test, to be performed every 10 years in individuals of average risk starting from the age of 50. However, a significant problem is the so-called post-screening (interval) polyps and cancers found some years after the index colonoscopy. In order to reduce the rate of interval cancers it is extremely necessary to optimize the quality and effectiveness of colonoscopy. Bowel preparation is of paramount importance for both accurate diagnosis and subsequent treatment of lesions found on colonoscopy. The quality of bowel preparation could be significantly improved by splitting the dose regimens, a strategy that has been shown to be superior to single-dose regimen. A good endoscopic technique and optimal withdrawal time offering adequate time for inspection, would further optimize the rate of cecal intubation and the number of lesions detected. During the last years, sophisticated devices have been introduced that would further facilitate cecal intubation. The percentage of total colonoscopies is now super-passing the level of 95 % allowing the adenoma detection rate to be greater than the suggestive level of 25 % in men and 15 % in women. This review aims to provide the reader with the current knowledge concerning indications, usefulness, limitations and future perspectives of this probably most important screening technique for colorectal cancer available today.

Patient: Male, 70 • Male, 84 Final Diagnosis: Appendiceal mucocele and pseudomyxoma peritonei Symptoms: — Medication: — Clinical Procedure: — Specialty: Surgery Objective: Rare disease Background: Mucocele of the appendix is an uncommon cystic lesion characterized by distension of the appendiceal lumen with mucus. Most commonly, it is the result of epithelial proliferation, but it can also be caused by inflammation or obstruction of the appendix. When an underlying mucinous cystadenocarcinoma exists, spontaneous or iatrogenic rupture of the mucocele can lead to mucinous intraperitoneal ascites, a syndrome known as pseudomyxoma peritonei. Case Report: We report 2 cases that represent the clinical extremities of this heterogeneous disease; an asymptomatic mucocele of the appendix in a 70-year-old female and a case of pseudomyxoma peritonei in an 84-year-old male. Subsequently, we review the current literature focusing to the optimal management of both conditions. Conclusions: Mucocele of the appendix is a rare disease, usually diagnosed on histopathologic examination of appendectomized specimens. Due to the existing potential for malignant transformation and pseudomyxoma peritonei caused by rupture of the mucocele, extensive preoperative evaluation and thorough intraoperative gastrointestinal and peritoneal examination is required.

The aim of this study was the evaluation of the diagnostic accuracy of a specific high-definition white light endoscopy (HD-WLE) system for the optical recognition of intestinal metaplasia (IM) and the assessment of its correlation with histologic and clinical data.A total of 234 patients undergoing upper gastrointestinal endoscopy in an outpatient endoscopy suite for various indications were prospectively enrolled in this cross-sectional study. Gastric IM was diagnosed on the basis of three mucosal patterns identified using HD-WLE in a per-patient analysis. Histological evaluation was used as the gold standard, and special staining was conducted for subtyping of IM. Main outcome measurements were sensitivity, specificity, and likelihood ratio of HD-WLE and secondary associations with histologic and clinical data.IM was found in 63/234 (27%) patients and low-grade dysplasia in 6/63 patients (9.5%). Sensitivity, specificity, accuracy, and likelihood ratio of all mucosal patterns were 74.6, 94, 88% and 13, respectively. All clinically significant type III IM and dysplasia lesions were endoscopically detected. All nonvisible lesions were of types I and II with mild grade and no dysplasia. Ten patients were considered false positives and the lesions were associated with severe inflammation and antralization.The specific HD-WLE system showed satisfactory accuracy and high specificity during real-time, routine endoscopy practice. Specific mucosal patterns were correlated with level and grade of lesions. The sensitivity of the system is even higher when only clinically significant IM lesions are considered.

Irritable bowel syndrome (IBS) is a very common functional gastrointestinal disorder characterized by abdominal pain or discomfort and altered bowel habits. The disease affects a large part of the world population. The clinical course is mostly characterized by a cyclic recurrence of symptoms. Therefore, IBS patients should receive, as an initial therapeutic approach, a short course of treatment, and long-term treatment should be reserved for those patients with recurrent symptoms. The available clinical trials show that significant improvement of the symptoms over placebo could be achieved with various drugs, although this improvement is frequently time dependent and with high relapse rates after the cessation of the treatment. In a proportion of patients, clinically obvious relapse could appear long after stopping the treatment. Some of the available pharmacologic agents, including otilonium bromide (OB), are able to significantly prolong the time to the appearance of relapse, compared with placebo. As a consequence, some authors suggest that a cyclic treatment could be of benefit. Antispasmodic drugs have been used for many years in an effort to control the symptoms of IBS. OB is a poorly absorbed spasmolytic drug, exerting significantly greater control of the symptoms of IBS compared with placebo. Recent data suggest that the drug could effectively be used for the long-term management of patients with IBS. The aim of this review is to provide the reader with an evidence-based overview of the efficacy and tolerability of OB in the long-term management of IBS patients, based on the results of the clinical trials published so far.

Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohn's and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Total parenteral nutrition (TPN) represents a therapeutic modality that could save the life of a patient with inflammatory bowel disease (IBD) facing severe nutritional problems, by restoring the patient's impaired nutritional status. TPN does not compete with enteral nutrition (EN), the latter being the first choice for all patients having anatomically intact and functionally normal digestive tract. TPN allows bowel rest while supplying adequate calorific intake and essential nutrients, and removes antigenic mucosal stimuli. The value of TPN in malnourished patients with intestinal failure due to CD is beyond doubt. However, it is difficult to suggest TPN as a sole treatment for active CD. An increased rate of remission could not be expected by applying TPN. The utility of TPN is restricted to certain cases involving efforts to close enterocutaneous or other complicated fistulas in patients with fistulizing CD, the treatment of short bowel syndrome following extensive resections for CD, or when EN is impractical for other reasons. There are no advantages of TPN therapy over EN therapy regarding fistula healing. TPN has no influence on the surgical intervention rate and little benefit by bypassing the intestinal passage could be expected. Also TPN shows no advantage if the disease is chronically active. However, an optimal supply of nutrients improves bowel motility, intestinal permeability and nutritional status, and reduces inflammatory reactions. TPN might be associated with an increased risk of adverse events, although TPN undertaken by experienced teams does not cause more complications than does EN.

Orally administered iron can induce colonic inflammation in healthy animals and aggravate experimental colitis.To investigate the influence of the biologic agents infliximab and adalimumab on the severity of TNBS colitis following orally supplemented iron.204 Wistar rats were allocated into 14 groups. Colitis was induced by TNBS. Iron was administered via a mouth catheter at a dose of 0.027, 0.3, and 3%/kg diet per day, respectively. Infliximab was subcutaneously administered on the 2In normal rats both agents significantly worsen the degree of inflammation induced by moderate or high iron supplementation despite the disappearance of t-TNF-α, and reduction of t-MDA. In the groups of TNBS colitis and moderate or high iron administration, both agents again significantly worsen the degree of inflammation despite the significant reduction in the t-TNF-α and t-MDA.Adalimumab and infliximab do not ameliorate the inflammation in TNBS-induced colitis aggravated by orally administered iron. These findings might be clinically relevant in patients with active IBD under concurrent treatment with biologic agents and per oral iron.

Mastic (Pistacia lentiscus) of the Anacardiaceae family has exhibited anti-inflammatory and antioxidant properties in patients with Crohn's disease. This study was based on the hypothesis that mastic inhibits intestinal damage in inflammatory bowel disease, regulating inflammation and oxidative stress in intestinal epithelium. Four different dosages of P. lentiscus powder in the form of powder were administered orally to trinitrobenzene sulfonic acid-induced colitic rats. Eighty-four male Wistar rats were randomly assigned to seven groups: A, control; B, colitic; C-F, colitic rats daily supplemented with P. lentiscus powder at (C) 50 mg/kg, (D) 100 mg/kg, (E) 200 mg/kg, and (F) 300 mg/kg of body weight; and G, colitic rats treated daily with cortisone (25 μg/kg of body weight). Colonic damage was assessed microscopically. The cytokines tumor necrosis factor-α, intercellular adhesion molecule-1 (ICAM-1), interleukin (IL)-6, IL-8, and IL-10 and malonaldehyde were measured in colonic specimens. Results were expressed as mean ± SE values. Histological amelioration of colitis (P≤.001) and significant differences in colonic indices occurred after 3 days of treatment. Daily administration of 100 mg of P. lentiscus powder/kg of body weight decreased all inflammatory cytokines (P≤.05), whereas 50 mg of P. lentiscus powder/kg of body weight and cortisone treatment reduced only ICAM-1 (P≤.05 and P≤.01, respectively). Malonaldehyde was significantly suppressed in all treated groups (P≤.01). IL-10 remained unchanged. Cytokines and malonaldehyde remained unaltered after 6 days of treatment. Thus P. lentiscus powder could possibly have a therapeutic role in Crohn's disease, regulating oxidant/antioxidant balance and modulating inflammation.

A case of gastric outlet obstruction accompanied by diffuse gastritis and gastric ulcer due to cytomegalovirus infection is presented. The patient, a woman aged 67 years with a long history of rheumatoid arthritis under immunosuppressive treatment (methotrexate), was admitted to our department complaining mostly of abdominal pain located in the epigastrium and the right abdomen. Upper gastrointestinal endoscopy revealed the presence of gastritis accompanied by ulcer in the prepyloric area and gastric outlet obstruction due to cytomegalovirus infection which was confirmed histologically. The patient responded well – although after many weeks – to specific treatment with antiviral treatment (ganciclovir). It is concluded that gastric outlet obstruction caused by cytomegalovirus infection can be observed in immunocompromised patients. The clinician must search for possible cytomegalovirus infection in all immunocompromised patients presenting with a clinical picture of gastric outlet obstruction by obtaining enough biopsies and by asking the histopathologist to specifically stain the specimen for the presence of cytomegalovirus, especially if infection by Helicobacter pylori is not present.

Objectives Immunoproliferative small intestinal disease (IPSID) represents a spectrum of clinicopathological entities including alpha-chain disease and other types of lymphoplasmacytic proliferations of the lamina propria of the small intestine, presenting with severe malabsorption. IPSID has been described mainly in the Mediterranean, Middle East, and African countries. It occurs rarely in western countries. We present here our experience from Greece describing some interesting findings in cases diagnosed during the years 1970-2002. Methods Current immunological and immunohistochemical methods for the detection of alpha heavy chains and the presence of clonality have been used to study 13 cases of IPSID diagnosed in Greece, two of whom were Albanian residents. Results The patients were categorized in three subgroups of IPSID: alpha-chain disease (n=8), non-alpha chain disease with other monoclonal immunoglobulins (n=3), and polyclonal 'non-malignant' IPSID (n=2). In several patients the disease had unusual features, and this in some cases delayed the diagnosis. In suspected cases it is thus of the utmost importance to proceed to an exploratory laparatomy. Patients with stage C disease had a short survival, whereas two patients with stage A alpha-chain disease responded to treatment with cyclophosphamide, vincristine and prednisolone, and cyclophosphamide, doxorubicine, vincristine and prednisolone, respectively, have a disease-free long survival of 35 and 12 years, and appear to be cured.

Enteral nutrition (EN) is considered to be of great importance in patients with inflammatory bowel disease (IBD) and nutritional problems. This comprehensive review is aiming to provide the reader with an update on the role of EN in IBD patients. EN can reduce Crohn’s disease (CD) activity and maintain remission in both adults and children. Nutritional support using liquid formulas should be considered for CD patients and in serious cases of ulcerative colitis (UC), especially for those who may require prolonged cycles of corticosteroids. Given that the ultimate goal in the treatment of CD is mucosal healing, this advantage of EN over corticosteroid treatment is valuable in therapeutic decision-making. EN is indicated in active CD, in cases of steroid intolerance, in patient’s refusal of steroids, in combination with steroids in undernourished individuals, and in patients with an inflammatory stenosis of the small intestine. No differences between the efficiency of elemental diets and nonelemental formulas have been noticed. EN must be the first choice compared to TPN. EN has a restricted value in the treatment of patients with large bowel CD. In conclusion, it seems important not to underestimate the role of nutrition as supportive care in patients with IBD.

Ulcerative colitis is a chronic disorder of unknown etiology. Conservative treatment remains empirical, even today. The aim of this study was to test the efficacy of a novel non-steroidal anti-inflammatory agent [5-(2-hydroxy-ethylamino)-1-cyclohexyl-2-pentanone] (compound A), with basic character and antioxidant properties on an experimental model of ulcerative colitis in rats. The effect of this compound was compared with that of methylprednisolone on the histological abnormalities and serum levels of tumor necrosis factor-alpha (TNF-alpha) in experimental colitis produced by 2,4,6-trinitrobenzenesulfonic acid (TNB). A total number of 24 rats were randomly assigned to one of four groups of six rats each. Group 1: colitis without treatment (disease control), group 2: normal animals (control), group 3: induction of experimental colitis treated with methylprednisolone (5.3 x 10(-3) mmol/kg i.v. every day for 7 days) and group 4: induction of experimental colitis plus administration of compound A (0.6 mmol/kg i.v. every day for 7 days). The administration of compound A resulted in a statistically significant reduction of the extent of tissue damage and of certain histological features (edema, inflammatory infiltration) (P0.05). Compound A also resulted in a statistically significant reduction of the levels of serum TNF-alpha, compared to those of controls (P0.005). The beneficial effect of this compound was probably due to the combination, on a single molecule, of anti-inflammatory and antioxidant properties as well as to its basic character. The reduction of the serum TNF-alpha levels could be one of the possible mechanism(s) of action of the compound. Further studies are necessary to establish the direct mechanism of action(s) of the drug and to evaluate its long-term efficacy and safety.

Background. Experimental data suggest that oral iron (I.) supplementation can worsen colitis in animals.Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M.) and Prednisolone (P.) on the severity of TNBS colitis following orally administered I.Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α(t-TNF-α) and tissue malondialdehyde (t-MDA) were estimated in all animal groups.Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet) resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-αlevels (17.67±4.92versus14.58±5.71,P=0.102), although it significantly reduced the t-MDA levels (5.79±1.55versus3.67±1.39,P=0.000). Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet) did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α(16.57 ± 5.61versus14.65±3.88,P=0.296). However, M. significantly reduced the t-MDA levels (5.99±1.37versus4.04±1.41,P=0.000). Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-αlevels (17.67±4.92versus12.64±3.97,P=0.003) and the t-MDA levels (5.79±1.54versus3.47±1.21,P=0.001). Administration of P on TNBS colitis after high I. supplementation resulted in a significant improvement of the overall histological score and three individual histological parameters and significantly reduced the levels of t-TNF-α(16.6±5.6versus11.85±1.3,P=0.001).Conclusion. I. can induce colonic inflammation and aggravate TNBS colitis. M. and P. can significantly improve the inflammatory process in the colonic mucosa in TNBS colitis aggravated by orally administered I. P. has a stable anti-TNF-αeffect. These findings suggest that the harmful.

In this study, the clinical characteristics and course of all patients with ulcerative colitis in whom diagnosis of the disease was made at or after the age of 60 (older group), were analyzed and compared with those of patients with ulcerative colitis in whom diagnosis of the disease was made before the age of 60 (younger group). Methods: The older group consisted of 51 patients (28 men and 23 women; aged 64 ± 3.1 years) and the younger group consisted of 362 patients (192 men and 170 women; aged 38.4 ± 14.9 years). The mean follow-up times in the two groups were 9.3 and 12.6 years, respectively. Results: No significant differences between the two groups were found as far as the extent of the disease, the severity of the initial episode, and the outcome of the first episode of ulcerative colitis were concerned. However, significantly fewer elderly patients were operated on for their disease compared with younger patients (6.25% vs 22.3%; P = 0.0268). Although some differences in the course of the disease between elderly and younger patients were observed, such as the number of exacerbations and recurrences and the number of patients who developed colorectal cancer, these differences did not reach statistical significance. Conclusion: It is concluded that ulcerative colitis in elderly Greek patients runs a rather similar course to that in younger patients. However, some unique characteristics observed in the elderly patients (lower rate of colectomy, absence of patients with colorectal cancer, and increased death rate) could be attributed either to truly different disease behavior in the elderly people or to factors directly related to their advanced age.

The aim of this prospective study was to elucidate the clinical features and natural history of Crohn’s disease in Greece. One hundred and fifty-five Greek patients with definite diagnosis of Crohn’s disease were followed-up for a mean period of 9.7 years and evaluated for clinical patterns and course of illness. The male/female ratio was 1.58:1. The peak incidence of the disease was observed between 20 and 30 years of age. The majority of patients were urban dwellers and of higher socio-economic level compared to the general population of Greece. In almost 50% of the patients symptoms of the disease started below the age of 30, although in almost one in every 5 cases, symptoms appeared after the age of 50. Familial clustering of inflammatory bowel disease was observed in 1.3%. The pattern of anatomic involvement was: ileocolic 33.3%, colon 33.3% and small bowel 33.3%. The kind of predominant symptoms at the time of diagnosis was related to the anatomic location of the disease. At least one extraintestinal manifestation appeared in 42% of patients. Perianal disease was noticed in 21.3% with fistulae and abscesses being the most common manifestation. Fifty-one percent of patients were operated upon at least once during the follow-up period because of acute abdomen, bad response to conservative treatment and fistulae and abscesses. Emergency operation was required in 17.3% of the patients. Evolution to cancer was observed in 3 patients (2%). During the follow-up period of 9.7 ± 6.5 years, 18 patients (11.6%) died. A considerable mortality was noticed in the surgically treated group of patients, while in the nonoperated group the disease was running with milder symptoms. It is concluded that some of the clinicoepidemiological characteristics of patients with Crohn’s disease in Greece are in accordance with those reported from western as well as the neighboring Mediterranean countries. However, other parameters such as the higher incidence of the disease in males, the low incidence of familial clustering, and the low incidence of perianal disease, underline the importance of environmental, genetic and other factors on the evolution and behavior of the disease in different parts of the world.

The role of psychological distress and personality as predisposing factors for the development of inflammatory bowel disease (IBD) remains controversial. Attempts to investigate the role of psychological factors in IBD exhibited rather conflicting results. Among the studies concerning the effects of stress or depression on the course of IBD, the majority suggest that stress worsened IBD, the rest giving either negative or inconclusive results. However, application of strategies, including avoidance of coping and training patients in problem solving or emotion-oriented, could influence the course of IBD. Large controlled clinical trials are needed in order to clarify the impact of psychological interventions on the quality of life and the course of disease.

Dear Sir, Many studies have shown that patients with inflammatory bowel disease (IBD) exhibit a lower prevalence of Helicobacter pylori infection ( Hp ) compared with the normal population.1 During the 21st century, a decrease in the incidence of both gastric cancer and peptic ulcer was noticed, concurrently accompanied by an increase in the incidence of IBD. These changes in the epidemiology of IBD and gastric disorders have been attributed –among others– to the decline in the rate of Hp infection in the general population.2 So far, there are no data concerning over-time …

Am J Gastroenterol

Pyoderma gangrenosum is an extraintestinal manifestation of inflammatory bowel disease requiring meticulous medical and/or surgical treatment. We describe a 46-year-old patient who developed harsh pyoderma gangrenosum during a severe flare-up of the underlying Crohn disease of the terminal ileum. The patient responded favorably to treatment with infliximab--the chimeric antibody against tumor necrosis factor-alpha. The drug was administered intravenously at a dose 5 mg/kg/BW at baseline and weeks 2 and 6. Abdominal signs and symptoms as well as the skin lesions improved markedly before the second infusion. The patient is presently on infliximab maintenance regimen at a dose of 5 mg/kg/BW being administered as a 3 dose loading regimen at 0, 2 and 6 weeks with a treatment-free interval of 10 weeks until the next loading dose. The skin lesions remained in remission. Infliximab is a promising therapeutic modality for patients with Crohn disease and pyoderma gangrenosum.

Many patients with inflammatory bowel disease use alteranative therapy, mainly probiotics and synbiotics, to manage this intestinal condition. Despite widespread use of these natural therapies by patients, health care providers may be unfamiliar with probiotics as a treatment modality. This review describes the rationale for use of probiotics in patients with active or inactive inflammatory bowel disease, their mechanism(s) of action, and recent controlled clinical studies in which efficacy of probiotics, prebiotics and synbiotics in patients with active or inactive inflammatory bowel disease has been explored. Certain probiotics, particularly E. coli Nissle 1917 and a multi-agent mixture VSL#3, may be benefit patients with UC or pouchitis, while LactoBacillus rhamnosus GG appears less useful. In general, probiotics show potential for therapeutic application mainly in pouchitis and to a lesser degree in UC, while their effects in maintenance therapy for CD have been much less promising. While there is suggestion of benefit when patients with ulcerative colitis use bacterial therapies small sample sizes and methodological weeknesses in study designs necessitate that additional studies must be conducted before probiotics and or synbiotics can be routinely recommended in clinical practice.

Acute idiopathic pancreatitis complicating active Crohn's disease: favorable response to infliximab treatment

Introduction Crohn's disease is a disease involving the whole gastrointestinal tract from the mouth to the anus. Oral lesions are considered to be an important extraintestinal manifestation. Granulomatous cheilitis has been recognized as an early manifestation of Crohn's disease. It may follow, coincide with or precede the onset of Crohn's disease. The aim of this presentation is to describe a rare case of a patient with Crohn's disease in whom significant swelling of the lower lip not only preceded the diagnosis of Crohn's disease for two years, but it manifested as an early clinical index of the recurrence of the intestinal disease as well. Case presentation A man aged 25 was admitted in our department on August 1999 with chronic diarrhea and loss of weight. His bowel symptoms started in 1998 at the age of 24. However, two years previously (June 1996) he noticed a swelling of the lower lip, which contrasted significantly with the previously normal appearance of his mouth. A lip biopsy performed at that time was compatible with granulomatous cheilitis. Crohn's disease involving the terminal ileum and large bowel was diagnosed in 1998 and confirmed on the basis of colonoscopy, enteroclysis and histology findings of the small and large bowel. Conservative treatment resulted in clinical and laboratory improvement of the bowel symptoms and lip swelling. During the following years the disease was active with exacerbations and remissions of mild to moderate severity. The swelling of the lower lip occurred in parallel with the exacerbations of the bowel disease, returning to normal during periods of remission. Conclusion Significant swelling of the lower lip due to granulomatous cheilitis could be the first manifestation of Crohn's disease, preceding intestinal symptoms. Exacerbation of the lip lesion could be an early clinical sign of a relapse of the underlying intestinal disease.

Int J Psychiatry Med

Although psychiatric disturbances and personality features are possibly involved in inflammatory bowel disease, little attention has been given to the potential role of defense mechanisms in the formation, course, or prognosis of the disease. The purpose of the present study was to determine whether certain defense styles and ego mechanisms of defense are associated with inflammatory bowel disease, including both ulcerative colitis and Crohn’s disease. Seventy-six consecutive unselected outpatients participated in the study. The sample consisted of 39 patients with Crohn’s disease, 33 with ulcerative colitis, and 4 with an intermediate form of inflammatory bowel disease. The Symptom Distress Checklist (SCL-90-R), Defense Style Questionnaire (DSQ), and Hostility and Direction of Hostility Questionnaire (HDHQ) were used. Crohn’s disease patients presented a more immature defensive profile than ulcerative colitis patients, using a “maladaptive action” style, as well as “consumption” and “pseudo-altruism” defense mechanisms more often. These differences were statistically significant and they were independent of age, sex, educational level, disease extension, and pharmacologic treatment. A significant positive correlation was also found between disease activity and defensive profiles in both ulcerative colitis and Crohn’s disease patients. In contrast, there was no statistically significant difference between ulcerative colitis and Crohn’s disease patients in terms of psychiatric symptoms. Crohn’s disease patients presented a different and more immature defensive profile than patients with ulcerative colitis. In addition, the more psychologically mature inflammatory bowel disease patients had lower rates of relapses and surgical operations, providing evidence that these aspects of personality are likely to influence the patients’ adaptation to the disease.

Dear Sir, It has been suggested that patients with Crohn's Disease (CD) exhibit a higher prevalence of psychiatric disorders compared to the normal population.1 Psychiatric disturbances and stress could be psychological factors participating in the exacerbation of inflammatory bowel disease (IBD).2 Patients with IBD are thought to be at a rather increased risk for suicide.3 So far, psychosis appearing as a cardinal clinical manifestation preceding diagnosis of CD has not been described. We report a patient with extensive small bowel CD, who was admitted to the hospital because of psychiatric …

Dear Sir, It is well established that haematological malignancies could develop during the clinical course of Inflammatory Bowel Disease (IBD).1,2 Epidemiological data suggest that this risk might be increased3 and be related with the use of either immunosuppressants or biologic agents.4 So far, these malignancies have been observed after the establishment of diagnosis of IBD. We describe the case of a patient in whom the diagnosis of Crohn's disease (CD) was made 6 years after the diagnosis of chronic lymphoid leukaemia. To the best of our knowledge, the appearance of CD years after the establishment of chronic lymphoid leukaemia has not yet been described. A 71-year old man was admitted to …

The clinical course and prognosis of ulcerative colitis was studied in a group of 413 Greek patients. The study lasted for 16 years and follow-up was achieved in 95% of the patients. Both sexes were almost equally affected, mainly between the ages of 40-49. Most of the patients lived in cities and had high educational levels. Familial clustering for inflammatory bowel disease was found in 2.7% of the patients. In most of them the disease was confined to the rectosigmoid area or left bowel and was of mild to moderate severity. The disease course included exacerbations--mainly of mild to moderate severity--and remissions. Mortality was absent during first attack, and it was generally low at the completion of the study. Excluding deaths caused by colorectal cancer, most of the deaths were unrelated to the ulcerative colitis itself. Unusual combinations of ulcerative colitis with other diseases, including diseases of autoimmune origin, were noted. There were no differences between men and women in the various clinicoepidemiologic parameters or in the course of the disease. Surgery was performed in 16.7% of patients, whereas surgery at first attack was required in 0.5%. In comparison with the nonoperated group, patients who were operated on were significantly younger at the time of onset of symptoms and had significantly more extensive disease. Factors prognostic of severe attacks and colectomy were extensive disease, young age at onset, and severe recurrences. Evolution to cancer was observed in 1.45%, whereas extraintestinal cancers also appeared in 1.5%. At the completion of the follow-up period, 5.8% of the patients were dead, 16% had only one attack, 2.7% experienced continuous symptoms, whereas in 58.8% of them, the disease course included exacerbations and remissions. On the basis of the outcome of severe attacks and the more favorable short-term prognosis, it could be argued that ulcerative colitis in Greece runs a milder course compared with that of other developed countries in Western Europe and North America.

We describe the clinicoepidemiologic features, natural history, and therapeutic manipulations in three Greek patients with A-beta-lipoproteinemia (two brothers aged 15 and 29 years, respectively, and one sister aged 30 years). Diarrhea started in infancy in the two brothers and from the age of 13 in the sister. During the second decade of life, central nervous system symptoms became prominent, with fatigue and disturbance in gait and balance. Night blindness developed at a later phase of the disease in the brothers, whereas cavus developed in both legs in the sister. Apolipoprotein B was absent in all patients, and each had more than 50% of acanthocytes present on peripheral smear. The diagnosis of A-beta-lipoproteinemia was established on the basis of small bowel histology and serum lipid estimations. Family studies revealed normal lipid profiles in all healthy members. The human leukocyte antigen (HLA) pattern in the two most severely affected patients was identical. The only detectable difference between the severely ill patients and other members of the family, however, was homozygosity for the HLA B18 antigen, whereas the third patient had no alleles for the HLA B18 antigen. Treatment consisted of a low-fat diet and high doses of vitamins A and E. A modified diet substituting medium-chain triglycerides for dietary fat was also given, with significant improvement in the nutritional status of patients but not in symptoms related to advanced disease, such as retinal and cardiac manifestations. We conclude that the course of the disease in untreated patients is characterized by continuous symptoms. Some of the symptoms, however, especially those related to malabsorption, as well as some anthropometric parameters can be improved by the application of a modified diet including medium-chain triglycerides. We suggest the routine measurement of plasma lipids and apoproteins not only in children with failure to thrive, with unexplained malabsorption, or with neurologic symptoms, but also in adults with chronic diarrhea accompanied by neurologic symptoms or clinical and laboratory signs of malabsorption.

Dear Sir, Psoriasis is a chronic, relapsing, autoimmune disease that represents a relatively rare extraintestinal manifestation especially in patients with inflammatory bowel disease.1,2 In Germany the relative risk of developing psoriasis in a patient with Crohn's disease (CD) has been estimated to be 2.1.3 The underlying relationship between these two disorders is largely unknown although it seems to comprise genetic data (involvement of shared predisposing loci or genes), immunological data (inflammation mechanisms such as activation pathway of Th17 lymphocytes), and environmental co-factors (smoking, possibly certain …

The low prevalence of helicobacter infection in patients with inflammatory bowel disease could be attributed to previous antibiotic treatment

Re: Fefferman et al. —“recurrence” of chronic pancreatitis appearing on a patient with underlying Crohn's disease

During the last decade a large number of biological agents against tumor necrosis factor-α (TNF-α), as well as many biochemical substances and molecules specifically for the medical treatment of patients with inflammatory bowel disease (IBD), have been developed. This enormous progress was a consequence of the significant advances in biotechnology along with the increased knowledge of the underlying pathophysiological mechanisms involved in the pathogenesis of IBD. However, conventional therapies remain the cornerstone of treatment for most patients. During recent years conventional and biologic IBD therapies have been optimized. Newer mesalazine formulations with a reduced pill size and only one dose per day demonstrate similar efficacy to older formulations. New corticosteroids retain the efficacy of older corticosteroids while exhibiting a higher safety profile. The role of antibiotics and probiotics has been further clarified. Significant progress in understanding thiopurine metabolism has improved the effective dose along with adjunctive therapies. Quite a large number of substances and therapies, including biologic agents other than TNF-α inhibitors, unfractionated or low-molecular-weight heparin, omega-3 polyunsaturated fatty acids, microbes and microbial products, leukocytapheresis, and other substances under investigation, could offer important benefits to our patients. In this paper we review the established and emerging therapeutic strategies in patients with Crohn’s disease and ulcerative colitis.