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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.

Background: Pancreatic cancer represents the most lethal malignancy among all digestive cancers. Despite the therapeutic advances achieved during recent years, the prognosis of this neoplasm remains disappointing. An enormous amount of experimental (mainly) and clinical research has recently emerged referring to the effectiveness of various plants administered either alone or in combination with chemotherapeutic agents. Apart from Asian countries, the use of these plants and herbals in the treatment of digestive cancer is also increasing in a number of Western countries as well. The aim of this study is to review the available literature regarding the efficacy of plants and herbals in pancreatic cancer. Methods: The authors have reviewed all the experimental and clinical studies published in Medline and Embase, up to June 2021. Results: More than 100 plants and herbals were thoroughly investigated. Favorable effects concerning the inhibition of cancer cell lines in the experimental studies and a favorable clinical outcome after combining various plants with established chemotherapeutic agents were observed. These herbals and plants exerted their activity against pancreatic cancer via a number of mechanisms. The number and severity of side-effects are generally of a mild degree. Conclusion: A quite high number of clinical and experimental studies confirmed the beneficial effect of many plants and herbals in pancreatic cancer. More large, double-blind clinical studies assessing these natural products, either alone or in combination with chemotherapeutic agents should be conducted.

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.

Background COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to the frequent administration of immune-modifying treatments. Methods We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via the unbiased reporting of all cases that were registered during the first and second waves of the pandemic. Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnosis of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies were analysed against adverse outcomes (hospitalization, ICU admission, and death). Results We identified 80 patients with IBD who were diagnosed with COVID-19 during the study period (male:65%; median age=44 [IQR=26] years; CD:62.5%). Adverse outcomes were reported in 16 patients (20%), including 3 ICU admissions (3.75%) and 2 deaths (2.5%). Negative prognostic factors for adverse outcomes included age, Body Mass Index, and hypertension, as well as dyspnoea, fatigue and abdominal pain at presentation. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable course COVID-19. Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous medications. Conclusion Patients with IBD who developed COVID-19 had a benign course with adverse outcomes being scarce. Treatment with biologics had a beneficial effect, supporting the continuation of therapy during the pandemic.

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.

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.

Background Endoscopic submucosal dissection (ESD) requires special skills and a long procedure time for a quality-controlled procedure. A universal training system remains to be established. Hands-on courses in animal models before advancing to the human colon appear to be essential, especially in Europe. The learning curve is a prerequisite in ESD, in order to improve technical outcomes and decrease the rate of procedural adverse events. Methods In the experimental research center of ELPEN Pharmaceuticals, 18 European endoscopists, inexperienced at ESD, performed gastric ESDs in porcine models. The course lasted two days and was conducted under the supervision of experts. Results A total of 72 of 76 ESDs were completed en bloc (94.7%). The procedural time and cutting speed differed significantly between the first and second day: 48±4.4 vs. 43±4.8 min (P=0.0045), and 1.38±0.20 vs. 1.63±0.23 cm2/min (P=0.0033), respectively. The complications were not significantly different between the two groups: five (13.88%) vs. four (11%) episodes of bleeding (P>0.05). The perforation rate was similar, at two episodes per day (5.55%). We documented an acceptable rate of en bloc resections and complications. Conclusion ESD demands a new level of endoscopic skills in Europe. A formal sequential training program, using porcine models, may benefit countries with a low volume of cases. Keywords Endoscopic submucosal dissection, animal models, ESD training, hands-on course, procedural time Ann Gastroenterol 2017; 30 (4): 446-449

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.

The use of herbal therapy for inflammatory bowel disease is increasing worldwide. The aim of this study was to review the available literature on the efficacy of herbal therapy in experimental colitis. All relevant studies published in Medline and Embase up to June 2015 have been reviewed. The results of bowel histology and serum parameters have been recorded. A satisfactory number of published experimental studies, and a quite large one of both herbal and plant products tested in different studies have been reported. The results showed that in the majority of the studies, herbal therapy reduced the inflammatory activity of experimental colitis and diminished the levels of many inflammatory indices, including serum cytokines and indices of oxidative stress. The most promising plant and herbal products were tormentil extracts, wormwoodherb, Aloe vera, germinated barley foodstuff, curcumin, Boswellia serrata, Panax notoginseng, Ixeris dentata, green tea, Cordia dichotoma, Plantago lanceolata, Iridoidglycosides, and mastic gum. Herbal therapies exert their therapeutic benefit via various mechanisms, including immune regulation, anti-oxidant activity, inhibition of leukotriene B4 and nuclear factor-κB, and antiplatelet activity. Large, double-blind clinical studies assessing these natural substances should be urgently conducted.

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.

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.

Chronic gastrointestinal disorders are a source of substantial morbidity, mortality, and cost. They are common in general practice, and the primary care physician (PCP) has a central role in the early detection and management of these problems. The need to make cost-effective diagnostic and treatment decisions, avoid unnecessary investigation and referral, provide long-term effective control of symptoms, and minimize the risk of complications constitute the main challenges that PCPs face. The literature review shows that, although best practice standards are available, a considerable number of PCPs do not routinely follow them. Low rates of colorectal cancer screening, suboptimal testing and treatment of Helicobacter pylori infection, inappropriate use of proton pump inhibitors, and the fact that most PCPs are still approaching the irritable bowel disease as a diagnosis of exclusion represent the main gaps between evidence-based guidelines and clinical practice. This manuscript points out that updating of knowledge and skills of PCPs via continuing medical education is the only way for better adherence with standards and improving quality of care for patients with gastrointestinal diseases.

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

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.

Patients with long-standing ulcerative colitis and Crohn's disease have an increased risk of developing colorectal cancer and patients with small intestinal Crohn's disease are at increased risk of small bowel adenocarcinoma. Colorectal cancer appearing on the ground of inflammatory bowel disease is the result of a process which is believed to begin from no dysplasia progressing to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma, although colorectal cancer can arise without proceeding through each of these steps. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, although the anal transition zone should be monitored periodically, especially if chronic pouchitis is present with associated severe villous atrophy. Concerning the risk factors predisposing to colorectal cancer in the setting of ulcerative colitis or Crohn's disease, it seems that the risk increases with longer duration and greater anatomic extent of colitis, the degree of inflammation, and the presence of primary sclerosing cholangitis and family history of colorectal cancer. Concerning the mechanisms of carcinogenesis, it is now well established that the molecular alterations responsible for sporadic colorectal cancer, namely chromosomal instability, microsatellite instability and hypermethylation, also play a role in colitis-associated colon carcinogenesis. Chemoprevention strategies include the administration of agents such as aminosalicylates, ursodeoxycholic acid, and possibly folic acid and statins, the exact role of which remains to be further elucitated.

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.

AIM: To assess the effects of mastic administration on cytokine production of circulating mononuclear cells of patients with active Crohn's disease (CD). METHODS: The study was conducted in patients with established mildly to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Recruited to a 4 wk treatment with mastic caps (6 caps/d,0.37 g/cap) were 10 patients and 8 controls, all of who successfully completed the protocol. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), macrophage migration inhibitory factor (MIF) and intracellular antioxidant glutathione (GSH) were evaluated in peripheral blood mononuclear cells (PBMC) before and after treatment. RESULTS: Treating CD patients with mastic resulted in the reduction of TNF-α secretion (2.1 ± 0.9 ng/mL vs 0.5 ± 0.4 ng/mL, P = 0.028). MIF release was significantly increased (1.2 ± 0.4 ng/mL vs 2.5 ± 0.7 ng/mL, P = 0.026) meaning that random migration and chemotaxis of monocytes/macrophages was inhibited. No significant changes were observed in IL-6, MCP-1 and GSH concentrations. CONCLUSION: This study shows that mastic acts as an immunomodulator on PBMC, acting as a TNF-α inhibitor and a MIF stimulator. Although further double-blind, placebo-controlled studies in a large number of patients is required to clarify the role of this natural product, this finding provides strong evidence that mastic might be an important regulator of immunity in CD.

The Authors report a case of a woman aged 35, with concurrent appearance of Crohns disease and Inflammatory Fibroid Polyp of the terminal ileum.The combination of the two disorders was clinically manifested as an obstructive ileus. On the operative table, a 4-cm polypoid mass causing intussusception of the bowel was obvious. The resected specimen of the ileum showed profound distention, several ulcerations and fissures. The histological examination confirmed the diagnosis of Crohn's disease coexisting with an Inflammatory Fibroid Polyp. Immunostaining of the lesion for actin showed focal positivity. However, staining for desmin, CD31, S100-protein, PGM-1 CD34, CD117, and bc1-2, was negative.Coexistence of Inflammatory Fibroid Polyp with Crohn's disease causing obstructive ileus could be the first manifestation of the disease. The combination of the two disorders corroborates the reparative character of the lesion. Nevertheless, the exact etiopathogenetic relationship between the two entities remains obscure.

Int J Psychiatry Med

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 …

Oncology

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 …

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.

AIM To evaluate the effectiveness of mastic administration on the clinical course and plasma inflammatory mediators of patients with active Crohn's disease (CD). METHODS This pilot study was conducted in patients with established mild to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Activity Index (CDAI), Nutritional Risk Index (NRI), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values +/- SE and P < 0.05 was considered to indicate statistical significance. RESULTS Patients exhibited significant reduction of CDAI (222.9 +/- 18.7 vs 136.3 +/- 12.3, P = 0.05) as compared to pretreament values. Plasma IL-6 was significantly decreased (21.2 +/- 9.3 pg/mL vs 7.2 +/- 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 +/- 13.1 mg/mL vs 19.7 +/- 5.5, P = 0.028). TAP was significantly increased (0.15 +/- 0.09 vs 0.57 +/- 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION The results suggest that mastic significantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately active CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD.

To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats.Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1: colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7(th) d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) were also measured.Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-alpha in all groups of treated animals as compared with the untreated ones was found (0.47+/-0.44, 1.09+/-0.86, 0.43+/-0.31 vs 18.73+/-10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4.Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-alpha and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-alpha than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/kg BW.