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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.

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.

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

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.

The aim of the study was to determine the effect of β-glucan on the cytotoxicity and genotoxicity of polypectomized patient's fecal water (FW). Polypectomized volunteers (n = 69) were randomly assigned to consume bread with or without β-glucan, for 3 months. FW was collected at the beginning (t = 0), the 30th and 90th day and 2 wk after the intervention. Cytotoxicity and genotoxicity were estimated on Caco-2 cells, using trypan blue exclusion test and comet assay, respectively. Gastrointestinal symptoms were recorded and subjects kept a 3-day food diary at baseline and after completion. Trypan blue exclusion test revealed cell survival of approximately 87% after incubation with FW. The FW samples showed 49% genotoxicity at the baseline. Genotoxicity in the intervention group decreased during the trial reaching statistical significance on the 90th day compared to control. An increase was noticed 2 wk after the trial, but it still remained significantly lower compared to control. Group-specific analysis for β-glucan also revealed significant decrease in the genotoxicity on the 90th day compared to baseline. β-glucan ingestion in polypectomized patients significantly decreased the genotoxicity of their FW. Our findings suggest that β-glucan consumption could possibly provide protection against colon cancer development.

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.

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.

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.

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.

Increased number of CD5+ and CD20+ B-lymphocyte subpopulation in gastroenterology endoscopy staff

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

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.

To evaluate epidermal growth factor receptor (EGFR) gene status in pancreatic ductal adenocarcinoma correlating the results to protein expression and clinicopathological featuresUsing tissue microarray technology (TMArrayer 100), fifty (n = 50) paraffin-embedded tissue samples of histologically-confirmed primary tumors were cored twice at a diameter of 1 mm and re-embedded into the final recipient block. Immunohistochemistry was performed by the use of anti-EGFR monoclonal antibody (31G7). Also, a chromogenic in situ hybridization protocol was applied based on the use of EGFR gene and chromosome 7 centromeric probes, respectively.EGFR protein overexpression was observed in 29/50 (58%) cases and correlated to stage (p = 0.001) but not to grade (p = 0.206). EGFR gene analysis identified numerical alterations in 6/50 (12%), including 2 cases characterized by low-level gene amplification and 4 by absence of one allele. Gene status was associated to tumor grade (p = 0.023) and stage (p = 0.02). Chromosome 7 analysis detected aneuploidy in 14 (28%) cases.A subset of pancreatic ductal adenocarcinomas (PDACs) is characterized by EGFR gene numerical alterations including sporadic cases of amplification or absence of one allele (maybe due to gene deletion or intragenic point mutation and allelic silence). Those alternative mechanisms maybe influence the efficacy of novel targeted therapeutic strategies based on monoclonal antibodies or intracellular tyrosine-kinase inhibitors in PDACs.

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

In controlled clinical trials, rabeprazole effectively improves symptoms and heals oesophageal erosions in patients with gastro-oesophageal reflux disease (GORD).To examine symptom relief during week 1 of rabeprazole therapy, in addition to GORD healing, in a clinical practice setting.In this 8-week, prospective, multicentre, postauthorisation surveillance study conducted in Greece, patients with GORD (intent-to-treat: efficacy, 272; safety, 273) were treated with rabeprazole 20 mg once daily. The primary efficacy end point was the change from baseline in GORD symptom severity on day 1, 2, 3 and 7 using a 5-point Likert scale (1 = no symptoms; 5 = severe symptoms). Oesophageal healing was also evaluated by comparing the results of endoscopic findings at baseline and after 4 and 8 weeks of treatment.On day 1 of treatment, rabeprazole relieved GORD symptoms across all grades of oesophagitis, with statistically significant (p = 0.0001) improvement in heartburn, regurgitation, epigastric pain and dysphagia. Oesophageal healing was achieved in 77% of patients at week 4 and in 90% at week 8 and treatment was well tolerated.In a clinical practice setting, rabeprazole provided rapid relief of GORD symptoms, confirming results seen in controlled clinical trials.