Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1-q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

SURGICAL INTERVENTION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY BOWEL DISEASE AND PERIANAL DISEASE.

OBJECTIVE: Aim: The aim of the study was to investigate the incidence of IBD in gastrointestinal surgery patients and record the disease's characteristics and treatment. PATIENTS AND METHODS: Materials and Methods: A search was carried out in the archives of the gastroenterology clinics of the University General Hospital of Ioannina and the General Hospital of Ioannina "G. Hatzikosta" in Greece. All cases of operated patients from 1980 to 2018 were examined. The duration of the study was 4 months. Data were analyzed with the SPSS program, v.28. RESULTS: Results: The total sample consisted of 1464 patients (n=1464). Most of them (915-62.5%) came from the University General Hospital of Ioannina, while the rest (549-37.5%) came from the GHI hospital "G. Hatzikosta". The mean age of the patients was 47 years (M=47.26, SD=17.34, Min=<1 month, Max=95 years). From the total sample, 58 patients (4%) suffered from IBD; most were men (42-72.41%). Their mean age was approximately 50 years (M=49.63, SD=16.48, Min=25 years, Max=77 years, range=52 years) and most belonged to the age groups of 31-40 years (11 patients- 19.6%) and 21-30 years and 61-70 years (10 patients-17.9%). The perianal disease was present in 43.1% (25 patients). The most frequent type of operation was fistula resection, ligation, curettage-biopsy (24.1%) and opening-drainage (22.4%-13 patients) and the most frequent type of anesthesia was general anesthesia (93.1%-54 patients). CONCLUSION: Conclusions: This long-term study of the patients' data followed up over time showed that the possibility of surgery in patients with IBD is mitigated through systematic monitoring and multifaceted therapeutic treatment.The perianal disease which appeared more often in men shows that it can be diagnosed early and at an early stage and with the new minimally invasive techniques the patient with IBD can be treated with a better quality of life.

Medical, Endoscopic and Surgical Management of Stricturing Crohn's Disease: Current Clinical Practice.

The development of fibrostenotic intestinal disease occurs in approximately one-third of patients with Crohn's disease and is associated with increased morbidity. Despite introducing new biologic agents, stricturing Crohn's disease remains a significant clinical challenge. Medical treatment is considered the first-line treatment for inflammatory strictures, and anti-TNF agents appear to provide the most considerable benefit among the available medical treatments. However, medical therapy is ineffective on strictures with a mainly fibrotic component, and a high proportion of patients under anti-TNF will require surgery. In fibrotic strictures or cases refractory to medical treatment, an endoscopic or surgical approach should be considered depending on the location, length, and severity of the stricture. Both endoscopic balloon dilatation and endoscopic stricturoplasty are minimally invasive and safe, associated with a small risk of complications. On the other hand, the surgical approach is indicated in patients not suitable for endoscopic therapy. This review aimed to present and analyze the currently available medical, endoscopic, and surgical management of stricturing Crohn's disease.

Gastric metastasis from breast cancer presenting as dysphagia.

Gastric metastasis from breast cancer occurs infrequently and causes non-specific symptoms, usually attributed to the underlying disease. Furthermore, endoscopic findings are almost identical to primary gastric cancer, making the immunohistochemical examination of biopsies necessary for diagnosis. We present the case of a 64-year-old woman who was diagnosed with lobular breast cancer 3 years ago and received chemotherapy with evidence of remission. The patient presented with dyspepsia and progressive dysphagia for the last 6 months, not responsive to PPI treatment. Upper endoscopy revealed partial occlusion of the cardio-esophageal junction and thickened gastric folds resembling linitis plastica. However, immunohistochemical analysis of endoscopic biopsies showed infiltration of gastric mucosa by lobular breast cancer cells, making the diagnosis of gastric metastasis. Therefore, clinicians' awareness of possible gastric metastasis is warranted in patients with a history of advanced breast cancer and severe gastric symptoms.

The efficacy of immunomodulators in the prevention and suppression of anti-drug antibodies to anti-tumor necrosis factor therapy in inflammatory bowel disease.

The development of biological agents against tumor necrosis factor (TNF) has revolutionized the management of inflammatory bowel disease (IBD), frequently achieving induction and maintenance of remission in both ulcerative colitis and Crohn's disease. However, a loss of response due to the development of anti-drug antibodies (ADA) is seen annually in approximately 20% of IBD patients receiving anti-TNF therapy. Current evidence suggests that the use of immunomodulators (IMM), such as thiopurines (azathioprine and 6-mercaptopurine) or methotrexate, may prevent or suppress ADA formation. In this article, we present a comprehensive review of the available literature regarding the efficacy of IMM in the prevention and suppression of ADA development to anti-TNF therapy in patients with IBD.

Current noninvasive modalities in Crohn's disease monitoring.

Crohn's disease (CD) is characterized by a remitting and relapsing course. Longstanding active CD may result in accumulating intestinal damage and disease-related complications. In contrast, mucosal healing is associated with significant improvement in the health-related quality of life, longer periods of disease remission and lower risk of disease progression, complications, hospitalizations, intestinal surgeries, as well as a lower risk of developing colorectal cancer. Mucosal healing, the new treatment endpoint in CD, made necessary the development of noninvasive, accurate, objective and reliable tools for the evaluation of CD activity. Ileocolonoscopy with biopsies remains the reference standard method for the evaluation of the colonic and terminal ileal mucosa. However, it is an invasive procedure with a low risk of complications, allowing the investigation of only a small part of the small bowel mucosa without being able to assess transmural inflammation. These disadvantages limit its role in the frequent follow up of CD patients. In this review, we present the currently available biomarkers and imaging modalities for the noninvasive assessment of CD activity.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: 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 frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Diagnosis, epidemiology and management of serrated polyposis syndrome: a comprehensive review of the literature.

Serrated polyp associated colorectal cancer (CRC) develops from an alternative mechanism of colorectal carcinogenesis and accounts for 10-15% of all CRC. Serrated polyposis syndrome (SPS) occurs infrequently and is characterized by the occurrence of multiple serrated polyps (hyperplastic polyps, sessile serrated lesions and traditional serrated adenomas) throughout the colon and/or rectum and has been strongly associated with development of CRC. However, SPS is frequently unrecognized, due to application failure of the WHO criteria regarding diagnosis and/or missed serrated polyps during endoscopy. The management of SPS requires surveillance at regular intervals and removal of large serrated polyps. Endoscopic resection suitability and technique depends on lesion size and the endoscopist's experience. In this manuscript, we present an update regarding SPS epidemiology, molecular characteristics, management, surveillance strategies and endoscopic resection techniques.

Effect of golimumab on health-related quality of life, other patient-reported outcomes and healthcare resource utilization in patients with moderate-to-severe ulcerative colitis: a real-world multicenter, noninterventional, observational study in Greece.

BACKGROUND AND AIMS: This real-world study assessed the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with ulcerative colitis over 12 months in Greece. METHODS: GO-LIFE was a noninterventional, prospective, multicenter, 12-month study. Patients who had moderately-to-severely active ulcerative colitis were naïve to antitumor necrosis factor (anti-TNFα) therapy and had failed previous conventional therapy. Patients received golimumab as per label. The primary endpoint was patients achieving inflammatory bowel disease questionnaire 32-item (IBDQ-32) remission at 12 months. Secondary endpoints, at 6 and 12 months, included patients achieving IBDQ-32 response; the mean change in the treatment satisfaction questionnaire for medication (TSQM) and the work productivity and activity impairment in ulcerative colitis (WPAI:UC) questionnaires; changes in healthcare utilization; patients achieving clinical response and remission; adherence rates and the percentage of patients who discontinued golimumab. RESULTS: IBDQ-32 remission was achieved by 76.9% of patients at 12 months. Mean changes in all TSQM and WPAI:UC domain scores at 12 months were statistically significant. Clinical remission was achieved by 49.4 and 50.6% of patients at 6 and 12 months, and clinical response by 59.3 and 56.8%, respectively. All patients but one (80/81) had high adherence (≥80%) to golimumab treatment over 12 months. Ulcerative colitis-related health care resource utilization was reduced during the follow-up period. CONCLUSIONS: In real-world settings, treatment with golimumab resulted in meaningful improvements in HRQoL and other PROs, and in disease activity at 6 and 12 months in patients with moderately-to-severely active ulcerative colitis who were naïve to anti-TNFa therapy.

Immuno-oncology: a narrative review of gastrointestinal and hepatic toxicities.

Vaccines, cytokines, and adoptive cellular therapies (ACT) represent immuno-therapeutic modalities with great development potential, and they are currently approved for the treatment of a limited number of advanced malignancies. The most up-to-date knowledge on the regulation of the anti-cancer immune response has recently led to the development and approval of inhibitors of immune checkpoints, which have produced unprecedented clinical activity in several hard to treat solid malignancies. However, severe adverse events (AEs) represent a limitation to the use of these drugs. Currently approved checkpoint inhibitors block cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand (PD-L1), resulted in increased survival of patients with several solid and hematologic malignancies. The most common treatment AEs associated with these drugs are fatigue, rash, and auto-immune/inflammatory reactions. Many of the immune-related AEs are reversible and the strategies for their management include supportive care either with or without treatment withdrawal; nevertheless, in severe cases, hospitalization and treatment with immune suppressants, and/or immunomodulators may be required. Steroid therapy is a critical component of the treatment algorithm; nevertheless, the associated immunosuppression may compromise the antitumor response. This article provides a comprehensive and narrative review of luminal gastrointestinal and hepatic complications, including recommendations for their investigation and management.

The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study.

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice. AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease. METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists. RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)). CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

Clostridium Difficile Infection in Patients Impact Suspected Cytomegalovirus Infection in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Clostridium difficile infection (CDI) has been reported to be a cause of flare-ups in patients with inflammatory bowel disease (IBD). Cytomegalovirus (CMV) infection can cause severe disease and complications in immunocompromised patients in consequence of disease or therapy. AIM: Our aim was to describe the prevalence and clinical outcomes of CDI with concomitant CMV infection in IBD patients hospitalized for flare-ups in association with the disease itself and medication used. METHODS: We prospectively identified consecutive patients referred for CDI management during 2015-2017. Stool samples were tested for Clostridium difficile toxin A and/or B and Glutamate Dehydrogenase in patients with clinical symptoms. CDI patients with IBD history were tested for anti-CMV IgG and IgM antibodies by chemiluminescent microparticle immunoassay and underwent histological analysis for CMV on colon biopsies. Data were collected for demographic characteristics, treatment and outcome. RESULTS: 125 patients with CDI were enrolled. Among these patients, 14 (11.2%) were diagnosed with IBD. The mean patient age of IBD patients was 52.5±15.4 years at diagnosis of CDI, 85.7% had UC, 14.3% CD, while the age of patients was shared. Eleven of the total of 14 patients (78.6%) tested positive for anti-CMV IgG. Of these, 3 patients (21.4%) exhibited high CMV IgG avidity, without detectable anti-CMV IgM and biopsy-proven CMV colitis. Of the 14 IBD patients with CDI, 8 patients (57.1%) were receiving anti-tumor necrosis factor (anti-TNF) therapy (21.4 % infliximab or golimumab, 7.1% vedolizumab or adalimumab) and 43.5% of patients were being treated with systemic corticosteroids. Four UC patients (28.6%) on steroids of the 14 CDI patients underwent a colectomy whereas none of the not on steroids patients underwent colectomy (p=0.25). Among them, 1 patient (7.1%) had recurrent CDI after 5 months from the first episode of CDI.These patients were treated with vancomycin, metronidazole and fidaxomicin. The mean age of patients that had a colectomy 65.5±9.32 (n=4) was higher than the mean age of those 47.30±14.49 (n=10) who improved (UMann-Whitney=6. p=0.04). CONCLUSIONS: Immunosuppressive medications and older age are associated with increased risk of CDI and poor outcome. Although, CMV is a rare colonic pathogen in the immunocompetent patient, it should be included and screened when exacerbation of IBD occurs in patients receiving any type of immunosuppressive therapy.

Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study.

BACKGROUND: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up. METHODS: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery. FINDINGS: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001). INTERPRETATION: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease. FUNDING: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd.

Ocular manifestations in celiac disease: an overview.

PURPOSE: To review and highlight the ocular manifestations associated with celiac disease (CD) and presentation of their pathogenetic mechanisms. METHODS: A thorough review of the literature was performed using PubMed to identify articles about serrated polyposis syndrome. The search was performed using the search string: ("celiac disease" OR "coeliac disease") AND ("ocular manifestations" OR "eye" OR "orbitopathy" OR "uveitis" OR "neuro-ophthalmic manifestations"). Only articles in English were reviewed. RESULTS: Several ocular symptoms and disorders have been associated with CD and are a result of defective intestinal absorption and immunological mechanisms. These include nyctalopia, dry eye, cataract, thyroid-associated orbitopathy, uveitis, central retinal vein occlusion and neuro-ophthalmic manifestations. In addition, CD-related ocular disease may represent the first manifestation of CD. CONCLUSION: CD may hold accountable for the development of ocular diseases of obscure etiology.

Comparison of the Uptake of Screening Colonoscopy between Physicians and the General Population in Greece.

AIM: To evaluate the uptake of screening colonoscopy among physicians as compared to the general population. METHODS: Asymptomatic physicians, aged 45-67 years, at average risk for colorectal cancer (CRC), working in the participating National Health System hospitals were asked to complete a questionnaire regarding the uptake of screening colonoscopy. The results were compared to those in a background healthy population, aged 50-75 years, inhabitants of a Greek county, who were offered a free access to a screening colonoscopy program for CRC. High-risk adenomas were those ≥10 mm in diameter or any adenoma, regardless of size, with villous histology or high-grade dysplasia. RESULTS: Overall, 267 of 782 physicians and 402 of 6,534 nonphysicians underwent a screening colonoscopy (uptake rates 34.2 and 6.2% respectively, p = 0.00001). Screening colonoscopy has yielded 4 adenocarcinomas (1.6%), 14 high-risk adenomas (5.5%), and 61 low-risk adenomas (25.7%) in the physicians' group. Corresponding figures in the nonphysician arm were 4 (1), 26 (6.5), and 107 (26.6%), respectively. The main reason among physicians for nonadherence was indifference/negligence (n = 213). CONCLUSION: The proportion of physicians undergoing screening colonoscopy for CRC is significantly higher compared to the general population; however, it does remain suboptimal.

Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study.

BACKGROUND: Hepatobiliary and pancreatic manifestations have been reported in patients with Crohn's disease or ulcerative colitis. Our aim was to describe the prevalence of hepatobiliary and pancreatic manifestations in inflammatory bowel disease and their association with the disease itself and the medications used. METHODS: Data were retrospectively extracted from the clinical records of patients followed up at our tertiary IBD referral Center. RESULTS: Our study included 602 IBD patients, with liver function tests at regular intervals. The mean follow-up was 5.8 years (Std. Dev.: 6.72). Abdominal imaging examinations were present in 220 patients and revealed findings from the liver, biliary tract and pancreas in 55% of examined patients (120/220). The most frequent findings or manifestations from the liver, biliary tract and pancreas were fatty liver (20%, 44/220), cholelithiasis (14.5%, 32/220) and acute pancreatitis (0.6%, 4/602), respectively. There were 7 patients with primary sclerosing cholangitis. Regarding hepatitis viruses, one-third of the patients had been tested for hepatitis B and C. 5% (12/225) of them had positive hepatitis B surface antigen and 13.4% had past infection with hepatitis B virus (positive anti-HBcore). In addition, most of the patients were not immune against hepatitis B (negative anti-HBs), while 3% of patients were anti-HCV positive and only one patient had active hepatitis C. Furthermore, 24 patients had drug-related side effects from the liver and pancreas. The side effects included 21 cases of hepatotoxicity and 3 cases of acute pancreatitis. Moreover, there were two cases of HBV reactivation and one case of chronic hepatitis C, which were successfully treated. CONCLUSION: In our study, approximately one out of four patients had some kind by a hepatobiliary or pancreatic manifestation. Therefore, it is essential to monitor liver function at regular intervals and differential diagnosis should range from benign diseases and various drug related side effects to severe disorders, such as primary sclerosing cholangitis.

Presence of pseudopolyps in ulcerative colitis is associated with a higher risk for treatment escalation.

BACKGROUND: Pseudopolyps in ulcerative colitis (UC) are considered as indicators of previous episodes of severe inflammation and ulceration of the mucosa. The aim of the study was to investigate the long-term outcomes of patients treated for UC, with or without pseudopolyps. METHODS: This was a retrospective single-center study. Consecutive patients with UC and available endoscopic data from 2000 until 2016 were eligible for the study and were followed until June 2017. Patients with incomplete medical/endoscopic charts or interrupted follow up were excluded from the study. Primary outcomes included time to treatment escalation, treatment escalation to biological agents or surgery, and UC-related hospitalization. RESULTS: Eighty-three UC patients were included in the study, of whom 25 (30%) had pseudopolyps. The median duration of follow up was 2.8 years (interquartile range: 1.1-4.9). Multiple Cox regression analysis identified the presence of pseudopolyps as the only variable independently associated with treatment escalation (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.2-4.3; P=0.014) and escalation to biological agents or surgery (HR 6.3, 95%CI 1.9-20.7; P=0.002). CONCLUSION: This retrospective single-center study provides the first preliminary evidence that patients with UC and pseudopolyps may represent a subpopulation with a higher inflammatory burden and a greater need for treatment escalation, including to biological agents or surgery. Large, prospective multicenter studies are certainly warranted to confirm these findings.

Perioperative Use of Anti-TNFa Biological Agents in Open and Laparoscopic Surgery for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) consists of two disorders: Crohn's disease (CD) and ulcerative colitis (UC). Over the past few decades, a great body of knowledge has accumulated regarding the pathogenesis of IBD, and effective pharmaceutical agents, such as inhibitors of tumor necrosis factor (anti-TNF), have been introduced. Although these agents have dramatically improved the outcome of IBD, up to 70% of patients with CD and 10-30% of those with UC still undergo surgery within 10 years from diagnosis. Because of their young age and high recurrence rates, these patients are appropriate candidates for laparoscopic surgery as an alternative to laparotomy. Recently, considerable attention has been focused on perioperative outcomes of patients who are receiving anti-TNF agents and require surgery. The aim of this narrative review is to discuss the current evidence regarding the impact of perioperative anti-TNF treatment on post-operative complication rates with a special focus on laparoscopic surgery.

The Developing Story of Predictive Biomarkers in Colorectal Cancer.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Microsatellite instability (MSI) has been suggested as a predictive marker for response to anti-programmed-cell-death protein 1 (PD-1) therapy in solid tumors, including CRC. It should be noted that not all cancers with MSI phenotype respond to anti-PD-1 immunotherapy, highlighting the urgent need for even better predictive biomarkers. Mitogen-Activated Protein Kinase (MAPK) pathway genes KRAS, NRAS, and BRAF represent important molecular targets and could serve as independent prognostic biomarkers in CRC, and identify those who potentially benefit from anti-epidermal growth factor receptor (EGFR) treatment. Emerging evidence has attributed a significant role to inflammatory markers including blood cell ratios in the prognosis and survival of CRC patients; these biomarkers can be easily assessed in routine blood exams and be used to identify high-risk patients or those more likely to benefit from chemotherapy, targeted therapies and potentially immunotherapy. Analysis of cell-free DNA (cfDNA), circulating tumor cells (CTC) and/or micro RNAs (miRNAs) could provide useful information for the early diagnosis of CRC, the identification of minimal residual disease and, the evaluation of the risk of recurrence in early CRC patients. Even the selection of patients suitable for the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Finally, the development of treatment resistance with the emergence of chemo-resistance clones after treatment remains the most important challenge in the clinical practice. In this context it is crucial to identify potential biomarkers and therapeutic targets which could lead to development of new and more effective treatments.

Specific Features of Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic and progressive disease of the biliary tract. PSC is strongly associated with inflammatory bowel disease (IBD), mainly with ulcerative colitis, and most PSC patients have underlying IBD. The pathophysiological interactions between IBD and PSC are unclear, although it seems that the patients with IBD and PSC have a distinct phenotype. IBD with coexisting PSC is more extensive and is characterized by milder activity compared to IBD alone. The coexistence of PSC increases the risk for colorectal cancer in IBD patients and lifelong annual surveillance colonoscopy is recommended. Also, liver transplantation (LT) for PSC may affect the course of IBD. In addition, the management of IBD after LT includes many specific problems. On the other hand, the effect of IBD on the natural history of PSC appears to be milder. However, IBD may increase the risk of postsurgical complications after LT and is a risk factor for recurrent PSC after LT. Overall, the coexistence of IBD with PSC changes the management, natural history and prognosis of both diseases.