Texture and color enhancement imaging versus high definition white-light endoscopy for detection of colorectal neoplasia: a randomized trial.

BACKGROUND: Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection during colonoscopy. This international, multicenter randomized trial assessed the efficacy of TXI in detection of colorectal neoplasia. METHODS: Consecutive patients aged ≥ 40 years undergoing screening, surveillance, or diagnostic colonoscopies at five centers (Italy, Germany, Japan) between September 2021 and May 2022 were enrolled. Patients were randomly assigned (1:1) to TXI or WLI. Primary outcome was adenoma detection rate (ADR). Secondary outcomes were adenomas per colonoscopy (APC) and withdrawal time. Relative risks (RRs) adjusted for age, sex, and colonoscopy indication were calculated. RESULTS: We enrolled 747 patients (mean age 62.3 [SD 9.5] years, 50.2 % male). ADR was significantly higher with TXI (221/375, 58.9 %) vs. WLI (159/372, 42.7 %; adjusted RR 1.38 [95 %CI 1.20-1.59]). This was significant for ≤ 5 mm (RR 1.42 [1.16-1.73]) and 6-9 mm (RR 1.36 [1.01-1.83]) adenomas. A higher proportion of polypoid (151/375 [40.3 %] vs. 104/372 [28.0 %]; RR 1.43 [1.17-1.75]) and nonpolypoid (136/375 [36.3 %] vs. 102/372 [27.4 %]; RR 1.30 [1.05-1.61]) adenomas, and proximal (143/375 [38.1 %] vs. 111/372 [29.8 %]; RR 1.28 [1.05-1.57]) and distal (144/375 [38.4 %] vs. 98/372 [26.3 %]; RR 1.46 [1.18-1.80]) lesions were found with TXI. APC was higher with TXI (1.36 [SD 1.79] vs. 0.89 [SD 1.35]; incident rate ratio 1.53 [1.25-1.88]). CONCLUSIONS: TXI increased ADR and APC among patients undergoing colonoscopy for various indications. TXI increased detection of polyps < 10 mm, both in the proximal and distal colon, and may help to improve colonoscopy quality indicators.

The use of ace inhibitors influences the risk of progression of BD-IPMNs under follow-up.

BACKGROUND: Chemoprevention's ability to slow down or prevent the progression of BD-IPMNs is extremely appealing. Aspirin (ASA), Ace Inhibitors/Angiotensin Receptor Blockers (ACEIs/ARBs) and Statins (STATs) are frequently prescribed drugs with a possible beneficial effect on different cancer types. Their effect on IPMNs is largely unknown. AIM: To evaluate the association between the use of ASA, ACEIs/ARBs and STATs and the risk of progression of BD-IPMNs in follow-up. MATERIALS AND METHODS: multicenter, retrospective cohort study on patients with presumed BD-IPMNs without relative or absolute indication for surgery. Pharmacological exposures and risk factors were collected. We identified clinically relevant progression (occurrence of radiological absolute or relative indication for surgery) and any progression (occurrence of clinically relevant progression OR any dimension increase OR the occurrence of new cysts). RESULTS: Overall 594 patients were included. ACEIs were associated with a lower occurrence of any progression (HR = 0.70; 95% CI 0.49-0.98, p = 0.04) and clinically relevant progression, HR = 0.42 (95% CI 0.20-0.88; p = 0.02). No significant effect was shown for factors associated with the occurrence of pancreas cancer such as smoking, alcohol consumption and 1st degree family history of pancreas cancer. Among pharmacological exposures, no convincing effect was shown for the chronic use of ASA, ARB and STAT. CONCLUSIONS: ACEIs might have an effect in slowing the progression of BD-IPMNs. ASA, STAT and ARBs show no convincing effect on the progression of BD-IPMNs. Further, prospective, and long-term multicenter studies are needed to verify such association and to define the potential underlying mechanisms.

The baseline nutritional status assessed by MUST score has a low accuracy in predicting the risk of hospitalization during follow-up in patients with chronic pancreatitis: A cohort study.

BACKGROUND: Hospitalization and death in patients with chronic pancreatitis (CP) are often due to extra-pancreatic events. Recent guidelines recommend the use of the MUST score to assess CP patients' nutritional status, but its association with clinical outcomes has been poorly investigated. The aims of this study are to evaluate the incidence of extra-pancreatic events in patients with CP during follow-up and their association with the nutritional status. METHODS: Retrospective analysis of single-centre cohort of CP patients prospectively enrolled and followed-up. Exocrine pancreatic insufficiency (EPI) was assessed by fecal elastase, MUST score calculated at diagnosis. The occurrence of hospitalizations or death were recorded. Differences between subgroups were analysed by Fisher's and T-test and hospitalization-free survival with Kaplan-Meier curves and Cox regression analysis. RESULTS: Of 111 enrolled patients (64% male; mean age 57); 52% had alcoholic aetiology, 53% EPI, 10% severe CP and 26% a MUST score≥2 at diagnosis. During a median follow-up of 37 months, 3.6% of patients died and 34.2% needed hospitalization, in 50% of cases for extrapancreatic events (2% cardiovascular events, 8% infections and 3% cancer). There was no significant association between EPI, BMI<20 kg/m2, MUST score≥2, alcoholic aetiology and extra pancreatic events or need of hospitalization. A baseline MUST score≥2 had an accuracy of only 64.8% in predicting subsequent hospitalization. CONCLUSIONS: A sizeable portion of CP patients are at high risk of malnutrition and are hospitalized during the follow-up, often for extra-pancreatic events. The nutritional status evaluated with the MUST score lacks accuracy in predicting the risk of these events.

Association between Corrected QT Interval and C-Reactive Protein in Patients with Inflammatory Bowel Diseases.

Background and objectives: Electrocardiograph abnormalities (i.e., QT interval prolongation) have been described in inflammatory bowel diseases (IBD). We aimed to measure the QT interval in a cohort of patients with IBD and to analyze its relationship with clinical and inflammatory activity. Materials and Methods: We performed a cross-sectional study that included 38 IBD outpatients and 38 "age- and sex-matched" healthy controls. Nine patients had active IBD, and 29 were in clinical remission. Among the latter, 10 patients had sustained (lasting >1 year) and 19 had short-term remission (≤1 year). Corrected QT (QTc) interval was measured on standard 12-lead electrocardiograph. A systematic review of the literature on studies investigating the QT interval in patients with IBD was also performed. Results: QTc interval values were similar between IBD patients and healthy controls (417.58 ± 22.05 ms vs. 409.13 ± 19.61 ms, respectively; p: 0.479). Patients with active IBD had significantly higher QTc values (435.11 ± 27.31 ms) than both controls (409.13 ± 19.61 ms) and patients in remission (412.14 ± 17.33 ms) (p: 0.031). Post hoc analysis showed that the difference in QTc values between active IBD and remission was attributable to the group of patients with sustained remission (p < 0.05). Lastly, a significant correlation between QTc interval and C-reactive protein (CRP) values was observed (Spearman test: r = 0.563; p: 0.0005). Conclusions: Our study demonstrates an association between QTc duration and both clinical and inflammatory activity in patients with IBD. The higher the CRP value, the longer is the QTc duration. For practical purposes, all patients with active IBD should undergo a standard ECG. Prescription of drugs able to modify the QT interval should be avoided in patients with active IBD. The systematic review of the literature indicated that this is the first published study demonstrating an association between the QTc duration and CRP values in patients with IBD.

Systematic review and meta-analysis: Prevalence of incidentally detected pancreatic cystic lesions in asymptomatic individuals.

BACKGROUND & AIMS: Pancreatic cystic lesions (PCLs) are frequent incidental findings. As most PCLs require costly diagnostic evaluation and active surveillance, it is important to clarify their prevalence in asymptomatic individuals. We therefore aimed at performing a systematic review and meta-analysis to determine it. METHODS: a systematic search was conducted and studies meeting inclusion criteria were included. The prevalence of PCLs was pooled across studies. A random effect model was used with assessment of heterogeneity. RESULTS: 17 studies, with 48,860 patients, were included. Only 3 were prospective; 5 studies were conducted in the US, 7 in Europe, 4 in Asia and 1 in Brazil. The pooled prevalence of PCLs was 8% (95% CI 4-14) with considerable heterogeneity (I2 = 99.5%). This prevalence was higher in studies of higher quality, examining older subjects, smaller cohorts, and employing MRCP (24.8% vs 2.7% with CT-scan). The pooled rate of PCLs was four times higher in studies conducted in the US than in Asia (12.6% vs 3.1%). 7 studies reported the prevalence of mucinous lesions, with a pooled rate of 4.3% (95% CI 2-10; I2 = 99.2%), but of 0.7% only for worrisome features or high risk stigmata. CONCLUSION: The rate of incidentally detected PCLs is of 8%. Mucinous lesions are the most common incidentally detected PCLs, although they rarely present with potential indication for surgery. The observed different rates in the US and other geographic Areas suggest that different protocols might be necessary to help balancing costs and effectiveness of follow-up investigations in asymptomatic subjects.

Pancreatic cyst surveillance imposes low psychological burden.

BACKGROUND/OBJECTIVES: For the currently recommended pancreatic cyst surveillance to be feasible, participant adherence is a prerequisite. Our objective was to evaluate the psychological burden of pancreatic cyst surveillance from a participant's perspective. METHODS: The present participant survey is part of an international cohort study (PACYFIC study, www.pacyfic.net), which prospectively records the outcome of surveillance of asymptomatic pancreatic cysts. Participants are invited to complete questionnaires before and during cyst surveillance. RESULTS: 109 participants, 31 enrolled before and 78 during surveillance (median time since cyst diagnosis 16.5 (IQR 36) months), returned a total of 179 questionnaires. The majority indicated that surveillance reduces concerns of developing pancreatic cancer (82%), gives a sense of certainty (81%) and is a good method to detect cancer (91%). Participants already undergoing surveillance reported more negative aspects than those still to commence, like sleeping worse (30% vs 13%, P = 0.035), postponing plans (32% vs 13%, P = 0.031), and finding the follow-up burdensome (33% vs 13%, P = 0.044). Overall, the vast majority (94%) deemed advantages to outweigh disadvantages. Anxiety and depression scores were low (median Hospital Anxiety and Depression Scale 4 for anxiety (IQR 6), 2 for depression (IQR 5)). CONCLUSION: The psychological burden of pancreatic cyst surveillance is low. Therefore, participant adherence is expected to be high and annual surveillance seems feasible.

The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients.

Different inflammation-based scores such as the neutrophil/lymphocyte ratio (NLR), the Odonera Prognostic Nutritional Index (PNI), the Glasgow Prognostic Score, the platelet/lymphocyte ratio, and the C-reactive protein/albumin ratio have been found to be significantly associated with pancreatic cancer (PDAC) prognosis. However, most studies have investigated patients undergoing surgery, and few of them have compared these scores. We aimed at evaluating the association between inflammatory-based scores and PDAC prognosis. In a single center cohort study, inflammatory-based scores were assessed at diagnosis and their prognostic relevance as well as that of clinic-pathological variables were evaluated through multiple logistic regression and survival probability analysis. In 206 patients, age, male sex, tumor size, presence of distant metastasis, access to chemotherapy, and an NLR > 5 but not other scores were associated with overall survival (OS) at multivariate analysis. Patients with an NLR < 5 had a median survival of 12 months compared to 4 months in those with an NLR > 5. In the 81 patients with distant metastasis at diagnosis, an NLR > 5 resulted in the only variable significantly associated with survival. Among patients with metastatic disease who received chemotherapy, the median survival was 3 months in patients with an NLR > 5 and 7 months in those with an NLR < 5. The NLR might drive therapeutic options in PDAC patients, especially in the setting of metastatic disease.

The Use of Complementary and Alternative Medicine is Frequent in Patients With Pancreatic Disorders.

BACKGROUND: Herbal remedies and other complementary and alternative medicine (CAM) are used by 30% of the patients with liver and inflammatory bowel diseases. However, there are no data regarding CAM use in patients with pancreatic disorders, including potential pancreatotoxicity. AIM OF THE STUDY: The aim of the study was to assess the prevalence of CAM use in patients with pancreatic disorders and screen for pancreatotoxicity. MATERIALS AND METHODS: This was a cross-sectional survey of consecutive outpatients seen at a Pancreas Center. Data were collected in a specific questionnaire. Descriptive statistics were used to analyze the prevalence and the patterns of CAM use. Characteristics associated with CAM use were analyzed by appropriate statistics. RESULTS: Of 108 patients (52% male; mean age, 65±13 years), 47 (43.5%) used CAM. The use of CAM was more frequent among patients with previous acute pancreatitis (47%). Reported reasons for the use of CAM were to help standard therapies and for an overall better feeling. About 61% of the patients reported advantages with treatment. As compared with nonusers, CAM users were more often female (55% vs. 42%), with a higher school degree (43% vs. 36%), more frequently performing physical activity (51% vs. 41%), and reporting anxiety (45% vs. 31%). However, none of these differences were statistically significant. Three patients with previous acute pancreatitis reported the use of Serenoa repens that is potentially pancreatotoxic. DISCUSSION: The rate of CAM use in patients with pancreatic disorders is similar to those reported for other digestive diseases. CAM use seems to be more frequent in women with a higher education level and a "healthier lifestyle." Patients might not be aware of the potential pancreatotoxicity of CAM, which should be carefully considered by physicians.

Early onset pancreatic cancer: risk factors, presentation and outcome.

BACKGROUND: About 10% of pancreatic cancer patients are aged ≤50 at diagnosis and defined as Early Onset Pancreatic Cancer (EOPC). There is limited information regarding risk factors for EOPC occurrence and their outcome. AIM: To investigate risk factors, presentation features and outcome of EOPC patients. METHODS: Consecutive, histologically confirmed, pancreatic cancer patients enrolled. Data regarding environmental and genetic risk factors, clinical and pathological information, treatment and survival were recorded. EOPC patients (aged ≤50 at diagnosis) were compared to older subjects. RESULTS: Twenty-five of 293 patients (8.5%) had EOPC. There was no difference regarding sex distribution, medical conditions and alcohol intake between EOPC and older subjects. EOPC patients were more frequently current smokers (56% vs 28% p = 0.001) and started smoking at a significantly lower mean age (19.8 years, 95%CI 16.7-22.9) as compared to older patients (26.1, 95%CI 24.2-28) (p = 0.001). Current smoking (OR 7.5; 95%CI 1.8-30; p = 0.004) and age at smoking initiation (OR 0.8 for every increasing year; 95%CI 0.7-0.9; p = 0.01) were significant and independent risk factors for diagnosis of EOPC. There were no differences regarding genetic syndromes and pancreatic cancer family history. EOCP presented less frequently with jaundice (16% vs 44%, p = 0.006) and had a higher rate of unresectable disease, albeit not significantly (84% vs 68%, p = 0.1). EOPC patients were more frequently fit for surgery or chemotherapy than their counterpart, resulting in similar stage-specific survival probability. CONCLUSION: EOPC seems related to active and early smoking but not to familial syndromes. Young patients display aggressive disease but not worse outcome.

Role of the gut barrier in acute pancreatitis.

The small intestine is one of the distant organs that become damaged during severe acute pancreatitis, due to microcirculation disturbance associated with loss of fluids in the "third space," hypovolemia, splanchnic vasoconstriction, and finally an ischemia-reperfusion injury. In this scenario, the gut acts as the starter for severe systemic complications, as the failure of the intestinal barrier is associated with translocation of bacteria and inflammatory and toxic products produced in the intestinal wall, which can be responsible for sepsis and infection of the necrotic pancreas and for systemic inflammatory response. Therefore, one of the main goals of treatment in the early phases of severe acute pancreatitis should be to maintain the integrity of the gut barrier in the small intestine. These strategies include appropriate fluid resuscitation to limit the damage due to the relative hypovolemia and early enteral feeding. The role of intravenous antibiotics to prevent infection of the pancreatic necrosis is controversial and the role of probiotics, which seemed a promising tool in vitro and in early clinical trials, needs to be further investigated to better understand the effects of the single specific strains at various doses and timing before designing new clinical trials.

Gastroenteropancreatic Neuroendocrine Neoplasms in Patients with Inflammatory Bowel Disease: An ECCO CONFER Multicentre Case Series.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms [GEP-NENs] have rarely been reported in association with inflammatory bowel diseases [IBDs]. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collects cases of GEP-NENs diagnosed in patients with IBD. RESULTS: GEP-NEN was diagnosed in 100 IBD patients; 61% female, 55% Crohn's disease, median age 48 years (interquartile range [IQR] 38-59]). The most common location was the appendix [39%] followed by the colon [22%]. Comprehensive IBD-related data were available for 50 individuals with a median follow-up of 30 months [IQR 11-70] following NEN diagnosis. Median duration of IBD at NEN diagnosis was 84 months [IQR 10-151], and in 18% of cases NEN and IBD were diagnosed concomitantly. At diagnosis, 20/50 were stage-I [T1N0M0], and 28/50 were graded G1 [ki67 ≤2%]. Incidental diagnosis of NEN and concomitantly IBD diagnosis were associated with an earlier NEN stage [p = 0.01 and p = 0.02, respectively]. Exposure to immunomodulatory or biologic therapy was not associated with advanced NEN stage or grade. Primary GEP-NEN were more frequently found in the segment affected by IBD [62% vs 38%]. At the last follow-up data, 47/50 patients were alive, and only two deaths were related to NEN. CONCLUSIONS: In the largest case series to date, prognosis of patients with GEP-NEN and IBD seems favourable. Incidental NEN diagnosis correlates with an earlier NEN stage, and IBD-related therapies are probably independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis.

What are the challenges in selecting pharmacotherapy for pregnant women with inflammatory bowel disease?

The peak of incidence of inflammatory bowel disease (IBD) overlaps with the peak of reproductive age. Moreover, women affected by IBD are often concerned with the possible negative effects of their disease and medications on pregnancy and birth outcomes. From a physician point of view, managing IBD in pregnancy is challenging. Disease activity is the major cause of poor pregnancy outcomes and, therefore, achieving and maintaining IBD remission for the whole duration of pregnancy is the main therapeutic goal. The challenges in selecting therapy lie in balancing the proven efficacy of each drug with the level of safety uncertainty. Except for methotrexate and thalidomide, for which it exits an absolute contraindication in pregnancy, the evidence actually available suggest that most medications can be safely used during pregnancy if appropriately prescribed. The risks associated with drug withdrawal may be higher than the known risks of the medications themselves on pregnancy outcomes. However, all the decisions should be shared with the patient, all available information should be discussed and any therapeutic strategy must be tailored according to patient's context, including disease pattern, activity, severity and acceptance of risk.

Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study.

BACKGROUND: The long-term course of ulcerative colitis after a severe attack is poorly understood. Second-line rescue therapy with cyclosporine or infliximab is effective for reducing short-term colectomy but the impact in the long-term is controversial. OBJECTIVE: The purpose of this study was to evaluate the long-term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy. METHODS: This was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005 to 2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within 3 months from the index attack), we recorded the date of colectomy, last follow-up visit or death. The primary end-point was long-term colectomy rate in patients avoiding early colectomy. RESULTS: From the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow-up was 44 months (interquartile range, 21-85). Colectomy-free survival probability was 93.5%, 81.5% and 79.4% at 1, 3 and 5 years, respectively. Colectomy risk was higher among rescue therapy users than in steroid-responders (log-rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long-term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2-0.8), while previous exposure to antitumour necrosis factor-α agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5-5.7). Approximately 50% of patients required additional therapy or new hospitalisation within 5 years due to a recurrent flare. Death occurred in three patients (0.9%). CONCLUSIONS: Patients with acute severe ulcerative colitis avoiding early colectomy are at risk of long-term colectomy, especially if previously exposed to antitumour necrosis factor-α agents or if rescue therapy during the acute attack was required because of steroid refractoriness.

Factors Associated With the Risk of Progression of Low-Risk Branch-Duct Intraductal Papillary Mucinous Neoplasms.

Importance: Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are common pancreatic preneoplastic lesions, but their surveillance is not personalized. Objective: To investigate patient- and cyst-related factors associated with progression into worrisome features (WFs) or high-risk stigmata (HRS) categories of BD-IPMNs. Design, Setting, and Participants: Cyst- and patient-related factors of consecutive BD-IPMNs without WFs or HRS in 540 patients diagnosed from 2009 to 2018 with at least 12 months' surveillance until February 28, 2020, were registered in a 2-center ambispective cohort study in Italy. In a subgroup, the ABO blood group was studied for the first time in this setting. Exposure: Cyst-related and patients-related factors and ABO blood group. Main Outcomes and Measures: The study outcome was the appearance of WFs or HRS according to the 2017 International Association of Pancreatology guidelines. Survival probability was calculated using Kaplan-Meier curve and risk factors identified by Cox proportional hazards regression. ABO blood group was inferred through genotypes with DNA extraction. Results: Of 540 patients with BD-IPMNs (median age, 66 years [interquartile range, 58.5-72.0 years]; 337 women [62.4%]) undergoing surveillance for a median of 51.5 months (interquartile range, 28-84 months) for 2758 person-years, 130 patients (24.1%) experienced progression. Probability of progression was 3.7% at 1 year, 23.4% at 5 years, and 43.3% at 10 years; 15 patients (2.8%) underwent surgery, 7 patients (1.3%) had malignant histologic findings, and 3 patients (0.56%) died of pancreatic-associated disease. Initial cyst size greater than 15 mm (hazard ratio [HR], 2.05; 95% CI, 1.44-2.91), body mass index greater than 26.4 (HR, 1.72; 95% CI, 1.19-2.50), and heavy smoking (HR, 1.81; 95% CI, 1.14-2.86) were significant independent factors associated with progression risk. The AA blood genotype was also associated with progression risk (HR, 3.49; 95% CI, 1.04-11.71) compared with the OO genotype in the investigated subgroup. Conclusions and Relevance: This analysis of factors associated with progression of BD-IPMNs according to recent guidelines suggests that cyst size alone is not a reliable factor for estimation of progression risk; however, along with other readily available data, size is helpful for planning personalized surveillance of BD-IPMNs.

[The advantages of patient's active involvement in the management of chronic Inflammatory Bowel Diseases.] / L'importanza del coinvolgimento attivo del paziente nella gestione delle malattie infiammatorie croniche dell'intestino.

The patient's active involvement is an emerging hot-topic, which can be applied in to the management of chronic inflammatory bowel diseases (IBD). Since in this field most of the therapeutic strategies are not based on sturdy scientific evidences, the patient's role has become central and it is believed essential for any patients to have an active cognitive, behavioural and emotive profile. Moreover different patient's aspects should be considered, such as the patient's activation, the patient's engagement and the patient's disease knowledge. The initial evidences available on this topic within IBD context have showed how a higher patient's active profile and a deeper disease knowledge have had a positive effect on compliance, perceived health-care satisfaction, self-management and health costs. Therefore, considering the favourable outcomes so far highlighted, we hope that the evaluation of patient's involvement may become a standard procedure, allowing patients who need it to undergo active programmes which have proved to be effective in improving patient's degree of activation.

[Towards new therapeutic paradigms beyond symptom control in the management of inflammatory bowel diseases.] / Malattie infiammatorie croniche dell'intestino: perché il controllo dei sintomi non è sufficiente?

Inflammatory bowel diseases, Crohn's disease and ulcerative colitis are chronic relapsing conditions that may result in progressive bowel damage, high risk of complications, surgery and permanent disability. The conventional therapeutic approach for inflammatory bowel diseases is based mainly on symptom control. Unfortunately, a symptom-based therapeutic approach has little impact on major long-term disease outcomes. In other chronic disabling conditions such as diabetes, hypertension and rheumatoid arthritis, the development of new therapeutic approaches has led to better outcomes. In this context a "treat to target" strategy has been developed. This strategy is based on identification of high-risk patients, regular assessment of disease activity by means of objective measures, adjustment of treatment to reach the pre-defined target. A treat to target approach has recently been proposed for inflammatory bowel disease with the aim at modifying the natural history of the disease. In this review, the evidence and the limitations of the treat to target paradigm in inflammatory bowel disease are analyzed and discussed.

A safety evaluation of budesonide MMX for the treatment of ulcerative colitis.

INTRODUCTION: Budesonide belongs to low-bioavailability steroids class. A novel oral formulation of budesonide, which uses the Multi-Matrix System (MMX) for delivering drugs to the colon, is now available as a possible treatment of ulcerative colitis patients intolerant or not-responding to first-line therapy with 5-ASA. Areas covered: in this review we present information about the development and the use of budesonide MMX and we provide data about its mechanism of action as well as, pharmacodynamics and pharmacokynetics. Moreover, we present the available literature data about the efficacy and, mainly, the safety of budesonide-MMX. Expert opinion: budesonide-MMX is a new therapeutic option in mild-to-moderate UC patients. Its good safety profile in clinical trials undoubtedly represents a strength for a possible wide use in clinical practice, mainly if it will be confirmed by post-marketing data. Other indications, such as treatment of colonic Crohn's disease, could theoretically be considered, if sustained by reliable scientific data.

Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with "familial pancreatic cancer" (FPC) and specific syndromes are limited and heterogeneous. OBJECTIVE: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs. METHODS: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated. RESULTS: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years. CONCLUSION: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.

The prevalence of pancreatic cystic lesions in patients with liver cirrhosis is double that in controls.

BACKGROUND AND AIMS: Pancreatic cystic lesions (PCLs) are commonly diagnosed incidentally and are often preneoplastic. Their presence may influence the management of patients with chronic diseases such as liver cirrhosis (LC). This study evaluated the prevalence and nature of PCLs in LC patients. METHODS: The images of 192 LC patients and 192 controls who underwent either computed tomography scan or nuclear magnetic resonance were reviewed for the presence and nature of PCLs. The prevalence of PCLs in both groups and differences between LC patients with and without PCLs were analysed. Multiple logistic regression analysis was used to investigate factors associated with PCLs. RESULTS: Thirty-five of 192 LC patients (18%) and 19/192 controls (10%) had PCLs (p = .027). The prevalence of presumptive intraductal pancreatic mucinous neoplasm (IPMN) was double in LC patients compared with controls (14% vs 7%; p = .065). In multivariate analysis, age, LC and having undergone a magnetic resonance cholangiopancreatography were factors associated with PCLs and IPMNs. LC patients with PCLs were older at the time of imaging and had a longer history of liver disease (67 vs. 43 months; p = 0.039) compared with LC patients without PCLs. CONCLUSIONS: PCLs are more common in LC patients than in controls, and most are IPMNs. The occurrence of PCLs in LC patients seems to be related to age and disease duration.

Exclusive and Combined Use of Statins and Aspirin and the Risk of Pancreatic Cancer: a Case-Control Study.

Data on the association between aspirin and statin use and Pancreatic Ductal AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed, but no studies evaluated the potential combined or confounding effect of the two at the same time. We aimed to investigate the association between aspirin and statin exclusive and combined use and PDAC occurrence. Data on environmental factors, family and medical history were screened in a case-control study. PDAC cases were matched to controls for age and gender. Power calculation performed ahead. Odds ratios (OR) and 95% confidence intervals(CI) were obtained from multivariable logistic regression analysis. In 408 PDAC patients and 816 matched controls, overall statin (OR 0.61; 95%CI,0.43-0.88), but not aspirin use was associated to reduced PDAC risk. Compared to non-users, exclusive statin (OR 0.51; 95%CI,0.32-0.80) and exclusive aspirin users (OR 0.64; 95%CI,0.40-1.01) had reduced PDAC risk. Concomitant statin and aspirin use did not further reduce the risk compared with statin use alone and no interaction was evident. Statin protective association was dose-dependent, and consistent in most subgroups, being stronger in smokers, elderly, obese and non-diabetic patients. The present study suggests that statin use is associated to reduced PDAC risk, supporting a chemopreventive action of statins on PDAC.