Relapse rates and predictors for relapse in a real-life cohort of IBD patients after discontinuation of anti-TNF therapy

Objective: We investigated relapse rates after anti-tumor necrosis factor (anti-TNF) withdrawal in inflammatory bowel disease (IBD) patients, response to restart of anti-TNF treatment and predictors for relapse.

Methods: IBD patients in remission receiving infliximab or adalimumab treatment for ≥1 year who discontinued treatment were included. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis.

Results: In total, 101 patients were included (77?CD, 24 UC). A total of 56 patients (55%) experienced a relapse (CD 38, UC 18) with a median time to relapse of 32 and 18 months in CD and UC, respectively. Of patients that were retreated with the same anti-TNF agent, 84% responded. A trough serum concentration ≥2 µg/ml within 1 year prior to anti-TNF discontinuation was associated with a higher relapse rate in CD patients (HR 2.89; p?=?.018), which was more evident in patients requiring retreatment with biologicals, bowel-related surgery or experimental medication (HR: 4.18; p?=?.009). A young age (<17 years) at diagnosis was associated with a higher relapse rate (HR: 2.29; p?=?.040) and fecal calprotectin levels <25?µg/g with a lower relapse rate in CD patients (HR: 0.34; p?=?.041). Relapse rates, requiring treatment with biologicals or experimental medication, was lower in UC patients who continued immunosuppressive treatment (HR: 0.26; p?=?.042).

Conclusions: Approximately 55% of patients relapsed after anti-TNF withdrawal with a median time to relapse of 32 and 18 months in CD and UC, respectively. Retreatment with the same anti-TNF was successful in 84% of patients.     

Adalimumab in the treatment of chronic pouchitis. A randomized double-blind,placebo-controlled trial

Background: Pouchitis is a complication of ileal pouch-anal anastomosis and occurs in up to 50% of patients 10 years after IPAA with 10% developing refractory pouchitis.

Objective: To evaluate the effect of a TNF-α inhibitor (Adalimumab) in the treatment of refractory pouchitis.

Materials and methods: A multicenter, randomized double-blind, placebo-controlled trial includes patients with refractory pouchitis for more than 4 weeks despite antibiotic treatment. Patients were randomized to Adalimumab or placebo for 12 weeks. Primary outcome was reduction in clinical pouchitis disease activity index (PDAI) of ≥2 at any time. Secondary endpoints were remission of pouchitis, endoscopic and histologic effect and quality of life.

Results: Thirteen patients were included; six patients received active treatment and seven patients received placebo. Nine patients (5/4, Adalimumab/placebo) completed the 12-week program. Reduction in clinical PDAI ≥ 2 was achieved in three patients in each group (50%/43%, Adalimumab/placebo, p?>?.5). Total PDAI improved in six patients treated with Adalimumab and two patients on placebo (100%/29%, p?=?.13). There were no differences in secondary endpoints between the groups.

Conclusions: In this randomized controlled trial of treatment with Adalimumab in patients with refractory pouchitis, we were not able to identify any clinical benefit in the primary or secondary endpoints.     

Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated – an open-label pilot study

Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules.

Methods: Seven patients with active UC, aged 27–50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months.

Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p?=?.001) and 6 (p?=?.001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800?mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported.

Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.     

Biochemical response to ursodeoxycholic acid among PBC patients: a nationwide population-based study

Objective: To assess the proportion of PBC patients with a biochemical response to ursodeoxycholic acid (UDCA) in a population-based cohort and the association of biochemical response with outcomes.

Methods: All patients diagnosed with PBC in Iceland from 1991–2015 were identified. Patients taking UDCA for an adequate period of time were analyzed for treatment response according to the Barcelona, Paris I, Paris II and Toronto criteria and outcomes.

Results: Overall 182 females and 40 males were diagnosed with PBC and 135 patients were treated with UDCA. Overall 99 (73%) patients had adequate data on UDCA treatment and results of liver tests to assess biochemical response according to the Barcelona criteria, 95 (70%) according to the Toronto criterion and 85 (63%) according to the Paris I and II criteria. In all 74% (n?=?63), 67% (n?=?64), 54% (n?=?53) and 46% (n?=?39) responded to treatment according to the Paris I, Toronto, Barcelona and Paris II criteria. Among nonresponders according to the Paris I, Toronto, Paris II and Barcelona criteria, 50%, 39%, 33% and 30% developed cirrhosis versus 10%, 6%, 5% and 11% of responders, HR 5.36 (p?=?.002), 6.61 (p?=?.002), 10.94 (p?=?.003) and 2.21(p?=?.11), respectively. Age-adjusted mortality was significantly lower among responders according to the Paris I and Paris II criteria, HR 0.33 (p?=?.02) and 0.31 (p?=?.02), respectively.

Conclusion: Development of cirrhosis and higher mortality was significantly associated with a lack of biochemical response to UDCA. Frequent development of cirrhosis and increased mortality in nonresponders underlines the need for a more effective therapy than UDCA for this sizeable subgroup of patients.     

Galectin 4 is a biomarker for early recurrence and death after surgical resection for pancreatic ductal adenocarcinoma

Background: Galectins are a group of carbohydrate-binding proteins that are involved in neoplastic development and progression. In a previous mass spectrometry-based study, we identified galectin 4 as a down-regulated protein in short-term survivors of pancreatic cancer. This study was performed to validate the prognostic value of galectin 4 in a larger cohort of pancreatic cancer patients undergoing surgical resection.

Methods: Galectin 4 expression was evaluated by tissue microarrays and immunohistochemistry in 140 patients with surgically resected pancreatic cancer. Kaplan-Meier and Cox proportional hazards modeling were used to explore the association between galectin 4 and survival.

Results: Galectin 4 staining expression was positive in 111 cases (79.3%). The expression of galectin 4 was significantly associated with tumor size (p?=?.008) and differentiation (p?=?.001). Galectin 4 expression was significantly correlated with disease recurrence within 1 year of surgery (adjusted HR 0.485, p?=?.027). There was also a significant association between galectin 4 and overall survival at 1 year (adjusted HR 0.482, p?=?.047) and at 3 years (adjusted HR 0.550, p?=?.025).

Conclusion: Galectin 4 expression is a novel biomarker for early recurrence and mortality after surgical resection for pancreatic cancer.     

Attention deficit and hyperactivity disorder symptoms respond to gluten-free diet in patients with coeliac disease

Introduction: Patients with coeliac disease commonly report symptoms of ‘brain fog’. The aim of this study was to assess self-reported symptoms of impaired concentration in coeliac disease before and after treatment with gluten-free diet, compared with healthy controls and patient controls.

Methods: Patients with newly diagnosed coeliac disease were included consecutively from two out-patient clinics. The patients completed the questionnaires Adult ADHD Self-Report Scale v1.1 Symptoms Checklist (ASRS), Hospital Anxiety and Depression Scale (HADS) and Gastrointestinal Symptom Rating Scale (GSRS) prior to start of a gluten-free diet and after at least 12 months on the diet. Patients with an established diagnosis of inflammatory bowel disease served as patient controls (n?=?36). Health care personnel at Oslo University Hospital served as healthy controls (n?=?60) and filled out ASRS and HADS.

Results: A total of 31 newly diagnosed coeliac patients were included in the study. Of these, 26 patients met for follow-up and repeated the questionnaires. Prior to treatment, patients with coeliac disease had significantly higher scores than healthy controls on both the ASRS (p?=?.0014) and HADS (p=.0004). After a gluten-free diet, their scores improved and were not significantly different from healthy controls. There were no significant differences between patients with coeliac disease prior to treatment and patient controls with inflammatory bowel disease.

Conclusion: Prior to treatment, coeliac disease patients reported significantly more symptoms than healthy controls on ASRS and HADS. The differences disappeared after a minimum of 12 months on a gluten-free diet.     

Roseburia intestinalis inhibits oncostatin M and maintains tight junction integrity in a murine model of acute experimental colitis

Objective: Levels of oncostatin M (OSM) and the composition of gut microbiota predict responses to anti-TNF agents used for IBD therapy. Here, the aim was to investigate the effects of Roseburia intestinalis, a gut microbiota, on OSM and on intestinal barrier in colitis.

Methods: In the murine model of 3% dextran sulfate sodium (DSS)-induced colitis, we tested disease activity index (DAI), colon length, histological score and expression of tight junction (TJ) proteins (ZO-1, occludin and claudin-1), OSM, TNF-α and TLR5. In addition, a cellular model was used to examine the role of R. intestinalis during secretion of OSM by lipopolysaccharide (LPS)-induced bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) and TLR5 knockout (TLR5 KO) mice. Furthermore, we evaluated the impact of OSM on expressions of TJ proteins by Caco-2 cells.

Results: R. intestinalis in DSS-induced colitis decreased DAI score (p?<?.001), colon length shortening (6.46?±?0.36?cm vs 5.65 ± 0.47 cm, p?=?.022), histological score (2.667?±?1.15 vs 5.33 ± 1.14, p?=?.018) and increased expression of TJ proteins (p?<?.05). In addition, R. intestinalis reduced expression of OSM (p?<?.05) and TNF-α (p?<?.05), while increasing expression of TLR5 (p?<?.05). Furthermore, R. intestinalis reduced secretion of OSM (p?<?.05) by LPS-induced BMDMs isolated from WT and TLR5 KO mice. Moreover, OSM downregulated expression of TJ proteins (p?<?.05) by Caco-2 cells in a concentration-dependent manner.

Conclusions: These results indicate that R. intestinalis attenuates inflammation in IBD by decreasing secretion of OSM and by promoting intestinal barrier function. Taken together, the data provide insight into the role of the gut microbiota in patients with IBD who are resistant to anti-TNF therapy.     

Evaluation of fatigue in inflammatory bowel disease - a useful tool in daily practice

Background: Fatigue is a common symptom reported in inflammatory bowel disease (IBD) patients. It can be severe and modify the self-perception of disease.

Objective: To evaluate the contribution of clinical and demographic factors to the level of fatigue in IBD patients.

Methods: Patients consecutively observed in an outpatient IBD clinic during a 9-month period were studied. Demographic and clinical data were collected. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). A FACIT-F score <30 was considered as severe fatigue.

Results: One hundred and five patients were evaluated. Of them, 57.1% had Crohn´s Disease (CD) and 42.9% had Ulcerative Colitis. Also 85.0% and 77.8% were in clinical remission, respectively. The mean FACIT-F score was 39.63?±?9.67. Severe fatigue was observed in 17.1% of patients. Female gender and active CD were significantly associated with a severe level of fatigue (p?=?.05 and p?=?.04). There was no significant correlation between the level of fatigue (severe vs. non-severe) and type of IBD, hemoglobin, C-reactive protein, ferritin levels or previous surgeries. Patients under biological therapy had a significantly higher level of fatigue and a higher rate of previous hospitalizations (p?=?.02).

Conclusions: Fatigue level is a simple and useful tool to evaluate the disease’s impact in patients’ life, and it should, therefore, be included in clinical practice. Biological therapy was associated to higher levels of fatigue. Future studies should evaluate the impact of therapy on the level of fatigue.     

Treatment with Noripurum EV® is effective and safe in pediatric patients with inflammatory bowel disease and iron deficiency anemia

Objectives: To evaluate the therapeutic response and adverse effects of Noripurum EV^® in children and adolescents with inflammatory bowel disease (IBD) and iron deficiency anemia.

Materials and methods: Cohort study involving patients with Crohn’s disease (CD) and ulcerative colitis (UC) who received treatment for iron deficiency anemia with Noripurum EV^®. Anemia was defined according to WHO 2011 criteria. Iron deficiency anemia was established when ferritin <30µg/l and transferrin saturation <16%. Iron deficiency anemia and anemia of chronic disease were established when ferritin was between 30 and 100µg/l and transferrin saturation <16%. The total dose of Noripurum EV^® was estimated by the Ganzoni formula and divided into weekly administrations. When there was an increase in hemoglobin (Hb) by a minimum of 2g/dl and or when Hb reached the target determined by WHO, treatment was considered a therapeutic success.

Results: Noripurum EV^® was administered to 16 patients (9.3% of total patients with IBD). Ten (65.5%) were male, the mean (SD) age was 11.3(4.6) years old, 75%(12/16) had CD and 25%(4/16) had UC. All patients presented an increase in Hb (p?<?.001) at a mean (SD) of 2.8(1.3)g/dl, after median and interquartile range(IQR) of 4.5(3.0–6.0) weeks that iron infusions were completed. It was found that the proportion of patients that achieved therapeutic success (68.8%) was statistically higher (p?=?.031) than those who did not (31.2%). No adverse events were reported.

Conclusion: Noripurum EV^® in pediatric patients with IBD and iron deficiency anemia was effective and safe, making it an appropriate option for the clinical management of these patients.     

Efficacy of preoperative colonoscopic tattooing with indocyanine green on lymph node harvest and factors associated with inadequate lymph node harvest in colorectal cancer

Objective: Adequate lymph node harvest (LNH) in colorectal cancer is closely related to survival. This study aimed to evaluate the effect of preoperative colonoscopic tattooing (PCT) with indocyanine green (ICG) on adequate LNH in colorectal cancer.

Materials and methods: A total of 1079 patients who underwent surgical resection for colorectal cancer were divided into two groups: a tattooing group and a non-tattooing group. The patients were retrospectively analyzed for the number and adequacy of LNH according to tumor locations and stages. Univariate and multivariate analysis for factors associated with adequate LNH were done.

Results: There was no significant difference between the two groups in the number and adequacy of LNH according to tumor locations. However, T1 colorectal cancer in the tattooing group had significantly higher adequate LNH (91.6% vs 82.1%, OR 2.370, p?=?.048) and T1 and N0 rectal cancer in the tattooing group also had higher adequate LNH although there was no statistical significance (100% vs 82.4%, OR 12.088, p?=?.095; 96.9% vs 84.8%, OR 5.570, p?=?.099) when compared to the non-tattooing group. Male sex and T1 stage were significantly associated with inadequate LNH in multivariate analysis (OR 0.556 (95% CI 0.340–0.909), p?=?.019; OR 0.555 (95% CI 0.339–0.910), p?=?.019, respectively).

Conclusion: PCT with ICG did not improve adequate LNH in colorectal cancer but effectively improved adequate LNH in early colorectal cancer. Male sex and early cancer were risk factors for inadequate LNH in colorectal cancer, so PCT is needed for adequate LNH in these patients.     

Acute pancreatitis in elderly patients: a single-center retrospective evaluation of clinical outcomes

Introduction: Acute pancreatitis (AP) incidence in the elderly population has increased in the last years. However, the role of age as influencing factor on the AP clinical course is still debated.

Methods: We reviewed clinical records of consecutive patients admitted with diagnosis of AP. Patients were divided in elderly (≥65 years) and non-elderly (<65 years). Primary endpoint was comparison of overall mortality. Secondary endpoint included ICU admission, in-hospital length of stay (LOS) and surgical procedures.

Results: We enrolled 352 elderly and 532 non-elderly patients. A higher mortality rate (7.4% vs 1.9%; p?<?.001), ICU admission rate (18.9% vs 6.3%; p?<?.001) and prolonged length of hospital stay (9 (6–14) vs 7 (5–11.7) days; p?=?.01) were registered in the ≥65 years group. Multivariate analysis identified age (OR: 3.5; 95% CI:1.645–7.555; p?=?.001), a higher Ranson score at admission (OR: 5.52; 95% CI:1.11–27.41; p<.001) and necrotic pancreatitis (OR: 8.6; 95% CI:2.46–30.27; p?=?.001) as independent predictors of mortality. Conversely age and necrotic pancreatitis were independent risk factors for higher LOS and ICU admission.

Conclusions: Patients with AP and age ≥65 years have a higher mortality, ICU admission and prolonged LOS. Early recognition and prompt treatment are key elements to improve outcomes in this population.     

Indirect comparison of vedolizumab and adalimumab for biologic-naive patients with ulcerative colitis

Aim: Indirect comparison of efficacy and safety of vedolizumab with adalimumab in biologic-naïve patients with moderate to severe ulcerative colitis (UC).

Methods: Vedolizumab is a gut-selective medication for moderate to severe UC. Since no comparative trials are available for direct comparison of vedolizumab vs adalimumab in UC, a systematic review of literature databases was conducted to identify randomized, placebo-controlled trials of the two drugs in patients with moderate to severe UC after failure of conventional treatment. Studies were screened for eligibility by two reviewers based on predefined inclusion criteria. Bucher’s adjusted indirect comparison was used to compare vedolizumab and adalimumab indirectly through placebo as common comparator.

Results: One vedolizumab study (GEMINI 1) and three adalimumab studies (ULTRA 1, ULTRA 2 and M10-447) met the eligibility criteria. Baseline characteristics of the included populations were similar in biologic-naïve UC patients across study arms. Although no statistically significant differences between treatments were found for induction efficacy endpoints, there was a trend toward a benefit of vedolizumab over adalimumab. There were also no significant differences between treatments for any maintenance efficacy endpoints, with no clear trend favoring either agent. Vedolizumab exhibited statistically superior maintenance safety compared with adalimumab, with significant reductions in risks of adverse events (relative risk 0.67 [95% confidence interval 0.57–0.80]; p?<?.0001), serious adverse events (0.20 [0.09–0.42]; p?<?.0001) and adverse events leading to discontinuation (0.14 [0.05–0.43]; p?=?.0006).

Conclusion: This analysis indicates that vedolizumab has comparable efficacy to adalimumab with improved safety in biologic-naïve patients with moderate to severe UC.     

Adjuvant transcatheter arterial chemoembolization after radical resection of hepatocellular carcinoma patients with tumor size less than 5 cm: a retrospective study

Objective: Our aim is to retrospectively compare the disease-free survival (DFS) of adjuvant TACE after surgical resection on patients with tumor less than 5?cm.

Methods: A total of 307 patients with HCC underwent hepatic resection between January 2014 to December 2016 were enrolled in this study. Among these, 172 patients underwent surgical treatment only (group A) and 135 patients received surgical resection followed by adjuvant TACE (group B). Propensity score matching (PSM) analysis is used to minimize baseline differences between two groups. DFS was compared between the two groups and Cox proportional hazard model was used to predict the factor for recurrence.

Results: Before PSM, the 1, 2, 3 year DFS rate of group A and B were 90.1%, 83.3%, 75.3% versus 85.2%, 73.9%, 68.1%, respectively (p?=?.286). After PSM, the 1, 2, 3 year DFS rate of group A and group B were 90.3%, 80.8%, 71.9% versus 89.2%, 77.8%, 71.3%, respectively (p?=?.791). In subgroup analysis where patients presented with microvascular invasion (MiVI), before PSM the 1, 2, 3 year DFS rate were 77.8%, 77.8%, 77.8% and 70%, 70%, 47.3%, for group A and B, respectively (p?=?.491). After PSM the 1, 2, 3 year DFS rate for group A and B were 71.4%, 71.4%, 71.4% and 100%, 100%, 50%, respectively (p?=?.440). Cox proportional hazard model identified tumor size ≥3?cm as factor related to recurrence.

Conclusions: Adjuvant TACE does not improve the DFS of HCC patients with tumor size less than 5?cm.     

Emu Oil reduces disease severity in a mouse model of chronic ulcerative colitis

Objective: Ulcerative colitis (UC) is characterized by mucosal inflammation and ulceration of the large intestine. Emu Oil (EO) has been reported to protect the intestine against mucositis, NSAID-enteropathy, UC-associated colorectal cancer and acute UC. We aimed to determine whether EO could reduce the severity chronic UC in mice.

Methods: Female C57BL/6 mice (n?=?10/group) were orally administered (gavage) water (Groups 1–2) or EO (Groups 3: low dose-80?µl and 4: high dose-160?µl), thrice weekly. Group 1 mice consumed plain drinking water throughout the trial. Groups 2–4 mice underwent two cycles [each consisting of seven days dextran sulfate sodium (DSS; 2% w/v) and 14 days water], followed by a third DSS week. All mice were euthanized two days later (day 51). Bodyweight, disease activity index (DAI), burrowing activity, myeloperoxidase activity, crypt depth and histologically assessed damage severity were assessed. p?<?.05 was considered significant.

Results: DSS decreased bodyweight and increased DAI compared to normal controls (p?<?.05), which was partially attenuated by both EO doses (p?<?.05). Burrowing activity was impaired in DSS-controls compared to normal controls (days 27 and 40); an effect prevented by both EO doses (p?<?.05). DSS increased colonic myeloperoxidase activity and crypt depth compared to controls (p?<?.05), with no significant EO effect. Moreover, DSS increased colonic damage severity compared to normal controls (p?<?.001). Importantly, both EO doses decreased distal colonic damage severity compared to DSS-controls (p?<?.001).

Conclusions: Emu Oil attenuated clinically- and histologically-assessed disease severity in a mouse model of chronic UC. Emu Oil demonstrates promise as an adjunct to conventional treatment options for UC management.     

Does postoperative adjuvant transarterial chemoembolization benefit for all patients with hepatocellular carcinoma combined with microvascular invasion: a meta-analysis

Purpose: To evaluate the clinical efficacy of postoperative adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) patients combined with microvascular invasion (MVI).

Patients and methods: Eligible studies were searched by PubMed, MedLine, Embase, the Cochrane Library, Web of Science, from 1st January 2000 to 31st December 2018, comparing the overall survival (OS) rates and disease-free survival (DFS) rates between postoperative adjuvant TACE and operation only for HCC patients with MVI. Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size.

Results: Eight studies were enrolled in this meta-analysis, including 774 patients in the postoperative adjuvant TACE group and 856 patients in the operation only group. The pooled HR for the OS and DFS rates were significantly different between the postoperative adjuvant TACE group and the operation only group (HR 0.57, 95%CI 0.48?～?0.68, p?<?.00001; HR 0.66, 95%CI 0.58?～?0.74, p?<?.00001; respectively). However, in the subgroup analysis stratified by proportion of multiple-nodules, no significant differences were observed in the pooled HR for the OS/DFS rates between the postoperative adjuvant TACE group and the operation only group (HR 0.83, 95%CI 0.60?～?1.13, p?=?.23; HR 0.76, 95%CI 0.41?～?1.40, p?=?.37; respectively).

Conclusions: Postoperative adjuvant TACE will benefit patients with HCC and MVI, but not for multiple-HCC with MVI. However, more high-quality studies are warranted to validate the conclusion.     

Surgery combined with post-operative trancatheter arterial chemoembolization improves survival of intermediate hepatocellular carcinoma

Aim: To investigate the efficacy of surgery combined with post-operative trancatheter arterial chemoembolization (TACE) for intermediate hepatocellular carcinoma (HCC).

Methods: A total of 102 patients were divided into two groups: Radical liver resection only (LR group, 52 patients) and radical liver resection combined with post-operative TACE (combined group, 50 patients). Survival analysis was performed using the Kaplan–Meier method. Univariate and multivariate analysis were performed using Cox proportional analysis to detect prognostic factors of survival outcomes.

Results: The 1-, 3- and 5-year survival rate in the LR group were significantly lower compared with those in combined group (p?=?.019). The 1-, 3- and 5-year progression-free survival rate in the LR group were also lower than those in the combined group (p?=?.048). Multivariate analysis detected that tumor number (multiple vs single), tumor distribution (both lobes vs semi-liver), treatment strategy (surgery?+?TACE vs surgery) were independent factors for OS (HR values were 2.307, 3.155 and 0.526, respectively) and PFS (HR values were 1.938, 3.425 and 0.633, respectively; p?<?.05).

Conclusion: In conclusion, surgery combined with post-operative TACE may improve survival outcomes for patients with intermediate HCC. Tumor number, tumor distribution and treatment strategy (surgery?+?TACE) were significantly associated with the prognosis of patients with intermediate HCC.     

Fully covered self-expanding metal stents for benign refractory pancreatic duct strictures in chronic pancreatitis

Background: Pancreatic duct (PD) stricture is a common adverse event in chronic pancreatitis (CP). Primary treatment for refractory PD strictures is endotherapy (ET), including the insertion of multiple plastic stents. In addition, fully covered self-expandable metal stents (FC-SEMSs) have also been successfully used. More long-term studies are necessary to clarify the complication rate and efficiency, however.

Methods: This retrospective study was comprised of 17 patients with symptomatic CP and refractory fibrotic main pancreatic duct (MPD) stricture treated with FC-SEMSs between 2010–2018 at the Helsinki University Hospital. Treated strictures were located in the pancreatic head. Technical success was defined as the accurate positioning of the stent and resolution of the MPD stricture. Clinical success was defined as pain relief at the end of the follow-up.

Results: In 12 patients (71%), stricture resolution was accomplished. Clinical success was achieved in 12 patients (71%). The median duration of stenting was 169 days (range 15–804). Ten patients (58.8%) underwent a follow-up of two years or more. Early complications (≤7 days) occurred in two patients (12%): one pancreatitis and one cholestasis. Late complications (≥7 days) included severe abdominal pain (n?=?2, 12%), pancreatitis (n?=?3, 18%), cholestasis (n?=?1, 6%) and stent migration (n?=?7, 35%). Significant differences in stricture resolution and pain improvement were evident in patients with stent migration compared to patients without stent migration [1(14.3%) vs. 11(84.6%), p?=?.004 and 2(28.6%) vs. 11(84.6%), p?=?.022].

Conclusion: FC-SEMS placement is a safe and potentially effective treatment for this challenging group of patients. However, stent migration appears to affect the clinical and technical outcome.     

Patient-oriented education and visual-aid intervention are inadequate to identify patients with potential capsule retention: a prospective randomized study

Background/aims: The key procedure-related risk with video capsule endoscopy (VCE) is capsule retention, which should be suspected in patients who have not reported capsule passage. The study aims were to determine the frequency of capsule passage visualization and the difference in self-reporting of capsule passage between patients who receive patient-oriented education (POE) and patients who receive POE and a visual aid intervention in the form of a wrist band (WB).

Methods: This was a prospective randomized study that enrolled patients undergoing VCE. Patients were randomly assigned to a POE group versus a POE and WB group. POE consisted of verbal education and an information booklet. Both groups received instructions to notify the study team regarding capsule passage.

Results: Sixty patients (mean age 57?±?18 years; 61% female) were included. A total of 57 patients were included in the analysis (3 lost to follow-up; 28 in POE group; 29 in WB group). Capsule passage status was reported by 68% without significant difference between POE and WB groups (72% vs. 64%; p?=?.51). Capsule passage status was obtained from all 57 patients with the addition of a proactive follow-up. Only 56% (n?=?32) reported visualizing capsule passage. Of the remaining patients who did not visualize capsule passage, 60% (n?=?15) reported on this without significant difference between the POE and WB groups (p?=?.23).

Conclusions: Lack of visualization of capsule passage is a poor indicator of retention. Self-reporting of VCE passage status is suboptimal and the addition of a visual aid did not improve this parameter.     

Correlation and concordance measures between clinical,endoscopic and histological scores activity in Crohn’s disease under treatment

Aim: Our aim was to evaluate the correlation and concordance measures between clinical, endoscopic and histologic remission in Crohn’s disease (CD) under treatment.

Method: Twenty-four patients with CD under treatment were included in a prospective consecutive cross-sectional study from January to September 2018. Clinical activity was assessed by Crohn’s Disease Activity Index (CDAI). All of the patients were submitted an ileocolonoscopy with biopsy and classified by Simple Endoscopic Score (SES-CD). Histologic activity was assessed by Global Histologic Activity Score (GHAS) modified. Remission was considered with CDAI <150; SES-CD ≤2 and GHAS ≤4.

Results: Clinical remission was established in 53%, however, only 50% had mucosal healing (MH) and 70% had inflammatory histologic activity. Correlation between endoscopic and histological measures was strong and positive (σ = 0.73, p?<?.0003). The concordance remission agreement between SES-CD and GHAS was weak with (κ) = 0.3 (IC 95%: ?0.09; 0.69). The greatest disparity arose when clinical activity (CDAI) was compared with histological measures (σ?=?0.20, p?=?.45), (κ)?=?0.26 (IC?=??0.03; 0.56).

Conclusion: The score SES-CD correlates well with histological score GHAS in CD under treatment, however, there is low concordance between both mainly in patients with anti-TNFs treatment. CDAI score had low correlation and concordance with histological score GHAS. In this sample, patients under treatment and without symptoms had low MH and histologic healing.     

Blood platelet function abnormalities in cirrhotic patients with esophageal varices in relation to the variceal bleeding history*

Objective: The study aimed at assessing the effect of thrombocytopenia and platelet function abnormalities on the occurrence of variceal bleeding in patients with cirrhosis.

Methods: The results of impedance aggregometry, von Willebrand factor antigen level and thromboelastometry (TEM) with and without the addition of a platelet inhibitor (FIBTEM^®, EXTEM^® test, respectively) were compared in two patient groups: Group 1 (n?=?32) – patients with moderate or large esophageal or gastric varices, who had never had symptoms of acute gastrointestinal bleeding and Group 2 (n?=?26) – patients with history of variceal bleeding.

Results: Standard clotting test indicated more hypocoagulable profile in Group 2 compared to Group 1. However, no differences in any TEM component were observed between groups in EXTEM^® test. The contribution of platelets to clot strength was significantly higher in Group 2 than in Group 1 [PLT%?=?74.2 (67.5–80.4) versus 68.8 (63.7–76.5) %; p?=?.039]. The aggregation index was also higher in Group 2 compared to Group 1, although not statistically significant [% of healthy = 96.9 (73.2–140.1) versus 67.6 (52.5–118.8) %, p?=?.195]. No differences in vWF antigen levels were observed between groups.

Conclusions: The results of thromboelastometry and aggregometry indicate increased contribution of platelets in clot formation in patients with a history of variceal bleeding compared to cirrhotic patients who never bled. Comparable effectiveness of hemostasis in both groups is most likely associated with the compensatory role of platelets. Increased platelet activity in this group of patients is probably due to a mechanism independent of the von Willebrand factor antigen level.