Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Endoscopic ultrasound-guided fine-needle aspiration of solid lesions on clopidogrel may not be a high-risk procedure for bleeding: A case series.

The major gastrointestinal endoscopy society guidelines list endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a high-risk procedure for bleeding. However, there are no studies evaluating the risk of bleeding for EUS-FNA of solid organs while patients continue to take clopidogrel. The aim of the present case series was to evaluate the rate of bleeding in a cohort of patients who underwent EUS-FNA for solid lesions while on clopidogrel. Bleeding was measured at the time of the procedure by bleeding seen on EUS, endoscopic visualization of blood, or drop in hemoglobin after the procedure. From 2013 to 2015, 10 patients were identified for this case series. Lesions that underwent EUS-FNA included gastric and rectal subepithelial lesions, pancreas masses, and liver masses. No immediate or delayed bleeding was observed in any of the patients. EUS-FNA of solid lesions on clopidogrel may not be a high-risk procedure for bleeding. Larger studies are needed to confirm this finding.

Systematic review and meta-analysis of single-balloon enteroscopy-assisted ERCP in patients with surgically altered GI anatomy.

BACKGROUND: Surgically altered pancreaticobiliary anatomy increases the difficulty of performing ERCP. Single-balloon enteroscopy (SBE) is a relatively new technique that can be used for ERCP in patients with surgically altered anatomy. OBJECTIVE: To evaluate the therapeutic and diagnostic success of SBE-ERCP among patients with surgically altered anatomy. DESIGN/SETTING: Systematic review and meta-analysis of studies involving SBE-ERCP in patients with Roux-en-Y gastric bypass, hepaticojejunostomy, or Whipple procedure. Enteroscopy success was defined as success in reaching the papilla and/or biliary anastomosis by using SBE. Diagnostic success was defined as obtaining a cholangiogram. Procedural success was defined as the ability to provide successful intervention, if appropriate. A random-effects model was used. RESULTS: A total of 461 patients underwent SBE-ERCP from 15 trials. The pooled enteroscopy, diagnostic, and procedural success rates were 80.9% (95% confidence interval [CI], 75.3%-86.4%), 69.4% (95% CI, 61.0%-77.9%), and 61.7% (95% CI, 52.9%-70.5%), respectively. There was statistical large heterogeneity for enteroscopy, diagnostic, and therapeutic success (P < .001 for all). Adverse events occurred in 6.5% (95% CI, 4.7%-9.1%) of patients. There was no evidence of publication bias in this meta-analysis. LIMITATIONS: Our findings and interpretations are limited by the quantity and heterogeneity of the studies included in the analysis. CONCLUSION: SBE-ERCP has high diagnostic and procedural success rates in this challenging patient population. It should be considered a first-line intervention when biliary access is required after Roux-en-Y gastric bypass, hepaticojejunostomy, or Whipple procedure.

Use of a cap in single-balloon enteroscopy-assisted endoscopic retrograde cholangiography.

BACKGROUND AND STUDY AIM: Cannulation of the native papilla in surgically altered anatomy is difficult in endoscopic retrograde cholangiography (ERC). There are limited data regarding the success of single-balloon enteroscopy-assisted ERC (SBE-ERC) in patients with a native papilla and Roux-en-Y gastric bypass. Use of a plastic cap may assist cannulation in these cases. The aim of the current study was to investigate the use of SBE-ERC with a cap (Cap-SBE-ERC) in patients with surgically altered anatomy referred for ERC. PATIENTS AND METHODS: Patients with surgically altered anatomy (hepaticojejunostomy, gastric bypass surgery, and Whipple's surgery) who underwent Cap-SBE-ERC were identified from a prospectively maintained database. Outcomes were diagnostic and procedural success. Patients with a native papilla were compared with those with a biliary-enteric anastomosis. RESULTS: Among 56 patients with surgically altered anatomy, high rates of diagnostic and procedural success were observed (78.6 % and 71.4 %, respectively). High diagnostic and procedural success rates of 72.7 % and 65.9 %, respectively, were also observed for patients with Roux-en-Y gastric bypass anatomy with a native papilla (n = 44). CONCLUSION: High rates of diagnostic and procedural success were reported for SBE-ERC with the use of a cap, including a large subgroup of patients with Roux-en-Y gastric bypass and a native papilla.

Role of long-term biliary stenting in choledocholithiasis.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is the treatment of choice for the management of choledocholithiasis. Biliary stenting facilitates repeated attempts at stone extraction. The aim of the present paper was to assess long-term outcomes of patients where biliary stenting was used as the primary treatment for the management of choledocholithiasis. METHODS: We undertook a review of a prospectively maintained database of all ERCP carried out at a single institution. All patients had stones not amenable to endoscopic retrieval. RESULTS: Between January 1998 and December 2008, 3655 ERCP were carried out in our unit. Of these, 201 (120 female) patients met our inclusion criteria. All patients underwent ERCP and sphincterotomy, followed by insertion of a double pigtail 7-Fr plastic stent. Repeat ERCP was not scheduled routinely. Stent change was only carried out in patients when clinical suspicion of stent blockage occurred. Median stent patency was 59.6 months (interquartile range 47.7-71.2). At 6 months, stent patency was 93.5%, and at 24 months, it was 81.9%. Serious adverse outcomes with blocked stents were uncommon, and tended to occur early. Cholangitis was seen in only 7.4% (6) of patients (median stent patency 11.8 months) and jaundice was seen in 18.5% (15 patients, median stent patency 7.2 months). CONCLUSION: Our data demonstrate median stent patency of almost 5 years. The low incidence of significant complications with blocked stents and excellent stent patency rates suggest that long-term biliary stenting is an acceptable alternative in elderly, frail patients with stones that are not endoscopically retrievable.

It's a man's world: does orthotopic liver transplantation in the elderly male confer an additional risk on survival?

BACKGROUND: Orthotopic liver transplantation (OLT) in a well-selected population is a highly successful procedure, with one-year survival rates reported to be as high as 90%. Advanced age is considered to be a contraindication. Survival rates in patients >60 years of age appear to be comparable with those of younger patients. However, little objective data exist on the outcomes of patients >65 years of age undergoing OLT. OBJECTIVE: To review the outcomes of OLT in the Irish National Transplant Unit in patients >65 years of age and to compare outcomes with patients ≤65 years of age. Second, to identify any factors that may provide valuable prognostic information regarding outcomes. METHOD: Patients >65 years of age who underwent OLT since the inception of the National Liver Unit in 1993 were identified from a prospectively maintained database. Medical records were reviewed. Survival was compared with the overall cohort using the Kaplan-Meier technique. Independent variables between the two groups were assessed using logistic regression analysis. RESULTS: Between January 1993 and December 2009, 551 patients underwent 639 transplants in the Irish National Liver Transplant Unit. Forty-three transplants were performed in 40 patients >65 years of age. Unadjusted one- and three-year survival rates for the elderly cohort were 77.8% and 64.5%, respectively. This compared with 93% and 85%, respectively, in the unselected cohort. Using Kaplan-Meier analysis, a significant benefit in survival was observed in patients ≤65 years of age (P=0.017). Similarly, when adjusted for sex, a significant difference was noted between the groups. Male patients >65 years of age had poorer survival compared with their female counterparts >65 years of age and all patients ≤65 years of age (P=0.02). There was no significant difference between the groups with respect to preoperative variables such as bilirubin, creatinine and sodium levels, and Model for End-stage Liver Disease score. A significant difference was seen in male patients >65 years of age with more than one comorbidity, compared with female patients and male patients ≤65 years of age. CONCLUSION: Male sex was associated with poorer survival in patients >65 years of age undergoing OLT. Multiple comorbidities in elderly male patients should be considered a relative contraindication in patients being assessed for OLT.

Dorsal root ganglionopathy in a hepatitis C patient: a case report.

We report an unusual clinical presentation of dorsal root ganglionopathy in a hepatitis C patient with negative cryoglobulins characterized by both motor and sensory symptoms. This mixed clinical picture in a hepatitis C patient is rare but should be considered a potential complication of HCV infection.

Surgery, Crohn's disease, and the biological era: has there been an impact?

INTRODUCTION: The management of Crohn's disease (CD) has changed considerably over the last 20 years. Immunomodulators and biological therapies now play a role in treating patients with CD, but little is known of their influence on surgical rates. AIM: To review the surgery rates for CD in an Irish university hospital over a 20-year period and to determine whether newer therapies had an impact on surgical rates. METHOD: Seven hundred twenty-two patients attending St Vincent's University Hospital, Dublin, with CD over a 20-year period (January 1986 to December 2005) were identified. The patients were divided into quartiles. Resection rates were determined in all the quartiles, at both 1 and 3 years from diagnosis. RESULTS: A decline in surgery, 3 years from diagnosis, was noted between the first quartile (72 patients, 40%) and the second quartile (58 patients, 32%; P=0.03). No significant change in surgical rates at 3 years occurred between the other 3 quartiles (32%, 30%, and 35%, respectively; P=NS). The patients who required a resection within 3 years were diagnosed at a younger age in later years. There was a similar predominance of 60% of female patients requiring surgery in all groups. The patients requiring surgery were twice as likely to be ex-smokers or current smokers in all groups. Use of infliximab, within 3 years from diagnosis, increased from 0, 0, and 16 patients (8.8%) to 40 patients (22.1%) in the last quartile. The majority of patients were treated with infliximab on an "on demand" basis. Use of infliximab earlier within the course of the disease was seen in later quartiles (ie, within 1 y of diagnosis): 0, 0, 6, and 21 patients. CONCLUSION: Despite the introduction of infliximab over the past 10 years, no demonstrable difference has been seen in the rates of patients requiring resection surgery within 3 years of diagnosis. The reasons for this are unclear, but may relate to episodic treatment, rather than regular maintenance treatment. Female patients and smokers seem to be particularly at risk of resection surgery.

Impact of photodocumentation of caecal intubation on colonoscopy outcomes.

OBJECTIVES: The European and American colonoscopy guidelines recommend mandatory photodocumentation of caecal intubation to allow retrospective analysis and improve outcomes. We aim to demonstrate whether photodocumentation of caecal intubation improves colonoscopy outcomes. METHODS: We extracted images and procedural data from 317 consecutive colonoscopies. Images were anonymised and reviewed by four expert reviewers who scored their certainty that caecal intubation was achieved. Statistical analysis correlated adequately and inadequately photodocumented cases with polyp detection rate (PDR) and adenoma detection rate (ADR). RESULTS: The patients' mean age was 59.4 years and 52% were male. Eighty-one percent were performed by consultant endoscopists and 19% by specialist registrar. Sixty-five percent of these procedures were performed by gastroenterologists and 35% by surgical endoscopists. Fifty-three percent were deemed to have adequately demonstrated photographic evidence of caecal intubation. Statistical analysis comparing adequately and inadequately photodocumented cases: the PDR of procedures with confirmed caecal intubation was greater than procedures without photographic evidence (40% vs 34%). Similarly, the ADR of photographically confirmed cases was greater than that of inadequately photodocumented cases (25% vs 18%). The number of images taken per procedure positively correlated with photographic documentation of caecal intubation. CONCLUSION: While failing to reach statistical significance, there was a nominal difference in ADR and PDR demonstrated between the two groups, and with predominantly positive confidence intervals, this might suggest that a larger sample size could result in significance in favour of photodocumentation of caecal intubation. Future studies would be warranted. However, endoscopists that take more images were more likely to have proven caecal intubation.

D-lactic acidosis presenting as metabolic encephalopathy in a patient with short bowel syndrome.

We present a case of D-lactic acidosis presenting as a metabolic encephalopathy secondary to small intestinal bacterial overgrowth. This patient had a known history of short bowel syndrome. Of note, this case required the alteration of treatment to promote a sustained clinical and biochemical improvement. We discuss the pathophysiological mechanisms thought to be involved. We also review the current therapies as well as potential future strategies. This case highlights the importance of the prompt clinical recognition of signs and symptoms as well as the rapid initiation of management strategies to ameliorate this condition.

A case of human cystic echinococcosis acquired in Ireland.

Cystic echinococcosis (CE) is caused by the cestodes of the Echinococcus granulosus sensu lato complex and, in the majority of cases, is associated with hepatic or pulmonary involvement. Human CE is not thought to be endemic in Ireland. We describe the first reported case of human CE possibly acquired in Ireland.

Is Endoscopic Band Ligation a Superior Treatment Modality for Gastric Antral Vascular Ectasia Compared to Argon Plasma Coagulation?

BACKGROUND/AIMS: Gastric antral vascular ectasia (GAVE) is a rare acquired vascular lesion of the gastric antrum. The most frequent presentation of GAVE is iron deficiency anemia. Endoscopic therapy is the mainstay of treatment. However, there is no consensus regarding the optimal treatment modality. METHODS: A retrospective cohort study was performed on patients with GAVE, including patients receiving endoscopic therapy. Treatment was with either argon plasma coagulation (APC) or endoscopic band ligation (EBL). Basic demographic data, indication for index procedure, number of sessions, and pre- and post-hemoglobin levels were collected. The aim of the study was to compare outcomes across the two treatment modalities. RESULTS: One hundred and seventeen diagnoses of GAVE were made. Sixty-two patients (53%) required endoscopic treatment for symptomatic GAVE (female, n=38, 61%; mean age of 74.4 years). Two hundred and eighteen procedures were performed during the study period. APC was performed (n=161, 74%) more frequently than EBL (n=57, 26%). Patients treated with APC at index required a median 5 subsequent therapeutic interventions (APC or EBL), while those treated with EBL at index required a further 2.9 treatments (EBL only) (p<0.05). CONCLUSION: APC was the most common treatment modality employed. We demonstrate an increasing incidence of EBL. Patients treated with EBL at index treatment required fewer subsequent treatment sessions and had a greater mean rise in hemoglobin. This suggests a more effective endoscopic response with EBL.

Changes in alanine aminotransferase in adults with severe and complicated obesity during a milk-based meal replacement programme.

INTRODUCTION: Excess adiposity is associated with fat accumulation within the liver, and non-alcoholic steatohepatitis (NASH) is highly prevalent in bariatric patients. Elevated alanine aminotransferase (ALT) is associated with prevalent NASH. We sought to determine the influence of a milk-based meal replacement weight-loss programme on ALT levels in adults with severe and complicated obesity. METHODS: We conducted a retrospective cohort study of patients who completed a 24-week meal replacement programme, comprised of a weight loss phase followed by weight stabilisation and maintenance phases, each 8 weeks long. ALT was quantified using an enzymatic assay with spectrophotometric detection. We examined changes over time in ALT using the non-parametric Wilcoxon singed-rank test and the Friedman test. RESULTS: Of 105 patients, 56 were female, mean age was 51.2 ± 11.2 (range 18.0-71.6) years. There was an unanticipated but transient increase in ALT from 28.0 [20.0, 40.5] iu/L at baseline to 40.0 [26.0, 55.0] iu/L after 2 weeks (p < 0.0005), followed by a gradual reduction to 21.0 [17.0, 28.3] iu/L by 24 weeks (p < 0.0005). The overall reductions in ALT were more pronounced in patients who had elevated levels at baseline. Body weight decreased from 144.2 ± 28.0 kg at baseline to 121.6 ± 25.4 kg at 24 weeks (p < 0.0005) and body mass index (BMI) decreased from 50.7 ± 8.1 kg m-2 at baseline to 43.0 ± 7.6 kg m-2 by 24 weeks (p < 0.0005). CONCLUSION: In adults with severe and complicated obesity undergoing a milk-based meal replacement programme, there was an initial unanticipated rise in ALT in the first 2 weeks, followed by a gradual overall reduction by 24 weeks. These findings suggest that rapid weight loss secondary to significant caloric restriction might induce a transient deterioration in hepatic steatosis prior to an ultimate overall improvement.

Inflammatory Cutaneous Lesions in Inflammatory Bowel Disease Treated With Vedolizumab or Ustekinumab: An ECCO CONFER Multicentre Case Series.

This was a multicentre case series supported by the European Crohn's and Colitis Organisation [ECCO] and performed as part of the Collaborative Network of Exceptionally Rare case reports [CONFER] project. The aim was to report on whether cutaneous lesions associated with inflammatory bowel disease [IBD] and refractory to standard medical therapy including anti-tumour necrosis factors [anti-TNFs], would respond to the newer biologic agents ustekinumab [UST] or vedolizumab [VDZ]. This report includes 28 patients with cutaneous lesions from 14 centres, all of whom had failed immunomodulator and anti-TNF therapy. Metastatic Crohn's disease [MCD] was diagnosed in 10 patients: UST led to remission in five cases and partial response in four cases, with a single report of VDZ inducing remission. All cases of MCD treated with UST responded after the first or second dose, and the median time for the five cases that attained remission was 5 months. Pyoderma gangrenosum [PG] was diagnosed in four cases: three of these attained remission with UST [median time to remission 4 months] and one case did not respond to VDZ. There were seven cases of erythema nodosum [EN]: UST led to remission in four cases and partial response in 1 case whilst VDZ had partial response in 2 cases and non-response in two cases. There were seven single cases of other inflammatory lesions. In summary, UST appears to be useful for different cutaneous lesions including MCD, PG, and EN, whereas VDZ does not appear to be useful for lesions that are independent of disease activity.

Comparison of medium to long-term outcomes of acute severe ulcerative colitis patients receiving accelerated and standard infliximab induction.

INTRODUCTION: Accelerated dose infliximab (IFX) induction is associated with reduced short-term colectomy rate in acute severe ulcerative colitis (ASUC). Data on medium/long-term outcomes of this strategy are limited. AIMS: Evaluate medium/long-term outcomes in patients receiving IFX induction for ASUC, comparing accelerated dose (AD) and standard dose (SD) induction. METHODS: Retrospective study of consecutive patients admitted with corticosteroid-refractory ASUC in four tertiary referral centres within INITIative IBD research network (www.initiativeibd.ie). IFX rescue was given either as SD (weeks 0, 2, 6) or AD (<28 days) from January 2010 to September 2017. AD induction has been utilised in participating centres since 2014. Consequently SD patients were subdivided based on time period of IFX rescue: historical SD group (SD1) (2010-2013) and current SD group (SD2) (2014-2017). Primary endpoint was time to colectomy; secondary endpoint was time to IFX discontinuation if induction was complete. RESULTS: 145 patients received rescue IFX (AD=58, SD1=32, SD2=55). Disease severity at induction was comparable between AD and SD1 groups; however, SD2 group had less severe disease: median C-reactive protein (CRP) 39, 44 and 20 mg/L for AD, SD1 and SD2 groups, respectively (p=0.026, Kruskal-Wallis); median CRP: albumin ratio was 1.4, 1.8 and 0.6 (p=0.016). Median follow-up for AD, SD1 and SD2 groups was 1.6 (IQR 1.1-3.1), 4.9 (IQR 2.6-5.5) and 1.5 (IQR 0.9-2.3) years. Time to colectomy was shorter in SD1 (log rank p=0.0013); no significant difference in time to colectomy was observed comparing AD and SD2 groups (log rank p=0.32). 123 patients (84%) completed IFX induction and received maintenance therapy. Time to IFX discontinuation was shorter in SD1 (log rank p=0.009). CONCLUSION: Time to colectomy is significantly prolonged with use of AD IFX in selected ASUC patients with more severe disease. Historical use of standard IFX induction for all ASUC patients is associated with inferior long-term outcomes.

Golimumab effectiveness and safety in clinical practice for moderately active ulcerative colitis.

BACKGROUND AND AIMS: Golimumab (GLB) is an antitumour necrosis factor-α (anti-TNF) therapy that has shown efficacy as induction and maintenance therapy for ulcerative colitis (UC). We aimed to describe the outcome of GLB therapy for UC in a real-world clinical practice. PATIENTS AND METHODS: Consecutive patients receiving GLB for UC in six Irish Academic Medical Centres were identified. The primary study endpoint was the 6-month corticosteroid-free remission rate. The secondary endpoints included the 3-month clinical response, time free of GLB discontinuation and adverse events. RESULTS: Seventy-two patients were identified [57% men; median (range) age of 41.4 years (20.3-76.8); disease duration 6.6 years (0-29.9); follow-up 8.7 months (0.4-39.2)]. Sixty-four percent of patients were anti-TNF naive. The 3-month clinical response and the 6-month corticosteroid-free remission rates were 55 and 39%, respectively. Forty-four percent of patients discontinued GLB during the follow-up, median (95% confidence interval) time to GLB discontinuation 18.7 months (9.2-28.1). A C-reactive protein more than 5 mg/l at baseline was associated with failure to achieve 6-month corticosteroid-free remission and a shorter time to GLB discontinuation, odds ratio 0.2 (0.1-0.7), P=0.008, and hazard ratio (95% confidence interval) 2.8 (1.3-5.7), P=0.007, respectively. Adverse events occurred in 7% of patients (n=5), all of which were minor and self-limiting. CONCLUSION: These real-world clinical data suggest that GLB is an effective and safe therapy for a UC cohort with significant previous anti-TNF exposure. An elevated baseline C-reactive protein, likely reflective of increased inflammatory burden, is associated with a reduced likelihood of a successful outcome of GLB therapy.

Intravenous proton pump inhibitor use in hospital practice.

AIM: North American studies suggest that intravenous proton pump inhibitors are used inappropriately in hospital practice, but little is known of prescribing patterns in Europe. Our aim was to examine intravenous proton pump inhibitors prescribing in a single university teaching hospital. METHODS: Observational study of 101 consecutive hospital patients administered intravenous proton pump inhibitors over a 3-month period in a single hospital in Dublin, Ireland. Demographic, clinical, biochemical, haematological, endoscopic and follow-up data were collected and analysed. RESULTS: Sixty-five percent (65 of 101) of the patients had no objective evidence of gastrointestinal blood loss and 85 were haemodynamically stable before treatment. Two patients underwent endoscopic haemostasis before IV administration. The remaining 99 were treated for ulcer prophylaxis, presumed gastrointestinal haemorrhage, unrelated gastrointestinal conditions or for unknown reasons. Relatively senior nonconsultant staff prescribed intravenous therapy in most cases. Only six patients in the study were deemed to have received intravenous therapy for an appropriate indication. CONCLUSIONS: Intravenous proton pump inhibitors use in hospital practice is usually inappropriate. It may be that other valid indications exist within hospital practice, but these might reasonably be evaluated in randomized trials that would assess the risks and costs of intravenous treatments as well as their benefits.