Clinical management of liver cyst infections: an international, modified Delphi-based clinical decision framework.

Liver cyst infections often necessitate long-term hospital admission and are associated with considerable morbidity and mortality. We conducted a modified Delphi study to reach expert consensus for a clinical decision framework. The expert panel consisted of 24 medical specialists, including 12 hepatologists, from nine countries across Europe, North America, and Asia. The Delphi had three rounds. The first round (response rate 21/24 [88%]) was an online survey with questions constructed from literature review and expert opinion, in which experts were asked about their management preferences and rated possible management strategies for seven clinical scenarios. Experts also rated 14 clinical decision-making items for relevancy and defined treatment outcomes. During the second round (response rate 13/24 [54%]), items that did not reach consensus and newly suggested themes were discussed in an online panel meeting. In the third round (response rate 16/24 [67%]), experts voted on definitions and management strategies using an online survey based on previous answers. Consensus was predefined as a vote threshold of at least 75%. We identified five subclassifications of liver cyst infection according to cyst phenotypes and patient immune status and consensus on episode definitions (new, persistent, and recurrent) and criteria for treatment success or failure was reached. The experts agreed that fever and elevated C-reactive protein are pivotal decision-making items for initiating and evaluating the management of liver cyst infections. Consensus was reached on 26 management statements for patients with liver cyst infections across multiple clinical scenarios, including two treatment algorithms, which were merged into one after comments. We provide a clinical decision framework for physicians managing patients with liver cyst infections. This framework will facilitate uniformity in the management of liver cyst infections and can constitute the basis for the development of future guidelines.

Unraveling factors associated with textbook outcome after cholecystectomy in patients with uncomplicated cholecystolithiasis: A posthoc analysis of individual data of 1,124 patients.

BACKGROUND: A textbook outcome for the management of uncomplicated cholecystolithiasis is the targeted clinical scenario and is characterized by no recurrent biliary colic, absence of surgical and biliary complications, and absence or relief of abdominal pain. The aim of this study was to assess the incidence of textbook outcomes after cholecystectomy and identify associated baseline factors. METHODS: Patients from 2 Dutch multicenter prospective trials between 2014 and 2019 (SECURE and SUCCESS trial) were included. The primary outcome was the proportion of patients with textbook outcomes after cholecystectomy at 6-month follow-up. Regression analysis was used to identify which factors before surgery were associated with textbook outcomes. RESULTS: A total of 1,124 patients underwent cholecystectomy. A textbook outcome at 6-month follow-up was reached in 67.9% of patients. Persistent abdominal pain was the main reason for the failure to achieve textbook outcome. Patients who did achieve textbook outcomes more often reported severe pain attacks (89.4% vs 81.7%, P < .001) and/or biliary colic (78.6% vs 68.4%, P < .001) at baseline compared with patients without textbook outcomes. The presence of biliary colic at baseline (odds ratio = 1.56, 95% confidence interval: 1.16-2.09, P = .003) and nausea/vomiting at baseline (odds ratio = 1.33, 95% confidence interval: 1.01-1.74, P = .039) were associated with textbook outcome. The use of non-opioid analgesics (odds ratio = 0.76, 95% confidence interval: 0.58-0.99, P = .043) and pain frequency ≥1/month (odds ratio = 0.56, 95% confidence interval: 0.43-0.73, P < .001) were negatively associated with textbook outcome. CONCLUSION: Textbook outcome is achieved in two-thirds of patients who undergo cholecystectomy for uncomplicated cholecystolithiasis. Intensity and frequency of pain, presence of biliary colic, and nausea/vomiting at baseline are independently associated with achieving textbook outcomes. A more stringent selection of patients may optimize the textbook outcome rate in patients with uncomplicated cholecystolithiasis.

Multisegmented esophageal fully covered self-expandable metal stent for palliation of malignant dysphagia: a prospective, multicenter feasibility and safety study.

BACKGROUND AND AIMS: A novel multisegmented esophageal fully covered self-expandable metal stent (FCSEMS) was designed to reduce stent migration, which is seen in up to 30% of patients. The goal of this study was to evaluate the safety and efficacy of the multisegmented FCSEMS. METHODS: This multicenter prospective study aimed to include 30 patients undergoing palliative stent placement. Efficacy, defined as technically successful stent placement and dysphagia scores, and safety, defined as the number of adverse events (AEs) and serious AEs (SAEs), were measured. RESULTS: The study was prematurely terminated due to safety concerns after including 23 patients (mean ± standard deviation age, 72 ± 10 years; 78% male). Stent placement was technically successful in 21 patients (91%), and dysphagia scores had improved in all patients with successful stent placement. SAEs were reported in 16 (70%) patients. Stent-related mortality occurred in 3 patients (13%). CONCLUSIONS: The multisegmented FCSEMS successfully treated malignant dysphagia. The study was prematurely terminated, however, because stent placement was associated with a relatively high SAE rate. (Clinical trial registration number: NCT04415463.).

Persistent and new-onset symptoms after cholecystectomy in patients with uncomplicated symptomatic cholecystolithiasis: A post hoc analysis of 2 prospective clinical trials.

BACKGROUND: Laparoscopic cholecystectomy is the gold standard for treating biliary colic in patients with gallstones, but post-cholecystectomy abdominal pain is commonly reported. This study investigates which symptoms are likely to persist and which may develop after a cholecystectomy. METHODS: Patients from 2 previous prospective trials who underwent laparoscopic cholecystectomy for symptomatic cholecystolithiasis were included. Patients completed questionnaires on pain and gastrointestinal symptoms before surgery and at 6 months follow-up. The prevalence of persistent and new-onset abdominal symptoms was evaluated. RESULTS: A total of 820 patients received cholecystectomy and were included, 75.4% female (n = 616/820) mean age 49.4 years (standard deviation 13.7). At baseline, 74.1% (n = 608/820) of patients met all criteria for biliary colic. Cholecystectomy successfully resolved biliary colic in 94.8% (n = 327/345) of patients, but 36.5% (n = 299/820) of patients reported persistent abdominal pain after 6 months of follow-up. The prevalence of most abdominal symptoms reduced significantly. Symptoms such as flatulence (17.8%, n = 146/820) or restricted eating (14.5%, n = 119/820) persisted most often. New-onset symptoms were frequent bowel movements (9.6%, n = 79/820), bowel urgency (8.5%, n = 70/820), and new-onset diarrhea (8.4%, 69/820). CONCLUSION: Postcholecystectomy symptoms are mainly flatulence, frequent bowel movements, and restricted eating. Newly reported symptoms are mainly frequent bowel movements, bowel urgency, and diarrhea. The present findings give clinical guidance in informing, managing, and treating patients with symptoms after cholecystectomy.

A mixed-methods study to define Textbook Outcome for the treatment of patients with uncomplicated symptomatic gallstone disease with hospital variation analyses in Dutch trial data.

BACKGROUND: International consensus on the ideal outcome for treatment of uncomplicated symptomatic gallstone disease is absent. This mixed-method study defined a Textbook Outcome (TO) for this large group of patients. METHODS: First, expert meetings were organised with stakeholders to design the survey and identify possible outcomes. To reach consensus, results from expert meetings were converted in a survey for clinicians and for patients. During the final expert meeting, clinicians and patients discussed survey outcomes and a definitive TO was formulated. Subsequently, TO-rate and hospital variation were analysed in Dutch hospital data from patients with uncomplicated gallstone disease. RESULTS: First expert meetings returned 32 outcomes. Outcomes were distributed in a survey among 830 clinicians from 81 countries and 645 Dutch patients. Consensus-based TO was defined as no more biliary colic, no biliary and surgical complications, and the absence or reduction of abdominal pain. Analysis of individual patient data showed that TO was achieved in 64.2% (1002/1561). Adjusted-TO rates showed modest variation between hospitals (56.6-74.9%). CONCLUSION: TO for treatment of uncomplicated gallstone disease was defined as no more biliary colic, no biliary and surgical complications, and absence or reduction of abdominal pain.TO may optimise consistent outcome reporting in care and guidelines for treating uncomplicated gallstone disease.

Patients with Clinically Suspected Gallstone Disease: A More Selective Ultrasound May Improve Treatment Related Outcomes.

This study aimed to quantify the confirmation of gallstones on ultrasound (US) in patients with suspicion of gallstone disease. To aid general practitioners (GPs) in diagnostic workup, a model to predict gallstones was developed. A prospective cohort study was conducted in two Dutch general hospitals. Patients (≥18 years) were eligible for inclusion when referred by GPs for US with suspicion of gallstones. The primary outcome was the confirmation of gallstones on US. A multivariable regression model was developed to predict the presence of gallstones. In total, 177 patients were referred with a clinical suspicion of gallstones. Gallstones were found in 64 of 177 patients (36.2%). Patients with gallstones reported higher pain scores (VAS 8.0 vs. 6.0, p < 0.001), less frequent pain (21.9% vs. 54.9%, p < 0.001), and more often met criteria for biliary colic (62.5% vs. 44.2%, p = 0.023). Predictors for the presence of gallstones were a higher pain score, frequency of pain less than weekly, biliary colic, and an absence of heartburn. The model showed good discrimination between patients with and without gallstones (C-statistic 0.73, range: 0.68-0.76). Clinical diagnosis of symptomatic gallstone disease is challenging. The model developed in this study may aid in the selection of patients for referral and improve treatment related outcomes.

Spleen Stiffness Measurement Across the Spectrum of Liver Disease Patients in Real-World Practice.

Objectives: Spleen stiffness measurement (SSM) provides a non-invasive surrogate marker for clinical significant portal hypertension (CSPH). Results obtained in highly selected populations were promising but require validation across the spectrum of liver disease. We aimed to investigate the clinical applicability of SSM in a real-world setting. Methods: We prospectively enrolled patients referred for liver ultrasound (January-May 2021). Patients with a portosystemic shunt, liver transplant, or extrahepatic etiology of portal hypertension were excluded. We performed liver ultrasound, liver stiffness measurement (LSM) and SSM (dedicated software, 100 Hz-probe). Probable CSPH was established if ≥1 of the following items occurred: ascites, varices, encephalopathy, splenomegaly, recanalized umbilical vein, collaterals, dilated portal veins, hypertensive gastropathy, or LSM ≥25 kPa. Results: We enrolled 185 patients (53% male; age 53years [37-64], 33% viral hepatitis, 21% fatty liver disease). Of them, 31% of patients had cirrhosis (68% Child-Pugh A) and 38% of patients had signs of portal hypertension. SSM (23.8 kPa [16.2-42.3]) and LSM (6.7 kPa [4.6-12.0]) were successful and met reliability criteria in 70% and 95%, respectively. Spleen size was inversely associated with SSM failure (odds ratio: 0.66 increment/cm, 95% confidence interval: 0.52-0.82). Optimal spleen stiffness cut-off to detect probable CSPH was >26.5 kPa (likelihood ratio: 4.5, sensitivity: 83%; specificity: 82%). Spleen stiffness did not outperform liver stiffness in detecting probable CSPH (P = 1.0). Conclusions: In real-world practice, reliable SSM were obtained in 70% and could potentially stratify patients between high- and low-risk of probable CSPH. However, cut-offs for CSPH might be substantially lower than previously reported. Future studies validating these results are required. Clinical trial number: Netherlands Trial Register (Registration number: NL9369).

Functional Dyspepsia and Irritable Bowel Syndrome are Highly Prevalent in Patients With Gallstones and Are Negatively Associated With Outcomes After Cholecystectomy: A Prospective, Multicenter, Observational Study (PERFECT - Trial).

OBJECTIVE: To determine the prevalence of FD and IBS in patients eligible for cholecystectomy and to investigate the association between presence of FD/ IBS and resolution of biliary colic and a pain-free state. SUMMARY BACKGROUND DATA: More than 30% of patients with symptomatic cholecystolithiasis reports persisting pain postcholecystectomy. Coexistence of FD/IBS may contribute to this unsatisfactory outcome. METHODS: We conducted a multicenter, prospective, observational study (PERFECT-trial). Patients ≥18 years with abdominal pain and gallstones were included at 5 surgical outpatient clinics between 01/2018 and 04/2019. Follow-up was 6 months. Primary outcomes were prevalence of FD/IBS, and the difference between resolution of biliary colic and pain-free state in patients with and without FD/IBS. FD/IBS was defined by the Rome IV criteria, biliary colic by the Rome III criteria, and pain-free by an Izbicki Pain Score ≤10 and visual analogue scale ≤4. RESULTS: We included 401 patients with abdominal pain and gallstones (assumed eligible for cholecystectomy), mean age 52 years, 76% females. Of these, 34.9% fulfilled criteria for FD/IBS. 64.1% fulfilled criteria for biliary colic and 74.9% underwent cholecystectomy, with similar operation rates in patients with and without FD/IBS. Postcholecystectomy, 6.1% of patients fulfilled criteria for biliary colic, with no significant difference between those with and without FD/IBS at baseline (4.9% vs 8.6%, P = 0.22). Of all patients, 56.8% was pain-free after cholecystectomy, 40.7% of FD/IBS-group vs 64.4% of no FD/IBS-group, P < 0.001. CONCLUSIONS: One third of patients eligible for cholecystectomy fulfil criteria for FD/IBS. Biliary colic is reported by only a few patients postcholecys-tectomy, whereas nonbiliary abdominal pain persists in >40%, particularly in those with FD/IBS precholecystectomy. Clinicians should take these symptom-dependent outcomes into account in their shared decision-making process. TRIAL REGISTRATION: The Netherlands Trial Register NTR-7307. Registered on 18 June 2018.

Web-Based Educational Intervention for Patients With Uninvestigated Dyspepsia Referred for Upper Gastrointestinal Tract Endoscopy: A Randomized Clinical Trial.

Importance: Diagnostic yield of upper gastrointestinal (GI) tract endoscopy for uninvestigated dyspepsia is low, and its clinical implications are limited. There is an unmet need for better strategies to reduce the volume of upper GI tract endoscopic procedures for dyspepsia. Objective: To study the effectiveness of a web-based educational intervention as a tool to reduce upper GI tract endoscopy in uninvestigated dyspepsia. Design, Setting, and Participants: This open-label, multicenter, randomized clinical trial enrolled participants between November 1, 2017, and March 31, 2019, with follow-up 52 weeks after randomization, at 4 teaching hospitals in the Netherlands. Participants included patients with uninvestigated dyspeptic symptoms who were referred for upper GI tract endoscopy by their general health care clinician without prior consultation of a gastroenterologist. A total of 119 patients, aged 18 to 69 years, were included. Patients were excluded if any of the following red flag symptoms were present: (indirect) signs of upper GI tract hemorrhage (hematemesis, melena, hematochezia, or anemia), unintentional weight loss of 5% or higher of normal body weight during a period of 6 to 12 months, persistent vomiting, dysphagia, or jaundice. Interventions: Patients were randomly assigned (1:1) to education (intervention) or upper GI tract endoscopy (control). Education consisted of a self-managed web-based educational intervention, containing information on gastric function, dyspepsia, and upper GI tract endoscopy. Main Outcomes and Measures: Difference in the proportion of upper GI tract endoscopy procedures between those who received access to the web-based educational intervention and those who did not at 12 weeks and 52 weeks after randomization, analyzed in the intention-to-treat population. Secondary outcomes included quality of life (Nepean Dyspepsia Index) and symptom severity (Patient Assessment of Gastrointestinal Disorders Symptom Severity Index) measured at baseline and 12 weeks. Results: Of 119 patients included (median age, 48 years [interquartile range, 37-56 years]; 48 men [40%]), 62 were randomized to web-based education (intervention) and 57 to upper GI tract endoscopy (control). Significantly fewer patients compared with controls underwent upper GI tract endoscopy after using the web-based educational intervention: 24 (39%) vs 47 (82%) (relative risk, 0.46; 95% CI, 0.33-0.64; P < .001). Symptom severity and quality of life improved equivalently in both groups. One additional patient in the intervention group required upper GI tract endoscopy during follow-up. Conclusions and Relevance: Findings of this study indicate that web-based patient education is an effective tool to decrease the need for upper GI tract endoscopy in uninvestigated dyspepsia. Trial Registration: ClinicalTrials.gov Identifier: NCT03205319.

The yield of upper gastrointestinal endoscopy in patients below 60 years and without alarm symptoms presenting with dyspepsia.

BACKGROUND AND AIMS: Upper gastrointestinal (GI) endoscopy is frequently performed in patients with upper abdominal symptoms. Although guidelines recommend withholding an endoscopy in the absence of alarm symptoms, dyspeptic symptoms remain a predominant indication for endoscopy. We aimed to investigate the yield of upper GI endoscopy in patients with low-risk dyspeptic symptoms. METHODS: We conducted an analysis in a prospectively maintained endoscopy reporting database. We collected the results of all upper GI endoscopy procedures between 2015 and 2019 that was performed in adult patients aged <60 years with dyspeptic symptoms. Patients with documented alarm symptoms were excluded. We categorized endoscopic findings into major and minor endoscopic findings. RESULTS: We identified 26,440 patients with dyspeptic symptoms who underwent upper GI endoscopy. A total of 13,978 patients were considered low-risk and included for analysis (median age 46 years, interquartile range (IQR) [36-53], 62% female). In 11,353 patients (81.2%), no endoscopic abnormalities were detected. Major endoscopic findings were seen in 513 patients (3.7%) and minor endoscopic findings in 2178 patients (15.6%). Endoscopic findings indicative of upper GI cancer were reported in 47 patients (0.3%), including 16 (0.1%) oesophageal, 28 (0.2%) gastric and 5 (0.04%) duodenal lesions. Despite an initial unremarkable endoscopy result, 1015 of 11,353 patients (8.9%) underwent a follow-up endoscopy after a median of 428 days [IQR 158-819]. This did not lead to the additional identification of malignancy. CONCLUSIONS: The yield of upper GI endoscopy in low-risk (<60 years, no alarm symptoms) patients with dyspepsia is very limited. This study further supports a restrictive use of upper GI endoscopy in these patients.

Clinical Outcomes of Covid-19 in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study.

BACKGROUND AND AIMS: The COVID-19 risk and disease course in inflammatory bowel disease [IBD] patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease course, and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population. METHODS: We conducted a multicentre, nationwide IBD cohort study in The Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population. RESULTS: We established an IBD cohort of 34 763 patients. COVID-19 was diagnosed in 100/34 763 patients [0.29%]; 20/100 of these patients [20%] had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalisation occurred in 59/100 [59.0%] patients and 13/100 [13.0%] died. All patients who died had comorbidities and all but one were ≥65 years old. In line, we identified ≥1 comorbidity as an independent risk factor for hospitalisation (odds ratio [OR] 4.20, 95% confidence interval [CI] 1.58-11.17,; p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 [95% CI 236.6-349.7] versus 333.0 [95% CI 329.3-336.7] per 100000 patients, respectively; p = 0.15). CONCLUSIONS: Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% were hospitalised and 13% died. A comparable COVID-19 risk was found between the IBD cohort [100/34 763 = 0.29%] and the general Dutch population. The presence of ≥1 comorbidities was an independent risk factor for hospitalisation due to COVID-19.

Impact of the COVID-19 pandemic on gastrointestinal endoscopy in the Netherlands: analysis of a prospective endoscopy database.

BACKGROUND: COVID-19 has dramatically affected gastrointestinal endoscopy practice. We aimed to investigate its impact on procedure types, indications, and findings. METHODS: We retrospectively analyzed endoscopies performed in 15 Dutch hospitals by comparing periods 15 March to 25 June of 2019 and 2020 using the prospective Trans.IT database. RESULTS: During lockdown in 2020, 9776 patients underwent endoscopy compared with 19 296 in 2019. Gastroscopies decreased by 57 % (from 7846 to 4467) and colonoscopies by 45 % (from 12219 to 5609), whereas endoscopic retrograde cholangiopancreatography volumes remained comparable (from 578 to 522). Although endoscopy results indicative of cancer decreased (from 524 to 340), the likelihood of detecting cancer during endoscopy increased (2.7 % [95 % confidence interval (CI) 2.5 - 3.0] in 2019 versus 3.5 % [95 %CI 3.1 - 3.9] in 2020; P < 0.001). After lifting of lockdown, endoscopy volumes started to return to normal, except for colorectal cancer screening. CONCLUSIONS: Fewer endoscopies were performed during the COVID-19 lockdown, leading to a significant reduction in the absolute detection of cancer. Endoscopies increased rapidly after lockdown, except for colorectal cancer screening.

Systematic review with meta-analysis: age-related malignancy detection rates at upper gastrointestinal endoscopy.

BACKGROUND: Age is an important and objective risk factor for upper gastrointestinal (GI) malignancy. The accuracy of various age limits to detect upper GI malignancy is unclear. Determination of this accuracy may aid in the decision to refer symptomatic patients for upper GI endoscopy. The aim of this analysis was to synthesize data on upper GI malignancy detection rates for various age limits worldwide through meta-analysis. METHODS: We searched MEDLINE, EMBASE, and Web of Science in November 2018. Selection criteria included studies addressing malignant findings at upper GI endoscopy in a symptomatic population reporting age at time of diagnosis. Meta-analyses were conducted to derive continent-specific cancer detection rates. RESULTS: A total of 33 studies including 346,641 patients across 21 countries fulfilled the inclusion criteria. To detect >80% of malignant cases all symptomatic patients over 40 years of age should be investigated in Africa, over 50 years of age in South America and Asia, and over 55 years of age in North America and Europe. CONCLUSION: This systematic review and meta-analysis provides data on intercontinental variation in age at time of upper GI malignancy diagnosis in symptomatic patients referred for upper GI endoscopy. Guideline recommendations for age-based selection should be tailored to local age-related detection rates.

Efficacy and safety of selective decontamination of the digestive tract (SDD) to prevent recurrent hepatic cyst infections in polycystic liver disease: a retrospective case series.

BACKGROUND: Hepatic cyst infection is a complication of polycystic liver disease (PLD) that causes substantial morbidity. Repetitive infection is frequent and is increasingly difficult to treat. As translocated gut bacteria are considered the cause, we hypothesize that selective decontamination of the digestive tract (SDD) reduces recurrence of hepatic cyst infection. METHODS: We performed a retrospective, observational study in two referral centres. All patients with PLD treated with SDD for hepatic cyst infection were included. Efficacy was determined by calculating the infection incidence (hepatic cyst infections per month) before and during SDD therapy. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: We identified eight patients who received SDD (88% female, 88% polycystic kidney disease). The median age was 65 years (IQR: 51-74 years). SDD lowered the median incidence from 0.09 episodes per month (IQR: 0.06-0.25 episodes per month) to 0.01 episodes per month (IQR: 0.00-0.05 episodes per month) (P = 0.12). Discontinuation of SDD led to rapid recurrence of cyst infection (71% within 6 weeks). SDD consisted of polymyxins with/without aminoglycosides. The median SDD treatment duration was 20 months (range: 3-89 months). Six patients (75%) developed adverse events [CTCAE Grade 1 (gastrointestinal: n = 3) or Grade 3 (ototoxicity: n = 1; fungal infection: n = 1)], mostly attributable to aminoglycosides; one patient developed polymyxin E resistance. CONCLUSIONS: SDD prophylaxis provides a novel strategy for limiting recurrent hepatic cyst infection in PLD patients. However, adverse events are frequent and curtail its use. As most were attributable to aminoglycosides, polymyxin E is considered the preferred therapy.

The Dyspepsia Educational Tool As a Novel Aid in Dyspepsia Management.

Digital educational tools have a well-established role in current healthcare. In particular, disorders that are managed non-pharmacologically benefit from this development, as it enables patient engagement in self-management. Dyspepsia is a condition thought to arise from gastric and duodenal perturbations, brain-gut axis disturbances, and dietary factors. Behavioral interventions are a major part of dyspepsia treatment, hence patient engagement and motivation through education is essential. Protocols that describe the development process of such educational tools are scarce. We provide a methodology describing development of a dyspepsia educational tool. Assessment of users' needs is the first step, followed by a literature search. The content is developed based on the main themes and entered into a content management system, to build the program. Final adjustments are made after a pilot test of the tool. The presented protocol can be used as a guide for development of a digital dyspepsia educational tool or as a tool for similar situations.