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.)</p

Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease:An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

Introduction and Aims The DIPAK-1 Study investigates the reno-and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. Methods The DIPAK-1 Study is an ongoing investigatordriven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18-60 years, estimated glomerular filtration rate 30-60 mL/min/1.73 m(2)) were randomized 1: 1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. Results We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48-55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m(2) [interquartile range: 41-58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p <0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p <0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. Conclusions These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk-benefit ratio

Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

Introduction and Aims: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. Methods: The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18–60 years, estimated glomerular filtration rate 30–60 mL/min/1.73 m2) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. Results: We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48–55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m2 [interquartile range: 41–58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. Conclusions: These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk–benefit ratio. ClinicalTrials.gov identifier: NCT 01616927

Can we predict the future of patients with liver cirrhosis using volumetrics?

In the article on computed tomography (CT) volumetrics in liver cirrhosis Romero-Cristóbal et al. investigated the relationship between changes in liver-spleen volume and features of cirrhosis in patients with compensated or decompensated liver cirrhosis who either underwent liver transplantation or partial hepatectomy for hepatocellular carcinoma (HCC) The authors showed in this Spanish cross-sectional single center study that changes in liver volume, liver segmental volume ratio and liver-spleen volume ratio evaluated by CT reflected the course of disease progression through the different stages of liver cirrhosis. Specific changes in volumetrics appeared to be related to compensated cirrhosis, compensated cirrhosis with development of portal hypertension and decompensated liver cirrhosis. Interestingly, these changes were independent of the predictive value of histological level of liver fibrosis. The authors concluded that the observed changes in liver and spleen volumes correlate with the different clinical stages in the course of liver disease progression. In turn, this would suggest that CT volumetrics of liver and spleen could be a readily available non-invasive tool to provide prognostic information in cirrhotic patients. [...

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)

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

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

Management of renal cyst infection in patients with autosomal dominant polycystic kidney disease: A systematic review

Background. Renal cyst infection is one of the complications faced by patients with autosomal dominant polycystic kidney disease (ADPKD). Cyst infection is often difficult to treat and potentially leads to sepsis and death. No evidence-based treatment strategy exists. We therefore performed a systematic review to develop an effective approach for the management of renal cyst infection in ADPKD patients based on the literature. Methods. A systematic search was performed in PubMed (January 1948-February 2014), EMBASE (January 1974-February 2014) and the Cochrane Library (until February 2014) according to the PRISMA guidelines. Results. We identified 60 manuscripts that included 85 ADPKD patients with renal cyst infection (aged 52 6 12 years, 45% male, 27% on dialysis, 13% history of renal transplantation and 6% diabetes mellitus). Included patients received a total of 160 treatments of which 92 were antimicrobial, 29 percutaneous and 39 surgical. Initial management often consisted of antimicrobials (79%), and quinolone-based regimens were favoured (34%). Overall, 61% of patients failed initial treatment, but treatment failure has decreased over time (before the year 2000: 75%; during and after the year 2000: 51%, P = 0.03). Post-renal obstruction, urolithiasis, atypical or resistant pathogens, short duration of antimicrobial treatment and renal function impairment were documented in patients failing treatment. Conclusions. First-line treatment of renal cyst infection in ADPKD consists of antimicrobials and is associated with a high rate of failure, but treatment success has increased over recent years. A large-scale unbiased registry is needed to define the optimal strategy for renal cyst infection management in ADPKD