Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Metabolomics as a tool to predict the risk of decompensation or liver-related death in patients with compensated cirrhosis.

BACKGROUND AND AIMS: Patients with compensated cirrhosis with clinically significant portal hypertension (CSPH: HVPG > 10 mm Hg) have a high risk of decompensation. HVPG is, however, an invasive procedure not available in all centers. The present study aims to assess whether metabolomics can improve the capacity of clinical models in predicting clinical outcomes in these compensated patients. APPROACH AND RESULTS: This is a nested study from the PREDESCI cohort (an RCT of nonselective beta-blockers vs. placebo in 201 patients with compensated cirrhosis and CSPH), including 167 patients for whom a blood sample was collected. A targeted metabolomic serum analysis, using ultra-high-performance liquid chromatography-mass spectrometry, was performed. Metabolites underwent univariate time-to-event cox regression analysis. Top-ranked metabolites were selected using Log-Rank p -value to generate a stepwise cox model. Comparison between models was done using DeLong test. Eighty-two patients with CSPH were randomized to nonselective beta-blockers and 85 to placebo. Thirty-three patients developed the main endpoint (decompensation/liver-related death). The model, including HVPG, Child-Pugh, and treatment received ( HVPG/Clinical model ), had a C-index of 0.748 (CI95% 0.664-0.827). The addition of 2 metabolites, ceramide (d18:1/22:0) and methionine (HVPG/Clinical/Metabolite model), significantly improved the model's performance [C-index of 0.808 (CI95% 0.735-0.882); p =0.032]. The combination of these 2 metabolites together with Child-Pugh and the type of treatment received (Clinical/Metabolite model) had a C-index of 0.785 (CI95% 0.710-0.860), not significantly different from the HVPG-based models including or not metabolites. CONCLUSIONS: In patients with compensated cirrhosis and CSPH, metabolomics improves the capacity of clinical models and achieves similar predictive capacity than models including HVPG.

Zenker's peroral endoscopic myotomy for management of large Zenker's diverticulum.

BACKGROUND: Zenker's diverticulum peroral endoscopic myotomy (zPOEM) is a minimally invasive treatment strategy for Zenker's diverticulum, with excellent results for management of small-to-moderate Zenker's diverticulum. We evaluated its use in the management of large Zenker's diverticulum. METHODS: This was a retrospective multicenter cohort study across 11 international centers including adult patients with large Zenker's diverticulum ≥ 40 mm treated by zPOEM between March 2017 and March 2022. The primary outcome was clinical success (dysphagia score ≤ 1 without need for further intervention). Secondary outcomes included technical success (complete myotomy as intended), adverse events (AEs), and rate of recurrence. RESULTS: 83 patients (male 62.7 %, mean age 72.6 [SD 11.5] years) underwent zPOEM for treatment of large Zenker's diverticulum (median size 50 mm, interquartile range [IQR] 41-55 mm, range 40-80 mm). The zPOEM procedure was technically successful in 82 patients (98.8 %), with a mean procedure time of 48.7 (SD 23.2) minutes. Clinical success was achieved in 71 patients (85.5 %). Median (IQR) symptom scores improved significantly from baseline for dysphagia (2 2 3 vs. 0 [0-2]; P < 0.001), regurgitation (3 2 3 4 vs. 0 [0-0]; P < 0.001), and respiratory symptoms (2 [0-3] vs. 0 [0-0]; P < 0.001). Among patients achieving clinical success, only one recurrence (1.4 %) was recorded during a median follow-up of 12.2 months (IQR 3-28). Post-procedure AEs, all mild to moderate, occurred in four patients (4.8 %). CONCLUSION: This study demonstrated safe and effective use of zPOEM in the management of large Zenker's diverticulum.

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

BACKGROUND & AIMS: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.

Angled-tip vs. straight-tip guidewire in ERCP: a randomized, multicenter study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the mainstay for interventional treatment of biliopancreatic diseases, and guidewires are decisive for successful treatment. METHODS: A randomized, multicenter, open-label study was conducted in patients in whom a guidewire was required in ERCP. Success rate and duration of the investigation were evaluated by randomly applying hydrophilic guidewires with a straight tip (ST) or an angled tip (AT) configuration, with normal (type NF) or enhanced (type EF) flexibility. Randomization was stratified by indication, i.e., stricture of the intra-hepatic bile ducts, stricture of the extrahepatic bile ducts, obstruction by bile duct stones, or interventions involving the pancreas. Cross-over was allowed if the initially allocated guidewire did not result in treatment success. RESULTS: Four hundred fifty-three patients were included, and 422 were finally analyzed. In 363 procedures (86%), the initially allocated wirés use resulted in treatment success. The success rate for using a guidewire with an angled tip configuration was 87.5 vs. 79.9% in a straight tip configuration (p = 0.049), and in negotiating an intrahepatic stricture the success rate was 90.7 vs. 69.1%, respectively (p = 0.008). No significant differences were observed in other indications. Procedural duration time did not differ in between the treatment groups. CONCLUSION: ERCP guidewires with an angled tip were more frequently successful when compared to straight tipped wires and most successful in treating intrahepatic strictures. Guidewires with standard vs. enhanced tip flexibility showed equal success rates in all indications.

Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends that patients with compensated advanced chronic liver disease (ACLD; due to viruses, alcohol, and/or nonobese [BMI < 30 kg/m2] nonalcoholic steatohepatitis) and clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] > 10 mmHg and/or liver stiffness by transient elastography > 25 kPa) should receive, if no contraindications, nonselective beta blocker (NSBB) therapy (preferably carvedilol) to prevent the development of variceal bleeding.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in those patients unable to receive NSBB therapy with a screening upper gastrointestinal (GI) endoscopy that demonstrates high risk esophageal varices, endoscopic band ligation (EBL) is the endoscopic prophylactic treatment of choice. EBL should be repeated every 2-4 weeks until variceal eradication is achieved. Thereafter, surveillance EGD should be performed every 3-6 months in the first year following eradication.Strong recommendation, moderate quality evidence. 3: ESGE recommends, in hemodynamically stable patients with acute upper GI hemorrhage (UGIH) and no history of cardiovascular disease, a restrictive red blood cell (RBC) transfusion strategy, with a hemoglobin threshold of ≤ 70 g/L prompting RBC transfusion. A post-transfusion target hemoglobin of 70-90 g/L is desired.Strong recommendation, moderate quality evidence. 4 : ESGE recommends that patients with ACLD presenting with suspected acute variceal bleeding be risk stratified according to the Child-Pugh score and MELD score, and by documentation of active/inactive bleeding at the time of upper GI endoscopy.Strong recommendation, high quality of evidence. 5 : ESGE recommends the vasoactive agents terlipressin, octreotide, or somatostatin be initiated at the time of presentation in patients with suspected acute variceal bleeding and be continued for a duration of up to 5 days.Strong recommendation, high quality evidence. 6 : ESGE recommends antibiotic prophylaxis using ceftriaxone 1 g/day for up to 7 days for all patients with ACLD presenting with acute variceal hemorrhage, or in accordance with local antibiotic resistance and patient allergies.Strong recommendation, high quality evidence. 7 : ESGE recommends, in the absence of contraindications, intravenous erythromycin 250 mg be given 30-120 minutes prior to upper GI endoscopy in patients with suspected acute variceal hemorrhage.Strong recommendation, high quality evidence. 8 : ESGE recommends that, in patients with suspected variceal hemorrhage, endoscopic evaluation should take place within 12 hours from the time of patient presentation provided the patient has been hemodynamically resuscitated.Strong recommendation, moderate quality evidence. 9 : ESGE recommends EBL for the treatment of acute esophageal variceal hemorrhage (EVH).Strong recommendation, high quality evidence. 10 : ESGE recommends that, in patients at high risk for recurrent esophageal variceal bleeding following successful endoscopic hemostasis (Child-Pugh C  ≤ 13 or Child-Pugh B > 7 with active EVH at the time of endoscopy despite vasoactive agents, or HVPG > 20 mmHg), pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) within 72 hours (preferably within 24 hours) must be considered.Strong recommendation, high quality evidence. 11 : ESGE recommends that, for persistent esophageal variceal bleeding despite vasoactive pharmacological and endoscopic hemostasis therapy, urgent rescue TIPS should be considered (where available).Strong recommendation, moderate quality evidence. 12 : ESGE recommends endoscopic cyanoacrylate injection for acute gastric (cardiofundal) variceal (GOV2, IGV1) hemorrhage.Strong recommendation, high quality evidence. 13: ESGE recommends endoscopic cyanoacrylate injection or EBL in patients with GOV1-specific bleeding.Strong recommendations, moderate quality evidence. 14: ESGE suggests urgent rescue TIPS or balloon-occluded retrograde transvenous obliteration (BRTO) for gastric variceal bleeding when there is a failure of endoscopic hemostasis or early recurrent bleeding.Weak recommendation, low quality evidence. 15: ESGE recommends that patients who have undergone EBL for acute EVH should be scheduled for follow-up EBLs at 1- to 4-weekly intervals to eradicate esophageal varices (secondary prophylaxis).Strong recommendation, moderate quality evidence. 16: ESGE recommends the use of NSBBs (propranolol or carvedilol) in combination with endoscopic therapy for secondary prophylaxis in EVH in patients with ACLD.Strong recommendation, high quality evidence.

Impact of prior treatment on feasibility and outcomes of Zenker's peroral endoscopic myotomy (Z-POEM).

BACKGROUND: Zenker's peroral endoscopic myotomy (Z-POEM) is a novel procedure for the management of symptomatic Zenker's diverticulum. This study aims to report the technical feasibility and outcomes of Z-POEM in the management of Zenker's diverticulum after prior failed interventions. METHODS: Patients with persistent or recurrent symptoms after prior endoscopic and/or surgical intervention for Zenker's diverticulum were retrospectively included. The primary outcome was clinical success, defined as complete or near complete resolution of dysphagia (dysphagia score of 0 or 1) without the need for repeat endoscopic or surgical intervention during follow-up. RESULTS: Z-POEM was technically successful in 30/32 patients (93.8 %). Clinical success was achieved in 29/30 patients (96.7 %), and Z-POEM significantly reduced the median (interquartile range [IQR]) dysphagia score of patients from 2 (1 - 2) to 0 (0) (P < 0.001) over a median duration of follow up of 166 days (IQR 39 - 566). Four patients (12.5 %) had adverse events (two inadvertent mucosotomies and two leaks found on post-procedural esophagrams). CONCLUSION: Z-POEM is feasible, safe, and effective in the majority of patients with recurrent symptoms after prior surgical or endoscopic interventions.

Management of patients after failed peroral endoscopic myotomy: a multicenter study.

BACKGROUND: Although peroral endoscopic myotomy (POEM) is highly effective for the management of achalasia, clinical failures may occur. The optimal management of patients who fail POEM is not well known. This study aimed to compare the outcomes of different management strategies in patients who had failed POEM. METHODS: This was an international multicenter retrospective study at 16 tertiary centers between January 2012 and November 2019. All patients who underwent POEM and experienced persistent or recurrent symptoms (Eckardt score > 3) were included. The primary outcome was to compare the rates of clinical success (Eckardt score ≤ 3) between different management strategies. RESULTS : 99 patients (50 men [50.5 %]; mean age 51.4 [standard deviation (SD) 16.2]) experienced clinical failure during the study period, with a mean (SD) Eckardt score of 5.4 (0.3). A total of 29 patients (32.2 %) were managed conservatively and 70 (71 %) underwent retreatment (repeat POEM 33 [33 %], pneumatic dilation 30 [30 %], and laparoscopic Heller myotomy (LHM) 7 [7.1 %]). During a median follow-up of 10 (interquartile range 3 - 20) months, clinical success was highest in patients who underwent repeat POEM (25 /33 [76 %]; mean [SD] Eckardt score 2.1 [2.1]), followed by pneumatic dilation (18/30 [60 %]; Eckardt score 2.8 [2.3]), and LHM (2/7 [29 %]; Eckardt score 4 [1.8]; P = 0.12). A total of 11 patients in the conservative group (37.9 %; mean Eckardt score 4 [1.8]) achieved clinical success. CONCLUSION : This study comprehensively assessed an international cohort of patients who underwent management of failed POEM. Repeat POEM and pneumatic dilation achieved acceptable clinical success, with excellent safety profiles.

Inflammation, Tumoral Markers and Interleukin-17, -10, and -6 Profiles in Pancreatic Adenocarcinoma and Chronic Pancreatitis.

BACKGROUND: Interleukin profiles can be used as biochemical markers regarding the early diagnosis of pancreatic cancer. AIMS: To assess CRP, CA 19-9, CEA levels, and interleukin-6, -10, and -17 profiles in pancreatic ductal adenocarcinoma, chronic pancreatitis was compared with a control group, and the correlation with pancreatic cancer survival. METHODS: A total of 87 patients were prospective divided in pancreatic cancer (n = 53), chronic pancreatitis (n = 22) ,and control group (n = 12). The diagnosis of PDAC was made histologically. The diagnosis of chronic pancreatitis was based on medical history, imaging methods, and endoscopic ultrasound. Systemic concentrations of interleukins were measured using ELISA kits. The patients were followed at 1, 3, and 6 months. RESULTS: CRP, CA 19-9, and CEA were higher in the pancreatic cancer group (p < 0.001). Interleukin-10 was significantly higher in the pancreatic cancer and chronic pancreatitis groups (p < 0.001). Interleukin-17 was statistically higher in the pancreatic cancer group (p < 0.0001). The cut-off of interleukin-17 of 0.273 had a sensitivity of 90.9 and a specificity of 80.9 with a curve under ROC of 0.80 in order to differentiate between pancreatic cancer and chronic pancreatitis. The serum levels of interleukins are not correlated with the stage of the disease. CRP, CA 19-9, CEA, and interleukin-6, -10, and -17 were lower in patients with survival more than 6 months. CONCLUSIONS: We detected high levels of interleukin-6, -10, and -17 in chronic pancreatitis and pancreatic cancer. Serum interleukin-17 levels can discriminate between pancreatic cancer and chronic pancreatitis. The prognostic role of interleukins needs to be established.

Preemptive-TIPS Improves Outcome in High-Risk Variceal Bleeding: An Observational Study.

Patients admitted with acute variceal bleeding (AVB) and Child-Pugh C score (CP-C) or Child-Pugh B plus active bleeding at endoscopy (CP-B+AB) are at high risk for treatment failure, rebleeding, and mortality. A preemptive transjugular intrahepatic portosystemic shunt (p-TIPS) has been shown to improve survival in these patients, but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high-risk patients. This multicenter, international, observational study included 671 patients from 34 centers admitted for AVB and high risk of treatment failure. Patients were managed according to current guidelines, and use of drugs and endoscopic therapy (D+E) or p-TIPS was based on individual center policy. p-TIPS in the setting of AVB is associated with a lower mortality in CP-C patients compared with D+E (1 year mortality 22% vs. 47% in D+E group; P = 0.002). Mortality rate in CP-B+AB patients was low, and p-TIPS did not improve it. In CP-C and CP-B+AB patients, p-TIPS reduced treatment failure and rebleeding (1-year cumulative incidence function probability of remaining free of the composite endpoint: 92% vs. 74% in the D+E group; P = 0.017) and development of de novo or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion: p-TIPS must be the treatment of choice in CP-C patients with AVB. Because of the strong benefit in preventing further bleeding and ascites, p-TIPS could be a good treatment strategy for CP-B+AB patients.

Liver Stiffness Assessed by Ultrasound Shear Wave Elastography from General Electric Accurately Predicts Clinically Significant Portal Hypertension in Patients with Advanced Chronic Liver Disease.

PURPOSE: Clinically significant portal hypertension (CSPH) is responsible for most of the complications in patients with cirrhosis. Liver stiffness (LS) measurement by vibration-controlled transient elastography (VCTE) is currently used to evaluate CSPH. Bi-dimensional shear wave elastography from General Electric (2D-SWE.GE) has not yet been validated for the diagnosis of PHT. Our aims were to test whether 2D-SWE.GE-LS is able to evaluate CSPH, to determine the reliability criteria of the method and to compare its accuracy with that of VCTE-LS in this clinical setting. MATERIALS AND METHODS: Patients with chronic liver disease referred to hepatic catheterization (HVPG) were consecutively enrolled. HVPG and LS by both VCTE and 2D-SWE.GE were performed on the same day. The diagnostic performance of each LS method was compared against HVPG and between each other. RESULTS: 2D-SWE.GE-LS was possible in 123/127 (96.90 %) patients. The ability to record at least 5 LS measurements by 2D-SWE.GE and IQR < 30 % were the only features associated with reliable results. 2D-SWE.GE-LS was highly correlated with HVPG (r = 0.704; p < 0.0001), especially if HVPG < 10 mmHg and was significantly higher in patients with CSPH (15.52 vs. 8.14 kPa; p < 0.0001). For a cut-off value of 11.3 kPa, the AUROC of 2D-SWE.GE-LS to detect CSPH was 0.91, which was not inferior to VCTE-LS (0.92; p = 0.79). The diagnostic accuracy of LS by 2D-SWE.GE-LS to detect CSPH was similar with the one of VCTE-LS (83.74 % vs. 85.37 %; p = 0.238). The diagnostic accuracy was not enhanced by using different cut-off values which enhanced the sensitivity or the specificity. However, in the subgroup of compensated patients with alcoholic liver disease, 2D-SWE.GE-LS classified CSPH better than VCTE-LS (93.33 % vs. 85.71 %, p = 0.039). CONCLUSION: 2D-SWE.GE-LS has good accuracy, not inferior to VCTE-LS, for the diagnosis of CSPH.

SRED-ARCE Recommendations for Minimally Invasive Interventions During the COVID-19 Pandemic in Romania.

The Romanian Society of Digestive Endoscopy (SRED) and the Romanian Association of Endoscopic Surgery (ARCE) have decided to establish a joint working group to elaborate specific recommendations for organizing the diagnostic and the minimally invasive interventional procedures, in the context of the COVID-19 pandemic. The recommendations are based on the guidelines of the international societies of endoscopy and gastroenterology (ESGE / BSG / ASGE / ACG / AGA), respectively endoscopic surgery (EAES SAGES) (4-8), on the experience of countries severely affected by the pandemic (Italy, France, Spain, USA, Germany, etc.) and they will be applied within the limits of measures imposed at local and governmental level by the competent authorities. On the other hand, these recommendations should have a dynamic evolution, depending on the upward or downward trend of the COVID-19 pandemic at regional and local level, but also according to the findings of professional and academic societies, requiring regular reviews based on the publica tion of further recommendations or international clinical trials. The objectives of the SRED and ARCE recommendations target the endoscopic and laparoscopic surgery activities, to support their non discriminatory used for diagnostic or therapeutic purposes, pursuing the demonstrated benefits of these procedures, in safe conditions for patients and medical staff.

Multicenter Evaluation of Clinical Efficacy and Safety of Per-oral Endoscopic Myotomy in Children.

OBJECTIVES: Per-oral endoscopic myotomy (POEM) is a recommended treatment modality for achalasia, but there is little published data for its use in children. The objective of the present study was to evaluate whether POEM is clinically effective and safe for children. METHODS: International multicenter retrospective study conducted in 14 tertiary centers that included consecutive children who underwent POEM between January 2012 and August 2018. Outcomes, such as clinical response were assessed whenever available. Adverse events and factors associated with clinical failure were also investigated. RESULTS: A total of 117 patients (mean ±â€ŠSD age: 14.2 ±â€Š3.7 years) underwent POEM for achalasia (type I, n = 36; type II n=66; type III, n=8). Among these, 30 (26%) were pretreated (botulinum injection and/or pneumatic dilatation). Mean ±â€ŠSD baseline Eckardt score was 7.5 ±â€Š2.0. Clinical success was achieved in 90.6% of cases (95%CI [83.8%;95.2%]) in the intention-to-treat analysis. The mean ±â€ŠSD Eckardt score post-POEM was 0.9 ±â€Š1.2 (P < 0.001). The mean duration of follow-up time 545 days (range: 100-1612). A total of 7 adverse events occurred (4 mucosotomies, 2 subcutaneous emphysema, 1 esopleural fistula). Gastroesophageal reflux symptoms were seen in 17 patients (15%); missing data for 10 patients (9%). There was a trend towards more frequent clinical failure in achalasia associated with genetic disorders (40% vs 8%, P = 0.069). CONCLUSIONS: POEM in pediatric patients appears to be effective and safe, although there was a trend towards more frequent clinical failure achalasia associated with genetic disorders. Further studies are needed to assess the long-term outcomes, especially the consequences of GERD.

Real-world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis.

BACKGROUND: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile. MATERIAL AND METHODS: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). RESULTS: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105 /mm3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). CONCLUSIONS: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count.

Barrett's Esophagus - State of the Art.

Barrett's Esophagus (BE) is defined as a premalignant condition, where the esophageal squamous epithelium is replaced by intestinal epithelium. Specialized intestinal columnar metaplasia, typical for Barrett's esophagus, does not generate any symptoms. Most of the patients are initially seen for symptoms associated with the gastroesophageal reflux disease (GERD), such as heartburn, regurgitation and dysphagia. The histological progression from intestinal metaplasia to dysplasia and then to BE-associated adenocarcinoma forms the argument for screening and endoscopic monitoring. The examination of Barrett's esophagus is controversial. Certain groups suggest a screening of the patients who exhibit more risk factors for the development of esophageal adenocarcinoma (for instance, gastroesophageal reflux disease, age 50, male, high body mass index with abdominal fat distribution). The main reason behind the treatment of acid reflux is that it may lead to chronic esophageal inflammation, which in its turn may predispose to the development of cancer.

Peroral Endoscopic Myotomy Versus Heller Myotomy for Achalasia: Pros and Cons.

Achalasia is an esophageal motor disorder that has multiple endoscopic and surgical methods of treatment. However, there is no consensus on optimal therapy in patients suffering from this disorder. This review discusses two therapies with similar but technically different concepts, peroral endoscopic myotomy and Heller surgical myotomy. After a brief introduction to the basic problems of achalasia, technical considerations, intra and postprocedural complications are presented and the advantages and disadvantages of the two procedures are discussed, based on the relevant articles in the literature. Heller surgical myotomy and peroral endoscopic myotomy appear to be similar in performance with similar results in terms of gastroesophageal reflux rates. However, with experience being gained in the field of endoscopic myotomy, this procedure seems more advantageous, with similar success rates to those of the established surgical technique, but offering shorter operating times, shorter hospitalizations and, ultimately, lower costs.

Zenker Diverticulum Treatment: Endoscopic or Surgical?

Introduction: The Zenker Diverticulum is a rare pathology, the selection of patients for invasive treatments is questionable, as well as the applied therapeutic method. The aim of the study is to evaluate the main methods of classical and endoscopic surgical treatment in this pathology and to correlate pathophysiological aspects with clinical consequences. MATERIAL AND METHOD: We included 36 patients with Zenker hypopharyngeal diverticulum treated in 2010/2017 in two university clinics: 7 patients by classical surgical approach at the General and Esophageal Surgery Clinic of St. Mary's Hospital Bucharest and 29 patients with endoscopic approach at Department of Diagnostic and Interventional Digestive Endoscopy of the Regional Institute of Hepatology and Gastroenterology Prof Dr Octavian Fodor, Cluj-Napoca. The age of the patients ranged from 42 to 84 years and in the 7th to 15th decade. Results: Cricopharyngeal myotomy was performed in all patients. Diverticullectomy was performed in 7 patients treated surgically. The average hospitalization duration was 4 days. Intra-procedural complications showed 3 patients treated endoscopically and consisted of laminar haemorrhage. Two patients were treated with endoscopic endoscopic hemostasis and hot pens and one patient had endoscopic hemostasis with clips. The post-procedural complications were: local pain, leukocytosis, melena, fever, cervical hematoma. These post-treatment events were seen in 6 patients. The posttreatment morbidity was 16.66%. Conclusions: In patients included in the batch, the endoscopic treatment efficiency was 80%. Peristent postinterventional symptomatology was mainly represented by dysphagia, post-procedural syndrome was associated with dysphagia persistence. Patients with persistent post-surgical symptoms were required to reintervention.

Non-invasive ménage à trois for the prediction of high-risk varices: stepwise algorithm using lok score, liver and spleen stiffness.

BACKGROUND & AIMS: Liver stiffness (LS), spleen stiffness (SS) and serum markers have been proposed to non-invasively assess portal hypertension or oesophageal varices (EV) in cirrhotic patients. We aimed to evaluate the performance of a stepwise algorithm that combines Lok score with LS and SS for diagnosing high-risk EV (HREV) and to compare it with other already-validated non-invasive methods. METHODS: We performed a cross-sectional study including 136 consecutive compensated cirrhotic patients with various aetiologies, divided into training (90) and validation (46) set. Endoscopy was performed within 6 months from inclusion for EV screening. Spleen diameter was assessed by ultrasonography. LS and SS were measured using Fibroscan. Lok score, platelet count/spleen diameter ratio, LSM-spleen diameter to platelet ratio score and oesophageal varices risk score (EVRS) were calculated and their diagnostic accuracy for HREV was assessed. The algorithm classified patients as having/not-having HREV. Its performance was tested and compared in both groups. RESULTS: In the training set, all variables could select patients with HREV with moderate accuracy, the best being LSPS (AUROC = 0.818; 0.93 sensitivity; 0.63 specificity). EVRS, however, was the only independent predictor of HREV (OR = 1.521; P = 0.032). The algorithm correctly classified 69 (76.66%) patients in the training set (P < 0.0001) and 36 (78.26%) in the validation one. In the validation group, the algorithm performed slightly better than LSPS and EVRS, showing 100% sensitivity and negative predicted value. CONCLUSION: The stepwise algorithm combining Lok score, LS and SS could be used to select patients at low risk of having HREV and who may benefit from more distanced endoscopic evaluation.

Intra-esophageal whitish mass - a challenging diagnosis.

BACKGROUND: Whitish intraluminal esophageal masses might represent the endoscopic feature of a bezoar or a pedunculated tumor, most likely a fibrovascular polyp, without exclusion of other mesenchymal tumors (leiomyoma, lipoma, gastrointestinal stromal tumor, leiomyosarcoma, granular cell tumor). If a process of dystrophic calcification is also encountered the differential diagnosis can be a challenge even after histological analysis, as it is highlighted by our case. CASE PRESENTATION: A 65-year-old female whom took lactate calcium tablets for 5 years presented with progressive dysphagia. A whitish esophageal mass with an appearance of a pharmacobezoar was detected at esophagoscopy. A pedunculated tumor was considered in the differential diagnosis, but the imagistic studies ruled out a pedicle. This intraluminal esophageal mass highly suggestive for a pharmacobezoar was endoscopically removed. The challenge of correct diagnosis was raised by histological examination performed after immersion into trichloracetic acid for decalcification. The identification of hyaline fibrous tissue, with numerous crystalline basophils deposits of minerals, rare fibrocytes and very few vessels brought in discussion a mesenchymal originating mass, most likely a fibrovascular polyp, even the pedicle was not detected. CONCLUSION: Based on our challenging and difficult to diagnose case we proposed an uncommon evolution: auto-amputation and calcification of an esophageal mesenchymal originating tumor (most likely a fibrovascular polyp).