Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. METHODS: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. RESULTS: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07). CONCLUSIONS: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

Training in basic gastrointestinal endoscopic procedures: a European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) Position Statement.

This ESGE Position Statement provides structured and evidence-based guidance on the essential requirements and processes involved in training in basic gastrointestinal (GI) endoscopic procedures. The document outlines definitions; competencies required, and means to their assessment and maintenance; the structure and requirements of training programs; patient safety and medicolegal issues. 1: ESGE and ESGENA define basic endoscopic procedures as those procedures that are commonly indicated, generally accessible, and expected to be mastered (technically and cognitively) by the end of any core training program in gastrointestinal endoscopy. 2: ESGE and ESGENA consider the following as basic endoscopic procedures: diagnostic upper and lower GI endoscopy, as well as a limited range of interventions such as: tissue acquisition via cold biopsy forceps, polypectomy for lesions ≤ 10 mm, hemostasis techniques, enteral feeding tube placement, foreign body retrieval, dilation of simple esophageal strictures, and India ink tattooing of lesion location. 3: ESGE and ESGENA recommend that training in GI endoscopy should be subject to stringent formal requirements that ensure all ESGE key performance indicators (KPIs) are met. 4: Training in basic endoscopic procedures is a complex process and includes the development and acquisition of cognitive, technical/motor, and integrative skills. Therefore, ESGE and ESGENA recommend the use of validated tools to track the development of skills and assess competence. 5: ESGE and ESGENA recommend incorporating a multimodal approach to evaluating competence in basic GI endoscopic procedures, including procedural thresholds and the measurement and documentation of established ESGE KPIs. 7: ESGE and ESGENA recommend the continuous monitoring of ESGE KPIs during GI endoscopy training to ensure the trainee's maintenance of competence. 9: ESGE and ESGENA recommend that GI endoscopy training units fulfil the ESGE KPIs for endoscopy units and, furthermore, be capable of providing the dedicated personnel, infrastructure, and sufficient case volume required for successful training within a structured training program. 10: ESGE and ESGENA recommend that trainers in basic GI endoscopic procedures should be endoscopists with formal educational training in the teaching of endoscopy, which allows them to successfully and safely teach trainees.

Assessing the impact of center volume on the cost-effectiveness of centralizing ERCP.

BACKGROUND AND AIMS: ERCP is a complex endoscopic procedure in which the center's procedure volume influences outcomes. With the increasing healthcare expenses and limited resources, promoting cost-effective care becomes essential for healthcare provision. This study performed a cost-effectiveness analysis to evaluate the hypothesis that high-volume (HV) centers perform ERCP with higher quality at lower costs than low-volume (LV) centers. METHODS: A baseline case compared the current distribution of ERCPs among HV and LV centers with a hypothetical scenario in which all ERCPs are performed at HV centers. A cost-effectiveness analysis was constructed, followed by one-way and two-way sensitivity analyses and probabilistic sensitivity analysis (PSA) using Monte Carlo simulations. RESULTS: In the baseline case, the ICER was -141,017€/year, due to the hypothetical scenario's lower costs and slightly higher QALYs. The model was most sensitive to changes in the transportation costs (109.34%), probability of significant adverse events (AEs) after successful ERCP at LV centers (42.12%), utility after ERCP with significant AEs (30.10%), and probability of significant AEs after successful ERCP at HV centers (23.53%) but only transportation cost above 3,407€ changed the study outcome. The current ERCP distribution would only be cost-effective if LV centers achieved higher success (≥ 92.4% vs. 89.3%) with much lower significant AEs (≤ 0.5% vs 6.7%). The study's main findings remained unchanged while combining all model parameters in the PSA. CONCLUSIONS: Our findings show that HV centers have high-performance rates at lower costs, raising the need to consider the principle of centralization of ERCPs into HV centers to improve the quality of care.

Face and content validity of a biological papilla designed for the Boskoski-Costamagna ERCP simulator.

BACKGROUND AND AIMS: A biological papilla made of chicken heart tissue, incorporated into the Boskoski-Costamagna ERCP Trainer simulator, was recently designed to allow training in sphincterotomy. This study aimed to evaluate the face and content validity of this tool. METHOD: Participants from 2 groups (nonexperienced and experienced [<600 or >600 lifetime ERCPs, respectively]) were invited to perform standardized assignments on the model: sphincterotomy and precut for both groups and papillectomy for the experienced group. Following these assignments, all participants filled out a questionnaire to rate their appreciation of the realism of the model, and experienced endoscopists were also asked to evaluate its didactic value using a 5-point Likert scale. RESULTS: A total of 19 participants were included (nonexperienced, n = 10; experienced, n = 9). Parameters regarding the realism of the tool in terms of general appearance, sphincterotomy, precut, and papillectomy were overall considered realistic (4 of 5), with good agreement rates in terms of overall realism between groups. Experienced operators reported the highest realism for "positioning the scope and needle-knife in the field of view" and "during precut," "cutting in small increments during precut," and "controlling the scope during papillectomy," and they highly agreed that this papilla should be included for training novice and intermediate trainees in sphincterotomy, precut, and papillectomy. CONCLUSIONS: Our results show good face validity and excellent content validity of this biological papilla combined with the Boskoski-Costamagna ERCP Trainer. This new tool provides a useful, inexpensive, versatile, and easy tool for training regarding sphincterotomy, precut, and papillectomy. Future studies should explore whether including this model in real-life training improves the learning curve of endoscopy trainees.

A simple clinical score to stratify the risk of procedure-related adverse events in ERCP procedures with trainee involvement.

BACKGROUND : Optimal training strategies in endoscopic retrograde cholangiopancreatography (ERCP) remain controversial despite the shift toward competence-based training models, with limited data available on patient safety during training. We aimed to assess whether pre-procedural clinical predictors could identify patients at low risk of developing procedure-related adverse-events (AEs) in a training environment. METHODS : We performed a prospective, multicenter, cohort study in five training centers. A data collection system documenting indication, clinical data, trainee performance (assessed using a validated competence assessment tool), technical outcomes, and AEs over a 30-day follow-up was utilized. We developed a clinical risk score (Trainee Involvement in ERCP Risk Score [TIERS]) for patients undergoing ERCP and compared the rate of AEs in a training environment between low-risk and high-risk groups. The association between trainee performance and AE rate was also evaluated. RESULTS : 1283 ERCPs (409 [31.9 %, 95 %CI 29.3 %-34.4 %] with trainee involvement) performed by 11 trainers and 10 trainees were analyzed. AEs were more frequent in the high-risk compared with the low-risk group: 26.7 % (95 %CI 20.5 %-34.7 %) vs. 17.1 % (95 %CI 12.8 %-22.2 %). TIERS demonstrated a high negative predictive value for AEs (82.9 %, 95 %CI 79.4 %-85.8 %) and was the only predictor of AEs on multivariable analysis (odds ratio 1.38, 95 %CI 1.09-1.75). Suboptimal trainee performance was associated with an increase in AE rates. CONCLUSION : Simple, clinical-based predictive tools could improve ERCP training by selecting the most appropriate cases for hands-on training, with the aim of increasing patient safety.

Wet-suction versus slow-pull technique for endoscopic ultrasound-guided fine-needle biopsy: a multicenter, randomized, crossover trial.

BACKGROUND : It is unknown whether there is an advantage to using the wet-suction or slow-pull technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) with new-generation needles. We aimed to compare the performance of each technique in EUS-FNB. METHODS: This was a multicenter, randomized, single-blind, crossover trial including patients with solid lesions of ≥ 1 cm. Four needle passes with 22 G fork-tip or Franseen-type needles were performed, alternating the wet-suction and slow-pull techniques in a randomized order. The primary outcome was the histological yield (samples containing an intact piece of tissue of at least 550 µm). Secondary end points were sample quality (tissue integrity and blood contamination), diagnostic accuracy, and adequate tumor fraction. RESULTS: Overall, 210 patients with 146 pancreatic and 64 nonpancreatic lesions were analyzed. A tissue core was retrieved in 150 (71.4 %) and 129 (61.4 %) cases using the wet-suction and the slow-pull techniques, respectively (P = 0.03). The mean tissue integrity score was higher using wet suction (P = 0.02), as was the blood contamination of samples (P < 0.001). In the two subgroups of pancreatic and nonpancreatic lesions, tissue core rate and tissue integrity score were not statistically different using the two techniques, but blood contamination was higher with wet suction. Diagnostic accuracy and tumor fraction did not differ between the two techniques. CONCLUSION: Overall, the wet-suction technique in EUS-FNB resulted in a higher tissue core procurement rate compared with the slow-pull method. Diagnostic accuracy and the rate of samples with adequate tumor fraction were similar between the two techniques.

Dipeptidyl peptidase-3 is associated with severity of liver disease and circulatory complications in patients with cirrhosis.

BACKGROUND: Patients with cirrhosis suffer from a complex multiorgan disturbance and their prognosis is influenced by the development of portal hypertension and systemic circulatory dysfunction. Although non-invasive techniques such as transient elastography aid in early detection, there is an unmet need for reliable markers of these clinically significant complications. METHODS: We conducted an exploratory single-center study investigating dipeptidyl peptidase-3 (DPP3) concentrations in various vascular beds in a cohort of 48 patients with cirrhosis and 16 healthy controls. Liver vein catheterisation with sampling from femoral artery and femoral, renal and hepatic veins as well as measurement of hepatic pressure and liver function via indocyanine green and galactose elimination tests were performed. RESULTS: DPP3 concentrations were higher in cirrhotic patients compared to controls (12.6 vs. 7.4 ng/mL, p = 0.006) and increased according to the severity of cirrhosis. DPP3 associated with MELD-Na score, Child class, indocyanine green clearance, increased DPP3 with the increased hepatic venous pressure gradient (p = 0.015) as well as increased heart rate and reduced systemic vascular resistance. DPP3 concentrations predicted the presence of clinically significant portal hypertension in cirrhotic patients (AUROC 0.78, 95% CI 0.65-0.9). CONCLUSION: DPP3 is a promising marker for portal hypertension and systemic hemodynamic changes in cirrhosis.

Impact of trainee involvement on the outcome of ERCP procedures: results of a prospective multicenter observational trial.

BACKGROUND: Training in advanced endoscopic techniques such as endoscopic retrograde cholangiopancreatography (ERCP) should be driven by key performance measures and standardized competence assessment in order to provide safe and high-quality interventions. We aimed to determine whether the involvement of trainees influences the outcome of the procedure and the incidence of ERCP-related adverse events. METHODS: This was an international, multicenter, prospective, observational study conducted at six high- and low-volume centers across Europe between October 2016 and October 2018, and included independent operators and their trainees. Standard report forms documenting indication, trainee involvement, technical outcome, and complications over a 30-day follow-up of consecutive ERCP procedures were included in the analysis. Technical success of the procedure and procedure-related adverse events were compared between procedures in the trainee group and the control group using bivariable and multivariable analysis. RESULTS: 21 trainees and 16 control endoscopists performed 1843 ERCPs during the study period. Trainee involvement in ERCP procedures did not decrease technical success (92.4 % vs. 93.7 %; P = 0.30) or increase the risk of adverse events (14.7 % vs. 14.6 %; P > 0.99). Conversely, there were significantly more moderate or severe adverse events in the control group compared with the trainee group (6.2 % vs. 3.4 %, P = 0.01). On multivariable analysis, only increased bilirubin levels, time to cannulation, and procedure difficulty level increased the risk of any procedure-related adverse event. CONCLUSION: Trainee involvement in ERCP interventions within a proper teaching setting is safe and does not compromise the success of the procedure.

Pancreas divisum and recurrent pancreatitis: long-term results of minor papilla sphincterotomy.

Background and aims: Pancreas divisum (PD) is the most common congenital variant of the pancreatic ductal system and a potential cause of acute recurrent pancreatitis (ARP). Endoscopic therapy is a therapeutic option for symptomatic PD, but there is limited data on long-term results. We aimed to assess the effect of minor papilla endoscopic sphincterotomy (MiES) in the setting of ARP in patients with PD. Methods: Consecutive patients treated by MiES were included. Clinical data, including gender, age, smoking and drinking habits, number of episodes of acute pancreatitis (AP) as well as technical data pertaining to the endoscopic therapy were reviewed. Patients available for follow-up were contacted to assess the long-term impact of MiES using the Patient's Global Impression of Change (PGIC) questionnaire. Results: A total of 138 patients with PD including 77 patients with ARP underwent MiES; 48 patients were available for long-term follow-up using the PGIC score, with a mean follow-up period of 9.7 years. Procedure-related adverse events developed in 10 cases (12.9%): 5 post-MiES delayed bleeding and 5 mild pancreatitis. MiES was clinically successful in 35 patients (72.9%) who did not experience any more episodes of AP. Improvement in quality of life (PGIC ≥6) occurred in 41/48 patients (85.4%). On multivariate analysis, stenosis of the MiES was the only predictive factor for increased risk of recurrent pancreatitis after initial therapy. Conclusion: MiES resulted an efficient treatment for ARP in patients with PD with clinical benefit, patient satisfaction and improved quality of life even at long-term follow-up.

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.

Clinical Pattern of Surgical Crohn Disease Patients.

Backround/Objective: The aim of investigation was to evaluate if there is a pattern regarding the anatomical location of the disease and type of surgery performed/surgical indication. Also a analysis was performed regarding the complication rate in two subgroups deriving from urban and rural environments. Methods: Data was obtained from the medical records of patients with CD and centralized. Tests of statistical analysis included the CHY-SQUARE test and the results were presented as a retrospective, longitudinal study. Results: The group was formed of 60 patients. Patients with ileocolic disease were frequently diagnosed with obstruction and benefited from an enterectomy with anastomosis. Patients with colonic disease were frequently diagnosed with perforation and benefited from colectomy and stomy. Patients from rural areas had a milder evolution when compared with patients from urban enviroments. Conclusions: Although most patients with CD eventually require surgery, the indication could be anticipated by recognition of the concept of clinical patterns, and type of surgery required could be predicted if the clinical aspect of the patient/disease were identified.

Reintervention Rate Following Emergency Surgery for Crohn Disease.

Backround/Objective: To assess the impact of emergency surgery and postoperative recurrence in Crohn's disease (CD) and to evaluate the disease course while observing different factors that may influence it. Methods: Information on 37 consecutive patients which were diagnosed and operated in emergency for CD complications and the the relapse rate (regarded as a second surgery) were retrospectively evaluated. Results: The risk of relapse and second surgery was increased in males under 50 years and in those who benefited from an anastomosis during the first invervention while stomy seemed to reduce the rate of surgical relapse. The median duration until relapse was 2,3 years while a percentage of 33% required reintervention. Conclusions: The majority of patients with CD will undergo at least one surgical intervention during their lifetime and one third of them will relapse requiring a second intervention. Although medical treatment has seen great advancements, surgery requirements have remained unchanged as the mainstay treatment in emergent complications of CD. The age of the patients, smoking status and the postoperative medication influence the rate of postoperative recurrence.

Bile acids and cardiovascular function in cirrhosis.

Cirrhotic cardiomyopathy and the hyperdynamic syndrome are clinically important complications of cirrhosis, but their exact pathogenesis is still partly unknown. Experimental models have proven the cardiotoxic effects of bile acids and recent studies of their varied receptor-mediated functions offer new insight into their involvement in cardiovascular dysfunction in cirrhosis. Bile acid receptors such as farnesoid X-activated receptor and TGR5 are currently under investigation as potential therapeutic targets in a variety of pathological conditions. These receptors have also recently been identified in cardiomyocytes, vascular endothelial cells and smooth muscle cells where they seem to play an important role in cellular metabolism. Chronic cholestasis leading to abnormal levels of circulating bile acids alters the normal signalling pathways and contributes to the development of profound cardiovascular disturbances. This review summarizes the evidence regarding the role of bile acids and their receptors in the generation of cardiovascular dysfunction in cirrhosis.

Bowel preparation for colonoscopy: state of the art.

PURPOSE OF REVIEW: Bowel preparation for colonoscopy is a key quality indicator that impacts on all aspects of the procedure, such as patient comfort, diagnostic yield, and adverse events. Although most laxative regimens currently employed have been compared in a multitude of settings, the optimal preparation regimen still remains an open question. RECENT FINDINGS: Recent studies have focused on developing new regimens by modifying dosage, timing of administration or by combining laxatives with synergic mechanisms of action with the purpose of increasing patient tolerability while maximizing bowel cleansing. Several low-volume preparations and combinations of laxatives and adjunctive medication have shown promise in delivering both adequate preparation of the colon and good patient tolerability. Also, we have gained a better understanding of the influence of patient-related factors such as health literacy and education on the quality of bowel preparation. SUMMARY: Although several novel regimens have been tested in recent trials, it remains unclear which, if any, of these bowel preparations can replace the standard bowel cleansing regimens in clinical practice. Also, further data are required on how to improve bowel cleansing by choosing the appropriate regimen for the individual patient.

Endocan, Novel Potential Biomarker for Systemic Sclerosis: Results of a Pilot Study.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease characterized by vascular alterations of small arteries and microvessels with subsequent tissue fibrosis. Endocan is expressed by endothelial cells and associated with endothelial dysfunction; therefore it could be a potential biomarker for Ssc patients. METHODS: Twenty-one Ssc patients and 20 sex- and age-matched healthy controls were recruited for the study. Serum endocan levels were determined using ELISA method in all patients and controls. RESULTS: Serum endocan levels were superior in Ssc patients (median 2.53 (1.10-7 ng/ml)) compared with controls (0.79 (0-2 ng/ml), P < 0.05). Higher serum endocan expression was seen in diffuse Ssc subset and associated with the presence of digital ulcers and daily Raynaud's phenomenon (P < 0.05). Higher serum endocan levels were associated with a modified Rodnan skin score >14 and longer disease duration (P < 0.05). Values of areas under the receiver operating curves showed that serum endocan had good discriminative power for Ssc diagnosis, differentiating diffuse from limited subset type and differentiating patients with modified Rodnan skin score above and under 14 (area under curve: 0.94, 0.81, 0.75, respectively). CONCLUSION: The results of this pilot study suggest endocan as a potential biomarker for microvascular manifestations and complications in Ssc patients. These encouraging results could promote future prospective studies in order to determine the exact role played by endocan as a biomarker for Ssc.