Diagnostic accuracy and interobserver agreement of cholangioscopy for indeterminate biliary strictures: A single-center experience.

BACKGROUND AND STUDY AIMS: Characterization of indeterminate biliary strictures (IDBS) still represents a major challenge. Digital single-operator cholangioscopy (DSOC) could potentially overcome limits of conventional biopsy and brush sampling. The aim of this study was to compare diagnostic accuracy of visual evaluation and DSOC-guided biopsies to conventional trans-papillary sampling techniques and to evaluate the inter-observer agreement (IOA) on visual diagnosis. PATIENTS AND METHODS: All consecutive patients undergoing DSOC-guided biopsy after conventional sampling techniques for IDBS during a six-year period were retrospectively evaluated. Final diagnosis was based on histological evaluation of the surgical specimen if available or a clinical follow-up of at least 6 months. For IOA, 20-second DSOC clips were retrospectively reviewed by 6 experts and 6 trainees and classified according to the Monaco Classification. RESULTS: Thirty-five patients underwent DSOC for IDBS in the study period; 14 patients (F = 9) with a median age of 64 years (range 53-76) met the study aim. After DSOC, strictures location was changed in three patients (additional yield of 21.4 %). Intraductal DSOC-guided biopsy were technically successful in all cases, with an adequacy of 92.8 %. No adverse events were recorded. Final diagnosis was benign disease in five cases and cholangiocarcinoma in the others. For IOA, 29 videos were evaluated with almost perfect agreement for final diagnosis (kappa 0.871; agreement 93.1, p <0.001), although overall accuracy of DSOC visual finding was 73.6 % and 64.4 % for experts and trainees, respectively. CONCLUSIONS: DSOC could improve diagnostic accuracy for IDBS, since it showed high sensitivity for visual finding and high specificity for DSOC guided-biopsy. Visual diagnosis seems reliable for diagnosis using the Monaco Classification.

Locating community smells in software development processes using higher-order network centralities.

Community smells are negative patterns in software development teams' interactions that impede their ability to successfully create software. Examples are team members working in isolation, lack of communication and collaboration across departments or sub-teams, or areas of the codebase where only a few team members can work on. Current approaches aim to detect community smells by analysing static network representations of software teams' interaction structures. In doing so, they are insufficient to locate community smells within development processes. Extending beyond the capabilities of traditional social network analysis, we show that higher-order network models provide a robust means of revealing such hidden patterns and complex relationships. To this end, we develop a set of centrality measures based on the MOGen higher-order network model and show their effectiveness in predicting influential nodes using five empirical datasets. We then employ these measures for a comprehensive analysis of a product team at the German IT security company genua GmbH, showcasing our method's success in identifying and locating community smells. Specifically, we uncover critical community smells in two areas of the team's development process. Semi-structured interviews with five team members validate our findings: while the team was aware of one community smell and employed measures to address it, it was not aware of the second. This highlights the potential of our approach as a robust tool for identifying and addressing community smells in software development teams. More generally, our work contributes to the social network analysis field with a powerful set of higher-order network centralities that effectively capture community dynamics and indirect relationships.

Bayesian inference of transition matrices from incomplete graph data with a topological prior.

Many network analysis and graph learning techniques are based on discrete- or continuous-time models of random walks. To apply these methods, it is necessary to infer transition matrices that formalize the underlying stochastic process in an observed graph. For weighted graphs, where weighted edges capture observations of repeated interactions between nodes, it is common to estimate the entries of such transition matrices based on the (relative) weights of edges. However in real-world settings we are often confronted with incomplete data, which turns the construction of the transition matrix based on a weighted graph into an inference problem. Moreover, we often have access to additional information, which capture topological constraints of the system, i.e. which edges in a weighted graph are (theoretically) possible and which are not. Examples include transportation networks, where we may have access to a small sample of passenger trajectories as well as the physical topology of connections, or a limited set of observed social interactions with additional information on the underlying social structure. Combining these two different sources of information to reliably infer transition matrices from incomplete data on repeated interactions is an important open challenge, with severe implications for the reliability of downstream network analysis tasks. Addressing this issue, we show that including knowledge on such topological constraints can considerably improve the inference of transition matrices, especially in situations where we only have a small number of observed interactions. To this end, we derive an analytically tractable Bayesian method that uses repeated interactions and a topological prior to perform data-efficient inference of transition matrices. We compare our approach against commonly used frequentist and Bayesian approaches both in synthetic data and in five real-world datasets, and we find that our method recovers the transition probabilities with higher accuracy. Furthermore, we demonstrate that the method is robust even in cases when the knowledge of the topological constraint is partial. Lastly, we show that this higher accuracy improves the results for downstream network analysis tasks like cluster detection and node ranking, which highlights the practical relevance of our method for interdisciplinary data-driven analyses of networked systems.

Long versus short peroral endoscopic myotomy for the treatment of achalasia: results of a non-inferiority randomised controlled trial.

OBJECTIVE: Peroral endoscopic myotomy (POEM) has become standard treatment for achalasia with comparable efficacy to surgery. In most of published series, the length of myotomy is 12-13 cm. Shorter cuts could have the advantage of shorter procedure time and possibly reduced gastro-oesophageal reflux disease (GORD) rate. DESIGN: This single-centre, patient-blinded, randomised, non-inferiority clinical trial included 200 patients, who were randomly allocated, to receive either a long-POEM (13 cm; 101 patients) or a short-POEM (8 cm; 99 patients). Primary outcome was defined as an Eckardt symptom score of ≤3 at 24 months after the procedure; a non-inferiority design was chosen with an accepted success range of 6% between the two treatments. Secondary outcomes included operating time, complication rate, postoperative manometry, GORD rate and quality of life. RESULTS: In the intention-to-treat analysis, clinical success rates were 89.1% in the long-POEM and 98.0% in the short-POEM group, resulting in an absolute between-group difference of -8.9% (90% CI -14.5 to -3.3).Procedure time was significantly reduced in the short-POEM as compared with the long-POEM group (40 vs 50 min, p<0.0001). Severe adverse events occurred in one patient in both groups.No differences were observed in postoperative GORD: acid exposure >6% on pH monitoring study at 6 months was seen in 34.3% (long-POEM) vs 31.1% (short-POEM), while endoscopic oesophagitis was diagnosed in 37.6% vs 51.5% at 6 months and in 21% vs 24.5% at 24 months. Regular proton pump inhibitor use was not different either (36.8% vs 37.5%). CONCLUSIONS: Our study demonstrates non-inferiority of a shorter cut length of POEM as compared with the standard treatment, which saved some procedural time. GORD rate was not reduced by reducing cutting length. TRIAL REGISTRATION NUMBER: NCT03450928.

Endoscopic electroincision of challenging benign biliopancreatic strictures.

Background and study aims Endoscopic drainage of benign biliary and pancreatic strictures can be challenging, especially when tightness of the stenosis does not allow passage of mechanical and pneumatic dilation catheters. Electroincision of benign biliopancreatic can be considered in selected cases. Patients and methods Three male patients (mean age 33 years, range 9-60) underwent endoscopic retrograde cholangiopancreatography to drain anastomotic biliary stricture (ABS) following orthotopic liver transplantation (n = 2) and pancreatic duct stenosis due to abdominal trauma (n = 1). The biliopancreatic strictures could be passed only with a thin 0.020-inch hydrophilic guidewire. Conventional mechanical and pneumatic dilators failed to pass the strictures due to weakness of the guidewire. Therefore, electrosurgical incision by over-the-wire 6Fr cystotome or needle-knife was attempted using pure cut current. Results The two cases of ABS were approached also by cholangioscopy and the 6Fr cystotome easily passed the strictures, allowing subsequent pneumatic dilatation and insertion of multiple plastic stents. The patient with a pancreatic duct stricture underwent electrosurgical incision using a thin needle knife over-the-wire, resulting in insertion of a 7Fr pancreatic stent. No adverse events occurred; all the patients were discharged within 24 to 48 hours. Conclusions Electrosurgical incision of benign biliopancreatic strictures could be considered in selected patients whom conventional dilation techniques fail.

Radiofrequency ablation for intraductal extension of ampullary adenomatous lesions: proposal for a standardized protocol.

Background and study aims Intraductal extension of ampullary adenoma represents a challenging endoscopic issue. Intraductal radiofrequency ablation (RFA) has been recently suggested, but evidence and standardization of this technique are still lacking. This study aimed to provide a long-term evaluation of clinical efficacy and safety of intraductal RFA ablation with a standardized algorithm of treatment. Patients and methods Data were prospectively collected from consecutive patients with intraductal extension of adenomatous ampullary lesions from January 2016 to November 2018. Endpoints of the study were clinical success evaluated on histology results at the last follow-up, technical success, and adverse events assessment. Results Nine patients with intraductal (biliary ± pancreatic) extension of ampullary adenomas were treated with RFA during the study period. Histology on the papillectomy specimen confirmed intraductal involvement with low-grade dysplasia (LGD) in five cases (56 %), high-grade dysplasia (HGD) in three (33 %), and HGD with intramucosal adenocarcinoma in one patient (11 %). Additional argon plasma coagulation to ablate the adenoma on the duodenal mucosa was applied in five patients (56 %). Technical success was 100 %. One patient (11 %) with failed pancreatic stenting, developing acute pancreatitis after RFA, recovered with medical therapy. After a median follow-up of 21 months (IQR 20-31), six patients (67 %) achieved clinical success being free of recurrence, whereas one was diagnosed with persistence of adenocarcinoma, one with recurrent HGD, and one with recurrent LGD. Conclusions In our experience, intraductal RFA achieved acceptable results after a 2-year follow-up. Further studies are required to confirm our results and to select those patients most likely to respond.

Personalized Endoscopy in Complex Malignant Hilar Biliary Strictures.

Malignant hilar biliary obstruction (HBO) represents a complex clinical condition in terms of diagnosis, surgical and medical treatment, endoscopic approach, and palliation. The main etiology of malignant HBO is hilar cholangiocarcinoma that is considered an aggressive biliary tract's cancer and has still today a poor prognosis. Endoscopy plays a crucial role in malignant HBO from the diagnosis to the palliation. This technique allows the collection of cytological or histological samples, direct visualization of the suspect malignant tissue, and an echoendoscopic evaluation of the primary tumor and its locoregional staging. Because obstructive jaundice is the most common clinical presentation of malignant HBO, endoscopic biliary drainage, when indicated, is the preferred treatment over the percutaneous approach. Several endoscopic techniques are today available for both the diagnosis and the treatment of biliary obstruction. The choice among them can differ for each clinical scenario. In fact, a personalized endoscopic approach is mandatory in order to perform the proper procedure in the singular patient.

Pediatric T-tube in adult liver transplantation: Technical refinements of insertion and removal.

BACKGROUND: With the increasing use of extended-criteria donor organs, the interest around T-tubes in liver transplantation (LT) was restored whilst concerns regarding T-tube-related complications persist. AIM: To describe insertion and removal protocols implemented at our institution to safely use pediatric rubber 5-French T-tubes and subsequent outcomes in a consecutive series of adult patients. METHODS: Data of consecutive adult LT patients from brain-dead donors, treated from March 2017 to December 2019, were collected (i.e., biliary complications, adverse events, treatment after T-Tube removal). Patients with upfront hepatico-jejunostomy, endoscopically removed T-tubes, those who died or received retransplantation before T-tube removal were excluded. RESULTS: Seventy-two patients were included in this study; T-tubes were removed 158 d (median; IQR 128-206 d) after LT. In four (5.6%) patients accidental T-tube removal occurred requiring monitoring only; in 68 (94.4%) patients Nelaton drain insertion was performed according to our protocol, resulting in 18 (25%) patients with a biliary output, subsequently removed after 2 d (median; IQR 1-4 d). Three (4%) patients required endoscopic retrograde cholangiopancreatography (ERCP) due to persistent Nelaton drain output. Three (4%) patients developed suspected biliary peritonitis, requiring ERCP with sphincterotomy and nasobiliary drain insertion (only one revealing contrast extravasation); no patient required percutaneous drainage or emergency surgery. CONCLUSION: The use of pediatric rubber 5-French T-tubes in LT proved safe in our series after insertion and removal procedure refinements.

Fibrin glue injection: Rescue treatment for refractory post-sphincterotomy and post-papillectomy bleedings.

OBJECTIVES: Endoscopic sphincterotomy (ES) and papillectomy (EP) are associated with a non-negligible risk of post-procedural bleeding. Despite first-line endoscopic hemostasis being achieved by several methods, patients may experience bleeding persistence or recurrence. In such cases, fibrin glue (FG) injection may be used as a rescue therapy before more invasive approaches. The aim of this study was to evaluate the efficacy and safety of endoscopic FG injection to treat refractory post-ES and post-EP bleeding. METHODS: Data were collected retrospectively from patients with refractory immediate or delayed bleeding following ES or EP, between October 2007 and November 2019, at a single institution. Clinical success was defined as bleeding control after FG injection. RESULTS: Overall, 70 patients were included. Clinical success was reached in 64 (91.4%) patients after one session of FG injection. Of six (8.6%) patients in whom the treatment failed, one required subsequent insertion of a fully covered self-expanding metal stent (FC-SEMS) due to immediate massive bleeding, while five experienced bleeding recurrence. Such events were managed with an additional session of FG injection that failed in two cases. Therefore, one patient underwent FC-SEMS plus selective embolization, whereas the other underwent diagnostic arteriography. No severe periprocedural complications occurred. Two cases of intrabiliary glue migration were treated by endoscopic removal with a retrieval basket. CONCLUSIONS: Rescue therapy with endoscopic FG injection appears to be effective and safe to treat refractory post-ES and post-EP bleeding. Further studies are required to confirm these preliminary data.

Endoscopic management of non-anastomotic biliary strictures following liver transplantation: Long-term results from a single-center experience.

OBJECTIVES: Studies on endoscopic treatment of non-anastomotic biliary strictures (NABS) following orthotopic liver transplantation (OLT) are scanty and with a short follow-up. The long-term results of endoscopic treatment with plastic stents of NABS following OLT were analyzed. METHODS: Retrospective analysis of consecutive enrolled patients who underwent endoscopic treatment for NABS after OLT between 1997 and 2015. Endoscopic treatment success was defined as stricture resolution, without recurrence. RESULTS: During the study period, 33 patients with NABS underwent endoscopic retrograde cholangiopancreatography (ERCP) in our center. A total of 68 ERCP were performed with a 4.4% of procedure-related adverse events. Mortality related to cholangitis secondary to endoscopic procedures was 12%. After median follow-up of 70.3 months from stents removal, NABS resolution was obtained in 12 out of 24 (50%) patients. Only one case of late NABS recurrence was observed which was successfully retreated endoscopically. According to our data analysis NABS occurring <12 months from OLT showed a worse prognosis (P < 0.04). CONCLUSIONS: The follow-up of this study confirms that endoscopic treatment of NABS is unsatisfactory. However, patients who respond to endoscopic treatment maintain the response over time. Prompt treatment of acute cholangitis due to stents occlusion is advised in these patients to avoid high mortality rates.

Bilio-pancreatic endoscopy during COVID-19 pandemic.

On 31 December 2019, the WHO China Country Office was informed of cases of pneumonia of unknown etiology detected in Wuhan (Hubei Province of China). In January 2020, a new coronavirus named SARS-CoV2 was isolated and, since that time, SARS-CoV2 related disease (COVID-19) rapidly spread all over the world becoming pandemic in March 2020. The COVID-19 outbreak dramatically affected the public-health and the health-care facilities organization. Bilio-pancreatic endoscopy is considered a high-risk procedure for cross-contamination and, even though it is not directly involved in COVID-19 diagnosis and management, its reorganization is crucial to guarantee high standards of care minimizing the risk of SARS-CoV2 transmission among patients and health-care providers. Bilio-pancreatic endoscopic procedures often require a short physical distance between the endoscopist and the patient for a long period of time, a frequent exchange of devices, the involvement of a large number of personnel, the use of complex endoscopes difficult to reprocess. On this basis, endoscopic units should take precautions with adjusted management of bilio-pancreatic endoscopy. The aim of this article is to discuss the approach to bilio-pancreatic endoscopy in the COVID-19 era with focus on diagnostic algorithms, indications, management of the endoscopic room, proper use of Personal Protective Equipment and correct reprocessing of instrumentation.

Endoscopic snare papillectomy for adenoma of the ampulla of vater: Long-term results in 135 consecutive patients.

BACKGROUND: The premalignant nature of ampullary adenomas justifies their radical excision. AIMS: Aim of this study is to evaluate the long-term results of endoscopic snare papillectomy in a consecutive series of patients with ampullary adenomas. METHODS: Patients who underwent endoscopic snare papillectomy between October 1999 and October 2017 were identified from an electronic database. Endoscopic snare papillectomy was performed en bloc, when possible; a pancreatic stent or a nasopancreatic drainage were inserted. Endoscopic follow-up was scheduled after 3, 6 and 12 months for the first year, then yearly. RESULTS: Endoscopic snare papillectomy was performed in 135 patients (70 M, mean age 60.5 years) by en bloc (83%) or piecemeal (17%) resection. Delayed bleeding occurred in 16 patients (11.8%), infected retroperitoneal collections in 6 patients (4.4%), pancreatitis in 4 patients (3%). One patient died (0.7%). Follow-up was available in 103/114 (90.3%) patients. In case of residual (24.3%) and recurrent (23.3%), adenomas endoscopic retreatment was successful in 42/49 cases (85.7%). After a mean follow-up of 40 months, 93.2% (96/103) of the patients were disease free CONCLUSION: Endoscopic snare papillectomy of ampullary adenomas is effective with favorable long-term outcomes. Compliance to the scheduled follow-up is important for the early detection and re-treatment of recurrences.

Metabolic endoscopy by duodenal mucosal resurfacing: expert review with critical appraisal of the current technique and results.

INTRODUCTION: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for type 2 diabetes (T2D) consisting of circumferential hydrothermal ablation of the duodenal mucosa. AREAS COVERED: A review was conducted on the reports available up to March-2020. On a total of 79 patients, DMR induced a significant mean HbA1c, FPG and HOMA-IR reduction at 6 months (0.9 ± 0.2%, 1.7 ± 0.5 mmol/L and 2.9 ± 1.1 mUI/L respectively - P < 0.001). DMR metabolic efficacy directly correlates with the length of the ablated mucosa (mean 3 months HbA1c reduction 1.2% vs 2.5% after short and long ablation respectively - P < 0.05), while it is independent of weight-loss. Severe AEs were registered in 3.7% of the cases. EXPERT OPINION: DMR plays a promising role in metabolic impairment improvement inducing a morpho-functional duodenal alteration not necessarily depending on weight-loss. Technical-functional improvements of the device and appropriate training aimed at its correct use are needed to lower the rate of severe AEs and technical failure. The current role of DMR needs to be clarified, but it might be proposed for poorly controlled T2D in accurately selected patients. Evidence on DMR is still scanty and further research is mandatory to standardize the endoscopic technique and its indications.

Blind-eye cannulation as a new method for ERCP training: Can we do more than merely teach?

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) requires extensive hands-on training. Currently in ERCP training there are two very important problems that need attention: lack of standardized commands for communication, and misunderstanding between the trainee and the trainer. Methods A method of "blind-eye" cannulation was developed with two paired trainees using the Boskoski-Costamagna ERCP Trainer. The trainee who was holding the duodenoscope was blind-folded and the other trainee gave instructions on what maneuvers were necessary to achieve cannulation, under the supervision of a trainer. Before starting cannulation, a standard list of commands was agreed by the operators. Results The blind-eye method of cannulation teaches the operator trainee to listen and the assistant trainee to teach. Trainees use standardized commands. During the training session the two trainees swapped roles. Conclusions Currently, we do not have proof that this type of training is useful, therefore, scientific studies are needed for confirmation. However, we believe that this ERCP model may provide an entirely safe means of improving communication and technical proficiency.

Endotherapy of postcholecystectomy biliary strictures with multiple plastic stents: long-term results in a large cohort of patients.

BACKGROUND AND AIMS: Endoscopic therapy of benign biliary strictures with multiple plastic stent (MPS) placement has shown satisfactory results. However, the literature describes various benign biliary stricture etiologies. The aim of this study was to evaluate long-term MPS results in patients with postcholecystectomy biliary strictures (PCBSs). METHODS: PCBS patients without complete bile duct transection were included. ERCP consisted of placing an increasing plastic stent number over time, exchanged at regular intervals (3-4 months), until complete morphologic stricture disappearance. After stent removal, patient follow-up comprised liver function tests and clinical assessment. RESULTS: One hundred fifty-four patients (43.5% men; mean age, 53 years) were enrolled; in 43% of the cases, PCBSs were involved or were close to the main hepatic confluence. PCBS resolution rate was 96.7% (n = 149). A mean maximum number of 4.3 ± 1.6 stents were placed side-by-side; a mean of 4.2 ± 1.5 ERCPs per patient was needed to obtain PCBS resolution during a mean treatment period of 11.8 ± 6.4 months. Unscheduled stent exchange because of cholangitis, jaundice, or pain occurred in 7.4% of cases. Procedure-related mortality was absent. Follow-up data were available in 85.2% of cases. After a mean follow-up of 11.1 ± 4.9 years, stricture recurrence rate was 9.4% (n = 12). Subsequent to retreatment, 83.3% of patients (n = 10) were asymptomatic after a mean time of 9 years, whereas 2 patients underwent hepaticojejunostomy because of failed retreatment. Statistical analysis revealed no risk factors for PCBS recurrence after MPS. CONCLUSIONS: Endoscopic therapy of PCBSs with MPSs is safe and effective at long-term follow-up. PCBSs involving or close to the main hepatic confluence were successfully treated with MPSs. PCBS recurrence rate is low and can be successful endoscopically retreated without precluding possible surgical treatment.