The high rate of spontaneous migration of small size common bile duct stones may allow a significant reduction in unnecessary ERCP and related complications: results of a retrospective, multicenter study.

INTRODUCTION: Common bile duct stones (CBDS) can spontaneously migrate through the duodenal papilla. In this case, ERCP could be unnecessary and a significant rate of complications could be avoided. In this study, we aim at retrospectively evaluating the rate of spontaneous stone passage in patients with an imaging diagnosis of CBDS and at analysing the factors associated to spontaneous stone migration. METHODS: We conducted a retrospective multi-centre analysis of patients undergoing ERCP for CBDS in a 12-month period. 1016 patients with CBDS were analysed. In all patients CBDS was diagnosed with adequate imaging methods performed prior to ERCP. ERCPs with failed biliary cannulation were excluded. Data regarding patients' characteristics, imaging findings and ERCP procedure were analysed. RESULTS: 1016 patients with CBDS undergoing ERCP were analysed (male sex 43.3%; mean age 69.9 ± 16.5 years). Diagnosis of CBDS was obtained by EUS in 415 patients (40.8%), MR in 343 (33.8%), CT in 220 (21.7%), and US in 38 (3.7%). No stones were found at ERCP in 179 patients (17.6%), in 14 (6.2%) when ERCP was performed within 6 h from imaging study, in 114 (18.5%) between 7 h and 7 days, in 32 (24.6%) between 8 and 29 days, and in 19 (43.2%) after 30 days. The rate of unnecessary ERCP occurred significantly more frequently in patients in whom imaging methods demonstrated either sludge or ≤ 5 mm CBDS (29.9 vs. 8.3%; p < 0.001). DISCUSSION: Spontaneous migration of small CBDS is a frequent event, and ≤ 5 mm size and a delay in ERCP > 7 days represent predictive factors for it. We suggest that CBDS ≤ 5 mm should not undergo immediate removal and this fact would allow reducing the rate of unnecessary ERCP with their related complications. Prospective studies are needed to confirm these results and demonstrate the safety of a conservative management in this setting.

16S rRNA of Mucosal Colon Microbiome and CCL2 Circulating Levels Are Potential Biomarkers in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in the Western world and intestinal dysbiosis might contribute to its pathogenesis. The mucosal colon microbiome and C-C motif chemokine 2 (CCL2) were investigated in 20 healthy controls (HC) and 20 CRC patients using 16S rRNA sequencing and immunoluminescent assay, respectively. A total of 10 HC subjects were classified as overweight/obese (OW/OB_HC) and 10 subjects were normal weight (NW_HC); 15 CRC patients were classified as OW/OB_CRC and 5 patients were NW_CRC. Results: Fusobacterium nucleatum and Escherichia coli were more abundant in OW/OB_HC than in NW_HC microbiomes. Globally, Streptococcus intermedius, Gemella haemolysans, Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were significantly increased in CRC patient tumor/lesioned tissue (CRC_LT) and CRC patient unlesioned tissue (CRC_ULT) microbiomes compared to HC microbiomes. CCL2 circulating levels were associated with tumor presence and with the abundance of Fusobacterium nucleatum, Bacteroides fragilis and Gemella haemolysans. Our data suggest that mucosal colon dysbiosis might contribute to CRC pathogenesis by inducing inflammation. Notably, Fusobacterium nucleatum, which was more abundant in the OW/OB_HC than in the NW_HC microbiomes, might represent a putative link between obesity and increased CRC risk.

Efficacy and Safety of Digital Single-Operator Cholangioscopy for Difficult Biliary Stones.

BACKGROUND & AIMS: It is not clear whether digital single-operator cholangioscopy (D-SOC) with electrohydraulic and laser lithotripsy is effective in removal of difficult biliary stones. We investigated the safety and efficacy of D-SOC with electrohydraulic and laser lithotripsy in an international, multicenter study of patients with difficult biliary stones. METHODS: We performed a retrospective analysis of 407 patients (60.4% female; mean age, 64.2 years) who underwent D-SOC for difficult biliary stones at 22 tertiary centers in the United States, United Kingdom, or Korea from February 2015 through December 2016; 306 patients underwent electrohydraulic lithotripsy and 101 (24.8%) underwent laser lithotripsy. Univariate and multivariable analyses were performed to identify factors associated with technical failure and the need for more than 1 D-SOC electrohydraulic or laser lithotripsy session to clear the bile duct. RESULTS: The mean procedure time was longer in the electrohydraulic lithotripsy group (73.9 minutes) than in the laser lithotripsy group (49.9 minutes; P < .001). Ducts were completely cleared (technical success) in 97.3% of patients (96.7% of patients with electrohydraulic lithotripsy vs 99% patients with laser lithotripsy; P = .31). Ducts were cleared in a single session in 77.4% of patients (74.5% by electrohydraulic lithotripsy and 86.1% by laser lithotripsy; P = .20). Electrohydraulic or laser lithotripsy failed in 11 patients (2.7%); 8 patients were treated by surgery. Adverse events occurred in 3.7% patients and the stone was incompletely removed from 6.6% of patients. On multivariable analysis, difficult anatomy or cannulation (duodenal diverticula or altered anatomy) correlated with technical failure (odds ratio, 5.18; 95% confidence interval, 1.26-21.2; P = .02). Procedure time increased odds of more than 1 session of D-SOC electrohydraulic or laser lithotripsy (odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P < .001). CONCLUSIONS: In a multicenter, international, retrospective analysis, we found D-SOC with electrohydraulic or laser lithotripsy to be effective and safe in more than 95% of patients with difficult biliary stones. Fewer than 5% of patients require additional treatment with surgery and/or extracorporeal shockwave lithotripsy to clear the duct.

The Role of Colonoscopy in the Diverticular Disease.

Colonic diverticula are one of the most frequent conditions found during the endoscopic examination of the lower digestive tract, interestingly in >70% of people after 80 years old. Of them, only a few percentage develop complications such as acute diverticulitis or diverticular bleeding. Up to now, colonoscopy represents the most important diagnostic and therapeutic tool on the hands of the clinicians. On the basis of this the need for a standardized and reproducible approach is now emerging. This short review article is tasked to point out some open issues concerning the role of colonoscopy in diverticular disease.

Can esophageal symptoms be associated with sleep disorders in esophageal rare diseases?. A prospective case-control study across achalasia, eosinophilic esophagitis and gastroesophageal reflux disease.

BACKGROUND: The association between sleep disorders and gastroesophageal reflux disease (GERD) has been the subject of several studies; however, quality of sleep has been under investigated in adult patients with eosinophilic esophagitis (EoE) and achalasia (Ach). This study aims to evaluate the prevalence of sleep disturbances in patients with EoE and Ach compared to GERD patients and their associations with esophageal symptoms. METHODS: Thirty Ach patients and 20 EoE patients were consecutively enrolled and compared to a control group of 46 GERD patients. All patients underwent a standardized questionnaire investigating the intensity-frequency scores (from 0 to 6) of esophageal symptoms, Pittsburgh Sleep Quality Index (PSQI) questionnaire to assess sleep quality, a SF-36 survey to investigate health-related quality of life (both physical (PCS) and mental (MCS) component scales), Beck Depression Inventory-II (BDI-II) and State Trait Anxiety Inventory (STAI) to assess the presence of depression and anxiety. RESULTS: The prevalence of sleep disturbances was 66.7% in Ach, 50% in EoE, and 60% in GERD patients (P=0.5). PCS and MCS significantly correlated with depression and anxiety levels. Ach patients showed significantly higher intensity-frequency scores of dysphagia for solids (Scheffè P<0.001) and liquids (Scheffè P<0.001) than EoE and GERD patients. No differences were found in the intensity-frequency scores of the esophageal symptoms among the three groups. There was a significant association between worst quality of sleep and higher intensity-frequency scores of regurgitation. CONCLUSIONS: Sleep disturbances are common with Ach and EoE, similar to GERD patients. Moreover, there is a significant association between regurgitation, a typical GERD symptom, and poor quality of sleep, independent from diagnosis.

Herbal products: benefits, limits, and applications in chronic liver disease.

Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology). The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population.

Novel Hemostatic Gel As Rescue Therapy for Postsphincterotomy Bleeding Refractory to Self-Expanding Metallic Stent Placement.

Endoscopic sphincterotomy (ES) is commonly performed during endoscopic retrograde cholangiopancreatography, and bleeding is a severe adverse event. PuraStat is a peptide developed as a hemostatic agent for endoscopy. We report its use as a hemostatic strategy in post-ES bleeding refractory to combined hemostasis. A patient with choledocholithiasis underwent endoscopic retrograde cholangiopancreatography for stone removal. After the ES, severe bleeding refractory to the injection of diluted epinephrine around the bleeding source and metal stent placement occurred. Hemostasis was achieved with the application of the hemostatic gel. We reported the use of novel self-assembling hemostatic gel as an effective therapeutic tool for post-ES refractory bleeding.

An international experience with single-operator cholangiopancreatoscopy in patients with altered anatomy.

Background and study aims The utility of digital single- operator cholangiopancreatoscopy (D-SOCP) in surgically altered anatomy (SAA) is limited. We aimed to evaluate the technical success and safety of D-SOCP in patients SAA. Patients and methods Patients with SAA who underwent D-SOCP between February 2015 and June 2020 were retrospectively evaluated. Technical success was defined as completing the intended procedure with the use of D-SOCP. Results Thirty-five patients underwent D-SOCP (34 D-SOC, 1 D-SOP). Bilroth II was the most common type of SAA (45.7 %), followed by Whipple reconstruction (31.4 %). Twenty-three patients (65.7 %) patients had prior failed ERCP due to the presence of complex biliary stone (52.2 %). A therapeutic duodenoscope was utilized in the majority of the cases (68.6 %), while a therapeutic gastroscope (22.7 %) or adult colonoscope (8.5 %) were used in the remaining procedures. Choledocholithiasis (61.2 %) and pancreatic duct calculi (3.2 %) were the most common indications for D-SOCP. Technical success was achieved in all 35 patients (100 %) and majority (91.4 %) requiring a single session. Complex interventions included electrohydraulic or laser lithotripsy, biliary or pancreatic stent placement, stricture dilation, and target tissue biopsies. Two mild adverse events occurred (pancreatitis and transient bacteremia). Conclusions In SAA, D-SOCP is a safe and effective modality to diagnose and treat complex pancreatobiliary disorders, especially in cases where standard ERCP attempts may fail.

Digital single-operator cholangioscopy in diagnostic and therapeutic bilio-pancreatic diseases: A prospective, multicenter study.

BACKGROUND AND AIM: Digital single-operator cholangioscopy (D-SOC) is an endoscopic procedure that is increasingly used for the management of bilio-pancreatic diseases. We aimed to investigate the efficacy and safety of D-SOC for diagnostic and therapeutic indications. METHODS: This is a multicenter, prospective study(January 2016-June 2019) across eighteen tertiary centers. The primary outcome was procedural success of D-SOC. Secondary outcomes were: D-SOC visual assessment and diagnostic yield of SpyBite biopsy in cases of biliary strictures, stone clearance rate in cases of difficult biliary stones, rate of adverse events(AEs) for all indications. RESULTS: D-SOC was performed in 369 patients (201(54,5%) diagnostic and 168(45,5%)therapeutic). Overall, procedural success rate was achieved in 360(97,6%) patients. The sensitivity, specificity, PPV, NPV and accuracy in biliary strictures were: 88,5%, 77,3%, 83,3%, 84,1% and 83,6% for D-SOC visual impression; 80,2%, 92,6%, 95,1%, 72,5% and 84,7% for the SpyBite biopsy, respectively. For difficult biliary stones, complete duct clearance was obtained in 92,1% patients (82,1% in a single session). Overall, AEs occurred in 37(10%) cases.The grade of AEs was mild or moderate for all cases, except one which was fatal. CONCLUSION: D-SOC is effective for diagnostic and therapeutic indications.Most of the AEs were minor and managed conservatively, even though a fatal event has happened that is not negligible and should be considered before using D-SOC.

Endoscopic Application of Purastat® in the Treatment of Solitary Rectal Ulcer Syndrome.

A 49-years-old woman with a recent history of tenesmus, constipation, abdominal and rectal pain referred to our Unit. There was no previous history of rectal bleeding or a family history of gastrointestinal diseases. Laboratory tests showed haemoglobin 10.9 g/dl, MCV 72fl, ferritin 18 U/l. Physical examination was normal. The patient underwent a colonoscopy which identified a single ulcer of 2.5 cm of diameter without bleeding signs in the distal rectum, 4 cm from the anal margin. Histopathological examination revealed shallow ulceration with fibrosis in lamina propria. We decided to treat the ulcer with one application of Purastat. Four weeks later, a follow-up colonoscopy revealed a complete mucosal healing with only mild residual mucosal erythema. Solitary Rectal Ulcer Syndrome (SRUS) is an uncommon benign proctologic disease usually affecting young adults with a prevalence of 1:100.000 per year, equally affecting women and men with a slight predominance in young women. SRUS is characterized by chronic rectal pain and bleeding, constipation, incomplete evacuation, tenesmus and mucous discharge impairing the patients' quality of life. In past years several topical agents have been used reporting clinical improvements, also if none of them has been evaluated in prospective controlled trials. Purastat (3D-Matrix Europe SAS, France) is a novel self-assembling peptide developed as a haemostatic agent for endoscopic and surgical procedures. In addition to the known haemostatic effect, it has been hypothesized that the activated Purastat nanostructure favors the cell and tissue proliferative process since the similarity of the activated Purastat 3-D nanostructure with the natural extracellular matrix (ECM-SM) scaffold material would result in an adequate adherence of cells and regenerative tissues, achieving more effective healing of the mucosa. Based on this hypothetical re-epithelizing property of Purastat, we decided to use it in this patient, achieving mucosal healing and symptoms improvement.

Multicenter experience with digital single-operator cholangioscopy in pregnant patients.

Background and study aims The use of fluoroscopy during pregnancy should be minimized given that a clear-cut safe radiation dose in pregnancy is unknown. The role of digital single-operator cholangioscopy (D-SOC) as an alternative to standard enodoscopic retrograde cholangiopancreatography (ERCP) in pregnant patients has not been comprehensively studied. This study assessed 1 Technical success defined as performance of ERCP with D-SOC without the use of fluoroscopy in pregnant patients; 2 safety of D-SOC in pregnancy; and 3 maternal and neonatal outcomes after D-SOC during/after pregnancy. Patients and methods This was an international, multicenter, retrospective study at 6 tertiary centers. Pregnant patients who underwent D-SOC for the treatment of bile duct stones and/or strictures were included. Results A total of 10 patients underwent D-SOC. Indications for ERCP were choledocholithiasis, strictures, previous stent removal, and choledocholithiasis/stent removal. Bile duct cannulation without fluoroscopy was achieved in 10 of 10 patients (100 %). Moreover, 50 % of patients (5/10) completed a fluoroless ERCP with D-SOC. Mean fluoroscopy dose and fluoroscopy time were 3.4 ±â€Š7.2 mGy and 0.5 ±â€Š0.8 min, respectively. One case of mild bleeding and one case of moderate post-ERCP pancreatitis occurred. The mean gestational age at delivery was 36.2 ±â€Š2.6 weeks. Median birth weight was 2.5 kg [IQR: 2.2-2.8]. No birth defects were noted. Conclusion ERCP guided by D-SOC appears to be a feasible and effective alternative to standard ERCP in pregnant patients. It enables avoidance of radiation in half of cases.

Fatal Outcome Consequent to an Endoscopic Full Thickness Resection of a Colonic Lateral Spreading Tumor: A Case Report.

BACKGROUND Endoscopic full-thickness resection represents an innovative procedure, used in selected patients that allows lesions en-bloc resection with an integral wall specimen available for histopathological definition. Bleeding and perforation are known to be the most frequent procedure-related adverse events. We report a case of entero-colonic fistula as complication of an endoscopic full-thickness resection. CASE REPORT A 77-year-old male, with a personal history of right-hemicolectomy for a colonic adenocarcinoma presented to our department for a routine colonoscopy that showed the presence of a 25 mm lateral spreading tumor localized at about 50 cm from the anal margin. A full-thickness resection of the lateral spreading tumor using the over-the-scope clip device was performed. After 4 weeks, because of abdominal pain, weight loss, diarrhea, and signs of malnutrition, the patient underwent a new colonoscopy showing hyperemic mucosa with ulcerations in all colonic segments and, at the site of the previous endoscopic full-thickness resection, an orifice of an entero-colonic fistula. The histological definition was suggestive for ulcerative proctocolitis and confirmed the presence of small bowel mucosa at fistula orifice. An intussusception at the level of fistula with consequent intestinal obstruction caused a worsening of clinical conditions and finally the patient death for a septic peritonitis. CONCLUSIONS Full thickness resection represents an innovative tool for en-bloc resection of gastrointestinal tumoral lesion, but procedural complications and limitations must be considered before performing this procedure.

Gastroesophageal Reflux After Sleeve Gastrectomy: New Onset and Effect on Symptoms on a Prospective Evaluation.

BACKGROUND: Gastroesophageal reflux disease (GERD) is present in half of the obese candidates for bariatric surgery. Variability of symptoms and new onset of GERD are often debated. Prior studies have demonstrated that sleeve gastrectomy (SG) is associated with significant weight loss. OBJECTIVES: We prospectively evaluated the effect of a standardized SG technique on GERD symptoms in 104 patients. METHODS: All patients were surveyed on the presence of heartburn and/or regurgitation with a specific questionnaire (GERD-HRQL). Esophagogastroduodenoscopy (EGDS) was performed in the preoperative phase and after 12 months. RESULTS: All patients completed a 12-month follow-up. In the preoperative phase, 27.9% presented GERD symptoms (29 cases), while endoscopic findings were observed in 19.2% (20 cases). Preoperative GERD was ameliorated/solved in 65.5% of cases. The mean value of the GERD-HRQL score was significantly lower in postoperative evaluation (33.8 vs 19.4; p < 0.05). At 12-month EGDS, esophagitis was present in 13.5%, and GERD-HRQL symptoms were recorded in 10.6%. Considering patients treated until December 2015 (group 1, 44 patients) and those treated after December 2015 (group 2, 60 patients), all new clinical and endoscopic GERD diagnoses were observed in group 1; the majority of unsolved GERD cases was present in Ggoup 1 (8 vs 2; p < 0.05). CONCLUSION: Significant amelioration on preoperative GERD was confirmed after SG. New characteristics of reflux are emerging in SG patients, often asymptomatic. Standardization is necessary to define the real effect of SG on GERD.

Endoscopic papillary large balloon dilation in patients with large biliary stones and periampullary diverticula: Results of a multicentric series.

INTRODUCTION: Stone extraction represents the most frequent indication for endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic papillary large balloon dilation (EPLBD) is a recent introduced approach consisting of an endoscopic papillary large balloon dilation following limited endoscopic sphyncterotomy (ES), which has been proven to be safe and effective for extraction of large common bile duct (CBD) stones. Peri-ampullary diverticula (PAD) are described in 10-20% of patients undergoing ERCP. Aim of our study is to evaluate efficacy and safety of EPLBD for the extraction of large biliary stones in patients with PAD. METHODS: The prospectively collected endoscopy databases of 4 Italian ERCP high-volume centers were reviewed retrospectively, and all consecutive patients with an instrumental diagnosis of large biliary stones and PAD, between September 2014 and October 2016, were included in this study. RESULTS: Eighty-one patients (36 males, median age 75 years) were treated between September 2014 and October 2016. Deep biliary cannulation was reached in 78/80 patients. Successful extraction was achieved in 74/78 patients at the first attempt. AEs occurred in 8 patients (1 severe). Younger age, stone size and incomplete stone extraction were significantly associated with AEs. CONCLUSIONS: EPLBD is an effective and safe technique in patients with PAD and large biliary stones, which avoids the need of other techniques, thereby reducing the risks of adverse events.

Endoscopic ultrasound-guided gallbladder drainage for acute cholecystitis with a silicone-covered nitinol short bilaterally flared stent: a case series.

BACKGROUND AND STUDY AIM: Gallbladder drainage in patients with cholecystitis who are unsuitable for surgery may be performed by endoscopic ultrasound (EUS)-guided placement of specifically designed fully covered metal stents. We describe the first case series of patients treated with a silicone-covered nitinol stent with bilateral anchor flanges. PATIENTS AND METHODS: Data from consecutive patients with acute cholecystitis who were deemed unsuitable candidates for surgery were collected. The stent placement procedure was performed in two tertiary endoscopy centers by four experienced endoscopists. Technical and clinical success rates, as well as adverse events and clinical outcome at follow-up, were assessed. RESULTS: EUS-guided drainage for cholecystitis was performed in 16 patients (mean age 84 years; nine males). Technical and clinical success rates were 100 % (16/16) and 94 % (15/16), respectively; an early failure due to stone impaction occurred in the remaining case and required placement of a new stent. Symptom relief occurred in 11/15 cases (73 %) within 1 day, and within 2 days in the remaining 4 patients. Bleeding occurred in two patients (13 %): in one patient intraprocedural bleeding was successfully stopped during endoscopy; and delayed bleeding occurred in one patient requiring arterial embolization for catastrophic bleeding (patient died 10 days later). No cases of cholecystitis recurrence or biliary obstruction were observed during a median follow-up of 112 days (range 49 - 180 days). CONCLUSIONS: Our data showed that EUS-guided gallbladder drainage with a specially designed stent is feasible and successful in patients with acute cholecystitis who are unfit for surgery.