Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four ...distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos.
Main Recommendations
Prophylaxis
1
ESGE recommends routine rectal administration of 100 mg of diclofenac or indomethacin immediately before endoscopic retrograde cholangiopancreatography (ERCP) in ...all patients without contraindications to nonsteroidal anti-inflammatory drug administration.
Strong recommendation, moderate quality evidence.
2
ESGE recommends prophylactic pancreatic stenting in selected patients at high risk for post-ERCP pancreatitis (inadvertent guidewire insertion/opacification of the pancreatic duct, double-guidewire cannulation).
Strong recommendation, moderate quality evidence.
3
ESGE suggests against routine endoscopic biliary sphincterotomy before the insertion of a single plastic stent or an uncovered/partially covered self-expandable metal stent for relief of biliary obstruction.
Weak recommendation, moderate quality evidence.
4
ESGE recommends against the routine use of antibiotic prophylaxis before ERCP.
Strong recommendation, moderate quality evidence.
5
ESGE suggests antibiotic prophylaxis before ERCP in the case of anticipated incomplete biliary drainage, for severely immunocompromised patients, and when performing cholangioscopy.
Weak recommendation, moderate quality evidence.
6
ESGE suggests tests of coagulation are not routinely required prior to ERCP for patients who are not on anticoagulants and not jaundiced.
Weak recommendation, low quality evidence.
Treatment
7
ESGE suggests against salvage pancreatic stenting in patients with post-ERCP pancreatitis.
Weak recommendation, low quality evidence.
8
ESGE suggests temporary placement of a biliary fully covered self-expandable metal stent for post-sphincterotomy bleeding refractory to standard hemostatic modalities.
Weak recommendation, low quality evidence.
9
ESGE suggests to evaluate patients with post-ERCP cholangitis by abdominal ultrasonography or computed tomography (CT) scan and, in the absence of improvement with conservative therapy, to consider repeat ERCP. A bile sample should be collected for microbiological examination during repeat ERCP.
Weak recommendation, low quality evidence.
This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the removal of foreign bodies in the upper gastrointestinal tract in adults.
...Recommendations
Nonendoscopic measures
1
ESGE recommends diagnostic evaluation based on the patient’s history and symptoms. ESGE recommends a physical examination focused on the patient’s general condition and to assess signs of any complications (strong recommendation, low quality evidence).
2
ESGE does not recommend radiological evaluation for patients with nonbony food bolus impaction without complications. We recommend plain radiography to assess the presence, location, size, configuration, and number of ingested foreign bodies if ingestion of radiopaque objects is suspected or type of object is unknown (strong recommendation, low quality evidence).
3
ESGE recommends computed tomography (CT) scan in all patients with suspected perforation or other complication that may require surgery (strong recommendation, low quality evidence).
4
ESGE does not recommend barium swallow, because of the risk of aspiration and worsening of the endoscopic visualization (strong recommendation, low quality evidence).
5
ESGE recommends clinical observation without the need for endoscopic removal for management of asymptomatic patients with ingestion of blunt and small objects (except batteries and magnets). If feasible, outpatient management is appropriate (strong recommendation, low quality evidence).
6
ESGE recommends close observation in asymptomatic individuals who have concealed packets of drugs by swallowing (“body packing”). We recommend against endoscopic retrieval. We recommend surgical referral in cases of suspected packet rupture, failure of packets to progress, or intestinal obstruction (strong recommendation, low quality evidence).
Endoscopic measures
7
ESGE recommends emergent (preferably within 2 hours, but at the latest within 6 hours) therapeutic esophagogastroduodenoscopy for foreign bodies inducing complete esophageal obstruction, and for sharp-pointed objects or batteries in the esophagus. We recommend urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for other esophageal foreign bodies without complete obstruction (strong recommendation, low quality evidence).
8
ESGE suggests treatment of food bolus impaction in the esophagus by gently pushing the bolus into the stomach. If this procedure is not successful, retrieval should be considered (weak recommendation, low quality evidence).
The effectiveness of medical treatment of esophageal food bolus impaction is debated. It is therefore recommended, that medical treatment should not delay endoscopy (strong recommendation, low quality evidence).
9
In cases of food bolus impaction, ESGE recommends a diagnostic work-up for potential underlying disease, including histological evaluation, in addition to therapeutic endoscopy (strong recommendation, low quality evidence).
10
ESGE recommends urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for foreign bodies in the stomach such as sharp-pointed objects, magnets, batteries and large/long objects. We suggest nonurgent (within 72 hours) therapeutic esophagogastroduodenoscopy for medium-sized blunt foreign bodies in the stomach (strong recommendation, low quality evidence).
11
ESGE recommends the use of a protective device in order to avoid esophagogastric/pharyngeal damage and aspiration during endoscopic extraction of sharp-pointed foreign bodies. Endotracheal intubation should be considered in the case of high risk of aspiration (strong recommendation, low quality evidence).
12
ESGE suggests the use of suitable extraction devices according to the type and location of the ingested foreign body (weak recommendation, low quality evidence).
13
After successful and uncomplicated endoscopic removal of ingested foreign bodies, ESGE suggests that the patient may be discharged. If foreign bodies are not or cannot be removed, a case-by-case approach depending on the size and type of the foreign body is suggested (weak recommendation, low quality evidence).
Main Recommendations
ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.
Strong ...recommendation, low quality evidence.
ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.
Strong recommendation, moderate quality evidence.
ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.
Strong recommendation, moderate quality evidence.
ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:
– severe, as soon as possible and within 12 hours for patients with septic shock
– moderate, within 48 – 72 hours
– mild, elective.
Strong recommendation, low quality evidence.
ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.
Strong recommendation, moderate quality of evidence.
ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones.
Strong recommendation, high quality evidence.
ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.
Strong recommendation, moderate quality evidence.
ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events.
Strong recommendation, moderate quality evidence.
Automatic image detection of colonic polyps is still an unsolved problem due to the large variation of polyps in terms of shape, texture, size, and color, and the existence of various polyp-like ...mimics during colonoscopy. In this paper, we apply a recent region-based convolutional neural network (CNN) approach for the automatic detection of polyps in the images and videos obtained from colonoscopy examinations. We use a deep-CNN model (Inception Resnet) as a transfer learning scheme in the detection system. To overcome the polyp detection obstacles and the small number of polyp images, we examine image augmentation strategies for training deep networks. We further propose two efficient post-learning methods, such as automatic false positive learning and offline learning, both of which can be incorporated with the region-based detection system for reliable polyp detection. Using the large size of colonoscopy databases, experimental results demonstrate that the suggested detection systems show better performance than other systems in the literature. Furthermore, we show improved detection performance using the proposed post-learning schemes for colonoscopy videos.
This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It provides practical advice on how to achieve successful cannulation and sphincterotomy at ...minimum risk to the patient. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence.
Main recommendations
1
ESGE suggests that difficult biliary cannulation is defined by the presence of one or more of the following: more than 5 contacts with the papilla whilst attempting to cannulate; more than 5 minutes spent attempting to cannulate following visualization of the papilla; more than one unintended pancreatic duct cannulation or opacification (low quality evidence, weak recommendation).
2
ESGE recommends the guidewire-assisted technique for primary biliary cannulation, since it reduces the risk of post-ERCP pancreatitis (moderate quality evidence, strong recommendation).
3
ESGE recommends using pancreatic guidewire (PGW)-assisted biliary cannulation in patients where biliary cannulation is difficult and repeated unintentional access to the main pancreatic duct occurs (moderate quality evidence, strong recommendation).
ESGE recommends attempting prophylactic pancreatic stenting in all patients with PGW-assisted attempts at biliary cannulation (moderate quality evidence, strong recommendation).
4
ESGE recommends needle-knife fistulotomy as the preferred technique for precutting (moderate quality evidence, strong recommendation).
ESGE suggests that precutting should be used only by endoscopists who achieve selective biliary cannulation in more than 80 % of cases using standard cannulation techniques (low quality evidence, weak recommendation).
When access to the pancreatic duct is easy to obtain, ESGE suggests placement of a pancreatic stent prior to precutting (moderate quality evidence, weak recommendation).
5
ESGE recommends that in patients with a small papilla that is difficult to cannulate, transpancreatic biliary sphincterotomy should be considered if unintentional insertion of a guidewire into the pancreatic duct occurs (moderate quality evidence, strong recommendation).
In patients who have had transpancreatic sphincterotomy, ESGE suggests prophylactic pancreatic stenting (moderate quality evidence, strong recommendation).
6
ESGE recommends that mixed current is used for sphincterotomy rather than pure cut current alone, as there is a decreased risk of mild bleeding with the former (moderate quality evidence, strong recommendation).
7
ESGE suggests endoscopic papillary balloon dilation (EPBD) as an alternative to endoscopic sphincterotomy (EST) for extracting CBD stones < 8 mm in patients without anatomical or clinical contraindications, especially in the presence of coagulopathy or altered anatomy (moderate quality evidence, strong recommendation).
8
ESGE does not recommend routine biliary sphincterotomy for patients undergoing pancreatic sphincterotomy, and suggests that it is reserved for patients in whom there is evidence of coexisting bile duct obstruction or biliary sphincter of Oddi dysfunction (moderate quality evidence, weak recommendation).
9
In patients with periampullary diverticulum (PAD) and difficult cannulation, ESGE suggests that pancreatic duct stent placement followed by precut sphincterotomy or needle-knife fistulotomy are suitable options to achieve cannulation (low quality evidence, weak recommendation).
ESGE suggests that EST is safe in patients with PAD. In cases where EST is technically difficult to complete as a result of a PAD, large stone removal can be facilitated by a small EST combined with EPBD or use of EPBD alone (low quality evidence, weak recommendation).
10
For cannulation of the minor papilla, ESGE suggests using wire-guided cannulation, with or without contrast, and sphincterotomy with a pull-type sphincterotome or a needle-knife over a plastic stent (low quality evidence, weak recommendation).
When cannulation of the minor papilla is difficult, ESGE suggests secretin injection, which can be preceded by methylene blue spray in the duodenum (low quality evidence, weak recommendation).
11
In patients with choledocholithiasis who are scheduled for elective cholecystectomy, ESGE suggests intraoperative ERCP with laparoendoscopic rendezvous (moderate quality evidence, weak recommendation).
ESGE suggests that when biliary cannulation is unsuccessful with a standard retrograde approach, anterograde guidewire insertion either by a percutaneous or endoscopic ultrasound (EUS)-guided approach can be used to achieve biliary access (low quality evidence, weak recommendation).
12
ESGE suggests that in patients with Billroth II gastrectomy ERCP should be performed in referral centers, with the side-viewing endoscope as a first option; forward-viewing endoscopes are the second choice in cases of failure (low quality evidence, weak recommendation).
A straight standard ERCP catheter or an inverted sphincterotome, with or without the guidewire, is recommended by ESGE for biliopancreatic cannulation in patients who have undergone Billroth II gastrectomy (low quality evidence, strong recommendation).
Endoscopic papillary ballon dilation (EPBD) is suggested as an alternative to sphincterotomy for stone extraction in the setting of patients with Billroth II gastrectomy (low quality evidence, weak recommendation).
In patients with complex post-surgical anatomy ESGE suggests referral to a center where device-assisted enteroscopy techniques are available (very low quality evidence, weak recommendation).
This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage ...(NVUGIH).
Main Recommendations
MR1.
ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence).
MR2.
ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence).
MR3.
ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 – 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence).
MR4.
ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence).
MR5.
ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence).
MR6.
ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 – 120 minutes prior to upper gastrointestinal GI endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence).
MR7.
Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence).
MR8.
ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence).
MR9.
ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence).
MR10.
In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence).
MR11.
ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence).
MR12.
ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence).
MR13.
ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence).
MR14.
In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of
Helicobacter pylori
in the acute setting with initiation of appropriate antibiotic therapy when
H. pylori
is detected. Re-testing for
H. pylori
should be performed in those patients with a negative test in the acute setting. Documentation of successful
H. pylori
eradication is recommended (strong recommendation, high quality evidence).
MR15.
In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).
Fatigue is increasingly recognized as a major complaint in patients with chronic inflammatory and autoimmune diseases. Although fatigue is assumed to represent a significant problem in celiac ...disease, existing knowledge is scarce, and opinions are conflicting. This study aimed to investigate the prevalence and severity of fatigue in patients with newly diagnosed celiac disease and compare it with healthy control subjects. Ninety patients with newly diagnosed celiac disease were compared with 90 age- and sex-matched healthy subjects. The primary endpoints were fatigue severity as measured by: the fatigue Visual Analog Scale (fVAS), the Fatigue Severity Scale (FSS), and the inverted Vitality subscale of the MOS36 (SF-36vs). Higher scores indicate more severe fatigue. Clinically relevant fatigue was determined using predefined cut-off values. Secondary endpoints were the associations between fatigue, and sex, age, depression, pain, and selected biochemical variables. The median (IQR) fVAS-scores were 43.0 (18.0-64.5) in patients, and 9.0 (2.0-16.0) in the control group (p < 0.001); and the FSS scores 3.8 (2.0-4.8) in patients, and 1.4 (1.0-1.9) in control subjects (p < 0.001). Inverted SF-36vs scores had a mean (SD) value of 58.8 (23.6) in patients, and 29.7 (14.3) in healthy subjects (p < 0.001). The presence of clinically relevant fatigue ranged from 41 to 50% in patients. Increased fatigue severity was associated with female sex, younger age, and elevated pain and depression scores, but not with levels of selected biochemical variables, including hemoglobin. Fatigue is a severe and frequent phenomenon in patients with untreated celiac disease.
MAIN RECOMMENDATIONS
1
ESGE/EASL recommend that, as the primary diagnostic modality for PSC, magnetic resonance cholangiography (MRC) should be preferred over endoscopic retrograde ...cholangiopancreatography (ERCP).
Moderate quality evidence, strong recommendation.
2
ESGE/EASL suggest that ERCP can be considered if MRC plus liver biopsy is equivocal or contraindicated in patients with persisting clinical suspicion of PSC. The risks of ERCP have to be weighed against the potential benefit with regard to surveillance and treatment recommendations.
Low quality evidence, weak recommendation.
6
ESGE/EASL suggest that, in patients with an established diagnosis of PSC, MRC should be considered before therapeutic ERCP.
Weak recommendation, low quality evidence.
7
ESGE/EASL suggest performing endoscopic treatment with concomitant ductal sampling (brush cytology, endobiliary biopsies) of suspected significant strictures identified at MRC in PSC patients who present with symptoms likely to improve following endoscopic treatment.
Strong recommendation, low quality evidence.
9
ESGE/EASL recommend weighing the anticipated benefits of biliary papillotomy/sphincterotomy against its risks on a case-by-case basis.
Strong recommendation, moderate quality evidence.
Biliary papillotomy/sphincterotomy should be considered especially after difficult cannulation.
Strong recommendation, low quality evidence.
16
ESGE/EASL suggest routine administration of prophylactic antibiotics before ERCP in patients with PSC.
Strong recommendation, low quality evidence.
17
EASL/ESGE recommend that cholangiocarcinoma (CCA) should be suspected in any patient with worsening cholestasis, weight loss, raised serum CA19-9, and/or new or progressive dominant stricture, particularly with an associated enhancing mass lesion.
Strong recommendation, moderate quality evidence.
19
ESGE/EASL recommend ductal sampling (brush cytology, endobiliary biopsies) as part of the initial investigation for the diagnosis and staging of suspected CCA in patients with PSC.
Strong recommendation, high quality evidence.
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