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.
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.
The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the ...IAP/APA evidence-based guidelines for the management of AP.
Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group.
600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013.
With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality.
Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP.
MAIN RECOMMENDATION
1
ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence ...of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible.
Weak recommendation, low quality evidence.
2
ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections.
Strong recommendation, moderate quality evidence.
FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear.
Weak recommendation, low quality evidence.
3
ESGE recommends initial goal-directed intravenous fluid therapy with Ringer’s lactate (e. g. 5 – 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals.
Strong recommendation, moderate quality evidence.
4
ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis.
Strong recommendation, high quality evidence.
5
ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis.
Strong recommendation, low quality evidence.
ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient.
Weak recommendation, low quality evidence.
6
ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise.
Strong recommendation, moderate quality evidence.
7
ESGE suggests that, in the absence of improvement following endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery (if percutaneous drainage has already been performed) is to be preferred over open surgery as the next therapeutic step, taking into account the location of the walled-off necrosis and local expertise.
Weak recommendation, low quality evidence.
8
ESGE recommends long-term indwelling of transluminal plastic stents in patients with disconnected pancreatic duct syndrome.
Strong recommendation, low quality evidence.
Lumen-apposing metal stents should be retrieved within 4 weeks to avoid stent-related adverse effects.
Strong recommendation, low quality evidence.
Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural ...inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are especially important in the process of tumor invasion, progression and the metastasis of colorectal cancer (CRC). It has been proposed that MMPs and TIMPs might play a part not only in tumor invasion and initiation of metastasis but also in carcinogenesis from colorectal adenomas. Several recent studies demonstrated that high preoperative serum or plasma MMP-2, MMP-9 and TIMP-1 antigen levels are strong predictive factors for poor prognosis in patients with CRC and their determination might be useful for identification of patients with higher risk for cancer recurrence. MMP-9 and TIMP-1 have significant potential tumor marker impact in CRC. Their diagnostic sensitivity is consistently higher than those of conventional biomarkers. The pharmacological targeting of CRC by the development of a new generation of selective inhibitors of MMPs, that is highly specific for certain MMPs, is a promising and challenging area for the future.
The Toll‐like receptor 4 (TLR4) that recognizes endotoxin, a trigger of inflammation in alcoholic liver disease (ALD), activates two signaling pathways utilizing different adapter molecules: the ...common TLR adapter, myeloid differentiation factor 88 (MyD88), or Toll/interleukin immune‐response–domain‐containing adaptor inducing interferon (IFN)‐β. The MyD88 pathway induces proinflammatory cytokine activation, a critical mediator of ALD. Here we evaluated the role of MyD88 in alcohol‐induced liver injury in wild‐type, TLR2‐deficient, TLR4‐deficient, or MyD88‐deficient (knockout KO) mice after administration of the Lieber‐De‐Carli diet (4.5% volume/volume ethanol) or an isocaloric liquid control diet for 5 weeks. Alcohol feeding resulted in a significant increase in serum alanine aminotransferase levels, liver steatosis and triglyceride levels suggesting liver damage in WT, TLR2‐KO, and MyD88‐KO but not in TLR4‐KO mice. Expression of inflammatory mediators (tumor necrosis factor–α and interleukin‐6) and TLR4 coreceptors (CD14 and MD2) was significantly higher in livers of alcohol‐fed WT, TLR2‐KO, or MyD88‐KO, but not in TLR4‐KO mice, compared to controls. Reactive oxygen radicals produced by cytochrome P450 and the nicotinamide adenine dinucleotide phosphate complexes contribute to alcoholic liver damage. Alcohol feeding–induced expression and activation of cytochrome P450 and the nicotinamide adenine dinucleotide phosphate complex were prevented by TLR4‐deficiency but not by MyD88‐deficiency. Liver expression of interferon regulatory factor 3 (IRF3), a MyD88‐independent signaling molecule, was not affected by chronic alcohol treatment in whole livers of WT mice or in any of the KO mice. However, the induction of IRF7, an IRF3‐inducible gene, was found in Kupffer cells of alcohol‐fed WT mice. Alcohol feeding also induced nuclear factor–κB activation in a TLR4‐dependent MyD88‐independent manner. Conclusion: While TLR4 deficiency was protective, MyD88 deficiency failed to prevent alcohol‐induced liver damage and inflammation. These results suggest that the common TLR adapter, MyD88, is dispensable in TLR4‐mediated liver injury in ALD. (HEPATOLOGY 2008.)
Extracellular vesicles (EV) carry their cargo in a membrane protected form, however, their value in early diagnostics is not well known. Although pancreatic cysts are heterogeneous, they can be ...clustered into the larger groups of pseudocysts (PC), and serous and mucinous pancreatic cystic neoplasms (S-PCN and M-PCN, respectively). In contrast to PCs and S-PCNs, M-PCNs may progress to malignant pancreatic cancers. Since current diagnostic tools do not meet the criteria of high sensitivity and specificity, novel methods are urgently needed to differentiate M-PCNs from other cysts. We show that cyst fluid is a rich source of EVs that are positive and negative for the EV markers CD63 and CD81, respectively. Whereas we found no difference in the EV number when comparing M-PCN with other pancreatic cysts, our EV-based biomarker identification showed that EVs from M-PCNs had a higher level of miR-200b. We also prove that not only EV-derived, but also total cyst fluid miR-200b discriminates patients with M-PCN from other pancreatic cysts with a higher sensitivity and specificity compared to other diagnostic methods, providing the possibility for clinical applications. Our results show that measuring miR-200b in cyst fluid-derived EVs or from cyst fluid may be clinically important in categorizing patients.
Toll-like receptor 4 (TLR4) and its coreceptor, myeloid differentiation factor-2 (MD-2), are key in recognition of lipopolysaccharide (LPS) and activation of proinflammatory pathways. Here we tested ...the hypothesis that TLR4 and its coreceptor MD-2 play a central role in nonalcoholic steatohepatitis (NASH) and liver fibrosis in nonalcoholic fatty liver disease. Mice of control genotypes and those deficient in MD-2 or TLR4 knockout (KO) received methionine choline-deficient (MCD) or methionine choline-supplemented (MCS) diet. In mice of control genotypes, MCD diet resulted in NASH, liver triglycerides accumulation, and increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, compared with MCS diet. These features of NASH were significantly attenuated in MD-2 KO and TLR4 KO mice. Serum alanine aminotransferase, an indicator of liver injury, was increased in MCD diet-fed genotype controls but was attenuated in MD-2 KO and TLR4 KO mice. Inflammatory activation, indicated by serum TNF-α and nictoinamide adenine dinucleotide phosphate oxidase complex mRNA expression and activation, was significantly lower in MCD diet-fed MD-2 KO and TLR4 KO compared with corresponding genotype control mice. Markers of liver fibrosis collagen by Sirius red and α-smooth muscle actin (SMA) staining, procollagen-I, transforming growth factor-β1, α-SMA, matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-1 mRNA were attenuated in MD-2 and TLR4 KO compared with their control genotype counterparts. In conclusion, our results demonstrate a novel, critical role for LPS recognition complex, including MD-2 and TLR4, through NADPH activation in liver steatosis, and fibrosis in a NASH model in mice.
Liver damage in COVID-19 patients was documented as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or an elevated AST/ALT ratio, known as the De Ritis ratio. ...However, the prognostic value of the elevated De Ritis ratio in COVID-19 patients is still unknown. The aim of our study was to evaluate the prognostic value of the De Ritis ratio compared to other abnormal laboratory parameters and its relation to mortality. We selected 322 COVID-19 patients in this retrospective study conducted between November 2020 and March 2021. The laboratory parameters were measured on admission and followed till patient discharge or death. Of the 322 COVID-19 patients, 57 (17.7%) had gastrointestinal symptoms on admission. The multivariate analysis showed that the De Ritis ratio was an independent risk factor for mortality, with an OR of 29.967 (95% CI 5.266-170.514). In ROC analysis, the AUC value of the the De Ritis ratio was 0.85 (95% CI 0.777-0.923,
< 0.05) with sensitivity and specificity of 80.6% and 75.2%, respectively. A De Ritis ratio ≥1.218 was significantly associated with patient mortality, disease severity, higher AST and IL-6 levels, and a lower ALT level. An elevated De Ritis ratio on admission is independently associated with mortality in COVID-19 patients, indicating liver injury and cytokine release syndrome.
Of all the possible complications associated with endoscopic retrograde cholangiopancreatography (ERCP), acute pancreatitis undoubtedly represents the heaviest burden for patients and healthcare ...professionals. The overall incidence, ranging from 3.5% to around 10%, and annual estimated costs exceeding $150 million in the USA should signal caution for everyone carrying out ERCP. In-depth knowledge of the risk factors and the pharmacological and endoscopic treatment options is required to avoid this adverse event. In this review, we evaluate the relevant data published in the literature since the appearance of the latest recommendations of the leading gastroenterological societies. Thus, we intend to provide a comprehensive and up-to-date overview of the factors to consider and possible interventions applicable before and after the intervention to prevent the development of post-ERCP pancreatitis.
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