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Background: The treatment of people with acute abdominal pain differs if they have acute pancreatitis. It is important to know the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis, so that an informed decision can be made as to whether the person with abdominal pain has acute pancreatitis. There is currently no Cochrane review of the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis., Objectives: To compare the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase, either alone or in combination, in the diagnosis of acute pancreatitis in people with acute onset of a persistent, severe epigastric pain or diffuse abdominal pain., Search Methods: We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase., Selection Criteria: We included all studies that evaluated the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis. We excluded case-control studies because these studies are prone to bias. We accepted any of the following reference standards: biopsy, consensus conference definition, radiological features of acute pancreatitis, diagnosis of acute pancreatitis during laparotomy or autopsy, and organ failure. At least two review authors independently searched and screened the references located by the search to identify relevant studies., Data Collection and Analysis: Two review authors independently extracted data from the included studies. The thresholds used for the diagnosis of acute pancreatitis varied in the trials, resulting in sparse data for each index test. Because of sparse data, we used -2 log likelihood values to determine which model to use for meta-analysis. We calculated and reported the sensitivity, specificity, post-test probability of a positive and negative index test along with 95% confidence interval (CI) for each cutoff, but have reported only the results of the recommended cutoff of three times normal for serum amylase and serum lipase, and the manufacturer-recommended cutoff of 50 mg/mL for urinary trypsinogen-2 in the abstract., Main Results: Ten studies including 5056 participants met the inclusion criteria for this review and assessed the diagnostic accuracy of the index tests in people presenting to the emergency department with acute abdominal pain. The risk of bias was unclear or high for all of the included studies. The study that contributed approximately two-thirds of the participants included in this review was excluded from the results of the analysis presented below due to major concerns about the participants included in the study. We have presented only the results where at least two studies were included in the analysis.Serum amylase, serum lipase, and urinary trypsinogen-2 at the standard threshold levels of more than three times normal for serum amylase and serum lipase, and a threshold of 50 ng/mL for urinary trypsinogen-2 appear to have similar sensitivities (0.72 (95% CI 0.59 to 0.82); 0.79 (95% CI 0.54 to 0.92); and 0.72 (95% CI 0.56 to 0.84), respectively) and specificities (0.93 (95% CI 0.66 to 0.99); 0.89 (95% CI 0.46 to 0.99); and 0.90 (95% CI 0.85 to 0.93), respectively). At the median prevalence of 22.6% of acute pancreatitis in the studies, out of 100 people with positive test, serum amylase (more than three times normal), serum lipase (more than three times normal), and urinary trypsinogen (more than 50 ng/mL), 74 (95% CI 33 to 94); 68 (95% CI 21 to 94); and 67 (95% CI 57 to 76) people have acute pancreatitis, respectively; out of 100 people with negative test, serum amylase (more than three times normal), serum lipase (more than three times normal), and urinary trypsinogen (more than 50 ng/mL), 8 (95% CI 5 to 12); 7 (95% CI 3 to 15); and 8 (95% CI 5 to 13) people have acute pancreatitis, respectively. We were not able to compare these tests formally because of sparse data., Authors' Conclusions: As about a quarter of people with acute pancreatitis fail to be diagnosed as having acute pancreatitis with the evaluated tests, one should have a low threshold to admit the patient and treat them for acute pancreatitis if the symptoms are suggestive of acute pancreatitis, even if these tests are normal. About 1 in 10 patients without acute pancreatitis may be wrongly diagnosed as having acute pancreatitis with these tests, therefore it is important to consider other conditions that require urgent surgical intervention, such as perforated viscus, even if these tests are abnormal.The diagnostic performance of these tests decreases even further with the progression of time, and one should have an even lower threshold to perform additional investigations if the symptoms are suggestive of acute pancreatitis.

Background: In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure., Objectives: To assess the effects of different pharmacological interventions in people with acute pancreatitis., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials., Selection Criteria: We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review., Data Collection and Analysis: Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model., Main Results: We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials., Source of Funding: seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life., Authors' Conclusions: Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

Background: The treatment of people with pancreatic necrosis differs from that of people with oedematous pancreatitis. It is important to know the diagnostic accuracy of serum C-reactive protein (CRP), serum procalcitonin, and serum lactate dehydrogenase (LDH) as a triage test for the detection of pancreatic necrosis in people with acute pancreatitis, so that an informed decision can be made as to whether the person with pancreatic necrosis needs further investigations such as computed tomography (CT) scan or magnetic resonance imaging (MRI) scan and treatment for pancreatic necrosis started. There is currently no standard clinical practice, although CRP, particularly an increasing trend of CRP, is often used as a triage test to determine whether the person requires further imaging. There is also currently no systematic review of the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis., Objectives: To compare the diagnostic accuracy of CRP, procalcitonin, or LDH (index test), either alone or in combination, in the diagnosis of necrotising pancreatitis in people with acute pancreatitis and without organ failure., Search Methods: We searched MEDLINE, Embase, Science Citation Index Expanded, National Institute for Health Research (NIHR HTA and DARE), and other databases until March 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase., Selection Criteria: We included all studies that evaluated the diagnostic test accuracy of CRP, procalcitonin, and LDH for the diagnosis of pancreatic necrosis in people with acute pancreatitis using the following reference standards, either alone or in combination: radiological features of pancreatic necrosis (contrast-enhanced CT or MRI), surgeon's judgement of pancreatic necrosis during surgery, or histological confirmation of pancreatic necrosis. Had we found case-control studies, we planned to exclude them because they are prone to bias; however, we did not locate any. Two review authors independently identified the relevant studies from the retrieved references., Data Collection and Analysis: Two review authors independently extracted data, including methodological quality assessment, from the included studies. As the included studies reported CRP, procalcitonin, and LDH on different days of admission and measured at different cut-off levels, it was not possible to perform a meta-analysis using the bivariate model as planned. We have reported the sensitivity, specificity, post-test probability of a positive and negative index test along with 95% confidence interval (CI) on each of the different days of admission and measured at different cut-off levels., Main Results: A total of three studies including 242 participants met the inclusion criteria for this review. One study reported the diagnostic performance of CRP for two threshold levels (> 200 mg/L and > 279 mg/L) without stating the day on which the CRP was measured. One study reported the diagnostic performance of procalcitonin on day 1 (1 day after admission) using a threshold level of 0.5 ng/mL. One study reported the diagnostic performance of CRP on day 3 (3 days after admission) using a threshold level of 140 mg/L and LDH on day 5 (5 days after admission) using a threshold level of 290 U/L. The sensitivities and specificities varied: the point estimate of the sensitivities ranged from 0.72 to 0.88, while the point estimate of the specificities ranged from 0.75 to 1.00 for the different index tests on different days of hospital admission. However, the confidence intervals were wide: confidence intervals of sensitivities ranged from 0.51 to 0.97, while those of specificities ranged from 0.18 to 1.00 for the different tests on different days of hospital admission. Overall, none of the tests assessed in this review were sufficiently accurate to suggest that they could be useful in clinical practice., Authors' Conclusions: The paucity of data and methodological deficiencies in the studies meant that it was not possible to arrive at any conclusions regarding the diagnostic test accuracy of the index test because of the uncertainty of the results. Further well-designed diagnostic test accuracy studies with prespecified index test thresholds of CRP, procalcitonin, LDH; appropriate follow-up (for at least two weeks to ensure that the person does not have pancreatic necrosis, as early scans may not indicate pancreatic necrosis); and clearly defined reference standards (of surgical or radiological confirmation of pancreatic necrosis) are important to reliably determine the diagnostic accuracy of CRP, procalcitonin, and LDH.

Background: Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions., Objectives: To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions., Search Methods: We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively., Selection Criteria: We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively., Data Collection and Analysis: Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical summary receiver operating characteristic (HSROC) to compare the tests and assess heterogeneity, but used simpler models (such as univariate random-effects model and univariate fixed-effect model) for combining studies when appropriate because of the sparse data. We were unable to compare the diagnostic performance of the tests using formal statistical methods because of sparse data., Main Results: We included 54 studies involving a total of 3,196 participants evaluating the diagnostic accuracy of various index tests. In these 54 studies, eight different target conditions were identified with different final diagnoses constituting benign, precancerous, and cancerous lesions. None of the studies was of high methodological quality. None of the comparisons in which single studies were included was of sufficiently high methodological quality to warrant highlighting of the results. For differentiation of cancerous lesions from benign or precancerous lesions, we identified only one study per index test. The second analysis, of studies differentiating cancerous versus benign lesions, provided three tests in which meta-analysis could be performed. The sensitivities and specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95% confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00); EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to 0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39 to 0.84). The third analysis, of studies differentiating precancerous or cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence intervals reflecting the heterogeneity between the studies). The fourth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (dysplasia) provided three tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing invasive carcinoma were: CT: sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97); EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to 0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI 0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high-grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate-grade dysplasia) provided six tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing cancer (high-grade dysplasia or invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity 0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92), specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to 0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen 200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19 to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI 0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95% CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in which meta-analysis was performed. The seventh analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests in which meta-analysis was performed. The sensitivity and specificity for diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity 0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92), specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed.There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing., Authors' Conclusions: We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons.

Background: Acute necrotising pancreatitis carries significant mortality, morbidity, and resource use. There is considerable uncertainty as to how people with necrotising pancreatitis should be treated., Objectives: To assess the benefits and harms of different interventions in people with acute necrotising pancreatitis., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 4), MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers to April 2015 to identify randomised controlled trials (RCT). We also searched the references of included trials to identify further trials., Selection Criteria: We considered only RCTs performed in people with necrotising pancreatitis, irrespective of aetiology, presence of infection, language, blinding, or publication status for inclusion in the review., Data Collection and Analysis: Two review authors independently identified trials and extracted data. We calculated the odds ratio (OR) and mean difference with 95% confidence intervals (CI) using Review Manager 5 based on an available-case analysis using fixed-effect and random-effects models. We planned a network meta-analysis using Bayesian methods, but due to sparse data and uncertainty about the transitivity assumption, performed only indirect comparisons and used Frequentist methods., Main Results: We included eight RCTs with 311 participants in this review. After exclusion of five participants, we included 306 participants in one or more outcomes. Five trials (240 participants) investigated the three main treatments: open necrosectomy (121 participants), minimally invasive step-up approach (80 participants), and peritoneal lavage (39 participants) and were included in the network meta-analysis. Three trials (66 participants) investigated the variations in the main treatments: early open necrosectomy (25 participants), delayed open necrosectomy (11 participants), video-assisted minimally invasive step-up approach (12 participants), endoscopic minimally invasive step-up approach (10 participants), minimally invasive step-up approach (planned surgery) (four participants), and minimally invasive step-up approach (continued percutaneous drainage) (four participants). The trials included infected or sterile necrotising pancreatitis of varied aetiology.All the trials were at unclear or high risk of bias and the overall quality of evidence was low or very low for all the outcomes. Overall, short-term mortality was 30% and serious adverse events rate was 139 serious adverse events per 100 participants. The differences in short-term mortality and proportion of people with serious adverse events were imprecise in all the comparisons. The number of serious adverse events and adverse events were fewer in the minimally invasive step-up approach compared to open necrosectomy (serious adverse events: rate ratio 0.41, 95% CI 0.25 to 0.68; 88 participants; 1 study; adverse events: rate ratio 0.41, 95% CI 0.25 to 0.68; 88 participants; 1 study). The proportion of people with organ failure and the mean costs were lower in the minimally invasive step-up approach compared to open necrosectomy (organ failure: OR 0.20, 95% CI 0.07 to 0.60; 88 participants; 1 study; mean difference in costs: USD -11,922; P value < 0.05; 88 participants; 1 studies). There were more adverse events with video-assisted minimally invasive step-up approach group compared to endoscopic-assisted minimally invasive step-up approach group (rate ratio 11.70, 95% CI 1.52 to 89.87; 22 participants; 1 study), but the number of interventions per participant was less with video-assisted minimally invasive step-up approach group compared to endoscopic minimally invasive step-up approach group (difference in medians: 2 procedures; P value < 0.05; 20 participants; 1 study). The differences in any of the other comparisons for number of serious adverse events, proportion of people with organ failure, number of adverse events, length of hospital stay, and intensive therapy unit stay were either imprecise or were not consistent. None of the trials reported long-term mortality, infected pancreatic necrosis (trials that included participants with sterile necrosis), health-related quality of life at any time frame, proportion of people with adverse events, requirement for additional invasive intervention, time to return to normal activity, and time to return to work., Authors' Conclusions: Low to very low quality evidence suggested that the minimally invasive step-up approach resulted in fewer adverse events, serious adverse events, less organ failure, and lower costs compared to open necrosectomy. Very low quality evidence suggested that the endoscopic minimally invasive step-up approach resulted in fewer adverse events than the video-assisted minimally invasive step-up approach but increased the number of procedures required for treatment. There is currently no evidence to suggest that early open necrosectomy is superior or inferior to peritoneal lavage or delayed open necrosectomy. However, the CIs were wide and significant benefits or harms of different treatments cannot be ruled out. The TENSION trial currently underway in Netherlands is assessing the optimal way to perform the minimally invasive step-up approach (endoscopic drainage followed by endoscopic necrosectomy if necessary versus percutaneous drainage followed by video-assisted necrosectomy if necessary) and is assessing important clinical outcomes of interest for this review. Implications for further research on this topic will be determined after the results of this RCT are available.

Background: Pancreatic pseudocysts are walled-off peripancreatic fluid collections. There is considerable uncertainty about how pancreatic pseudocysts should be treated., Objectives: To assess the benefits and harms of different management strategies for pancreatic pseudocysts., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2015, Issue 9, and MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers until September 2015. We also searched the references of included trials and contacted trial authors., Selection Criteria: We only considered randomised controlled trials (RCTs) of people with pancreatic pseudocysts, regardless of size, presence of symptoms, or aetiology. We placed no restrictions on blinding, language, or publication status of the trials., Data Collection and Analysis: Two review authors independently identified trials and extracted data. We calculated the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CI) with RevMan 5, based on an available-case analysis for direct comparisons, using fixed-effect and random-effect models. We also conducted indirect comparisons (rather than network meta-analysis), since there were no outcomes for which direct and indirect evidence were available., Main Results: We included four RCTs, with 177 participants, in this review. After one participant was excluded, 176 participants were randomised to endoscopic ultrasound (EUS)-guided drainage (88 participants), endoscopic drainage (44 participants), EUS-guided drainage with nasocystic drainage (24 participants), and open surgical drainage (20 participants). The comparisons included endoscopic drainage versus EUS-guided drainage (two trials), EUS-guided drainage with nasocystic drainage versus EUS-guided drainage alone (one trial), and open surgical drainage versus EUS-guided drainage (one trial). The participants were mostly symptomatic, with pancreatic pseudocysts resulting from acute and chronic pancreatitis of varied aetiology. The mean size of the pseudocysts ranged between 70 mm and 155 mm across studies. Although the trials appeared to include similar types of participants for all comparisons, we were unable to assess this statistically, since there were no direct and indirect results for any of the comparisons.All the trials were at unclear or high risk of bias, and the overall quality of evidence was low or very low for all outcomes. One death occurred in the endoscopic drainage group (1/44; 2.3%), due to bleeding. There were no deaths in the other groups. The differences in the serious adverse events were imprecise. Short-term health-related quality of life (HRQoL; four weeks to three months) was worse (MD -21.00; 95% CI -33.21 to -8.79; participants = 40; studies = 1; range: 0 to 100; higher score indicates better) and the costs were higher in the open surgical drainage group than the EUS-guided drainage group (MD 8040 USD; 95% CI 3020 to 13,060; participants = 40; studies = 1). There were fewer adverse events in the EUS-guided drainage with nasocystic drainage group than in the EUS-guided drainage alone (OR 0.20; 95% CI 0.06 to 0.73; participants = 47; studies = 1), or the endoscopic drainage group (indirect comparison: OR 0.08; 95% CI 0.01 to 0.61). Participants with EUS-guided drainage with nasocystic drainage also had shorter hospital stays compared to EUS-guided drainage alone (MD -8.10 days; 95% CI -9.79 to -6.41; participants = 47; studies = 1), endoscopic drainage (indirect comparison: MD -7.10 days; 95% CI -9.38 to -4.82), or open surgical drainage group (indirect comparison: MD -12.30 days; 95% CI -14.48 to -10.12). The open surgical drainage group had longer hospital stays than the EUS-guided drainage group (MD 4.20 days; 95% CI 2.82 to 5.58; participants = 40; studies = 1); the endoscopic drainage group had longer hospital stays than the open drainage group (indirect comparison: -5.20 days; 95% CI -7.26 to -3.14). The need for additional invasive interventions was higher for the endoscopic drainage group than the EUS-guided drainage group (OR 11.13; 95% CI 2.85 to 43.44; participants = 89; studies = 2), and the open drainage group (indirect comparison: OR 23.69; 95% CI 1.40 to 400.71). The differences between groups were imprecise for the other comparisons that could be performed. None of the trials reported long-term mortality, medium-term HRQoL (three months to one year), long-term HRQoL (longer than one year), time-to-return to normal activities, or time-to-return to work., Authors' Conclusions: Very low-quality evidence suggested that the differences in mortality and serious adverse events between treatments were imprecise. Low-quality evidence suggested that short-term HRQoL (four weeks to three months) was worse, and the costs were higher in the open surgical drainage group than in the EUS-guided drainage group. Low-quality or very low-quality evidence suggested that EUS-guided drainage with nasocystic drainage led to fewer adverse events than EUS-guided or endoscopic drainage, and shorter hospital stays when compared to EUS-guided drainage, endoscopic drainage, or open surgical drainage, while EUS-guided drainage led to shorter hospital stays than open surgical drainage. Low-quality evidence suggested that there was a higher need for additional invasive procedures with endoscopic drainage than EUS-guided drainage, while it was lower in the open surgical drainage than in the endoscopic drainage group.Further RCTs are needed to compare EUS-guided drainage, with or without nasocystic drainage, in symptomatic patients with pancreatic pseudocysts that require treatment. Future trials should include patient-oriented outcomes such as mortality, serious adverse events, HRQoL, hospital stay, return-to-normal activity, number of work days lost, and the need for additional procedures, for a minimum follow-up period of two to three years.