Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma:A systematic review and meta-analysis

BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.

Interplay between nitric oxide and VIP in CCK-8-induced phasic contractile activity in the rabbit sphincter of Oddi

AIM: The sphincter of Oddi (SO) plays an important role in delivery of bile into the duodenum. To establish whether vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) were involved in phasic contractile activity of the rabbit SO stimulated by cholecystokinin-octapeptide (CCK-8).METHODS: Isolated SO muscle rings were cleaned of fat and mounted horizontally on two small L-shaped hooksone of which was connected to a force transducer for the measurement of isometric tension. The experiments were carried out in a thermostatically controlled (37±0.2℃)organ bath (5 mL) containing Krebs solution. The organ fluid was gassed with 95% O2 and 50 mL/L CO2 to keep the pH at 7.40±0.05. Contractile responses to CCK-8 (1μmol/L) were evaluated in the presence and absence of N^G-nitro-L-arginine (LNNA), an inhibitor of NO synthase (100μmol/L), and (p-chloro-D-Phe^6-Leu^17)-VIP (VIPa,30μmol/L), a VIP receptor antagonist.RESULTS: CCK-8 stimulated the phasic activity of the SO.NO synthase inhibition increased the frequency and amplitude of contractions with a slight increase in developed tension.Pre-incubation with VIPa also attenuated this CCK-8 effect.The combined application of LNNA and VIPa abolished the phasic activity of the muscle rings with a marked increase in tension in response to CCK-8.CONCLUSION: VIP and NO together contribute to an increase in phasic activity of SO.

Intralesional steroid is beneficial in benign refractory esophageal strictures:A meta-analysis

AIM To analyze the effect of intralesional steroid injections in addition to endoscopic dilation of benign refractory esophageal strictures.METHODS A comprehensive search was performed in three databases from inception to 10 April 2017 to identify trials, comparing the efficacy of endoscopic dilation to dilation combined with intralesional steroid injections. Following the data extraction, meta-analytical calculations were performed on measures of outcome by the randomeffects method of Der Simonian and Laird. Heterogeneity of the studies was tested by Cochrane's Q and I^2 statistics. Risk of quality and bias was assessed by the Newcastle Ottawa Scale and JADAD assessment tools.RESULTS Eleven articles were identified suitable for analyses, involving 343 patients, 235 cases and 229 controls in total. Four studies used crossover design with 121 subjects enrolled. The periodic dilation index(PDI) was comparable in 4 studies, where the pooled result showed a significant improvement of PDI in the steroid group(MD:-1.12 dilation/month, 95% CI:-1.99 to -0.25 P = 0.012; I^2 = 74.4%). The total number of repeat dilations(TNRD) was comparable in 5 studies and showed a non-significant decrease(MD:-1.17, 95%CI:-0.24-0.05, P = 0.057; I^2 = 0), while the dysphagia score(DS) was comparable in 5 studies and did not improve(SMD: 0.35, 95%CI:-0.38, 1.08, P = 0.351; I^2 = 83.98%) after intralesional steroid injection.CONCLUSION Intralesional steroid injection increases the time between endoscopic dilations of benign refractory esophageal strictures. However, its potential role needs further research.

Prophylactic transcatheter arterial embolization reduces rebleeding in non-variceal upper gastrointestinal bleeding: A meta-analysis

BACKGROUND Despite the improvement in the endoscopic hemostasis of non-variceal upper gastrointestinal bleeding(NVUGIB),rebleeding remains a major concern.AIM To assess the role of prophylactic transcatheter arterial embolization(PTAE)added to successful hemostatic treatment among NVUGIB patients.METHODS We searched three databases from inception through October 19th,2020.Randomized controlled trials(RCTs)and observational cohort studies were eligible.Studies compared patients with NVUGIB receiving PTAE to those who did not get PTAE.Investigated outcomes were rebleeding,mortality,reintervention,need for surgery and transfusion,length of hospital(LOH),and intensive care unit(ICU)stay.In the quantitative synthesis,odds ratios(ORs)and weighted mean differences(WMDs)were calculated with the random-effects model and interpreted with 95%confidence intervals(CIs).RESULTS We included a total of 3 RCTs and 9 observational studies with a total of 1329 patients,with 486 in the intervention group.PTAE was associated with lower odds of rebleeding(OR=0.48,95%CI:0.29–0.78).There was no difference in the 30-d mortality rates(OR=0.82,95%CI:0.39–1.72)between the PTAE and control groups.Patients who underwent PTAE treatment had a lower chance for reintervention(OR=0.48,95%CI:0.31–0.76)or rescue surgery(OR=0.35,95%CI:0.14–0.92).The LOH and ICU stay was shorter in the PTAE group,but the difference was non-significant[WMD=-3.77,95%CI:(-8.00)–0.45;WMD=-1.33,95%CI:(-2.84)–0.18,respectively].CONCLUSION PTAE is associated with lower odds of rebleeding and any reintervention in NVUGIB.However,further RCTs are needed to have a higher level of evidence.

Ethanol inhibits the motility of rabbit sphincter of Oddi in vitro

AIM: The role of the sphincter of Oddi (SO) in ethanol (ETOH)-induced pancreatitis is controversial. Our aim was to characterise the effect of ETOH on basal and stimulated SO motility.METHODS: SOs removed from white rabbits were placed in an organ bath (Krebs solution, pH7.4, 37℃). The effects of 2 mL/L, 4 mL/L, 6 mL/L and 8 mL/L of ETOH on the contractile responses of the sphincter were determined.1 SOs were stimulated with either 0.1μol/L carbachol, 1μol/L erythromycin or 0.1μol/L cholecystokinin (CCK).RESULTS: ETOH at a dose of 4 mL/L significantly decreased the baseline contractile amplitude from 11.98±0.05 mN to 11.19±0.07 mN. However, no significant changes in the contractile frequency were observed. ETOH (0.6%) significantly decreased both the baseline amplitude and the frequency compared to the control group (10.50±0.01 mN,12.13±0.10 mN and 3.53±0.13 c/min, 5.5±0.13 cycles(c)/min,respectively). Moreover, 0.8% of ETOH resulted in complete relaxation of the SO. Carbachol (0.1μol/L)or erythromycin (1μol/L) stimulated the baseline amplitudes (by 82% and 75%, respectively) and the contractile frequencies (by 150% and 106%, respectively). In the carbachol or en/thromydn-stimulated groups 2-6 mL/L of ETOH significantly inhibited both the amplitude and the frequency. Interestingly,a 4-5 min administration of 6 mL/L ETOH suddenly and completely relaxed the SO. CCK (0.1μol/L) stimulated the baseline amplitude from 12.37±0.05 mN to 27.40±1.82 mN within 1.60±0.24 min. After this peak, the amplitudede creased to 17.17±0.22 mN and remained constant during the experiment. The frequency peaked at 12.8±0.2 c/min,after which the constant frequency was 9.43±0.24 c/min throughout the rest of the experiment. ETOH at a dose of 4 mL/L significantly decreased the amplitude from 16.13±0.23 mN to 14.93±0.19 mN. However, no significant changes in the contractile frequency were observed. ETOH at a dose of 6 mL/L inhibited both the amplitudes and the frequencies in the CCK-stimulated group, while 8 mL/L of ETOH completely relaxed the SO.CONCLUSION: ETOH strongly inhibits the basal, carbachol,erythromycin, and CCK-stimulated rabbit SO motility.Therefore, it is possible that during alcohol-intake the relaxed SO opens the way for pancreatic fluid to flow out into the duodenum in rabbits. This relaxation of the SO may protect the pancreas against alcohol-induced damage.

One in four patients with gastrointestinal bleeding develops shock or hemodynamic instability:A systematic review and meta-analysis

BACKGROUND Hemodynamic instability and shock are associated with untoward outcomes in gastrointestinal bleeding.However,there are no studies in the existing literature on the proportion of patients who developed these outcomes after gastrointestinal bleeding.AIM To determine the pooled event rates in the available literature and specify them based on the bleeding source.METHODS The protocol was registered on PROSPERO in advance(CRD42021283258).A systematic search was performed in three databases(PubMed,EMBASE,and CENTRAL)on 14^(th) October 2021.Pooled proportions with 95%CI were calculated with a random-effects model.A subgroup analysis was carried out based on the time of assessment(on admission or during hospital stay).Heterogeneity was assessed by Higgins and Thompson’s I^(2) statistics.The Joanna Briggs Institute Prevalence Critical Appraisal Tool was used for the risk of bias assessment.The Reference Citation Analysis(https://www.referencecitationanalysis.com/)tool was applied to obtain the latest highlight articles.RESULTS We identified 11589 records,of which 220 studies were eligible for data extraction.The overall proportion of shock and hemodynamic instability in general gastrointestinal bleeding patients was 0.25(95%CI:0.17-0.36,I^(2)=100%).In non-variceal bleeding,the proportion was 0.22(95%CI:0.14-0.31,I^(2)=100%),whereas it was 0.25(95%CI:0.19-0.32,I^(2)=100%)in variceal bleeding.The proportion of patients with colonic diverticular bleeding who developed shock or hemodynamic instability was 0.12(95%CI:0.06-0.22,I^(2)=90%).The risk of bias was low,and heterogeneity was high in all analyses.CONCLUSION One in five,one in four,and one in eight patients develops shock or hemodynamic instability on admission or during hospitalization in the case of non-variceal,variceal,and colonic diverticular bleeding,respectively.

A nuclear import inhibitory peptide ameliorates the severity of cholecystokinin-induced acute pancreatitis

AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-κB p50 subunit.METHODS: Pancreatitis was induced in male Wistar rats by administering 2×100 μg/kg body weight of cholecystokininoctapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity,pancreatic levels of TNF-α and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-κB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide.According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.CONCLUSION: Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-κB might be clinically useful for the suppression of the severity of acute pancreatitis.

Body-mass index correlates with severity and mortality in acute pancreatitis: A meta-analysis

BACKGROUND Obesity rates have increased sharply in recent decades. As there is a growing number of cases in which acute pancreatitis(AP) is accompanied by obesity, we found it clinically relevant to investigate how body-mass index(BMI) affects the outcome of the disease.AIM To quantify the association between subgroups of BMI and the severity and mortality of AP.METHODS A meta-analysis was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis(PRISMA) Protocols. Three databases(PubMed, EMBASE and the Cochrane Library) were searched for articles containing data on BMI, disease severity and mortality rate for AP. Englishlanguage studies from inception to 19 June 2017 were checked against our predetermined eligibility criteria. The included articles reported all AP cases with no restriction on the etiology of the disease. Only studies that classified AP cases according to the Atlanta Criteria were involved in the severity analyses. Odds ratios(OR) and mean differences(MD) were pooled using the random effects model with the DerSimonian-Laird estimation and displayed on forest plots. The meta-analysis was registered in PROSPERO under number CRD42017077890.RESULTS A total of 19 articles were included in our meta-analysis containing data on 9997 patients. As regards severity, a subgroup analysis showed a direct association between AP severity and BMI. BMI < 18.5 had no significant effect on severity;however, BMI > 25 had an almost three-fold increased risk for severe AP in comparison to normal BMI(OR = 2.87, 95%CI: 1.90-4.35, P < 0.001). Importantly,the mean BMI of patients with severe AP is higher than that of the non-severe group(MD = 1.79, 95%CI: 0.89-2.70, P < 0.001). As regards mortality, death rates among AP patients are the highest in the underweight and obese subgroups. A BMI < 18.5 carries an almost two-fold increase in risk of mortality compared to normal BMI(OR = 1.82, 95%CI: 1.32-2.50, P < 0.001). However, the chance of mortality is almost equal in the normal BMI and BMI 25-30 subgroups. A BMI >30 results in a three times higher risk of mortality in comparison to a BMI < 30(OR = 2.89, 95%CI: 1.10-7.36, P = 0.026).CONCLUSION Our findings confirm that a BMI above 25 increases the risk of severe AP, while a BMI > 30 raises the risk of mortality. A BMI < 18.5 carries an almost two times higher risk of mortality in AP.

Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatmentof acute pediatric pancreatitis. The preferred reporting items for systematic review(PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (Pub Med: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly(SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence.

Compared efficacy of preservation solutions on the outcome of liver transplantation:Meta-analysis

AIM To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.METHODS A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31^(st), 2017. The inclusion criteria were comparative, randomized controlled trials(RCTs) for deceased donor liver(DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin(UW) solution or histidinetryptophan-ketoglutarate(HTK), Celsior(CS) and Institut Georges Lopez(IGL-1) solutions. Fifteen RCTs(1830 livers) were included; the primary outcomes were primary non-function(PNF) and one-year posttransplant graft survival(OGS-1). RESULTS All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1(RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1(RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.CONCLUSION Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.

IL23R single nucleotide polymorphisms could be either beneficial or harmful in ulcerative colitis

AIM To investigate the association of seven single nucleotide polymorphisms(SNPs) of the IL23 R gene with the clinical picture of ulcerative colitis(UC). METHODS Genomic DNA samples of 131 patients (66 males, 65 females, mean age 55.4 ± 15.8 years) with Caucasian origin, diagnosed with UC were investigated. The diagnosis of UC was based on the established clinical, endoscopic, radiological, and histopathological guidelines. DNA was extracted from peripheral blood leukocytes by routine salting out method. Polymerase chain reaction and restriction fragment length polymorphism were used to identify the alleles of seven SNPs of IL23 R gene(rs11209026, rs10889677, rs1004819, rs2201841, rs7517847, rs10489629, rs7530511).RESULTS Four out of seven analyzed SNPs had statistically significant influence on the clinical picture of UC. Two SNPs were associated with greater colonic extension(rs2201841 P = 0.0084; rs10489629 P = 0.0405). For two of the SNPs, there was more frequently need for operations (rs2201841 P = 0.0348, OR = 8.0; rs10889677 P = 0.0347, OR = 8.0). The rs2201841 showed to be a risk factor for the development of iron deficiency (P = 0.0388, OR = 6.1837). For patients with the rs10889677, a therapy with azathioprine was more frequently necessary(P = 0.0116, OR = 6.1707). Patients with rs10489629 SNP had a lower risk for weight loss(P = 0.0169, OR = 0.3394). Carriers of the heterozygous variant had a higher risk for an extended disease (P = 0.0284). The rs7517847 showed a protective character leading to mild bowel movements. Three SNPs demonstrated no statistically significant influence on any examined clinical features of UC.CONCLUSION We demonstrated susceptible or protective character of the investigated IL23 R SNPs on the phenotype of UC, confirming the genetic association.

Chronic kidney disease severely deteriorates the outcome of gastrointestinal bleeding: A meta-analysis

AIM To understand the influence of chronic kidney disease(CKD) on mortality, need for transfusion and rebleeding in gastrointestinal(GI) bleeding patients.METHODS A systematic search was conducted in three databases for studies on GI bleeding patients with CKD or endstage renal disease(ESRD) with data on outcomes of mortality, transfusion requirement, rebleeding rate and length of hospitalization(LOH). Calculations were performed with Comprehensive Meta-Analysis software using the random effects model. Heterogeneity was tested by using Cochrane's Q and I2 statistics. Mean difference(MD) and OR(odds ratio) were calculated.RESULTS1063 articles(EMBASE: 589; PubM ed: 459; Cochrane: 15) were found in total. 5 retrospective articles and 1 prospective study were available for analysis. These 6 articles contained data on 406035 patients, of whom 51315 had impaired renal function. The analysis showed a higher mortality in the CKD group(OR = 1.786, 95%CI: 1.689-1.888, P < 0.001) and the ESRD group(OR = 2.530, 95%CI: 1.386-4.616, P = 0.002), and a rebleeding rate(OR = 2.510, 95%CI: 1.521-4.144, P < 0.001) in patients with impaired renal function. CKD patients required more unit red blood cell transfusion(MD = 1.863, 95%CI: 0.812-2.915, P < 0.001) and spent more time in hospital(MD = 13.245, 95%CI: 6.886-19.623, P < 0.001) than the controls.CONCLUSION ESRD increases mortality, need for transfusion, rebleeding rate and LOH among GI bleeding patients. Prospective patient registries and observational clinical trials are crucially needed.

Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis

AIM: In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8), the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated. In rats that were also diabetic (induced by streptozotocin, STZ), pancreatic regeneration was not observed. The aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats.METHODS: Male Wistar rats were used for the experiments.Diabetes mellitus was induced by administering 60 mg/kg body mass of STZ intraperitoneally (i.p.), then, on d 8, pancreatitis was induced by 200 mg/100 g body mass Argi.p. twice at an interval of 1 h. The animals were injected subcutaneously twice daily (at 7 a.m. and 7 p.m.) with 1 μglkg of CCK-8 and/or 2 IU mixed insulin (300 g/L shortaction and 700 g/L intermediate-action insulin) for 14 d after pancreatitis induction. Following this the animals were killed and the serum amylase, glucose and insulin levels as well as the plasma glucagon levels, the pancreatic mass/body mass ratio (pm/bm), the pancreatic contents of DNA, protein, amylase, lipase and trypsinogen were measured. Pancreatic tissue samples were examined by light microscopy on paraffin-embedded sections.RESULTS: In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein, amylase and lipase vs the rats receiving only CCK-8 treatment. CCK-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities, whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats.CONCLUSION: Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats,the simultaneous administration of exogenous insulin restored this effect. Our results clearly demonstrate that insulin is necessary for the hypertrophic effect of low-doses of CCK-8 following acute pancreatitis.

Network meta-analysis of randomized controlled trials on esophagectomies in esophageal cancer:The superiority of minimally invasive surgery

BACKGROUND Previous meta-analyses,with many limitations,have described the beneficial nature of minimal invasive procedures.AIM To compare all modalities of esophagectomies to each other from the results of randomized controlled trials(RCTs)in a network meta-analysis(NMA).METHODS We conducted a systematic search of the MEDLINE,EMBASE,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and CENTRAL databases to identify RCTs according to the following population,intervention,control,outcome(commonly known as PICO):P:Patients with resectable esophageal cancer;I/C:Transthoracic,transhiatal,minimally invasive(thoracolaparoscopic),hybrid,and robot-assisted esophagectomy;O:Survival,total adverse events,adverse events in subgroups,length of hospital stay,and blood loss.We used the Bayesian approach and the random effects model.We presented the geometry of the network,results with probabilistic statements,estimated intervention effects and their 95% confidence interval(CI),and the surface under the cumulative ranking curve to rank the interventions.RESULTS We included 11 studies in our analysis.We found a significant difference in postoperative pulmonary infection,which favored the minimally invasive intervention compared to transthoracic surgery(risk ratio 0.49;95%CI:0.23 to 0.99).The operation time was significantly shorter for the transhiatal approach compared to transthoracic surgery(mean difference-85 min;95%CI:-150 to-29),hybrid intervention(mean difference-98 min;95%CI:-190 to-9.4),minimally invasive technique(mean difference-130 min;95%CI:-210 to-50),and robot-assisted esophagectomy(mean difference-150 min;95%CI:-240 to-53).Other comparisons did not yield significant differences.CONCLUSION Based on our results,the implication of minimally invasive esophagectomy should be favored.

Insufficient etiological workup of COVID-19-associated acute pancreatitis: A systematic review

BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection, mostly causing respiratory symptoms, is also known to affect the gastrointestinal tract. Several case reports hypothesize that SARS-CoV-2 could be an etiological factor in acute pancreatitis(AP).AIM To assess all the available evidence in the literature relating to coronavirus disease 2019(COVID-19) and AP.METHODS We performed a systematic review of the available literature on the topic. The systematic search was conducted on 15 May 2020 on MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus with a search key using the terms "amylase," "lipase," "pancr*," "COVID-19" and synonyms. Due to the low quality and poor comparability of the studies, a meta-analysis was not performed.RESULTS Six case reports and two retrospective cohorts were included, containing data on eleven COVID-19 patients with AP. Five patients had AP according to the Atlanta classification. Other publications did not provide sufficient information on the diagnostic criteria. Most cases were considered SARS-CoV-2-induced, while several established etiological factors were not investigated. We were able to identify other possible causes in most of them.CONCLUSION We strongly highlight the need for adherence to the guidelines during a diagnostic and etiological workup, which could alter therapy.

Effect of herpesvirus infection on pancreatic duct cell secretion

AIM: To examine the effect of acute infection caused by herpesvirus (pseudorabies virus, PRV) on pancreatic ductal secretion.METHODS: The virulent Ba-DupGreen (BDG) and nonvirulent Ka-RREpOlacgfp (KEG) genetically modified strains of PRV were used in this study and both of them contain the gene for green fluorescent protein (GFP). Small intra/interlobular ducts were infected with BDG virus (107 PFU/mL for 6 h) or with KEG virus (1010 PFU/mL for 6 h), while non-infected ducts were incubated only with the culture media. The ducts were then cultured for a further 18 h.The rate of HCO3- secretion [base efflux -J(B-)] was determined from the buffering capacity of the cells and the initial rate of intracellular acidification (1) after sudden blockage of basolateral base loaders with dihydro-4,4,-diisothiocyanatostilbene-2,2,-disulfonic acid (500 μmol/L)and amiloride (200 μmol/L), and (2) after alkali loading the ducts by exposure to NH4Cl. All the experiments were performed in HCO3--buffered Ringer solution at 37 ℃ (n = 5ducts for each experimental condition). Viral structural proteins were visualized by immunohistochemistry. Virallyencoded GFP and immunofluorescence signals were recorded by a confocal laser scanning microscope.RESULTS: The BDG virus infected the majority of accessible cells of the duct as judged by the appearance of GFP and viral antigens in the ductal cells. KEG virus caused a similarly high efficiency of infection. After blockage of basolateral base loaders, BDG infection significantly elevated -J(B-) 24 h after the infection, compared to the non-infected group. However, KEG infection did not modify -J(B-). After alkali loading the ducts, -J(B-) was significantly elevated in the BDG group compared to the control group 24 h after the infection. As we found with the inhibitor stop method, no change was observed in the group KEG compared to the non-infected group.CONCLUSION: Incubation with the BDG or KEG strains of PRV results in an effective infection of ductal epithelial cells. The BDG strain of PRV, which is able to initiate a lytic viral cycle, stimulates HcO3- secretion in guinea pig pancreatic duct by about four- to fivefold, 24 h after the infection. However, the KEG strain of PRV, which can infect,but fails to replicate, has no effect on HCO3- secretion.We suggest that this response of pancreatic ducts to virulent PRV infection may represent a defense mechanism against invasive pathogens to avoid pancreatic injury.