The diagnostic yield of exome sequencing in liver diseases from a curated gene panel.

Exome sequencing (ES) has been used in a variety of clinical settings but there are limited data on its utility for diagnosis and/or prediction of monogenic liver diseases. We developed a curated list of 502 genes for monogenic disorders associated with liver phenotypes and analyzed ES data for these genes in 758 patients with chronic liver diseases (CLD). For comparison, we examined ES data in 7856 self-declared healthy controls (HC), and 2187 patients with chronic kidney disease (CKD). Candidate pathogenic (P) or likely pathogenic (LP) variants were initially identified in 19.9% of participants, most of which were attributable to previously reported pathogenic variants with implausibly high allele frequencies. After variant annotation and filtering based on population minor allele frequency (MAF ≤ 10-4 for dominant disorders and MAF ≤ 10-3 for recessive disorders), we detected a significant enrichment of P/LP variants in the CLD cohort compared to the HC cohort (X2 test OR 5.00, 95% CI 3.06-8.18, p value = 4.5e-12). A second-level manual annotation was necessary to capture true pathogenic variants that were removed by stringent allele frequency and quality filters. After these sequential steps, the diagnostic rate of monogenic disorders was 5.7% in the CLD cohort, attributable to P/LP variants in 25 genes. We also identified concordant liver disease phenotypes for 15/22 kidney disease patients with P/LP variants in liver genes, mostly associated with cystic liver disease phenotypes. Sequencing results had many implications for clinical management, including familial testing for early diagnosis and management, preventative screening for associated comorbidities, and in some cases for therapy. Exome sequencing provided a 5.7% diagnostic rate in CLD patients and required multiple rounds of review to reduce both false positive and false negative findings. The identification of concordant phenotypes in many patients with P/LP variants and no known liver disease also indicates a potential for predictive testing for selected monogenic liver disorders.

Serological Investigation of Persistent Villous Atrophy in Celiac Disease.

INTRODUCTION: Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD). METHODS: We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0-2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi. RESULTS: Autoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group ( P = 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not. DISCUSSION: tTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.

Colorectal Signet Ring Cell Carcinoma Presenting as Ulcerating Rectosigmoid Stricture.

Colorectal signet ring cell carcinoma is a rare type of colon cancer. Early diagnosis remains challenging because of nonspecific colonoscopy findings, such as diffuse circumferential thickening, stricture, and ulcerations, and the potential absence of typical pathological features in the initial biopsy sample. In this article, we report a 41-year-old man with ulcerating rectosigmoid stricture in the rectosigmoid colon with inconclusive histology. Subsequently, the patient developed small bowel obstruction and was diagnosed with stage 4 colorectal signet ring cell carcinoma with peritoneal carcinomatosis.

Global increase of colorectal cancer in young adults over the last 30 years: an analysis of the Global Burden of Disease Study 2019.

OBJECTIVES: The US Preventive Services Task Force lowered the recommended starting age for colorectal cancer (CRC) screening in average-risk adults from 50 to 45 years. We aimed to estimate the global burden and trends of colorectal cancer in adults aged 20-49 years (early-onset CRC). METHODS: This is an analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). The GBD 2019 estimation methods were used to describe the incidence, mortality, and disability-adjusted life years (DALYs) of early CRC from 1990 to 2019. Data from 204 countries and geographic areas were available. RESULTS: The global incidence rate of early-onset CRC increased from 4.2/100 000 to 6.7/100 000 from 1990 to 2019. Mortality and DALYs of early-onset CRC also increased. The CRC incidence rate increased faster in younger adults (1.6%) than in adults aged 50-74 years (0.6%) as measured by the annual percentage change. The increase in early-onset CRC incidence was consistently observed in all five socio-demographic index (SDI) regions and 190 out of 204 countries and territories. Middle and high-middle SDI regions had faster annual increases in early-onset CRC, which warrants further attention. CONCLUSIONS: The global incidence, mortality, and DALYs of early-onset CRC increased from 1990 to 2019. The increase in early-onset CRC incidence was prevalent worldwide. Several countries were found to have higher incidence rates than the United States or fast increase in early-onset CRC, which warrants further attention.

Comparative efficacy and tolerability of targeted and immunotherapy combined with chemotherapy as first-line treatment for advanced gastric cancer: a Bayesian network meta-analysis.

The use of target agents and immune checkpoint inhibitors have changed the treatment landscape for AGC in the first-line setting. However, the crosswise comparison between each regimen is rare. Therefore, we estimated the efficacy and safety of targeted therapy or immunotherapy with chemotherapy in AGC patients as the first-line treatment. Included studies were divided into "average" or "specific positivity" group according to whether the patients were selected by a certain pathological expression. We conducted a Bayesian network meta-analysis for all regimens in both groups. In average group, no regimen showed significant improvements in overall survival (OS) and progression free survival (PFS), while pembrolizumab and nivolumab combined with chemotherapy were ranked first and second respectively without an obvious safety difference. In specific positivity group, zolbetuximab plus chemotherapy significantly prolonged OS (HR 0.53, 95% CI 0.36-0.79) and PFS (HR 0.45, 95% CI 0.25-0.81). The top three regimens were zolbetuximab-chemotherapy, trastuzumab plus pertuzuma-chemotherapy and nivolumab-chemotherapy respectively, with no significant safety risk. For average patients, immune checkpoint inhibitor PD-1 plus chemotherapy will be the promising regimen. For patients with overexpression of CLDN18.2, zolbetuximab combined with chemotherapy comes with greater survival benefits, while for patients who have PD-L1 expression with no HER-2 or CLDN18.2 positivity, additional immune checkpoint inhibitor of PD-1 will be a good considered option.

Overexpression of Dermokine-α enhances the proliferation and epithelial-mesenchymal transition of pancreatic tumor cells.

Pancreatic cancer is a prevalent malignancy of the digestive system and a major cause of cancer-associated deaths. Previous studies have shown that mutation in the dermokine-ß (DMKN-ß) gene causes pancreatic and colorectal cancer. The role of the carboxy-terminal domain of DMKN-ß and dermokine-α (DMKN-α) genes in cancer tumorigenesis. Herein, the role of DMKN-α in pancreatic cancer (PC) tumorigenesis and the mechanisms underlying this process were investigated. Differentially expressed genes between PC and matched normal cells were identified through RNA-seq analysis, and the corresponding protein expression levels were verified using Western blot analysis. In vivo tumor formation experiment was also performed in nude mice. We found that the DMKN-α gene was overexpressed in cancerous pancreatic cell lines compared to normal pancreatic cell lines. CCK-8, colony formation, RTCA test, wound healing, as well as transwell test showed that the overexpression of DMKN-α enhanced the proliferation, migration, invasion, and EMT of PC cells. In vivo assays confirmed that DMKN-α promotes tumorigenesis. The findings of this study show that DMKN-α is a potential oncogene for pancreatic cancer.

Periplocin Induces Apoptosis of Pancreatic Cancer Cells through Autophagy via the AMPK/mTOR Pathway.

Periplocin, a natural compound, has been shown to induce apoptosis in a variety of cancer cells. However, no research has been conducted to demonstrate that Periplocin has a regulatory effect on autophagy. This study is aimed to determine the effect of Periplocin treatment on autophagy in human pancreatic cancer cells, as well as the underlying mechanisms. Pancreatic cancer cells were treated with different concentrations of Periplocin, and real-time cell analysis (RTCA), colony formation assay, and Ki67 immunofluorescence detection were used to determine cell proliferation. Autophagy protein was detected by immunofluorescence and western blotting. Western blotting was also used to detect the caspase family of apoptotic proteins. Flow cytometry and TUNEL staining were used to detect cell apoptosis. Following treatment with Periplocin, the expression of autophagy genes was detected using RNA-seq. In vivo examination of the effect of Periplocin on autophagy in pancreatic was performed using a xenograft model. Periplocin inhibits the proliferation of CFPAC1 and PANC1 cells and induces autophagy by regulating the AMPK/mTOR pathway. Using the AMPK inhibitor Compound C(CC), both the Periplocin-induced inhibition of cell proliferation and autophagy activation was reduced, which further verified this conclusion. Periplocin inhibits CFPAC1 xenograft tumor growth in nude mice and increases tumor cell autophagy. Collectively, these results have shown that Periplocin promotes autophagy in human pancreatic cancer cells by regulating the AMPK/mTOR pathway.

Prediction of Patient Hepatic Encephalopathy Risk with Freiburg Index of Post-TIPS Survival Score Following Transjugular Intrahepatic Portosystemic Shunts: A Retrospective Study.

Background: Hepatic encephalopathy is a complication of portal hypertension. The Freiburg index of transjugular portosystemic shunt (TIPS) and patient outcomes have recently been described. This retrospective study was conducted at a single center in China and included 241 patients with portal hypertension who underwent TIPS implantation to evaluate the Freiburg index of post-TIPS survival score (FIPS) to predict hepatic encephalopathy. Methods: A single-center retrospective study including 241 patients who underwent TIPS operation between April 2015 and July 2019 was conducted. Clinical demographics and relevant clinical parameters within 24h after admission were collected. The prediction performances of FIPS, Child-Pugh and the model for end-stage liver disease (MELD) scores were compared by decision curve analysis and receiver operating characteristic (ROC) curve analysis. In addition, multivariate analyses were performed to identify independent predictors. Results: Eighty-three out of 241 patients (34.4%) finally developed post-TIPS hepatic encephalopathy. The area under the ROC curve of FIPS was 0.744 (95% confidence interval: 0.684-0.798). FIPS was identified as an independent risk factor for post-TIPS hepatic encephalopathy (hazard ratio: 2.23, 95% confidence interval: 1.71-2.90, p<0.001). Moreover, we further grouped the FIPS scores into two categories (FIPS ≤-0.97, low-risk; FIPS >-0.97, high risk) to improve its applicability. Patients with high FIPS scores had a significantly higher incidence of hepatic encephalopathy than patients with low FIPS scores (P<0.05). Conclusion: This study showed that FIPS could be used to evaluate the risk of hepatic encephalopathy in this patient group with improved predictive performance when compared with the Child-Pugh and MELD scores.

Immunogenetics of gastrointestinal cancers: A systematic review and retrospective survey of inborn errors of immunity in humans.

BACKGROUND AND AIM: Humans with inborn errors of immunity (IEI), or primary immunodeficiencies, may be associated with a potential risk factor for early-onset gastrointestinal (GI) cancer. METHODS: We systematically reviewed all cases with clinical diagnoses of both an IEI and a GI cancer in three databases (MEDLINE, SCOPUS, and EMBASE). In total, 76 publications satisfying our inclusion criteria were identified, and data for 149 cases were analyzed. We also searched our institutional cancer registry for such cases. RESULTS: We identified 149 patients with both an IEI and a GI cancer, 95 presented gastric cancer, 13 small bowel cancer, 35 colorectal cancer, and 6 had an unspecified cancer or cancer at another site. Gastric and colon adenocarcinomas were the most common. For both gastric and colorectal cancers, age at onset was significantly earlier in patients with IEIs than in the general population, based on the SEER database. Common variable immunodeficiency (CVID) was the most common IEI associated with gastrointestinal cancer. About 12% of patients had molecular genetic diagnoses, the three most frequently implicated genes being ATM, CARMIL2, and CTLA4. Impaired humoral immunity and Epstein-Barr virus (EBV) infection were frequently reported as factors potentially underlying early-onset GI cancers in patients with IEIs. We identified one patient with CVID and early-onset gastric adenocarcinoma, recurrent diarrhea, and gastrointestinal CMV infection from a retrospective survey. CONCLUSION: Patients with IEIs should be considered at risk of early-onset GI cancers and should therefore undergo cancer screening at an earlier age.

IFN-γ facilitates liver fibrogenesis by CD161+CD4+ T cells through a regenerative IL-23/IL-17 axis in chronic hepatitis B virus infection.

OBJECTIVES: This study aimed to determine the role of CD161+CD4+ T cells in chronic hepatitis B virus (HBV) infection. METHODS: A total of 94 patients with chronic hepatitis B (CHB), 73 with liver cirrhosis (LC) and 28 healthy controls were enrolled to determine frequency, cytokine production and chemokine receptor expression of circulating CD161+CD4+ T cells. Among these, 50 CHB and 34 LC patients were followed up for a period of 52-week entecavir monotherapy to assess the association of CD161+CD4+ T cells with seroconversion of HBV e antigen (HBeAg). In addition, 15 patients with hepatocellular carcinoma (HCC) and 15 with hepatic haemangioma (HHA) were enrolled to compare the paired circulating and intrahepatic CD161+CD4+ T cells. RESULTS: CD161+CD4+ T cells were found to accumulate in the circulation of HBV cohorts, which showed a significant correlation with the clinical parameters of disease progression. In addition, higher numbers of circulating CD161+CD4+ T cells were associated with an improved serological response of HBeAg to antiviral treatment. Moreover, CD161+CD4+ T cells as compared to homologous CD161-CD4+ T cells produced more pro-inflammatory cytokines including interleukin (IL)-17 and interferon (IFN)-γ and expressed higher levels of liver-homing chemokine receptors including CCR6, CXCR6 and CX3CR1. Notably, a significant enrichment of CD161+CD4+ T cell subsets co-expressing IFN-γ and IL-17 was observed in HBV-associated cirrhotic livers. During in vitro co-cultures, circulating CD161+CD4+ T cells in the chronic HBV setting exhibited prominent pro-fibrogenic effects by regulating primary hepatic stellate cells through a regenerative IFN-γ/IL-23/IL-17 axis. CONCLUSIONS: In chronic HBV infection, CD161+CD4+ T cells play antiviral, pro-inflammatory and pro-fibrogenic roles.

Inflammation Disturbed the Tryptophan Catabolites in Hippocampus of Post-operative Fatigue Syndrome Rats via Indoleamine 2,3-Dioxygenas Enzyme and the Improvement Effect of Ginsenoside Rb1.

AIM: Post-operative fatigue syndrome (POFS) is a common complication that prolongs the recovery to normal function and activity after surgery. The aim of the present study was to explore the mechanism of central fatigue in POFS and the anti-fatigue effect of ginsenoside Rb1. METHOD: We investigated the association between inflammation, indoleamine 2,3-dioxygenase (IDO) enzyme, and tryptophan metabolism in the hippocampus of POFS rats. A POFS rat model was induced by major small intestinal resection. Rats with major small intestinal resection were administered ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Fatigue was assessed with the open field test (OFT) and sucrose preference test (SPT). ELISA, RT-PCR, Western blot, immunofluorescence, and high-performance liquid chromatography (HPLC) were used to test the inflammatory cytokines; p38MAPK, NF-κB/p65, and IDO enzyme expressions; and the concentrations of tryptophan, kynurenine, and serotonin, respectively. RESULT: Our results showed that POFS was associated with increased expressions of inflammatory cytokines and p38MAPK and higher concentrations of kynurenine and tryptophan on post-operative days 1 and 3; a lower serotonin level on post-operative day 1; and an enhanced translocation of NF-κB/p65 and the IDO enzyme on post-operative days 1, 3, and 5. Ginsenoside Rb1 had an improvement effect on these. CONCLUSION: Inflammatory cytokines induced by large abdominal surgery disturb tryptophan metabolism to cause POFS through the activation of the p38MAPK-NF-κB/p65-IDO pathway in the hippocampus. Ginsenoside Rb1 had an anti-fatigue effect on POFS by reducing inflammation and IDO enzyme.

Correlation of Severity of COVID-19 Disease With Gastrointestinal Manifestations and Liver Injury - A North Brooklyn Community Hospital Experience: A Retrospective Cohort Study.

Introduction The primary receptor for SARS-CoV-2 infection, angiotensin-converting enzyme-2 (ACE-2), is expressed in the gastrointestinal tract and liver parenchyma. The involvement of the gastrointestinal tract with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has remained unclear. The following study retrospectively reviews gastrointestinal symptoms and liver function tests at the time of hospital admission to identify patient outcomes including prolonged hospital stay, the requirement for intensive care, and all-cause in-hospital 30-day mortality. Methods A retrospective review of patient charts at the Woodhull Medical and Mental Health Center (WMC) was conducted at the time of hospital admission, using a pre-determined selection criterion. All adult patients, both inpatient and outpatient, were included from March 2020 till May 2020. A 95% confidence interval was used to estimate the odds ratio (OR) for patient outcomes. Results Of the 520 patients, gastrointestinal symptoms including nausea (OR = 0.375, p = 0.015), and nausea and vomiting in combination (OR = 0.400, p = 0.016) had an inverse protective relationship with all-cause in-hospital 30-day mortality among COVID-19 patients. Gastrointestinal symptoms including diarrhea (OR = 1.008, p < 0.001), and nausea and vomiting (OR = 1.291, p = 0.043) had a mild impact on the length of hospital stay. Conclusion Elevated liver transaminases including alanine transaminase (ALT) and aspartate transaminase (AST) at the time of hospital admission can predict critical care requirement and all-cause 30-day hospital mortality in patients with COVID-19 infection. Presence of gastrointestinal symptoms is associated with worsened outcomes.

HMGB1-induced autophagy facilitates hepatic stellate cells activation: a new pathway in liver fibrosis.

High-mobility group box-1 (HMGB1) plays a context-dependent role in autophagy, which is required for hepatic stellate cells (HSCs) activation. However, the significance of HMGB1-induced HSCs autophagy in liver fibrosis has not been elucidated. Here, we first documented an enrichment of peripheral and intrahepatic HMGB1 signal in hepatitis B virus (HBV)-related liver fibrosis progression, and presented a direct evidence of anatomic proximity of HMGB1 with a-SMA (a marker for HSCs activation) in cirrhotic liver specimens. Then, we demonstrated the autophagy-inducing effects by serum-sourced HMGB1 in both primary murine HSCs and human HSCs cell line (LX-2), reflected by increased number of autophagic vacuoles (AVs) under the transmission electron microscope (TEM) and up-regulated protein expression of lipidated microtubule-associated light chain 3 (LC3-II) (a marker for autophagosome) in Western blot analysis. Intriguingly, there is a possible translocation of endogenous HMGB1 from the nucleus to cytoplasm to extracellular space, during exogenous HMGB1-induced HSCs autophagy. Meanwhile, the dose- and time-dependent effects by recombinant HMGB1 (rHMGB1) in enhancing LX-2 autophagy and fibrogenesis have been revealed with activated extracellular regulated protein kinase (ERK)/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) and restrained mammalian target of rapamycin (mTOR)/STAT3 signaling pathways. Additionally, the ERK or JNK inhibitor could not only inhibit rHMGB1-induced autophagy and fibrogenesis in LX-2 cells, but also restore the suppressed mTOR and STAT3 pathways. Furthermore, using LC3-siRNA transfected LX-2, we found HMGB1-induced fibrogenesis is dependent on its autophagy-inducing effects. Finally, we elucidated the involvement of extracellular HMGB1-receptor for advenced glycation end product (RAGE) axis and endogenous HMGB1 in exogenous HMGB1-induced effects. Our findings could open new perspectives in developing an antifibrotic therapy by targetting the HSCs autophagy.

The hedgehog/Gli-1 signaling pathways is involved in the inhibitory effect of resveratrol on human colorectal cancer HCT116 cells.

OBJECTIVES: The study aimed to investigate the effects of resveratrol on colorectal cancer HCT116 cells, including cell viability, apoptosis, and migration, and the partial mechanisms focused on hedgehog/gli-1 signaling pathways. MATERIALS AND METHODS: We chose the appropriate time and concentration of recombinant human Sonic hedgehog (Shh) stimulation by cell viability. The proportion of cell apoptosis was detected by flow cytometry; HCT116 cell migration was measured by scratch test; the expression of Ptch, Smo, and Gli-1 was measured by Western blot analysis. RESULTS: Shh signaling increased HCT116 cell viability and migration, inhibited cell apoptosis, and upregulated the expression of Ptch, Smo, and Gli-1. Resveratrol obviously inhibited HCT116 cell viability and migration, promoted cell apoptosis, and suppressed the protein of Ptch, Smo, and Gli-1. Furthermore, the effects of resveratrol and Shh on human colorectal cancer HCT116 cells were in a dose- and time-dependent manner. CONCLUSION: The inhibitory effect of resveratrol on HCT116 cells may be mediated by hedgehog/gli-1 signaling pathways.

Impact of different surgical traumas on postoperative ileus in rats and the mechanisms involved.

The degree of postoperative ileus and the underlying pathophysiological mechanism among different types of surgical traumas have not been examined. The aim of this study was to investigate the inflammatory and oxidative stress changes in rat intestinal muscularis and gastrointestinal transit among three types of surgical traumas. Rats were randomized assigned to four groups: control group, intestinal manipulation (IM) group, intestinal ischemia/reperfusion injury (IR) group and peritoneal air exposure (AE) group. Gastrointestinal transit was measured 24 hours after surgery. Malondialdehyde (MDA), glutathione (GSH) and inflammatory mediators in intestinal muscularis were measured. Influx of neutrophil in intestinal muscularis was also determined. The degree of gastrointestinal motility impairment was equal between the IM and AE groups. However, the IR group was subject to a less impairment of gastrointestinal motility compared with the IM and AE groups. The IM group showed the most significant increase of inflammatory response, while the AE group showed the most significant increase of oxidative stress. The IR group showed a moderate increase of inflammatory response and oxidative stress. Rats subjected to IM, IR and AE could all develop into POI. We speculate that oxidative stress should be an equally important pathophysiological mechanism of POI as inflammation.

Laparoscopic versus open colorectal surgery within enhanced recovery after surgery programs: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic surgery and enhanced recovery after surgery (ERAS) programs were two major improvements for the management of colorectal diseases. The purpose of this systemic review was to examine whether laparoscopic colorectal surgery still improved short-term postoperative outcomes in comparison with open surgery when both groups of patients received ERAS programs. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared laparoscopic with open surgery in patients undergoing colorectal resection in the context of ERAS programs. The outcome measures were analyzed, and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Five randomized clinical trials encompassing 598 patients were included in the final analysis. Two of them were multicenter trials. The ERAS programs implemented in the five included trials cannot be classified as optimal ERAS programs, but suboptimal ERAS programs. Laparoscopic colorectal surgery significantly reduced total hospital stay (weighted mean difference (WMD) -1.92 days; 95 % confidence interval (CI) -2.61--1.23 days; P < 0.00001) and number of complications (relative risk (RR) 0.78; 95 % CI 0.66-0.94; P = 0.007) compared with open surgery in the setting of ERAS programs. No significant differences were found between groups for primary hospital stay, number of patients with complications, readmission rates, and mortality. The quality of evidence for all outcomes was low-to-moderate on the GRADE scale, and none had high quality. CONCLUSIONS: Laparoscopic colorectal resection significantly reduced total hospital stay and number of complications when compared with open surgery in the setting of suboptimal ERAS programs, but the benefits of laparoscopic colorectal resection remain to be proved within optimal ERAS programs.