Extrachromosomal circular MiR-17-92 amplicon promotes HCC.

BACKGROUND AND AIMS: Extrachromosomal circular DNAs (eccDNAs) are prevalent in cancer genomes and emerge as a class of crucial yet less characterized oncogenic drivers. However, the structure, composition, genome-wide frequency, and contribution of eccDNAs in HCC, one of the most fatal and prevalent cancers, remain unexplored. In this study, we provide a comprehensive characterization of eccDNAs in human HCC and demonstrate an oncogenic role of microRNA (miRNA)-17-92-containing eccDNAs in tumor progression. APPROACH AND RESULTS: Using the circle-sequencing method, we identify and characterize more than 230,000 eccDNAs from 4 paired samples of HCC tumor and adjacent nontumor liver tissues. EccDNAs are highly enriched in HCC tumors, preferentially originate from certain chromosomal hotspots, and are correlated with differential gene expression. Particularly, a series of eccDNAs carrying the miRNA-17-92 cluster are validated by outward PCR and Sanger sequencing. Quantitative PCR analyses reveal that miRNA-17-92-containing eccDNAs, along with the expression of their corresponding miRNAs, are elevated in HCC tumors and associated with poor outcomes and the age of HCC patients. More intriguingly, exogenous expression of artificial DNA circles harboring the miR-17-92 cluster, which is synthesized by the ligase-assisted minicircle accumulation method, can significantly accelerate HCC cell proliferation and migration. CONCLUSIONS: These findings delineate the genome-wide eccDNAs profiling of HCC and highlight the functional significance of miRNA-containing eccDNAs in tumorigenesis, providing insight into HCC pathogenesis and cancer therapy, as well as eccDNA and miRNA biology.

Clinical significance of tumor deposits in gastric cancer after radical gastrectomy: a propensity score matching study.

OBJECTIVE: The value of tumor deposits (TDs) in the prognosis and staging of gastric cancer (GC) is still under debate. This study aims to evaluate the prognostic value of TDs and the best ways to incorporate TDs in the TNM classification of GC. METHODS: Patients (n = 3460) undergoing curative gastrectomy for GC in the West China Hospital from 2005 to 2017 were retrospectively reviewed and divided into two groups according to the TD status (positive vs. negative). Later, clinicopathological features and overall survival (OS) between the two groups were compared. Thereafter, the associations between the presence of TD and other clinicopathological factors were evaluated through logistic regression. In addition, univariate and multivariate Cox regression were conducted for determining prognostic factors. The possibility of selection bias was reduced through conducting the 1:1 propensity score matching (PSM) analysis. The modified classification systems proposed previously that incorporated TDs into the TNM staging system were assessed. RESULTS: There were 10.5% of patients (362/3460) diagnosed with TDs. TDs were significantly related to unfavorable factors such as advanced T stage and N stage and independently associated with poor prognosis. The 5-year OS of patients with TDs was significantly lower than that of patients without TDs (31.0% vs. 60.9%, P < 0.001), whereas higher than that of patients with peritoneal metastasis (31.0% vs. 5.0%, P < 0.001). In patients receiving chemotherapy, the 5-year OS of patients with TDs was also significantly lower than that of patients without TDs (42.0% vs. 50.9%, P = 0.026). Moreover, the system incorporating TDs in the TNM classification as metastatic lymph nodes outperformed others. CONCLUSIONS: TDs are related to the aggressive characteristics and are an independent prognostic factor for GC. Incorporating TDs in the TNM classification as the metastatic lymph nodes increases the accuracy in predicting prognosis.

Is No. 12a Lymph Node Dissection Compliance Necessary in Patients Who Undergo D2 Gastrectomy for Gastric Adenocarcinomas? A Population-Based Retrospective Propensity Score Matching Study.

LN dissection is essential for accurately staging and improving GC patient prognosis. However, the compliance rate for No. 12a LND in practice is low, and its necessity is controversial. Data from GC patients who underwent total gastrectomy (TG)/distal gastrectomy (DG) plus D2 lymphadenectomy between January 2000 and December 2017 at West China Hospital, Sichuan University were reviewed. No. 12a LND noncompliance's effect on the long-term prognosis of patients with GC after D2 gastrectomy was explored. Of the 2788 patients included, No. 12a LND noncompliance occurred in 1753 patients (62.9%). Among 1035 patients with assessable LNs from station 12a, 98 (9.5%) had positive LNs detected at station 12a. No. 12a LN metastasis patients (stage IV not included) had significantly better overall survival (OS) than TNM stage IV patients (p = 0.006). Patients with No. 12a LND compliance had a significantly higher OS than those without, both before (p < 0.001) and after (p < 0.001) PSM. Cox multivariate analysis confirmed that No. 12a LND noncompliance was an independent prognostic factor before (HR 1.323, 95% CI 1.171-1.496, p < 0.001) and after (HR 1.353, 95% CI 1.173-1.560, p < 0.001) PSM. In conclusion, noncompliance with No. 12a LND compromised the long-term survival of patients who underwent D2 gastrectomy for GC.

Application of Gross Tissue Response System in Gastric Cancer After Neoadjuvant Chemotherapy: A Primary Report of a Prospective Cohort Study.

OBJECTIVE: We previously established a gross tissue response (GTR) system to evaluate the intraoperative response of perigastric tissue in patients with gastric cancers to neoadjuvant chemotherapy. This prospective cohort study aims to confirm the relationship between gross tissue response and clinicopathological characteristics and explore the possibility of using the GTR system to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days. METHODS: A total of 102 patients with gastric cancer from January 2019 to April 2020 were enrolled in this study. The degrees of fibrosis, edema, and effusion in the perigastric tissues were assessed intraoperatively according to the GTR system. We systematically analyzed the relations between GTR and clinicopathological characteristics, and then a prediction model that includes GTR was established to predict the difficulty of surgery and the occurrence of postoperative complications within 30 days. RESULTS: Finally, the study included 71 male patients and 31 female patients. The patients had an average age of 58.79 ± 1.03 years, BMI of 22.89 ± 0.29, and tumor diameter of 4.50 ± 0.27 cm. Among these patients, 17 underwent laparoscopic gastrectomy, 85 underwent open gastrectomy, the average operation time was 294.63 ± 4.84 minutes, and the mean volume of intraoperative blood loss was 94.65 ± 5.30 ml. The overall 30-day postoperative complication rate was 19.6% (20/102). The total GTR was significantly related to the primary tumor stage, operation time and 30-day postoperative complication rate (p<0.05). Edema and effusion were significantly related to intraoperative blood loss (p<0.05). The logistic regression analysis identified that the total GTR score (score: 4-9, OR 2.888, 95% CI: 1.035-8.062, p = 0.043) was an independent risk factor for postoperative complications within 30 days, and the total GTR score (score 4-9, OR 3.32, 95% CI 1.219-9.045, p=0.019) was also an independent risk factor for operation time. The AUC of the total GTR score for predicting postoperative complications within 30 days was 0.681. CONCLUSION: According to the results of the present study, the gross tissue response (GTR) system is an effective tool that may be used to predict the risk of a difficult operation after neoadjuvant chemotherapy and postoperative complications. Although neoadjuvant chemotherapy improves the therapeutic effect, it also increases the risk of surgical trauma and postoperative complications. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03791268.

Roux-En-Y Gastric Bypass Versus Sleeve Gastrectomy Plus Procedures for Treatment of Morbid Obesity: Systematic Review and Meta-Analysis.

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed bariatric procedures globally, but both techniques have shortcomings. Several modifications of SG (SG plus procedures) have been developed, but the efficacy of the different procedures has not been completely elucidated. In this meta-analysis, we aimed to evaluate the efficacy and safety of SG plus procedures. Out of the initially identified 2357 studies, thirteen were selected for this meta-analysis: two studies on banded sleeve gastrectomy (BSG), four studies on sleeve gastrectomy plus duodenal-jejunal bypass (SG + DJB) or sleeve gastrectomy with loop duodenal-jejunal bypass (SADJB), two studies on sleeve gastrectomy with jejunal-jejunal bypass (SG + JJB), four studies on single anastomosis duodenal-ileal switch (SADI-S), and one study on stomach intestinal pylorus-sparing surgery (SIPS). SADI-S procedure was found to achieve significantly greater percentage of excess weight loss than the RYGB. SG + DJB and SADJB achieved greater weight loss than the RYGB. Major complications were fewer with SG + JJB than with RYGB, but the difference was not significant. Overall, SG plus procedures appear to achieve better weight loss and cause fewer complications than RYGB.

Nomogram to Predict Intensive Care Following Gastrectomy for Gastric Cancer: A Useful Clinical Tool to Guide the Decision-Making of Intensive Care Unit Admission.

BACKGROUND: We aimed to generate and validate a nomogram to predict patients most likely to require intensive care unit (ICU) admission following gastric cancer surgery to improve postoperative outcomes and optimize the allocation of medical resources. METHODS: We retrospectively analyzed 3,468 patients who underwent gastrectomy for gastric cancer from January 2009 to June 2018. Here, 70.0% of the patients were randomly assigned to the training cohort, and 30.0% were assigned to the validation cohort. Least absolute shrinkage and selection operator (LASSO) method was performed to screen out risk factors for ICU-specific care using the training cohort. Then, based on the results of LASSO regression analysis, multivariable logistic regression analysis was performed to establish the prediction nomogram. The calibration and discrimination of the nomogram were evaluated in the training cohort and validated in the validation cohort. Finally, the clinical usefulness was determined by decision curve analysis (DCA). RESULTS: Age, the American Society of Anesthesiologists (ASA) score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were selected for the model. The concordance index (C-index) of the model was 0.843 in the training cohort and 0.831 in the validation cohort. The calibration curves of the ICU-specific care risk nomogram suggested great agreement in both training and validation cohorts. The DCA showed that the nomogram was clinically useful. CONCLUSIONS: Age, ASA score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were identified as risk factors for ICU-specific care after gastric surgery. A clinically friendly model was generated to identify those most likely to require intensive care.

Comparison of total joint arthroplasty outcomes between renal transplant patients and dialysis patients-a meta-analysis and systematic review.

OBJECTIVES: End-stage renal disease (ESRD) patients are at an increased risk of needing total joint arthroplasty (TJA); however, both dialysis and renal transplantation might be potential predictors of adverse TJA outcomes. For dialysis patients, the high risk of blood-borne infection and impaired muscular skeletal function are threats to implants' survival, while for renal transplant patients, immunosuppression therapy is also a concern. There is still no high-level evidence in the published literature that has determined the best timing of TJA for ESRD patients. METHODS: A literature search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (up to November 2019) was performed to collect studies comparing TJA outcomes between renal transplant and dialysis patients. Two reviewers independently conducted literature screening and quality assessments with the Newcastle-Ottawa Scale (NOS). After the data were extracted, statistical analyses were performed. RESULTS: Compared with the dialysis group, a lower risk of mortality (RR = 0.56, Cl = [0.42, 0.73], P < 0.01, I2 = 49%) and revision (RR = 0.42, CI = [0.30, 0.59], P < 0.01, I2 = 43%) was detected in the renal transplant group. Different results of periprosthetic joint infection were shown in subgroups with different sample sizes. There was no significant difference in periprosthetic joint infection in the small-sample-size subgroup, while in the large-sample-size subgroup, renal transplant patients had significantly less risk (RR = 0.19, CI = [0.13, 0.23], P < 0.01, I2 = 0%). For dislocation, venous thromboembolic disease, and overall complications, there was no significant difference between the two groups. CONCLUSION: Total joint arthroplasty has better safety and outcomes in renal transplant patients than in dialysis patients. Therefore, delaying total joint arthroplasty in dialysis patients until renal transplantation has been performed would be a desirable option. The controversy among different studies might be partially accounted for that quite a few studies have a relatively small sample size to detect the difference between renal transplant patients and dialysis patients.

Gastroesophageal reflux disease complicating laparoscopic sleeve gastrectomy: current knowledge and surgical therapies.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is currently the most commonly performed bariatric procedure worldwide. However, the incidence of gastroesophageal reflux disease (GERD) after LSG is high. OBJECTIVES: The aim of this systematic review was to identify the optimal surgical strategy for treating GERD after LSG. SETTING: West China Hospital, Sichuan University, Chengdu, China. METHODS: A systematic literature search was performed to identify studies on surgical treatments for GERD after LSG. The effectiveness and safety profile of surgical management on GERD after LSG were analyzed. RESULTS: A total of 40 articles enrolling 2049 patients were included in this review. Surgical strategies to prevent GERD after LSG were mainly of 2 types: concomitant LSG + antireflux procedures (hiatal hernia repair or fundoplication) and secondary procedures (conversion to Roux-en-Y gastric bypass [RYGB] or repeat sleeve gastrectomy). The short-term remission or improvement rate of GERD was 34.6%-100% after concomitant LSG + antireflux procedures. The postoperative complication rate was the same (3.0%) for both LSG + antireflux procedures and LSG alone. The remission or improvement rate of GERD was 57.1%-100% after conversion to RYGB and 100% after repeat sleeve gastrectomy. CONCLUSIONS: The effectiveness and safety profile of concomitant LSG + antireflux procedures is uncertain. However, secondary operations after LSG, such as conversion to RYGB, appear to provide good results. The data overall are heterogeneous, with imprecise methods of documenting and defining GERD complicating LSG. More cohort studies or RCT studies of high quality with long-term follow-up are needed in the future.

Patient-specific instrument for unicompartmental knee arthroplasty does not reduce the outliers in alignment or improve postoperative function: a meta-analysis and systematic review.

BACKGROUND: Unsatisfactory alignment in unicompartmental knee arthroplasty (UKA) is one potential cause of postoperative failure. Patient-specific instruments (PSIs) are designed to improve the alignment of the prostheses, but the effect of PSIs on the alignment or clinical outcome is controversial and lacks validated evidence. We conducted a meta-analysis and systematic review to determine the effect of PSIs on UKA outcomes for the first time. MATERIALS AND METHODS: A systematic literature search in MEDLINE, EMBASE, CNKI (Chinese database) and Cochrane Central Register of Controlled Trials (up to June 2019) was performed to collect studies that compared PSIs with conventional instruments. Two reviewers independently screened all the records on the basis of inclusion and exclusion criteria. Quality assessments with Cochrane's quality assessment tool or Newcastle-Ottawa scale (NOS) were conducted, the data were extracted, and statistical analyses were completed. RESULTS: Ten studies with 444 knees were included. The meta-analysis confirmed that PSIs contributed to reduced errors in the alignment of the femoral compartment in the sagittal plane (mean difference = - 2.53, CI [- 3.14, - 1.99], P < 0.01) and the tibial compartment in both the coronal (mean difference = - 0.97, CI [- 1.44, - 0.49], P < 0.01) and the sagittal plane (mean difference = - 1.29, CI [- 1.81, - 0.76], P < 0.01). One study supported that PSIs reduced outliers in inexperienced surgeons; however, all studies investigating PSIs among experienced surgeons suggested that PSIs cannot reduce the percentage of outliers. There was no significant difference in the postoperative score (mean difference = - 0.06, CI [- 0.36, 0.23], P = 0.68) or rate of complications (RR = 1.02, CI [0.15, 6.79], P = 0.99) between PSIs and conventional instruments. CONCLUSION: The findings of this study suggest PSIs could not reduce the percentage of outliers in UKA patients for experts, and postoperative scores and complication rates are not improved by PSIs, compared with conventional instruments. Based on this meta-analysis and systematic review, no practical benefit to UKAs in experts was detected in PSIs. The findings of this study also suggest that PSIs improved alignment of UKA and might be beneficial to inexperienced surgeons, but it is still unclear whether this improvement is clinically significant and the evidence of inexperienced surgeons is limited. Therefore, more high-quality RCTs are need to be carried out in the future.

Resolution of metabolic syndrome and related metabolic disorders after bariatric surgery: comparison of sleeve gastrectomy and gastric bypass.

BACKGROUND: The effects of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) on metabolic syndrome (MS) in morbidly obese patients have not been well studied. OBJECTIVE: To compare the effectiveness of LSG and LRYGB in Chinese morbidly obese patients with MS. SETTING: University Hospital, China. METHODS: Patients who underwent LRYGB or LSG surgery and had completed at least 1 year of follow-up were retrospectively reviewed. Bariatric and metabolic outcomes in the 2 groups were compared. Univariate and multivariate analyses were performed to identify the predictors of MS remission. RESULTS: Of the 176 patients enrolled in this study, 79 underwent LSG and 97 underwent LRYGB. Eighty-three met 3 of the International Diabetes Federation criteria for diagnosis of MS, 69 met 4 of the criteria, and 24 met 5 of the criteria. At 1 year after bariatric surgery, 79% of patients achieved remission of MS. In both LSG and LRYGB groups, the number of MS criteria met by patients decreased significantly after surgery. The MS remission rate was not significantly different between the 2 groups (74.7% in LSG versus 82.5% in LGB; P = .21). In LSG patients, there was no significant decrease in blood pressure or increase in the high-density lipoprotein cholesterol at 1 year. On logistic regression analysis, younger age, lower body mass index, and lower homeostatic model of assessment-insulin resistance were independently associated with MS remission at 1 year after surgery. Both groups showed satisfactory and comparable weight loss (percentage of excess weight loss: 71.7% in LSG versus 74.4% in LRYGB). No surgery-related mortality occurred. CONCLUSIONS: Both LSG and LRYGB are feasible, safe, and effective in Chinese obese patients with MS. LSG seems to be inferior to LRYGB with regard to control of hypertension and high-density lipoprotein cholesterol.

New ADCY3 Variants Dance in Obesity Etiology.

The genetic etiology for obesity-related traits remains elusive. Recent studies link novel ADCY3 variants to obesity and diabetes, and identify an important role of ADCY3-mediated signaling at neuronal primary cilia in the predisposition of obesity. These findings provide new information on obesity etiology and suggest potential anti-obesity therapeutic strategies.

Resected gastric volume has no influence on early weight loss after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a popular procedure for treatment of obesity, but it is still undecided whether resected gastric volume (RGV) is related to weight loss after LSG. OBJECTIVE: The aim of this study was to investigate the influence of RGV and other factors on weight loss at 1 year after LSG in a Chinese population. SETTING: University Hospital, China. METHODS: A total of 53 patients who underwent LSG between August 2015 and July 2016 were enrolled. The LSG procedure and RGV measurement were performed using standardized techniques. Patients were followed-up every 3 months in the first year and 6 monthly after that. Correlations between the percentage of excess weight loss at 1 year (%EWL-1 yr) and RGV and other parameters were evaluated. RESULTS: All patients completed at least 1 year of follow-up. No major complications or cases of underweight were seen. Mean body mass index (BMI) at 1 year after LSG was significantly lower than the baseline BMI (31.1 ± 3.8 kg/m2 versus 39.0 ± 6.6 kg/m2; P<.001). Mean %EWL-1 yr was 58.8%, and mean RGV was 862.6 ± 209.5 mL. No correlation was observed between %EWL-1 yr and RGV (r = -0.071; P = .613). The %EWL-1 yr was correlated with preoperative weight, BMI, RGV/weight, and RGV/BMI. RGV was positively correlated with preoperative weight and BMI. Patients who achieved satisfactory weight loss (%EWL ≥50%) had significantly lower baseline BMI, and higher RGV/weight and RGV/BMI, than those who had inadequate weight loss. However, RGV was not significantly different between the 2 groups. CONCLUSIONS: Weight loss effect at 1 year after LSG was not associated with RGV in this Chinese population. RGV was influenced by the weight and BMI.