Ferroptosis-related lncRNA NRAV affects the prognosis of hepatocellular carcinoma via the miR-375-3P/SLC7A11 axis.

Ferroptosis has important value in cancer treatment. It is significant to explore the new ferroptosis-related lncRNAs prediction model in Hepatocellular carcinoma (HCC) and the potential molecular mechanism of ferroptosis-related lncRNAs. We constructed a prognostic multi-lncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HCC. qRT-PCR was applied to determine the expression of lncRNA in HCC cells. The biological roles of NRAV in vitro and in vivo were determined by performing a series of functional experiments. Furthermore, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of NRAV with miR-375-3P. We identified 6 differently expressed lncRNAs associated with the prognosis of HCC. Kaplan-Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HCC. Moreover, the AUC of the lncRNAs signature showed utility in predicting HCC prognosis. Further functional experiments show that the high expression of NRAV can strengthen the viciousness of HCC. Interestingly, we found that NRAV can enhance iron export and ferroptosis resistance. Further study showed that NRAV competitively binds to miR-375-3P and attenuates the inhibitory effect of miR-375-3P on SLC7A11, affecting the prognosis of patients with HCC. In conclusion, We developed a novel ferroptosis-related lncRNAs prognostic model with important predictive value for the prognosis of HCC. NRAV is important in ferroptosis induction through the miR-375-3P/SLC7A11 axis.

Adsorption removal of fluoride from polluted drinking waters using Mn-Al-La oxide.

Trimetal oxides have received high attention in treatment of fluoride-polluted drinking waters. In this study, Mn-Al-La (MAL) oxide with a mole ratio of 2:1:1 was successively prepared and characterized by XRD, FTIR, XPS, and TEM. It exhibited as cotton-like assemblages (500-800 nm of axial lengths), and BET specific surface area was 52 m2/g. It was used to study fluoride adsorptions in aqueous solutions by batch experiments, under different adsorbent/adsorbate levels, times, temperatures, pH and coexisting anions, and treat simulated groundwater (with 2.85 mg/L fluoride and pH 7.0) by batch and column tests. Adsorption data well fitted to pseudo-second-order rate model (R2 = 0.996-0.999), and Langmuir (R2 = 0.962 - 0.997) and Freundlich (R2 = 0.964-0.989) isothermal models. Their maximum adsorption capacities could reach 45-113 mg/g. Only H2PO4- anions had a restrictive impact at pH 7.0, and there was a good removal ability at pH 3-9. Adsorption processes were spontaneous, endothermic, and random. Adsorption mechanisms were electrostatic interaction and ligand exchange at pH 7.0. Adsorption capacity could reach 73% of initial value at pH 7.0, after three cycles. All application data on the polluted groundwater treatments show MAL oxide is a potential adsorbent for fluoride removals.

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most frequent and potentially life-threatening complications following pancreatic surgery. Fibrin sealants have been used in some centres to reduce POPF rate. However, the use of fibrin sealant during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2020. OBJECTIVES: To evaluate the benefits and harms of fibrin sealant use for the prevention of POPF (grade B or C) in people undergoing pancreatic surgery compared to no fibrin sealant use. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 09 March 2023, together with reference checking, citation searching, and contacting study authors to identify additional studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 RCTs, randomising 1989 participants, comparing fibrin sealant use versus no fibrin sealant use for different locations: stump closure reinforcement (eight trials), pancreatic anastomosis reinforcement (five trials), or main pancreatic duct occlusion (two trials). Six RCTs were carried out in single centres; two in dual centres; and six in multiple centres. One RCT was conducted in Australia; one in Austria; two in France; three in Italy; one in Japan; two in the Netherlands; two in South Korea; and two in the USA. The mean age of the participants ranged from 50.0 years to 66.5 years. All RCTs were at high risk of bias. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included eight RCTs involving 1119 participants: 559 were randomised to the fibrin sealant group and 560 to the control group after distal pancreatectomy. Fibrin sealant use may result in little to no difference in the rate of POPF (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.73 to 1.21; 5 studies, 1002 participants; low-certainty evidence) and overall postoperative morbidity (RR 1.20, 95% CI 0.98 to 1.48; 4 studies, 893 participants; low-certainty evidence). After fibrin sealant use, approximately 199 people (155 to 256 people) out of 1000 developed POPF compared with 212 people out of 1000 when no fibrin sealant was used. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto odds ratio (OR) 0.39, 95% CI 0.12 to 1.29; 7 studies, 1051 participants; very low-certainty evidence) and total length of hospital stay (mean difference (MD) 0.99 days, 95% CI -1.83 to 3.82; 2 studies, 371 participants; very low-certainty evidence). Fibrin sealant use may reduce the reoperation rate slightly (RR 0.40, 95% CI 0.18 to 0.90; 3 studies, 623 participants; low-certainty evidence). Serious adverse events were reported in five studies (732 participants), and there were no serious adverse events related to fibrin sealant use (low-certainty evidence). The studies did not report quality of life or cost-effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included five RCTs involving 519 participants: 248 were randomised to the fibrin sealant group and 271 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF (RR 1.34, 95% CI 0.72 to 2.48; 3 studies, 323 participants; very low-certainty evidence), postoperative mortality (Peto OR 0.24, 95% CI 0.05 to 1.06; 5 studies, 517 participants; very low-certainty evidence), reoperation rate (RR 0.74, 95% CI 0.33 to 1.66; 3 studies, 323 participants; very low-certainty evidence), and total hospital cost (MD -1489.00 US dollars, 95% CI -3256.08 to 278.08; 1 study, 124 participants; very low-certainty evidence). After fibrin sealant use, approximately 130 people (70 to 240 people) out of 1000 developed POPF compared with 97 people out of 1000 when no fibrin sealant was used. Fibrin sealant use may result in little to no difference both in overall postoperative morbidity (RR 1.02, 95% CI 0.87 to 1.19; 4 studies, 447 participants; low-certainty evidence) and in total length of hospital stay (MD -0.33 days, 95% CI -2.30 to 1.63; 4 studies, 447 participants; low-certainty evidence). Serious adverse events were reported in two studies (194 participants), and there were no serious adverse events related to fibrin sealant use (very low-certainty evidence). The studies did not report quality of life. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two RCTs involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto OR 1.41, 95% CI 0.63 to 3.13; 2 studies, 351 participants; very low-certainty evidence), overall postoperative morbidity (RR 1.16, 95% CI 0.67 to 2.02; 2 studies, 351 participants; very low-certainty evidence), and reoperation rate (RR 0.85, 95% CI 0.52 to 1.41; 2 studies, 351 participants; very low-certainty evidence). Fibrin sealant use may result in little to no difference in the total length of hospital stay (median 16 to 17 days versus 17 days; 2 studies, 351 participants; low-certainty evidence). Serious adverse events were reported in one study (169 participants; low-certainty evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report POPF, quality of life, or cost-effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealant use may result in little to no difference in the rate of POPF in people undergoing distal pancreatectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF in people undergoing pancreaticoduodenectomy. The effect of fibrin sealant use on postoperative mortality is uncertain in people undergoing either distal pancreatectomy or pancreaticoduodenectomy.

Duct-to-mucosa versus other types of pancreaticojejunostomy for the prevention of postoperative pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula is a common and serious complication following pancreaticoduodenectomy. Duct-to-mucosa pancreaticojejunostomy has been used in many centers to reconstruct pancreatic digestive continuity following pancreatoduodenectomy, however, its efficacy and safety are uncertain. OBJECTIVES: To assess the benefits and harms of duct-to-mucosa pancreaticojejunostomy versus other types of pancreaticojejunostomy for the reconstruction of pancreatic digestive continuity in participants undergoing pancreaticoduodenectomy, and to compare the effects of different duct-to-mucosa pancreaticojejunostomy techniques. SEARCH METHODS: We searched the Cochrane Library (2021, Issue 1), MEDLINE (1966 to 9 January 2021), Embase (1988 to 9 January 2021), and Science Citation Index Expanded (1982 to 9 January 2021). SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared duct-to-mucosa pancreaticojejunostomy with other types of pancreaticojejunostomy (e.g. invagination pancreaticojejunostomy, binding pancreaticojejunostomy) in participants undergoing pancreaticoduodenectomy. We also included RCTs that compared different types of duct-to-mucosa pancreaticojejunostomy in participants undergoing pancreaticoduodenectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CIs). For all analyses, we used the random-effects model. We used the Cochrane RoB 1 tool to assess the risk of bias. We used GRADE to assess the certainty of the evidence for all outcomes. MAIN RESULTS: We included 11 RCTs involving a total of 1696 participants in the review. One RCT was a dual-center study; the other 10 RCTs were single-center studies conducted in: China (4 studies); Japan (2 studies); USA (1 study); Egypt (1 study); Germany (1 study); India (1 study); and Italy (1 study). The mean age of participants ranged from 54 to 68 years. All RCTs were at high risk of bias. Duct-to-mucosa versus any other type of pancreaticojejunostomy We included 10 RCTs involving 1472 participants comparing duct-to-mucosa pancreaticojejunostomy with invagination pancreaticojejunostomy: 732 participants were randomized to the duct-to-mucosa group, and 740 participants were randomized to the invagination group after pancreaticoduodenectomy. Comparing the two techniques, the evidence is very uncertain for the rate of postoperative pancreatic fistula (grade B or C; RR 1.45, 95% CI 0.64 to 3.26; 7 studies, 1122 participants; very low-certainty evidence), postoperative mortality (RR 0.77, 95% CI 0.39 to 1.49; 10 studies, 1472 participants; very low-certainty evidence), rate of surgical reintervention (RR 1.12, 95% CI 0.65 to 1.95; 10 studies, 1472 participants; very low-certainty evidence), rate of postoperative bleeding (RR 0.85, 95% CI 0.51 to 1.42; 9 studies, 1275 participants; very low-certainty evidence), overall rate of surgical complications (RR 1.12, 95% CI 0.92 to 1.36; 5 studies, 750 participants; very low-certainty evidence), and length of hospital stay (MD -0.41 days, 95% CI -1.87 to 1.04; 4 studies, 658 participants; very low-certainty evidence). The studies did not report adverse events or quality of life outcomes. One type of duct-to-mucosa pancreaticojejunostomy versus a different type of duct-to-mucosa pancreaticojejunostomy We included one RCT involving 224 participants comparing duct-to-mucosa pancreaticojejunostomy using the modified Blumgart technique with duct-to-mucosa pancreaticojejunostomy using the traditional interrupted technique: 112 participants were randomized to the modified Blumgart group, and 112 participants were randomized to the traditional interrupted group after pancreaticoduodenectomy. Comparing the two techniques, the evidence is very uncertain for the rate of postoperative pancreatic fistula (grade B or C; RR 1.51, 95% CI 0.61 to 3.75; 1 study, 210 participants; very low-certainty evidence), postoperative mortality (there were no deaths in either group; 1 study, 210 participants; very low-certainty evidence), rate of surgical reintervention (RR 1.93, 95% CI 0.18 to 20.91; 1 study, 210 participants; very low-certainty evidence), rate of postoperative bleeding (RR 2.89, 95% CI 0.12 to 70.11; 1 study, 210 participants; very low-certainty evidence), overall rate of surgical complications (RR 1.10, 95% CI 0.80 to 1.51; 1 study, 210 participants; very low-certainty evidence), and length of hospital stay (15 days versus 15 days; 1 study, 210 participants; very low-certainty evidence). The study did not report adverse events or quality of life outcomes. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of duct-to-mucosa pancreaticojejunostomy compared to invagination pancreaticojejunostomy on any of the outcomes, including rate of postoperative pancreatic fistula (grade B or C), postoperative mortality, rate of surgical reintervention, rate of postoperative bleeding, overall rate of surgical complications, and length of hospital stay. The evidence is also very uncertain whether duct-to-mucosa pancreaticojejunostomy using the modified Blumgart technique is superior, equivalent or inferior to duct-to-mucosa pancreaticojejunostomy using the traditional interrupted technique. None of the studies reported adverse events or quality of life outcomes.

Gases for establishing pneumoperitoneum during laparoscopic abdominal surgery.

BACKGROUND: This is the second update of a Cochrane Review first published in 2013 and last updated in 2017. Laparoscopic surgery is now widely performed to treat various abdominal diseases. Currently, carbon dioxide is the most frequently used gas for insufflation of the abdominal cavity (pneumoperitoneum). Although carbon dioxide meets most of the requirements for pneumoperitoneum, the absorption of carbon dioxide may be associated with adverse events. Therefore, other gases have been introduced as alternatives to carbon dioxide for establishing pneumoperitoneum. OBJECTIVES: To assess the safety, benefits, and harms of different gases (e.g. carbon dioxide, helium, argon, nitrogen, nitrous oxide, and room air) used for establishing pneumoperitoneum in participants undergoing laparoscopic abdominal or gynaecological pelvic surgery. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Ovid Embase, four other databases, and three trials registers on 15 October 2021 together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different gases for establishing pneumoperitoneum in participants (irrespective of age, sex, or race) undergoing laparoscopic abdominal or gynaecological pelvic surgery under general anaesthesia. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 10 RCTs, randomising 583 participants, comparing different gases for establishing pneumoperitoneum: nitrous oxide (four trials), helium (five trials), or room air (one trial) was compared to carbon dioxide. All the RCTs were single-centre studies. Four RCTs were conducted in the USA; two in Australia; one in China; one in Finland; one in Iran; and one in the Netherlands. The mean age of the participants ranged from 27.6 years to 49.0 years. Four trials randomised participants to nitrous oxide pneumoperitoneum (132 participants) or carbon dioxide pneumoperitoneum (128 participants). None of the trials was at low risk of bias. The evidence is very uncertain about the effects of nitrous oxide pneumoperitoneum compared to carbon dioxide pneumoperitoneum on cardiopulmonary complications (Peto odds ratio (OR) 2.62, 95% CI 0.78 to 8.85; 3 studies, 204 participants; very low-certainty evidence), or surgical morbidity (Peto OR 1.01, 95% CI 0.14 to 7.31; 3 studies, 207 participants; very low-certainty evidence). There were no serious adverse events related to either nitrous oxide or carbon dioxide pneumoperitoneum (4 studies, 260 participants; very low-certainty evidence). Four trials randomised participants to helium pneumoperitoneum (69 participants) or carbon dioxide pneumoperitoneum (75 participants) and one trial involving 33 participants did not state the number of participants in each group. None of the trials was at low risk of bias. The evidence is very uncertain about the effects of helium pneumoperitoneum compared to carbon dioxide pneumoperitoneum on cardiopulmonary complications (Peto OR 1.66, 95% CI 0.28 to 9.72; 3 studies, 128 participants; very low-certainty evidence), or surgical morbidity (5 studies, 177 participants; very low-certainty evidence). There were three serious adverse events (subcutaneous emphysema) related to helium pneumoperitoneum (3 studies, 128 participants; very low-certainty evidence). One trial randomised participants to room air pneumoperitoneum (70 participants) or carbon dioxide pneumoperitoneum (76 participants). The trial was at high risk of bias. There were no cardiopulmonary complications, serious adverse events, or deaths observed related to either room air or carbon dioxide pneumoperitoneum.    AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of nitrous oxide, helium, and room air pneumoperitoneum compared to carbon dioxide pneumoperitoneum on any of the primary outcomes, including cardiopulmonary complications, surgical morbidity, and serious adverse events. The safety of nitrous oxide, helium, and room air pneumoperitoneum has yet to be established, especially in people with high anaesthetic risk.

Abdominal drainage to prevent intra-peritoneal abscess after appendectomy for complicated appendicitis.

BACKGROUND: This is the second update of a Cochrane Review first published in 2015 and last updated in 2018. Appendectomy, the surgical removal of the appendix, is performed primarily for acute appendicitis. Patients who undergo appendectomy for complicated appendicitis, defined as gangrenous or perforated appendicitis, are more likely to suffer postoperative complications. The routine use of abdominal drainage to reduce postoperative complications after appendectomy for complicated appendicitis is controversial. OBJECTIVES: To assess the safety and efficacy of abdominal drainage to prevent intraperitoneal abscess after appendectomy (irrespective of open or laparoscopic) for complicated appendicitis; to compare the effects of different types of surgical drains; and to evaluate the optimal time for drain removal. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, Web of Science, the World Health Organization International Trials Registry Platform, ClinicalTrials.gov, Chinese Biomedical Literature Database, and three trials registers on 24 February 2020, together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared abdominal drainage versus no drainage in people undergoing emergency open or laparoscopic appendectomy for complicated appendicitis. We also included RCTs that compared different types of drains and different schedules for drain removal in people undergoing appendectomy for complicated appendicitis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We used the GRADE approach to assess evidence certainty. We included intraperitoneal abscess as the primary outcome. Secondary outcomes were wound infection, morbidity, mortality, hospital stay, hospital costs, pain, and quality of life. MAIN RESULTS: Use of drain versus no drain We included six RCTs (521 participants) comparing abdominal drainage and no drainage in participants undergoing emergency open appendectomy for complicated appendicitis. The studies were conducted in North America, Asia, and Africa. The majority of participants had perforated appendicitis with local or general peritonitis. All participants received antibiotic regimens after open appendectomy. None of the trials was assessed as at low risk of bias. The evidence is very uncertain regarding the effects of abdominal drainage versus no drainage on intraperitoneal abscess at 30 days (risk ratio (RR) 1.23, 95% confidence interval (CI) 0.47 to 3.21; 5 RCTs; 453 participants; very low-certainty evidence) or wound infection at 30 days (RR 2.01, 95% CI 0.88 to 4.56; 5 RCTs; 478 participants; very low-certainty evidence). There were seven deaths in the drainage group (N = 183) compared to one in the no-drainage group (N = 180), equating to an increase in the risk of 30-day mortality from 0.6% to 2.7% (Peto odds ratio 4.88, 95% CI 1.18 to 20.09; 4 RCTs; 363 participants; low-certainty evidence). Abdominal drainage may increase 30-day overall complication rate (morbidity; RR 6.67, 95% CI 2.13 to 20.87; 1 RCT; 90 participants; low-certainty evidence) and hospital stay by 2.17 days (95% CI 1.76 to 2.58; 3 RCTs; 298 participants; low-certainty evidence) compared to no drainage. The outcomes hospital costs, pain, and quality of life were not reported in any of the included studies. There were no RCTs comparing the use of drain versus no drain in participants undergoing emergency laparoscopic appendectomy for complicated appendicitis. Open drain versus closed drain There were no RCTs comparing open drain versus closed drain for complicated appendicitis. Early versus late drain removal There were no RCTs comparing early versus late drain removal for complicated appendicitis. AUTHORS' CONCLUSIONS: The certainty of the currently available evidence is low to very low. The effect of abdominal drainage on the prevention of intraperitoneal abscess or wound infection after open appendectomy is uncertain for patients with complicated appendicitis. The increased rates for overall complication rate and hospital stay for the drainage group compared to the no-drainage group are based on low-certainty evidence. Consequently, there is no evidence for any clinical improvement with the use of abdominal drainage in patients undergoing open appendectomy for complicated appendicitis. The increased risk of mortality with drainage comes from eight deaths observed in just under 400 recruited participants. Larger studies are needed to more reliably determine the effects of drainage on morbidity and mortality outcomes.

c-Myc affects hedgehog pathway via KCNQ1OT1/RAC1: A new mechanism for regulating HSC proliferation and epithelial-mesenchymal transition.

BACKGROUND: This study aimed to probe into the potential mechanism of KCNQ1OT1 in liver fibrosis. METHODS: The pathological changes in liver tissues were observed by Masson and hematoxylin-eosin (HE) staining. The proliferation or cell cycle of hepatic stellate cells (HSCs) was analyzed by MTT or flow cytometry. The expressions of epithelial markers E-cadherin, interstitial markers Snail and Vimentin, and hedgehog signaling pathway-related molecules Hhip, Shh, and Gli2 were detected by Western blot. The interaction or binding of c-Myc with the KCNQ1OT1 promoter was analyzed by dual-luciferase reporter gene or Chromatin immunoprecipitation (ChIP)-qPCR, and the interaction between KCNQ1OT1 and RAC1 was assessed by RNA immunoprecipitation and RNA pull-down. Moreover, the stability of RAC1 protein was detected by cycloheximide-chase and ubiquitination. RESULTS: c-Myc and KCNQ1OT1 were up-regulated in liver fibrosis tissues and cells. After the interference with c-Myc in primary-1-Day HSCs, the down-regulated KCNQ1OT1 restrained HSC proliferation and EMT by down-regulating RAC1 expression and restraining the hedgehog pathway. CONCLUSION: Our results indicated that the interference with c-Myc down-regulated RAC1 expression and restrained the hedgehog pathway by down-regulating KCNQ1OT1, thus restraining HSC proliferation and EMT in liver fibrosis.

miR­375 affects the hedgehog signaling pathway by downregulating RAC1 to inhibit hepatic stellate cell viability and epithelial­mesenchymal transition.

MicroRNAs (miRNAs/miRs) are a class of non­coding RNAs that serve crucial roles in liver cancer and other liver injury diseases. However, the expression profile and mechanisms underlying miRNAs in liver fibrosis are not completely understood. The present study identified the novel miR­375/Rac family small GTPase 1 (RAC1) regulatory axis in liver fibrosis. Reverse transcription­quantitative PCR was performed to detect miR­375 expression levels. MTT, flow cytometry and western blotting were performed to explore the in vitro roles of miR­375. The dual­luciferase reporter gene assay was performed to determine the potential mechanism underlying miR­375 in liver fibrosis. miR­375 expression was significantly downregulated in liver fibrosis tissues and cells compared with healthy control tissues and hepatocytes, respectively. Compared with the pre­negative control group, miR­375 overexpression inhibited mouse hepatic stellate cell (HSC) viability and epithelial­mesenchymal transition, and alleviated liver fibrosis. The dual­luciferase reporter assay results demonstrated that miR­375 bound to RAC1. Moreover, the results indicated that miR­375 regulated the hedgehog signaling pathway via RAC1 to restrain HSC viability and EMT, thus exerting its anti­liver fibrosis function. The present study identified the miR­375/RAC1 axis as a novel regulatory axis associated with the development of liver fibrosis.

Extended lymphadenectomy in hilar cholangiocarcinoma: What it will bring?

Lymph node dissection is always a hot issue in radical resection of hilar cholangiocarcinoma (HCCA). There are still controversies regarding whether some lymph nodes should be dissected, of which the para-aortic lymph nodes are the most controversial. This review synthesized findings in the literature using the PubMed database of articles in the English language published between 1990 and 2019 on the effectiveness of extended lymphadenectomy including para-aortic lymph nodes dissection in radical resection of HCCA. Hepatobiliary surgeons have basically achieved a consensus that enough lymph nodes should be obtained to accurately stage HCCA. Only a very small number of studies have focused on the effectiveness of extended lymphadenectomy including para-aortic nodes dissection on HCCA. They reported that extended lymphadenectomy can bring some survival benefits for patients with potential para-aortic lymph node metastasis and more lymph nodes can be obtained to make the patient's tumor staging more accurate without increasing the related complications. Extended lymphadenectomy should not be adopted for HCCA patients with intraoperatively confirmed distant lymph node metastases. For these patients, radical resection combined with postoperative adjuvant chemotherapy seems to be a better choice. A prospective, multicenter, randomized, controlled clinical study of regional lymphotomy and extended lymphadenectomy in HCCA should be conducted to guide clinical practice. A standardized extended lymphadenectomy may help to more accurately stage HCCA. Future studies are required to further assess whether extended lymphadenectomy can improve long-term survival in negative celiac, superior mesenteric, and para-aortic lymph node diseases.

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants have been used in some centers to reduce postoperative pancreatic fistula. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2018. OBJECTIVES: To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. SEARCH METHODS: We searched trial registers and the following biomedical databases: the Cochrane Library (2019, Issue 2), MEDLINE (1946 to 13 March2019), Embase (1980 to 11 March 2019), Science Citation Index Expanded (1900 to 13 March 2019), and Chinese Biomedical Literature Database (CBM) (1978 to 13 March 2019). SELECTION CRITERIA: We included all randomised controlled trials that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio (OR) for very rare outcomes), and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS: We included 12 studies involving 1604 participants in the review. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included seven studies involving 860 participants: 428 were randomised to the fibrin sealant group and 432 to the control group after distal pancreatectomy. Fibrin sealants may lead to little or no difference in postoperative pancreatic fistula (fibrin sealant 19.3%; control 20.1%; RR 0.96, 95% CI 0.68 to 1.35; 755 participants; four studies; low-quality evidence). Fibrin sealants may also lead to little or no difference in postoperative mortality (0.3% versus 0.5%; Peto OR 0.52, 95% CI 0.05 to 5.03; 804 participants; six studies; low-quality evidence), or overall postoperative morbidity (28.5% versus 23.2%; RR 1.23, 95% CI 0.97 to 1.58; 646 participants; three studies; low-quality evidence). We are uncertain whether fibrin sealants reduce reoperation rate (2.0% versus 3.8%; RR 0.51, 95% CI 0.15 to 1.71; 376 participants; two studies; very low-quality evidence) or length of hospital stay (MD 0.99 days, 95% CI -1.83 to 3.82; 371 participants; two studies; very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included four studies involving 393 participants: 186 were randomised to the fibrin sealant group and 207 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (16.7% versus 11.7%; RR 1.14, 95% CI 0.28 to 4.69; 199 participants; two studies; very low-quality evidence). We are uncertain whether fibrin sealants reduce postoperative mortality (0.5% versus 2.4%; Peto OR 0.26, 95% CI 0.05 to 1.32; 393 participants; four studies; low-quality evidence) or length of hospital stay (MD 0.01 days, 95% CI -3.91 to 3.94; 323 participants; three studies; very low-quality evidence). There is probably little or no difference in overall postoperative morbidity (52.6% versus 50.3%; RR 1.04, 95% CI 0.87 to 1.24; 323 participants; three studies; moderate-quality evidence) between the groups. We are uncertain whether fibrin sealants reduce reoperation rate (5.2% versus 7.7%; RR 0.74, 95% CI 0.33 to 1.66; 323 participants; three studies, very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two studies involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. Fibrin sealants may lead to little or no difference in postoperative mortality (8.4% versus 6.1%; Peto OR 1.41, 95% CI 0.63 to 3.13; 351 participants; two studies; low-quality evidence) or length of hospital stay (median 16 to 17 days versus 17 days; 351 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (32.0% versus 27.6%; RR 1.16, 95% CI 0.67 to 2.02; 351 participants; two studies; very low-quality evidence), or reoperation rate (13.6% versus 16.0%; RR 0.85, 95% CI 0.52 to 1.41; 351 participants; two studies; very low-quality evidence). Serious adverse events were reported in one study (169 participants; low-quality evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report postoperative pancreatic fistula, quality of life, or cost effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealants may have little or no effect on postoperative pancreatic fistula in people undergoing distal pancreatectomy. The effects of fibrin sealants on the prevention of postoperative pancreatic fistula are uncertain in people undergoing pancreaticoduodenectomy.

Abdominal drainage to prevent intra-peritoneal abscess after open appendectomy for complicated appendicitis.

BACKGROUND: Appendectomy, the surgical removal of the appendix, is performed primarily for acute appendicitis. Patients who undergo appendectomy for complicated appendicitis, defined as gangrenous or perforated appendicitis, are more likely to suffer from postoperative complications. The routine use of abdominal drainage to reduce postoperative complications after appendectomy for complicated appendicitis is controversial.This is an update of the review first published in 2015. OBJECTIVES: To assess the safety and efficacy of abdominal drainage to prevent intra-peritoneal abscess after open appendectomy for complicated appendicitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 6), Ovid MEDLINE (1946 to 30 June 2017), Ovid Embase (1974 to 30 June 2017), Science Citation Index Expanded (1900 to 30 June 2017), World Health Organization International Clinical Trials Registry Platform (30 June 2017), ClinicalTrials.gov (30 June 2017) and Chinese Biomedical Literature Database (CBM) (1978 to 30 June 2017). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared abdominal drainage and no drainage in people undergoing emergency open appendectomy for complicated appendicitis. DATA COLLECTION AND ANALYSIS: Two review authors identified the trials for inclusion, collected the data, and assessed the risk of bias independently. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio for very rare outcomes), and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). We used GRADE to rate the quality of evidence. MAIN RESULTS: We included six RCTs (521 participants), comparing abdominal drainage and no drainage in patients undergoing emergency open appendectomy for complicated appendicitis. The studies were conducted in North America, Asia and Africa. The majority of the participants had perforated appendicitis with local or general peritonitis. All participants received antibiotic regimens after open appendectomy. None of the trials was at low risk of bias.There was insufficient evidence to determine the effects of abdominal drainage and no drainage on intra-peritoneal abscess at 14 days (RR 1.23, 95% CI 0.47 to 3.21; 5 RCTs; 453 participants; very low-quality evidence) or for wound infection at 14 days (RR 2.01, 95% CI 0.88 to 4.56; 5 RCTs; 478 participants; very low-quality evidence). The increased risk of 30-day overall complication rate (morbidity) in the drainage group was rated as very low-quality evidence (RR 6.67, 95% CI 2.13 to 20.87; 1 RCT; 90 participants). There were seven deaths in the drainage group (N = 183) compared to one in the no drainage group (N = 180), equating to an increase in the risk of 30-day mortality from 0.6% to 2.7% (Peto odds ratio (OR) 4.88, 95% CI 1.18 to 20.09; 4 RCTs; 363 participants; moderate-quality evidence). There is 'very low-quality' evidence that drainage increases hospital stay compared to the no drainage group by 2.17 days (95% CI 1.76 to 2.58; 3 RCTs; 298 participants).Other outlined outcomes, hospital costs, pain, and quality of life, were not reported in any of the included studies. AUTHORS' CONCLUSIONS: The quality of the current evidence is very low. The effect of abdominal drainage on the prevention of intra-peritoneal abscess or wound infection after open appendectomy is uncertain for patients with complicated appendicitis. The increased rates for overall complication rate and hospital stay for the drainage group compared to no drainage group is also subject to great uncertainty. Thus, there is no evidence for any clinical improvement by using abdominal drainage in patients undergoing open appendectomy for complicated appendicitis. The increased risk of mortality with drainage comes from eight deaths observed in just under 400 people recruited to the studies. Larger studies are needed to determine the effects of drainage on morbidity and mortality outcomes more reliably.

Conditional survival of patients with hepatocellular carcinoma: results from the Surveillance, Epidemiology, and End Results registry.

BACKGROUND: Compared with overall survival, conditional survival is a more relevant measure of prognosis in surviving patients over time. The aim of this study was to describe the conditional survival of patients with hepatocellular carcinoma according to different prognostic variables through an analysis of a national population-based cancer registry. METHODS: We analyzed data from 3,082 hepatocellular carcinoma patients who were diagnosed between 2004 and 2014. RESULTS: The conditional overall and cause-specific survival improved from 37.6% to 68.9% and 45% to 79.1%, respectively, in the entire study population. The conditional overall and cause-specific survival improved from 32.6% to 69.3% and 40.1% to 74.8%, respectively, in patients aged 65 to 74 years. The conditional overall and cause-specific survival improved from 8.4% to 44.1% and 12.1% to 66.1%, respectively, in the stage IVB group. The conditional overall and cause-specific survival improved from 32.8% to 71.4% and 40.3% to 78.4%, respectively, in the positive/elevated AFP group. CONCLUSIONS: Conditional survival exhibited an improved prognosis over time. For hepatocellular carcinoma patients who survived for a specific period of time after diagnosis, more dramatic improvements occurred in patients aged 65-74 years, patients with AJCC stage IVB, and patients with a positive/elevated AFP value.

Long Noncoding RNA AFAP1-AS1 Promoted Tumor Growth and Invasion in Cholangiocarcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been shown to play important roles in a wide range of pathophysiological processes, including cancer progression. Our previous study has shown that AFAP1-AS1 was upregulated and acted as an oncogene in hepatocellular carcinoma. However, the expression and biological functions of lncRNA AFAP1-AS1 in intrahepatic cholangiocarcinoma (CCA) remains largely unknown. METHODS: The expression level of AFAP1-AS1 was measured in 56 pairs of human cholangiocarcinoma tumor tissues and corresponding adjacent normal bile duct tissues. The correlation between AFAP1-AS1 and the clinicopathological features were evaluated by chi-square test. The effects of AFAP1-AS1 on CCA cells were determined by CCK-8 assay, clone formation assay, flow cytometry and transwell assay. Finally, to determine the effect of AFAP1-AS1 on tumor growth in vivo, AFAP1-AS1 knockdowned CCLP-1 cells were subcutaneously into nude mice to evaluate tumor growth. RESULTS: In this study, we found that lncRNA AFAP1-AS1 was increased in CCA tissues and patients with high AFAP1-AS1 expression had a shorter overall survival. SiRNA-mediated AFAP1-AS1 knockdown significantly decreased cell proliferation of the CCA cells, with downregulation of C-myc and Cycling D1 in vitro. Furthermore, AFAP1-AS1 silencing inhibited cell migration partly due to decrease the expression of MMP-2 and MMP-9. In addition, CCLP-1 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on the tumorigenesis in vivo. CONCLUSIONS: Taken together, our findings suggested that AFAP1-AS1 might promote the CCA progression and provided a novel potential therapeutic target for CCA.

A multidrug cocktail approach attenuates ischemic-type biliary lesions in liver transplantation from non-heart-beating donors.

Ischemic-type biliary lesions (ITBL) are the most troublesome biliary complication after liver transplantation (LT) from non-heart-beating donors (NHBD) and frequently result in death or re-transplantation. In transplantation process, warm ischemia (WI) in the donor, cold ischemia and reperfusion injury in the recipient altogether inducing ischemia-reperfusion injury (IRI) is strongly associated with ITBL. This is a cascading injury process, involving in a complex series of inter-connecting events causing variety of cells activation and damage associated with the massive release of inflammatory cytokines and generation of reactive oxygen species (ROS). These damaged cells such as sinusoidal endothelial cells (SECs), Kupffer cells (KCs), hepatocytes and biliary epithelial cells (BECs), coupled with immunological injury and bile salt toxicity altogether contribute to ITBL in NHBD LT. Developed therapeutic strategies to attenuate IRI are essential to improve outcome after LT. Among them, single pharmaceutical interventions blocking a specific pathway of IRI in rodent models play an absolutely dominant role, and show a beneficial effect in some given controlled experiments. But this will likely prove ineffective in complex clinical setting in which more risk parameters are involved. Therefore, we intend to design a multidrug cocktail approach to block different pathways on more than one stage (WI, cold ischemia and reperfusion) of the process of IRI-induced ITBL simultaneously. This multidrug cocktail will include six drugs containing streptokinase, epoprostenol, thiazolidinediones (TZDs), N-Acetylcysteine (NAC), hemin and tauroursodeoxycholic acid (TUDC). These drugs show protective effects by targeting the different key events of IRI, such as anti-inflammatory, anti-fibrosis, anti-oxidation, anti-apoptosis and reduced bile salt toxicity. Ideally, the compounds, dosage, and method of application of drugs included in cocktail should not be definitive. We can consider removing or adding some drugs to the proposed cocktail based on further research. But given the multitude of different combinations, it is extremely difficult to determent which combination is the optimization design. Nevertheless, regardless of the difficulty, our multidrug cocktail approach designed to block different mechanisms on more than one stage of IRI simultaneously may represent a future preventive and therapeutic avenue for ITBL.

Repair of a common bile duct defect with a decellularized ureteral graft.

AIM: To evaluate the feasibility of repairing a common bile duct defect with a decellularized ureteral graft in a porcine model. METHODS: Eighteen pigs were randomly divided into three groups. An approximately 1 cm segment of the common bile duct was excised from all the pigs. The defect was repaired using a 2 cm long decellularized ureteral graft over a T-tube (T-tube group, n = 6) or a silicone stent (stent group, n = 6). Six pigs underwent bile duct reconstruction with a graft alone (stentless group). The surviving animals were euthanized at 3 mo. Specimens of the common bile ducts were obtained for histological analysis. RESULTS: The animals in the T-tube and stent groups survived until sacrifice. The blood test results were normal in both groups. The histology results showed a biliary epithelial layer covering the neo-bile duct. In contrast, all the animals in the stentless group died due to biliary peritonitis and cholangitis within two months post-surgery. Neither biliary epithelial cells nor accessory glands were observed at the graft sites in the stentless group. CONCLUSION: Repair of a common bile duct defect with a decellularized ureteral graft appears to be feasible. A T-tube or intraluminal stent was necessary to reduce postoperative complications.

Primary malignant hepatic paraganglioma mimicking liver tumor: A case report.

An extra-adrenal pheochromocytoma is also known as a paraganglioma. The present study reported the case of a 47-year-old female patient with an extremely rare primary nonfunctioning hepatic paraganglioma without any clinical signs and symptoms. A computed tomography scan of the entire abdomen region revealed a hyper-enhanced, well-marginated round mass located in segment 3 of the liver. A preoperative diagnosis of hepatocellular carcinoma was established and a left lateral hepatic lobectomy was performed. During the removal of the mass, the patient experienced extreme fluctuations in blood pressure. Analysis of hepatic and peripheral venous blood test results confirmed the increase of noradrenaline secretion. Postoperatively, the patient's blood pressure and catecholamine level returned to the normal range. However, three years after surgery, a plasma catecholamine examination revealed a high noradrenaline level. Abdominal magnetic resonance imaging scans revealed two metastases, located in the spleen and below the right posterior lobe of the liver, which were identified as malignant paragangliomas. Therefore, the patient was diagnosed with primary malignant hepatic paraganglioma recurrence three years after hepatic resection.

Xanthogranulomatous cholecystitis mimicking gallbladder carcinoma: An analysis of 42 cases.

AIM: To review and evaluate the diagnostic dilemma of xanthogranulomatous cholecystitis (XGC) clinically. METHODS: From July 2008 to June 2014, a total of 142 cases of pathologically diagnosed XGC were reviewed at our hospital, among which 42 were misdiagnosed as gallbladder carcinoma (GBC) based on preoperative radiographs and/or intra-operative findings. The clinical characteristics, preoperative imaging, intra-operative findings, frozen section (FS) analysis and surgical procedure data of these patients were collected and analyzed. RESULTS: The most common clinical syndrome in these 42 patients was chronic cholecystitis, followed by acute cholecystitis. Seven (17%) cases presented with mild jaundice without choledocholithiasis. Thirty-five (83%) cases presented with heterogeneous enhancement within thickened gallbladder walls on imaging, and 29 (69%) cases presented with abnormal enhancement in hepatic parenchyma neighboring the gallbladder, which indicated hepatic infiltration. Intra-operatively, adhesions to adjacent organs were observed in 40 (95.2%) cases, including the duodenum, colon and stomach. Thirty cases underwent FS analysis and the remainder did not. The accuracy rate of FS was 93%, and that of surgeon's macroscopic diagnosis was 50%. Six cases were misidentified as GBC by surgeon's macroscopic examination and underwent aggressive surgical treatment. No statistical difference was encountered in the incidence of postoperative complications between total cholecystectomy and subtotal cholecystectomy groups (21% vs 20%, P > 0.05). CONCLUSION: Neither clinical manifestations and laboratory tests nor radiological methods provide a practical and effective standard in the differential diagnosis between XGC and GBC.

Histological examination of frozen sections for patients with acute cholecystitis during cholecystectomy.

BACKGROUND: Unexpected gallbladder cancer may present with acute cholecystitis-like manifestations. Some authors recommended that frozen section analysis should be performed during laparoscopic cholecystectomy for all cases of acute cholecystitis. Others advocate selective use of frozen section analysis based on gross examination of the specimen by the surgeon. The aim of the present study was to evaluate whether surgeons could effectively identify suspected gallbladder with macroscopic examination alone. If not, is routine frozen section analysis worth advocating? METHODS: A total of 1162 patients with acute cholecystitis who had undergone simple cholecystectomy in our hospital from February 2009 to February 2014 were enrolled in the study. The data of patients with acute cholecystitis especially those with concurrent gallbladder cancer in terms of clinical characteristics, operative records, frozen section diagnosis and histopathology reports were analyzed. RESULTS: Thirteen patients with acute cholecystitis were found to have concurrent gallbladder cancer, with an incidence of 1.1% in acute cholecystitis. Forty patients with acute cholecystitis were suspected to have gallbladder cancer by macroscopic examination and specimens were taken for frozen section analysis. Six patients with gallbladder cancer were correctly identified by macroscopic examination alone but 7 patients with gallbladder cancer missed, including 3 patients with advanced cancer (2 T3 and 1 T2). Meanwhile, in 6 gallbladder cancer specimens sent for frozen section analysis, 3 early gallbladder cancers (2 Tis and 1 T1a) were missed by frozen section analysis. However, the remaining 3 patients with advanced gallbladder cancers (2 T3 and 1 T2) were correctly diagnosed. CONCLUSIONS: The incidence of comorbidity of gallbladder cancer and acute cholecystitis is higher than that of non-acute cholecystitis. The accurate diagnosis of gallbladder cancer by surgeons is poor and frozen section analysis is necessary.

Selective histology of cholecystectomy specimens--is it justified?

BACKGROUND: Gallbladder cancer (GBC) is rare but the most common malignancy of biliary tract with a dismal prognosis. The early diagnosis and surgical treatment of GBC offers the only chance of long-term survival. Despite advances in radiological imaging, early diagnosis of GBC is still rarely achieved without histopathology. In our hospital, routine histologic examination of all resected gallbladder specimens has been standard practice. This study seeks to define whether selective histologic examination for gallbladder specimens based on preoperative imaging or intraoperative findings is justified. MATERIALS AND METHODS: From September 2008-September 2013, all histopathology reports of gallbladder specimens after elective cholecystectomy were retrospectively analyzed in a single surgical unit. Preoperative imaging, intraoperative findings, and histology notes were analyzed in all cases. RESULTS: Out of 14,369 (60% female and 40% male) patients undergoing cholecystectomy, GBC was found in only 46 cases (0.32%). More than one fifth (10/46) of GBC patients presented with acute cholecutitis (AC). All 10 AC patients coexisted with GBC harbored "significantly inflamed' gallbladders, and about 83.49% AC patients were judged with "significant inflammation." Carcinoma in situ and early GBC (T1a, T1b) accounted for 61% of all cases. Only two patients with Tis and T1a respectively did not show suspicious lesion on preoperative and intraoperative findings, but for the remaining cases (44/46), GBC was suspected either by preoperative imaging and/or intraoperative findings. CONCLUSIONS: Almost all cases of invasive GBC will show macroscopic abnormalities following examination by a simple procedure-a full dissection, inspection, and palpation of the gallbladder. Any patient with early GBCs "missed" on macroscopic examination can still receive the appropriate treatment by the cholecystectomy alone. The gallbladder should be sent for histology only if macroscopic examination raises suspicion. This selective policy is more cost-effective, and does not appear to compromise patients outcome.