ERCP for patients who have undergone Billroth Ⅱ gastroenterostomy and Braun anastomosis

Endoscopic retrograde cholangiopancreatography (ERCP) is efficacious in patients who have undergone Billroth II gastroenterostomies, but the success rate decreases in patients who also have experienced Braun anastomoses. There are currently no reports describing the preferred enterography route for cannulation in these patients. We first review the patient’s previous surgery records, which most often indicate that the efferent loop is at the greater curvature of the stomach. We recommend extending the duodenoscope along the greater curvature of the stomach and then advancing it through the “lower entrance” at the site of the gastrojejunal anastomosis, along the efferent loop, and through the “middle entrance” at the site of the Braun anastomosis to reach the papilla of Vater. Ten patients who had each undergone Billroth II gastroenterostomy and Braun anastomosis between January 2009 and December 2011 were included in our study. The overall success rate of enterography was 90% for the patients who had undergone Billroth II gastroenterostomy and Braun anastomosis, and the therapeutic success rate was 80%. We believe that this enterography route for ERCP is optimal for a patient who has had Billroth II gastroenterostomy and Braun anastomosis and helps to increase the success rate of the procedure.

Duct-to-duct biliary reconstruction after radical resection of Bismuth Ⅲ a hilar cholangiocarcinoma

At present, radical resection remains the only effective treatment for patients with hilar cholangiocarcinoma. The surgical approach for R0 resection of hilar cholangiocarcinoma is complex and diverse, but for the biliary reconstruction after resection, almost all surgeons use Roux-en-Y hepaticojejunostomy. A viable alternative to Roux-en-Y reconstruction after radical resection of hilar cholangiocarcinoma has not yet been proposed. We report a case of performing duct-to-duct biliary reconstruction after radical resection of Bismuth Ⅲa hilar cholangiocarcinoma. End-to-end anastomosis between the left hepatic duct and the distal common bile duct was used for the biliary reconstruction, and a singlelayer continuous suture was performed along the bile duct using 5-0 prolene. The patient was discharged favorably without biliary fistula 2 wk later. Evidence for tumor recurrence was not found after an 18 mo follow- up. Performing bile duct end-to-end anastomosis in hilar cholangiocarcinoma can simplify the complex digestive tract reconstruction process.

Retrieval-balloon-assisted enterography for ERCP after Billroth Ⅱ gastroenterostomy and Braun anastomosis

AIM: To describe an optimal route to the Braun anastomosis including the use of retrieval-balloon-assisted enterography.METHODS: Patients who received a Billroth Ⅱ gastroenterostomy(n = 109) and a Billroth Ⅱ gastroenterostomy with Braun anastomosis(n = 20) between January 2009 and May 2013 were analyzed in this study. Endoscopic ret-rograde cholangiopancreatography(ERCP) was performed under fluoroscopic control using a total length of 120 cm oblique-viewing duodenoscope with a 3.7-mm diameter working channel. For this procedure, we used a triplelumen retrieval balloon catheter in which a 0.035-inch guidewire could be inserted into the "open-channel" guidewire lumen while the balloon could be simultaneously injected and inflated through the other 2 lumens.RESULTS: For the patients with Billroth Ⅱ gastroenterostomy and Braun anastomosis, successful access to the papilla was gained in 17 patients(85%) and there was therapeutic success in 16 patients(80%). One patient had afferent loop perforation, but postoperative bleeding did not occur. For Billroth Ⅱ gastroenterostomy, there was failure in accessing the papilla in 15 patients(13.8%). ERCP was unsuccessful because of tumor infiltration(6 patients), a long afferent loop(9 patients), and cannulation failure(4 patients). The papilla was successfully accessed in 94 patients(86.2%), and there was therapeutic success in 90 patients(82.6%). Afferent loop perforation did not occur in any of these patients. One patient had hemorrhage 2 h after ERCP, which was successfully managed with conservative treatment.CONCLUSION: Retrieval-balloon-assisted enterography along an optimal route may improve the ERCP success rate after Billroth Ⅱ gastroenterostomy and Braun anastomosis.

Long-term outcomes after radical gastrectomy in gastric cancer patients with overt bleeding

AIM: To investigate the difference in long-term outcomes between gastric cancer patients with and without a primary symptom of overt bleeding(OB).METHODS: Consecutive patients between January 1, 2007 and March 1, 2012 were identified retrospectively by reviewing a gastric cancer database at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. A follow-up examination was performed on patients who underwent a radical gastrectomy. OB due to gastric cancer included hematemesis, melena or hematochezia, and gastric cancer was confirmed as the source of bleeding by endoscopy. Patients without OB were defined as cases with occult bleeding and those with other initial presentations, including epigastric pain, weakness, weight loss and obstruction. The 3-year overall survival(OS) rate, age, gender, AJCC T stage, AJCC N stage, overall AJCC stage, tumor size, histological type, macroscopic(Borrmann) type, lymphovascular invasion and R status were compared between patients with and without OB. Moreover, we carried out a subgroup analysis based on tumor location(upper, middle and lower).RESULTS: We identified 939 patients. Of these, 695(74.0%) were hospitalized for potential radical gastrectomy and another 244 received palliative resection, rerouting of the gastrointestinal tract, chemotherapy, radiotherapy or no treatment due to the presence of unresectable tumors. Notably, there was no significant difference in the percentage of OB patients between resectable cases and unresectable cases(20.3 % vs 22.1 %, P = 0.541). Fo l l o w- u p examination was performed on 653 patients(94%) who underwent radical gastrectomy. We found no significant difference in 3-year OS rate(68.2% vs 61.2%, P = 0.143) or clinicopathological characteristics(P > 0.05) between these patients with and without OB. Subgroup analysis based on tumor location showed that the 3-year OS rate of upper gastric cancer was significantly higher in patients with OB(84.6%) than in those without OB(48.1%, P < 0.01) and that AJCC stagesⅠ-Ⅱ(56.4% vs 35.1%, P = 0.017) and T1-T2 category tumors(30.8% vs 13%, P = 0.010) were more frequent in patients with OB than in those without OB. There was no significant difference in 3-year OS rate or clinicopathological characteristics between patients with and without OB(P > 0.05) for middle or lower gastric cancer.CONCLUSION: Upper gastric cancer patients with OB exhibited tumors at less advanced pathological stages and had a better prognosis than upper gastric cancer patients without OB.

Overexpression of lysine specific demethylase 1 predicts worse prognosis in primary hepatocellular carcinoma patients

AIM:To investigate the clinicopathological features and prognostic value of lysine specific demethylase 1(LSD1) in hepatocellular carcinoma(HCC).METHODS:We examined LSD1 expression in 60 paired liver cancer tissues and adjacent noncancerous tissues by quantitative real time polymerase chain reaction(qRT-PCR) and Western blotting.In addition,we analyzed LSD1 expression in 198 HCC samples by immunohistochemistry.The relationship between LSD1 expression,clinicopathological features and patient survival was investigated.RESULTS:Immunohistochemistry,Western blotting,and qRT-PCR consistently confirmed LSD1 overexpression in HCC tissues compared to adjacent non-neoplastic tissues(P < 0.01).Additionally,immunostaining showed more LSD1-positive cells in the higher tumor stage(T3-4) and tumor grade(G3) than in the lower tumor stage(T1-2,P < 0.001) and tumor grade(G1-2,P < 0.001),respectively.Moreover,HCC patients with high LSD1 expression had significantly lower 5-year overall survival rates(P < 0.001) and lower 5-year disease-free survival rates(P < 0.001),respectively.A Cox proportional hazards model further demonstrated that LSD1 over-expression was an independent predictor of poor prognosis for both 5-year disease-free survival [hazards ratio(HR) = 1.426,95%CI:0.672-2.146,P < 0.001] and 5-year overall survival(HR = 2.456,95%CI:1.234-3.932,P < 0.001) in HCC.CONCLUSION:Our data suggest for the first time that the overexpression of LSD1 protein in HCC tissues indicates tumor progression and predicts poor prognosis.

Surgical management of patients with bowel obstructions secondary to gastric cancer

AIM: To assess whole-body fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the management of small bowel obstructions (SBOs) secondary to gastric cancer and its role in treatment strategies. METHODS: The medical records of all of the patients who were admitted for an intestinal obstruction after curative resection for gastric cancer were retrospectively reviewed. PET/CT was performed before a clinical treatment strategy was established for each patient. The patients were divided into 2 groups: patients with no evidence of a tumor recurrence and patients with evidence of a tumor recurrence. Tumor recurrences included a local recurrence, peritoneal carcinomatosis or distant metastases. The primary endpoint was the 1-year survival rate, and other variables included patient demographics, the length of hospital stay, complications, and mortality. RESULTS: The median time between a diagnosis of gastric cancer and the detection of a SBO was 1.4 years. Overall, 31 of 65 patients (47.7%) had evidence of a tumor recurrence on the PET/CT scan, which was the only factor that was associated with poor survival. Open and close surgery was the main type of surgical procedure reported for the patients with tumor recurrences. R0 resections were performed in 2 patients, including 1 who underwent combined adjacent organ resection. In the group with no evidence of a tumor recurrence on PET/CT, bowel resections were performed in 7 patients, adhesiolysis was performed in 7 patients, and a bypass was performed in 1 patient. The 1-year survival curves according to PET/CT evidence of a tumor recurrence vs no PET/CT evidence of a tumor recurrence were significantly different, and the 1-year survival rates were 8.8% vs 93.5%, respectively. There were no significant differences (P = 0.71) in the 1-year survival rates based on surgical vs nonsurgical management (0% with nonoperative treatment vs 20% after exploratory laparotomy). CONCLUSION: 18 F-FDG PET/CT can be used to identify the causes of bowel obstructions in patients with a history of gastric cancer, and this method is useful for planning the surgical management of these patients.

Retrieval-balloon-assisted enterography in post-pancreaticoduodenectomy endoscopic retrograde cholangiopancreatography

This case reports an application of conventional duodenoscope in a post pancreaticoduodenectomy patient with the help of retrieval balloon assisted enterography.The 56-year-old woman had pancreaticoduodenectomy with Child reconstruction 9 mo ago because of pancreatic adenocarcinoma and now there are recurrent enlarged lymph nodes in the anastomotic stoma of hepaticojejunostomy.Considering the patient's late-stage cancer,a plastic stent was then successfully placed there to drainage.The main challenge in this case was the extremely long afferent loop and blind cannulation through the anastomotic stoma of hepaticojejunostomy.Retrieval balloon assisted enterography is very helpful for duodenoscope going through the reconstructed intestinal tract and for the cannulation.After two weeks,the patient remained free of painful symptoms and free of fever.Liver function improved well.Four months after the placement of stent,the patient died of cachexia without jaundice,fever and abdominal pain according to her daughter's statement.

ZBTB20 is involved in liver regeneration after partial hepatectomy in mouse

BACKGROUND: A better understanding of the molecular mechanisms in liver regeneration holds promise for exploring the new potential therapy for liver failure. The present study was to investigate the role of zinc finger and BTB domain-containing protein 20(ZBTB20), a potential factor associated with liver regeneration, in a model of 70% hepatectomy in mice. METHODS: Parameters for liver proliferation such as liver/body ratio and BrdU positivity were obtained via direct measurement and immunohistochemistry. The levels of zinc fingers and homeoboxes 2(ZHX2), ZBTB20, alpha-fetoprotein(AFP) and glypican 3(GPC3) transcripts in the regenerating liver tissue of a 70% hepatectomy rodent model were monitored by real-time PCR analysis at different time points. Knockdown of ZBTB20 was performed to characterize its regulatory function. RESULTS: A negatively regulating relationship between ZHX2, ZBTB20 and AFP, GPC3 was revealed from 24 to 72 hours after 70% hepatectomy. ZBTB20 appears to negatively regulate AFP and GPC3 transcription since the knockdown of ZBTB20 promoted the proliferation of hepatocytes and the expression of AFP and GPC3. CONCLUSION: In addition to AFP, GPC3 and ZHX2, ZBTB20 is a new regulator in liver regeneration and the decrease of ZBTB20 expression following 70% hepatectomy promotes AFP and GPC3 expression.

Management of hepatocellular carcinoma rupture in the caudate lobe

AIM: To demonstrate that caudate lobectomy is a valid treatment in cases of hepatocellular carcinoma(HCC) rupture in the caudate lobe based on our experience with the largest case series reported to date.METHODS: A retrospective study of eight patients presenting with spontaneous rupture and hemorrhage of HCC in the caudate lobe was conducted.Two patients underwent ineffective transarterial embolization preoperatively.Caudate lobectomy was performed in all eight patients.Bilateral approach was taken in seven cases for isolated complete caudate lobectomy.Left-sided approach was employed in one case for isolated partial caudate lobectomy.Transarterial chemoembolization was performed postoperatively in all patients.RESULTS: Caudate lobectomy was successfully completed in all eight cases.The median time delay from the diagnosis to operation was 5 d(range: 0.25-9).Median operating time was 200 min(range: 120-310) with a median blood loss of 900 m L(range: 300-1500).Five patient remained in long-term follow-up,with one patient becoming lost to followup at 3 years and two patients currently alive at 7 and 19 mo.One patient required reoperation due to recurrence.Gamma knife intervention was performed for brain metastasis in another case.Two patients survived for 10 and 84 mo postoperatively,ultimately succumbing to multiple organ metastases.CONCLUSION: Caudate lobectomy is the salvage choice for HCC rupture in the caudate lobe.Local anatomy and physiologic features of the disease render caudate lobectomy a technically difficult operation.Postponement of surgical intervention is thus recommended while the rupture remains hemodynamically stable until an experienced surgeon becomes available.Prognosis is confounded by numerous factors,but long-term survival can be expected in the majority of cases.

Impact of being overweight on the surgical outcomes of patients with gastric cancer: A meta-analysis

AIM: To investigate the effect of being overweight on the surgical results of patients with gastric cancer. METHODS: Comprehensive electronic searches of the PubMed, Web of Science, and Cochrane Library databases were conducted. Studies were identified that included patients with surgical complications from gastric cancer who were classified as normal weight [body mass index (BMI) < 25 kg/m 2 ] or overweight (BMI ≥ 25 kg/m 2 ). The operative time, retrieved lymph nodes, blood loss, and long-term survival were analyzed. A subgroup analysis was conducted based on whether patients received laparoscopic or open gastrectomy procedures. All statistical tests were performed using ReviewerManager 5.1.2 software. RESULTS: This meta-analysis included 23 studies with 20678 patients (15781 with BMI < 25 kg/m 2 ; 4897 with BMI ≥ 25 kg/m 2 ). Overweight patients had significantly increased operation times [MD: -29.14; 95%CI: -38.14-(-20.21); P < 0.00001], blood loss [MD: -194.58; 95%CI: -314.21-(-74.95); P = 0.001], complications (RR: 0.75; 95%CI: 0.66-0.85; P < 0.00001), anastomosis leakages (RR: 0.59; 95%CI: 0.42-0.82; P = 0.002), and pancreatic fistulas (RR: 0.486; 95%CI: 0.34-0.63; P < 0.00001), whereas lymph node retrieval was decreased significantly in the overweight group (MD: 1.69; 95%CI: 0.75-2.62; P < 0.0001). In addition, overweight patients had poorer long-term survival (RR: 1.14; 95%CI: 1.07-1.20; P < 0.0001). No significant difference was detected for the mortality and length of hospital stay. CONCLUSION: This meta-analysis demonstrates that a high BMI not only increases the surgical difficulty and complications but also impairs the long-term survival of patients with gastric cancer.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer:Results from 24 hospitals in China

BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of debate.AIM To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China.The logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch only.To investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch only.Seven(9.1%)patients in the Ch+RL group had lymph node metastasis.The 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent Ch.Hep+Ch showed no improvement in prognosis in T1b GBC patients.Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC patients.Routine Ch+RL should be advised in T1b GBC.

Application of single balloon enteroscopy-assisted therapeutic endoscopic retrograde cholangiopancreatography in patients after bilioenteric Roux-en-Y anastomosis: Experience of multi-disciplinary collaboration

BACKGROUND Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.

Comparison of postoperative complications between internal and external pancreatic duct stenting during pancreaticoduodenectomy: a meta-analysis

Background：Two types of pancreatic duct stents are used to improve postoperative outcomes of pancreatic anastomosis.The aim of this meta-analysis was to evaluate and compare the postoperative outcomes of patients with internal or external stenting during pancreaticoduodenectomy（PD）.Methods：We searched Pub Med,EMBASE,the Cochrane Library and Web of Science databases until the end of December,2014.Studies comparing outcomes of external vs.internal stent placement in PD were eligible for inclusion.Included literature was extracted and assessed by two independent reviewers.Results：Seven articles were identified for inclusion：three randomized controlled trials（RCTs）and four observational clinical studies（OCS）.The meta-analyses revealed that use of external stents had advantage on reducing the incidences of pancreatic fistula（PF）in total[odds ratio（OR）=0.69;95%confidence interval（CI）,0.48-0.99;P=0.04],PF in soft pancreas（OR=0.30;95%CI,0.16-0.56;P=0.0002）and delayed gastric emptying（DGE）（OR=0.58;95%CI,0.38-0.89;P=0.01）compared with internal stents.There were no significant differences in other postoperative outcomes between two stenting methods,including postoperative morbidity（OR=0.93;95%CI,0.39-2.23;P=0.88）,overall mortality（OR=0.70;95%CI,0.22-2.25;P=0.55）,and intra-abdominal collections（OR=0.67;95%CI,0.26-1.71;P=0.40）.Conclusions：Based upon this meta-analysis,the use of external pancreatic stents might have potential benefit in reducing the incidence of PF and DGE.Due to the limited number of original studies,more RCTs are needed to further support our result and clarify the issue.

Diagnosis and Treatment of Cholangiocarcinoma: A Consensus from Surgical Specialists of China

Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.

Burden of biliary tract carcinoma in China(1990–2021):Findings from the 2021 Global Burden of Disease Study

Biliary tract carcinoma(BTC)is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China.Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels,and little is known about the demographic,temporal,and geographic patterns of epidemiological characteristics and disease burden of BTC in China.The incidence,mortality,disability-adjusted life-years(DALYs),years of life lost(YLLs)due to premature death and years lived with disability(YLDs)of BTC were comprehensively examined by age,sex,and calendar year in the Chinese population,using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study.All-age incidence increased from 17,077 to 51,720between 1990 and 2021,and the age-standardized incidence rate rose by 13.62%;all-age deaths increased from 17,251 to 37,833,but the age-standardized mortality rate fell by nearly one-fifth.The DALYs rose by 89.57%while the age-standardized DALY rate fell by 23.24%.Variations of the tendencies in BTC burden were found between sexes and age groups.Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels,whereas northern provincial regions have higher mortality,DALY,and YLL levels.The proportions of DALYs attributable to high body mass index(BMI)illustrate the growing attribution obesity has made,and high BMI usually puts more burden on northern provincial regions.These results provide evidence to support precise,targeted,and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.

Modified FOLFIRINOX for unresectable locally advanced or metastatic gallbladder cancer,a comparison with GEMOX regimen

Background:The first-line chemotherapy regimen for advanced gallbladder cancer(GBC)is gemcitabine plus platinum(GP),despite its efficacy is limited.The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX(mFOLFIRINOX)and gemcitabine plus oxaliplatin(GEMOX)as the first-line chemotherapy for unresectable locally advanced or metastatic GBC.Methods:The data of patients with unresectable locally advanced or metastatic GBC,who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,were retrieved.This retrospective study evaluated the clinical characteristics,survival outcomes and adverse events.Results:A total of 44 patients(n=25 in mFOLFIRINOX,n=19 in GEMOX)were included.There were no significant differences between groups in baseline characteristics.The median progression free survival(mPFS)was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group[P=0.021;hazard ratio(HR),0.499;95%CI,0.266 to 0.937].The median overall survival(mOS)was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group(P=0.019;HR,0.471;95%CI,0.239 to 0.929).Disease control rate(DCR)was 76.0%in the mFOLFIRINOX group and 47.4%in the GEMOX group(P=0.051).The rate of grade 3-4 adverse events was 48%in the mFOLFIRINOX group and 36.8%in the GEMOX group(P=0.459).The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group,while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group.Conclusions:mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC,and the results need to be further verified by prospective clinical studies.

TopoisomeraseⅡalpha promotes gallbladder cancer proliferation and metastasis through activating phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Background:TopoisomeraseⅡalpha(TOP2A)has been reported to play a crucial role in the tumorigenesis of various cancer types.However,the biological role of TOP2A in gallbladder cancer(GBC)remains unknown.The current study aimed to explore the function and potential mechanism of TOP2A in GBC.Methods:Based on Gene Expression Profiling Interactive Analysis data,we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival.Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues.In vitro,cell proliferation,migration,and invasion ability were examined by cell counting kit-8 and transwell assay,respectively.Epithelial-mesenchymal transition(EMT)related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway-related markers were measured by Western blotting.Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.Results:TOP2A was found up-regulated in GBC(tumor vs.normal,12.62 vs.0.34)and correlated with the late tumor node metastasis stage(P=0.0032),present of lymph node metastasis(P=0.0273),and poor prognosis in GBC patients(log-rank P=0.028).In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation,migration,invasion,EMT process,and tumor growth in GBC.In addition,TOP2A down-regulation significantly decreased the protein levels of phosphor(p)-PI3K,p-Akt,and p-mTOR.Conclusion:Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients.TOP2A promotes GBC cell proliferation,migration,invasion,EMT process,and tumor growth through activating PI3K/Akt/mTOR signaling pathway,and may serve as a novel prognostic biomarker and therapeutic target for GBC.