Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization.

BACKGROUND: Endoscopic variceal treatment (EVT) is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis. Proton pump inhibitors (PPIs) are widely used for various gastric acid-related diseases. However, the effects of PPIs on the development of post-EVT complications, especially gastrointestinal bleeding (GIB), remain controversial. AIM: To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization. METHODS: Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command, treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included. Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 143 patients were included. The incidence of post-EVT GIB and other post-EVT complications was 4.90% and 46.85%, respectively. In the overall analyses, postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB (OR = 0.525, 95%CI = 0.113-2.438, P = 0.411) or other post-EVT complications (OR = 0.804, 95%CI = 0.413-1.565, P = 0.522). In the subgroup analyses according to the enrollment period, type and route of PPIs after the index EVT, use of PPIs before the index EVT, use of vasoactive drugs after the index EVT, indication of EVT (prophylactic and therapeutic), and presence of portal venous system thrombosis, ascites, and hepatocellular carcinoma, the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant. CONCLUSION: Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.

Effect of oral simethicone on the quality of colonoscopy: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: In this systematic review and meta-analysis, we aimed to investigate the effect of oral simethicone (SIM), an antifoaming agent, on the quality of colonoscopy in terms of bowel preparation quality, adenoma or polyp detection rate (ADR/PDR) and cecal intubation rate (CIR). METHODS: All randomized controlled trials (RCTs) on the use of SIM during bowel preparation for colonoscopy published up to 17 March 2021 were identified from the PubMed, EMBASE and Cochrane Library databases. Bowel preparation quality, ADR/PDR/CIR, cecal intubation time (CIT), withdrawal time (WT), patients' tolerability, acceptability and volume of foam and bubbles were compared between the SIM and non-SIM groups. RESULTS: Thirty-eight RCTs with 10 505 patients were included. Oral SIM significantly increased the rate of total Boston bowel preparation scale (BBPS) score ≥6 (risk ratio [RR]  1.13, P < 0.0001), acceptability (RR  1.15, P = 0.01) and the rate of no or minimal foam and bubbles (RR  1.28, P < 0.00001) and decreased abdominal distension (RR  0.64, P < 0.0001). However, it had no significant impact on overall ADR, overall PDR, CIR, CIT or WT. The rate of total BBPS score ≥6 remained significantly higher in the SIM group when a single-dose laxative regimen or a SIM dosage of ≥320 mg was employed; and ADR, PDR and CIR were significantly increased in the SIM group among colonoscopy clinicians who achieved an ADR <31%, PDR <45% and CIR <96%, respectively. CONCLUSIONS: Oral SIM can improve bowel preparation quality, especially in patients receiving a SIM dosage of ≥320 mg or a single-dose laxative regimen. SIM may be preferred by junior colonoscopy physicians/trainees with a lower ADR/PDR or CIR.

Successful treatment of acute symptomatic extensive portal venous system thrombosis by 7-day systemic thrombolysis.

Acute portal venous system thrombosis (PVST) can cause acute mesenteric ischemia and even intestinal infarction, which are potentially fatal, and requires recanalization in a timely fashion. Herein, we report a 56-year-old man with acute non-cirrhotic symptomatic extensive PVST who achieved portal vein recanalization after systemic thrombolysis combined with anticoagulation. Initially, anticoagulation with enoxaparin sodium for 4 d was ineffective, and then systemic thrombolysis for 7 d was added. After that, his abdominal pain completely disappeared, and portal vein system vessels became gradually patent. Long-term anticoagulation therapy was maintained. In conclusion, 7-d systemic thrombolysis may be an effective and safe choice of treatment for acute symptomatic extensive PVST which does not respond to anticoagulation therapy.

[Early hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: the risk factors and long-time survival].

OBJECTIVE: To identify the risk factors of early post-TIPS hepatic encephalopathy (HE) and the long-time survival of patients with or without early post-TIPS HE. METHODS: Consecutive cirrhotic patients who underwent TIPS for variceal rebleeding or refractory ascites in our center from January 2003 to December 2008 were included in this study. More than 60 clinical characteristics were enrolled in univariate analysis and logistic regression analysis to define the risk factors of HE in 3 months after TIPS procedure (early post-TIPS HE). The long-time survival of patients with or without early post-TIPS HE was compared by Cox regression with several covariates. RESULTS: According to our inclusion criteria, 190 patients were included. The median follow-up was 30.5 months. Lower serum concentration of fibrinogen and higher Child-Pugh score were the independent risk factors for suffering early post-TIPS HE. Patients without early post-TIPS HE after TIPS showed better prognosis than those with early post-TIPS HE after TIPS (P = 0.044). CONCLUSION: Patients with lower serum fibrinogen and higher Child-Pugh score before TIPS might be more probably attacked by early post-TIPS HE which indicated worse long-term survival.

Portal hypertension in a patient with biliary hamartomas: A case report.

BACKGROUND: Biliary hamartomas (BH) are a rare benign disease caused by malformation of the intrahepatic bile ducts. BH are occasionally diagnosed, but often lack obvious clinical symptoms. They are usually diagnosed by biopsy and imaging tests in clinical practice. Few studies have reported the association of BH with portal hypertension. CASE SUMMARY: A 40-year-old man was repeatedly admitted to our hospital due to hematochezia. The source of bleeding was considered to be gastroesophageal varices and portal hypertensive gastropathy by endoscopy. He had no history of hepatitis virus infection, alcohol abuse, drug-induced liver injury, or autoimmune liver disease. He underwent magnetic resonance imaging, which showed rounded, irregular, low-signal-T1 and high-signal-T2 lesions diffusely distributed on the liver, that were not communicated with the biliary system on magnetic resonance cholangiopancreatography. According to the imaging examination, the patient was considered to have a diagnosis of BH with portal hypertension. CONCLUSION: Based on the present case report, BH may be a potential etiology of portal hypertension.

Esophageal collateral veins in predicting esophageal variceal recurrence and rebleeding after endoscopic treatment: a systematic review and meta-analysis.

BACKGROUND: Endoscopic treatment is recommended for the management of esophageal varices. However, variceal recurrence or rebleeding is common after endoscopic variceal eradication. Our study aimed to systematically evaluate the prevalence of esophageal collateral veins (ECVs) and the association of ECVs with recurrence of esophageal varices or rebleeding from esophageal varices after endoscopic treatment. METHODS: We searched the relevant literature through the PubMed, EMBASE, and Cochrane Library databases. Prevalence of paraesophageal veins (para-EVs), periesophageal veins (peri-EVs), and perforating veins (PVs) were pooled. Risk ratio (RR) and odds ratio (OR) with 95% confidence intervals (CIs) were calculated for cohort studies and case-control studies, respectively. A random-effects model was employed. Heterogeneity among studies was calculated. RESULTS: Among the 532 retrieved papers, 28 were included. The pooled prevalence of para-EVs, peri-EVs, and PVs in patients with esophageal varices was 73%, 88%, and 54%, respectively. The pooled prevalence of para-EVs and PVs in patients with recurrence of esophageal varices was 87% and 62%, respectively. The risk for recurrence of esophageal varices was significantly increased in patients with PVs (OR = 9.79, 95% CI: 1.95-49.22, P = 0.006 for eight case-control studies), but not in those with para-EVs (OR = 4.26, 95% CI: 0.38-38.35, P = 0.24 for four case-control studies; RR = 1.81, 95% CI: 0.83-3.97, P = 0.14 for three cohort studies). Patients with para-EVs had a significantly higher incidence of rebleeding from esophageal varices (RR = 13.00, 95% CI: 2.43-69.56, P = 0.003 for two cohort studies). Statistically significant heterogeneity was notable across the meta-analyses. CONCLUSIONS: ECVs are common in patients with esophageal varices. Identification of ECVs could be helpful for predicting the recurrence of esophageal varices or rebleeding from esophageal varices after endoscopic treatment.

Correlation analysis of collagen proportionate area in Budd-Chiari syndrome: A preliminary clinicopathological study.

BACKGROUND: Collagen proportionate area (CPA) is an important index for assessing the severity of liver fibrosis. Budd-Chiari syndrome can frequently progress to liver fibrosis and cirrhosis. CPA might play an important role in the pathological progress of Budd-Chiari syndrome. AIM: To explore the role of CPA in predicting the outcomes of patients with Budd-Chiari syndrome. METHODS: Nine patients with Budd-Chiari syndrome undergoing transjugular intrahepatic portosystemic shunt (TIPS) were included. The median CPA level and correlation of CPA and prognosis of TIPS were determined. RESULTS: Median CPA was 23.07% (range: 0%-40.20%). Pearson's χ2 test demonstrated a significant correlation of CPA with history of gastrointestinal bleeding (Pearson's coefficient: 0.832, P = 0.005), alanine aminotransferase (Pearson's coefficient: -0.694, P = 0.038), and prothrombin time (Pearson's coefficient: 0.68, P = 0.044). Although CPA was not significantly correlated with shunt dysfunction or hepatic encephalopathy after TIPS, the absolute CPA was relatively larger in patients who developed shunt dysfunction or hepatic encephalopathy after TIPS. CONCLUSION: This preliminary clinicopathological study found a marginal effect of CPA on the outcomes of Budd-Chiari syndrome patients treated with TIPS.

Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients.

Endoscopic retrograde cholangiopancreatography with double balloon enteroscope in patients with altered gastrointestinal anatomy: A meta-analysis.

BACKGROUND/AIMS: The aim of this study was to evaluate the effectiveness and safety of endoscopic retrograde cholangiopancreatography with double balloon enteroscope (DBE-ERCP) in patients with altered gastrointestinal anatomy in a meta-analysis. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane library covering the period from January 2001 to December 2015. Data were selected and abstracted from eligible studies and were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. RESULTS: Ten studies involving a total of 301 patients were included in the analysis. The pooled enteroscopy, diagnostic, and therapeutic success rates were 89.75% [95% confidence interval (CI): 79.65-94.30%], 79.92% (95% CI: 68.06-89.59%), and 63.55% (95% CI: 53.70-72.86%), respectively. DBE-ERCP-related complications occurred in 18 patients including perforation (5), pancreatitis (3), cholangitis (9), and bleeding (1). The incidence of DBE-ERCP-related complication was 6.27% (95% CI: 2.61-11.38%). CONCLUSION: Diagnostic and therapeutic DBE-ERCPs are feasible in patients with altered gastrointestinal anatomy. DBE-ERCP may be considered when pancreaticobiliary diseases occur in patients undergoing Roux-en-Y reconstruction or pancreaticoduodenectomy.

Esophageal Stent for Refractory Variceal Bleeding: A Systemic Review and Meta-Analysis.

Background. Preliminary studies suggest that covered self-expandable metal stents may be helpful in controlling esophageal variceal bleeding. Aims. To evaluate the effectiveness and safety of esophageal stent in refractory variceal bleeding in a systematic review and meta-analysis. Methods. A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane Library covering the period from January 1970 to December 2015. Data were selected and abstracted from eligible studies and were pooled using a random-effects model. Heterogeneity was assessed using I (2) test. Results. Five studies involving 80 patients were included in the analysis. The age of patients ranged from 18 to 91 years. The mean duration of follow-up was 46.8 d (range, 30-60 d). The success rate of stent deployment was 96.7% (95% CI: 91.6%-99.5%) and complete response to esophageal stenting was in 93.9% (95% CI: 82.2%-99.6%). The incidence of rebleeding was 13.2% (95% CI: 1.8%-32.8%) and the overall mortality was 34.5% (95% CI: 24.8%-44.8%). Most of patients (87.4%) died from hepatic or multiple organ failure, and only 12.6% of patients died from uncontrolled bleeding. There was no stent-related complication reported and the incidence of stent migration was 21.6% (95% CI: 4.7%-46.1%). Conclusion. Esophageal stent may be considered in patients with variceal bleeding refractory to conventional therapy.

Hepatic Resection after Initial Transarterial Chemoembolization Versus Transarterial Chemoembolization Alone for the Treatment of Hepatocellular Carcinoma: A Meta-analysis of Observational Studies.

BACKGROUND: There is no consensus regarding the selection of treatment options for hepatocellular carcinoma (HCC) after initial transarterial chemoembolization (TACE). This meta-analysis aimed to explore the survival benefit of hepatic resection after initial TACE for the treatment of HCC. MATERIALS AND METHODS: We searched three major databases to identify all relevant papers comparing the outcomes of hepatic resection after initial TACE versus TACE alone for the treatment of HCC. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to evaluate the survival benefit of hepatic resection after initial TACE over TACE alone. RESULTS: Three of 2,037 initially identified papers were included. All of them were cohort studies from Asia. There was a significantly better overall survival (OS) in patients undergoing hepatic resection after initial TACE than in those undergoing TACE alone (HR=0.63, 95%CI=0.52-0.76, P<0.00001). The heterogeneity among studies was not statistically significant (P=0.96; I2=0%). CONCLUSIONS: Hepatic resection could improve the OS of HCC patients treated initial TACE. Further randomized controlled trials are now necessary to identify the target populations for the sequential use of hepatic resection after initial TACE and to compare the outcomes between patients undergoing hepatic resection after initial TACE session versus those undergoing TACE alone.

MET inhibitors for treatment of advanced hepatocellular carcinoma: A review.

The current standard treatment option for advanced hepatocellular carcinoma (HCC) is sorafenib, but its clinical benefit is modest. In spite of many attempts, few drugs can provide any significant improvement of survival as the first- or second-line therapy of choice in phase III randomized controlled trials. Recently, the subgroup analysis of a phase II randomized controlled trial has shown that tivantinib, a selective MET inhibitor, can significantly improve the overall survival in patients with MET-positive advanced HCC after the failure or intolerance of a prior systemic therapy. These findings enlighten the role of MET inhibitors in the treatment of advanced HCC. In this paper, we review all ongoing and completed clinical trials regarding this topic. As for the first-line therapy of advanced HCC, INC280 and foretinib are being evaluated in 2 phase II single-arm trials; and MSC2156119J and golvatinib plus sorafenib are being compared with sorafenib alone in 2 phase II randomized controlled trials. As for the second-line therapy of advanced HCC, tivantinib and cabozantinib are being compared with placebo in 2 phase III randomized controlled trials.

Hepatic Re-resection Versus Transarterial Chemoembolization for the Treatment of Recurrent Hepatocellular Carcinoma after Initial Resection: a Systematic Review and Meta-analysis.

BACKGROUND: A systematic review and meta-analysis were performed to compare the post-recurrence survival with hepatic re-resection versus transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after initial resection. MATERIALS AND METHODS: All relevant papers were searched via PubMed, EMBASE, and Cochrane Library databases. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analysis was performed according to country. Sensitivity analysis was performed in studies which clearly reported the recurrent regions, in moderate/high-quality studies, in studies published in full-text form, and in studies published after 2005. RESULTS: In total, twelve papers were included in our study. Five and seven of them were of moderate- and poor-quality, respectively. The overall meta-analysis demonstrated a statistically significantly higher post-recurrence survival in the hepatic re-resection group than in those undergoing TACE (HR=0.64, 95%CI=0.52-0.79, P<0.0001). Heterogeneity was statistically significant and statistical significance remained in the subgroup analysis. Sensitivity analyses were also consistent with the overall analysis. CONCLUSIONS: Hepatic re-resection might provide a better post-recurrence survival than TACE for recurrent HCC after initial resection. However, considering the low quality of published studies and the potential bias of treatment selection, further randomized trials should be warranted to confirm these findings.

Nonselective beta-blockers in cirrhotic patients with no or small varices: A meta-analysis.

AIM: To explore effects of nonselective beta-blockers (NSBBs) in cirrhotic patients with no or small varices. METHODS: The PubMed, EMBASE, Science Direct, and Cochrane library databases were searched for relevant papers. A meta-analysis was performed using ORs with 95%CI as the effect sizes. Subgroup analysis was conducted according to the studies including patients without varices and those with small varices. RESULTS: Overall, 784 papers were initially retrieved from the database searches, of which six randomized controlled trials were included in the meta-analysis. The incidences of large varices development (OR = 1.05, 95%CI: 0.25-4.36; P = 0.95), first upper gastrointestinal bleeding (OR = 0.59, 95%CI: 0.24-1.47; P = 0.26), and death (OR = 0.70, 95%CI: 0.45-1.10; P = 0.12) were similar between NSBB and placebo groups. However, the incidence of adverse events was significantly higher in the NSBB group compared with the placebo group (OR = 3.47, 95%CI: 1.45-8.33; P = 0.005). The results of subgroup analyses were similar to those of overall analyses. CONCLUSION: The results of this meta-analysis indicate that NSBBs should not be recommended for cirrhotic patients with no or small varices.

Hepatic venous pressure gradient measurement before TIPS for acute variceal bleeding.

Hepatic venous pressure gradient (HVPG) is an independent predictor of variceal rebleeding in patients with cirrhosis. After pharmacological and/or endoscopic therapy, the use of a transjugular intrahepatic portosystemic shunt (TIPS) may be necessary in HVPG non-responders, but not in responders. Thus, HVPG measurement may be incorporated into the treatment algorithm for acute variceal bleeding, which further identifies the candidates that should undergo early insertion of TIPS or maintain the traditional pharmacological and/or endoscopic therapy. The potential benefits are to reduce the cost and prevent TIPS-related complications.

Nonselective ß-blockers may induce development of portal vein thrombosis in cirrhosis.

Currently, nonselective ß-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac output by blockade of ß1 receptors and vasoconstriction of the splanchnic circulation by the blockade of ß2 receptors. The prognostic value of occlusive portal vein thrombosis (PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during follow-up is compared between the two groups. Additionally, subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.

Selection of a TIPS stent for management of portal hypertension in liver cirrhosis: an evidence-based review.

Nowadays, transjugular intrahepatic portosystemic shunt (TIPS) has become a mainstay treatment option for the management of portal hypertension-related complications in liver cirrhosis. Accumulated evidence has shown that its indications are being gradually expanded. Notwithstanding, less attention has been paid for the selection of an appropriate stent during a TIPS procedure. Herein, we attempt to review the current evidence regarding the diameter, type, brand, and position of TIPS stents. Several following recommendations may be considered in the clinical practice: (1) a 10-mm stent may be more effective than an 8-mm stent for the management of portal hypertension, and may be superior to a 12-mm stent for the improvement of survival and shunt patency; (2) covered stents are superior to bare stents for reducing the development of shunt dysfunction; (3) if available, Viatorr stent-grafts may be recommended due to a higher rate of shunt patency; and (4) the placement of a TIPS stent in the left portal vein branch may be more reasonable for decreasing the development of hepatic encephalopathy. However, given relatively low quality of evidence, prospective well-designed studies should be warranted to further confirm these recommendations.

TIPS improves liver transplantation-free survival in cirrhotic patients with refractory ascites: an updated meta-analysis.

AIM: To compare the liver transplantation-free (LTF) survival rates between patients who underwent transjugular intrahepatic portosystemic shunts (TIPS) and those who underwent paracentesis by an updated meta-analysis that pools the effects of both number of deaths and time to death. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched from the inception to October 2012. LTF survival, liver transplantation, liver disease-related death, non-liver disease-related death, recurrent ascites, hepatic encephalopathy (HE) and severe HE, and hepatorenal syndrome were assessed as outcomes. LTF survival was estimated using a HR with a 95%CI. Other outcomes were estimated using OR with 95%CIs. Sensitivity analyses were performed to assess the effects of potential outliers in the studies according to the risk of bias and the study characteristics. RESULTS: Six randomized controlled trials with 390 patients were included. In comparison to paracentesis, TIPS significantly improved LTF survival (HR = 0.61, 95%CI: 0.46-0.82, P < 0.001). TIPS also significantly decreased liver disease-related death (OR = 0.62, 95%CI: 0.39-0.98, P = 0.04), recurrent ascites (OR = 0.15, 95%CI: 0.09-0.24, P < 0.001) and hepatorenal syndrome (OR = 0.32, 95%CI: 0.12-0.86, P = 0.02). However, TIPS increased the risk of HE (OR = 2.95, 95%CI: 1.87-4.66, P = 0.02) and severe HE (OR = 2.18, 95%CI: 1.27-3.76, P = 0.005). CONCLUSION: TIPS significantly improved the LTF survival of cirrhotic patients with refractory ascites and decreased the risk of recurrent ascites and hepatorenal syndrome with the cost of increased risk of HE compared with paracentesis. Further studies are warranted to validate the survival benefit of TIPS in clinical practice settings.

Selection of treatment modalities for Budd-Chiari Syndrome in China: a preliminary survey of published literature.

AIM: To evaluate the frequency of use of various treatment modalities for Budd-Chiari syndrome (BCS) in China by conducting a preliminary survey of relevant literature. METHODS: All papers regarding the treatment of BCS in Chinese patients were identified by searching PubMed, Chinese Scientific and Technological Journal, and China National Knowledge Infrastructure databases. Data regarding the number of BCS patients treated with different treatment modalities over time were collected. The proportions of BCS patients undergoing various treatment modalities were calculated. RESULTS: Overall, 300 of 3005 papers initially retrieved were included. These papers included 23352 BCS patients treated with different treatment modalities. The treatment modalities include surgery (n = 8625), interventional treatment (n = 13940), surgery combined with interventional treatment (n = 363), medical therapy (n = 277), other treatments (n = 91), and no treatment (n = 56). After 2005, the number of BCS patients treated with surgery was drastically decreased, but the number of BCS patients who underwent interventional treatment was almost maintained. Shunt surgery was the most common type of surgery (n = 3610). Liver transplantation was rarely employed (n = 2). Balloon angioplasty with or without stenting was the most common type of interventional treatment (n = 13747). Transjugular intrahepatic portosystemic shunt was rarely employed (n = 81). CONCLUSION: Selection of treatment modalities for BCS might be different between China and Western countries. Further work should be necessary to establish a unanimous therapeutic strategy for BCS in China.