The decreased risk of hepatocellular carcinoma in hepatitis B virus-related cirrhotic portal hypertension patients after laparoscopic splenectomy and azygoportal disconnection.

BACKGROUND: Posthepatitic cirrhosis is one of the leading risk factors for hepatocellular carcinoma (HCC) worldwide, among which hepatitis B cirrhosis is the dominant one. This study explored whether laparoscopic splenectomy and azygoportal disconnection (LSD) can reduce the risk of HCC among patients with hepatitis B virus (HBV)-related cirrhotic portal hypertension (CPH). METHODS: A total of 383 patients with HBV-related CPH diagnosed as gastroesophageal variceal bleeding and secondary hypersplenism were identified in our hepatobiliary pancreatic center between April 2012 and April 2022, and conducted an 11-year retrospective follow-up. We used inverse probability of treatment weighting (IPTW) to correct for potential confounders, weighted Kaplan-Meier curves, and logistic regression to estimate survival and risk differences. RESULTS: Patients were divided into two groups based on treatment method: LSD (n = 230) and endoscopic therapy (ET; n = 153) groups. Whether it was processed through IPTW or not, LSD group showed a higher survival benefit than ET group according to Kaplan-Meier analysis (P < 0.001). The incidence density of HCC was higher in the ET group compared to LSD group at the end of follow-up [32.1/1000 vs 8.0/1000 person-years; Rate ratio: 3.998, 95% confidence intervals (CI) 1.928-8.293]. Additionally, in logistic regression analyses weighted by IPTW, LSD was an independent protective predictor of HCC incidence compared to ET (odds ratio 0.516, 95% CI 0.343-0.776; P = 0.002). CONCLUSION: Considering the ability of LSD to improve postoperative survival and prevent HCC in HBV-related CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, it is worth promoting in the context of the shortage of liver donors.

In vivo CRISPR screen identifies LTN1 as a novel tumor suppressor ubiquitinating insulin-like growth factor 2 mRNA-binding protein 1 in hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a frequent and aggressive kind of cancer. Although E3 ligases play important roles in HCC development, several E3 ligases remain unknown. APPROACH AND RESULTS: Through in vivo CRISPR knockout (KO) screens targeting related E3 ligase genes in HCC nude mice models, we discovered LTN1 as a novel tumor suppressor in HCC. Co-IP paired with 2D-LC-MS/MS and subsequent western blotting in HCC cells were used to identify the interactome of LTN1. Compared to matched normal tissues, the expression of LTN1 was decreased in human HCC tissues (ANT) (157/209). Clinically, patients with HCC who expressed low levels of LTN1 had a poor prognosis. Forced expression of LTN1 decreased cell growth in vitro and in vivo, whereas knockdown of LTN1 increased cell growth. Mechanistically, elevated LTN1 expression inhibited HCC cell growth by ubiquitinating and destabilizing the IGF2BP1 protein, which inhibited the c-Myc and IGF-1R signaling pathways. There was a negative correlation between the LTN1 protein expression and the IGF2BP1 protein expression in HCC tissues (R2=0.2799, P=0.0165). CONCLUSIONS: LTN1 may be a crucial tumor suppressor for determining the prognosis and a possible therapeutic target since it inhibits the proliferation of HCC cells by ubiquitinating IGF2BP1.

Splenectomy and azygoportal disconnection decreases the risk of hepatocellular carcinoma for cirrhosis patients with portal hypertension bleeding: a 10-year retrospective follow-up study based on the inverse probability of treatment weighting method.

BACKGROUND: Liver cirrhosis is the highest risk factor for hepatocellular carcinoma (HCC) worldwide. However, etiological therapy is the only option in cirrhosis patients to decrease the HCC risk. The aim of this study was to explore whether laparoscopic splenectomy and azygoportal disconnection (LSD) decreases the risk of HCC for patients with cirrhotic portal hypertension (CPH). METHODS: Between April 2012 and April 2021, we identified 595 CPH patients in our hepatobiliary pancreatic center who were diagnosed with gastroesophageal variceal bleeding and secondary hypersplenism, and performed a 10-year retrospective follow-up. Inverse probability of treatment weighting (IPTW) was used to adjust for potential confounders, weighted Kaplan-Meier curves and logistic regression to estimate survival and risk differences. RESULTS: According to the method of therapy, patients were divided into LSD (n = 345) and endoscopic therapy (ET; n = 250) groups. Kaplan-Meier analysis revealed that patients who underwent LSD had higher survival benefit with those who underwent ET (P < 0.001). At the end of the follow-up, ET group was associated with a higher HCC incidence density compared with LSD group (28.1/1000 vs 9.6/1000 person-years; Rate ratio [RR] 2.922, 95% confidence intervals [CI] 1.599-5.338). In addition, logistic regression analyses weighted by IPTW revealed that, compared with ET, LSD was an independent protective predictor of HCC incidence (odds ratio [OR] 0.440, 95% CI 0.316-0.612; P < 0.001). CONCLUSIONS: Considering the better postoperative survival and the ability to prevent HCC in CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, LSD is worth popularization in situations where liver donors are scarce.

Identification of the mitophagy-related diagnostic biomarkers in hepatocellular carcinoma based on machine learning algorithm and construction of prognostic model.

Background and aims: As a result of increasing numbers of studies most recently, mitophagy plays a vital function in the genesis of cancer. However, research on the predictive potential and clinical importance of mitophagy-related genes (MRGs) in hepatocellular carcinoma (HCC) is currently lacking. This study aimed to uncover and analyze the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance. Methods: In our research, by using Least absolute shrinkage and selection operator (LASSO) regression and support vector machine- (SVM-) recursive feature elimination (RFE) algorithm, six mitophagy genes (ATG12, CSNK2B, MTERF3, TOMM20, TOMM22, and TOMM40) were identified from twenty-nine mitophagy genes, next, the algorithm of non-negative matrix factorization (NMF) was used to separate the HCC patients into cluster A and B based on the six mitophagy genes. And there was evidence from multi-analysis that cluster A and B were associated with tumor immune microenvironment (TIME), clinicopathological features, and prognosis. After then, based on the DEGs (differentially expressed genes) between cluster A and cluster B, the prognostic model (riskScore) of mitophagy was constructed, including ten mitophagy-related genes (G6PD, KIF20A, SLC1A5, TPX2, ANXA10, TRNP1, ADH4, CYP2C9, CFHR3, and SPP1). Results: This study uncovered and analyzed the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance. Based on the mitophagy-related diagnostic biomarkers, we constructed a prognostic model(riskScore). Furthermore, we discovered that the riskScore was associated with somatic mutation, TIME, chemotherapy efficacy, TACE and immunotherapy effectiveness in HCC patients. Conclusion: Mitophagy may play an important role in the development of HCC, and further research on this issue is necessary. Furthermore, the riskScore performed well as a standalone prognostic marker in terms of accuracy and stability. It can provide some guidance for the diagnosis and treatment of HCC patients.

Radiofrequency ablation versus liver resection and liver transplantation for small combined hepatocellular-cholangiocarcinoma stratified by tumor size.

PURPOSE: Although radiofrequency ablation (RFA) has been proven to provide a good survival benefit for small hepatocellular carcinoma (HCC), there is limited information about RFA for combined hepatocellular-cholangiocarcinoma (cHCC-CC). The purpose of this study was to explore the clinicopathological features of cHCC-CC and the curative effect of RFA in small cHCC-CC without distant metastases compared with liver resection (LR) and liver transplantation (LT). METHODS: Patients with cHCC-CC, intrahepatic cholangiocarcinoma, or HCC were identified in the Surveillance, Epidemiology, and End Results database. RESULTS: cHCC-CC had the highest rate of poor pathological grade and the lowest rate of bone metastases compared with intrahepatic cholangiocarcinoma and HCC (all P < 0.05). In patients with cHCC-CC after surgery, multivariate analysis showed that compared with RFA, LR and LT were independent protective factors for survival (all P < 0.05). But in cHCC-CC stratified by tumor size, for tumor size ≤ 3.0 cm, there was no significant difference among RFA, LR, and LT in univariate survival analysis (P = 0.285). For tumor size 3.0-5.0 cm, multivariate analysis showed that RFA for cHCC-CC yielded worse survival outcomes in comparison with that of LR (hazard ratio [HR]: 7.51, 95% confidence interval [CI]: 2.09-26.94, P = 0.002) and LT (HR: 4.48, 95% CI: 1.20-16.64, P = 0.025). CONCLUSIONS: In patients with cHCC-CC without distant metastases, for tumor size ≤ 3.0 cm, there was no significant survival difference among RFA, LR, and LT. However, for tumor size 3.0-5.0 cm, RFA may provide a worse survival benefit than LT and LR.

Comparison of Repeated Recurrence of Common Bile Duct Stones and Occurrence of Hepatolithiasis After Synchronous Laparoscopic Cholecystectomy Combined with Laparoscopic Common Bile Duct Exploration or with Endoscopic Sphincterotomy: a 10-Year Retrospective Study.

BACKGROUND: The optimal treatment options for gallstones together with common bile duct stones (CBDS) remain controversial. The aim of this study was to further compare the recurrence rate of stones after synchronous laparoscopic cholecystectomy combined with laparoscopic common bile duct exploration (SLCL) and synchronous laparoscopic cholecystectomy combined with intraoperative endoscopic sphincterotomy (SLCE) and to determine which option is more effective in reducing the rate of repeated recurrence of CBDS and the incidence rate of hepatolithiasis. METHODS: We retrospectively investigated the clinical data of patients who underwent SLCL or SLCE at our hepatobiliary center between August 2012 and August 2020. The primary and secondary endpoints of this study were the recurrence of CBDS and the occurrence of hepatolithiasis, respectively. RESULTS: In total, 1005 patients were enrolled in this study, including 431 patients in the SLCL group and 574 patients in the SLCE group. SLCL was associated with a significantly decreased rate of CBDS recurrence (4.18% vs. 7.84%, P = 0.018), repeated CBDS recurrence (0.70% vs. 3.00%, P = 0.010), and incidence of hepatolithiasis (0.00% vs. 1.05%, P = 0.040). Compared with SLCE, SLCL was an independent protective predictor of the recurrence of CBDS (relative risk, 0.505; 95% confidence interval, 0.286-0.891; P = 0.018) and repeated recurrence of CBDS (relative risk, 0.226; 95% confidence interval, 0.066-0.777; P = 0.018). CONCLUSIONS: SLCL is an optimal treatment option to SLCE for patients with gallstones combined with CBDS.

Vagus nerve-guided (modified Bai-Jiang-style) robotic-assisted laparoscopic splenectomy and azygoportal disconnection.

BACKGROUND: How to precisely protect and preserve anterior and posterior vagal trunks and all their branches during the procedure of splenectomy and azygoportal disconnection is studied rarely. We firstly developed a vagus nerve-guided robotic-assisted laparoscopic splenectomy and azygoportal disconnection (VGRSD). The aim of this study was to evaluate whether VGRSD is feasible and safe and to determine whether VGRSD can effectively eliminate postoperative digestive system complications by protecting vagal nerve precisely. METHOD: In this prospective clinical study, 10 cirrhotic patients with oesophagogastric variceal bleeding and hypersplenism who underwent VGRSD between January 2022 and March 2022 were gathered, and compared with a retrospective cohort who received a part of the vagus nerve-preserving robotic-assisted laparoscopic splenectomy and azygoportal disconnection (VPRSD). They were all followed up for 6 months. RESULTS: In VGRSD group, the operation time was 173.5 ± 16.2 min, blood loss was 68.0 ± 39.1 ml, VAS pain score on the first day was 1.9 ± 0.7, and the postoperative hospital stay was 7.7 ± 0.7 days. There was no incisional complications, pneumonia, gastric fistula, pancreatic fistula, and abdominal infection. No patients suffered from diarrhoea, delayed gastric emptying, and epigastric fullness. Compared with VPRSD, operation time was significantly longer for VGRSD (p < 0.05). However, VGRSD was significantly associated with less diarrhoea and shorter postoperative hospital stay (all p < 0.05). CONCLUSION: VGRSD procedure is not only technically feasible and safe, it also effectively eliminate postoperative digestive system complications. TRIAL REGISTRATION: We registered our research at https://www. CLINICALTRIALS: gov/. The name of research registered is 'Vagus Nerve-guided Robotic-assisted Splenectomy and Azygoportal Disconnection'. The trial registration identifier at clinicaltrials.gov is NCT05300516.

Radiofrequency ablation is an inferior option to liver resection for solitary hepatocellular carcinoma ≤ 5 cm without cirrhosis: A population-based study with stratification by tumor size.

BACKGROUND: About 10%-20% of all individuals who develop hepatocellular carcinoma (HCC) do not have cirrhosis. Comparisons are rarely reported regarding the effectiveness of radiofrequency ablation (RFA) and liver resection (LR) in survival of HCC without cirrhosis and stratification by tumor size ≤ 5 cm. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database and identified 1505 patients with a solitary HCC tumor ≤ 5 cm who underwent RFA or LR during 2004-2015. Patients were classified into non-cirrhosis and cirrhosis groups and each group was categorized into three subgroups, according to tumor size (≤ 30 mm, 31-40 mm, 41-50 mm). RESULTS: In patients without cirrhosis, LR showed better 5-year HCC cancer-specific survival than RFA in all tumor size subgroups (≤ 30 mm: 82.51% vs. 56.42%; 31-40 mm: 71.31% vs. 46.83%; 41-50 mm: 74.7% vs. 37.5%; all P < 0.05). Compared with RFA, LR was an independent protective factor for HCC cancer-specific survival in multivariate Cox analysis [≤ 30 mm: hazard ratio (HR) = 0.533, 95% confidence interval (CI): 0.313-0.908; 31-40 mm: HR = 0.439, 95% CI: 0.201-0.957; 41-50 mm: HR = 0.382; 95% CI: 0.159-0.916; all P < 0.05]. In patients with cirrhosis, for both tumor size ≤ 30 mm and 31-40 mm groups, there were no significant survival differences between RFA and LR in multivariate analysis (all P > 0.05). However, in those with tumor size 41-50 mm, LR showed significantly better 5-year HCC cancer-specific survival than RFA in both univariate (54.72% vs. 23.06%; P < 0.001) and multivariate analyses (HR = 0.297; 95% CI: 0.136-0.648; P = 0.002). CONCLUSIONS: RFA is an inferior treatment option to LR for patients without cirrhosis who have a solitary HCC tumor ≤ 5 cm.

Novel Preoperative Type IV Collagen to Predict the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Related Cirrhotic Portal Hypertension After Laparoscopic Splenectomy and Azygoportal Disconnection.

Purpose: Although laparoscopic splenectomy and azygoportal disconnection (LSD) can significantly decrease portal vein pressure and even the incidence of hepatocellular carcinoma (HCC) in patients with cirrhotic portal hypertension (CPH), postoperative HCC inevitably occurs in certain patients. The purpose of this study was to seek a novel preoperative non-invasive predictive indicator to predict the occurrence of postoperative HCC. Patients and Methods: From April 2012 to April 2022, we collected clinical data of 178 hepatitis B virus (HBV)-related CPH patients. Based on inverse treatment probability weighting, candidate variables for predicting postoperative HCC were determined by means analysis. Then, a novel preoperative non-invasive prediction indicator (ie, type IV collagen-alpha fetoprotein-fibrosis-4 score [IVAF-FIB-4]) was established based on candidate variables, and its predictive ability was explored. Results: Postoperative HCC occurred in 9 (5.1%) patients. Correlation analyses showed that the IVAF-FIB-4 had a significant positive correlation with HCC (r = 0.835, P < 0.001). IVAF-FIB-4 showed a high accuracy (the area under the receiver operating characteristic curve: 0.939, 95% confidence interval [CI]: 0.818-1.000; sensitivity: 88.9%; specificity: 93.5%). At the end of follow-up, the incidence density of HCC in patients with IVAF-FIB-4 (1) was significant higher than that in patients with IVAF-FIB-4 (0) (138.1/1000 vs 1.1/1000 person-years; rate ratio: 130.475, 95% CI: 16.318-1043.227). In logistic regression, IVAF-FIB-4 was an independent risk factor for HCC (odds ratio: 668.000, 95% CI: 53.895-8279.541; P < 0.001). Conclusion: IVAF-FIB-4 is a novel preoperative noninvasive predictive indicator for predicting postoperative HCC in HBV-related CPH patients after LSD, with satisfactory predictive ability.

Comprehensive analysis of the clinical significance, immune infiltration, and biological role of MARCH ligases in HCC.

The membrane-associated RING-CH (MARCH) family, a member of the E3 ubiquitin ligases, has been confirmed by a growing number of studies to be associated with immune function and has been highlighted as a potential immunotherapy target. In our research, hepatocellular carcinoma (HCC) patients were divided into C1 and C2 MARCH ligase-related patterns by the non-negative matrix factorization (NMF) algorithm. Multiple analyses revealed that the MARCH ligase-related cluster was related to prognosis, clinicopathological characteristics, and the tumor immune microenvironment (TIME). Next, the signature (risk score) of the MARCH prognosis was constructed, including eight genes associated with the MARCH ligase (CYP2C9, G6PD, SLC1A5, SPP1, ANXA10, CDC20, PON1, and FTCD). The risk score showed accuracy and stability. We found that the correlations between risk score and TIME, tumor mutation burden (TMB), prognosis, and clinicopathological characteristics were significant. Additionally, the risk score also had important guiding significance for HCC treatment, including chemotherapy, immunotherapy, and transarterial chemoembolization (TACE).

Vagus Nerve-Preserving Laparoscopic Splenectomy and Azygoportal Disconnection with Versus Without Intraoperative Endoscopic Variceal Ligation: a Randomized Clinical Trial.

BACKGROUND: Esophagogastric variceal bleeding is the most common lethal factor for patients with cirrhotic portal hypertension. We firstly developed a laparoscopic splenectomy and azygoportal disconnection (LSD) with intraoperative endoscopic variceal ligation (LSDL) technique. In this study, we aimed to evaluate whether LSDL is feasible and safe and whether LSDL can effectively prevent esophagogastric variceal re-bleeding (EVR), as compared with single LSD. METHODS: In this randomized controlled single-center study, 88 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism were randomly assigned to receive either LSD (n = 44) or LSDL (n = 44) between January 2020 and December 2021. The primary outcome was EVR. RESULTS: No patients withdrew from the study. There were no significant differences in estimated blood loss, incidence of blood transfusion, time to first flatus and off-bed activity, or postoperative hospital stay between the two groups. Compared with that in the LSD group, operation time was significantly longer in the LSDL group (138.5 ± 19.4 min vs. 150.3 ± 19.0 min, P < 0.05); however, LSDL was associated with a significantly decreased EVR rate at 1-year follow-up (8/44 vs. 1/44, P < 0.05). Univariate analysis and multivariate logistic regression revealed that LSDL was a significant independent protective factor against EVR in comparison with LSD (relative risk: 0.105, 95% confidence interval 0.012-0.877; P = 0.037). CONCLUSIONS: Our newly developed LSDL procedure is not only technically feasible and safe; it also contributed to lowering the EVR risk more so than single LSD. TRIAL REGISTRATION: We registered our research at https://www. CLINICALTRIALS: gov/ . The name of research registered is "Laparoscopic Splenectomy and Azygoportal Disconnection with Intraoperative Endoscopic Variceal Ligation." The trial registration identifier at clinicaltrials.gov is NCT04244487.

Down-regulation of circPTTG1IP induces hepatocellular carcinoma development via miR-16-5p/RNF125/JAK1 axis.

Circular RNAs are known to regulate the biological processes of hepatocellular carcinoma (HCC), and humans with Down syndrome are at low risk of developing solid tumors due to the amplification of several tumor suppressor genes on human chromosome 21 (HSA21). Here, we aimed to investigate the potential role of circRNAs originating from HSA21 in the progression of HCC. CircRNA-sequencing was performed to analyze differentially expressed circRNAs in 4 HCC and peritumor tissues, and circRNAs originating from HSA21 were further analyzed. Circ_0061984 (circPTTG1IP) was chosen for further study because it showed the lowest expression in HCC tissues, and qRT-PCR was used to confirm the expression of circPTTG1IP in HCC patient tissues. The biological function of circPTTG1IP was detected in HCC cells both in vivo and in vitro. Moreover, luciferase reporter assays, circRNA immunoprecipitation, and fluorescence in situ hybridization (FISH) were used to investigate the potential mechanism of circPTTG1IP. Finally, the possible mechanisms of filgotinib in circPTTG1IP-driven HCC were assessed. CircPTTG1IP expression was decreased in HCC compared to peritumoral tissues. Moreover, low circPTTG1IP expression was revealed to be associated with a poor prognosis of HCC patients. Elevation of circPTTG1IP was revealed to inhibit HCC development both in vitro and in vivo. Mechanistically, circPTTG1IP was shown to function as a competing endogenous RNA (ceRNA) of RNF125 by binding miR-16-5p to increase the level of the E3 ubiquitin ligase RNF125, which further ubiquitinated and degraded JAK1 protein. Finally, we demonstrated that administration of filgotinib, a JAK1 inhibitor, restricted HCC progression induced by low circPTTG1IP expression. Thus, we revealed that circPTTG1IP is a novel tumor suppresser circRNA in HCC and that a low circPTTG1IP level promotes HCC development via the miR-16-5p/RNF125/JAK1 axis. Patients with low circPTTG1IP may benefit from filgotinib treatment.

Clinical effects of cluster technology optimization and innovations on laparoscopic splenectomy and azygoportal disconnection: a single-center retrospective study with 500 consecutive cases.

BACKGROUND: In Asia, laparoscopic splenectomy and azygoportal disconnection (LSD) has been widely regarded as a preferential treatment modality for cirrhotic portal hypertension (PH). However, LSD involves high surgical risk, technical challenges, and many potential postoperative complications. Technology optimization and innovation in LSD aiming to solve to these difficulties has scarcely been reported. In this retrospective study, we aimed to evaluate the clinical therapeutic effect of our cluster technology optimization and innovation on LSD for PH. METHODS: From February 2012 to January 2020, 500 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism underwent LSD in our department. According to different operation periods, patients were divided into the early-, intermediate-, and late-period groups. We collected information regarding clinical characteristics of all patients as well as their preoperative and postoperative follow-up data. RESULTS: Compared with the early-period group, operation time and postoperative hospital stay were all significantly different and gradually declined from the intermediate- and late-period groups, respectively (all P < 0.05). Intraoperative blood loss of these three groups was gradually decreased, with significant differences (P < 0.05). The incidences of delayed gastric emptying and diarrhea in the late-period group were all significantly lower than those in the early- and intermediate-period groups, respectively (all P < 0.05). Compared with the early-period group, the incidence of variceal re-bleeding was significantly lower in the intermediate- and late-period groups (all P < 0.05). CONCLUSION: Our cluster technology optimization and innovation of LSD not only contributed to faster recovery and fewer complications but also enhanced surgical safety for patients. It is worth promoting this approach among patients with EVB and hypersplenism secondary to cirrhotic PH.

Robotic-assisted versus laparoscopic approach of Bai-Jiang-style vagus nerve-preserving splenectomy and azygoportal disconnection.

Robotic surgery has been widely accepted in many kinds of surgical procedures. Little is known about clinical effects of robotic-assisted splenectomy and azygoportal disconnection (RSD) for gastroesophageal variceal bleeding and secondary hypersplenism owing to cirrhotic portal hypertension. The aim of this study was to evaluate whether RSD is feasible and safe for patients with cirrhotic portal hypertension and whether RSD is superior to laparoscopic splenectomy and azygoportal disconnection (LSD). We retrospectively investigated the clinical effects of 50 patients with cirrhosis who underwent vagus nerve-preserving RSD (n = 20) and LSD (n = 30) between September 2020 and October 2021. We compared patients' demographic, intraoperative, and perioperative variables. RSD and LSD were successful in all patients. Operative time did not differ significantly between the RSD group and LSD group (151.15 ± 21.78 min vs. 144.50 ± 24.30 min, P > 0.05), but intraoperative blood loss were significantly reduced in the RSD group (61.00 ± 34.93 mL vs. 105.00 ± 68.77 mL, P < 0.05). No statistically significant differences were found regarding intraoperative allogeneic transfusion rate, visual analog scale pain score on the postoperative first day, time to first oral intake, initial passage of flatus, initial off-bed activity, postoperative hospital stay, and overall perioperative complication rate (all P > 0.05). In conclusion, RSD is not only a technically feasible and safe procedure but it was associated with less blood loss than LSD for cirrhotic portal hypertension with gastroesophageal variceal bleeding and secondary hypersplenism. Registered at researchregistery.com: trial registration number is researchregistry7244, date of registration October 10, 2021, registered retrospectively.

Predictors of portal vein thrombosis after laparoscopic splenectomy and azygoportal disconnection in hepatitis B cirrhosis: a prospective study.

BACKGROUND: The thrombosis of the main and intrahepatic branches of the portal vein (TMIP) is potentially lethal and deemed a common complication following laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension (PH). The predictors of TMIP after LSD remain unclear. The aim of this prospective study was to explore the predictive and risk factors for TMIP after LSD in cirrhotic patients with PH caused only by hepatitis B virus. METHODS: From September 2014 to March 2017, we enrolled 115 patients with hepatitis B cirrhosis and PH who successfully underwent LSD. Patients were subdivided into a TMIP group and a non-TMIP group. Univariate and multivariate logistic regression analysis was conducted on 24 items of demographic and preoperative data, to explore the risk factors of TMIP. RESULTS: Twenty-nine (25.22%) patients developed TMIP on postoperative day (POD) 7 and 26 (22.81%) patients developed TMIP on POD 30. From POD 7 to POD 30, 12 patients who did not have TMIP at POD 7 were newly diagnosed with TMIP, with portal vein diameter 15.05 ± 2.58 mm. Another 14 patients in whom TMIP had resolved had portal vein diameter 14.02 ± 1.76 mm. Univariate analysis and multivariate logistic regression revealed that portal vein diameter ≥ 13 mm [relative risk (RR) 5.533, 95% confidence interval (CI) 1.222-25.042; P = 0.026] and portal vein diameter ≥ 15 mm (RR 3.636, 95% CI 1.466-9.021; P = 0.005) were significant independent risk factors for TMIP on POD 7 and 30, respectively. CONCLUSION: Portal vein diameter ≥ 13 mm and ≥ 15 mm were significant independent predictors for TMIP after LSD in patients with hepatitis B cirrhosis and PH on POD 7 and POD 30, respectively. TRIAL REGISTRATION: We registered our research at https://www. CLINICALTRIALS: gov/ . The name of research registered is "Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection." The trial registration identifier at clinicaltrials.gov is NCT02247414.

Impact of Socioeconomic Factors on Prognosis and Clinical Management in Patients with Hepatocellular Carcinoma.

BACKGROUND: The prognosis for patient survival using the tumor-node-metastasis (TNM) staging system may be imperfect, as it based only on biological factors and does not include the socioeconomic factors (SEFs). We integrated the SEFs into the TNM system (TNMSEF), and evaluated whether the novel TNM-SEF staging system showed better prediction capacity and improved clinical guidance in hepatocellular carcinoma (HCC). METHODS: We selected data of 12 514 cases with HCC between 2010 and 2015 from the SEER database. The Kaplan-Meier survival curves and Cox proportional hazards regression were used to analyze cancer-specific survival (CSS) among the TNM-SEF stages. RESULTS: Multivariate Cox analyses showed that insurance status, marital status, year of diagnosis, and income were prominent prognostic SEFs (all P < .05). When compared with the SEF0 stage, the SEF1 stage was significantly associated with a 36.1% increased risk of cancer-specific mortality in HCC overall, a 22.2% increased risk of metastatic HCC, and a 41.8% increased risk of non-metastatic HCC (all P < .001). The concordance index of the TNM-SEF stage (0.768) was better than that of the TNM stage (0.764). Furthermore, patients with SEF0 stage showed higher 5-year CSS than those with SEF1 stage (I: 48.7% vs. 28.1%; II: 41.0% vs. 25.1%; IIIA: 12.8% vs. 5.0%; IIIB: 7.8% vs. 6.0%; IIIC: 6.4% vs. 6.7%; IVA: 8.4% vs. 2.5%; IVB: 2.1% vs. 0.8%; all P < .05). CONCLUSION: We have proved that the SEF stage is an independent predictor for HCC. The combined SEF stage with TNM staging warrants more clinical attention, for improved prognostic prediction and clinical guidance.

Preoperative Alpha-Fetoprotein Has No Prognostic Role in Small Hepatocellular Carcinoma in Non-Cirrhotic Patients After Surgical Resection.

BACKGROUND: Alpha-fetoprotein (AFP) has been widely used as a tumor marker in the treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, a large number of HCC patients are diagnosed without cirrhosis, and the prognostic capability of AFP was unclear in HCC patients without cirrhosis. Our purpose was to investigate the prognostic efficiency of AFP in patients with non-cirrhosis, single, and small HCC who were treated with surgical resection. METHODS: Among the 111 374 liver cancer patients included in the Surveillance, Epidemiology, and End Results database, we selected 224 patients without cirrhosis with a single HCC ≤3 cm in diameter who were identified at diagnosis and treated with surgical resection. The AFP test results were recorded as AFP-positive and AFP-negative levels. RESULTS: Kaplan-Meier method showed that there was no significant survival difference between the AFP-positive and AFP-negative groups (P = .566). The same results were found in the subgroups of patients with tumor size ≤2 cm and 2-3 cm (P = .710 and .687, respectively). Receiver operating characteristic (ROC) curve analysis showed that AFP had inadequate accuracy to discriminate survivors and deceased patients in subgroups of patients with tumor size ≤3 cm, 2-3 cm, or ≤2 cm (area under the ROC curve = 0.449, 0.458, 0.443; 95% confidence interval = 0.366-0.533, 0.346-0.571, 0.317-0.569, respectively). CONCLUSION: AFP levels have no predictive value in well-compensated non-cirrhosis patients with single, small HCC (≤3 cm) treated with surgical resection for curative intent.

The growth rate of hepatocellular carcinoma is different with different TNM stages at diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) progresses fast and has a poor prognosis, but the growth rate in different TNM stages is not clear. The present study was to estimate the growth rate of HCC with different TNM stages at diagnosis. METHODS: Baseline demographics and tumor characteristics were analyzed for 10145 patients in Surveillance, Epidemiology, and End Results (SEER) Program-registered HCC. Multiple linear regression models were used for age adjustment with patient race, sex, marital status, and HCC grade. RESULTS: The age at diagnosis was younger in Caucasians and males. The adjusted average age of patients with stage I HCC was 65.26 years. The adjusted age of patients with stage II, IIIA, IIIB, and IIIC was -0.17, -0.25, -0.29, and -0.55 adjusted-year younger compared with patients with stage I HCC (all P < 0.001). The adjusted average age of patients with T1 was 65.26 years. The age adjustment was -0.17, -0.26, and -0.55 respectively (all P < 0.001) for T2, T3 or T4 tumors without distant metastases. CONCLUSIONS: These findings demonstrated that the more advanced the HCC stage at diagnosis, the younger the age at diagnosis and the faster the HCC growth from tumor occurrence.

Can Patients with Pancreatic Cancer and Liver Metastases Obtain Survival Benefit from Surgery? A Population-Based Study.

Background: Surgery for pancreatic cancer with liver metastases (PCL) is not recommended in the international guidelines, and investigation of its clinical significance in patients with PCL is very limited. This study explored whether surgery, especially synchronous resection of the primary tumor and liver metastases (SPL), could improve survival in PCL. Methods: Data of 14,248 patients with PCL from Surveillance, Epidemiology, and End Results database was analyzed. Patients were divided into following groups: SPL, synchronous primary site, and other resection (SPO), single resection of the primary site (SPS), and no resection (NR). Results: In this study, only 93 (0.7%) underwent SPL, 88 (0.6%) for SPO, and 232 (1.6%) for SPS. Multivariate Cox analysis showed surgical procedures of both the primary site and other sites were independent protective prognostic factors for pancreatic cancer cause-specific survival (PCSS) (all P < 0.001). Patients in the SPL group showed the most survival benefit, with a significant and gradually increased difference as compared with the SPO, SPS, and NR groups (median survival: 54, 34, 15, and 3 months, respectively, all P < 0.001). Compared with the NR group, mortalities were significant and gradually declining in the SPS, SPO, and SPL groups, with hazard ratio 0.329 (95% confidence interval [CI], 0.281 to 0.386), 0.220 (95% CI, 0.164 to 0.294), and 0.162 (95% CI, 0.118 to 0.222), respectively (all P < 0.001). Conclusions: Surgical procedures for both primary site and other sites improved survival. SPL, particularly, showed a considerable survival benefit in well-selected patients with PCL.

Novel noninvasive liver fibrotic markers to predict postoperative re-bleeding after laparoscopic splenectomy and azygoportal disconnection: a 1-year prospective study.

BACKGROUND: Esophagogastric variceal re-bleeding (EGVR) is a common and potentially lethal complication after open or laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension. Currently, noninvasive biomarkers for predicting EGVR are lacking. This prospective study focused on developing a noninvasive and convenient clinical model for predicting postoperative EGVR. METHODS: Between September 2014 and March 2017, we enrolled 164 patients with cirrhosis who successfully underwent LSD. Based on the absence or presence of EGVR, patients were divided into EGVR and non-EGVR groups. We used correlation analysis to determine significant candidate variables among the liver fibrotic markers procollagen type III (PC-III), hyaluronidase (HA), laminin (LN), and type IV collagen (C-IV). RESULTS: Postoperative EGVR occurred in 22 (13.41%) patients. Correlation analyses showed that LN (r = 0.375; p < 0.001) and C-IV (r = 0.349; p < 0.001) were significantly positively associated with EGVR. The area under the receiver operating characteristic curve (AUC) of LN was 0.817 (95% confidence interval [CI] 0.722-0.913); that of C-IV was 0.795 (95% CI 0.710-0.881). In logistic multivariate regression, cutoff values LN ≥ 64 µg/L and of C-IV ≥ 65 µg/L were independent risk factors for EGVR. LN ≥ 64 µg/L combined with C-IV ≥ 65 µg/L was the best performing model, with AUC 0.867 (95% CI 0.768-0.967). CONCLUSION: LN and C-IV are potential markers to predict EGVR. Combining the two markers showed satisfactory ability to predict EGVR in patients with cirrhosis and portal hypertension after LSD.