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.

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.

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.

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.

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.

Transjugular intrahepatic portosystemic shunt in patients treated with a balloon tamponade for variceal hemorrhage without response to high doses of vasoactive drugs: A real-world multicenter retrospective study.

OBJECTIVE: To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) and non-TIPS therapy (endoscopy and/or nonselective beta-blockers [NSBB]) in patients with cirrhosis and active variceal hemorrhage who did not respond to high-dose vasoactive drugs and required balloon tamponade for hemostasis. METHODS: Medical records of cirrhotic patients who did not respond to high-dose vasoactive drugs and required balloon tamponade for hemostasis at five university hospitals in China between January 2011 and December 2018 were reviewed. Treatment outcomes were compared between the TIPS and the non-TIPS groups. RESULTS: Treatment failure of variceal hemorrhage within 5 days was reported in six patients of the non-TIPS group (N = 70) and none of the TIPS group (N = 66) (P = .028). The TIPS group had a higher 1-year variceal rebleeding-free rate compared with the non-TIPS group (95.5% vs 60.0%, P < .001). One patient treated with TIPS and nine with non-TIPS therapy experienced rebleeding within 5 days and 6 weeks after the intervention (P = .009). The cumulative 1-year survival rate was higher in the TIPS group than in the non-TIPS group (93.9% vs 78.6%, P = .01). The TIPS group had a higher incidence of hepatic encephalopathy within one year compared with the non-TIPS group (18.2% vs 4.3%, P = .026). CONCLUSION: For patients with cirrhosis and active variceal bleeding who do not respond to high-dose vasoactive agents and require a balloon tamponade for hemostasis, TIPS may be an appropriate treatment choice.

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.

S-1-based combination therapy vs S-1 monotherapy in advanced gastric cancer: a meta-analysis.

AIM: To assess the efficacy and safety of combination therapy based on S-1, a novel oral fluoropyrimidine, vs S-1 monotherapy in advanced gastric cancer (AGC). METHODS: We searched PubMed, EMBASE and the Cochrane Library for eligible studies published before March 2013. Our analysis identified four randomized controlled trials involving 790 participants with AGC. The outcome measures were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3-4 adverse events. RESULTS: Meta-analysis showed that S-1-based combination therapy significantly improved OS (HR = 0.77, 95%CI: 0.66-0.91, P = 0.002), PFS (HR = 0.58, 95%CI: 0.46-0.72, P = 0.000) and ORR (OR = 2.23, 95%CI: 1.54-3.21, P = 0.000). Sensitivity analysis further confirmed this association. Lower incidence of grade 3-4 leucopenia (OR = 4.06, 95%CI: 2.11-7.81), neutropenia (OR = 3.94, 95%CI: 2.1-7.81) and diarrhea (OR = 2.41, 95%CI: 1.31-4.44) was observed in patients with S-1 monotherapy. CONCLUSION: S-1-based combination therapy is superior to S-1 monotherapy in terms of OS, PFS and ORR. S-1 monotherapy is associated with less toxicity.

Effects of CpG-ODNs on phenotype and function of monocyte-derived dendritic cells in chronic hepatitis B.

AIM: To study the effects of synthetic nonmethylated CpG-containing oligodeoxynucleotides (CpG-ODNs), either alone or combined with recombinant Hepatitis B surface antigen (HBsAg) polypeptide, on the phenotype, function, and intracellular signaling pathways of monocyte-derived dendritic cells (DCs) in patients with chronic hepatitis B (CHB). METHODS: Peripheral blood monocytes isolated from CHB patients and healthy volunteers were induced to be dendritic cells by recombinant human granulocyte-monocyte colony stimulating factor and interleukin-4. The DCs were then treated with CpG-ODNs, CpG-ODNs/HBsAg, or tumor necrosis factor (TNF)-α for 18 h. The expression of surface molecules including HLA-DR, CD86, and CD1a in DCs were detected by flow cytometry, and the expression of signal transducers and activators of transcription (STAT1, 3, 4, 5, 6) and suppressors of cell signaling (SOCS1, 3) were determined by Western blotting assay. In addition, the capacity of DCs to stimulate allogeneic T lymphocytes and the amount of IL-12p70 released from DCs were measured. RESULTS: In the DCs derived from patients with CHB, treatment with TNF-α, CpG-ODNs, or CpG-ODNs/HBsAg, as compared to the vector control, significantly increased the expression of HLA-DR, stimulated the release of IL-12p70, and enhanced the capacity of DCs to stimulate allogenic T lymphocytes. The expressions of STAT1/4/6 and SOCS1/3, but not STAT3/5, were upregulated by TNF-α, CpG-ODNs, and CpG-ODNs/HBsAg. In addition, the expression of CD1a was upregulated only in the presence of both CpG-ODNs and HBsAg. CONCLUSION: The treatment with CpG-ODNs, either alone or combined with HBsAg, has a remarkable stimulatory effect on the impaired phenotype and function of DCs in CHB, possibly by regulating the expression of STAT1, 4, 6 and SOCS1, 3.

[Effects of CpG-ODN combined with HBsAg on the phenotype, function and the activity of NF-kappa B and AP-1 of monocyte-derived dendritic cells in chronic hepatitis B patients].

OBJECTIVE: To investigate the effect of synthetic non-methylated CpG-ODN combined with recombined HBsAg on the phenotype, function and the expression level of nucleic transcription factor NF-kappa B (NF-kB) and AP-1 of monocyte-derived dendritic cells (DC) in patients with chronic hepatitis B (CHB). METHODS: Purified monocytes were isolated from the peripheral blood of CHB patients and healthy volunteers and cultured with human granulocyte-monocyte colony stimulating factor added together with interleukin-4. On the fifth day of culture, CpG-ODN, HBsAg and other reagents, such as TNF alpha and PBS, were added to the medium, and 18 hours later cells were collected for the detection of surface molecules (HLA-DR/CD86/CD1a). IL-12p70 levels in the supernatant and stimulating capacity to allogenic T lymphocytes were detected. The nucleic proteins of NF-kB and AP-1 in DC were extracted and purified for the gel shift assay. RESULTS: Compared with those of the PBS group, the expression rates of HLA-DR of DC treated with CpG-ODN and/or HBsAg were obviously increased. Both the IL-12p70 level and the stimulating capacity of DC to allogenic T lymphocytes in mixed lymphocyte reaction increased significantly in the CpG-ODN group and in the CpG-ODN/HBsAg combination group (P less than 0.01 and 0.05, respectively). The expression rates of CD1a were raised only in the CpG-ODN/HBsAg combination group. Three kinds of immunological adjuvants, TNF alpha, CpG-ODN and CpG-ODN/HBsAg enhanced the expression of nucleic NF-kB and inhibited the expression of AP-1 in DC. CONCLUSION: CpG-ODN, like TNF alpha, has remarkable stimulatory effect on the impaired phenotype and function of monocyte-derived DC in patients with CHB; CpG-ODN and HBsAg have a synergetic effect in increasing the antigen presenting function. The regulating ability of CpG-ODN and TNF alpha on the expression levels of NF-kB and AP-1 might be one of the mechanisms of their immunostimulatory effects on DC of the CHB patients.