Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To compare the recurrence of common bile duct stones (CBDS) in patients with gallstones and concurrent CBDS treated by two surgical approaches: synchronous laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct exploration (LCBDE) (LC+LCBDE) and synchronous LC combined with intraoperative endoscopic sphincterotomy (IO-EST) (LC+IO-EST).Methods:From Apr 2013 to Apr 2020, the clinical data of 903 patients with gallstones with CBDS who were admitted to the Clinical Medical College, Yangzhou University were retrospectively analyzed.Results:Based on the chosen surgical method, we categorized 389 cases into group A (LC+LCBDE) and 514 cases into group B (LC+IO-EST). Our findings revealed that group A had a significantly lower rate of CBDS recurrence and re-recurrent CBDS compared to group B (4.4% vs. 8.4%, P=0.024; 0.8% vs. 3.1%, P=0.010). Moreover, Logistic regression analysis after inverse probability of treatment weighting, revealed that the surgical approach implemented in group A was an independent protective factor of recurrent CBDS and second recurrence of CBDS ( OR=0.482, 95% CI: 0.365-0.637, P<0.001; OR=0.118, 95% CI:0.080-0.173, P<0.001). Conclusion:LC+LCBDE is an optimal treatment option to LC+IO-EST for patients with gallstones combined with CBDS and common bile duct ≥8 mm.

Objective:To evaluate whether vagus nerve-guided robotic splenectomy and azygoportal disconnection (VNRSD) is feasible and safe and to determine whether VNRSD can be competent for well protecting vagus nerve.Methods:In this prospective clinical study, 12 cirrhotic patients with portal hypertension, hypersplenism and esophagogastric variceal bleeding (EVB) who accepted VNRSD at the Clinical School of Medicine of Yangzhou University between January 2022 and March 2022 were included, including 5 females and 7 males, aged (56.6±11.6) years old. Clinical data such as visual analog scale (VAS) pain score, conversion to laparotomy, esophagogastric variceal bleeding, and death were collected. The patients were asked to reexamine in the outpatient department 1 month after the operation, and the diarrhea, delayed gastric emptying and epigastric fullness were followed up.Results:VNRSD was successfully performed in all patients. There was no conversion to open or laparoscopic operations. The operation time was (170.0±16.8) min, blood loss was (60.8±11.3) ml, VAS pain score on the first day was (2.2±0.9) scores, and the postoperative hospital stay was (7.7±0.7) d, the four patients had main portal vein system thrombosis on the 7th day after operation. At the first day after operation, all patients were mange to take semi-fluid and off-bed activity. There were no incisional complications, pneumonia, gastric fistula, pancreatic fistula, and abdominal infection. No patients suffered from diarrhea, delayed gastric emptying, and epigastric fullness. None of the patients suffered from esophagogastric variceal bleeding, hepatic encephalopathy or death after operation and one month after operation, and the esophagogastric variceal were significantly improved. And no patient complained of abdominal distension or diarrhea.Conclusion:VNRSD procedure is not only technically feasible and safe, but also effectively protects anterior and posterior vagal trunks and all their branches, completely eradicating digestive system complications.

Objective:To evaluate the clinical efficacy of laparoscopic splenectomy and azygoportal disconnection (LSD) with intraoperative endoscopic variceal ligation (LSDL) in the treatment of esophagogastric variceal bleeding (EVR).Method:In this study,90 cirrhotic patients with esophagogastric variceal bleeding (EVB) were divided to receive either LSD ( n=45) or LSDL ( n=45) from Jan 2020 and Dec 2021. Results:There were no significant differences in estimated blood loss, incidence of blood transfusion, time to first flatus, off-bed activity and postoperative hospital stay between the two groups (all P>0.05). Compared with LSD group, operation time was longer in LSDL group[ (140±21) min vs. (150±19) min, t=2.420, P=0.018]. LSDL was associated with significantly decreased EVR rate in one year follow-up (2% vs. 18%, P=0.030). Univariate analysis and multivariate logistic regression revealed that LSDL was a significant independent protective factor for EVR as compared with LSD ( P<0.05). Conclusion:LSDL procedure is not only technically feasible and safe, it also contributed to lower postoperative EVR risk than single LSD.

Objective:To investigate the influencing factors for portal vein thrombosis after laparoscopic splenectomy and azygoportal disconnection (LSD).Methods:The retrospective case-control study was conducted. The clinicopathological data of 106 patients with portal hypertension, type B viral hepatitis and cirrhosis who were admitted to Clinical Medical College of Yangzhou University from September 2014 to January 2017 were collected. There were 83 males and 23 females, aged (51±11)years. All patients underwent LSD. Observation indicators: (1) incidence of postoperative thrombosis and treatment; (2) influencing factors for portal vein thrombosis after LSD. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate analysis was conducted by corres-ponding statistic methods. Multivariate analysis was conducted by Logistic stepwise regression model with forward method. Results:(1) Incidence of postoperative thrombosis and treatment. All 106 pati-ents were followed up in the postoperative 1 month. During the follow-up period, 35 patients had thrombosis occurred in main and intrahepatic branches of portal vein, including 23 cases with thrombosis occurred in main portal vein, 1 case with thrombosis occurred in intrahepatic right branches of portal vein, 5 cases with thrombosis occurred in main and intrahepatic right branches of portal vein, 5 cases with thrombosis occurred in main and intrahepatic left branches of portal vein, 1 case with thrombosis occurred in intrahepatic left branches of portal vein. Of the 35 patients with portal vein thrombosis, 17 cases were treated with warfarin and 18 cases were treated with aspirin. (2) Influencing factors for portal vein thrombosis after LSD. Results of multivariate analysis showed that preoperative portal vein diameter was an independent factor influencing portal vein thrombosis after LSD ( odds ratio=1.559, 95% confidence interval as 1.200-2.027, P<0.05). Conclusion:Preoperative portal vein diameter is an independent factor influencing portal vein thrombosis after LSD .

Objective:To investigate the value of liver fibrosis serum markers in predicting esophagogastric variceal re-bleeding (EGVR) after laparoscopic splenectomy and azygoportal discon-nection (LSD).Methods:The prospective study was conducted. The clinical data of 155 cirrhotic portal hypertension patients with EGVR after LSD in the Clinical Medical College of Yangzhou University from September 2014 to January 2017 were selected. Observation indicators: (1) grouping situations of the enrolled patients; (2) risk factors analysis for postoperative EGVR; (3) prediction of postoperative EGVR; (4) follow-up. Follow-up was conducted using telephone interview, outpatient examination and hospitalization. Patients were followed up once every 3 months after operation to detect occurrence of EGVR and survival of patient up to January 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data wite skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups were conducted using the chi-square test or Fisher exact probability. Logistic regression model was used for multivariate analysis. The area under curve (AUC) of receiver operating characteristic (ROC) curve was used to estimate the diagnostic efficiency. The Youden index was used to determine the optimal cut-off point. Results:(1) Grouping situations of the enrolled patients. A total of 155 patients were selected for eligibility. There were 106 males and 49 females, aged (53±11)years. Of the 155 patients, there were 21 cases with EGVR in the postoperative 1 year and 134 cases without EGVR in the postoperative 1 year. The protein expression of laminin and collagen Ⅳ were 100.3(range, 16.1?712.2)μg/L and 68.4(range, 35.0?198.8)μg/L in patients with EGVR, vs 35.5(range, 2.0?521.2)μg/L and 43.5(range, 4.3?150.4)μg/L in patients without EGVR, showing significant differences between them ( Z=?4.55, ?4.52, P<0.05). (2) Risk factors analysis for postoperative EGVR. According to the Youden index, the optimal cut-off point of protein expression of laminin and collagen Ⅳ were 64.0 μg/L and 65.0 μg/L, respec-tively. Results of multivariate analysis showed that the protein expression of laminin ≥64.0 μg/L and the protein expression of collagen Ⅳ ≥65.0 μg/L were independent risk factors for postoperative EGVR ( odds ratio=9.69, 8.16, 95 confidence intervals as 3.05?30.82, 2.65?25.15, P<0.05). (3) Prediction of postoperative EGVR. Results of ROC curve showed that the AUC of laminin and collagen Ⅳ in predicting postoperative EGVR was 0.79 (95% confidence interval as 0.66?0.92), with sensi-tivity as 0.62 and specificity as 0.96. (4) Follow-up. All the 155 patients were followed up for 12(range, 1?12)months. During the follow-up, there were 21 of the 155 patients (13.55%) with post-operative EGVR, including 3 cases died of EGVR. Of the 21 patients with postoperative EGVR, there were 6 cases with postoperative EGVR during the first month after operation including 2 cases died, 5 cases with postoperative EGVR at postoperative 1?3 month, 6 cases with postoperative EGVR more than 3 month and less than 6 month after operation and 4 cases with postoperative EGVR at postoperative 6?12 months including 1 case died at postoperative 12 month. Conclusions:Laminin and collagen Ⅳ show satisfactory ability to predict EGVR after LSD.

Objective:To investigate the clinical efficacy of Da Vinci robotic assisted vagus nerve-preserving splenectomy and azygoportal disconnection.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 cirrhotic portal hypertension patients with esophagogastric variceal bleeding and hypersplenism who were admitted to Clinical Medical College of Yangzhou University from February to May 2021 were collected. There were 4 males and 6 females, aged from 43 to 64 years, with a median age of 55 years. All 10 patients underwent Da Vinci robotic assisted vagus nerve-preserving splenectomy and azygoportal discon-nection. Observation indicators: surgical situations, intraoperative autologous blood transfusion, conversion to open laparotomy, allogeneic blood transfusion, the operation time, volume of intra-operative blood loss, time to initial diet intake, time for out-of-bed activity, postoperative complica-tion, duration of postoperative hospital stay and follow-up. Follow-up was conducted using out-patient examination and telephone interview to detect recurrent gastrointestinal hemorrhage and gastric retention up to July 2021. Measurement data with normal distribution were represented as Mean± SD and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:All 10 patients underwent Da Vinci robotic assisted nerve-preserving splenectomy and azygoportal disconnection successfully, with intraopera-tive autologous blood transfusion and without conversion to open laparotomy or allogeneic blood transfusion. The operation time, volume of intraoperative blood loss, time to initial diet intake and time for out-of-bed activity of 10 patients were (180±14)minutes, (111±28)mL, (1.5±0.5)days and (2.5±0.7)days, respectively. Of the 10 patients, 1 case underwent mild pancreatic leakage, 1 case underwent pneumonia, 2 cases underwent portal vein thrombosis and 3 cases underwent splenic vein thrombosis. Patients with postoperative complications was cured after conservative treatment. The duration of postoperative hospital stay of 10 patients was (8.9±0.9)days. All 10 patients were discharged without perioperative death and followed up for 1 to 4 months, with a median follow-up time of 3 months. There was no patient undergoing gastrointestinal hemorrhage and gastric reten-tion.Conclusion:Da Vinci robotic assisted vagus nerve-preserving splenectomy and azygoportal disconnection is safe and feasible for the treatment of cirrhotic portal hypertension patients with esophagogastric variceal bleeding and hypersplenism.

Intrahepatic cholangiocarcinoma(ICC) is a malignant tumor that originates in the epithelium of the proximal proximal to the second-degree bile ducts and has a high degree of malignancy. The causes of ICC are widely geographically diverse. Pathogenesis of ICC involves multiple molecular alterations at the level of genome, epigenome and stromal environment resulting in several deregulated signal transduction pathways. There are three types of pathological classification: mass-forming, periductal infiltrating, and intraductal growth. The mixed type of mass-forming + periductal infiltrating has the highest degree of malignancy. Early diagnosis of ICC is not easy, and tumor biomarkers such as CA19-9, CEA and so on, have some reference values, and multiple imaging examinations are needed to confirm each other. The effect of surgery mainly depends on the characteristics of the tumor, the vascular invasion of the tumor, the resection margin of the tumor and lymphatic metastasis. Lymph node dissection is controversial. If local lymphatic metastasis is identified, standardized lymph node dissection can improve ICC prognosis. Some ICC patients benefit from laparoscopic staging. In experienced centers, minimally invasive treatment can provide oncological outcomes similar to open resection for specific ICC patients. Liver transplantation is feasible in early ICC patients, but further clinical validation is needed.