Objective:To evaluate the efficacy and safety of lenvatinib combined with camrelizumab as the second-line treatment for advanced intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with advanced ICC undergoing the second-line treatment of lenvatinib combined with camrelizumab in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from June 2021 to June 2022 were screened and analyzed. A total of 12 patients were enrolled, including seven males and five females, aged (67.5±8.6) years. Response evaluation criteria in solid tumor 1.1 was used to evaluate the efficacy of treatment. The safety assessment adopts the Adverse Event Evaluation Standard 5.0. Kaplan-Meier method was conducted to plot survival curves.Results:Among the 12 patients (after 1-7 cycles of immune and targeted therapy), three achieved partial response, four achieved stable disease, and five were defined as progression disease. Adverse events of different degrees occurred in seven cases, among which three patients had adverse events of grade ≥ 3: one with hypertension, which was managed after antihypertensive and symptomatic treatment; one with elevated serum total bilirubin, which was improved after reducing the dose of lenvatinib; one with liver dysfunction, which was considered as immune-related liver toxicity and alleviated after discontinuing camrelizumab. The 1-month, 3-month, and 6-month survival rates and progression-free survival rates of the patients were 100.0%, 91.7%, 66.7%, and 83.3%, 41.7%, and 25.0%, respectively. The median overall survival of patients was 14.7 months (95% CI: 9.2-21.2) and the median time to progression was 8.0 months (95% CI: 4.1-11.9). Conclusion:Combination of lenvatinib and camrelizumab could bring survival benefits with controllable adverse events as the second-line treatment of patients with advanced ICC.

Objective:To investigate the effect of high-dose vitamin B6 on stress-induced liver cell death in rats with severe trauma and its possible mechanism.Methods:Thirty-two male SD rats were selected and divided into sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group by using a random number table, with 8 rats in each group. Rat models of severe trauma were established by inducing abdominal wall injury, bilateral femoral fractures, unilateral cranial injury, and withdrawal of 4 ml blood from the femoral artery. The sham surgery+B6 group and trauma+B6 group were treated with saline solution plus high-dose vitamin B6, while the sham surgery group and trauma group with infusion of saline solution only. At 36 hours after injury, rat liver tissues were collected for the following experiments: (1) the genes differentially expressed in the liver tissues of the rats of the trauma group and the trauma+B6 group were screened with next-generation sequencing, followed by an analysis of the possible involvement of cell death pathways; (2) validation was conducted to ascertain whether high-dose vitamin B6 could influence various cell death pathways in the liver cells in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group: apoptosis was confirmed through terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining; necroptosis was verified by mixed lineage kinase domain-like protein (MLKL) immunohistochemical staining; autophagy was examined via transmission electron microscopy; ferroptosis was confirmed by detecting oxidative malondialdehyde (MDA) levels, oxidized glutathione levels, Prussian blue staining with diaminobenzidine (DAB) enhancement, transmission electron microscopy, and immunohistochemical staining for acyl-CoA synthetase long-chain family member 4 (ACSL4); (3) Biological information analyses [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Enrichment analysis (GSEA)] were performed for biological processes and signaling pathways represented by liver tissue sequencing results of rats between the trauma group and the trauma+B6 group.Results:(1) In the liver tissues of rats, there were 344 significantly differentially expressed genes between the trauma group and trauma+B6 group, comprising 137 upregulated genes and 207 downregulated genes, of which 18 genes were associated with apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. (2) No significant differences were found in TUNEL staining among the sham surgery group, sham surgery+B6 group, trauma group or trauma+B6 group; MLKL protein expression levels in the liver tissues after trauma were improved, of which the trauma+B6 group was lower than that of the trauma group; Electron microscopy showed that autophagic activity in the liver cells were significantly increased after trauma, which was significantly lower of the trauma+B6 group than that of the trauma group; MDA levels in the rat liver tissues were (0.20±0.05)nmol/mg, (0.17±0.07)nmol/mg, (0.69±0.11)nmol/mg and (0.52±0.07)nmol/mg in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group respectively ( P<0.01), with the trauma group having the highest MDA levels and trauma+B6 group having lower MDA levels than the trauma group; Oxidized glutathione levels in the liver tissues of the four groups were (11.75±2.09)μmol/g, (11.69±1.66)μmol/g, (19.75±3.40)μmol/g, and (14.51±1.46)μmol/g respectively ( P<0.01), with the trauma group having the highest levels and trauma+B6 group having lower levels than the trauma group; Significantly increased iron deposition was observed in the liver tissues after trauma, with lower iron deposition in trauma+B6 group than the trauma group; Electron microscopy revealed significantly lower mitochondrial membrane density in the trauma+B6 group compared to the trauma group. ACSL4 protein expression level was lower in the trauma+B6 group compared to the trauma group; (3) GO, KEGG and GSEA enrichment analyses suggested that high-dose vitamin B6 may enhance cholesterol synthesis metabolism in the liver cells and alleviate oxidative stress to reduce liver cell damage and restore normal liver cell function after trauma. Conclusions:High-dose vitamin B6 attenuates stress-induced liver injury in rats with severe trauma by inhibiting the progression of necroptosis, autophagy and ferroptosis. Its molecular mechanism may be associated with enhanced hepatic cholesterol synthesis metabolism and alleviation of oxidative stress in the liver cells.

Humans ; Brain Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioma/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; ATPases Associated with Diverse Cellular Activities/metabolism* ; Mitochondrial Proteins/metabolism* ; GTP-Binding Protein alpha Subunits/metabolism*

Objective:To investigate the feasibility and potential of fluorescent cholecystic bile duct visualization with direct intravenous injection of indocyanine green(ICG) in obese patients undergoing laparoscopic cholecystectomy(LC).Methods:The clinical data of 132 patients with LC combined with obesity admitted to the Department of Hepatobiliary and Pancreatic Surgery of the Second People′s Hospital of Changzhou City, affiliated to Nanjing Medical University, from January 2023 to July 2023 were retrospectively analyzed. They were divided into fluorescence group( n=65) and control group( n=67) according to whether indocyanine green fluorescence navigation was used or not. There were 50 males and 82 females, and all the enrolled patients body mass index≥28 kg/m 2. Two groups identify the time of the three tubes, intraoperative bleeding, operation time, postoperative hospitalization time, white blood cell count(WBC), C-reactive protein(CRP), alanine aminotransferase(ALT), gamma-glutamyl transferase(GGT), and postoperative follow-up in the fluorescent and control groups were counted respectively. Measurement data with skewed distribution were expressed as M( Q1, Q3), and intergroup comparisons were performed using the Mann-Whitney U test; counting data were described by frequency(rate), and intergroup comparisons were made by applying the chi-square test, Fisher′s exact probability method, and chi-square corrected test according to the difference in the minimum frequency. Results:Surgery was successfully completed in both groups. Preoperative inflammatory indicators and liver function levels were also not statistically significant( P>0.05). The time to identify the three tubes, operation time, intraoperative bleeding, and postoperative hospitalization in the fluorescence group were 18.00(13.50, 20.00) min, 40.00(30.00, 50.00) min, 5.00(5.00, 10.00) mL, and 2.00(1.50, 3.00) d, and in the control group were 32.00(25.00, 45.00) min, 65.00(50.00, 85.00) min, 41.00(41.00, 46.00) mL, and 4.00(3.00, 5.00) d. The differences between the two groups were statistically significant( P<0.05). The postoperative leukocyte count, postoperative CRP, and postoperative GGT were 9.15(7.10, 11.75)×10 9/L, 7.19(3.22, 20.00) mg/L, and 34.0(20.0, 49.0) U/L in the fluorescence group, and 13.05(11.02, 15.59)×10 9/L, and 18.78(12.90, 32.95) mg/L in the control group, respectively, 82.5(68.5, 114.5) U/L, and the differences between the two groups were statistically significant ( P<0.05). None of the patients showed abdominal pain, abnormal liver function and hepatobiliary ultrasound in the follow-up findings within 2 months after surgery. Conclusion:The effect of obesity, a factor that interferes with ICG fluorescence, is extremely limited, and ICG fluorescence cholangiography is a useful technique in the obese population that not only improves the efficiency of the procedure, but also increases intraoperative safety, with results superior to those of conventional laparoscopic cholecystectomy.

Objective:To investigate the clinical value of intraoperative intravenous injection of indocyanine green in differentiating extrahepatic bile duct structure in chronic atrophic cholecystitis.Methods:A retrospective analysis was performed on the data of 110 patients diagnosed with chronic AC who underwent laparoscopic cholecystectomy (LC) admitted to the Department of Hepatobiliary and pancreatic Surgery of Changzhou Second People′s Hospital from January 2020 to July 2021. All patients were confirmed by abdominal B-ultrasound before surgery. The patients in the experimental group were divided into experimental group ( n=55) and control group ( n=55) according to whether indocyanine green was intravenously injected during the operation. The experimental group was intravenously injected with 5 mg indocyanine green during the operation, and LC was navigated by indocyanine green fluorescence imaging technique during the operation. The control group received routine LC. The imaging rate and imaging time of the cystic duct, common bile duct, and common hepatic duct in the experimental group were compared. The clinical data, identify three tube time, operation time, intraoperative blood loss, abdominal cavity drainage placement and extubation time, transfer laparotomy and bile duct injury, postoperative hospital stay, postoperative first review of alanine aminotransferase (ALT), glutamine transferase (GGT) of leveling and follow-up were compared between the two groups. The measurement data subject to normal distribution were expressed by Mean±standard deviation ( ± s), and the two groups were compared by independent sample t test. The measurement data of skewness distribution were described by M( Q1, Q3)and the manhui method in nonparametric test was used Mann-whitney U test.The chi-square test or Fisher′s exact probability method was used for comparison between groups of count data. Results:Operation was performed successfully in both groups. In the experimental group, the common hepatic duct, common bile duct and gallbladder duct were developed successfully in all patients, 54 cases and 52 cases respectively, and the developing time of the three tubes was (15.8±1.2) min. In the experimental group, the time of three tubes, operation time, intraoperative blood loss and abdominal drainage tube placement were (18.5±1.3) min, (64.0±6.8) min, (16.3±6.7) mL, 43 cases, respectively. In the control group, there were (46.3±8.1) min, (98.7±10.5) min, (53.6±14.9) mL and 55 cases, respectively. The experimental group was significantly lower than the control group, and the difference between the two groups was statistically significant ( P< 0.05). There was no case of conversion to laparotomy and bile duct injury in the experimental group, and 1 case of conversion to laparotomy and 1 case of bile duct injury in the control group, and there was no statistical significance between the two groups ( P>0.05). There were significant differences in postoperative extubation time and postoperative hospital stay between the two groups ( P<0.05). ALT and GGT levels were 47(31, 75) U/L and 38(19, 114) U/L in the experimental group and 62(53, 92) U/L and 76(63, 96) U/L in the control group at the first postoperative review, with statistically significant differences between the two groups ( P<0.05). Patients in both groups were followed up for 3 months after discharge. There were no obvious complications in the experimental group, and 1 case had a small amount of peritoneal effusion 7 days after discharge in the control group. Conclusion:In the face of LC with chronic AC, intraoperative intravenous injection of indocyanine green to develop extrahepatic bile duct can help to distinguish its anatomical structure and avoid bile duct injury, improve the safety and progress of surgery, and maximize training and improve the level of the surgeon.

Objective:To investigate the feasibility and efficacy of transcystic injection of indocyanine green during laparoscopic cholecystectomy (LC) surgery in the treatment of patients with gallbladder stones combined with liver cirrhosis.Methods:The clinical data of 96 patients with cirrhosis who underwent LC for gallbladder stones with cholecystitis attacks in the Department of Hepatobiliary and Pancreatic Surgery of the Second People′s Hospital of Changzhou City from January 2018 to May 2022 were retrospectively analyzed. All patients were diagnosed by clinical history and auxiliary examination before surgery and underwent cholecystectomy according to their groups, which were divided into fluorescence group ( n=49) and white light group ( n=47) according to whether ICG was used or not, where the fluorescence group underwent LC in fluorescence mode after direct intraoperative injection of ICG via gallbladder. The two groups were compared in terms of identification time of the three tubes, operation time, intraoperative bleeding, intraoperative injury, intraoperative open abdomen and blood transfusion, postoperative drainage time, postoperative hospitalization time, postoperative complications and changes in infection and liver function indexes before and after surgery. The measurement data obeying normal distribution were expressed as mean±standard deviation( ± s), and independent sample t-test was used for comparison between groups. The measurement data obeying the skewed distribution were expressed by M( Q1, Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as rates (%), and the chi-square test or Fisher′s exact probability method was used for comparison between groups. Results:The procedure was successfully performed in both groups, and the identification of triple-tube time, operative time, intraoperative bleeding, postoperative drainage time, postoperative hospital stay, postoperative ALT, postoperative GGT, and postoperative TBIL in the fluorescent group were (14.96±1.49) min, (52.14±7.36) min, 5(5, 10) mL, (1.61±0.61) d, (2.37±0.49) d, 31.5(22.0, 44.8) U/L, 38.0(21.0, 91.5) U/L, 18.0(11.5, 22.8) μmol/L, and (29.87±3.37) min, (84.36±13.25) min, 10(10, 20) mL, (2.70±0.69) d, (3.15±0.42) d, 45.0(28.0, 64.8) U/L, 73.0(32.0, 132.0) U/L, 23.0(16.1, 29.3) μmol/L in the white light group and the differences were statistically significant compared with the two groups( P<0.05). In the fluorescence group, there was no intraoperative injury and no cases of intraoperative opening, and there were 2 cases of postoperative complications, while in the white light group, there were 2 cases of intraoperative injury, 1 case of intraoperative opening, and 5 cases of postoperative complications, and there were no cases of blood transfusion in both groups. There was no statistically significant difference between the fluorescence group and the white light group when comparing the preoperative laboratory indexes of both groups ( P>0.05). When comparing the first postoperative white blood cell count, C-reactive protein, aspartate aminotransferase, and alkaline phosphatase indexes in the fluorescence group and the white light group, there was no statistically significant difference between the two groups ( P>0.05). Conclusion:When LC is performed in patients with symptomatic gallbladder stones combined with cirrhosis, intraoperative injection of indocyanine green via the gallbladder to visualize the gallbladder and bile duct structures is simple and easy to perform, and the safe and efficient dissection of extrahepatic bile ducts and gallbladder bed speeds up the procedure while reducing postoperative trauma.

In the era of precision medicine, compared with open surgery, laparoscopic cholecystectomy has the advantages of less trauma, less postoperative complications and shorter hospital stay, but it cannot escape the risk of bile duct injury, and bile duct injury can occur at any time for various reasons, and its unpredictability greatly increases the difficulty of surgery. Although traditional cholangiography can avoid bile duct injury, it has not been widely used due to its limitations such as time consuming, high cost, high radiation and so on. Early indocyanine green has been widely used in lymph node examination, angiography, tumor localization and treatment due to its characteristics. Now, indocyane green fluorescence imaging technology has been gradually applied in LC, which can dynamically reflect the intraoperative situation and realize real-time surgical navigation, so it has achieved ideal effects in the identification of duct structure and prevention of bile duct injury. Indocyanine green injection preoperatively or intraoperatively through the gallbladder to develop extrahepatic bile ducts significantly improves the safety rate of surgery, but there is no unified standard for the use time and dosage of inddocyanine green. In this paper, the time and dose selection and clinical value of indocyanine green were reviewed based on the current research status and the author's experience.

Objective:To construct a three-dimensional imaging model of the pancreatic head based on the embryological fusion plane, and to provide morphological parameters of the pancreatic head for future developments of basic and clinical researches on the pancreas.Methods:Histologic cross-sections of the pancreatic head with its adjacent structures were made from healthy cadavers. Immunohistochemical analysis of pancreatic polypeptide antibody was then performed to verify the existence and location of the embryological fusion plane reported previously. The histologically positioning method of the embryological fusion plane was then applied to the corresponding sections on computed tomography (CT). Based on the results of the above work, volunteers from the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University were then used as research objects. A three-dimensional visualization reconstruction software was used to perform CT image-based structures to include the abdominal pancreas, dorsal pancreas head, and embryo fusion surface. Three-dimensional reconstruction of the pancreatic head, and morphological measurements of the relevant structures of the pancreatic head were then made.Results:Immunohistochemical analysis verified the existence and the position of the embryological fusion plane. The histologically positioning method was then successfully applied to the CT sections. The three-dimensional imaging model of the pancreatic head containing the embryological fusion plane, dorsal segment and ventral segment of head were built based on CT images. A total of 35 volunteers were included, including 19 males and 16 females, aged (48.26±8.26) years, and with a BMI of (22.29±1.78) kg/m 2. The morphological results showed that the volume of the pancreatic head, dorsal pancreas and abdominal pancreas were (32.80±8.15) cm 3, (22.21±6.94) cm 3, (10.59±3.87) cm 3, and the area of the embryo fusion surface was (12.46±3.20) cm 2. All volunteers were then grouped according to gender. Statistical analysis showed that there were no significant differences in the total pancreatic head volume, dorsal pancreatic head volume, abdominal pancreatic volume, and embryo fusion area among the groups ( P>0.05). Conclusions:It was feasible and practical to build a three-dimensional imaging model of the pancreatic head based on the embryological fusion plane by using a 3D computer system. This model and its morphological parameters could provide a new tool for research on pancreas.

Objective:To analyze the results in clinical application of backtracking full-thickness continuous everting suturing in primary closure of common bile duct after laparoscopic bile duct exploration.Methods:From February 2014 to November 2018 at the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, 82 patients with cholecystolithiasis and choledocholithiasis entered into this study. There were 45 males and 37 females, with an average age of 62.7 years. These patients underwent primary closure of common bile duct after laparoscopic bile duct exploration using backtracking full-thickness continuous everting suturing to close the incisions in common bile ducts. Clinical data on surgery, postoperative complications and follow-up were collected and analyzed retrospectively.Results:Primary closure of common bile duct was successfully carried out in all patients. The operation time ranged from 45 to 150 min (average 68.5 min). Intraoperative blood loss ranged from 5 to 150ml (average 18.4 ml). Postoperative bile leakage occurred in 2 patients (2.4%). There were no intra-abdominal or biliary bleeding, severe cholangitis, liver function derangement, abdominal infection or residual stones. Of 77 patients who were followed up (follow-up rate of 93.9%), the follow-up time ranged from 9 to 50 months (median 14 months). On follow-up, 2 patients (2.4%) developed recurrence of choledocholithiasis and 1 patient (1.2%) was diagnosed to have intrahepatic bile duct stones. There were no patients with bile duct stenosis or acute cholangitis.Conclusion:Primary closure of common bile duct with backtracking full-thickness continuous everting suturing has the advantage of reducing postoperative bile leakage in patients after laparoscopic bile duct exploration. The long-term effects of this technique still need further clinical studies.

Objective: To investigate the influencing factors for poor jaundice resolution after radical pancreaticoduodenectomy in patients with malignant obstructive jaundice. Methods: The retrospective case-control study was conducted. The clinicopathological data of 121 patients with malignant obstructive jaundice who were admitted to the Affiliated Changzhou No.2 People′s Hospital of Nanjing Medical University between March 2013 and June 2018 were collected. There were 70 males and 51 females, aged (69±9)years, with a range from 39 to 85 years. Of 121 patients, 112 underwent open radical pancreaticoduodenectomy, and 9 underwent totally laparoscopic radical pancreaticoduodenectomy. Observation indicators: (1) situations of jaundice resolution after pancreaticoduodenectomy; (2) influencing factors for poor jaundice resolution after pancreaticoduodenectomy. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers. Univariate analysis was performed using the chi-square test, t test, Fisher exact probability or Mann-Whitney U test. Multivariate analysis was performed by the Logistic regression model using P<0.10 as an inclusion criteria in the univariate analysis . Results: (1) Situations of jaundice resolution after pancreaticoduodenectomy: of 121 patients, 97 had good jaundice resolution after pancreaticoduodenectomy, and 24 had poor jaundice resolution after pancreaticoduodenectomy. (2) Influencing factors for poor jaundice resolution after pancreaticoduodenectomy: results of univariate analysis showd that preoperative level of serum total bilirubin, comorbidity with diabetes mellitus were influencing factors for poor jaundice resolution after pancreaticoduodenectomy (t=-2.073, χ²=10.201, P<0.05). Postoperative pancreatic fistula was also an influencing factor for poor jaundice resolution after pancreaticoduodenectomy (P<0.05). Results of multivariate analysis showed that comorbidity with diabetes mellitus and postoperative pancreatic fistula were independent risk factors for poor jaundice resolution after pancreaticoduodenectomy (odds ratio=0.258, 0.129, 95% confidence interval: 0.087-0.769, 0.023-0.726, P<0.05). Conclusions Preoperative level of serum total bilirubin, diabetes mellitus, and postoperative pancreatic fistula are influencing factors for poor jaundice resolution after pancreaticoduodenectomy. Comorbidity with diabetes mellitus and postoperative pancreatic fistula are independent risk factors for poor jaundice resolution after pancreaticoduodenectomy.