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Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.
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Objective:To review our clinical experience on total pancreatectomy in treatment of pancreatic diseases.Methods:The clinical data of 25 patients with pancreatic diseases who underwent total pancreatectomy at Nanjing Drum Tower Hospital from February 2016 to October 2019 were retrospectively analyzed. The data on general information, surgical methods, postoperative complications, changes in postoperative pancreatic endocrine and exocrine functions and quality of life were analyzed.Results:There were 16 males and 9 females, aged (60.9±9.4) years. Planned selective surgery was carried out in 16 patients while unplanned operations in 9 patients. There were 15 patients with pancreatic neoplasms with 4 patients who received neoadjuvant or conversion therapy, 6 patients with intraductal papillary mucinous neoplasms, 3 patients with chronic pancreatitis and 1 patient with pancreatic neuroendocrine carcinoma. The total postoperative complication rate was 36% (9/25). One patient died in the perioperative period, and one patient underwent a second operation. After 6 months of operation, 2 of 24 patients had died. The remaining patients had a fasting blood sugar of (8.9±1.6) mmol/L, with an insulin dosage of (30.7±10.6) U/d. The average dosage of trypsin was (1.1±0.3) g/d. The quality of life score reached or exceeded the preoperative levels.Conclusions:Total pancreatectomy was safe and feasible for some pancreatic diseases. For patients with pancreatic cancer, its long-term oncological outcomes need further studies.
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Objective:To study the risk factors and microbial spectrum for infectious complications for patients with biliary tract cancer after major hepatectomy with cholangiojejunostomy.Methods:Enrolled into this study were 78 consecutive patients (57 patients with perihilar cholangiocarcinoma, 17 with intrahepatic cholangiocarcinoma and 4 with gallbladder cancer), who underwent major hepatectomy with cholangiojejunostomy at Nanjing Drum Tower Hospital between September 2010 and March 2019. The clinical data were reviewed using multivariate analysis to find independent risk factors for postoperative infectious complications. Microorganisms isolated from bile and infected sites were determined to study the microbial spectrum.Results:A total of 45(57.7%) patients suffered from postoperative infectious complications. Male sex ( OR=7.765, 95% CI=1.895-31.815, P<0.05) was the independent risk factor, whereas increased preope-rative red blood cell (RBC) ( OR=0.151, 95% CI=0.038-0.592, optimal cut-off value=3.7×10 12/L) and increased total cholesterol (TC) on postoperative day (POD) 1 ( OR=0.227, 95% CI=0.083-0.626, optimal cut-off value=3.5 mmol/L) were protective factors (both P<0.05). The area under the receiver operating characteristic (ROC) curve was 0.805 (95% CI=0.707-0.902, P<0.05). 205 and 230 microorganisms were cultured respectively from 286 and 681 specimens which were collected from pre-/intraoperative bile and potentially infected sites. Staphylococcus, enterococcus, acinetobacter, klebsiella and pseudomonas were the most common pathogens on bile culture. The first 5 most frequently isolated microorganisms from the infected sites were enterococcus, staphylococcus, klebsiella, candida and xanthomonas. Sixteen (61.5%) of 26 patients had at least one pathogen being isolated from the infected sites with the pathogen being previously isolated in bile culture. Conclusions:Male sex were independent risk factors of infectious complications. Increased preoperative RBC and inreased TC on POD were proteetive factors. For patients without a positive bile culture, a third-generation cephalosporin can be considered as a prophylactic antibiotic. It is important to identify high-risk patients and monitor perioperative pathogens actively to prevent and to cure postoperative infectious complications.
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Objective:To investigate the influencing factors for pancreatic endocrine and exocrine insufficiency after pancreaticoduodenectomy.Methods:The retrospective case-control study was conducted. The clinicopathological data of 168 patients who underwent pancreaticoduodenectomy in the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to December 2017 were collected. There were 96 males and 72 females, aged (64±13)years, with a range from 38 to 75 years. Of the 168 patients, 36 had pancreatic endocrine insufficiency while 8 had pancreatic exocrine insufficiency preoperatively. All patients underwent pancreaticoduodenectomy. Observation indications: (1) surgical situations and follow-up; (2) analysis of influencing factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy; (3) analysis of influencing factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy. Follow-up using out-patient examination and telephone interview was performed to detect postoperative condition of blood glucose control, diet and nutrition, tumor recurrence and metastasis up to June 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Surgical situations and follow-up: all the 168 patients underwent pancreaticoduodenectomy successfully and recovered well after operation. All patients were followed up for 6 months. The level of fasting and postprandial blood glucose of the 168 patients after surgery were 7 mmol/L(range, 5-9 mmol/L) and 10 mmol/L(range, 7-14 mmol/L), respectively. The defecation frequency was (2.4±1.2)times per day. No tumor recurrence or metastasis occurred in either patient. One hundred and thirty-two of the 168 patients were included in the study excepting patients with pancreatic endocrine insufficiency before operation. At postoperative 6 months, 47 patients developed pancreatic endocrine insufficiency, with an incidence of 35.61%(47/132). One hundred and sixty of the 168 patients were included in the study excepting patients with pancreatic exocrine insufficiency before operation. At postoperative 6 months, 68 patients had pancreatic exocrine insufficiency, with an incidence rate of 42.50%(68/160). (2) Analysis of influencing factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy. Results of univariate analysis showed that gender, metabolic syndrome, chronic pancreatitis, excision point, and postoperative chemotherapy were the related factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy ( χ2=5.300, 6.270, 4.473, 4.392, 5.397, P<0.05). Results of multivariate analysis revealed that male and metabolic syndrome were independent risk factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy [ hazard ratio ( HR)=5.252, 5.364, 95% confidence interval ( CI): 1.362-6.382, 1.891-12.592, P<0.05)]. (3) Analysis of risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy. Results of univariate analysis showed that body mass index (BMI), chronic pancreatitis, total bilirubin, excision point, postoperative pancreatic fistula as grade B or C, and pancreatic fibrosis were related factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy ( χ2=1.691, 4.910, 7.763, 5.605, 4.663, 7.700, P<0.05). Results of multivariate analysis showed that BMI<18.5 kg/m 2, chronic pancreatitis, total bilirubin ≥171 μmol/L were independent risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy ( HR=3.695, 5.231, 7.623, 95% CI: 1.232-7.324, 2.161-6.893, 1.562-5.235, P<0.05). Conclusions:Male and metabolic syndrome are risk factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy. BMI<18.5 kg/m 2, chronic pancreatitis, and total bilirubin ≥171 μmol/L are risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy.
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Objective@#To investigate the role of gut microbiota in the amelioration of liver fibrosis induced by CCl4 in mice by 3-methyladenine (3-MA). @*Methods@#Fifteen mice were randomly divided into normal control group, liver fibrosis group and 3-MA treatment group. The liver fibrosis model was established by injecting CCl4, and the mice in the 3-MA treatment group were injected 3-MA additionally from the third week onwards. After 8 weeks, all of the mice were sacrificed and their blood, liver tissue and fecal samples were collected to analyze serum ALT, AST, GGT levels, liver histopathology and gut microbiota. @*Results@#Compared with the liver fibrosis group, serum ALT and AST levels in 3-MA treatment group decreased obviously ([68.6±4.2] U/L vs [111.0±7.8] U/L, [179.0±12.9] U/L vs [253.2±26.7] U/L, P＜0.01), and the degree of hepatic histopathological changes was reduced. The intestinal flora in three groups were distinguished by principal coordinate analysis (PCoA) and non-metric multi-dimensional scaling (NMDS) analysis. Compared with the normal control group, there were decreased Alpha diversity of intestinal community, reduced significantly abundance of Lachnospiraceae, and increased obviously abundance of Actinobacteria and Desulfovibrionacea in the liver fibrosis group (P＜0.05). Compared with the liver fibrosis group, there were increased Alpha diversity of intestinal community, increased significantly abundance of Lachnospiraceae and Blautia, and reduced abundance of Bifidobacteriaceae in the 3-MA treatment group (P＜0.05). In addition, the abundance of Lactobacillaceae in the 3-MA treatment group was significantly higher than that in the normal control group (P＜0.05). @*Conclusion@#3-MA improves the liver fibrosis of mice induced by CCl4, and gut microbiota may play an active role in this process.
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Objective@#To investigate the effects of Tim-3 on osteoclast-like cell (OLC) formation and bone resorption induced by peripheral blood mononuclear cells (PBMCs). @*Methods@#The expression levels of Tim-3 in of rheumatoid arthritis (RA) patients and healthy controls were detected by flow cytometry. The OLCs were induced by human PBMCs in vitro. The expression levels of tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK) and matrix metalloproteinase 9 (MMP9) mRNAs in the formation of OLCs were detected by real-time quantitative PCR. The morphology of OLCs was observed by Wright′s staining and G-actin staining, and the number of OLCs was counted by TRAP staining. The number and area of bone resorption pits in OLCs were detected by the Corning Osteo Assay Surface. @*Results@#The expression levels of Tim-3 in PBMCs of RA patients ([77.31±10.66]%) were significantly higher than that of healthy controls ([51.72±16.69]%, t=7.593, P＜0.01). When PBMCs with different Tim-3 levels were induced into OLCs, the area of bone resorption pits in the high Tim-3 level group ([1.054±0.085] S/mm 2 ) were significantly lower than those in the intermediate Tim-3 level group ([1.889±0.053] S/mm 2 ) and the low Tim-3 level group ([2.763±0.066] S/mm 2 , F=9.318, P＜0.05). @*Conclusion@#Tim-3 may negatively regulate the bone resorption of OLCs.
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Objective@#To investigate the clinical effect of bile reinfusion combined with enteral nutrition support before surgery for hilar cholangiocarcinoma.@*Methods@#A retrospective analysis of patients with hilar cholangiocarcinoma who underwent surgical treatment at Nanjing Drum Tower Hospital Hepato-biliary-pancreatic Surgery Department from July 2010 to August 2017 was completed.A total of 52 cases were finally enrolled in our study.All the patients included, on the basis of whether they received preoperative drainage and bile reinfusion, were divided into non-drainage group(n=15) and drainage group(n=37). Differences of clinical indicators, including operation time, intraoperative bleeding and serum liver function index levels at day 1, 3, 7 postoperative, postoperative complications(liver failure, biliary fistula, pleural effusion, peritoneal effusion, abdominal cavity infection, death in hospital), tumor classification, R0 resection, postoperative hospitalization time between the 2 groups were analyzed. At the same time, in the drainage group, patients were divided into non-enteral nutrition subgroup(n=13) and enteral nutrition subgroup(n=24) according to whether they received enteral nutrition before operation. The normal distribution data of the group was statistically analyzed by independent sample t test, the non-normal distribution data of the group was statistically analyzed by rank-sum test. The count data was statistically analyzed by non-calibration and correction of the square test.@*Results@#There was no statistically significant difference in general infomation such as age, gender, and serum liver function between non-drainage group and drainage group(P>0.05). There was no statistically significant difference in general information such as age, gender, and serum liver function between non-enteral nutrition group and enteral nutrition group(P>0.05). The rate of vascular resection and reconstruction(33.3%) and operating time(10.8(2.2)h) in drainage group were both higher than those in non-drainage group(6.7% and 8.3(3.0)h), the differences were both statistically significant(χ2=4.397, Z=1.595; both P<0.05). The level of AST at the 7th day after surgery in drainage group(32.8(17.3)U/L) was significantly lower than that in non-drainage group(55.0(64.7)U/L), the difference was statistically significant(Z=-2.212, P<0.05). The level of TBil at 1st day after surgery in drainage group(43.6(91.2)μmol/L) was lower than that in non-drainage group(91.2(188.4)μmol/L), the difference was statistically significant(Z=-2.150, P<0.05). The rate of pancreatoduodenectomy(25.0%) and average operating time(11.1(1.3)h) in the enteral nutrition group were both higher than those in the non-enteral nutrition group(0, 9.0(2.6)h). The differences were both statistically significant(χ2=3.879, Z=-2.693; P<0.05). The average level of AST at the 1st day after surgery in enteral nutrition group(396.4(268.3)U/L) was significantly lower than that in non-enteral nutrition group(642.5(341.1)U/L), the difference was statistically significant(Z=-2.483, P<0.05). The average level of TBil at the 1st, 3th day after surgery in enteral nutrition group(38.8(21.5)μmol/L and 30.0(25.6)μmol/L) were both lower than those in non-enteral nutrition group(60.9(75.2)μmol/L and 46.5(50.0)μmol/L), the differences were both statistically significant(Z=-2.416, -2.026; P<0.05). The level of CRP at 1st, 3th day after surgery((41.9±31.1)mg/L, (50.8±31.4)mg/L)in enteral nutrition subgroup was lower than that in non-enteral nutrition subgroup((64.4±33.6)mg/L, (74.1±35.3)mg/L), the differences were both statistically significant(t=1.456, 1.675; P<0.05).@*Conclusion@#Based on the present study , there is no effective improvement on postoperative recovery using bile reinfusion combined with nutrition support before R0 resection of hilar cholangiocarcinoma.
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Objective To compare the clinical outcomes of endoscopic nasobiliary drainage (ENBD) versus percutaneous transhepatic biliary drainage (PTBD) in patients with perihilar cholangiocarcinoma.Methods This retrospective case-control study was conducted on 55 patients with perihilar cholangiocarcinoma who were treated by of hepatobiliary and pancreatic surgeons at the Nanjing Drum Tower Hospital between December 2010 and August 2017.Results There was no significant difference in the effectiveness of the two drainage methods (P＞0.05).Morbidity after drainage was significantly higher in the ENBD group than the PTBD group (86.7％ vs 28.0％,P＜0.05).24 patients in the ENBD group developed postERCP pancreatic complications which included hyperamylasemia (n =20) and pancreatitis (n =4).All these patients responded well to conservative treatment.A patient in the PTBD group developed catheter tract tumor implantation.There were no significant differences in the surgical outcomes and in the different Clavien-Dindo grades of complications (P＞0.05).Abdominal infection after surgery was more common in the PTBD group than the ENBD group (64.3％ vs 26.3％,P＜0.05).Conclusion As PTBD caused catheter tract tumor implantation and increased the incidence of abdominal infection after surgery,ENBD was recommended for patients with perihilar cholangiocarcinoma treated in a tertiary medical center.