Individualized risk estimation for postoperative pulmonary complications after hepatectomy based on perioperative variables.

BACKGROUND: At present, there is no perfect system to evaluate pulmonary complications of liver surgery using perioperative variables. AIM: To design and verify a risk assessment system for predicting postoperative pulmonary complications (PPCs) after hepatectomy based on perioperative variables. METHODS: A retrospective analysis was performed on 1633 patients who underwent liver surgery. The variables were screened using univariate and multivariate analyses, and graded scores were assigned to the selected variables. Logistic regression was used to develop the liver operation pulmonary complication scoring system (LOPCSS) for the prediction of PPCs. The LOPCSS was verified using the receiver operating characteristic curve. RESULTS: According to the multivariate correlation analysis, the independent factors which influenced PPCs of liver surgery were age [≥ 65 years old/< 65 years old, odds ratio (OR) = 1.926, P = 0.011], medical diseases requiring drug treatment (yes/no, OR = 3.523, P < 0.001), number of liver segments to be removed (≥ 3/≤ 2, OR = 1.683, P = 0.002), operation duration (≥ 180 min/< 180 min, OR = 1.896, P = 0.004), and blood transfusion (yes/no, OR = 1.836, P = 0.003). The area under the curve (AUC) of the LOPCSS was 0.742. The cut-off value of the expected score for complications was 5. The incidence of complications in the group with ≤ 4 points was significantly lower than that in the group with ≥ 6 points (2.95% vs 33.40%, P < 0.001). Furthermore, in the validation dataset, the corresponding AUC of LOPCSS was 0.767. CONCLUSION: As a novel and simplified assessment system, the LOPCSS can effectively predict PPCs of liver surgery through perioperative variables.

Establishment of an Assessment System for the Prediction of Severe Post-operative Complications after Hepatectomy Based on Preoperative Parameters.

OBJECTIVE: At present, there is no appropriate system to evaluate the severe complications of liver surgery through the preoperative factors. This study aimed to design and verify a risk assessment system for the prediction of severe post-operative complications after a hepatectomy based on the preoperative parameters. METHODS: A retrospective analysis was performed on 1732 patients who had undergone liver surgery. The severity of the complications was graded by Accordion Severity Grading of post-operative complications. The variables were screened by multivariate analysis, and graded scores were assigned to the selected variables. A logistic regression equation was used to form the liver operation risk formula (LORF) for the prediction of severe post-operative complications. The LORF was verified by the receiver operating characteristic (ROC) curve. RESULTS: The multivariate correlation analysis revealed the independent influencing factors of the severe post-operative complications of liver surgery were Child-Pugh grade (OR=4.127; P<0.001), medical diseases requiring drug treatment (OR=3.092; P<0.001), the number of liver segments to be removed (OR=2.209; P=0.006), organ invasion (OR=4.538; P=0.024), and pathological type (OR=4.023; P=0.002). The binomial logistic regression model was established to obtain the calculation formula (LORF) of the severe complication risk. The area under the ROC curve (AUC) of the LORF was 0.815. The cut-off value of the expected probability of severe complications was 0.3225 (32.25%). Furthermore, in the validation data set, the corresponding AUC of the LORF was 0.829. CONCLUSION: As a novel and simplified assessment system, the LORF could effectively predict the severe post-operative complications of liver surgery through the preoperative factors, and therefore it could be used to evaluate the risk of severe liver surgical complications before surgery.

Effect of Postoperative ω-3 Fatty Acid Immunonutritional Therapy on NK Cell Gene Methylation in Elderly Patients with Gastric Cancer.

OBJECTIVE: This study aims to investigate the effect of ω-3 fatty acid immunonutritional therapy on natural killer (NK) cell gene methylation and function in elderly patients with gastric cancer. METHODS: A total of 70 cases of elderly patients with gastric cancer were randomized into the ω-3 fatty acid group and placebo group, according to the type of nutritional support administered. The methylation status of the tumor necrosis factor (TNF)-α gene promoter in peripheral NK cells was detected by methylation specific polymerase chain reaction, and the TNF-α level in peripheral NK cells was detected by enzyme-linked immunosorbent assay. RESULTS: After 14 days of immunonutritional therapy with ω-3 fatty acid or placebo, patients in the ω-3 group had significantly higher average NK cell activity (0.27 vs. 0.24, P=0.013) and lower percentages of TNF-α gene promoter methylation (25.7% vs. 60%, P<0.05) than the placebo group. However, there were no significant differences in the concentration of albumin, prealbumin and TNF-α in serum, and the NK cell count between the ω-3 group and placebo group. CONCLUSION: The postoperative application of ω-3 fatty acid may improve the activity of NK cells, which is correlated to the methylation status of the TNF-α gene promoter.

Assessment of complications after liver surgery: Two novel grading systems applied to patients undergoing hepatectomy.

Although quality assessment is gaining increasing attention, there is still no consensus on how to define and grade postoperative complications. The absence of a definition and a widely accepted ranking system to classify surgical complications has hampered proper interpretation of the surgical outcome. This study aimed to define and search the simple and reproducible classification of complications following hepatectomy based on two therapy-oriented severity grading system: Clavien-Dindo classification of surgical complications and Accordion severity grading of postoperative complications. Two classifications were tested in a cohort of 2008 patients who underwent elective liver surgery at our institution between January 1986 and December 2005. Univariate and multivariate analyses were performed to link respective complications with perioperative parameters, length of hospital stay and the quality of life. A total of 1716 (85.46%) patients did not develop any complication, while 292 (14.54%) patients had at least one complication. According to Clavien-Dindo classification of surgical complications system, grade I complications occurred in 150 patients (7.47%), grade II in 47 patients (2.34%), grade IIIa in 59 patients (2.94%), grade IIIb in 13 patients (0.65%), grade IVa in 7 patients (0.35%), grade IVb in 1 patient (0.05%), and grade V in 15 patients (0.75%). According to Accordion severity grading of postoperative complications system, mild complications occurred in 160 patients (7.97%), moderate complications in 48 patients (2.39%), severe complications (invasive procedure/no general anesthesia) in 48 patients (2.39%), severe complications (invasive procedure under general anesthesia or single organ system failure) in 20 patients (1.00%), severe complications (organ system failure and invasive procedure under general anesthesia or multisystem organ failure) in 1 patient (0.05%), and mortality was 0.75% (n=15). Complication severity of Clavien-Dindo system and Accordion system were all correlated with the length of hospital stay, the number of hepatic segments resected, the blood transfusion and the Hospital Anxiety and Depression Scale-Anxiety (HADS-A). The Clavien-Dindo classification system and Accordion classification system are the simple ways of reporting all complications following the liver surgery.

Assessment of Complications after Liver Surgery: Two Novel Grading Systems Applied to Patients Undergoing Hepatectomy / 华中科技大学学报（医学）（英德文版）

Although quality assessment is gaining increasing attention,there is still no consensus on how to define and grade postoperative complications.The absence of a defimition and a widely accepted ranking system to classify surgical complications has hampered proper interpretation of the surgical outcome.This study aimed to define and search the simple and reproducible classification of complications following hepatectomy based on two therapy-oriented severity grading system:Clavien-Dindo classification of surgical complications and Accordion severity grading of postoperative complications.Two classifications were tested in a cohort of 2008 patients who underwent elective liver surgery at our institution between January 1986 and December 2005.Univariate and multivariate analyses were performed to link respective complications with perioperative parameters,length of hospital stay and the quality of life.A total of 1716 (85.46％) patients did not develop any complication,while 292 (14.54％)patients had at least one complication.According to Clavien-Dindo classification of surgical complications system,grade Ⅰ complications occurred in 150 patients (7.47％),grade Ⅱ in 47 patients (2.34％),grade Ⅲa in 59 patients (2.94％),grade Ⅲb in 13 patients (0.65％),grade Ⅳa in 7 patients (0.35％),grade Ⅳb in 1 patient (0.05％),and grade Ⅴ in 15 patients (0.75％).According to Accordion severity grading of postoperative complications system,mild complications occurred in 160 patients (7.97％),moderate complications in 48 patients (2.39％),severe complications (invasive procedure/no general anesthesia) in 48 patients (2.39％),severe complications (invasive procedure under general anesthesia or single organ system failure) in 20 patients (1.00％),severe complications (organ system failure and invasive procedure under general anesthesia or multisystem organ failure) in 1 patient (0.05％),and mortality was 0.75％ (n=15).Complication severity of Clavien-Dindo system and Accordion system were all correlated with the length of hospital stay,the number of hepatic segments resected,the blood transfusion and the Hospital Anxiety and Depression Scale-Anxiety (HADS-A).The Clavien-Dindo classification system and Accordion classification system are the simple ways of reporting all complications following the liver surgery.

Impact of operative and peri-operative factors on the long-term prognosis of primary liver cancer patients undergoing hepatectomy.

This study examined the impact of the operative and peri-operative factors on the long-term prognosis of patients with primary liver cancer undergoing hepatectomy. A total of 222 patients with primary liver cancer who underwent hepatectomy were followed up from January 1986 to December 2010 at Chinese PLA General Hospital. The post-operative complication rate was 14.0% for all cases, 13.7% for hepatocellular carcinoma (HCC), 10.0% for cholangiocarcinoma. The 1-, 3-, 5- and 10-year overall survival rates in patients with primary liver cancer after resection were 76.6%, 57.6%, 41.4%, and 21.0%. The survival rates were significantly higher in the HCC group than in the cholangiocarcinoma group (P=0.000), in the non-anatomical resection group than in the anatomical resection group (P=0.005), in the female group than in the male group (P=0.002), in patients receiving no blood transfusion than in those who were given intra-operative blood transfusion (P=0.000), in patients whose intra-operative blood loss was less than 400 mL than in those who intra-operatively lost more than 400 mL (P=0.000). No significant difference was found in the survival rate between the HBsAg-positive group and the HBsAg-negative group (P=0.532). Our study showed that anatomical resection, blood loss and blood transfusion were predictors of poor survival after hepatectomy for primary liver cancer patients, and concomitant hepatitis B virus infection bore no relation with the post-resection survival.

[Application of persistent methylene blue dyeing method for anatomic hepatectomy of hepatocellular carcinoma with bile duct tumor thrombi].

OBJECTIVE: To evaluate the role of anatomic hepatectomy of hepatocellular carcinoma with bile duct tumor thrombi by application of persistent methylene blue dyeing method. METHODS: From January 2009 to February 2011, 11 hepatocellular carcinoma patients with bile duct tumor thrombi underwent anatomic hepatectomy with removal of the biliary tumor thrombus. There were 10 male and 1 female patients. The average age was 49 years (ranging from 31 to 67 years). The initial symptom of 9 out of the 11 patients was jaundice. After anatomy and ligation of Glissonean pedicle of pre-resection segment, methylene blue was injected into its far-end portal vein in order to dye the segment. RESULTS: Persistent methylene blue dyeing method was successful in all patients. Primary foci were found in all patients. Hepatectomy were performed, including 4 patients of segmentectomy, 3 patients of subsegmentectomy, 2 patients of hemihepatectomy, and 2 patients of hepatic sectionectomy. The mean operation time and blood loss was 137 minutes and 246 ml respectively. Severe complications such as liver function failure and sub-diaphragm abscess was avoided in all patients. No perioperative death. Post-operation radiotherapy was performed on 2 patients . Over a mean follow-up time of 14.6 months, liver cancer recurrence occurred in 2 patients, abdomen seeding metastasis in 1 patient, bile duct tumor thrombi recurrence in 1 case, and 2 patients died. CONCLUSIONS: Anatomic hepatectomy of hepatocellular carcinoma with bile duct tumor thrombi by application of persistent methylene blue dyeing method can make resection more precise and improve curative effect.

Resection of hepatic caudate lobe hemangioma: experience with 11 patients.

BACKGROUND: Caudate lobectomy is now considered to be the most appropriate surgical treatment for benign tumors in the caudate lobe. But how to resect the caudate lobe safely is a major challenge to current liver surgery and requires further study. This research aimed to analyze the perioperative factors and explore the surgical technique associated with liver resection in hepatic caudate lobe hemangioma. METHODS: Eleven consecutive patients with symptomatic hepatic hemangiomas undergoing caudate lobectomy from November 1990 to August 2009 at our hospital were investigated retrospectively. All patients were followed up to the present. RESULTS: In this series, 9 were subjected to isolated caudate lobectomy and 2 to additional caudate lobectomy (in addition to left lobe and right lobe resection, respectively). The average maximum diameter of tumors was 9.65+/-4.11 cm. The average operative time was 232.73+/-72.16 minutes. Five of the 11 patients required transfusion of blood or blood products during surgery. Ascites occurred in l patient, pleural effusion in the perioperative period in 1, and multiple organ failure in l on the 6th day after operation as a result of massive intraoperative blood loss, who had received multiple transcatheter hepatic arterial embolization preoperatively. The alternating left-right-left approach produced the best results for caudate lobe surgery in most of our cases. All patients who recovered from the operation are living well and asymptomatic. CONCLUSIONS: For large hemangioma of the caudate lobe, surgery is only recommended for symptomatic cases. Caudate lobectomy of hepatic hemangioma can be performed safely, provided it is carried out with optimized perioperative management and innovative surgical technique.

Hepatic resection: an analysis of the impact of operative and perioperative factors on morbidity and mortality rates in 2008 consecutive hepatectomy cases.

BACKGROUND: Hepatectomy is a standard hepatic surgical technique. The safety of hepatectomy has been improved in line with improvements in surgical techniques. This study analyzed the operative and perioperative factors associated with hepatectomy. METHODS: A total of 2008 patients who underwent consecutive hepatectomies between January 1986 and December 2005 were investigated retrospectively. Diagnoses were made based on pathological findings. RESULTS: Malignant and benign liver diseases accounted for 58.5% and 41.2%, respectively, of the conditions requiring resections. Primary liver cancers accounted for 76.1% of the malignant tumors, while hilar cholangiocarcinomas accounted for 6.7%. Hemangiomas (41.7%) and hepatolithiasis (29.6%) were the most common of the benign conditions. Microwave in-line coagulation was used in 236 of our liver resection cases. The overall postoperative complication rate was 14.44%, of which 12.54% of resections were performed for primary liver cancer, 16.40% for secondary liver cancer, and 16.32% for hepatolithiasis. The overall hospital mortality was 0.55%, and that for malignant liver disease was 0.51%. A high mortality (2.53%) was associated with extensive liver resections for hilar cholangiocarcinomas (two deaths in 79 cases). Microwave in-line pre-coagulation resection, Child-Pugh grading, operating time, postoperative length of stay, and preoperative serum albumin level were independent predictors of morbidity. Blood loss, Child-Pugh grading, operating time and preoperative serum albumin level were independent predictors of mortality. CONCLUSIONS: Hepatectomy can be performed safely with low morbidity and mortality, provided that it is carried out with optimal perioperative management and innovative surgical techniques.

Liver resection for benign hepatic lesions: a retrospective analysis of 827 consecutive cases.

AIM: To analyze the operative and perioperative factors associated with hepatectomy of benign hepatic lesions. METHODS: A total of 827 consecutive cases of benign hepatic lesion undergoing hepatectomy from January 1986 to December 2005 in the Chinese PLA General Hospital were investigated retrospectively according to their medical documentation. RESULTS: The effect of operative and perioperative factors on the outcome of patients were analyzed. Of the 827 cases undergoing hepatectomy for more than 3 liver segments accounted for 22.1%, 316 (38.21%) required transfusion of blood products during operation. The average operating time was 220.59 +/- 109.13 min, the average hospital stay after operation was 13.55 +/- 9.38 d. Child-Pugh A accounted for 98.13%. The postoperative complication rate was 13.54% and the in-hospital mortality rate was 0.24%. Multivariate analysis showed that operating time (P = 0.004, OR = 1.003) and albumin value (P = 0.040, OR = 0.938) were the independent predictors of morbidity and indicated that operating time, blood transfusion, complication rate, and LOS had a trend to decrease. CONCLUSION: Hepatectomy for benign hepatic lesions can be performed safely with a low morbidity and mortality, provided that it is carried out with optimized perioperative management and an innovative surgical technique.

[Liver resection: single center experiences of 2008 consecutive resections in 20 years].

OBJECTIVE: To analyze operative and perioperative factors associated with hepatectomy. METHODS: 2008 consecutive patients undergoing hepatectomy from January 1986 to December 2005 at Chinese People's Liberation Army General Hospital were investigated retrospectively according to their medical documentation. Diagnoses were made on basis of pathological results. RESULTS: Malignant and benign liver diseases accounted for 58.5% and 41.2%, respectively. In the former, primary liver cancer accounted for 76.1% and hilar cholangiocarcinoma for 6.7%. Hemangioma (41.7%) and hepatolithiasis (29.6%) were listed in the first two in the latter group with relatively more patient ratios. Isolated caudate lobe resection was performed in 25 patients and micro-wave inline coagulation was induced in 236 cases of liver resection. In all cases, those with blood loss less than 200 ml accounted for 50.5% (1015/2008), whereas those with more than 400 ml accounted for 28.4% (570/2008). In patients performed micro-wave inline coagulation liver resection, those with blood loss less than 200 ml and more than 400 ml accounted for 60.6% (143/236) and 19.9% (47/236), respectively, which differed significantly from the average level (P < 0.05). The postoperative complication incidence was 14.44% for all cases, 12.54% for primary liver cancer, 16.40% for secondary liver cancer, and 16.32% for hepatolithiasis. Complication incidence of primary liver cancer with tumor size smaller than 5 cm was 11.65% and that with tumor larger than 10 cm was 14.69%. There was no significant difference between the two groups. All-case hospital mortality was 0.55% and that for liver malignant disease was 0.60%, hilar cholangiocarcinoma 2.53%. CONCLUSION: Hepatectomy can be performed safely with low mortality and low complication incidence, provided that it is carried out with optimized perioperative management and innovative surgical technique.

[Liver resection in hepatolithiasis: 20-year's evolution].

OBJECTIVE: To analyze operative and perioperative factors associated with hepatectomy in hepatolithiasis. METHODS: 245 consecutive hepatolithiasis patients undergoing hepatectomy from January 1986 to December 2005 at Chinese People's Liberation Army General Hospital were investigated retrospectively according to medical documentation. RESULTS: Hepatolithiasis accounted for 29.6% (245/827) in all benign liver diseases treated with hepatectomy during this time period. There were 88 cases in male and 157 cases in female, the average age was (46.9 +/- 11.3) years. Cases of right liver resection and hepatic segments resection were much more than that in 1963 - 1985. Blood transfusion during operation was given in 45.3% of cases. Complication incidence was 16.3%, with infection 3.3% and bile leakage 2.4%. Length of stay after operation was (15.7 +/- 9.2) days. Perioperative mortality rate was 0.4% (1/245). CONCLUSIONS: Individualized hepatectomy is the important surgical treatment of hepatolithiasis. Hepatectomy can be performed safely with low mortality and low complication incidence, provided that it is carried out with optimized perioperative management and innovative surgical technique.

Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines.

AIM: To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitro, and to investigate the perspective of histone deacetylase inhibitor in its clinical application. METHODS: The survival rates of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazoy tetrazolium (MTT) assay. A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured. RESULTS: TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, the growth of cancer was inhibited in the model after treated with TSA. CONCLUSION: TSA can inhibit the growth of cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.

A clinicopathological analysis in unsuspected gallbladder carcinoma: a report of 23 cases.

AIM: To study the clinicopathological characteristics of unsuspected gallbladder carcinoma (UGC). METHODS: We retrospectively studied 23 cases of UGC in Tongji Hospital, and compared their clinicopathological characteristics with 33 cases of preoperatively diagnosed gallbladder carcinoma (PDGC). RESULTS: The proportion of UGC coexisting with cholecystolithiasis was significantly higher than that of PDGC (chi(2) = 13.53, P < 0.01). The infection rate of hepatitis B virus was 21.74% (5/23) in UGC and 30.30% (10/33) in PDGC. Nine (39.13%) of 23 patients with UGC and 8/33 (24.24) PDGC had contact with schistosome pestilent water. The rate of multiple pregnancies was 56.52% (13/23) in the patients with UGC and 42.42% (14/33) in PDGC. The primary location of the UGC was mostly in the neck and body of the gallbladder, and that of the PDGC was often in the body and bottom. The incidence of Nevin stage I and II UGC was significantly higher than that of PDGC (chi(2) = 4.44, P < 0.05 and chi(2) = 4.96, P < 0.05) while that of Nevin stage V UGC was significantly lower than that of PDGC (chi(2) = 7.59, P < 0.01). According to the grading of carcinoma, the incidence of well-differentiated UGC was significantly higher than that of PDGC (chi(2) = 4.16, P < 0.05), and that of poorly-differentiated UGC was significantly lower than that of PDGC (chi(2) = 4.48, P < 0.05). CONCLUSION: There are different characteristics between UGC and PDGC, such as in primary location, malignant degree and incidence of coexistence with cholecystolithiasis. Cholecystolithiasis, hepatitis B, schistosome and multiple pregnancies were high risk factors for gallbladder carcinoma.

Effect of antisense DNMT3b gene eukaryotic expression plasmid on expression of the DNMT3b gene in human biliary tract carcinoma cells.

BACKGROUND: Hypermethylation of the promoter region is one of the major mechanisms of tumor suppressor gene inactivation. DNA methyltransferase 3b (DNMT3b), an enzyme that participates in the establishment of de novo methylation patterns, is highly expressed in many tumor cells and tissues, and it is closely associated with hypermethylation of the promoter of tumor suppressor genes. The aim of this study was to explore the effect of transfection with antisense DNMT3b gene eukaryotic expression plasmid on the expression of the DNMT3b gene in human biliary tract carcinoma cell. METHODS: The constructed antisense DNMT3b gene eukaryotic expression plasmid was transfected into the human biliary tract carcinoma cell line QBC-939 with lipofectamine transfection reagent, and positive cell clones were formed using G418 selection after transfection. The constructed recombinant plasmid was transfected into QBC-939 cells successfully and was confirmed by amplification of the exogenous neoR gene with the polymerase chain reaction method. The expression of DNMT3b gene mRNA and protein was detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry respectively. RESULTS: Following transfection, the mRNA level of the DNMT3b gene decreased from 0.956+/-0.053 to 0.209+/-0.023, and the protein level of the DNMT3b gene also decreased from (75.38+/-3.22)% to (29.87+/-3.46)%. Very significant differences were observed both at the transcription and post-transcription levels in the expression of the DNMT3b gene between the non-transfection group and the antisense DNMT3b gene eukaryotic expression plasmid transfection group (P<0.01). CONCLUSIONS: Transfection with the antisense DNMT3b gene eukaryotic expression plasmid can significantly reduce the expression level of the DNMT3b gene in the human biliary tract carcinoma cell line QBC-939. This study may provide a valid method to investigate the function of the DNMT3b gene and its role in biliary tract carcinoma.

Hepatic injury in rats with obstructive jaundice: roles of the protein kinase C signal pathway and cytoprotection of fructose.

BACKGROUND: Fructose is cytoprotective during bile salt-induced apoptosis of hepatocytes by regulating protein kinase C (PKC). This study was undertaken to explore the regulating mechanism of hepatic injury in rats with obstructive jaundice, and to detect the PKC signal pathway. METHODS: Rat hepatocytes were isolated by in situ collagenase perfusion and primary culture, and pretreated with various concentrations of PKC agonist phorbol myristate acetale (PMA) and inhibitor chelerythrine for 20 minutes. After pretreatment, 50 mumol/L glycochenodeoxycholate (GCDC) was added for additional 24 hours. Subsequently, the cells were detected by FCM and TUNEL. After adding with different concentrations of fructose and 100 mumol GCDC, the hepatocytes were evaluated by FCM and TUNEL. Experimental obstructive jaundice was induced with fructose and without fructose via double ligation of the bile duct for 3, 7, 14, and 21 days. Apoptotic status in the liver of all rats was detected with TUNEL, and PKC protein in the liver of obstructive jaundice (OJ) with the immunohistochemistry method. RESULTS: PMA increased GCDC-induced apoptosis and chelerythrine decreased GCDC-induced apoptosis in a concentration-dependent manner. Adding with different concentration of fructose and 100 mumol GCDC, the decreased apoptotic rate was related to the concentration of fructose. The apoptotic rate of the liver was related to times of OJ. PKC and apoptosis index (AI) were the highest after a 14-day ligation of the bile duct without use of fructose. AI and PKC were decreasing from a 14-day ligation of the bile duct with fructose. CONCLUSIONS: PKC takes part in the regulation, occurrence, and progression of hepatic injury in OJ. Fructose is cytoprotective during bile salt-induced apoptosis of hepatocytes by regulating PKC.

Action and mechanism of Fas and Fas ligand in immune escape of gallbladder carcinoma.

AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor escape. METHODS: Streptavidin-biotin-peroxidase immunohistochemistry technique was used to study the expression of Fas and FasL protein in 26 gallbladder carcinoma tissues, 18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20 chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared with clinicopathological features of gallbladder carcinoma. RESULTS: The positive rates of Fas were not significantly different among carcinoma, adenoma, dysplasia and chronic cholecystitis. The positive rate of FasL in carcinoma was significantly higher than that in chronic cholecystitis (chi(2) = 4.89, P<0.05). The apoptotic index (AI) in carcinoma was significantly higher than that in adenoma (t' = 4.19, P<0.01) and chronic cholecystitis (t' = 8.06, P<0.01). The AI was significantly lower in well-differentiated carcinoma and Nevin I-III carcinoma than that in poorly-differentiated carcinoma (t' = 2.63, P<0.05) and Nevin IV-V carcinoma (t' = 3.33, P<0.01). The confidence interval (CI) of infiltrating lymphocytes in adenoma, chronic cholecystitis, well-differentiated carcinoma and Nevin I-III carcinoma was very significantly lower than that in carcinoma (t' = 6.99, P<0.01), adenoma (t' = 3.66, P<0.01), poorly-differentiated carcinoma (t' = 5.31, P<0.01) and Nevin IV-V carcinoma (t' = 3.76, P<0.01), respectively. The CI of apoptosis of infiltrating lymphocytes in well-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma (t = 2.52, P<0.05), and was not significantly lower in Nevin I-III carcinoma than in Nevin IV-V carcinoma (t = 1.42, P>0.05). Apoptosis of infiltrating lymphocytes was not discovered in adenoma and chronic cholecystitis. CONCLUSION: FasL expressed in gallbladder carcinoma cells permits tumor cells to escape from immune surveillance of organism by inducing apoptosis in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma.