Contrast of therapeutic effects between CBD incision and LLHD stump in biliary tract exploration of LLS for hepatolithiasis.

BACKGROUND: Laparoscopic left lateral sectionectomy (LLS) followed by a biliary tract exploration is used to treat left lateral hepatolithiasis. The purpose of this study was to compare the efficacy of two methods of biliary tract explorations in LLSs: biliary tract exploration through a common bile duct (CBD) incision or through the left lateral hepatic duct (LLHD) stump. METHODS: One hundred eight patients were retrospectively analyzed in our hospital from 2009 to 2018. To compare different methods of biliary tract explorations during LLSs, the patients were divided into 2 groups: 36 patients underwent biliary tract exploration through the LLHD stump (LLSS group), and 72 patients underwent biliary tract exploration through the CBD incision (LLSC group). Clinical data on disease characteristics, surgical outcomes, and surgery-related complications were compared between the 2 groups. RESULTS: Bile duct stones were successfully cleared in all patients. For 2 patients in the LLSS group and 3 patients in the LLSC group, treatment was switched to laparotomy. There were no significant differences in the total operation time (P = 0.09), incidence of bleeding volume (P = 0.33), and bile leakage (P = 0.12) between the two groups. The time of choledochoscopy in the LLSS group was significantly lower than that in the LLSC group (P = 0.03). No bile duct injuries, strictures, recurrent stones, or other adverse events were observed in any patients during follow-up. CONCLUSIONS: Exploration of the biliary tract through the LLHD stump is safe and provides satisfactory results for select patients.

miR-186 modulates hepatocellular carcinoma cell proliferation and mobility via targeting MCRS1-mediated Wnt/ß-catenin signaling.

Previous studies have revealed that miR-186 is involved in the pathogenesis of many malignancies. However, the role of miR-186 in hepatocellular carcinoma (HCC) carcinogenesis and its detailed mechanism are poorly understood. This study was to investigate the function of miR-186 in modulating HCC cell proliferation, cell cycle, migration, and invasion. We found that miR-186 was decreased in HCC tissues and cell lines. Loss-of-function experiments showed that reduction of miR-186 dramatically enhanced tumor cell proliferation and metastasis. Besides, miR-186 also participated in the modulation of the cell cycle. In addition, luciferase reporter assays and Western blot analysis showed that MCRS1 was a novel target of miR-186 in HCC cells. Notably, upregulation of miR-186 suppressed the nuclear ß-catenin accumulation and blocked the activation of Wnt/ß-catenin signaling in HCC cells. Forced MCRS1 expression abrogated the inhibitory effect of miR-186 on cell growth, metastasis and Wnt/ß-catenin signaling in HCC cells. Our findings may provide new insight into the pathogenesis of HCC and miR-186/ MCRS1 might function as new therapeutic targets for HCC.

Complication Analysis with Percutaneous Postoperative Choledochoscopy in 826 Patients: A Single-Center Study.

Background: Advances in choledochoscopy technology lead to an improvement in the treatment of hepatolithiasis. The aim of this study is to analyze the complications and efficacy of percutaneous postoperative choledochoscopy (PPOC) for residual stones. Materials and Methods: Retrospective analysis of patients who underwent PPOC for residual stones. Main outcome measures included the rate of stone removal and postoperative complications. Results: Eight hundred twenty-six patients received PPOC. The average duration of choledochoscopy was 30 min (range, 14-42 min). Complications included basket incarceration, T-tube dislodgement, bleeding, bile leaks, and infection. Residual stone clearance rate was achieved in 97% of the cases. Conclusions: PPOC is a safe and effective approach for residual stones.

Fli­1 promotes metastasis by regulating MMP2 signaling in hepatocellular carcinoma.

Friend leukemia virus integration 1 (Fli­1) is a newly identified ETS protein, and has critical roles in many malignancies. However, the physiological characters and potential mechanisms of Fli­1 in hepatocellular carcinoma (HCC) progression remains unclear. In the present study, Fli­1 was highly expressed in HCC samples and tumor cell lines. knockdown of Fli­1 with small interfering (si)RNAs significantly reduced the colony formation and metastasis capacity of HCC cell lines in vitro. Subsequent investigation identified that Fli­1 functioned as an oncogene in HCC carcinogenesis and it exerted its promoting metastatic effect primarily by modulating the matrix metalloproteinase (MMP)2 signaling pathway. Collectively, these data provide a novel insight into the mechanism of Fli­1/MMP2 signaling pathway in the pathogenesis of HCC, and Fli­1 may serve as a novel therapeutic target for HCC.

Association and Intragenic Single-Nucleotide Polymorphism Interactions of the XRCC1 Polymorphisms for Pancreatic Cancer Susceptibility.

OBJECTIVES: X-ray repair cross-complementing group 1 (XRCC1) gene is an important candidate gene for influencing human cancer risks. This study examined the main and interactive effect of 9 single-nucleotide polymorphisms (SNPs) (Arg194Trp, Arg280His, Arg399Gln, c.1254C>T, c.1517G>C, c.1471G>A, C310T, 539del542, and T1915C) of XRCC1 in contribution to pancreatic cancer (PC). METHODS: A total of 298 PC patients and 298 healthy controls were enrolled. Selected SNPs in XRCC1 were genotyped. The generalized multifactor dimensionality reduction method investigated gene-gene interactions. RESULTS: Single-locus analyses showed that, in the codominant model, the GO genotype of 539del542 might have a higher risk for PC (odds ratio [OR], 1.47; 95% confidence interval [95% CI], 1.05-2.08). For T1915C polymorphism, the TC and CC genotypes both had a higher risk for PC (OR, 1.76; 95% CI, 1.25-2.48; OR, 1.83; 95% CI, 1.05-3.19, respectively); and a similar result was observed in the dominant model (OR, 1.77; 95% CI, 1.28-2.46). A tendency of association between Arg280His and PC was also detected in the dominant model (OR, 0.70; 95% CI, 0.48-1.00). Furthermore, the generalized multifactor dimensionality reduction method showed that the 4-locus model was significant, involving Arg280His, 539del542, T1915C, and c.1517G>C (P < 0.05). CONCLUSIONS: Thus, XRCC1 polymorphisms may contribute to the risk of PC independently or in an interactive manner.

TGF-ß1 Reduces miR-29a Expression to Promote Tumorigenicity and Metastasis of Cholangiocarcinoma by Targeting HDAC4.

UNLABELLED: Transforming growth factor ß1 (TGF-ß1) and miRNAs play important roles in cholangiocarcinoma progression. In this study, miR-29a level was found significantly decreased in both cholangiocarcinoma tissues and tumor cell lines. TGF-ß1 reduced miR-29a expression in tumor cell lines. Furthermore, anti-miR-29a reduced the proliferation and metastasis capacity of cholangiocarcinoma cell lines in vitro, overexpression of miR-29a counteracted TGF-ß1-mediated cell growth and metastasis. Subsequent investigation identified HDAC4 is a direct target of miR-29a. In addition, restoration of HDAC4 attenuated miR-29a-mediated inhibition of cell proliferation and metastasis. CONCLUSIONS: TGF-ß1/miR-29a/HDAC4 pathway contributes to the pathogenesis of cholangiocarcinoma and our data provide new therapeutic targets for cholangiocarcinoma.

miR-216a may inhibit pancreatic tumor growth by targeting JAK2.

This study was aimed to investigate miR-216a expression in pancreatic cancer and determine its effects on proliferation. miR-216a was found downregulated in pancreatic cancer tissues as compared to benign pancreatic lesions. JAK2 was identified as a miR-216a gene target. Further, in vivo treatment of PANC-1 tumors with miR-216a reduced JAK2 protein levels in the tumor and reduced tumor volume. In conclusion, miR-216a may function as a tumor suppressor regulating pancreatic cancer cells by targeting the JAK/STAT pathway. Further studies with a larger number of patient samples are necessary to fully explore the diagnostic and therapeutic potential of miR-216a for pancreatic cancer.

[Application of three-dimensional visualization technology for laparoscopic resection of cystic carcinoma in the pancreatic body and tail].

OBJECTIVE: To study the application of three-dimensional visualization technology for laparoscopic resection of cystic carcinoma in the pancreatic body and tail. METHODS: Six cases of cystic carcinoma in the pancreatic body and tail treated between Nov, 2009 and Mar, 2011 were retrospectively analyzed. The original image data of 64-slice spiral CT were collected and using adaptive region growing algorithm, the serial CT images were segmented and automatically extracted to obtain the 3-dimensional reconstruction images with customized image manipulation software. The specific surgical approach (the trocar position) and surgical procedure were planned based on the reconstructed mode. RESULTS: The reconstructed 3-dimensional model clearly displayed cystic carcinoma in the pancreatic body and tail and the adjacent organs, showing distinct relationship between the cystoma and the splenic artery and vein. All the patients successfully underwent laparoscopic resection of the pancreatic body and tail without perioperative death. The spleen was preserved in 5 cases and removed in 1 case due to mucinous cystadenocarcinoma. The overall rate of pancreatic fistulae was 33.3% without incidences of postoperative hemorrhage. The average hospital stay of the patients was 12 days. CONCLUSION: Three-dimensional reconstruction based on pancreatic CT data provides valuable assistance for laparoscopic resection of cystic carcinoma in the pancreatic body and tail.

Protein kinase C beta mediates CD40 ligand-induced adhesion of monocytes to endothelial cells.

Accumulating evidence supports the early involvement of monocyte/macrophage recruitment to activated endothelial cells by leukocyte adhesion molecules during atherogenesis. CD40 and its ligand CD40L are highly expressed in vascular endothelial cells, but its impact on monocyte adhesion and the related molecular mechanisms are not fully understood. The present study was designed to evaluate the direct effect of CD40L on monocytic cell adhesion and gain mechanistic insight into the signaling coupling CD40L function to the proinflammatory response. Exposure of cultured human aortic endothelial cells (HAECs) to clinically relevant concentrations of CD40L (20 to 80 ng/mL) dose-dependently increased human monocytic THP-1 cells to adhere to them under static condition. CD40L treatment induced the expression of vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein expression in HAECs. Furthermore, exposure of HAECs to CD40L robustly increased the activation of protein kinase C beta (PKCß) in ECs. A selective inhibitor of PKCß prevented the rise in VCAM-1 and THP-1 cell adhesion to ECs. Moreover, stimulation of ECs to CD40L induced nuclear factor-κB (NF-κB) activation. PKCß inhibition abolished CD40L-induced NF-κB activation, and NF-κB inhibition reduced expression of VCAM-1, each resulting in reduced THP-1 cell adhesion. Our findings provide the evidence that CD40L increases VCAM-1 expression in ECs by activating PKCß and NF-κB, suggesting a novel mechanism for EC activation. Finally, administration of CD40L resulted in PKCß activation, increased VCAM-1 expression and activated monocytes adhesiveness to HAECs, processes attenuated by PKCß inhibitor. Therefore, CD40L may contribute directly to atherogenesis by activating ECs and recruiting monocytes to them.

[Expression of miR-216a in pancreatic cancer and its clinical significance].

OBJECTIVE: To explore the clinical significance of miRNA-216a expression in pancreatic cancer. METHODS: Fourteen patients with pancreatic cancer undergoing pancreaticoduodenectomy and 6 patients with benign pancreas lesions were examined for miR-216a expressions in the tumor or lesion tissues using Agilent Human miRNA Microarray (V12.0). The relationship between miR-216a expressions and the clinicopathological features of the patients was analyzed. RESULTS: The expression of miRNA-216a was significantly lower in pancreatic cancer than in benign pancreas lesions (P=0.000). The expression of miRNA-216a was significantly correlated with the T stage of the tumor (P=0.002), but not with the patients' age, gender, smoking status, tumor stage, lymph node metastases, distant metastasis, tumor differentiation, nerve invasion, vessel invasion or serum CA19-9 level (P>0.05). CONCLUSIONS: The down-regulated expression of miR-216a in pancreatic cancer suggests the involvement of miR-216a in the tumorigenesis and development of pancreatic cancer. miR-216a may potentially serve as a novel tumor marker and also a prognostic factor for pancreatic cancer.

[The diagnosis and therapy of pancreatic cystic tumors].

OBJECTIVE: To discuss the surgical option and the treatment of complications of pancreatic cystic tumors. METHODS: From January 1997 to December 2009, 32 patients with pancreatic cystic tumors in our center were reviewed retrospectively. There were 6 male and 26 female, aging from 24 to 76 years. Of the 32 patients, 16 patients had serous cystadenoma, 9 patients had mucinous cystadenoma; 1 patients had mucinous cystadenocarcinoma; 4 patients had intraductal papillary mucinous neoplasms and 3 patients had pancreatic solid pseudopapillary neoplasms. Tumor located in pancreatic head in 12 patients and in pancreatic body and tail in 20 patients. RESULTS: All patients received surgical treatment and there was no perioperative death. Pancreato-duodenectomy was performed in 10 patients, duodenum-preserving pancreatic head resection in 1 patient, distal pancreactomy in 13 patients, including laparoscopic distal pancreactomy in 2 patients, pancreatic tumor resection in 3 patients, middle segmental resection in 4 patients; 1 patients with mucinous cystadenocarcinoma received palliative surgery. Complication included gastroparesis in 3 patients and pancreatic fistula in 5 patients, and all recovered by conservative treatment. These 29 patients were followed up 4 - 120 months, 3 patients died from tumor metastasis or other disease within 4 to 34 months after surgery. Others were alive and there was no tumor recurrence or metastasis. CONCLUSIONS: CT scan should be the first choice of non-invasive examination for cystic pancreatic diagnosis. Positive and timely operation should be performed in the patient with cystic pancreatic tumor, and it acts as a cancer preventive treatment. The selection of surgical approach should be individualized, the principal of damage control surgery should be followed. Complications such as gastroparesis and pancreatic fistula should be paid more attention.

[Effects of early goal-directed fluid therapy on intra-abdominal hypertension and multiple organ dysfunction in patients with severe acute pancreatitis.].

OBJECTIVE: To observe the effects of early goal-directed fluid therapy with hydroxyethyl starch 130/0.4 on intra-abdominal hypertension (IAH), multiple organ dysfunction and fluid balance in severe acute pancreatitis (SAP) patients. METHODS: According to the criteria of selection and exclusion, 120 SAP patients within 72 hours after the symptom occurred from 4 study sites were recruited. They were given standard medication according to "the guideline of diagnosis and treatment of SAP in China" in SICU or PICU. The patients were randomly divided into two groups with crystalloid (control group) and colloid plus crystalloid resuscitation (research group). The objective of fluid therapy was to keep steady hemodynamics for 8 days. IAP was measured three times daily by means of urinary bladder transduction. Function of liver, renal and lung were detected daily. APACHE II score and fluid balance were calculated daily. RESULTS: Total 120 cases were recruited into research group (n = 59) and control group (n = 61). The demography and baseline data were comparable. IAP was lower in research group than that in control group at day 4 and day 5 (P < 0.05). There was no significant difference in APACHE II scores between two groups pre- and after admission. The decline of daily IAP to baseline (DeltaIAP) in research group was significantly higher than in research group from day 2 to day 8(P < 0.05), whilst the decline of daily APACHE II score to baseline (DeltaAPACHE II score) in research group were significantly higher from day 4 to day 8 (P < 0.05). Negative fluid balance emerged much earlier in the research group (P = 0.036). Percentage of patients with negative fluid balance within 8 days was significantly higher in research group than that in control group (94.9% vs. 62.3%). The amount of positive fluid balance was significantly lower in research group (P = 0.039). IAP correlated significantly with APACHE II score (r(2) = 0.322, P = 0.000). PaO2/FiO2 was significantly higer in research group at day 4 and day 8. CONCLUSIONS: It is very important to pay close attention to IAP in early fluid therapy of SAP patients. Early goal-directed fluid therapy with HES130/0.4 shortens the duration of positive fluid balance, decreases the amount of positive fluid balance, reduces APACHE II score, relieves IAH, and improves PaO2/FiO2.

[A survey of bile duct injuries sustained during laparoscopic cholecystectomy].

OBJECTIVE: To summarize the reasons for bile duct injury (BDI) after laparoscopic cholecystectomy (LC), and to determine the effect of multiple treatment after BDI. METHODS: A retrospective cohort study was performed. The medical records of 110 patients diagnosed with BDI after LC from October 1993 to November 2007, in ten large hospitals in Guangdong of China, were reviewed. RESULTS: Among 110 patients with BDI, 58 cases (52.7%) were local patients, whereas 52 cases (47.3%) were transferred from outside hospitals. Reasons for BDI following LC were: (1) Lack of experience of the LC operator (48.2%); (2) LC performed during acute cholecystitis (20.0%); (3) The structure of Calot triangle was unclear (15.5%); (4) Variable anatomical position (11.8%); (5) Intra-operation bleeding (4.5%). The commonest sites of injury were the choledochus and common hepatic duct (76.4%). Following BDI, endoscopic stenting or operative repair was performed in 106 patients. The overall success rate was 95.3% (101/106), with a mortality rate was 0.9% (1/106). Cholangitis occurred in 3.8% (4/106) cases. Choledocho-enterostomy operation was performed in almost 60.0% (63/106) cases, and the success rate was 93.7% (59/63). Endoscopic stenting or operative repair was performed immediately following BDI in 23.6% (25/106) patients, the success rate was 100%; and within 30 days in 63.2% (67/106) patients. Eighty-eight out of 106 patients who underwent repair were successful following the first operative procedure. CONCLUSIONS: Factors such as an un-experienced operator and unclear anatomical position were causes of BDI following LC. Early operative repair should be regarded as the treatment of choice, in patients diagnosed with BDI. Early refer to an experienced hepatobiliary operator ensures a high success rate.

[Value of perioperative adjuvant therapy in liver transplantation for advanced hepatocellular carcinoma].

OBJECTIVE: To evaluate the clinical value of perioperative adjuvant chemotherapy in prevention of tumor recurrence and improvement of patient survival after liver transplantation for advanced hepatocellular carcinoma (HCC). METHODS: Twenty patients with advanced HCC (pTNM stages III and IV a) receiving liver transplantation with preoperative transcatheter arterial chemoembolization (TACE) and postoperative adjuvant chemotherapy (ADM+5-Fu+CDDP) were retrospectively reviewed in comparison with 16 patients receiving liver transplantation only for tumor recurrence, cumulative and tumor-free survivals. The feasibility and side-effects of the treatments were also studied. RESULTS: The recurrence rate was lower in the perioperative treatment group than in non-treatment group (12/20, 60.0% vs 11/16, 87.5%, P<0.05). The 1- and 2-year overall survival rates were 70.8% and 47.1% for the chemotherapy group and 43.8% and 20.5% for the non-chemotherapy group respectively, showing significant differences between them (P<0.05). The 1- and 2-year tumor-free survival rates were 60.6%, 40.5% and 33.6%, 15.6% in the two groups, respectively, with also significant differences (P<0.05). CONCLUSIONS: Perioperative adjuvant treatment may significantly decrease the likeliness of tumor recurrence and prolong the survival of patients with advanced HCC after liver transplantation. Chemotherapy with ADM+5-Fu+CDDP can be effective and safe with only mild side-effects.

A new technique of hepatic segmentectomy by selective portal venous occlusion using a balloon catheter through a branch of the superior mesenteric vein.

BACKGROUND: We describe a new technique of segment-based liver resection by inserting a 6 French balloon catheter into the portal vein via a branch of the superior mesenteric vein. MATERIALS AND METHODS: The catheter was guided into the relevant portal branch supplying the liver segment that contained the tumor. Injection of methylene blue through the catheter delineated the liver segment(s) to be resected. This operation was carried out on 48 patients with a 0% in-hospital mortality. RESULTS: The 5-year overall survival was 52.1% and the 5-year disease-free survival was 20.8%. CONCLUSIONS: Our experience showed this technique to be a viable alternative for anatomical liver segmentectomy.

Surgical treatment of patients with intermediate-terminal pancreatic cancer.

AIM: To investigate the surgical treatment of patients with intermediate-terminal pancreatic cancer. METHODS: A retrospective analysis was made of the clinical data of 163 patients with intermediate-terminal pancreatic cancer who were surgically treated between August 1994 and August 2003. RESULTS: A total of 149 patients underwent palliative surgery. The mortality rate of those who underwent cholecystojejunostomy alone was 14.2%, the icterus or cholangitis recurrence rate was 61.9% with an average survival period of 7.1 mo. The mortality rate for those who received hepatic duct-jejunostomy (HDJS) was 5.7%, the icterus or cholangitis recurrence rate was 6.8% with an average survival period of 7.1 mo. But 31.8% of the patients developed duodenum obstruction within 6 mo after the surgery, six of seven patients with severe pain were given peri-abdominal aorta injection with absolute alcohol and their pain was alleviated. The other patients underwent percutaneous transhepatic cholangial drainage (PTCD) and their icterus index returned to normal level within 40 d with an average survival period of 7.5 mo. CONCLUSION: Roux-en-Y HDJS combined with prophylactic gastrojejunostomy is recommended for patients with intermediate-terminal pancreatic cancer, and biliary prosthesis can partly relieve biliary obstruction in a short term.

[Treatment and surgery of primary hepatic cancer with portal vengus tumor thrombosis].

OBJECTIVE: To study the methods of surgery for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (TTPV). METHODS: To Analyze and summarize the clinical information from 138 HCC patients with tumor thrombi in portal vein collected during January 1990 and January 2003. RESULTS: Thirty-seven patients receiving palliative therapy died from 1 to 8 months, and average survival time is 3.9 months. 101 patients had operation treatment, 23 of them underwent hepatoma resection, and average survival time was 10.9 months; 78 patients underwent hepatoma resection and removal of tumor thrombi, and average survival time was 26.8 months. 52 of whom underwent hepatic artery and portal vein chemoembolization, the 1-, 3-, 5-year survival rates was 96.2%, 51.9%, 11.5%, the 1-, 3-, 5-year survival rates of the 26 patients who didn't undergo chemoembolization were 76.9%, 23.1%, 0%. CONCLUSIONS: Operation treatment can comparatively extend the survival time of hepatocellular carcinoma with tumor thrombi in portal vein patients, and the best choice is hepatoma resection and removal of tumor thrombi, hepatic artery and portal vein chemoembolization after operation can enhance the effect.

[Surgical treatments for hilar cholangiocarcinoma].

OBJECTIVE: To explore the diagnosis and surgical treatment of hilar cholangiocarcinoma. METHODS AND RESULTS: Of 102 patients with hilar cholangiocarcinoma, 21 (20.6%) underwent surgical exploration and biopsy with an average survival time of 72 d, 18 (17.6%) received drainage with that of 8.3 months, and 63 (61.8%) were subjected to surgical resection and anastomosis with that of 25.7 months. The surgical approaches included resections of the perihepatic cholangiocarcinoma, of the quadrate lobe and outer bile ductule carcinoma, of the left half of the liver, of the caudal lobe and outer bile ductule carcinoma, and Roux-en-Y ligation of the intraheptic bile ductule-jeajunum. CONCLUSIONS: Resection is a the primary choice for treatment of hilar cholangiocarcinoma, and radical resection may prolong the patients' survival time and achieve better effect than simple drainage. In cases where resection is impossible, jaundice management should be carried out.

Biological effect of ectopic expression of angiopoietin-1 and -2 in hepatocellular carcinoma cell line.

OBJECTIVES: To observe the biological effect of ectopic expression of angiopoietin-1 and -2 cDNA on SMMC7721 hepatocellular carcinoma cell line and study the possible role of the angiopoietin gene in the growth or metastasis of implantation carcinoma. METHODS: Angiopoietin-1 and -2 cDNA were subcloned into the pcDNA3 vector and subsequently transfected into a human SMMC7721 hepatocellular carcinoma (HCC) cell line without detectable angiopoietin gene expression before transfection. Then HCC cells were injected subcutaneously into 30 nude mice and the tumor growth speed and amount of newborn vasculature in the HE stained tissue were observed every 2 days till 3 weeks or the death of animals. RESULTS: The tumor grew faster with angiopoietin-2 expression; much more blood vessels were seen in the tumor tissue than that without angiopoietin-2 expression. Angiopoietin-1 gene expression seems to have no obvious effect on the increase of vasculature and tumor growth. CONCLUSIONS: The angiopoietin gene may play a role in the growth and progression of HCC and angiopoietin-2 seems to promote the angiogenesis of the tumor.