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1.
World J Gastrointest Surg ; 15(11): 2413-2422, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38111760

ABSTRACT

BACKGROUND: Gallbladder cancer (GC) is a common malignant tumor and one of the leading causes of cancer-related death worldwide. It is typically highly invasive, difficult to detect in the early stages, and has poor treatment outcomes, resulting in high mortality rates. The available treatment options for GC are relatively limited. One emerging treatment modality is hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC involves delivering heated chemotherapy directly into the abdominal cavity. It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions, aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity. AIM: To determine the effects of cytoreductive surgery (CRS) combined with HIPEC on the short-term prognosis of patients with advanced GC. METHODS: Data from 80 patients treated at the Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed. The control group comprised 44 patients treated with CRS, and the research group comprised 36 patients treated with CRS combined with HIPEC. Then, the survival time and prognostic factors of the two groups were compared, as well as liver and kidney function indices before and six days after surgery. Adverse reactions and complications were recorded in both groups. RESULTS: The baseline data of the research and control groups were similar (P > 0.05). Six days after surgery, the alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups (P < 0.05). However, the values did not differ between the two groups six days postoperatively (P > 0.05). Similarly, the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups (P < 0.05), but they did not differ between the groups six days postoperatively (P > 0.05). Furthermore, the research group had fewer postoperative adverse reactions than the control group (P = 0.027). Finally, a multivariate Cox analysis identified the tumor stage, distant metastasis, and the treatment plan as independent factors affecting prognosis (P < 0.05). The three-year survival rate in the study group was higher than that in the control group (P = 0.002). CONCLUSION: CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.

2.
Oncol Lett ; 16(3): 3593-3602, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30127966

ABSTRACT

There is not yet a consensus regarding a difference in prognosis for patients with hepatocellular carcinoma (HCC) with and without bile duct invasion (BDI). The present study aimed to clarify the prognostic importance of BDI on the short and long-term outcome of patients with HCC who underwent surgical resection. The present study evaluated HCC with BDI, including peripheral microscopic biliary invasion and revealed that the prognosis of patients with BDI was poorer compared with those without BDI. It should be noted that peripheral BDI also had a negative impact on the prognosis of patients with HCC. The clinical prognosis assessment revealed that BDI should be considered when assigning a disease stage. BDI, either macroscopic or microscopic, indicated a poor prognosis in patients with HCC who underwent curative resection, however it was not a surgical contraindication. Macroscopic BDI and hyperbilirubinemia were significantly associated with a dismal prognosis, which should alert surgeons.

3.
Hepatobiliary Pancreat Dis Int ; 17(2): 163-168, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29567046

ABSTRACT

BACKGROUND: Postoperative pancreatic fistula (POPF) is a severe complication of the pancreaticoduodenectomy (PD). Recently, we introduced a method of suspender pancreaticojejunostomy (PJ) to the PD. In this study, we retrospectively analyzed various risk factors for complications after PD. We also introduced and assessed the suspender PJ to demonstrate its advantages. METHODS: Data from 335 patients with various periampullary lesions, who underwent the Whipple procedure (classic Whipple procedure or pylorus-preserving) PD by either traditional end-to-side invagination PJ or suspender PJ, were analyzed. The correlation between either perioperative or postoperative complications and corresponding PD approaches was evaluated by univariate analysis. RESULTS: A total of 147 patients received the traditional end-to-side invagination PJ, and 188 patients were given the suspender PJ. Overall, 51.9% patients had various complications after PD. The mortality rate was 2.4%. The POPF incidence in patients who received the suspender PJ was 5.3%, which was significantly lower than those who received the traditional end-to-side invagination PJ (18.4%) (P < 0.001). Univariate analysis showed that PJ approach and the pancreas texture were significantly associated with the POPF incidence rate (P < 0.01). POPF was a risk factor for both postoperative abdominal cavity infection (OR = 8.34, 95% CI: 3.99-17.42, P < 0.001) and abdominal cavity hemorrhage (OR = 4.86, 95% CI: 1.92-12.33, P = 0.001). CONCLUSIONS: Our study showed that the impact of the pancreas texture was a major risk factor for pancreatic leakage after a PD. The suspender PJ can be easily accomplished and widely applied and can effectively decrease the impact of the pancreas texture on pancreatic fistula after a PD and leads to a lower POPF incidence rate.


Subject(s)
Digestive System Neoplasms/surgery , Pancreatic Fistula/surgery , Pancreaticoduodenectomy/adverse effects , Pancreaticojejunostomy/methods , Aged , Chi-Square Distribution , China/epidemiology , Digestive System Neoplasms/mortality , Digestive System Neoplasms/pathology , Female , Humans , Incidence , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Pancreatic Fistula/diagnostic imaging , Pancreatic Fistula/etiology , Pancreatic Fistula/mortality , Pancreaticoduodenectomy/mortality , Pancreaticojejunostomy/adverse effects , Pancreaticojejunostomy/mortality , Retrospective Studies , Risk Factors , Treatment Outcome
4.
Oncotarget ; 8(20): 32523-32535, 2017 May 16.
Article in English | MEDLINE | ID: mdl-28430645

ABSTRACT

Midkine is overexpressed in hepatocellular carcinoma (HCC) and plays a role in tumor progression, but less is known about its role in resistance of circulating tumor cells (CTCs) to anoikis which leading to recurrence and metastasis. The aim of the present study was to analyze whether midkine was associated with HCC progression with anoikis resistance. We found that cultured HCC cells were more resistant to anoikis, which paralleled midkine expression, and midkine treatment significantly inhibited anoikis in a dose-dependent manner. Furthermore, in in vitro and in vivo assays, knockdown of midkine resulted in significant sensitivity to anoikis, decreased cell survival and significantly decreased tumor occurrence rate. Patients with midkine-elevated HCC had higher CTC counts and less apoptotic CTCs, as well as significantly higher recurrence rate and shorter recurrence-free interval. To understand the molecular mechanism underlying the midkine with HCC progression, we performed in vitro and in vivo studies. We found that midkine plays an important role in enhancement of HCC cell resistance to anoikis, thereby promoting subsequent metastasis. Activation of PI3K/Akt/NF-κB/TrkB signaling by midkine-activated anaplastic lymphomakinase (ALK) is responsible for anoikis resistance.


Subject(s)
Anoikis/genetics , Carcinoma, Hepatocellular/genetics , Cytokines/metabolism , Liver Neoplasms/genetics , Animals , Carcinoma, Hepatocellular/pathology , Disease Progression , Female , Humans , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Midkine , Neoplasm Metastasis , Neoplastic Cells, Circulating/pathology
5.
Sci Rep ; 7: 40446, 2017 01 11.
Article in English | MEDLINE | ID: mdl-28074862

ABSTRACT

The Wnt/ß-catenin signaling is abnormally activated in the progression of hepatocellular carcinoma (HCC). BCL9 is an essential co-activator in the Wnt/ß-catenin signaling. Importantly, BCL9 is absent from tumors originating from normal cellular counterparts and overexpressed in many cancers including HCC. But the mechanism for BCL9 overexpression remains unknown. Ample evidence indicates that hypoxia inducible factors (HIFs) play a role in the development of HCC. It was found in our study that BCL9 was overexpressed in both primary HCC and bone metastasis specimens; loss of BCL9 inhibited the proliferation, migration and angiogenesis of HCC; and that that hypoxia mechanically induced the expression of BCL9. BCL9 induction under the hypoxic condition was predominantly mediated by HIF-1α but not HIF2α. In vitro evidence from xenograft models indicated that BCL9 promoter/gene knockout inhibited HCC tumor growth and angiogenesis. Notably, we found that BCL9 and HIF-1α were coordinately regulated in human HCC specimen. The above findings suggest that hypoxia may promote the expression of BCL9 and associate with the development of HCC. Specific regulation of BCL9 expression by HIF-1α may prove to be an underlying crosstalk between Wnt/ß-catenin signaling and hypoxia signaling pathways.


Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Neoplasm Proteins/genetics , Wnt Signaling Pathway , Adult , Animals , Base Sequence , Basic Helix-Loop-Helix Transcription Factors/metabolism , Bone Neoplasms/secondary , Cell Hypoxia , Cell Movement/genetics , Cell Proliferation/genetics , Female , Genetic Engineering , Hep G2 Cells , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , Mice, Nude , Middle Aged , Neoplasm Proteins/metabolism , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Promoter Regions, Genetic/genetics , Response Elements/genetics , Transcription Activator-Like Effector Nucleases , Transcription Factors , Transcriptional Activation/genetics
6.
Oncotarget ; 8(10): 17246-17257, 2017 Mar 07.
Article in English | MEDLINE | ID: mdl-27783997

ABSTRACT

Patients with unresectable and advanced intrahepatic cholangiocarcinoma (ICC) usually have short survival due to a lack of effective treatment. This multicenter, single arm, open labeled, prospective study was conducted to evaluate the effectiveness and safety of sorafenib combined with best supportive care (BSC) in these patients. We enrolled 44 patients with unresectable and advanced ICC who were treated with sorafenib (400 mg, twice daily) and BSC. The primary endpoint was disease control rate (DCR) at week 12, and the secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and adverse events (AEs). Our results showed that the DCR was 15.9%, the median TTP was 5.6 months, and the median PFS and OS were 3.2 and 5.7 months (95% confidence interval [CI]: 2.4-4.1 months; 3.7-8.5 months), respectively. The median DOT was 1.8 months (95% CI: 1.9-3.9 months). AEs of grades 1 and 2 events occurred in 75% of patients, and AE of grade 4 (severe) was observed in 1 patient. Therefore, sorafenib in combination with BSC had an acceptable DCR and safety profile in patients with unresectable and advanced ICC.


Subject(s)
Bile Duct Neoplasms/drug therapy , Bile Ducts, Intrahepatic/drug effects , Cholangiocarcinoma/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Aged , Bile Ducts, Intrahepatic/pathology , Diarrhea/chemically induced , Drug Administration Schedule , Exanthema/chemically induced , Fatigue/chemically induced , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Niacinamide/adverse effects , Niacinamide/therapeutic use , Palliative Care , Phenylurea Compounds/adverse effects , Pilot Projects , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Sorafenib , Treatment Outcome
7.
Oncotarget ; 7(24): 37319-37330, 2016 Jun 14.
Article in English | MEDLINE | ID: mdl-27144432

ABSTRACT

As the conventional staging systems have poor prognosis prediction ability for patients with perihilar cholangiocarcinoma (pCCA), we established and validated an effective prognostic nomogram for pCCA patients based on their personal and tumor characteristics. A total of 235 patients who received curative intent resections at the Eastern Hepatobiliary Surgery Hospital from 2000 to 2009 were recruited as the primary training cohort. Age, preoperative CA19-9 levels, portal vein involvement, hepatic artery invasion, lymph node metastases, and surgical treatment outcomes (R0 or R1/2) were independent prognostic factors for pCCA patients in the primary cohort as suggested by the multivariate analyses and these were included in the established nomogram. The calibration curve showed good agreement between overall survival probability of pCCA patients for the nomogram predictions and the actual observations and the concordance index (C-index) was 0.68 (95% CI, 0.61-0.71). The C-index values and time-dependent ROC tests suggested that the nomogram is superior to the conventional staging systems including the Bismuth-Corlette, Gazzaniga, Memorial Sloan Kettering Cancer Center (MSKCC), American Joint Committee on Cancer (AJCC) TNM 7th edition, and Mayo Clinic. The nomogram also performed better than the traditional staging system in the internal cohort with 93 pCCA patients from the same institution and an external validation cohort including 84 pCCA patients from another institution in predicting the overall survival of the pCCA patients as suggested by the C-index values and the time-dependent ROC tests. In summary, the proposed nomogram has superior predictive accuracy of prognosis for resectable pCCA patients.


Subject(s)
Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Klatskin Tumor/mortality , Klatskin Tumor/surgery , Nomograms , Age Factors , Aged , Bile Duct Neoplasms/blood , Bile Duct Neoplasms/pathology , CA-19-9 Antigen/blood , Female , Follow-Up Studies , Hepatic Artery/pathology , Humans , Kaplan-Meier Estimate , Klatskin Tumor/blood , Klatskin Tumor/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Portal Vein/pathology , Prognosis , Retrospective Studies , Sex Factors , Treatment Outcome
8.
J Gastrointest Surg ; 20(5): 960-9, 2016 05.
Article in English | MEDLINE | ID: mdl-26831059

ABSTRACT

OBJECTIVES: This study aims to evaluate the role of dynamic change in total bilirubin after portal vein embolization (PVE) in predicting major complications and 30-day mortality in patients with hilar cholangiocarcinoma (HCCA). METHODS: Retrospective analysis of prospectively maintained data of 64 HCCA patients who underwent PVE before hepatectomy in our institution was used. Total bilirubin and other parameters were measured daily in peri-PVE period. The difference between them and the baseline value from days 0-5 to day -1 (∆D1) and days 5-14 to day -1 (∆D2) were calculated. The relationship between ∆D1 and ∆D2 of total bilirubin and major complications as well as 30-day mortality was analyzed. RESULTS: Out of 64 patients, 10 developed major complications (15.6 %) and 6 patients (9.3 %) had died within 30 days after surgery. The ∆D2 of total bilirubin after PVE was most significantly associated with major complications (P < 0.001) and 30-day mortality (P = 0.002). In addition, it was found to be an independent predictor of major complications after PVE (odds ratio (OR) = 1.050; 95 % CI 1.017-1.084). ASA >3 (OR = 12.048; 95 % CI 1.019-143.321), ∆D2 of total bilirubin (OR = 1.058; 95 % CI 1.007-1.112), and ∆D2 of prealbumin (OR = 0.975; 95 % CI 0.952-0.999) were associated with higher risk of 30-day mortality after PVE. Receiver operating characteristic curves showed that ∆D2 of total bilirubin were better predictors than ∆D1 for major complications (AUC (∆D2) 0.817; P = 0.002 vs. AUC (∆D1) 0.769; P = 0.007) and 30-day mortality (ACU(∆D2) 0.868; P = 0.003 vs. AUC(∆D1) 0.721;P = 0.076). CONCLUSION: Patients with increased total bilirubin in 5-14 days after PVE may indicate a higher risk of major complications and 30-day mortality if the major hepatectomy were performed.


Subject(s)
Bile Duct Neoplasms/surgery , Bilirubin/blood , Embolization, Therapeutic/methods , Hepatectomy/adverse effects , Klatskin Tumor/surgery , Postoperative Complications/prevention & control , Preoperative Care/methods , Adult , Aged , Bile Duct Neoplasms/mortality , Biomarkers, Tumor/blood , China/epidemiology , Female , Humans , Klatskin Tumor/mortality , Male , Middle Aged , Odds Ratio , Portal Vein , Postoperative Complications/blood , Postoperative Complications/epidemiology , Prognosis , Prospective Studies , ROC Curve , Retrospective Studies , Survival Rate/trends , Time Factors , Treatment Outcome
9.
Sci Rep ; 5: 16103, 2015 Nov 04.
Article in English | MEDLINE | ID: mdl-26534789

ABSTRACT

Cholangiocarcinoma (CCA) is a common biliary malignancy. Despite continuing advances, novel indicators are urgently needed to identify patients with a poor prognosis. Several microRNAs (miRNAs) have been reported to be dysregulated in CCA tissues. The purpose of the current study was to explore the potential use of certain miRNAs as serum indicators. A total of 157 individuals, including103 CCA patients, were recruited into this study. We first used qRT-PCR to evaluate 5 CCA-related miRNAs in the serum of 95 individuals to identify significantly deregulated miRNAs. A logistic regression was used to analyse the potential variables influencing lymph node metastasis. Cox proportional hazards regression models were applied to determine the association between possible prognostic variables and overall survival (OS). We observed that decreased serum miR-106a confers a higher likelihood of lymph node metastasis [hazard ratio (HR) 18.3, 95% confidence interval (CI) 5.9-56.4, p < 0.01]. Additionally, lower circulating miR-106a levels (HR 5.1; 95% CI 2.2-11.8; p < 0.01) and non-radical surgery (HR 4.2; 95% CI 2.3-7.7; p < 0.01) were independent predictors for poor prognosis. Together, reduced expression of serum miR-106a is a powerful prognostic indicator for CCA patients. The dismal outcome of these CCA patients might correlate with a higher risk of lymph node metastasis.


Subject(s)
Bile Duct Neoplasms/diagnosis , Cholangiocarcinoma/diagnosis , Lymphatic Metastasis , MicroRNAs/blood , Adult , Aged , Aged, 80 and over , Area Under Curve , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Case-Control Studies , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Down-Regulation , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proportional Hazards Models , ROC Curve
10.
Chin J Cancer Res ; 26(3): 299-308, 2014 Jun.
Article in English | MEDLINE | ID: mdl-25035657

ABSTRACT

OBJECTIVE: After pancreaticoduodenectomy (PD), the postoperative gastroduodenal artery stump (GDAS) hemorrhage is one of the most serious complications. The purpose of this study is to determine whether wrapping the GDAS during PD could decrease the postoperative GDAS hemorrhage incidence. METHODS: A retrospective review involving 280 patients who underwent PD from 2005 to 2012 was performed. Wrapping the GDAS during PD was defined as "Wrapping the GDAS using the teres hepatis ligamentum during PD". A total of 140 patients accepted the "wrapping" procedure (wrapping group). The other 140 patients didn't apply the procedure (non-wrapping group). Age, sex, preoperative data, estimated intraoperative blood loss, postoperative complications, pathologic parameters and hospitalization time were compared between two groups. RESULTS: There were no significant differences in patient characteristics between two groups. After wrapping, the incidence of postoperative GDAS bleeding decreased significantly (1/140 vs. 9/140, P=0.01). The rates of the other complications (such as intra-abdominal infection pancreatic fistula, billiary fistula, gastrointestinal bleeding, et al.) showed no significant differences. CONCLUSIONS: Wrapping the GDAS during PD significantly reduced the postoperative GDAS hemorrhage incidence. And the "wrapping" had no obvious influence on other complications.

11.
Chin J Cancer Res ; 26(3): 309-14, 2014 Jun.
Article in English | MEDLINE | ID: mdl-25035658

ABSTRACT

OBJECTIVE: To explore the risk factors of intra-abdominal bacterial infection (IAI) after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). METHODS: A series of 82 HCC patients who received LT surgeries in our department between March 2004 and April 2010 was recruited in this study. Then we collected and analyzed the clinical data retrospectively. Statistical analysis system (SPSS) software was adopted to perform statistical analysis. Chi-square test, t-test and Wilcoxon rank sum test were used to analyze the clinical data and compute the significance of the incidences of early-stage IAI after LT for HCC patients. Binary logistic regression was performed to screen out the risk factors, and multiple logistic regression analyses were performed to compute the independent risk factors. RESULTS: A series of 13 patients (13/82, 15.9%) had postoperative IAI. The independent risk factors of postoperative intra-abdominal bacterial infections after LT for HCC patients were preoperative anemia [Hemoglobin (HGB) <90 g/L] and postoperative abdominal hemorrhage (72 hours >400 mL), with the odds ratios at 8.121 (95% CI, 1.417 to 46.550, P=0.019) and 5.911 (95% CI, 1.112 to 31.432, P=0.037). CONCLUSIONS: Postoperative IAI after LT in patients with HCC was a common complication. Preoperative moderate to severe anemia, as well as postoperative intra-abdominal hemorrhage more than 400 mL within the first 72 hours might independently indicate high risk of IAI for these patients.

12.
Int J Clin Exp Pathol ; 7(1): 80-91, 2014.
Article in English | MEDLINE | ID: mdl-24427328

ABSTRACT

The poor overall prognosis of Gallbladder carcinoma (GBC) patients and the limited therapeutic regimens for these patients demonstrates the need for better therapeutic modalities, while the growing evidences have indicated that those genes contributed to epigenetic regulation may serve as therapeutic targets. The function of histone acetylation on growth and survival of GBC cells remains unknown. In present study, an RNAi screening of 16 genes involving histone acetyltransferases (HATs) was applied to GBC-SD cells and we found that KAT5 knockdown specifically inhibits the proliferation of GBC-SD cells by casp9-mediated apoptosis. Microarray data analysis showed that KAT5 RNAi may result in cleaved casp9 upregulation through p38MAPK activation in GBC-SD cells. The mRNA expression level of KAT5 was significantly upregulated in GBC tissues than in the adjacent normal tissues. In consistence with the mRNA level, the protein expression of KAT5 was markedly increased in tissues from patients with poor prognosis than those with good prognosis. These findings strongly indicated that KAT5 was implicated in GBC tumorigenesis and that its expression level was associated with the prognosis. Our work may also provide a potential therapeutic target for treatment of GBC patients.


Subject(s)
Caspase 9/biosynthesis , Gallbladder Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/genetics , Histone Acetyltransferases/biosynthesis , p38 Mitogen-Activated Protein Kinases/metabolism , Apoptosis/genetics , Blotting, Western , Caspase 9/genetics , Cell Line, Tumor , Cell Proliferation , Flow Cytometry , Gallbladder Neoplasms/genetics , Gene Silencing , Histone Acetyltransferases/genetics , Humans , Immunohistochemistry , Lysine Acetyltransferase 5 , Oligonucleotide Array Sequence Analysis , RNA, Small Interfering , Real-Time Polymerase Chain Reaction , Up-Regulation , p38 Mitogen-Activated Protein Kinases/genetics
13.
Mol Biosyst ; 10(3): 679-85, 2014 Mar 04.
Article in English | MEDLINE | ID: mdl-24445397

ABSTRACT

UNLABELLED: Transforming growth factor ß (TGF-ß) plays important roles in tumor metastasis by regulating miRNAs expression. miR-182 is an important molecule in the regulation of cancer progression. The aim of the study is to assess the role of miR-182 in TGF-ß-induced cancer metastasis. In the present study, we found that miR-182 levels are significantly upregulated in GBC tissues compared with normal controls, and miR-182 expression is remarkably increased in primary tumors that subsequently metastasized, when compared to those primary tumors that did not metastasize. TGF-ß induces miR-182 expression in GBC cells, and overexpression of miR-182 promotes GBC cell migration and invasion, whereas miR-182 inhibition suppresses TGF-ß-induced cancer cell migration and invasion. The blockage of miR-182 by a specific inhibitor effectively inhibits pulmonary metastases in vivo. We further identified that the cell adhesion molecule1 (CADM1) is a new target gene of miR-182. miR-182 negatively regulates CADM1 expression in vitro and in vivo. Importantly, re-expression of CADM1 in GBC cells partially abrogates miR-182-induced cell invasion. CONCLUSIONS: miR-182 is an important mediator of GBC metastasis, thus offering a new target for the development of therapeutic agents against GBC.


Subject(s)
Cell Adhesion Molecules/genetics , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Immunoglobulins/genetics , MicroRNAs/genetics , Transforming Growth Factor beta/metabolism , Cell Adhesion Molecule-1 , Cell Adhesion Molecules/metabolism , Cell Line, Tumor , Cell Movement/genetics , Gallbladder Neoplasms/pathology , Gene Knockdown Techniques , Humans , Immunoglobulins/metabolism , MicroRNAs/metabolism , Neoplasm Metastasis
14.
Hepatobiliary Pancreat Dis Int ; 11(4): 377-82, 2012 Aug 15.
Article in English | MEDLINE | ID: mdl-22893464

ABSTRACT

BACKGROUND: Caudate lobectomy has long been considered technically difficult. This study aimed to elaborate the significance of early control of short hepatic portal veins (SHPVs) in isolated hepatic caudate lobectomy or in hepatic caudate lobectomy combined with major partial hepatectomy, and to describe the anatomical characteristics of SHPVs. METHODS: The data of 117 patients who underwent either isolated or combined caudate lobectomy by the same team of surgeons from 2005 to 2009 were retrospectively analyzed. From 2005 to 2007 (group A, n=55), we carried out early control of short hepatic veins (SHVs) only; from 2008 to 2009 (group B, n=62), we carried out early control of both SHVs and SHPVs. The two groups were compared to evaluate which surgical procedure was better. A detailed anatomical study was then carried out on the last 25 consecutive patients in group B to study the number and distribution of SHPVs during surgery. RESULTS: Patients in group B had less intra-operative blood loss, less impairment of liver function, shorter postoperative hospital stay, fewer postoperative complications and required less blood transfusion (P<0.05). The number of SHPVs in the 25 patients was 183, with 7.3+/-2.7 per patient. The diameters of SHPVs were 1 to 4 mm. On average, 3.4 SHPVs/patient came from the left portal vein, 2.2 from the bifurcation, 1.4 from the right portal vein, and 0.3 from the main portal vein. On average, 3.3 SHPVs/patient supplied segment I of the liver, 0.4 for segment II, 2.1 for segment IV, 1.4 for segment V and 0.1 for segment VI. CONCLUSION: Early control of SHPVs in isolated or combined hepatic caudate lobectomy may be a useful method to decrease surgical risk and improve postoperative recovery.


Subject(s)
Hepatectomy/methods , Hepatic Veins/surgery , Portal Vein/surgery , Adult , Aged , Blood Loss, Surgical/prevention & control , Blood Transfusion , Chi-Square Distribution , China , Female , Hepatectomy/adverse effects , Hepatectomy/mortality , Hepatic Veins/pathology , Hospital Mortality , Humans , Length of Stay , Male , Middle Aged , Portal Vein/pathology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
15.
Mol Oncol ; 5(6): 545-54, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22032823

ABSTRACT

Gene therapy has become an important strategy for treatment of malignancies, but problems remains concerning the low gene transferring efficiency, poor transgene expression and limited targeting specific tumors, which have greatly hampered the clinical application of tumor gene therapy. Gallbladder cancer is characterized by rapid progress, poor prognosis, and aberrantly high expression of Survivin. In the present study, we used a human tumor-specific Survivin promoter-regulated oncolytic adenovirus vector carrying P53 gene, whose anti-cancer effect has been widely confirmed, to construct a wide spectrum, specific, safe, effective gene-viral therapy system, AdSurp-P53. Examining expression of enhanced green fluorecent protein (EGFP), E1A and the target gene P53 in the oncolytic adenovirus system validated that Survivin promoter-regulated oncolytic adenovirus had high proliferation activity and high P53 expression in Survivin-positive gallbladder cancer cells. Our in vitro cytotoxicity experiment demonstrated that AdSurp-P53 possessed a stronger cytotoxic effect against gallbladder cancer cells and hepatic cancer cells. The survival rate of EH-GB1 cells was lower than 40% after infection of AdSurp-P53 at multiplicity of infection (MOI) = 1 pfu/cell, while the rate was higher than 90% after infection of Ad-P53 at the same MOI, demonstrating that AdSurp-P53 has a potent cytotoxicity against EH-GB1 cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB1 xenografts when the total dose of AdSurp-P53 was 1 × 10(9) pfu, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was (33.4 ± 8.4)%. This oncolytic adenovirus system overcomes the long-standing shortcomings of gene therapy: poor transgene expression and targeting of only specific tumors, with its therapeutic effect better than the traditional Ad-P53 therapy regimen already on market; our system might be used for patients with advanced gallbladder cancer and other cancers, who are not sensitive to chemotherapy, radiotherapy, or who lost their chance for surgical treatment.


Subject(s)
Adenoviridae/genetics , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/therapy , Genes, p53 , Genetic Vectors/genetics , Inhibitor of Apoptosis Proteins/genetics , Animals , Cell Line , Cell Line, Tumor , Cell Proliferation , Gallbladder/metabolism , Gallbladder/pathology , Gallbladder Neoplasms/pathology , Genetic Therapy , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Promoter Regions, Genetic , Survivin
16.
Acta Pharmacol Sin ; 31(12): 1643-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21102481

ABSTRACT

AIM: to determine the efficacy and toxicities of sorafenib in the treatment of patients with multiple recurrences of hepatocellular carcinoma (HCC) after liver transplantation in a Chinese population. METHODS: twenty patients with multiple recurrences of HCC after liver transplantation were retrospectively studied. They received either transarterial chemoembolization (TACE) or TACE combined with sorafenib. RESULTS: the median survival times (MST) after multiple recurrences was 14 months (TACE+sorafenib group) and 6 months (TACE only group). The difference was significant in MST between the two groups (P=0.005). The TACE + sorafenib group had more stable disease (SD) patients than the TACE group. The most frequent adverse events of sorafenib were hand-foot skin reaction and diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are found to be significantly associated with tumor-free survival time, the survival time after multiple recurrences and overall survival time. TACE+sorafenib group showed a better outcome than single TACE treatment group. In the multivariate COX regression modeling, the preoperative high CHILD grade was found to be a risk factor of tumor-free survival time. In addition, the preoperative high bilirubin grade was also found to be a risk factor of survival time after recurrence and overall survival time. Furthermore, survival time after recurrence and overall survival time were also associated with therapeutic schedule, which was indicated by the GROUP. CONCLUSION: Treatment with TACE and sorafenib is worthy of further study and may have more extensive application prospects.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzenesulfonates/therapeutic use , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Liver Transplantation , Pyridines/therapeutic use , Adult , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Chemoembolization, Therapeutic , Combined Modality Therapy , Disease-Free Survival , Humans , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Neoplasm Recurrence, Local , Niacinamide/analogs & derivatives , Phenylurea Compounds , Retrospective Studies , Sorafenib
17.
Chin Med J (Engl) ; 123(11): 1413-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20819598

ABSTRACT

BACKGROUND: The Pringle maneuver, which has been the standard for hepatic resection surgery for a long time, has the major flaw of ischemic damage in the liver. The aim of this research was to evaluate hepatic blood inflow occlusion with/without hemihepatic artery control vs. the Pringle maneuver in hepatocellular carcinoma (HCC) resection. METHODS: Two hundred and eighty-one cases of resection of HCC with hepatic blood inflow occlusion (with/without hemihepatic artery control) and the Pringle maneuver from January 2006 to December 2008 in our hospital were analyzed and compared retrospectively; among them 107 were in group I (Pringle maneuver), 98 in group II (hepatic blood inflow occlusion), and 76 in group III (hepatic blood inflow occlusion without hemihepatic artery control). The operation time, intraoperative blood loss, postoperative liver function and complications were used as the endpoints for evaluation. RESULTS: The operative duration and intraoperative blood loss of three groups showed no significant difference; alanine aminotransferase, total bilirubin and incidence of postoperative complications were significantly lower in groups II and III postoperation than those in group I. CONCLUSION: Hepatic blood inflow occlusion without hemihepatic artery control is safe, convenient and feasible for resection of HCC, especially for cases involving underlying diseases such as cirrhosis.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Liver Neoplasms/surgery , Liver/blood supply , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
18.
Hepatogastroenterology ; 57(104): 1341-6, 2010.
Article in English | MEDLINE | ID: mdl-21443082

ABSTRACT

BACKGROUND/AIMS: Preoperative portal vein embolization (PVE) allows potentially curative hepatic resection to be carried out in patients with hepatobiliary malignancies who are otherwise not candidates for resection because of the small size of the future liver remnant (FLR). However, there have only been a few reports on PVE before hepatectomy for hilar cholangiocarcinoma due to the small number of patients who can be treated with radical surgery. METHODOLOGY: Between January 2007 and March 2009, 49 consecutive patients with hilar cholangiocarcinoma who were planned to have hemi-hepatectomy/extended hemi-hepatectomy plus caudate lobe resection in our tertiary referral center were studied. The change in size of the FLR and the operative outcomes were compared between patients with or without PVE. RESULTS: All patients had liver dysfunction as a result of biliary obstruction due to hilar cholangiocarcinoma although they had all received percutaneous transhepatic biliary drainage. PVE was used in 16 patients with an estimated FLR of <50%, while no PVE was carried out in 33 patients with an estimated FLR of >50%. Complications after PVE occurred in 3 patients (18.8%), which included bile leakage (n=1) and coil displacement (n=2). No complication precluded liver resection. The FLR to total liver volume (TLV) ratio at presentation was significantly smaller in patients who underwent PVE than those who did not undergo PVE (40.3 +/- 7.4% vs. 56.6 +/- 5.0%; p < 0.001). After PVE, the FLR to TLV ratio increased significantly (40.3 +/- 7.4% vs. 43.1 +/- 7.0%; p < 0.001) at a mean time of 14.2 +/- 3.5 days. The mean +/- S.D. increase in FLR was 4.6 +/- 3.0 cm3/day. At surgery, the FLR volume was still significantly smaller in the PVE group than the non-PVE (802 +/- 216 cm3 vs. 979 +/- 202 cm3; p = 0.007). In the PVE group, insufficient hypertrophy of the FRL prevented one patient from having surgery, while local tumor progression and peritoneal dissemination precluded hepatectomy in 2 more patients. Finally, 13 patients (81.3%) underwent radical surgery. The PVE group had similar complication and mortality rates compared with the non-PVE group (complication rate, 69.2% vs. 63.6%; mortality rate, 0.0% vs. 9.1%). The 1- and 2-year overall survivals for the PVE group (with intent-to-treat analysis), PVE group (radical surgery only) and the non-PVE group were 57.3% and 43.0%; 71.3% and 53.5%; 70.4% and 54.4%, respectively. There was no significant difference in the survival outcomes. CONCLUSIONS: The results suggested that PVE is a safe and efficacious procedure in inducing adequate hypertrophy of the FLR before major hepatic resection for hilar cholangiocarcinoma with obstructive jaundice which had been relieved by percutaneous transhepatic biliary drainage.


Subject(s)
Bile Duct Neoplasms/therapy , Embolization, Therapeutic/methods , Hepatic Duct, Common , Klatskin Tumor/therapy , Portal Vein , Chi-Square Distribution , Combined Modality Therapy , Female , Hepatectomy/methods , Humans , Liver Function Tests , Male , Middle Aged , Postoperative Complications , Treatment Outcome
19.
World J Gastroenterol ; 15(48): 6134-6, 2009 Dec 28.
Article in English | MEDLINE | ID: mdl-20027691

ABSTRACT

We report a case of a 56-year-old woman with intrahepatic biliary cystadenoma (IBC) accompanying a tumor embolus in the extrahepatic bile duct, who was admitted to our department on October 13, 2008. Imaging showed an asymmetry dilation of the biliary tree, different bile signals in the biliary tree, a multiloculated lesion and an extrahepatic bile duct lesion with internal septation. A regular left hemihepatectomy en bloc was performed with resection of the entire tumor, during which a tumor embolus protruding into the extrahepatic bile duct and originating from biliary duct of segment 4 was revealed. Microscopically, the multiloculated tumor was confirmed to be a biliary cystadenoma with an epithelial lining composed of biliary-type cuboidal cells and surrounded by an ovarian-like stroma. An aggressive en bloc resection was recommended for the multiloculated lesion. Imaging workup, clinicians and surgeons need to be aware of this different presentation.


Subject(s)
Bile Duct Neoplasms/pathology , Bile Ducts, Extrahepatic/pathology , Bile Ducts, Intrahepatic/pathology , Cystadenoma/pathology , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/surgery , Cystadenoma/complications , Cystadenoma/surgery , Female , Humans , Middle Aged
20.
World J Gastroenterol ; 15(13): 1625-9, 2009 Apr 07.
Article in English | MEDLINE | ID: mdl-19340906

ABSTRACT

AIM: To compare the treatment modalities for patients with massive pancreaticojejunal anastomotic hemorrhage after pancreatoduodenectomy (PDT). METHODS: A retrospective study was undertaken to compare the outcomes of two major treatment modalities: transcatheter arterial embolization (TAE) and open surgical hemostasis. Seventeen patients with acute massive hemorrhage after PDT were recruited in this study. A comparison of two treatment modalities was based upon the clinicopathological characteristics and hospitalization stay, complications, and patient prognosis of the patients after surgery. RESULTS: Of the 11 patients with massive hemorrhage after PDT treated with TAE, 1 died after discontinuing treatment, the other 10 stopped bleeding completely without recurrence of hemorrhage. All the 10 patients recovered well and were discharged, with a mean hospital stay of 10.45 d after hemostasis. The patients who underwent TAE twice had a re-operation rate of 18.2% and a mortality rate of 0.9%. Among the six patients who received open surgical hemostasis, two underwent another round of open surgical hemostasis. The mortality was 50%, and the recurrence of hemorrhage was 16.67%, with a mean hospital stay of 39.5 d. CONCLUSION: TAE is a safe and effective treatment modality for patients with acute hemorrhage after PDT. Vasography should be performed to locate the bleeding site.


Subject(s)
Embolization, Therapeutic/methods , Gastrointestinal Hemorrhage/surgery , Hemostasis , Pancreaticoduodenectomy/adverse effects , Pancreaticojejunostomy/adverse effects , Adult , Aged , Female , Gastrointestinal Hemorrhage/mortality , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Treatment Outcome
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