Functional anatomical hepatectomy guided by indocyanine green fluorescence imaging in patients with localized cholestasis: Report of four cases.

BACKGROUND: Liver cancer is a malignant tumor with a high incidence. At present, the most effective treatment is laparoscopic hepatectomy (LH). Indocyanine green fluorescence imaging (ICG-FI) has become an important tool in LH, and the most common fluorescent types of tumors are total fluorescence, partial fluorescence, and rim fluorescence. CASE SUMMARY: We presented four cases of LH guided by ICG-FI in which we also observed the fourth special fluorescent type. When the tumor or intrahepatic stone compresses the adjacent bile duct to cause local cholestasis, the liver segment or subsegment with obstructed bile drainage will show strong fluorescence. Complete removal of the lesion together with the fluorescent liver parenchyma may help reduce the risk of tumor or stone recurrence. CONCLUSION: This type of partial fluorescence can indicate local biliary compression, and the resection method is related to bile drainage, which may be called functional anatomical hepatectomy and ensures radical resection of the lesion.

AQP8 inhibits colorectal cancer growth and metastasis by down-regulating PI3K/AKT signaling and PCDH7 expression.

Colorectal cancer (CRC) is one of the most common malignant cancers and the leading cause of cancer-related deaths in worldwide. Although the monoclonal antibody therapy is prescribed for CRC, the metastasis resistant to therapy is the major cause of death of patients with CRC, which indicating the urgent demands for new therapeutic targets discovery. Aquaporin 8 (AQP8) has been identified alter expressed in several cancers including breast cancer, lung cancer and prostatic carcinoma. Our study demonstrated the functional significance of AQP8 in CRC cells growth and metastasis. Over-expression of AQP8 remarkably decreased growth, aggressiveness and colony formation in the CRC SW480 and HT-29 cells. Mechanistically, AQP8 over-expression inhibited tumorigenic phenotype by inactivating PI3K/AKT signaling and inhibiting PCDH7 expression. Furthermore, in vivo studies using nude mice xenograft and metastasis model identified the pivotal role of AQP8 in CRC cells growth and metastasis. Taken together, the present study verifies the vital role of the endogenous AQP8 in colorectal cancer progression.

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.

Elevated Preoperative Serum Hs-CRP Level as a Prognostic Factor in Patients Who Underwent Resection for Hepatocellular Carcinoma.

To evaluate the effects of preoperative highly sensitive C-reactive protein (Hs-CRP) in serum on the prognostic outcomes of patients with hepatocellular carcinoma (HCC) following hepatic resection in Chinese samples.From January 2004 to December 2008, a total of 624 consecutive HCC patients who underwent hepatic resection were incorporated. Serum levels of Hs-CRP were tested at preoperation via a collection of venous blood samples. Survival analyses adopted the univariate and multivariate analyses.In our study, among the 624 screened HCC patients, 516 patients were eventually incorporated and completed follow-up. Positive correlations were found regarding preoperative serum Hs-CRP level and tumor size, Child-Pugh class, or tumor stage (all P < 0.0001). Patients with recurrence outcomes and nonsurvivors had increased Hs-CRP levels at preoperation (both P < 0.0001). When compared to the Hs-CRP-normal group, the overall survival (OS) and recurrence-free survival rates were evidently decreased in the Hs-CRP-elevated group. Further, preoperative serum Hs-CRP level might be having possible prediction effect regarding survival and recurrence of HCC patients after hepatic section in the multivariate analysis.Preoperative increased serum Hs-CRP level was an independent prognostic indicator in patients with HCC following hepatic resection in Chinese samples.

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.

Tripartite comparison of single-incision and conventional laparoscopy in cholecystectomy: A multicenter trial.

AIM: To compare the characteristics of two single-incision methods, and conventional laparoscopy in cholecystectomy, and demonstrate the safety and feasibility. METHODS: Three hundred patients with gallstones or gallbladder polyps were admitted to two clinical centers from January 2013 to January 2014 and were randomized into three groups of 100: single-incision three-device group, X-Cone group, and conventional group. The operative time, intraoperative blood loss, complications, postoperative pain, cosmetic score, length of hospitalization, and hospital costs were compared, with a follow-up duration of 1 mo. RESULTS: A total of 142 males (47%) and 158 females (53%) were enrolled in this study. The population characteristics of these three groups is no significant differences exist in terms of age, sex, body mass index and American Society of Anesthesiology (P > 0.05). In results, there were no significant differences in blood loss, length of hospitalization, postoperative complications.The operative time in X-Cone group was significantly longer than other groups.There were significant differences in postoperative pain scores and cosmetic scores at diffent times after surgery (P < 0.05). CONCLUSION: This study shows that this two single-incision methods are safe and feasible. Both methods are superior to the conventional procedure in cosmetic and pain scores.

Involvement of discoidin domain 1 receptor in recurrence of hepatocellular carcinoma by genome-wide analysis.

Hepatocellular carcinoma (HCC) is highly invasive with a high frequency of recurrence following surgery and poor prognosis. The underlying molecular mechanisms for HCC recurrence are not well understood. Here, we used microarray technology for genome-wide analysis to identify genes who may be involved in tumor recurrence. cDNA from HCC tumor tissues of patients with early recurrence (ER; n = 10) and patients whose HCC had not recurred ≥ 2 years postsurgery (nER; n = 10) was hybridized to the Affymetrix Human Geome U133 plus 2.0 whole-genome microarray. Gene clusters were identified and used for hierarchial clustering and principal component analysis. Genes with more than twofold change in expression between ER and nER groups were further analyzed. Expression levels of a subset of genes were validated using RT-PCR and immunohistochemistry. A total of 1,646 genes had significantly different expression between the ER and nER groups (P < 0.05) with 61 and 49 genes in the ER upregulated and downregulated for more than twofold in comparison with the nER group, respectively. The cellular functions of differentially expressed genes included cell adhesion, motility, cytoskeleton, transcription, metabolism, signal transduction, and apoptosis. The discoidin domain receptor 1 (DDR1) mRNA expression was significantly higher in the ER (3.36 ± 0.39) compared with the nER group (3.01 ± 0.49; P = 0.020). A greater proportion of liver tissue samples from ER versus nER patients had DDR1 protein expression (80.0 vs. 40.0 %, P = 0.022). Using microarray technology, we identified a number of genes whose expression differed between patients with recurrent HCC compared to those without. DD1 mRNA and protein levels were higher in patients with recurrent HCC, suggesting this gene maybe involved in tumor invasion and metastasis.

[Expression of SOX4 gene and early recurrence of hepatocellular carcinoma: their relationship and the clinical significance].

OBJECTIVE: T To explore the relationship between the expression of SOX4 gene and early recurrence of hepatocellular carcinoma (HCC) after curative resection. METHODS: SOX4 expression was detected immunohistochemically in 60 HCC patients including 30 with and 30 without early recurrence after curative resection, with 30 normal liver specimens as the control. RESULTS: The expression of SOX4 was significantly higher in HCC than in normal liver (41.7% vs 16.7%, P<0.05), and in HCC tissues, the expression was significantly higher in early recurrent HCC after curative resection than in HCC without early recurrence (56.7% vs 26.7%, P<0.05). SOX4 expression was inversely correlated to the patients' gender, age, tumor size, HBsAg, and Edmonson grade (P<0.05). CONCLUSION: SOX4 is closely associated with early recurrence of HCC after curative resection, and its overexpression may contribute to early recurrence of HCC. SOX4 may serve as a new molecular indicator for evaluating the prognosis of HCC.

[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.

[Common failure reasons and improvement ways in treatment of gallstones by choledochoscope in operation].

OBJECTIVE: To analyze common problems, failing causes and improvement ways for curing gallstones by choledochoscope in operation. METHOD: To analyze a case group of 762 individual patients who had undergone choledochoscope operations in the period of Jan, 1995 approximately Sep, 2005. RESULTS: 136 cases are found with residual stones in the bile duct after the operations. Residual stone rate amounts to 17.8%. 55 patients are known that bile duct stones could not be remove completely during operations. 81 patients are proved that stones still remain in their bile ducts by T-tube cholangiography and choledochoscope after operations. Among them, 29 patients complicate with narrow in intrahepatic bile ducts and debouch of bile ducts, 39 patients complicate with stones of intrahepatic bile and variation of bile duct, 13 patients complicate with stones and narrow at the inferior segment of choledochus. CONCLUSIONS: It is important to pay attention for bile duct variation and debouch of affection bile duct or inferior segment of choledochus stenosis. B-ultrasound is useful to reduce residual stones in operations. The surgeon should check different lengths of the duct methodically, and use the endoscope to explore the bile duct in order not to omit any stones.

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.

[Causes of failure in choledochoscopic diagnosis and removal of gallstone].

OBJECTIVE: To discuss the causes for failure in diagnosis and removal of gallstone using choledochoscope. METHOD: A retrospective analysis was conducted in 714 cases of gallstone treated with choledochoscopic operations. RESULTS: Residual stones in the bile duct were found in 132 (18.5%) cases after the operation. In 54 cases the bile duct stones failed to be completely removed even before the closure. By T-tube cholangiography and choledochoscopy after the operation, 78 cases were found to have residual bile duct stones, among them 29 were complicated with intrahepatic bile duct and bile duct opening stenosis, 37 with intrahepatic bile stone and bile duct variation, and 12 with choledochus inferior segment stenosis and stone formation. CONCLUSION: Due attention should be paid during the choledochoscopic operation to bile duct variation, bile duct opening stenosis or choledochus inferior segment stenosis, which should be carefully inspected by segments in succession to minimize the possibility of residual stones.

[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.