[Multivariate analysis of risk factors for intra-abdominal infections after radical gastrectomy for gastric cancer].

OBJECTIVE: To explore the major risk factors for intra-abdominal infections after radical gastrectomy in patients with gastric cancer. METHODS: From October 2010 to January 2013, a total of 479 patients undergoing radical gastrectomy at Department of Gastric, Duodenal & Pancreatic Surgery, Hunan Provincial Tumor Hospital were divided into 2 groups according to an onset of postoperative intra-abdominal infections (n = 32, 6.68%) or not (n = 447, 93.32%). Their clinicopathological data, such as age, gender, co-morbidities, surgical duration, operative blood loss and pathological stage were retrospectively analyzed by Logistic regressive analysis with a case-control study model. RESULTS: As compared with the control group, the patients had a greater age ((59 ± 10) vs (53 ± 11) years, P < 0.01), lower lymphocyte count ((1.4 ± 0.7) ×10(9)/L vs (1.7 ± 0.6) ×10(9)/L, P = 0.02), lower hemoglobin level ( (108 ± 28) vs (117 ± 24) g/L, P = 0.04), lower albumin level ((34 ± 6) vs (37 ± 5) g/L, P < 0.01) and longer surgical duration ((244 ± 43) vs (216 ± 45) min, P < 0.01) in the postoperative intra-abdominal infection group. Univariate Logistic regressive analysis found that a history of abdominal surgery, body mass index (BMI) >25 kg/m(2), co-morbidities, diabetes mellitus, complications due to gastric cancer, lymphocyte count <1.5×10(9)/L, hemoglobin <100 g/L, albumin <30 g/L, ascites, perioperative transfusion, total mastectomy, combined organ resection and surgical duration >240 min were associated with the occurrence of postoperative intra-abdominal infections (all P < 0.05). Further multivariate analysis identified 4 independent risk factors for intra-abdominal infections after radical gastrectomy, including combined multiorgan resection (OR = 3.64, 95%CI: 1.39-9.55), BMI>25 kg/m(2) (OR = 3.04, 95%CI: 1.17-7.92), diabetes mellitus (OR = 3.41, 95%CI: 1.05-11.09) and perioperative transfusion (OR = 2.24, 95%CI: 1.02-5.13). CONCLUSION: A correction of modifiable risk factors may reduce the incidence of intra-abdominal infections after radical gastrectomy, shorten the length of hospital stays and improve outcomes in patients with gastric cancer.

[Clavien-Dindo classification and risk factors for complications after radical gastrectomy for gastric cancer].

OBJECTIVE: To explore the complications after radical gastrectomy in patients with gastric cancer according to Clavien-Dindo classification and examine the major risk factors for complications. METHODS: From October 2010 to June 2013, a total of 614 patients undergoing radical gastrectomy at Department of Gastric,Duodenal & Pancreatic Surgery at Hunan Provincial Tumor Hospital were divided into 2 groups according to the occurrence of complications (n = 76, 12.38%) or not (n = 538, 87.62%). Their clinicopathological data, such as age, gender, co-morbidities, surgical duration, operative blood loss volume and pathological stage were retrospectively analyzed by Logistic regression with a case-control model. RESULTS: Among them, 76 patients developed complications (12.38%). According to Clavien-Dindo classification, 56(9.12%), 14(2.28%), 3(0.49%) and 3(0.49%) patients suffered stage II, III, IV and V complications respectively. Comparing with the control group, the patients had a higher transfusion rate (43.42% (n = 33) vs 24.16% (n = 130), P < 0.01) and a longer postoperative hospital stay in the complication group ((23 ± 18) vs (14 ± 6) days, P < 0.01). There was no difference in age, gender, body mass index (BMI), number of dissected lymph node, levels of hemoglobin and albumin at admission, intraoperative hemorrhage, surgical duration and pathological TNM stage in two groups (all P > 0.05). Univariate analysis revealed that BMI > 25 kg/m(2), co-morbidities, diabetes mellitus, complications due to gastric cancer, hemoglobin <100 g/L, albumin <30 g/L, ascites, total gastrectomy, combined multi-organ resection, surgical duration >240 min and perioperative transfusion were associated with postoperative complications (all P < 0.05).Further multivariate analysis showed that perioperative transfusion (OR = 2.78, 95%CI: 1.42-5.43, P < 0.01) and combined multi-organ resection (OR = 1.72, 95%CI: 1.14-2.58, P = 0.01) were independent risk factors for postoperative complications after radical gastrectomy. CONCLUSIONS: Classifying the complications after radical gastrectomy according to Clavien-Dindo classification is important for comparisons and quality assessments among different studies. And decreasing perioperative transfusion and avoiding combined multi-organ resection may reduce the incidence of postoperative complications and shorten the length of hospital stay.

[Surgical treatment for cancer of the pancreatic head].

OBJECTIVE: To explore and evaluate the therapeutic efficacy of surgical treatment for cancer of the pancreatic head. METHODS: The clinical data of 96 patients with cancer of the pancreatic head admitted in our hospital from January 2002 to December 2009 were retrospectively analyzed. pancreatoduodenectomy was performed in 48 cases, extended pancreatoduodenectomy in 30 cases, and Roux-Y cholangiojejunostomy in 18 cases. RESULTS: The 1, 2 and 3-year survival rates were 59.2%, 41.8% and 13.2%, respectively, in the patients treated with pancreatoduodenectomy, and 73.2%, 58.2% and 24.1%, respectively, in the patients treated with extended pancreatoduodenectomy. The 1, 2 and 3-year survival rates were 36.8%, 15.8% and 5.3%, respectively, in the patients with unresectable tumor who received radiotherapy and (or) chemotherapy in Roux-Y cholangiojejunostomy. The postoperative morbidity was 29.2%, 30.0% and 27.8% in the patients treated with pancreatoduodenectomy, extended pancreatoduodenectomy and Roux-Y cholangiojejunostomy, respectively. CONCLUSIONS: Pancreatoduodenectomy is the most effective treatment. Extended pancreatoduodenectomy can improve the surgical resection rate, reduce the recurrence rate and improve the survival rate. Internal drainage is an important palliative measure.

JARID2 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition through PTEN/AKT signaling.

JARID2 is crucial for maintenance of pluripotency and differentiation of embryonic stem cells. However, little is known about the role of JARID2 in metastasis of hepatocellular carcinoma (HCC). This study found that JARID2 expression was significantly higher in HCC tissues than that in adjacent non-tumor liver tissues (ANLTs), and its expression level correlated with HCC metastasis. High JARID2 expression was significantly correlated with multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0.05) and indicated poor prognosis of HCC in training and validation cohorts (all P < 0.05) totaling 182 patients. High JARID2 expression was an independent and significant risk factor for disease-free survival (DFS; P = 0.017) and overall survival (OS; P = 0.041) after curative liver resection in training cohort, and also validated as an independent and significant risk factor for DFS (P = 0.033) and OS (P = 0.031) in validation cohort. Moreover, down-regulation of JARID2 dramatically inhibited HCC cell migration, invasion, proliferation in vitro and metastasis in vivo, whereas overexpression of JARID2 significantly increased migration, invasion, proliferation in vitro and metastasis in vivo. Mechanistically, the data showed that JARID2 exerted its function by repressing PTEN expression through increasing H3K27 trimethylation (H3K27me3) at PTEN promoter region, which subsequently resulted in activation of protein kinase B (AKT) and enhanced epithelial-mesenchymal transition (EMT). In conclusion, this study revealed that JARID2 promotes invasion and metastasis of HCC by facilitating EMT through PTEN/AKT signaling.

YMO1 suppresses invasion and metastasis by inhibiting RhoC signaling and predicts favorable prognosis in hepatocellular carcinoma.

Previous studies have shown that 4.1 proteins, which are deregulated in many cancers, contribute to cell adhesion and motility. Yurt/Mosaic eyes-like 1 (YMO1) is a member of 4.1 protein family but it is unclear whether YMO1 plays a role in tumor invasion. This study aimed to investigate the effects of YMO1 on hepatocellular carcinoma (HCC) and attempted to elucidate the underlying molecular mechanisms. YMO1 expression in HCC tissues and its correlation with clinicopathological features and postoperative prognosis was analyzed. The results showed that YMO1 was down-regulated in the highly metastatic HCC cell line and in human tumor tissues. Underexpression of YMO1 indicated poor prognosis of HCC patients. Restoration of YMO1 expression caused a significant decrease in cell migration and invasiveness in vitro. In vivo study showed that YMO1 reduced liver tumor invasion and metastasis in xenograft mice. YMO1 directly inhibited RhoC activation. YMO1 expression in HCC was regulated by PAX5. Analysis of YMO1 expression levels in human HCC patients revealed a significant correlation of YMO1 expression with PAX5 and RhoC. Our findings revealed that YMO1 predicts favorable prognosis and the data suggest that YMO1 suppresses tumor invasion and metastasis by inhibiting RhoC activity.

Ack1 overexpression promotes metastasis and indicates poor prognosis of hepatocellular carcinoma.

Despite the substantial data supporting the oncogenic role of Ack1, the predictive value and biologic role of Ack1 in hepatocellular carcinoma (HCC) metastasis remains unknown. In this study, both correlations of Ack1 expression with prognosis of HCC, and the role of Ack1 in metastasis of HCC were investigated in vitro and in vivo. Our results showed that Ack1 was overexpressed in human HCC tissues and cell lines. High Ack1 expression was associated with HCC metastasis and determined as a significant and independent prognostic factor for HCC after liver resection. Ack1 promoted HCC invasion and metastasis in vitro and in vivo. Mechanistically, we confirmed that Ack1 enhanced invasion and metastasis of HCC via EMT by mediating AKT phosphorylation. In conclusion, our study shows Ack1 is a novel prognostic biomarker for HCC and promotes metastasis of HCC via EMT by activating AKT signaling.

Transcatheter arterial chemoembolization combined with interferon-α is safe and effective for patients with hepatocellular carcinoma after curative resection.

OBJECTIVES: Intrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)- related hepatocellular carcinoma (HCC) after curative surgical resection. Several approaches have been reported to decrease the recurrence rate. The objective of our study was to compare the clinical effects of transcatheter arterial chemoembolization (TACE) combined with interferon-alpha (IFN-α) therapy on recurrence after hepatic resection in patients with HBV-related HCC with that of TACE chemotherapy alone. METHODS: We retrospectively analyzed the data from 228 patients who were diagnosed with HBV-related HCC and underwent curative resection between January 2001 to December 2008. The patients were divided into TACE (n = 126) and TACE-IFN-α (n = 102) groups for postoperative chemotherapy. The TACE regimen consisted of 5-fluorouracil (5-FU), cisplatin (DDP) , and the emulsion mixed with mitomycin C (MMC) and lipiodol. The recurrence rates, disease-free survival (DFS), overall survival (OS), and risk of recurrence were evaluated. RESULTS: The clinicopathological parameters and adverse effects were similar between the 2 groups (P > 0.05). The median OS for the TACE- IFN-α group (36.3 months) was significantly longer than that of the TACE group (24.5 months, P < 0.05). The 3-and 5-year OS for the TACE-IFN-α group were significantly longer than those of the TACE group (P < 0.05) and the recurrence rate was significantly lower (P < 0.05). The TACE and IFN-α combination therapy, active hepatitis HBV infection, the number of tumor nodules, microvascular invasion, liver cirrhosis, and the BCLC stage were independent predictors of OS and DFS. CONCLUSIONS: The use of the TACE and IFN-α combination chemotherapy after curative hepatic resection safely and effectively improves OS and decreases recurrence in patients with HBV-related HCC who are at high risk. Our findings can serve as a guide for the selection of postoperative adjuvant chemotherapy for patients with HBV-related HCC who are at high risk of recurrence.

Characterization of lymph node metastasis and its clinical significance in the surgical treatment of gastric cancer.

This study aimed to characterize lymph node metastasis and determine its clinical significance in the surgical treatment of gastric cancer. The medical charts of 920 gastric cancer patients who underwent radical surgical resection between March, 2010 and March, 2013, were retrospectively reviewed and statistically analyzed. Lymphatic metastasis was observed in 69.6% of the patients (640/920). The frequency of lymph node metastasis in patients with early-stage gastric cancer was 21.4% (18/84). Lymph node metastasis was observed in all the patients with stage IIIC-IV gastric cancer. The incidence of lymph node metastasis was higher among patients with tumors >7 cm in size. The most frequently affected lymph nodes in patients with proximal, central and distal gastric cancer were station no. 1 (34.2%), no. 3 (33.8%) and no. 6 (34.3%) lymph nodes, respectively. The frequency of lymph node metastasis in patients with Borrmann type IV cancer was significantly higher compared to that in patients with other Borrmann type cancers. Our study further demonstrated that lymphatic metastasis is closely correlated with TNM stage, location, depth of invasion and size of gastric tumors. Therefore, we recommend that a sufficient number of lymph nodes be examined from each patient to determine the extent of lymph node dissection based on Borrmann type, location, size, depth of invasion and histology of the cancer.

Mesohepatectomy for the treatment of patients with centrally located hepatocellular carcinoma.

Mesohepatectomy is considered a feasible option for patients with centrally located hepatocellular carcinoma (HCC). However, mesohepatectomy is a technically demanding and less frequently used procedure. In this study, we summarized the surgical experience and evaluated the clinical outcomes of mesohepatectomy in 24 patients with centrally located HCC. Of these patients, 9 were treated with hepatectomy of Couinaud's segments IV, V and VIII with concurrent cholecystectomy; 8 underwent resection of segments IVb, V and VIII, including 7 patients who also received a cholecystectomy; 4 underwent hepatectomy of segments IVa, V and VIII; and 3 patients were treated with hepatectomy of segments I, IV, V and VIII, with concurrent cholecystectomy. The Pringle maneuver was used on 17 patients during hepatectomy. Total hepatic vascular exclusion (HVE) was performed on 3 patients and HVE was not used on 4 patients. The average mesohepatectomy operative time was 238 min and the average intraoperative blood loss was 480 ml (200-2,200 ml). There was no intraoperative mortality and the postoperative morbidity rate was 25% (6/24). The 1- and 3-year overall survival rates were 76 and 46%, respectively. Therefore, mesohepatectomy is a safe and effective surgical procedure for the treatment of centrally located HCC and HVE during mesohepatectomy for centrally located HCC is crucial to the success of the operation and postoperative patient recovery.

[Inhibitory effects of cyclooxygenase-2 inhibitor celecoxib on growth and angiogenesis of human liver cancer HepG2 cell xenografts in small nude mice].

BACKGROUND & OBJECTIVE: Cyclooxygenase-2 (COX-2) is closely correlated to genesis of tumors, particularly digestive tract tumors, and its inhibitor has antitumor effect. This study was to investigate the inhibitory effects of COX-2 inhibitor celecoxib on growth and angiogenesis of human liver cancer HepG2 cell xenografts in small nude mice. METHODS: HepG2 cells were transplanted into the dorsal subcutaneous tissue of athymic nude mice. The mice were treated with celecoxib 4 days after transplantation, and were killed 58 days later. Tumor volume and weight were measured. The expression of COX-2, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang-2) were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and microvessel density (MVD) was observed by immunohistochemistry. RESULTS: The average tumor volume was significantly smaller and the average tumor weight was significantly lighter in celecoxib group than in control group [(709.11+/-108.53) mm3 vs. (1,417.55+/-69.50) mm3, and (2.63+/-0.34) g vs. (5.32+/-0.98) g, P<0.01]. The inhibitory rate of tumor growth was 55.21%. The expression levels of COX-2, VEGF, bFGF and Ang-2, and MVD were significantly lower in celecoxib group than in control group (2.43+/-0.29 vs. 4.50+/-0.25, 2.80+/-0.30 vs. 5.49+/-0.58, 2.23+/-0.41 vs. 4.03+/-0.47, 2.88+/-0.25 vs. 5.53+/-0.54, and 29.27+/-1.52 vs. 128.24+/-9.82, P<0.01, respectively). COX-2 expression was positively correlated to VEGF, bFGF and Ang-2 expression and MVD (r=0.862, r=0.882, r=0.857, r=0.837,P<0.01, respectively). CONCLUSIONS: Celecoxib inhibits the growth and angiogenesis of HepG2 cell xenografts in nude mice effectively via suppressing the expression of COX-2.