Pei-Wu Yu

Systemic and peritoneal inflammatory response after laparoscopic-assisted gastrectomy and the effect of inflammatory cytokines on adhesion of gastric cancer cells to peritoneal mesothelial cells

IntroductionThere still remain concerns over the potential for peritoneal metastasis after laparoscopic surgery. We designed this trial to investigate the effects of the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the interaction between gastric cancer cells and mesothelial cells, and to evaluate differences in both the peritoneal and systemic cytokine (IL-1β and TNF-α) concentrations after laparoscopic and conventional surgical approaches, thus offering another possible advantage of laparoscopic procedures for treatment of gastric cancer.Experimental designA reproducible human in vitro assay was developed to study adhesion of SGC-7901 and MKN-45 human gastric cancer cells to monolayers of primary cultured human peritoneal mesothelial cells (HPMCs). Tumor cell adhesion to a mesothelial monolayer was assessed after preincubation of the monolayer with IL-1β and TNF-α using flow cytometry. Expression of adhesion molecules (ICAM-1, VCAM-1, and CD44) and their counterparts (LFA-1 and VLA-4) was investigated by real-time polymerase chain reaction (PCR) immunocytochemical staining. Furthermore, the proinflammatory cytokines IL-1β and TNF-α were measured perioperatively in peritoneal drain fluid and in serum by enzyme immunoassay.ResultsPreincubation of the mesothelial monolayer with IL-1β and TNF-α resulted in enhanced tumor cell adhesion of SGC-7901 and MKN-45 cells. Mesothelial cells showed significant enhancement of expression of ICAM-1, VCAM-1, and CD44 after stimulation with IL-1β and TNF-α. Meanwhile their counterparts (LFA-1, VLA-4, and CD44) were identified in gastric cancer cells. The level of IL-1β in peritoneal drain fluid and in serum perioperatively in the laparoscopy-assisted gastrectomy group was lower than in the conventional open gastrectomy group, whereas there were no significant differences between the laparoscopic-assisted distal gastrectomy (LADG) and conventional open distal gastrectomy(CODG) groups with respect to TNF-α.ConclusionsThe presented results prove that IL-1β and TNF-α are significant stimulating factors in gastric cancer cell adhesion in vitro and may therefore partly account for local tumor recurrence and peritoneal metastasis in vivo. Owing to less impact on the postoperative abdominal regional and systemic immune responses, laparoscopic surgery not only shows clinically relevant advantages but also causes less effect of inflammatory factors on local recurrence and peritoneal metastasis of gastric cancer than conventional operations. Thus, we offer another possible advantage of laparoscopic procedures for treatment of gastric cancer.

Regulation of colon cancer cell migration and invasion by CLIC1-mediated RVD

The metastasis of colorectal cancer is one of the most common causes of death in the world. In this investigation, we used the human colon cancer cell lines LOVO and HT29 as model systems to determine the role of the chloride intracellular channel 1 (CLIC1) in the metastasis of colonic cancer. In the present study, we found that regulatory volume decrease (RVD) capacity was markedly up-regulated in LOVO cells, which are characterized by a high metastatic potential. Functionally suppressing CLIC1 using the specific chloride intracellular channel 1 blocker Indanyloxyacetic acid 94 inhibited RVD and decreased the migration and invasion of colon cancer cells. Moreover, these effects occurred in a dose-dependent manner. The migration and invasion abilities in two cell lines also were inhibited by the knockdown of CLIC1 using small interfering RNA transfection. The mRNA and protein expression of CLIC1 is up-regulated in LOVO cells. In human colon cancer cells, CLIC1 is primarily located in the plasma membrane, where it functions as a chloride channel. Taken together, the results suggest that CLIC1 modulates the metastasis of colon cancer through its RVD-mediating chloride channel function. This study demonstrates, for the first time, that CLIC1 regulates the migration and invasion of colon cancer.

Chloride intracellular channel 1 regulates colon cancer cell migration and invasion through ROS/ERK pathway

AIM To investigate the mechanisms of chloride intracellular channel 1 (CLIC1) in the metastasis of colon cancer under hypoxia-reoxygenation (H-R) conditions. METHODS Fluorescent probes were used to detect reactive oxygen species (ROS) in LOVO cells. Wound healing assay and transwell assay were performed to examine the migration and invasion of LOVO cells. Expression of CLIC1 mRNA and protein, p-ERK, MMP-2 and MMP-9 proteins was analyzed by reverse transcription-polymerase chain reaction and Western blot. METHODS H-R treatment increased the intracellular ROS level in LOVO cells. The mRNA and protein expression of CLIC1 was elevated under H-R conditions. Functional inhibition of CLIC1 markedly decreased the H-R-enhanced ROS generation, cell migration, invasion and phosphorylation of ERK in treated LOVO cells. Additionally, the expression of MMP-2 and MMP-9 could be regulated by CLIC1-mediated ROS/ERK pathway. CONCLUSION Our results suggest that CLIC1 protein is involved in the metastasis of colon cancer LOVO cells via regulating the ROS/ERK pathway in the H-R process.

Laparoscopic Radical Correction Combined With Extensive Lymphadenectomy and Pelvic Autonomic Nerve Preservation for Mid-to-Low Rectal Cancer

OBJECTIVE The purposes of this study were to confirm the definite metastasis and micrometastasis rate of upward and lateral lymph nodes of mid-to-low rectal cancer at stage II and stage III, and to evaluate the feasibility and safety of laparoscopic radical correction combined with extensive lymphadenectomy and pelvic autonomic nerve preservation (PANP). METHODS The study was performed in 68 patients who were diagnosed with mid-to-low rectal cancer at stage II or stage III and received laparoscopic radical correction combined with extensive lymphadenectomy and PANP from June 2006 to June 2008 in the General Surgery Department of Southwest Hospital. All lymph nodes resected in the surgeries were examined by hematoxylin and eosin (H & E) stain and immunohistochemistry with an antibody against cytokeratin 20 (CK20) to confirm the conditions of metastasis and micrometastasis. We compared the postoperative complications with those of traditional surgeries. RESULTS In 1571 lymph nodes, 16 lymph nodes were found to have definite metastasis in 6 patients (8.8%) and in 41 lymph nodes we found micrometastasis in 12 patients (17.6%). The total metastasis rate of upward and lateral lymph nodes was 19.1%. Compared with traditional surgeries, the new surgery had less blood loss and short convalescence and postoperative complications were not increased. CONCLUSION The total metastasis rate of upward and lateral lymph nodes is 19.1%. The laparoscopic radical correction combined with extensive lymphadenectomy and PANP is feasible and safe.

Mouse forestomach carcinoma cells immunosuppress macrophages through transforming growth factor-β1.

Peritoneal implantation metastasis of gastric cancer cells is associated with poor prognosis. Peritoneal macrophages are the most important immune cells in the abdominal cavity to control tumor metastasis. In the present study, the immunosuppressive effects of mouse forestomach cells on macrophages were examined. Conditioned medium from mouse forestomach cell cultures were used to treat isolated peritoneal macrophages. A colorimetry-based phagocytosis assay was performed to investigate the functional change of macrophages. The alteration of cytokine secretion by macrophages was measured by ELISA assay. Specific markers of macrophage polarization were analyzed by real-time RT-PCR. TGF-β1 signaling was evaluated by western blotting. Neutralization experiments were performed using an anti-TGF-β1 antibody. Conditioned medium reduced the phagocytotic capability of macrophages. Lower TNF-α and IL-1β levels and higher IL-10 and VEGF levels were observed. Real-time RT-PCR showed increased mRNA levels of M2 macrophage markers. Further study revealed that TGF-β1 was significantly elevated in the conditioned medium and TGF-β1 signaling was activated in the macrophages by the treatment of conditioned medium. Neutralization of TGF-β1 reversed the immunosuppressive effects on macrophages. Immunosuppressive macrophages can be induced by conditioned medium from mouse forestomach cell cultures. These effects appeared to occur through the production of TGF-β1 by the tumor cells. Targeted TGF-β1 intervention may help to control peritoneal metastasis of gastric cancers.

Influence of Laparoscopic Gastrectomy on the Detection Rate of Free Gastric Cancer Cells in the Peritoneal Cavity

BackgroundWhether laparoscopic gastrectomy affects the number of gastric cancer cells exfoliated from the cancer-invaded serosa remains unclear. This study aimed to compare the detection rate of free gastric cancer cells in the peritoneal cavity during laparoscopic and open gastrectomy.MethodsIntraoperative peritoneal washings were collected from 83 gastric cancer patients undergoing laparoscopic gastrectomy and 81 patients undergoing open surgery. Hematoxylin and eosin (H&E) staining and real-time reverse-transcription polymerase chain reaction (RT-PCR) were used to examine the free cancer cells.ResultsThe postoperative positive rates of free cancer cells detected by cytological and real-time RT-PCR were 39.76 and 43.20% in the laparoscopic and open groups, respectively. Depth of tumor invasion, area of invaded serosa, regional lymph node involvement, and higher pathological staging were significantly associated with presence of free cancer cells.ConclusionThe laparoscopic techniques used in gastric cancer surgery did not increase the detection rate of free cancer cells in the peritoneal cavity compared with conventional techniques.

Prognostic role of Gli1 expression in solid malignancies: a meta-analysis

Gli1 is a downstream transcriptional factor of Sonic hedgehog pathway in mammalians, and has been recognized as a proliferative indicator of carcinogenesis. However, its actual role in prognosis among solid malignancies remains unclear. Therefore we performed this meta-analysis aiming to discover the correlation between Gli1 positivity and clinical prognosis in patients suffering from diverse carcinomas. A total of 39 studies containing 4496 cases were selected into our quantitative analysis via electronic database search. Original data of 3-year, 5-year, 10-year overall survival and disease-free survival were extracted and calculated using odds ratio and Mantel-Haenszel model. Subgroup analysis was also conducted to clarify the possible confounding factors. P < 0.05 was considered significant in statistics. Gli1 redundancy was associated with worse 3-year, 5-year, 10-year overall survival and disease-free survival in solid malignancies. Different source regions, sample-size, mean-age and detection approaches had no impact on the negative prognostic effect of Gli1 over-expression. Nevertheless, stratified by cancer type and subcellular localization, cytoplasmic Gli1 expression and Gli1 positivity in intracranial tumors was not correlated to poorer 3-year and 5-year prognosis. The over-expression of Gli1 is a credible indicator of poorer prognosis in most of solid malignancies, irrespective of intracranial tumors.

Comparison of laparoscopic and open gastrectomy on cancer cells exfoliating from the cancer-invaded serosa.

Background Whether laparoscopic gastrectomy may reduce the frequency of gastric cancer cells exfoliating from the cancer-invaded serosa remains unclear. This study aimed to compare the detection of free gastric cancer cells in the peritoneal cavity during laparoscopic and open gastrectomy. Methods Intraoperative peritoneal washings were collected from 63 gastric cancer patients undergoing laparoscopic gastrectomy and 61 patients undergoing open surgery. Hematoxylin and eosin staining and real time reverse transcription-polymerase chain reaction were used to examine the free cancer cells. Results The postoperative positive rates of free cancer cells detected by cytologic and real time reverse transcription-polymerase chain reaction were 39.68% and 44.26% in the laparoscopic and open groups, respectively. The depth of tumor invasion, area of invaded serosa, regional lymph node involvement, and higher tumor node metastasis staging were significantly associated with the presence of free cancer cells. Conclusions The laparoscopic techniques used in gastric cancer surgery were not associated with a greater risk for the intraperitoneal dissemination of cancer cells than conventional techniques.

Novel method for esophagojejunal anastomosis after laparoscopic total gastrectomy: Semi-end-to-end anastomosis

AIM To test a new safe and simple technique for circular-stapled esophagojejunostomy in laparoscopic total gastrectomy (LATG). METHODS We selected 26 patients with gastric cancer who underwent LATG and Roux-en-Y gastrointestinal reconstruction with semi-end-to-end esophagojejunal anastomosis. RESULTS LATG with semi-end-to-end esophagojejunal anastomosis was successfully performed in all 26 patients. The average operation time was 257 ± 36 min, with an average anastomosis time of 51 ± 17 min and an average intraoperative blood loss of 88 ± 46 mL. The average postoperative hospital stay was 8 ± 3 d. There were no complications and no mortality in this series. CONCLUSION The application of semi-end-to-end esophagojejunal anastomosis after LATG is a safe and feasible procedure, which can be easily performed and has a short operation time in terms of anastomosis.

Erratum to: Laparoscopic splenectomy is a better surgical approach for spleen-relevant disorders: a comprehensive meta-analysis based on 15-year literatures

Background Currently, whether laparoscopic or open splenectomy is a gold standard option for spleen abnormalities remains in controversy. There is in deficiency of academic evidence concerning the surgical efficacy and safety of both comparative managements. In order to surgically appraise the applied potentials of both approaches, we hence performed this comprehensive meta-analysis on the basis of 15-year literatures.