Elevated visceral fat area is associated with adverse postoperative outcome of radical colectomy for colon adenocarcinoma patients.

OBJECTIVE: To assess the impact of visceral obesity quantified by preoperative computed tomography on short-term postoperative outcomes compared with body mass index (BMI) in stage I-III colon adenocarcinoma patients. METHODS: In this retrospective study, 107 patients treated with radical colectomy for stage I-III colon adenocarcinoma were classified as obese or non-obese by computed tomography-based measures or BMI (obese: BMI ≥28 kg/m2 , visceral fat area (VFA) to subcutaneous fat area ratio (V/S) ≥0.4, and VFA ≥100 cm2 ). Clinical variables, operation time, estimated blood loss, pathologic stage, histologic grade, postoperative complications, postoperative stay and hospitalization expenses were compared. RESULTS: Obese patients by VFA were more likely to have higher postoperative complication rate (32.9 versus 11.8%, P = 0.021), have longer operation time (184.6 ± 49.5 versus 163.1 ± 44.1 min, P = 0.033), postoperative stay (15.21 ± 7.59 versus 12.29 ± 5.40 days, P = 0.047) and cost more ($10 758.7 ± 3271.7 versus $9232.0 ± 2994.6, P = 0.023) than non-obese. CONCLUSION: Visceral obesity graded by VFA is associated with increased postoperative morbidity, operation time, postoperative stay and hospitalization expenses for colon adenocarcinoma patients and may be superior to BMI or V/S for the prediction of colon surgery.

MicroRNA 495 Inhibits Proliferation and Metastasis and Promotes Apoptosis by Targeting Twist1 in Gastric Cancer Cells.

Recently, microRNAs (miRNAs) have been reported to participate in multiple biological processes. However, the effects of miR-495 on gastric cancer (GC) remain unclear. The purpose of this study was to explore the functions of miR-495 in GC cell proliferation, metastasis, and apoptosis. SGC-7901 and BGC-823 cell lines were transfected with miR-495 mimic, miR-495 inhibitor, and negative controls (mimic control and inhibitor control). The expressions of miR-495, cell viability, migration, apoptosis, and apoptosis-related factors were examined by qRT-PCR, trypan blue staining, Transwell, flow cytometry, and Western blot, respectively. Simultaneously, key factor expression levels of EMT were detected by qRT-PCR and Western blot. The direct target of miR-495 was confirmed by dual-luciferase assay. Additionally, sh-Twist1, pc-Twist1, and corresponding controls were transfected into SGC-7901 and BGC-823 cells, and the protein levels of EMT-associated factors were detected by Western blot. miR-495 was downregulated in GC cells. miR-495 expression level was effectively overexpressed or suppressed in SGC-7901 and BGC-823 cells. Overexpression of miR-495 significantly decreased cell viability and migration, increased apoptosis, and inhibited the EMT process. Suppression of miR-495 showed contrary results. Twist1 was clarified as a target gene of miR-495, and Twist1 silencing obviously reduced the promoting effect of miR-495 suppression on these biological processes. Twist1 silencing significantly blocked the EMT process in both SGC-7901 and BGC-823 cells. miR-495 inhibited proliferation and metastasis and promoted apoptosis by targeting Twist1 in GC cells. These data indicated that miR-495 might be a novel antitumor factor of GC and provide a new method for the treatment of GC.

[NF-κb inhibitor PDTC enhances tumor necrosis factor α-induced apoptosis of gastric cancer cell SGC-7901].

OBJECTIVE: To investigate the effect of PDTC (inhibitor of NF-κb) on apoptosis of human gastric cancer cell line SGC-7901 induced by tumor necrosis factor α (TNF-α) and explore the related mechanisms. METHODS: After the treatment with different concentrations of PDTC, TNF-α or PDTC combined with TNF-α on gastric cancer cell line SGC-7901, the growth inhibition of SGC-7901 was measured by MTT assay. Hoechst was used to assess SGC-7901 cell apoptosis. The protein expressions of survivin and caspase-3 were detected by Western blot assay. RESULTS: The growth inhibition rate of SGC-7901 induced by PDTC (15, 30, 60, 100 µmol/L) was (12.14±0.91)%, (20.00±1.11)%, (37.63±1.01)% and (41.46±1.07)%. Different concentrations of PDTC all inhibited the growth of SGC-7901 significantly (all P<0.01), The growth inhibition rate of SGC-7901 induced by 25 mg/L TNF-α was (2.38±0.67)%, which could not significantly inhibit the growth of SGC-7901 [control (1.50±0.81)%], while TNF-α of 50, 100, 150 mg/L could inhibit the growth of SGC-7901 significantly [(4.53±0.85)%, (4.43±0.70)% and (4.74±1.07)%, all P<0.05]. PDTC (15 µmol/L) combined with TNF-α (25, 50, 100, 150 mg/L) significantly increased the cell growth inhibition rate compared with TNF-α alone or PDTC 15 µmol/L alone (all P<0.01). Hoechst assay showed that 100 mg/L TNF-α, 15 µmol/L PDTC and combination of above two all induced cell apoptosis (P<0.01), and the combination group had significantly higher percentage of cell apoptosis (P<0.01). Survivin protein was significantly down-regulated in combination group as compared with single TNF-α (100 mg/L) group, but was not significant down-regulated as compared with single PDTC (15 µmol/L) group. Caspase-3 protein expression was significantly increased in combination group as compared with other two groups. CONCLUSION: PDTC can enhance the cell apoptosis induced by TNF-α, which may be associated with the blocking of TNF-α-activated NF-κB signaling pathway by PDTC, the down-regulation of survivin expression, and up-regulation of caspase-3 expression.

Correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2.

BACKGROUND: The relationship between the presence of metalloproteinases and thyroid cancer remains unknown, and many controversies still exist in this field. The objective of this study was to investigate the correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2. METHODS: The correlations were studied by detecting the levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 by enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the peripheral blood of 30 patients with papillary thyroid carcinoma, 27 patients with benign thyroid disease, and 25 healthy volunteers. RESULTS: The levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood of patients with papillary thyroid carcinoma were significantly higher than those in the peripheral blood of patients with benign thyroid disease and healthy volunteers (P < 0.05). However, there were no significant differences between patients with benign thyroid disease and healthy volunteers (P > 0.05). The accuracy of detection by both enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the papillary thyroid cancer group was 83.33%. CONCLUSIONS: The levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood are helpful in identifying thyroid carcinoma and aid in preoperative assessment.

[Study of inhibiting and killing effects of transgenic LIGHT human umbilical cord blood mesenchymal stem cells on stomach cancer].

OBJECTIVE: To study the inhibition and killing effect of transgenic LIGHT umbilical cord blood mesenchymal stem cells (UCBMSCs) on stomach carcinoma. METHODS: The LIGHT gene was recombined to construct the transfer plasmid pGC-FU-LIGHT by infusion technique. The 293T cells were co-transfected with the transfer plasmid pGC-FU-LIGHT, the construction plasmid Helper 1.0 and the envelope plasmid Helper 2.0 with the help of lipofectamine 2000 to produce lentiviral particles. Transgenic UCBMSCs(MSC-LIGHT) and empty carrier UCBMSCs (MSC) were obtained. Human gastric cancer cell SGC-7901 was injected into nude mice subcutaneously groin. The model of transplanted human gastric cancer cell SGC-7901 in nude mice was established. Tumorigenesis nude mice were separated into three groups randomly with 5 in each group: MSC-LIGHT group, MSC group, and NS group. Three groups of nude mice were injected around the tumor with MSC-LIGHT, MSC and NS every other day for 3 times. Four weeks later, the transplanted gastric cancer volume was measured. The expressions of LIGHT in the three groups were determined by RT-PCR and ELISA method. The necrosis area in the tumors was calculated under pathological examination. RESULTS: The average volume of transplanted tumor was(0.45±0.25) cm(3) in MSG-LIGHT group, (0.64±0.36) cm(3) in MSG group, and(1.21±0.79) cm(3) in NS group, and the difference was statistically significant(P<0.05). The LIGHT mRNA was 2.96±0.27, 1.23±0.47, and 0.73±0.10 respectively. The LIGHT protein was(167.89±2.31), (73.22±5.74), and (49.66±5.25) ng/L. The differences were all statistically significant among the three groups(both P<0.01). Pathological examination showed that the necrosis area was largest in MSC-LIGHT group. CONCLUSION: Transgenic UCBMSCs secret LIGHT in a paracrine manner, which has inhibition and killing effects on stomach carcinoma.

[Analysis of prognostic factors for gastric stump cancer].

OBJECTIVE: To investigate the independent prognostic factors of long-term survival for gastric stump cancer after radical resection. METHODS: The clinicopathological and follow-up data of 63 patients with gastric stump cancer undergoing surgical treatment from January 1996 to December 2006 in our hospital were analyzed retrospectively, including age, gender, types of reconstruction, tumor location, histological types, TNM stages, surgical treatment, prognosis and etc. The survival was estimated using Kaplan-Meier method and compared using log-rank test. The effect of independent factors on prognosis was determined by Cox regression multivariate analysis. RESULTS: Radical resection was performed in 35 patients, including combined multiple organ resection (n=16). Surgery was palliative in 28 patients. All the 63 patients were followed up. The median survival time of these 63 patients was 21 months, and the overall 1-, 3-, 5-year survival rates were 76.2%, 31.7% and 18.8%, respectively. Univariate and multivariate analysis showed that surgical procedure, clinical stage and histological type were independent prognostic factors of gastric stump cancer, while age, gender, type of reconstruction and tumor location were not significantly correlated with prognosis. CONCLUSIONS: Radical resection, clinical stage and histological type are main prognostic factors for gastric stump cancer. Radical resection is an effective way to prolong the postoperative survival time in patients with gastric stump cancer, especially in the early stage.

[Surgical treatment and prognostic factors for obstructing left colorectal cancer].

OBJECTIVE: To investigate the outcomes of surgical treatment and the prognostic factors of long-term survival for obstructing left colorectal cancer. METHODS: Clinicopathological and follow-up data of 93 patients with obstructing left colorectal cancer undergoing surgical treatment from January 2001 to December 2006 in the Affiliated Hospital of Medical College of Qingdao University were analyzed retrospectively. RESULTS: There were 53 males and 40 females. The median age was 61 years old. Fifty-one patients had concurrent medical condition. Radical resection was performed in 67 patients, including one-stage resection (n=21), Hartmann procedure (n=35), and Miles procedure (n=11). Surgery was palliative in 26 patients, including diverting stoma (n=14), bypass surgery (n=7), and palliative resection (n=5). All the 93 patients were followed up. The 1-, 3-, and 5-year survival rates were 94%, 59%, and 38%, respectively. Univariate and multivariate analyses showed that radical resection, TNM staging, and preoperative level of carcinoembryonic antigen were independent prognostic factors (all P<0.05). CONCLUSIONS: Radical resection, TNM stage, and preoperative CEA level are prognostic factors of obstructing left colorectal cancer. Early diagnosis, radical resection, and selection of appropriate surgical procedure are helpful to prolong survival time of patients with obstructing left colorectal cancer.

CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma.

AIM: To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma. METHODS: In 40 cases of gastric cancer, expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistry assay. SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration. RESULTS: Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243, P < 0.05). The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338, P < 0.05). CXCR4 expression was significantly related to poorly differentiated, high tumor stage and lymph node metastasis. Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601, P < 0.05). The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r = 0.776, P < 0.01). Additionally, human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1. AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells. CONCLUSION: The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer. CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.

[Reconstructive approaches of alimentary canal for subtotal gastrectomy].

OBJECTIVE: To explore the optimal technique of digestive tract reconstruction for radical proximal gastrectomy. METHODS: The clinical data for 120 cases of proximal gastric cancer undergoing radical proximal gastrectomy at our hospital from 2000 to 2009 were analyzed retrospectively. They included three approaches of digestive tract reconstruction. The patients were divided into esophagogastric anterior wall anastomosis group (n = 50), jejunal interposition group (n = 26) and gastric tube group (n = 44). The quality of life was evaluated and compared among 3 groups. RESULTS: The rates of anastomotic fistula, anastomotic obstruction and the scores of heart burn and reflux esophagitis were higher in gastric tube group. And the increments of hemoglobin and body weight were less in gastric tube group than those in other groups (P < 0.05). The rates of gastric emptying in gastric tube group had no obvious differences with esophagogastric anterior wall anastomosis group at 120 min and 180 min (P > 0.05). And they were higher than those in jejunal interposition group (P < 0.05). There was no statistical difference in any parameter between esophagogastric anterior wall anastomosis and jejunal interposition groups (P > 0.05). CONCLUSION: The anastomosis of esophagogastric anterior wall is an ideal approach of digestive reconstruction for radical proximal gastrectomy. And it may improve the quality of life for surgical patients with proximal gastric cancer.

[Influence of obesity on short-term surgical outcome in patients with gastric cancer].

OBJECTIVE: To explore the influence of obesity on surgical procedure and short-term surgical outcome in patients with gastric carcinoma. METHODS: A total of 426 patients with gastric carcinoma underwent laparotomy in our hospital during January 2006 and June 2008. All the patients were divided into obesity group and non-obesity group according to body mass index (BMI). The thickness of subcutaneous fat (SCF), abdominal anterior-posterior diameter (APD) and transverse diameter (TD) at the umbilicus level were measured by abdominal CT. Furthermore, the surgical data and postoperative conditions including short-term outcome were reviewed and compared between two groups. RESULTS: The incidence of obesity was 29.8% in gastric carcinoma patients. Mean values of SCF thickness, APD and TD in obesity group and non-obesity group were (21.8+/-7.1) mm vs (14.4+/-7.5) mm, (223.2+/-24.6) mm vs (181.8+/-23.5) mm and (323.6+/-23.8) mm vs (285.8+/-24.4) mm (P=0.000). Longer operative time (P=0.007) and less amount of dissected lymph nodes were found in obesity group as compared to non-obesity group (P=0.000). Also, obesity group lasted a longer postoperative period of fever (P=0.000) and experienced more post-operative complications (P=0.005) than non-obesity group did. CONCLUSIONS: Abdominal CT scan may display the abdominal shape of gastric carcinoma patients, hence, it is useful to evaluate the difficulty of surgical procedure. These patients may involve in complicated surgical procedure and worse short-term outcome due to obese abdominal shape. Therefore, perioperative management should be emphasized for these patients.

[Risk factors of intra-abdominal infection following gastrectomy in gastric cancer patients].

OBJECTIVE: To investigate the main risk factors associated with intra-abdominal infection(IAI) following gastrectomy in gastric cancer patients. METHODS: Case-control study was used to investigate the clinical data of 1728 gastric carcinoma cases retrospectively by Logistic regressive analysis. RESULTS: Univariate Logistic regressive analysis showed 16 factors, including age, malnutrition, chronic obstructive pulmonary disease(COPD), diabetes mellitus(DM), heart diseases, prothrombin time, lymphocyte count, tumor size, ascites, invasion to the adjacent organ, neoplasm TNM staging (UICC, 1997), methods of gastrectomy, blood loss, operative time, blood transfusion and extent of lymph nodal dissection,were associated with postoperative intra-abdominal infection. Binary Logistic regression analysis found that extent of lymph nodal dissection(N(2)(+) approximately N(3) and N(2)), invasion to the adjacent organ, DM, operative time, age and lymphocyte count were the independent risk factors associated with mortality. CONCLUSION: Necessary interventions should be carried out to prevent IAI referring to above risk factors.

[Applying patial least-squares discriminant analysis on autofluorescence spectra to identify gastric cancer].

Measurement of fluorescence intensity was performed at excitation wavelength of 308 nm and emission wavelength in the range of 328-596 nm. The partial least-squares (PLS) method was used to analyze autofluorescence spectra of gastric cancer. The 42 normal samples and 42 cancer samples were taken from 42 gastric cancer patients. The normalized and centralized spectra of two kinds of samples showed similar but divergent patterns. PLS classification algorithm could differentiate cancer tissues from normal tissues with a sensitivity of 83.3%, a specificity of 95.2%, and a positive predictive value of 94.6%. We concluded therefore that the PLS method was a fast, effective choice for identification of gastric cancer.

[Effect of activated greater omental milky spots and peritoneal macrophages on tumoricidal activity against gastric carcinoma SGC-7901 in mice].

OBJECTIVE: To investigate the effect of activated greater omental milky spots and peritoneal macrophages in mice on tumoricidal activity against gastric carcinoma SGC-7901, following intraperitoneal (i.p.) injection of INF-gamma, staphylococcin aureus or NDV-L. METHODS: The quantitative changes of milky spots were determined by activated carbon, the number of the macrophage in milky spots was assessed by nonspecific esterase stain and the number of peritoneal macrophages was counted by trypan blue exclusion. The morphology of peritoneal macrophages was observed by scanning electron microscope, the amount of TNF-alpha and iNOS mRNA expressed by peritoneal macrophages was measured by fluorescence quantitative PCR and the cytotoxicity of peritoneal macrophages supernatant against SGC-7901 was evaluated by MTT assay. RESULTS: It was found in the treated groups that: 1. The amount of greater omental milky spots and the macrophages in milky spots increased, 2. The number of peritoneal macrophages increased. The peritoneal macrophages were in activated status. The effect TNF-alpha and iNOS mRNA expression increased and 3. The cytotoxicity against in vitro SGC-7901 increased. CONCLUSION: Intraperitoneal injection of IFN-gamma, staphylococcin aureus or NDV-L could activate the milky spots of the greater omentum and the macrophages in peritoneal cavity in mice, with IFN-gamma being the best. The supernatant of activated peritoneal macrophages has cytotoxicity against SGC-7901. Administration of LPS to macrophages cultured in vitro could amplify the activation and enhance the cytotoxicity of the supernatant against SGC-7901.