Cordycepin enhances the chemosensitivity of esophageal cancer cells to cisplatin by inducing the activation of AMPK and suppressing the AKT signaling pathway.

Although cisplatin (cDDP), is a first-line chemotherapy drug for esophageal cancer, it still has the potential to develop drug resistance and side effects. There is increasing evidence that cordycepin can work synergistically with other chemotherapy drugs. Therefore, we investigated whether combination therapy of cordycepin and cDDP may enhance the therapeutic effect of cDDP. We performed a series of functional tests to study the effect of medical treatment on esophageal cancer cells. We then used GO analysis to examine the pathways affected by treatment with cordycepin and cDDP. Next, we observed changes in the abundance of the selected pathway proteins. The in vivo animal model supported the results of the in vitro experiments. Co-treatment with cordycepin and cDDP inhibited cell growth, migration, and metastasis, as well as induced apoptosis. Cordycepin was found to effectively enhance activation of AMPK and inhibited activity of AKT. In all treatment groups, the expression levels of p-PI3K, p-Akt, p-p70S6K, Caspase-3, and Bcl-2 were significantly reduced, while the expression levels of p-AMPK, cleaved Caspase-3, and Bax increased, and the total levels of Akt, PI3K, and p70S6K levels remained unchanged. Overall, cordycepin was found to enhance the chemical sensitivity of esophageal cancer cells to cisplatin by inducing AMPK activation and inhibiting the AKT signaling pathway. Combination therapy of cordycepin and cisplatin represent a novel potential treatment of esophageal cancer.

Cordycepin Reverses Cisplatin Resistance in Non-small Cell Lung Cancer by Activating AMPK and Inhibiting AKT Signaling Pathway.

Cisplatin (DDP) is the first-line chemotherapeutic agent against lung cancer. However, the therapeutic effect of DDP loses over time due to the acquired drug resistance in non-small cell lung cancer (NSCLC) cells. In recent years, the role of the traditional Chinese medicine (TCM) cordycepin (Cor) in cancer treatment has been attracting attention. However, the effects of Cor on DDP resistance in NSCLC are unclear. In the present study, we aimed to investigate the effects of Cor in combination with DDP on cell proliferation and apoptosis in NSCLC and explore possible underlying mechanisms. The cell proliferation and apoptosis were analyzed in NSCLC parental (A549) and DDP-resistant (A549DDP) cells treated with DDP alone or in combination with Cor both in vitro and in vivo. Different genes and signaling pathways were investigated between DDP-sensitive and DDP-resistant A549 cells by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The perturbations of the MAPK and PI3K-AKT signaling pathways were evaluated by Western blot analysis. Our data showed that Cor markedly enhanced DDP inhibition on cell proliferation and promotion of apoptosis compared to the DDP-alone group in both A549 and A549DDP cells. The synergic actions were associated with activation of AMPK; inhibition of AKT, mTOR, and downstream P709S6K; and S6 phosphorylation in the AKT pathway compared with DDP alone. Collectively, combination of Cor and DDP has a synergistic effect in inhibiting proliferation and promoting apoptosis of NSCLC cells in the presence or absence of DDP resistance. The antitumor activity is associated with activation of AMPK and inhibition of the AKT pathway to enhance DDP inhibition on NSCLC. Our results suggested that Cor in combination with DDP could be an additional therapeutic option for the treatment of DDP-resistant NSCLC.

Risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Post-pancreaticoduodenectomy pancreatic fistula associated hemorrhage (PPFH) is one of the leading lethal complications. Our study was to analyze the risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy, and to evaluate treatment options. METHOD: We analyzed 445 patients who underwent pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy and evaluated the relevance between clinical data and PPFH. RESULTS: The incidence of postoperative pancreatic fistula (POPF) was 27.42% (122/445), and the incidence of PPFH was 4.49% (20/445). Among the 20 patients with PPFH, 7 died and 13 were cured. Interventional angiographic therapy was performed for 10 patients and 5 were successfully treated. Relaparotomy was performed for 5 patients and 2 were successfully cured. Univariate logistic regression analysis indicated that several risk factors were related to PPFH: the nature of tumor (carcinoid/low-grade or high-grade malignancy), preoperative day 1 serum prealbumin, preoperative day 1 total bilirubin (TBIL), operative time, blood loss in the operation, operative method (vascular resection and revascularization), postoperative day 3 TBIL, biliary fistula, and the grade of POPF. The multivariate stepwise logistic regression analysis demonstrated that the nature of tumor and the grade of POPF were independently risk factors of PPFH. Receiver operating characteristic curve indicated that preoperative day 1 serum prealbumin level <173 mg/L and postoperative day 3 TBIL level ≥168 µmol/L were the risk factors of PPFH. CONCLUSIONS: The risk of PPFH was found to be increased with high potential malignancy and high grade of POPF. Angiography-embolization is one of the major and effective therapies for PPFH. Extraluminal-intraluminal PPFH is more serious and needs more aggressive treatments.

HIF1/2α mediates hypoxia-induced LDHA expression in human pancreatic cancer cells.

Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages. The result of in vitro study demonstrated that hypoxia induced LDHA expression. To explore the relationship between HIF and LDHA, chromatin immunoprecipitation assay and luciferase assay were performed. The result showed that HIF-1/2α bound to LDHA at 89bp under the hypoxic condition. Furthermore, knockdown of endogenous HIF-1α and HIF-2α decreased the LDHA expression even in the hypoxic condition, which was accompanied with a significant decrease in lactate production and glucose utilization (p < 0.01). Immunofluorescence in the 244 specimens showed that HIF-1/2α was over-expressed and associated with LDHA over-expression (p < 0.0001). Forced expression of LDHA promoted the growth and migration of PC cells, while knocking down the expression of LDHA inhibited the cell growth and migration markedly. In summary, the present study proved that HIF1/2α could activate LDHA expression in human PC cells, and high expression of LDHA promoted the growth and migration of PC cells.

EDAG-1 promotes proliferation and invasion of human thyroid cancer cells by activating MAPK/Erk and AKT signal pathways.

Erythroid differentiation-associated gene (EDAG) is differentially expressed in normal hematopoietic progenitor/stem cells and a variety of embryonic tissues. High EDAG-1 expression is also found in human thyroid cancer cells and peripheral blood of patients with leukemia, but its functional significance was unclear. Current study aims to further clarify the expression pattern of EDAG-1 and tests its roles in proliferation and invasion of human thyroid cancer cells in vitro and in vivo. To this end, we have performed gain-of-function and loss-of-function studies to clarify how EDAG-1 regulates the proliferation, invasion, and adhesion ability of human thyroid cancer cells SW579cells. We found that overexpression of EDAG-1 promoted the proliferation, invasion, and adhesion of human thyroid cancer cells, whereas silencing of EDAG-1 reversed all these changes and reduced the tumorigenesis risk of nude mice. Mechanistically, we found that overexpression of EDAG-1 activated the MAPK/Erk and AKT signal pathways. These findings provide novel insights of the role of EDAG-1 in thyroid tumors, and may have direct clinical implication.

MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45α.

BACKGROUND: MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms. METHODS: We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting. RESULTS: miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45α down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45α expression in a xenograft model. Consistently, the knockdown of GADD45α expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45α mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways. CONCLUSION: miR-362-5p acts as an oncomiR that down-regulates GADD45α, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets.

Arsenite promotes intestinal tumor cell proliferation and invasion by stimulating epithelial-to-mesenchymal transition.

Arsenite (AS) is a ubiquitous environmental element that is widely present in food, soil, and water. Environmental exposure to AS represents a major global health concern, because AS is a well-established human carcinogen. We hypothesize that low concentration of AS could enhance metastasis and proliferation of transformed cancer cells by promoting EMT. To test this hypothesis, we treated human colorectal cancer cells with low concentration of AS, and then measured the multiple readouts of cell viability, proliferation, migration, and adhesion in vitro and in vivo. Collectively, our data indeed strongly support our hypothesis and shed novel light into this important pathophysiological process. These novel insights are not only of high interests to basic cancer research, but may also have direct implications in cancer prevention and treatment.

[Clinical application of reverse puncture device(RPD) in laparascopic esophagogastrectomy (esophagojejunostomy): a report of 18 cases].

OBJECTIVE: The authors report the newly developed reconstruction technique after laparoscopic total gastrectomy (LTG) or laparoscopic distal gastrectomy (LDG): intracorporeal circular stapling esophagojejunostomy(esophagojejunostomy) using the reverse puncture device(RPD). METHODS: After LTG or LDG, The anvil is then transorally inserted into the esophagus by using the RPD system. Double-stapling esophagojejunostomy with a circular stapler is performed intracorporeally, and the jejunal stump is closed with an Echelon. RESULTS: There was no intraoperative complication or conversion to open surgery, the mean operation time was 155 min and blood loss was 75 ml. Postoperative fluorography revealed no anastomosis leakage or stenosis Patients resumed an oral liquid diet on postoperative day 2, and discharged at day 8. CONCLUSIONS: We have successfully performed LTG or LDG, reconstruction using our technique in 18 patients without any anastomosis complications. We believe that our procedure is a safe and reliable reconstruction method, which is especially useful in obese patients, in whom conventional extracorporeal anastomosis is often difficult.

[Impacts of laparoscopic bariatric surgery on GLP-1 and Ghrelin level in patients with type 2 diabetes mellitus].

OBJECTIVES: To investigate the impacts of laparoscopic bariatric surgery on fasting glucagon-like peptide-1 (GLP-1) and Ghrelin level in patients with type 2 diabetes mellitus (T2DM), and the mechanism in surgical treatment of T2DM. METHODS: From March 2010 to August 2011, 44 patients with T2DM underwent laparoscopic bariatric, including laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 14), laparoscopic mini-gastric bypass (LMGB, n = 11), laparoscopic sleeve gastrectomy (LSG, n = 9) and laparoscopic adjustable gastric banding (LAGB, n = 10). The curative effects, changes of metabolism and gastrointestinal hormones were analyzed respectively. RESULTS: Within 6 months after surgery, the clinical complete remission of T2DM was 11, 8, 6, 3 cases in LRYGB, LMGB, LSG, LAGB group respectively; the clinical partial remission was 3, 3, 2, 4 cases respectively. The inefficacy was 1, 3 patients in LSG and LAGB group respectively. The effects of surgery within 6 months postoperative among 4 groups were different (χ(2) = 8.162, P < 0.05). The levels of body mass index (F = 275.29) and homeostasis model assessment of insulin resistance (F = 40.09) of 4 groups were declined in 6 months postoperatively (P < 0.01). The extents of decrease were no significance among 4 groups. Compared to preoperative level, GLP-1 in LRYGB ((116 ± 33) vs. (66 ± 20) ng/L and LMGB group ((103 ± 22) vs. (65 ± 16) ng/L) was higher in the first month after surgery (F = 21.76 and 139.21, P < 0.05). The changes in LSG and LAGB group were no significance (P > 0.05). The level of Ghrelin in LRYGB, LMGB, LSG group at the first week after surgery were (208 ± 79), (275 ± 102) and (258 ± 91) ng/L respectively, and they were lower than preoperative (there were (398 ± 114), (439 ± 96) and (446 ± 105) ng/L, F = 55.08, 49.96 and 46.47, all P < 0.01). But the level of Ghrelin in LRYGB and LMGB groups rebounded in the first postoperative month. The postoperative level of Ghrelin was higher in LAGB group (F = 29.24, P = 0.001). CONCLUSIONS: There are difference efficacies and impacts on gastrointestinal hormones among different modes of bariatric surgery. The change of gastrointestinal hormones is plausible mechanism of T2DM remission after surgery.

[Outcomes after laparoscopic surgery for 219 patients with obesity].

OBJECTIVE: To evaluate the outcomes after laparoscopic gastrointestinal surgery for patients with obesity and type 2 diabetes mellitus(T2DM). METHODS: From June 2003 to June 2010, 219 patients underwent laparoscopic gastrointestinal surgery for obesity and T2DM, including laparoscopic adjustable gastric banding(LAGB, n=201), laparoscopic mini gastric bypass(LMGB, n=13), and laparoscopic sleeve gastrectomy(LSG, n=5). Clinical data were analyzed retrospectively. RESULTS: The mean body mass index(BMI) of patients who received LAGB was 37.9 kg/m(2), and decreased to 32.4 kg/m(2) at 6 months and to 29.7 kg/m(2) at 12 months. In 43 patients who had concurrent T2DM, 11(25.6%) showed clinical partial remission(CPR) and 16(37.2%) clinical complete remission (CCR). Postoperative complications occurred in 26 patients(12.9%). The mean BMI of patients undergoing LMGB was 34.7 kg/m(2), and decreased to 31.6 kg/m(2) at 6 months and 26.9 kg/m(2) at 12 months after surgery. Ten patients had T2DM before operation, of whom 2(20.0%) had CPR and 7(70.0%) CCR postoperatively. Postoperative complications occurred in 2 patients(15.4%). The mean BMI of patients who underwent LSG was 43.8 kg/m(2), and was reduced to 38.1 kg/m(2) at 6 months and 34.3 kg/m(2) at 12 months after operation. Three patients were diagnosed with T2DM before operation. One patient (33.3%) had CPR and 1(33.3%) reached CCR after operation. There was 1(20.0%) patient who developed complication. No perioperative death occurred. CONCLUSION: Laparoscopic gastrointestinal surgery may result in satisfactory weight loss and clinical remission of T2DM with few complications.

Extraluminal laparoscopic wedge resection of gastric submucosal tumors: a retrospective review of 84 cases.

BACKGROUND: Laparoscopic resection of gastric stromal tumors is being performed with increased frequency. This study aims to evaluate the feasibility and safety of the extraluminal laparoscopic gastric wedge resection (ELWR) technique. METHODS: Clinical data of 84 patients who underwent ELWR for gastric submucosal tumors between September 2000 and December 2007 were reviewed and analyzed retrospectively. The operation includes: localization of the tumor, dissection of the omentum, mobilization of the upper stomach and the upper pole of the spleen, exposure of esophago-cardiac junction (ECJ), and wedge resection of the upper part of gastric body and/or the gastric fundus with endoscopic gastrointestinal anastomosis (Endo GIA) stapler. RESULTS: All of the procedures were performed successfully, with mean operation time of 62.6 +/- 8.9 min and mean intraoperative blood loss of 86.2 +/- 8.1 ml. Through extraluminal laparoscopic wedge resection, complete R0 resection was achieved for all tumors. All surgical margins were negative microscopically. No lesions were missed, nor were there any significant postoperative complications or intraoperative conversions to open surgery. A total of 78.6% of the patients recovered their gastrointestinal functions and began to eat and ambulate within 36 h of the operation. The smallest surgical margins were 0.7-2.5 cm, with a mean distance of 1.4 +/- 0.5 cm. Of the 84 cases of gastric submucosal tumors, 29 cases were leiomyomas, 51 cases were various types of stromal tumors, and 4 other cases were neurofibromas. Mean follow-up duration was 51 +/- 4.3 months (overall follow-up rate 73.8%, 62/84 cases), during which no recurrences or metastases were found. CONCLUSION: ELWR is a safe, simple, and effective procedure for treating submucosal tumors in the upper part of the stomach. It can avoid intraperitoneal contamination, possible tumor spillage, and postoperative esophageal stenosis, and provides unlimited scope for gastric resection.

[A new technique for esophagojejunostomy or esophagogastrostomy after laparoscopic gastrectomy].

OBJECTIVE: To report the newly developed reconstruction technique after laparoscopic total gastrectomy: intracorporeal circular stapling esophagojejunostomy using the transorally inserted anvil (OrVil; Covidien), and evaluate its feasibility, safety, and clinical outcomes. METHODS: After LTG (3 patients with gastric carcinoma in the body) or LPG (2 patients with gastric carcinoma in the cardiac and fundus, respectively, and 1 with cardiac stromal tumor), the anvil was then inserted transorally into the esophagus by using the OrVil system. Double-stapling esophagojejunostomy or esophagogastrostomy with a circular stapler was performed intracorporeally. RESULTS: The operations were uneventful. The operative time was (183.3+/-25.8) min, and blood loss was (128.3+/-90.2) ml. Postoperative fluorography revealed no anastomotic leakage or stenosis. Patients resumed an oral liquid diet on postoperative day (4.0+/-1.1), and were discharged on day (9.0+/-2.6). Patients were followed at 28 days and no complications were reported. CONCLUSIONS: LTG with Roux-en-Y reconstruction or LPG with esophagogastrostomy using the OrVil system appear to be safe and reliable with satisfactory short-term outcomes.

[Effects of Gastric bypass surgery on the apoptosis of islet ß-cells in type 2 nonobese diabetic (NOD) rats and its mechanism].

OBJECTIVE: To investigate the effects of Gastric bypass surgery on the apoptosis of islet ß-cells in type 2 nonobese diabetic (NOD) rats and its mechanisms. METHODS: Seventy-two 8-week-old GK rats were randomly divided into four groups:operation group (group O, n = 18), sham operation group (group S, n = 18), diet control group (group F, n = 18) and control group (group C, n = 18). The levels of fasting, postprandial blood glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured and compared among the 4 groups before the operation and at 1, 2, 4 and 8 weeks following the operation. The blood samples were collected at 2, 4 and 8 weeks after the operation for the measurement of postprandial blood glucose, and then the rats in batches (6 rats in each group) were decapitated to retrieve the pancreas. The apoptosis of the islet ß-cells was detected by using TUNEL assay, and the expression of apoptosis-related proteins Bcl-2, Bax was measured with immunohistochemistry. RESULTS: As for group O, the fasting blood glucose level decreased from (16.2 ± 0.8) mmol/L before the operation to respectively (9.2 ± 0.6) mmol/L and (9.7 ± 0.7) mmol/L at 4 and 8 weeks after the operation; postprandial blood glucose decreased from (31.1 ± 1.1) mmol/L before the operation to respectively (13.1 ± 0.7) mmol/L and (12.3 ± 0.7) mmol/L at 4 and 8 weeks after the operation. Fasting insulin level increased from (28.0 ± 1.2) mU/L before the operation to respectively (62.8 ± 1.9) mU/L and (61.7 ± 1.4) mU/L at 4 and 8 weeks after the operation; and at 4 and 8 weeks after the operation postprandial insulin level was (77.4 ± 1.1) mU/L and (77.1 ± 1.0) mU/L. At 2 weeks from the operation, the fasting GLP-1 in group O increased from (10.7 ± 1.0) pmol/L to (13.5 ± 0.8) pmol/L, and respectively to (26.1 ± 0.9) pmol/L and (25.3 ± 1.2) pmol/L at 4 and 8 weeks after the operation. The differences in the above-mentioned items before and after the operation were all significant in group O (P < 0.05), and the differences in the items among group O and the other three groups (P < 0.05) were all significant as well. In group O, the apoptosis rate of pancreatic islet cell decreased to (5.9 ± 0.7)% at 4 weeks from the operation, and (6.3 ± 1.1)% at 8 weeks from the operation (P < 0.05). The expression of Bcl-2 protein in group O was 31.3 ± 1.5, 35.7 ± 1.0 and 35.8 ± 0.8 at 2, 4 and 8 weeks post operation, which was significantly higher in statistics than those of the same time point in the other three groups (P < 0.05). The expression of Bax protein in group O was 13.3 ± 0.9, 10.8 ± 0.9 and 10.9 ± 1.1 at 2, 4 and 8 weeks from the operation, which was significantly lower in statistics than those of the same time point in the other three groups (P < 0.05). CONCLUSIONS: Gastric bypass surgery can significantly reduce the blood glucose level and promote the secretion of GLP-1, and therefore inhibit the apoptosis of the islet ß cells in diabetic rats through the Bcl-2 pathway.

[Laparoscopic adjustable gastric banding in the treatment of obesity: analysis of 172 cases].

OBJECTIVE: To evaluate the outcome of weight loss by laparoscopic adjustable gastric banding (LAGB) on obesity patients and the improvement of comorbidity. METHODS: From June 2003 to June 2009, the data 172 obesity patients(119 women, 53 men, mean age 28.5 years, mean body mass index 38.5 kg/m(2)) were analyzed. Comorbidities included 28 cases with diabetes, 36 with hypertension, 85 with dyslipidemia, 56 with sleep apnea and 138 with fatty liver. RESULTS: Mean body mass index(BMI) at 1,3,6,12, 24, 36 and 48 months was 37.2 kg/m(2),35.9 kg/m(2), 34.5 kg/m(2), 32.9 kg/m(2), 30.7 kg/m(2), 29.2 kg/m(2) and 28.1 kg/m(2), respectively. The percentage of excess weight loss(% EWL) at 1, 3, 6, 12, 24, 36, and 48 months was 10.1%, 16.2%, 25.1%, 37.4%, 51.3%, 59.0% and 62.1%, respectively. At 24, 36 and 48 months, respectively, 50.7%, 63.6% and 70.0% of patients had more than 50% excess weight loss. Complications included 6 cases of port infection, 3 of other port problem, 7 of gastric pouch dilatations, 4 of slippage and 1 of chronic intestinal obstruction. Bands of 5 patients were explanted. No death occurred. Blood glucose of 60.7% patients with diabetes was controlled well without any drug. The blood pressure of 22 hypertensive patients became normal. The blood fat of 49 hyperlipidemia cases returned to normal. The symptom of 29 patients with sleep apnea disappeared. All the patients with fatty liver were improved in different degree. CONCLUSION: Gastric banding provides good weight loss and significant reduction in comorbidities with few and minor complications.

[Short-term outcome of laparoscopic gastric bypass and minigastric bypass on obesity patients with type 2 diabetes mellitus].

OBJECTIVE: To evaluate the short-term outcome of laparoscopic gastric bypass on obesity patients with type 2 diabetes mellitus. METHODS: Seven obesity patients with type 2 diabetes mellitus received laparoscopic gastric bypass(n=1) or laparoscopic minigastric bypass(n=6), and their data of treatment outcomes were analyzed. RESULTS: The operations were all successfully performed without any complications. The average operation time was 125 minutes(range: 100 to 170 minutes). The patients underwent 1-18 months follow-up after operation. Diabetic indicators returned to normal without any medication and body weight reduced by on average of 24.3 kg. CONCLUSION: Laparoscopic gastric bypass and minigastric bypass have good short-term outcome in the treatment of obesity patients with type 2 diabetes mellitus.

[Effects of duodenal-jejunal bypass and sleeve gastrectomy on the expression of liver glucokinase in diabetic rats].

OBJECTIVE: To investigate the effects of duodenal-jejunal bypass(DJB) and sleeve gastrectomy(SG) on the expression of liver glucokinase(GCK) in diabetic rats. METHODS: Animal models of Goto-Kakizaki rats and Sprague-Dawley rats were established by DJB and SG. Results of fasting glycemia and insulin were compared. Liver tissue was harvested 8 weeks postoperatively.Quantitative real-time PCR and Western blot were used to detect liver GCK mRNA and protein expression after operation. RESULTS: Fasting plasma glucose levels of DJB group and SG group in GK rats were markedly declined 3 day and 1, 2, 4, 6, 8 weeks postoperatively(all P <0.01), while Sham group only dropped 3 day and 1 week postoperatively, and there were no significant differences 2 weeks postoperatively(P >0.05). Fasting plasma glucose levels of each group in SD rats did not change after operation. In GK rats, GCK mRNA level (1.45 +/-0.29) and protein expression (494.25 +/-30.25) after DJB were higher than Sham group (1.05 +/-0.19 and 409.13 +/-26.86) and control group (1.04 +/-0.17 and 404.75 +/-30.90). GCK mRNA level and protein expression after SG were 0.65 +/-0.25 and 345.25 +/-28.13 respectively, which were significantly lower than those in control group(all P <0.01). All the groups in SD rats experienced similar GCK expression change. CONCLUSION: Both DJB and SG can decrease the plasma glucose levels of GK rats, while there are different effects on the expression of liver GCK.

Extraluminal laparoscopic wedge-resection of submucosal tumors on the posterior wall of the gastric fundus close to the esophagocardiac junction.

PURPOSE: Laparoscopic resection of submucosal tumors in the gastric fundus, especially in the posterior wall near the esophagocardiac junction (ECJ), is difficult and time consuming and is and likely to cause esophageal stenosis and splenic injury. In this article, we report an extraluminal laparoscopic wedge-resection (ELWR) that minimizes these problems. METHODS: Thirty-seven patients with submucosal tumors in the posterior wall of the gastric fundus received ELWR. The operation consisted of four steps: 1) localization of the tumor, 2) dissection of the omentum, 3) mobilization of the gastric fundus/upper pole of the spleen and exposure of the ECJ, and 4) resection of the gastric fundus with a linear endoscopic gastrointestinal anastomosis stapler. RESULTS: None of the cases needed conversion to open surgery. Mean postoperative hospital stay was 5.5 +/- 1.0 days. The distance between the tumor and the incision margin ranged from 0.7 to 2.5 cm toward the ECJ. Pathologic examination revealed 7 cases of leiomyomas, 29 cases of stromal tumors (4 were low-grade malignant tumors), and 1 case of neurofibroma. There was no recurrence, metastasis, esophageal stenosis, or any other severe adverse event during the follow-up period (52 +/- 3.1 months). CONCLUSIONS: ELWR is a safe, effective treatment for submucosal tumors in the posterior wall of the gastric fundus.

[Application of neoadjuvant chemotherapy in laparoscopic gastrectomy for advanced gastric cancer].

OBJECTIVE: To explore the benefit of neoadjuvant chemotherapy in advanced gastric cancer patients treated by laparoscopy. METHODS: Fifteen patients with histologically proved gastric adenocarcinomas (stages II(, III(, IIII(M(0)) were treated with FOLFOX7 neoadjuvant chemotherapy followed by laparoscopy between June 2005 and March 2007( trial group). Thirty patients were assigned to the control group with only laparoscopic treatment in the same period. The clinicopathological data were compared between two groups. RESULTS: All the patients in trial group accepted four cycles of preoperative chemotherapy and the toxicity was less than grade 3. Two of them achieved complete response, 10 achieved partial response and 3 kept stable disease. Ten patients of trial group underwent laparoscopic-assisted radical gastrectomy. The rates of R(0)-resection(80.0%) and pN(0) (60.0%) in trial group were significantly higher than those in control group(46.7% and 20.0%), while the rate of positive lymph node 11.0%(34/309) was significantly lower than that of control group 23.8%(142/596). The operation time and postoperative complication were similar in two groups. CONCLUSIONS: Advanced gastric cancer after neoadjuvant chemotherapy can be down-regulated in the stage, increase the rate of R(0)-resection, diminish the infiltration extent of tumor, decrease the metastasis of lymph node, and increase the possibility of laparoscopic radical gastrectomy.

[Laparoscopic resection of submucosal tumors in gastric fundus].

OBJECTIVE: To investigate the feasibility and safety of extraluminal laparoscopic wedge resection (ELWR) in treating submucosal tumors in the gastric fundus. METHODS: Clinical data of 84 patients underwent ELWR for submucosal tumors in the gastric fundus between September 2000 and December 2006 were reviewed and analyzed retrospectively. The four-portal operation procedures were carried out as follows: localization of the tumor, dissection of the omentum, mobilization of the gastric fundus and the upper polar of spleen, exposure of ECJ, and resection of the gastric fundus with Endo GIA. RESULTS: The patients included 53 males and 31 females, age ranged from 32 to 78 years (mean, 59 years). The mean tumor diameter was (4.2 +/- 1.3) cm. The distance from the tumor edge to the ECJ was 1.1 - 3.0 cm. The operations were successful in all the 84 patients, with a mean operation time of (62.6 +/- 8.9) min and mean operative blood loss of (86.2 +/- 8.1) ml. No apparent tumor focus was left. No operation was converted to open surgery, and no significant postoperative complications occurred. The mean post-operative hospital stay was (5.6 +/- 0.5) days. The gastrointestinal function recovered within 36 h after operation in 66 cases (78.6%), and the patients returned to normal activity and restored oral feeding. The distance between the tumor and the resection margin was 0.7 - 2.5 cm from the ECJ [mean, (1.4 +/- 0.5) cm], and 2.5 - 6.0 cm from the other three sides [mean, (4.1 +/- 1.0) cm]. Of the 84 cases, 29 cases were diagnosed with leiomyoma, 51 cases different types of stromal tumor and 4 cases neurofibroma. The mean follow-up duration was (51.0 +/- 4.3) months, no recurrence or metastasis was found in the mean time. CONCLUSIONS: ELWR is a safe, simple and beneficial procedure for submucosal tumors in the gastric fundus, especially in the posterior wall near the ECJ. It avoids intraperitoneal infection, possible splenic injury and postoperative esophageal stenosis. In addition, the resection scope is not limited.