Endoscopic submucosal dissection of gastric lesions by using a Master and Slave Transluminal Endoscopic Robot (MASTER).

BACKGROUND: Performing endoscopic submucosal dissection (ESD) by using standard endoscopy platforms is technically challenging because of the equipment's lack of dexterity. OBJECTIVE: To explore the feasibility of using the Master and Slave Transluminal Endoscopic Robot (MASTER), a novel robotics-enhanced endosurgical system, to perform ESD. DESIGN: ESD was performed on simulated gastric lesions in 5 Erlangen porcine stomach models (ex vivo) and 5 live pigs (in vivo). Performance of ESD by using the MASTER was compared with that using the insulation-tipped (IT) diathermic knife. SETTING: SMART Laboratory, Advance Surgical Training Centre, National University Hospital, Singapore. SUBJECTS: Five Erlangen porcine stomach models and 5 pigs, 5 to 7 months old, each weighing about 35 kg. INTERVENTIONS: ESD. MAIN OUTCOME MEASUREMENTS: Lesion resection time, grasper and hook efficacy grade, completeness of resection, and presence of procedure-related perforation. RESULTS: In the Erlangen stomach models, 15 simulated lesions from the cardia, antrum, and body were removed en bloc (mean dimension, 37.4 x 26.5 mm) by electrocautery excision using the MASTER. The mean ESD time was 23.9 minutes (range 7-48 minutes). There was no difference in the dissection times of lesions at different locations (P = .449). In the live pigs, the MASTER took a mean of 16.2 minutes (range 3-29 minutes) to complete the ESD of 5 gastric lesions, whereas the IT diathermic knife took 18.6 minutes (range 9-34 minutes). There was no significant difference in the times taken (P = .708). All lesions were excised en bloc; the mean dimensions of lesions resected by the MASTER and the IT diathermic knife were 37.2 x 30.1 mm and 32.78 x 25.6 mm, respectively. The MASTER exhibited good grasping and cutting efficiency throughout. Surgical maneuvers were achieved with ease and precision. There was no incidence of excessive bleeding or stomach wall perforation. LIMITATIONS: Exploratory study with limited sample size. CONCLUSIONS: Performing ESD by using the MASTER is feasible.

Natural orifice transgastric endoscopic wedge hepatic resection in an experimental model using an intuitively controlled master and slave transluminal endoscopic robot (MASTER).

BACKGROUND: The lack of triangulation of standard endoscopic devices limits the degree of freedom for surgical maneuvers during natural orifice transluminal endoscopic surgery (NOTES). This study explored the feasibility of adapting an intuitively controlled master and slave transluminal endoscopic robot (MASTER) the authors developed to facilitate wedge hepatic resection in NOTES. METHODS: The MASTER consists of a master controller, a telesurgical workstation, and a slave manipulator that holds two end-effectors: a grasper, and a monopolar electrocautery hook. The master controller is attached to the wrist and fingers of the operator and connected to the manipulator by electrical and wire cables. Movements of the operator are detected and converted into control signals driving the slave manipulator via a tendon-sheath power transmission mechanism allowing nine degrees of freedom. Using this system, wedge hepatic resection was performed through the transgastric route on two female pigs under general anesthesia. Entry into the peritoneal cavity was via a 10-mm incision made on the anterior wall of the stomach by the electrocautery hook. Wedge hepatic resection was performed using the robotic grasper and hook. Hemostasis was achieved with the electrocautery hook. After the procedure, the resected liver tissue was retrieved through the mouth using the grasper. RESULTS: Using the MASTER, transgastric wedge hepatic resection was successfully performed on two pigs with no laparoscopic assistance. The entire procedure took 9.4 min (range, 8.5-10.2 min), with 7.1 min (range, 6-8.2 min) spent on excision of the liver tissue. The robotics-controlled device was able to grasp, retract, and excise the liver specimen successfully in the desired plane. CONCLUSION: This study demonstrated for the first time that the MASTER could effectively mitigate the technical constraints normally encountered in NOTES procedures. With it, the triangulation of surgical tools and the manipulation of tissue became easy, and wedge hepatic resection could be accomplished successfully without the need for assistance using laparoscopic instruments.

Endoscopic suturing without extracorporeal knots: a laboratory study.

BACKGROUND: To eliminate cumbersome extracorporeal knotting, we designed a new endoscopic suturing device, the Eagle Claw V. The efficacy of the new device was tested on the Erlangen model and was compared with the initial extracorporeal knotting version (Eagle Claw II). METHODS: Segments of porcine splenic arteries were placed on the mucosal surface of the anterior wall of a pig stomach. The two ends of the artery were brought out through the gastric wall and were connected to a two-channel manometer. The Eagle Claw V has a curved needle with a detachable tip. After puncturing the tissue, the needle tip was engaged into a catching cartridge, where the suture had been embedded in a tightening mechanism. The suture could be tightened by simply pulling the end. The Eagle Claw V was used to plicate the splenic arteries mounted on the stomach. Suturing was considered secure if the suture could withstand endoluminal pressure greater than 200 mm Hg that lasted at least 10 seconds. RESULTS: Eleven of 15 stitches (73.3%) gained secure plication of the vessels. The suturing time (mean +/- standard deviation 2.93 +/- 0.80 minutes) was significantly faster than that of the Eagle Claw II (9.38 +/- 1.51 minutes). The device consistently achieved penetration of the muscular layer, and 4 of 15 sutures included the serosa. The 4 failures were because of suture breakage in two, thread entanglement in one, and cartridge dislodgement in one. CONCLUSIONS: The present prototype represents significant improvements in the ease of operation and the security of the suture, bringing the technique closer to clinical use for a variety of applications.

Eagle Claw II: A novel endosuture device that uses a curved needle for major arterial bleeding: a bench study.

BACKGROUND: Control of bleeding from major arteries in the upper-GI tract remains difficult with currently available endoscopic devices. We designed an endosuture device that uses a curved needle and extracorporeal knotting, and assessed the device in stopping arterial bleeding in a bench model. METHODS: Harvested porcine splenic arteries (2-mm diameter) were tunneled submucosally in pig stomach with the open end protruding into an artificially created mucosal defect. The outer end of the vessel was connected to a pulsatile pump, and red ink was infused at a pressure of about 100 mm Hg. The stomach was installed on an Erlangen endo-training model. The suturing device (Eagle Claw II), mounted outside an endoscope, has an eyed, curved needle that carries a 3-0 nylon thread. After puncture, the thread was retrieved by using a hook. Three-throw square knots were tied at the thread extracorporeally and were pushed into place by using a knotting cap. The criteria of successful plication was defined as hemostasis after knotting, no leakage at pressures of >200 mm Hg, and the vessel was completely encircled by the suture. RESULTS: A total of 25 sutures were made with the mean time of 9.38 minutes (standard deviation 1.51). Control of the bleeding was obtained with 17 sutures (68%). The causes for failure were the following: a suture was too shallow (4), a loose knot (2), incorrect suture position (1), and stomach-wall edema (1). CONCLUSIONS: Control of bleeding from large arteries by using endoscopic suturing is possible. Continued refinements of the device are required.

Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a prospective cohort study.

BACKGROUND & AIMS: Helicobacter pylori-negative idiopathic ulcers are increasingly recognized. The secular trend and long-term outcome of this condition are unknown. METHODS: We prospectively studied consecutive patients with bleeding gastroduodenal ulcers from January to December 2000. The incidence and etiology of ulcers during this period were compared with that between September 1997 and August 1998. H. pylori-negative idiopathic ulcers were defined as negative tests for H. pylori, no exposure to analgesics within 4 weeks, and absence of other risk factors for ulcers. After the ulcers had healed, patients with H. pylori-negative idiopathic ulcers and patients with H. pylori ulcers who received eradication therapy were followed up for 12 months without anti-ulcer drugs. RESULTS: Six hundred thirty-eight patients had bleeding ulcers: 213 (33.4%) were H. pylori ulcers, and 120 (18.8%) were H. pylori-negative idiopathic ulcers (vs 480 [50.3%] H. pylori ulcers and 40 [4.2%] H. pylori-negative idiopathic ulcers in 1997-1998; P < .001). H. pylori-negative idiopathic ulcers accounted for 16.1% of patients who were admitted for bleeding and 42.4% of patients who bled while in the hospital (P < .0001); 28.3% of patients with H. pylori-negative idiopathic ulcers had histologic evidence of past H. pylori infection. The probability of recurrent ulcer complications in 12 months was 13.4% (95% CI: 7.3%-19.5%) in patients with H. pylori-negative idiopathic ulcers and 2.5% (95% CI: 0.4%-4.6%) in patients with H. pylori ulcers who received eradication therapy (P = .0002). CONCLUSIONS: The incidence of H. pylori-negative idiopathic bleeding ulcers is rising. These ulcers are prone to recurrent complications.

Premedication with orally administered midazolam in adults undergoing diagnostic upper endoscopy: a double-blind placebo-controlled randomized trial.

BACKGROUND: A double-blind placebo-controlled randomized trial was conducted to investigate the safety and the efficacy of orally administered midazolam as premedication for patients undergoing elective EGD. METHODS: A total of 130 patients were randomized to receive either 7.5 mg of midazolam orally (n = 65) or a placebo (n = 65) as premedication. Outcomes measures included the anxiety score (visual analog scale) during EGD, overall tolerance, extent of amnesia, overall satisfaction, patient willingness to repeat the procedure, recovery time, and hemodynamic changes after medication. RESULTS: The median (interquartile range) anxiety score during the procedure in the midazolam group was significantly lower than that in the control group (2.0 [0-4.9] vs. 3.8 [2.1-7.95], p < 0.001). A significantly greater number of patients in the midazolam group graded overall tolerance as "excellent or good" (70.8% vs. 49.2%, p = 0.012) and reported a partial to complete amnesia response (52.3% vs. 32.3%, p = 0.02) when compared with the control group. Patients in the midazolam group were more willing to repeat the procedure if necessary (89.2% vs. 69.2%, p = 0.005). The median (interquartile range) recovery time was significantly longer in the midazolam group than in the control group (5 [5-15] minutes vs. 5 [5-10] minutes, p = 0.014). There were no statistically significant differences in satisfaction score and hemodynamic changes between groups. CONCLUSIONS: Premedication by oral administration of midazolam is a safe and an effective method of sedation that significantly reduces anxiety and improves overall tolerance for patients undergoing EGD.

Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding.

BACKGROUND: Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients. METHODS: We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding. RESULTS: We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001). CONCLUSIONS: Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.

Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial.

BACKGROUND & AIMS: The gastric safety of cyclooxgenase-2 inhibitors and prophylactic antisecretory therapy in high-risk arthritis patients is unclear. We studied the ulcer incidence and factors predicting ulcer recurrence in a prospective, double-blinded trial. METHODS: We studied patients who presented with nonsteroidal anti-inflammatory drug-associated ulcer bleeding. After ulcer healing, patients who were negative for Helicobacter pylori were randomly assigned to celecoxib 200 mg twice a day plus omeprazole placebo once daily or diclofenac 75 mg twice daily plus omeprazole 20 mg once daily for 6 months. Patients underwent endoscopy if they developed recurrent bleeding. Those without recurrent events underwent endoscopy at their last follow-up visit. RESULTS: Two hundred eighty-seven patients were enrolled; 24 had recurrent gastrointestinal complications. Among 259 patients without events, 222 underwent endoscopy (116 received celecoxib and 106 received diclofenac plus omeprazole). The probability of recurrent ulcers in 6 months was 18.7% in the celecoxib group and 25.6% in the diclofenac plus omeprazole group (difference, -6.7%; 95% CI: -17.8% to 3.9%) (P = 0.21). Combining bleeding and endoscopic ulcers, 24.1% in the celecoxib group and 32.3% in the diclofenac plus omeprazole group had recurrent ulcers in 6 months (difference, -8.2%; 95% CI: -19.5% to 2.9%) (P = 0.15). Treatment-induced significant dyspepsia (hazard ratio, 5.3; 95% CI: 2.6-10.8), age > or =75 (hazard ratio, 2.0; 95% CI: 1.1-3.5), and comorbidity (hazard ratio, 2.1; 95% CI: 1.2-3.7) independently predicted ulcer recurrence. CONCLUSIONS: Among patients with previous ulcer bleeding, neither celecoxib nor diclofenac plus omeprazole adequately prevents ulcer recurrence. Treatment-induced significant dyspepsia is an indication for endoscopic evaluation.

Reversibility of leukocyte dysfunction in rats with obstructive jaundice.

BACKGROUND: The role of leukocytes in obstructive jaundice is obscure and the effect of relieving cholestasis on leukocyte function is unclear. We postulated that cholestasis affects systemic polymorphonuclear leukocyte function by deranging phagocytosis and hydrogen peroxide release and the leukocyte dysfunction is reversible by internal and external biliary drainage. MATERIALS AND METHODS: Sixty male Sprague Dawley rats were randomly assigned to four groups: obstructive jaundice (OJ), sham operation (SH), OJ with internal drainage (ID), and OJ with external drainage (ED). The phagocytic functions of neutrophils and monocytes in whole blood were measured with flow cytometry using fluorescent microspheres. Intracellular hydrogen peroxide production by leukocytes was assessed with flow cytometry using dihydrorhodamine-123 as probes. RESULTS: Leukocyte count and percentage of monocytes in rats with OJ was significantly increased compared with SH rats (P < 0.001). These elevations could be reversed by both ID and ED method (P < 0.001). The phagocytic function of neutrophils and monocytes was significantly depressed in OJ rats compared with that in SH rats (P < 0.001). After relief of the OJ, the suppressed phagocytic function of neutrophils and monocytes was completely improved in ID rats (ID versus OJ, P < 0.001), but only partially reversed in ED rats. The hydrogen peroxide production by monocytes and lymphocytes was significantly increased in OJ rats (P < 0.05). ID reversed the increased hydrogen peroxide generation (P < 0.05), but ED only partially did. CONCLUSIONS: In our rodent model of biliary obstruction, deranged phagocytosis, and hydrogen peroxide generation by leukocytes was found. Internal drainage is superior to external drainage for reversal of the distorted leukocyte function.

Randomized, double-blinded, placebo-controlled trial of intravenously administered hyoscine N-butyl bromide in patients undergoing colonoscopy with patient-controlled sedation.

BACKGROUND: A prospective, double-blinded, placebo-controlled randomized trial was conducted to investigate the effect of the antispasmodic hyoscine N-butyl bromide (Buscopan) during colonoscopy. METHODS: A total of 120 patients undergoing colonoscopy were randomized to receive either 40 mg of hyoscine N-butyl bromide (n=60) or normal saline solution (n=60) intravenously as premedication. Colonoscopy was performed under patient-controlled sedation. Outcome measures included cecal intubation and total procedure time, demanded and administered doses of patient-controlled sedation, spasm score, pain score, endoscopist satisfaction score, patient willingness to repeat colonoscopy, and vital signs (blood pressure, pulse rate) during colonoscopy. RESULTS: Mean cecal intubation time in the hyoscine N-butyl bromide group was significantly longer than the control group (12.20 vs. 9.74 minutes; p=0.04; but correction for multiple testing of data removed this significance). The use of hyoscine N-butyl bromide was associated with a significantly lower endoscopist mean satisfaction score (6.47 vs. 7.30; p=0.04; but correction for multiple testing of data removed this significance), higher demanded and administered mean doses of patient-controlled sedation (respectively, 34.80 and 7.25 vs. 24.20 and 5.87; p=0.045; p=0.04, respectively; but correction for multiple testing of data removed these findings of significance), fewer patients willing to repeat colonoscopy (60% vs. 83.9%; p=0.005), and more hemodynamic instability (p<0.001) when compared with the control group. No significant difference was found in the total procedure time, spasm score, or pain score. CONCLUSIONS: Premedication with intravenously administered hyoscine N-butyl bromide impedes colonoscope insertion and causes greater patient discomfort, as well as hemodynamic instability.

Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet agents: analysis of 1657 cases.

BACKGROUND: Anticoagulants and antiplatelet agents commonly are used to treat patients with cardiovascular and cerebrovascular diseases. Data on the safety of the use of these drugs before colonoscopic polypectomy are scanty. METHODS: An audit was conducted for a 2-year period of consecutive patients undergoing colonoscopy and polypectomy. Patient demographics, site and size of polyps, and the use of anticoagulants and antiplatelet agents were documented from a hospital on-line database. Bleeding episodes were classified as immediate or delayed and were graded as mild, moderate, or severe. Risk factors associated with postendoscopy bleeding were analyzed by multivariate logistic regression analysis. RESULTS: A total of 5593 cases were reviewed. Polypectomy was performed in 1657 patients. There were 37 cases of polypectomy-associated bleeding (2.2%); bleeding was immediate in 32 and delayed in 5. Multivariate analysis showed that warfarin use, after adjustment for the effects of each of the other factors, was an independent risk factor for bleeding, with an odds ratio 13.37: 95% CI[4.10, 43.65]. Age; the location and size of polyp; and the use of aspirin, non-steroidal anti-inflammatory drugs, and other antiplatelet agents were not associated with a higher risk of polypectomy-associated bleeding. CONCLUSIONS: The use of antiplatelet agents during polypectomy was not associated with an increase in post-polypectomy bleeding. In contrast, treatment with warfarin should be discontinued, because this was associated with a significant increase in post-polypectomy bleeding.

Superoxide and nitric oxide production by Kupffer cells in rats with obstructive jaundice: effect of internal and external drainage.

BACKGROUND AND AIMS: The role of Kupffer cells in obstructive jaundice (OJ) has not been fully understood. The aims of the present study were to measure superoxide and nitric oxide (NO) production by Kupffer cells in experimental OJ in rats and to investigate the response to internal and external biliary drainage. METHODS: Eighty male Sprague-Dawley rats were assigned to four groups: sham operation, OJ, and internal and external biliary drainage. Kupffer cells were isolated on day 7 in the sham operation and OJ group, and on day 7 after drainage procedures. Cells were cultured with or without lipopolysaccharide (LPS). Superoxide production was quantified in cultured Kupffer cells at 2 h and 48 h, respectively, after cell isolation using the superoxide dismutase inhibitable ferricytochrome c reduction method. Nitrite production in cell culture supernatants was measured 48 h later using Greiss reagents. RESULTS: Without LPS stimulation, Kupffer cells produced comparable superoxide and nitrite in each group (P > 0.05). With LPS stimulation, Kupffer cells in the OJ group produced significantly higher superoxide anions than the other groups (P = 0.006). Nitrite production was significantly increased in the OJ group and external biliary drainage group compared to rats in the sham operation and internal drainage groups (P < 0.01). CONCLUSIONS: Kupffer cells from rats with OJ produce great amounts of endotoxin-mediated oxidants. Both internal and external biliary drainage can decrease the elevated superoxide production. Internal drainage is superior to external drainage for reversing the distortional capacity of NO production by Kupffer cells.

Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells.

Both heme oxygenase-1 (HO-1) and p21(WAF1/Cip1) (p21) are involved in the pathogenesis of human cancer and their functions are closely associated with apoptosis. However, how these two molecules regulate apoptosis in human gastric cancer is unknown. In this study, we studied how HO-1 and p21 were regulated in two gastric cancer cell lines, MKN-45 with wild p53 and MKN-28 with mutant p53. The cells were treated with hemin and cadmium to induce HO-1. The result showed that HO-1 protein was significantly induced by hemin and cadmium in both cells tested. Following the HO-1 expression, p21 level was also markedly induced. The cells with increased HO-1 and p21 showed obviously resistantance to apoptotic stimuli. The levels of HO-1 and p21 induced were significantly inhibited by p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580) and extracellular-regulated kinase (ERK) inhibitor (PD098059). Parallel to decreased HO-1 and p21 expression, the kinase inhibitors also significantly attenuated the resistance of the cells to apoptosis. The elevated HO-1 and p21 was further found to be associated with increase activity of the nuclear NF-kappaB and the inhibition of NF-kappaB led to the block of their induction. The elevated HO-1 and p21 were also demonstrated to be related to increased cellular inhibitor of caspase inbitory protein-2 (c-IAP2) and decreased caspapse-3 activity. It was noted that the above changes observed were not different between MKN-45 and MKN-28 cells, suggesting the functions of HO-1 and p21 were irrespective of the status of p53. In conclusion, we demonstrate that the resistance to apoptosis in gastric cancer cells with elevated HO-1 and p21 is independent of p53 status in a p38 MAPK- and ERK-mediated pathway with elevated c-IAP2 and decreased caspase-3 activity and that this pathway is sensitive to the inhibition of NF-kappaB.

Allelic loss of chromosome 6q in gastric carcinoma.

Loss of the long arm of chromosome 6 (6q) has frequently been reported in gastric carcinoma, and most gastric cancer patients have evidence of intestinal metaplasia in the stomach. However, the relationship between loss of chromosome 6q and intestinal metaplasia has not been studied. In the first part of the study, we define the critical deletion region of chromosome 6q using loss of heterozygosity technique (LOH). Seventeen microsatellite markers were used to detect loss of heterozygosity (LOH) in 37 microdissected gastric tumors. We also examined intestinal metaplasia (IM) foci of the stomach in the same cancer patient (17 cases). Losses on chromosome 6q were detected in high frequency (51%) by LOH. Two distinct regions of common allelic loss were identified: one centered on the marker D6S300 (at 6q16.1) and the second on D6S446 (at 6q27), with LOH frequency of 36% and 31.3%, respectively. The deletions fall into 2 discrete regions, suggesting the existence of at least 2 tumor suppressor genes in 6q. The losses at 6q27 were confirmed by fluorescence in situ hybridization study (FISH). In the cases with LOH in the tumor, no LOH were detected in the autologous IM areas, but losses were detected by FISH. In some cases, these genetic changes may be acquired in the transition from normal gastric mucosa to intestinal metaplasia.

Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma.

Although gastric cancer with cyclooxygenase (COX)-2 overexpression is associated with poor prognosis, the mechanistic pathway remains unknown. We examined the associations between expressions of COX-2 and vascular endothelial growth factor (VEGF) in both gastric cancer cells and in human gastric cancer. The gastric cell line, Kato III, was transiently transfected with cox-2 expressing vector. The levels of COX-2, prostaglandin (PG) E2 and VEGF expression were measured post-transfection. Additionally, expressions of COX-2 and VEGF in human gastric cancer were determined by immunohistochemistry in archive gastrectomy specimens. Tumor angiogenesis was assessed by the microvessel density (MVD), which was determined by anti-CD34 immunostaining. Transient transfection of Kato III with cox-2 was associated with increased COX-2 expression, higher PGE2 production and upregulated VEGF expressions. Treatment with NS398, a specific COX-2 inhibitor, reduced VEGF expression in COX-2 expressing Kato III cells by 25%. Among the 67 gastric cancers examined, COX-2 overexpression was found in 45 (67%) cases whereas increased VEGF expression was detected in 46 (69%) cases. There was a significant association between COX-2 and VEGF expressions in gastric cancer (r=0.25, p=0.041). Additionally, tumor MVD was associated with both COX-2 (r=0.32, p=0.008) and VEGF (r=0.39, p=0.001) expressions. Our results showed that overexpression of COX-2 in both gastric cells and primary gastric cancer is associated with upregulation of VEGF and angiogenesis. Future studies should evaluate the potential anti-angiogenic effect of COX-2 inhibitors on human gastric cancer.

The effect of endoscopic therapy in patients receiving omeprazole for bleeding ulcers with nonbleeding visible vessels or adherent clots: a randomized comparison.

BACKGROUND: The optimal treatment of ulcers with nonbleeding visible vessels and adherent clots is unclear. OBJECTIVE: To compare intravenous omeprazole infusion plus endoscopic therapy with intravenous omeprazole infusion alone for prevention of recurrent bleeding from ulcers with nonbleeding visible vessels or adherent clots. DESIGN: Single-blind randomized study with blinded evaluation of study end points. SETTING: An endoscopy center in a university hospital in Hong Kong. PATIENTS: 156 persons with upper gastrointestinal bleeding and ulcers showing nonbleeding visible vessels or adherent clots. INTERVENTION: Combination of endoscopic therapy and omeprazole infusion versus sham endoscopic therapy and omeprazole infusion. MEASUREMENTS: Recurrent ulcer bleeding before discharge and within 30 days. RESULTS: 78 patients were recruited in each group. Ulcer bleeding recurred before discharge in seven patients who received intravenous omeprazole alone (9%) and no patients who received combined therapy (difference, 9 percentage points [95% CI, 1.7 to 17.6 percentage points]; P = 0.01). The probability of recurrent bleeding within 30 days was 11.6% (9 patients) in the omeprazole-alone group and 1.1% (1 patient) in the combined therapy group (difference, 10.5 percentage points [CI, 1.7 to 19.8 percentage points]; P = 0.009). Patients in the combined therapy group required less transfusion (difference in median units of blood transfused, 1 unit [CI, 0 to 2 units]; P = 0.02). One patient in the combined therapy group had surgery for ulcer perforation. Four patients receiving omeprazole alone (5.1%) and two patients receiving combined therapy (2.6%) died within 30 days. CONCLUSION: The combination of endoscopic therapy and omeprazole infusion is superior to omeprazole infusion alone for preventing recurrent bleeding from ulcers with nonbleeding visible vessels and adherent clots.

Imatinib (STI-571) heals a gastrocutaneous fistula resulting from a malignant gastric stromal tumor.

The management of inoperable giant malignant gastrointestinal stromal tumor (GIST) of the stomach sed to be a formidable task. We report our success with the use of STI-571 in treating a patient with huge GIST of the stomach complicated by gastrocutaneous fistula after an unsuccessful laparotomy. The patient was a 49-year-old man who presented to our center with a painful epigastric mass in December 2001. Endoscopy, biopsy, and magnetic resonance scan confirmed that it was a malignant stromal tumor arising from the gastric fundus. Laparotomy with an intention to resect the tumor was performed in view of the obstructing symptoms. However, massive bleeding was encountered during dissection of the tumor and gastrectomy was abandoned. The case was further complicated with the development of a gastrocutaneous fistula in the early postoperative period. The patient ws then managed with naso-duodenal tube feeding and enteral STI-571 was prescribed. The fistula healed up in 20 days and the mass became impalpable 1 month afterwards. Follow-up computed tonography (CT) scan 3 months later confirmed significant tumor reduction, and the patient has experienced no side effects from the treatment

Inactivation of helicase-like transcription factor by promoter hypermethylation in human gastric cancer.

Helicase-like transcription factor (HLTF), a member of the SWI/SNF (mating type switching/sucrose nonfermenting) chromatin-remodeling complex, is recently found to be inactivated by promoter hypermethylation in human colorectal cancer. However, the role of this putative tumor suppressor gene in other tumors has not been determined. We evaluated the role of HLTF promoter hypermethylation in gastric cancer. Expression of HLTF was examined by reverse-transcription (RT)-polymerase chain reaction (PCR), and promoter hypermethylation in HLTF was determined by methylation-specific PCR. Bisulfite DNA sequencing was performed to determine the detailed methylation profiles of the promoter region. HLTF expression was lost in two of five gastric cell lines and in 13 (28%) of 46 primary gastric cancers. Accordingly, promoter hypermethylation was detected in the two cell lines and in nine of 13 gastric cancer samples. Of the ten normal gastric specimens and ten paired adjacent nonneoplastic tissues, methylation was detected in only one adjacent nonneoplastic tissue. Bisulfite DNA sequencing of the promoter region of HLTF showed that the CpG island was densely methylated in cell lines and cancer samples; this also appeared to correlate with expression level. Treatment of gastric cell lines that lacked HLTF expression with the demethylating agent 5-azacytidine (5-azaDC) restored HLTF expression. These results suggest that HLTF promoter hypermethylation is frequently demonstrated in human gastric cancer, and inactivation of HLTF or the chromatin-remodeling complex may play a crucial role in gastric carcinogenesis.

Screening for colorectal cancer in Chinese: comparison of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy.

BACKGROUND AND AIMS: Fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), and colonoscopy are the most commonly recommended screening tests for colorectal cancer. The aim of this study was to compare the accuracy and safety of these 3 screening procedures in a general population of ethnic Chinese. METHODS: Asymptomatic adults older than 50 years were recruited from the general public through health exhibitions. All enrolled subjects were offered FOBT and full colonoscopy under sedation. Advanced colonic lesions (defined as adenoma > or = 10 mm, villous adenoma, adenoma with moderate or severe dysplasia, or invasive cancer) were recorded. Lesions at the distal 40 cm in the left colon and rectum were taken as findings of FS. RESULTS: A total of 505 subjects (56% women; mean age +/- SD, 56.5 +/- 5.4 years) were enrolled, and 476 (94.3%) had a complete colonoscopy. Advanced colonic neoplasms were documented in 63 subjects (12.5%), of which 45 had lesions in the distal colon and 26 in the proximal colon. Among the 385 subjects with a normal distal colon, 14 (3.6%) had advanced lesions in the proximal colon that would be missed by FS alone. The sensitivity and specificity of FOBT for advanced colonic lesions were 14.3% and 79.2% and the sensitivity and specificity of FS were 77.8% and 83.9%, respectively. Combining FOBT with FS would not significantly improve the results of FS alone. Among these 505 subjects who underwent colonoscopy and 148 who underwent polypectomy, there was no perforation and only one occurrence of postpolypectomy bleeding recorded. CONCLUSIONS: Colonoscopy is a safe and accurate method for the screening of colorectal neoplasms in Chinese subjects.