Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver.

Obesity is a major risk factor for cancers including hepatocellular carcinoma (HCC) that develops from a background of non-alcoholic fatty liver disease (NAFLD). Hypercholesterolemia is a common comorbidity of obesity. Although cholesterol biosynthesis mainly occurs in the liver, its role in HCC development of obese people remains obscure. Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models, we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T (NKT) cell-mediated antitumor immunosurveillance. Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients. Notably, cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development. Moreover, suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin (mTOR) inhibitor vistusertib preceded tumor regression, which was abolished by NKT inactivation but not CD8+ T cell depletion. Mechanistically, sterol regulatory element-binding protein 2 (SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells, which were supported by findings in people with obesity, NAFLD and NAFLD-HCC. This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment, providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.

A prospective 5-year study on the use of transient elastography to monitor the improvement of non-alcoholic fatty liver disease following bariatric surgery.

Liver stiffness measurement (LSM) by transient elastography (TE) is a non-invasive assessment for diagnosing and staging liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Evidence on its role as a longitudinal monitoring tool is lacking. This study aims to evaluate the role of TE in monitoring NAFLD improvement following bariatric surgery. This study prospectively recruited 101 morbidly obese patients undergoing laparoscopic bariatric surgery for intraoperative liver biopsy. Thirty-seven patients of the cohort received perioperative TE. Postoperative anthropometric, biochemical and LSM data were collected annually for 5 years. In 101 patients receiving liver biopsy (mean age 40.0 ± 10.3 years, mean body-mass-index (BMI) 40.0 ± 5.7 kg/m2), NASH and liver fibrosis were diagnosed in 42 (41.6%) and 48 (47.5%) patients respectively. There were 29 (28.7%) stage 1, 11 (10.9%) stage 2, 7 (6.9%) stage 3, and 1 (1.0%) stage 4 fibrosis. In 37 patients receiving TE (mean age 38.9 ± 10.8 years, mean BMI 41.1 ± 5.6 kg/m2), the percentages of total weight loss were 21.1 ± 7.6% at 1 year, 19.7 ± 8.3% at 3 years, and 17.1 ± 7.0% at 5 years after surgery. The mean LSM reduced significantly from 9.8 ± 4.6 kPa at baseline to 6.9 ± 3.4 kPa at 1 year, 7.3 ± 3.0 kPa at 3 years, and 6.8 ± 2.6 kPa at 5 years (P = 0.002). Using pre-defined LSM cut-offs, the rates of significant fibrosis, advanced fibrosis and cirrhosis being ruled out at 5 years improved from baseline values of 43.7 to 87.5% (P < 0.001), 56.8 to 91.7% (P < 0.001), and 64.9 to 91.7% (P < 0.001), respectively. TE was a useful monitoring tool in demonstrating the improvement of liver fibrosis following bariatric surgery.

The effect of bariatric surgery on the improvement of lower urinary tract symptoms in morbidly obese male patients.

BACKGROUND: Lower urinary tract symptoms (LUTS) are strongly linked with obesity. Whether bariatric surgery can effectively alleviate LUTS in morbidly obese men is unknown. The objective of the present study was to evaluate the effectiveness of bariatric surgery in reducing the prevalence and severity of male LUTS in obese patients. METHODS: This was a prospective observational study on consecutive morbidly obese men undergoing bariatric surgery. The International Prostate Symptom Score (IPSS) was used to assess for LUTS before and at 1-3 years after surgery. The 3-year changes in IPSS, the changes in LUTS severity, and the factors associated with LUTS improvement were evaluated. RESULTS: This study recruited 143 morbidly obese men (mean age 43.0 ± 10.4 years) undergoing sleeve gastrectomy (n = 89) and Roux-en-Y gastric bypass (n = 54). The rates of follow-up after surgery were 94.4% (n = 119/126) at 1 year, 90.6% (n = 96/106) at 2 years, and 81.2% (n = 69/85) at 3 years. After surgery, there was significant body mass index reduction from 39.1 ± 5.2 kg/m2 preoperatively to 30.1 ± 4.8 kg/m2 at 1 year and 31.5 ± 4.9 kg/m2 at 3 years (P < 0.001). There was significant reduction in IPSS total symptom score, quality of life score, frequency score, and nocturia score (P < 0.05). The prevalence of moderate to severe LUTS reduced from 35.0% (29.4% moderate; 5.6% severe) preoperatively to 21.8% (19.3% moderate; 2.5% severe) at 1 year and 30.4% (24.6% moderate; 5.8% severe) at 3 years (P < 0.001). LUTS improvement was significantly associated with body fat percentage reduction (P = 0.012) and was not associated with weight loss or improvement of metabolic parameters. CONCLUSIONS: Bariatric surgery was an effective and durable intervention for alleviating the prevalence and severity of LUTS in morbidly obese men for up to 3 years.

Bariatric surgery for Prader-Willi syndrome was ineffective in producing sustainable weight loss: Long term results for up to 10 years.

BACKGROUND: Obesity control in Prader-Willi syndrome (PWS) is notoriously difficult. The role of bariatric surgery in PWS remains controversial as long-term data are lacking. OBJECTIVES: To evaluate the 10-year outcomes of bariatric surgery in PWS. METHODS: This was a prospective observational study on PWS patients who received bariatric surgery and multidisciplinary follow-up programmes for obesity control. Outcomes on weight reduction and comorbidity resolution were evaluated. RESULTS: Between 2008 and 2013, five PWS patients (two males, mean age 19.2 ± 3.0 years) with body mass index of 47.3 ± 6.9 kg m-2 received sleeve gastrectomy (n = 2), one anastomosis gastric bypass (n = 2), and Roux-en-Y gastric bypass (n = 1) after failing all non-operative weight loss programmes. The median follow-up was 8.4 ± 2.2 years. The best mean percentage of total weight loss (%TWL) was achieved at 2 years (24.7%). %TWL dropped to 23.3% at 3 years, 11.9% at 5 years, 4.1% at 8 years, and 0% at 10 years. Each patient had at least three comorbidities preoperatively, but none of them had resolution of any one of the comorbidities at the last follow-up. CONCLUSIONS: Bariatric surgery could not produce sustainable long-term weight loss or comorbidity resolution in PWS. This study suggests that bariatric surgery cannot be recommended to PWS patients as a standard treatment.

Synthetic Biology Approaches in Immunology.

Breakthroughs in gene synthesis has allowed synthetic biologists the ability to design any DNA sequence of interest, enabling the possibility to create complex systems inside cells with novel functions to tackle problems in immunology. Synthetic immunology of mammalian cells expressing natural or synthetic genes can guide and induce immune responses in patients. Through recent developments in engineering chimeric receptors, it is now feasible to customize control over engineered cells to target the disease sites with specificity. These cells can avoid immune rejection if derived from expandable cell types (e.g., stem cells or T cells) and then can be grown in abundance before implantation. However, safety concerns of engineered cells in circulation necessitates the development of a wide range of mechanisms to kill cells after their therapeutic life ends. This therapeutic effect is still predominantly the secretion of therapeutic proteins, but novel therapeutic interventions have been explored by synthetic biologists. In the pursuit of engineering new cell functions for synthetic immunology, it is possible that many problems previously thought intractable may actually be possible.

Patterns of Care Related to Post-Operative Radiotherapy for Patients with Prostate Cancer among Canadian Radiation Oncologists and Urologists.

The American Society for Radiation Oncology (ASTRO) and American Urological Association (AUA) developed post-prostatectomy radiotherapy (RT) guidelines to aid patient counseling on adjuvant (ART) and salvage radiotherapy (SRT). Our study compared how aware and compliant Canadian radiation oncologists and urologists are to these guidelines. Our online survey was distributed through the Canadian Association of Radiation Oncology (CARO) and Canadian Urology Association (CUA) to radiation oncologists and urologists that treat prostate cancer. We used Wilcoxon rank-sum test and Chi-square test to compare radiation oncologists and urologists. P values for significant findings are reported. A total of 128 participants responded the survey, 52 radiation oncologists, and 76 urologists. The majority (82%) of radiation oncologists had read these guidelines, compared to only 49% of urologists (p < 0.001). Radiation oncologists were more likely to recommend ART >50% for adverse pathological findings post-radical prostatectomy compared to urologists (76 vs. 51%, p = 0.011). Urologists were more likely to monitor their patient's PSA level post-prostatectomy compared to radiation oncologists (93 vs. 77%, p = 0.016). Post-thematic analysis of open-ended questions revealed that urologists rarely refer patients to radiation oncologists for ART, with radiation oncologists confirming that they rarely receive referrals. This study demonstrates the low compliance to ASTRO/AUA guidelines. While radiation oncologists were more aware and compliant to guidelines, urologists were significantly more likely to monitor their patient's PSA. This study highlighted the need for better communication between urologists and radiation oncologists, especially in referrals for ART, to facilitate treatment delivery that is concordant with ASTRO/AUA guidelines.

Health-Related Quality of Life after Bariatric Surgery and its Correlation with Glycaemic Status in Hong Kong Chinese Adults.

BACKGROUND: To evaluate health-related quality of life (HRQOL) following bariatric surgery and its correlation with different glycaemic status in Hong Kong Chinese adults. MATERIALS AND METHODS: In 2002-2008, obese Chinese adults were recruited for bariatric surgery, undergoing laparoscopic adjustable gastric banding or laparoscopic sleeve gastrectomy. Patients were invited to complete the Chinese Hong Kong Medical Outcomes Study Short-Form Health Survey (SF-36) at baseline and at 1-year post operation. RESULTS: Sixty patients (60 % female) completed baseline and 1-year follow-up HRQOL assessments. Mean age was 38 years and mean BMI was 41.6 kg/m(2). At baseline, 30.0 % of patients had diabetes and 31.7 % prediabetes. Mean absolute weight reduction 1 year after bariatric surgery was 19.8 kg. Statistically significant improvements in SF-36 scores were demonstrated in all physical domains and in three of the four psychological domains. Greater body weight reduction was associated with greater improvements in certain physical domains postoperatively. After adjusting for co-variables, abnormal glucose tolerance was associated with greater improvements in five of the eight HRQOL domains. CONCLUSIONS: Bariatric surgery resulted in significant gains in HRQOL as well as significant reductions in body weight in obese Chinese adults. This study suggests that bariatric surgery offers greater HRQOL improvements in patients with prediabetes and diabetes compared with normoglycaemic individuals.

Long-term Results on Weight Loss and Diabetes Remission after Laparoscopic Sleeve Gastrectomy for A Morbidly Obese Chinese Population.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective stand-alone bariatric procedure with favorable short-term results on weight reduction and comorbidity resolution. This study aims to evaluate the long-term results of LSG to see if weight reduction and diabetic improvement are sustainable. METHODS: We conducted a prospective observational study on patients receiving LSG as an index stand-alone bariatric operation in our unit. RESULTS: Between 2006 and 2014, there were 140 patients (91 females) aged 37.9 ± 10.5 years with a body mass index of 41.0 ± 7.0 kg/m(2). At 1-year (n = 123), 2-year (n = 99), 3-year (n = 77), 4-year (n = 52), and 5-year (n = 44) follow-ups, the mean percentages of excess weight loss (%EWL) were 70.5, 65.2, 60.2, 53.2, and 57.2%, respectively, while the corresponding proportions with failed weight loss (%EWL <30%) were 7.3, 9.1, 13.0, 25.0, and 22.7%. Weight regain (>25% rebound in %EWL) was evident with time as 0, 1.0, 11.6, 19.2, and 29.5% in the first 5-year follow-ups. In 65 patients with type 2 diabetes mellitus, remission (complete and partial) was achieved in 34.5% at 1-year, 52.7% at 3-year, and 70.6% at 5-year follow-ups. Proportions of patients having optimal glycemic control (HbA1c <7%) increased significantly from 26.2% preoperatively to 80.9% at the first year and maintained at 78.6% at the fifth year (P < 0.001). CONCLUSIONS: LSG was effective in achieving substantial weight reduction and improved diabetic control for morbidly obese patients. Although weight regain was possible with time, majority of patients could maintain sustainable weight loss, diabetes remission, and glycemic improvement in the long run.

Recognition of goblet cells upon endocytoscopy indicates the presence of gastric intestinal metaplasia.

BACKGROUND: Gastric intestinal metaplasia (IM) is considered precancerous and is difficult to differentiate upon endoscopy. Endocytoscopy enables observation at a cellular level for focused biopsy. The present study examined the use of endocytoscopy for recognition of gastric IM. PATIENTS AND METHODS: Patients with a history of gastric IM were recruited. We first carried out narrow band imaging (NBI) endoscopy to look for suspicious areas of gastric IM. A prototype endocytoscope with a magnification of 450× was used to re-examine these areas. Areas examined were biopsied for histological comparison. Presence of goblet cells was considered as representative of IM upon endocytoscopy. RESULTS: Twenty patients were recruited with NBI demonstrating 102 suspicious lesions of gastric IM. Mean age of patients was 53.9 ± 7.6 years. Upon histology, 72 biopsies were confirmed as gastric IM, 15 showed IM and low-grade dysplasia, whereas 15were diagnosed as chronic gastritis. Endocytoscopy image quality was significantly better for areas of IM as compared to gastritis (P < 0.05; OR 21.7 [95% CI 4.5-105.9]). The presence of goblet cells upon endocytoscopy achieved a diagnostic accuracy of 0.86 for gastric IM. Receiver operator characteristics curve achieved an area under curve of 0.8 with the presence of goblet cells under endocytoscopy as compared to 0.64 for NBI alone. CONCLUSIONS: Presence of goblet cells upon endocytoscopy indicates a diagnosis of gastric IM. Image quality of endocytoscopy, however, is suboptimal. Further developments in endocytoscopy should focus on image quality and staining methods to enhance differentiation between IM, dysplasia and early gastric cancer.

Endoscopic suturing is superior to endoclips for closure of gastrotomy after natural orifices translumenal endoscopic surgery (NOTES): an ex vivo study.

BACKGROUND: Closure of gastrotomy remains a major barrier to clinical application of NOTES. Full-thickness closure of gastrotomy using endoscopic suturing device is presumed to be safer than that by endoclips. We evaluated the safety and feasibility of closing gastrotomy by Eagle Claw VIII, endoclips, and surgical suturing. METHODS: Fifty-one ex vivo porcine stomach models were included with 17 closures per arm. A 2-cm linear incision was created at the gastric body using scalpel externally. The time for gastrotomy closure, pneumatic bursting pressure, site of air leakage and number of suturing, or clips used were recorded. In addition, the technical difficulties of closure using Eagle Claw VIII and endoclips were assessed by a quantitative scale. RESULTS: All gastrotomies were successfully closed without leakage upon full gaseous distension. Closure time of Eagle Claw VIII was significantly longer than that of endoclips and surgical suturing. The median pneumatic bursting pressures were 56 (range 35-110) mmHg for Eagle Claw VIII, 19 (range 9-65) mmHg for endoclips, and 78 (range 63-110) mmHg for surgical suturing. The bursting pressures for surgical suturing and Eagle Claw VIII were significantly higher than that of endoclips (P < 0.001 for both surgical suturing vs. endoclips and Eagle Claw VIII vs. endoclips). The median scores for technical difficulties was not significantly different between endoclips and Eagle Claw VIII [9.5 (range 7-10) vs. 10 (range 8.5-10); P = 0.073]. CONCLUSIONS: The results indicated that closure of gastrotomy by Eagle Claw VIII could withstand higher endoluminal pneumatic bursting pressure than endoclips. The performance of endoscopic suturing with Eagle Claw is still difficult, and further refinement of the endoscopic suturing device is necessary for clinical application.

Peroral endoscopic myotomy for treatment of achalasia: from bench to bedside (with video).

BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy through a long submucosal tunnel. OBJECTIVE: This study aimed to investigate the feasibility and safety of POEM for treatment of achalasia. DESIGN: Preclinical animal study and prospective clinical study. PATIENTS: Consecutive patients diagnosed with achalasia with high-resolution manometry. INTERVENTIONS: POEM was standardized for preclinical and clinical studies. After submucosal injection, a mucosal incision was made 15 cm above the gastroesophageal junction (GEJ). A long submucosal tunnel was created to extend below the GEJ. The endoscopic myotomy started 10 cm above and extended 2 cm below the GEJ. We first conducted a preclinical animal study to confirm the safety of POEM. POEM was then performed for the treatment of achalasia in humans. MAIN OUTCOME MEASUREMENTS: Relief from dysphagia assessed by the dysphagia score and Eckhardt score. High-resolution manometry and pH monitoring were performed to evaluate the posttreatment effects and esophageal acid exposure. RESULTS: Seven 30-kg porcine models underwent POEM in the survival study. All of the pigs survived except 1, which sustained pneumomediastinum. POEM was performed for the treatment of achalasia in 16 patients. The mean operating time was 117.0 ± 34.1 minutes. All patients tolerated food on day 2, with a contrast study confirming no leakage. The median follow-up was 176.5 days (range 98-230 days). The postoperative basal lower esophageal sphincter pressure was significantly reduced (mean reduction, 13.9 ± 14.5 mm Hg; P = .005) and 4-second integrated relaxation pressure of the GEJ (mean reduction, 10.1 ± 7.4 mm Hg; P = .001). Of these patients, 58.3% had a normalized 4-second integrated relaxation pressure, whereas 20% had excessive esophageal acid exposure after the procedure. There was a significant improvement in quality of life 6 months after POEM measured by the Short Form-36 questionnaire. LIMITATION: Small sample size. CONCLUSIONS: POEM is a feasible, safe, and effective treatment for achalasia.

Ghrelin level and weight loss after laparoscopic sleeve gastrectomy and gastric mini-bypass for Prader-Willi syndrome in Chinese.

Prader-Willi syndrome (PWS) is a chromosomal disorder characterized by the presence of hyperghrelinemia, hyperphagia, and obesity. The optimal treatment for PWS patient remains controversial. Here, we present our experience of treating PWS with laparoscopic mini-gastric bypass (LMGBP) and laparoscopic sleeve gastrectomy (LSG). Three patients with genetic diagnosis of PWS and body mass index (BMI) greater than 40 kg/m(2) were referred for bariatric surgery. All of them had completed 2-year postoperative follow-up. Body weight, BMI, and ghrelin levels were recorded before and after surgery. They were two females and one male. Their age ranged from 15 to 23 years old, and the mean BMI was 46.7 kg/m(2) (range 44-50). Two patients underwent LSG and one patient underwent LMGBP. After a median follow-up of 33 months (range 24-36 months), mean weight loss and percentage of excessive weight loss at 2 years were 32.5 kg (24.9-38.3 kg) and 63.2 % (range 50.5-86.2 %), respectively. The mean fasting active ghrelin level decreased from 1,134.2 pg/ml preoperatively to 519.8 pg/ml 1 year after surgery. No major complication was observed. Iron deficiency anemia was observed in the patient who underwent LMGBP. Significant reduction of body weight and level of serum ghrelin can be achieved with minimal morbidity by LSG or LMGBP in patients with PWS.

Endoscopic submucosal dissection (ESD) compared with gastrectomy for treatment of early gastric neoplasia: a retrospective cohort study.

INTRODUCTION: This study aims to compare perioperative outcomes and oncological clearance of endoscopic submucosal dissection (ESD) versus gastrectomy for treatment of early gastric cancer (EGC). METHODS: This is a retrospective cohort study including all cases of EGC or severe dysplasia treated at a university-affiliated hospital from 1993 to 2010. Preoperative endoscopic ultrasound and image-enhanced endoscopy were employed to determine depth of invasion. Clinical outcomes including baseline demographics, pathology, postoperative complication, and hospital stay, as well as 3-year survival were compared. RESULTS: From 1993 to 2010, 114 patients with severe dysplasia or EGC were treated: 40 of them received gastrectomy, while 74 received ESD. There was no difference in age, gender, comorbidity or American Society of Anesthesiologists grade between the two groups. Of patients in the gastrectomy group, 92.5% presented with symptoms as compared with 27.0% of those treated by ESD (p < 0.001). More patients in the ESD group had atrophic gastritis (31.1 vs 10%; p = 0.009) and intestinal metaplasia (68.9 vs 55.0%; p = 0.04). Patients treated by gastrectomy sustained longer operative time [265 (150-360) min] when compared with ESD [89.6 (45-360) min; p < 0.001]. They also had longer median hospital stay [9.9 (6-26) days vs 3.0 (2-10) days; p < 0.001]. There was no perioperative mortality, but the overall complication rate was significantly higher in the gastrectomy group. The 3-year survival rate was 94.6% for ESD and 89.7% for gastrectomy group (log-rank test, p = 0.44). CONCLUSIONS: ESD achieved similar oncological outcomes when compared with radical gastrectomy for treatment of EGC. Patients receiving ESD had better perioperative outcomes in terms of operative time, complication rate, and hospital stay.

Transgastric endoluminal gastrojejunostomy: technical development from bench to animal study (with video).

BACKGROUND: Gastrojejunal anastomosis is commonly performed for palliative management of malignant gastric outlet obstruction and bariatric surgery. Natural orifice transluminal endoscopic surgery revolutionized the surgical approach to intra-abdominal surgery. This study explored the possibility of performing gastrojejunostomy (GJ) by using a hybrid natural orifice transluminal endoscopic surgery approach. OBJECTIVE: To develop a surgical technique for the performance of transgastric endoscopic GJ (TGEJ) in a porcine model. DESIGN: Prospective series of animal experiments. SETTING: University hospital animal laboratory. ANIMALS: Thirteen female domestic pigs. INTERVENTIONS: With the animals under general anesthesia, the endoscope is passed through the gastrotomy and a segment of small bowel is retrieved into the stomach. An enterotomy is then created, and an EndoGIA stapler is introduced through an intragastric port and passed between the small bowel and stomach wall. A GJ is formed after firing of the EndoGIA stapler. The pigs are allowed to resume their diet 1 day after the operation and are allowed to survive for 2 weeks before they are euthanized. The patency of the GJ is confirmed with a repeat endoscopy, contrast study, and postmortem examination. RESULTS: A total of 13 TEGJs were performed, 11 of which were successful. The mean operative time was 53.6 +/- 45.7 minutes. The mean time for gastrotomy was 4.7 minutes, and that for GJ was 42.5 minutes. One TEGJ was converted to open surgery because of malpositioning of the intragastric port, and the other failed because the enterotomy was too extensive. Ten of 11 pigs survived for 2 weeks, and endoscopic examination with contrast study confirmed that all the gastrojejunostomies were patent. On postmortem examination, the average size of the GJ was 30 mm. LIMITATIONS: The length between duodenojejunal flexure and the site chosen to perform the GJ could not be determined. CONCLUSIONS: TEGJ is technically feasible with a patent and sizable anastomosis.

Closure of a gastrotomy after transgastric tubal ligation by using the Eagle Claw VII: a survival experiment in a porcine model (with video).

BACKGROUND: Transgastric access to the peritoneal cavity presents new opportunities for novel endoscopic surgery. Secure closure of the gastrotomy site is critical to the success of transgastric endoscopic surgery. OBJECTIVE: To study the safety and efficacy of closure of a gastrotomy by using the Eagle Claw VII endoscopic suturing device after transgastric bilateral tubal ligation. DESIGN: A prospective survival study in a porcine model with ten 30-kg pigs. INTERVENTIONS: The gastrotomies were made by using a needle-knife and balloon dilation. Bilateral fallopian tube ligation was performed with detachable snares, and the tubes were transected by using the needle-knife. The gastrotomies were closed with endoscopic suturing by using the Eagle Claw VII. MAIN OUTCOME MEASUREMENTS: Included the survival of the pigs, security of the closure, number of plicating sutures used, operative time, peritoneal contamination, and histopathologic confirmation of the full-thickness healing of the gastrotomy. RESULTS: Transgastric fallopian-tube ligation was performed in 10 pigs, and all of the gastrotomies were successfully closed by using the Eagle Claw VII endoscopic suturing device. The operative time for bilateral tubal ligation was 38.2 minutes (range 18-50 minutes), whereas, the operative time for gastrotomy closure was 25.5 minutes (range 15-35 minutes). Three endoscopic sutures were necessary to achieve a secure gastrotomy closure. All the pigs survived and tolerated a full diet 24 hours after the operation. A postmortem confirmed full-thickness healing for all gastrotomies, with no evidence of leakage. One pig had an overtube-related esophageal perforation, which was successfully managed with endoscopic clip closure. LIMITATIONS: The porcine gastric wall is thicker than the human gastric wall, and the posterior wall of the porcine stomach becomes the anterior-inferior wall after gaseous distention. Hence, all the gastrotomies were made through the posterior wall. The tissue tolerance and healing of the porcine stomach may be different from that of the human stomach. CONCLUSIONS: Endoscopic suturing by using the Eagle Claw VII device is a feasible method for gastrotomy closure after a natural orifice transluminal endoscopic surgery procedure.

Laparoscopic sleeve gastrectomy in ethnic obese Chinese.

BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of laparoscopic sleeve gastrectomy (LSG) for the treatment of obesity in ethnic Chinese in Hong Kong. METHODS: Seventy consecutive Chinese patients (49 females; mean age 34.7+/-8.8 [range 18-56] years) received LSG for the treatment of obesity from May 2006 to Nov 2007 as a stand-alone procedure for weight reduction. Mean baseline body weight (BW) and body mass index (BMI) were 108.9+/-22.1 kg (range 71.0-164.9 kg) and 40.7+/-7.8 kg/m(2) (range 27.4-68.4 kg/m(2)), respectively. Outcome measures were collected and assessed in a prospective manner. RESULTS: All procedures were performed laparoscopically with no conversion. There was neither mortality nor any postoperative complications that required reoperation. Major complication occurred in two patients (2.9%; esophagogastric junction [EGJ] leak and stomach tube stricture). Mean follow-up was 7.1+/-5.0 months. Mean procedure time was 90.6+/-39.4 min, and mean hospital stay was 3.8+/-2.3 days. Mean BMI loss was 6.3+/-2.5, 9.0+/-3.4 and 12.3+/-4.5 kg/m(2) at 3, 6, and 12 months. Mean percent of excess BW loss was 48.5+/-28.4, 69.7+/-31.7, and 63.5+/-29.4 at 3, 6, and 12 months. CONCLUSION: LSG is safe and effective in achieving significant weight loss in obese ethnic Chinese patients.

Effects of long-term rofecoxib on gastric intestinal metaplasia: results of a randomized controlled trial.

PURPOSE: Gastric cancer and its premalignant gastric lesion, intestinal metaplasia (IM), frequently express cyclooxygenase-2 (COX-2) at high levels. We tested whether long-term use of specific COX-2 inhibitors regress gastric IM. EXPERIMENTAL DESIGN: This is a double-blind, randomized, placebo-controlled trial. Individuals with confirmed IM and Helicobacter pylori clearance were randomized to receive rofecoxib 25 mg daily or placebo. Endoscopy was done at baseline, at the end of year 1, and at the end of year 2, with multiple biopsies taken from the antrum and corpus. The primary end point was the proportion of subjects with regression of IM. Secondary end points were the severity of other histologic variables and the proportion of subjects with complete regression of IM. RESULTS: Two-hundred and thirteen subjects with confirmed IM were randomized. The proportion of subjects with the regression of IM did not differ significantly between rofecoxib and placebo groups (antrum, 24.5% versus 26.9%; P = 0.74; corpus, 4.3% versus 2.2%; P = 0.68). Patients on rofecoxib (19.1%) and on placebo (16.1%) had no IM detected in the stomach (P = 0.59). There was also no significant difference in the severity of IM between the two treatment groups (P >or= 0.3). CONCLUSIONS: There was no trend to suggest that treatment with rofecoxib for 2 years resulted in the regression of gastric IM. Although our findings cast doubt on the reversibility of gastric IM by COX-2 inhibitor, further studies are needed to establish the role of COX-2 inhibitors in different stages of gastric carcinogenesis.

Helicobacter pylori infection in 1st degree relatives of Chinese gastric cancer patients.

OBJECTIVE: Familial aggregation of gastric cancer has been linked to familial clustering of Helicobacter pylori infection. Patterns and risk factors associated with H. pylori infection were investigated in 1st degree relatives of Chinese gastric cancer patients. MATERIAL AND METHODS: Gastric cancer relatives were invited for screening endoscopy. H. pylori infection was diagnosed by endoscopic and serological methods. RESULTS: Among the 270 cancer relatives examined, 161 (59.6%) were found to be infected with H. pylori. The prevalence of infection in cancer relatives was significantly higher than age- and gender-matched dyspeptic control (45.5%, p=0.0006). The mean age of H. pylori-infected relatives was significantly older than that of non-infected relatives (43.9 versus 38.3 years; p<0.001). The prevalence of H. pylori infection was higher in those with more siblings (p=0.013, chi(2) test for trend). Moreover, individuals whose siblings had stomach cancer were more likely to have H. pylori infection than those with a parental history of cancer (68.2% versus 51.8%, p=0.007). In contrast, the youngest sibling had a significantly lower H. pylori infection rate than other siblings (39.2% versus 64.2%, p=0.001). Using multiple logistic regression, it was found that age >45 years (OR=1.8; 95% CI, 1.02-3.3) and a history of gastric cancer in siblings (OR=1.9; 95% CI, 1.06-3.3) were independent risk factors for H. pylori infection, and that the youngest sibling in the family had a reduced risk (OR=0.45; 95% CI, 0.24-0.84). CONCLUSIONS: This study identifies the patterns and risk factors for H. pylori in gastric cancer relatives, which may shed light on the evolving epidemiology of H. pylori infection in Chinese patients.

Risk factors associated with the development of intestinal metaplasia in first-degree relatives of gastric cancer patients.

Family relatives of gastric cancer patients have a higher risk of gastric cancer and premalignant gastric lesions. We sought to determine the risk factors associated with the presence of intestinal metaplasia in a large cohort of gastric cancer relatives. First-degree relatives of gastric cancer patients were invited for screening gastroscopy. Endoscopic gastric biopsies were obtained from the antrum and corpus. Gastric biopsies were analyzed for Helicobacter pylori infection, severity of inflammation, and presence of intestinal metaplasia. Stepwise logistic regressions were used to identify for risk factors associated with presence of intestinal metaplasia in cancer relatives. Two hundred seventy cancer relatives underwent screening endoscopy (median age, 42; 47% male and 48% siblings). Among them, 161 (59.6%) were H. pylori positive and 81 (30%) had confirmed intestinal metaplasia. The following factors were found to be associated with the presence of intestinal metaplasia: age, male sex, H. pylori infection, birth order, alcohol use, siblings with stomach cancer, childhood living conditions, and water supply. Individuals with intestinal metaplasia had more severe acute and chronic inflammation in the antrum and corpus (P < 0.003). With multiple logistic regression, H. pylori infection [odds ratio (OR), 3.23], male gender (OR, 2.09), age (OR, 1.07), and a history of gastric cancer in siblings (OR, 1.91) were independent factors associated with the development of intestinal metaplasia in cancer relatives. In conclusion, we have identified risk factors associated with gastric intestinal metaplasia in stomach cancer relatives, which may be useful in the understanding of gastric carcinogenesis in these high-risk individuals.