Lilian Kow

Change in liver size and fat content after treatment with Optifast Very Low Calorie Diet

Background: Laparoscopic adjustable gastric banding (LAGB) requires surgical access to the gastroesophageal junction, which may be compromised by the enlarged, fatty liver that is frequently encountered in the obese. Liver size appears reduced and surgical access improved following preoperative weight loss with Optifast® Very Low Calorie Diet (VLCD). The aim of this study was to assess the effects of 6 weeks Optifast® VLCD on liver volume and fat content. Methods: 18 morbidly obese subjects underwent magnetic resonance imaging and spectroscopy to measure liver size and fat content before and after intensive treatment with Optifast® VLCD for 6 weeks. Results: All subjects completing 6 weeks Optifast® VLCD lost weight. Body weight and BMI (median [interquartile range]) reduced from 119.7 [111.9-131.3] kg and 44 [40-51] kg/m2 respectively, to 110.6 [98.0124.5] kg and 40 [36-47] kg/m2, P<0.001. Median excess weight loss (EWL) was 15.1 [9.6-21.1]%. Baseline liver volume and fat content were related (r=0.633, P=0.005). After 6 weeks Optifast® VLCD, there was a 14.7% reduction in mean liver volume (P<0.001) and a 43% reduction in mean liver fat (P=0.016). The change in liver volume was predicted by the change in the liver fat (r = 0.610, P=0.012). Conclusion: This study has demonstrated that a 6week diet with Optifast® VLCD results in significant related reductions in liver size and liver fat content. This suggests that the reduction in liver volume is due to loss of fat. The reduction in liver fat and volume likely accounts for the perceived improved operability in patients undergoing LAGB.

Intra-abdominal vagal blocking (VBLOC therapy): Clinical results with a new implantable medical device

BACKGROUND A new medical device uses high-frequency electrical algorithms to create intermittent vagal blocking (VBLOC therapy). The aim is to assess the effects of vagal blocking on excess weight loss (EWL), safety, dietary intake, and vagal function. METHODS An open-label, 3-center study was conducted in obese subjects (body mass index [BMI] 35-50 kg/m(2)). Electrodes were implanted laparoscopically on both vagi near the esophagogastric junction to provide electrical block. Patients were followed for 6 months for body weight, safety, electrocardiogram, dietary intake, satiation, satiety, and plasma pancreatic polypeptide (PP) response to sham feeding. To specifically assess device effects alone, no diet or exercise programs were instituted. RESULTS Thirty-one patients (mean BMI, 41.2 +/- 1.4 kg/m(2)) received the device. Mean EWL at 4 and 12 weeks and 6 months after implant was 7.5%, 11.6%, and 14.2%, respectively (all P < .001); 25% of patients lost >25% EWL at 6 months (maximum, 36.8%). There were no deaths or device-related serious adverse events (AEs). Calorie intake decreased by >30% at 4 and 12 weeks and 6 months (all P <or= .01), with earlier satiation (P < .001) and reduced hunger (P = .005). After 12 weeks, plasma PP responses were suppressed (20 +/- 7 vs 42 +/- 19 pg/mL). Average percent EWL in patients with PP response <25 pg/mL was double that with PP response >25 pg/mL (P = .02). Three patients had serious AEs that required brief hospitalization, 1 each for lower respiratory tract, subcutaneous implant site seroma, and Clostridium difficile diarrhea. CONCLUSIONS Intermittent, intra-abdominal vagal blocking is associated with significant EWL and a desirable safety profile.

Effect of Reversible Intermittent Intra-abdominal Vagal Nerve Blockade on Morbid Obesity The ReCharge Randomized Clinical Trial

IMPORTANCE Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. OBJECTIVE To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. INTERVENTIONS One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. MAIN OUTCOMES AND MEASURES The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. RESULTS In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target (P = .71), although weight loss was statistically greater in the vagal nerve block group (P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. CONCLUSION AND RELEVANCE Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01327976.

IFSO-APC Consensus Statements 2011

AbstractAssociations of BMI with body composition and health outcomes may differ between Asian and European populations. Asian populations have also been shown to have an elevated risk of type 2 diabetes, hypertension, and hyperlipidemia at a relatively low level of BMI. New surgical indication for Asian patients should be discussed by the expert of this field. Forty-four bariatric experts in Asia-Pacific and other regions were chosen to have a voting privilege for IFSO-APC Consensus at the 2nd IFSO-APC Congress. A computerized audience-response voting system was used to analyze the agreement with the sentence of the consensus. Of all delegates, 95% agreed with the necessity of the establishment of IFSO-APC consensus statements, and 98% agreed with the necessity of a new indication for Asian patients.IFSO-APC Consensus statements 2011Bariatric surgery should be considered for the treatment of obesity for acceptable Asian candidates with BMI ≥ 35 with or without co-morbiditiesBariatric/GI metabolic surgery should be considered for the treatment of T2DM or metabolic syndrome for patients who are inadequately controlled by lifestyle alternations and medical treatment for acceptable Asian candidates with BMI ≥ 30The surgical approach may be considered as a non-primary alternative to treat inadequately controlled T2DM, or metabolic syndrome, for suitable Asian candidates with BMI ≥ 27.5. Other eight sentences are agreed with by majority of the voting delegates to form IFSO-APC consensus statements. This will help to make safe and wholesome the progress of bariatric and metabolic surgery in Asia.

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion

BACKGROUND Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy. METHODS A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20-89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses. RESULTS Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin <or=2 mm (P < 0.02), nodal involvement (P < 0.003), perineural infiltration (P < 0.0001) and lymphovascular invasion (P < 0.002) were associated with poorer prognosis. In a multivariate analysis, histologically identified perineural infiltration (P < 0.03) and lymphovascular invasion (P= 0.05) were significant factors influencing outcome. Five-year survival was 77% in patients negative for both factors and 15% in patients positive for both (P < 0.0001). In the pancreatic adenocarcinoma subgroup, patients who were negative for both factors had a 5-year survival of 71%, whereas those who were positive for both had a 5-year survival of 16% (P < 0.02). CONCLUSIONS The presence of perineural infiltration and lymphovascular invasion on histopathology is highly significant in predicting 5-year outcomes after pancreaticoduodenectomy for periampullary and pancreatic malignancies.

Vagal Blocking Improves Glycemic Control and Elevated Blood Pressure in Obese Subjects with Type 2 Diabetes Mellitus

Background. An active device that downregulates abdominal vagal signalling has resulted in significant weight loss in feasibility studies. Objective. To prospectively evaluate the effect of intermittent vagal blocking (VBLOC) on weight loss, glycemic control, and blood pressure (BP) in obese subjects with DM2. Methods. Twenty-eight subjects were implanted with a VBLOC device (Maestro Rechargeable System) at 5 centers in an open-label study. Effects on weight loss, HbA1c, fasting blood glucose, and BP were evaluated at 1 week to 12 months. Results. 26 subjects (17 females/9 males, 51 ± 2 years, BMI 37 ± 1 kg/m2, mean ± SEM) completed 12 months followup. One serious adverse event (pain at implant site) was easily resolved. At 1 week and 12 months, mean excess weight loss percentages (% EWL) were 9 ± 1% and 25 ± 4% (P < 0.0001), and HbA1c declined by 0.3 ± 0.1% and 1.0 ± 0.2% (P = 0.02, baseline 7.8 ± 0.2%). In DM2 subjects with elevated BP (n = 15), mean arterial pressure reduced by 7 ± 3 mmHg and 8 ± 3 mmHg (P = 0.04, baseline 100 ± 2 mmHg) at 1 week and 12 months. All subjects MAP decreased by 3 ± 2 mmHg (baseline 95 ± 2 mmHg) at 12 months. Conclusions. VBLOC was safe in obese DM2 subjects and associated with meaningful weight loss, early and sustained improvements in HbA1c, and reductions in BP in hypertensive DM2 subjects. This trial is registered with ClinicalTrials.gov NCT00555958.

Selection of electrical algorithms to treat obesity with intermittent vagal block using an implantable medical device

BACKGROUND A laparoscopically implantable electrical device that intermittently blocks both vagi near the esophagogastric junction led to significant excess weight loss (EWL) in an initial clinical trial in obese patients. The study objective was to optimize therapy algorithms and determine the EWL achieved with a second-generation device at university hospitals in Australia, Norway, and Switzerland. METHODS Data acquired during the initial clinical trial were analyzed and subsequently used to select alternative electrical algorithms. In the second trial, vagal blocking using one selected therapy algorithm was initiated 2 weeks after implanting the second-generation device. The patients were followed up for 6 months to assess the EWL and safety, including adverse events. RESULTS In the initial clinical trial, vagal blocking algorithm durations of 90-150 s were associated with greater EWL compared with either shorter or longer algorithm durations (P<.01). The second trial enrolled 27 patients (mean body mass index 39.3+/-.8 kg/m2) to evaluate a 120-s blocking algorithm. At 6 months, greater EWL was achieved (22.7%+/-3.1%, n=24) compared with the initial study and first-generation device (14.2%+/-2.2%, n=29, P=.03). In both trials, an association was found between the number of 90-150-s algorithms delivered daily and greater EWL (P=.03). No deaths, unanticipated device-related adverse events, or medically serious adverse events were associated with the device. CONCLUSION This second-generation vagal blocking device, using a therapy algorithm of 120-s duration, resulted in a clinically acceptable safety profile and significantly greater EWL compared with the first-generation device delivering a wider range of therapy algorithm durations.

Changes in gallbladder motility and gallstone formation following laparoscopic gastric banding for morbid obesity

UNLABELLED Morbid obesity is associated with cholesterol gallstone formation, a risk compounded by rapid weight loss. Laparoscopic gastric banding allows for a measured rate of weight loss, but the subsequent risk for developing gallstones is unknown. METHOD Twenty-six normal-weight volunteers (body mass index [BMI] less than 30) were compared with 14 morbidly obese patients (BMI greater than 40). Gallbladder volumes were measured ultrasonographically, after fasting and following stimulation with intravenous cholecystokinin-octapeptide (CCK-8) RESULTS Preoperatively, fasting gallbladder volume and residual volume after CCK stimulation were both two times greater in the obese group (P<0.02 versus controls). Per cent gallbladder emptying was not different. Gallbladder refilling was four times higher in the obese patients (P<0.01). By six weeks postoperatively, the obese patients lost 1.4+/-0.1% body weight per week. Gallbladder emptying decreased 18.4% (80.3+/-3.9% to 65.5+/-6.9%; P<0.05); residual volume rose one-third (not significant), and refilling fell 60.5% (0.43+/-0.09 to 0.26+/-0.04 mL/min; P=0.07). Three patients with weight losses of greater than 1.7% per week developed gallstones; gallbladder emptying fell outside the 95 percentile. By six months, weight loss slowed to 0.5+/-0.1% per week; gallbladder motility improved modestly. No further stones developed. CONCLUSION Rapid weight loss following laparoscopic gastric banding impairs gallbladder emptying and when pronounced, gallstones form by six weeks postoperatively. The accompanying reduction in gallbladder emptying, increased gallbladder residual volume and decreased refilling promote gallbladder stasis and hence stone formation.

The Early Effects of Weight Loss Surgery on Regional Adiposity

Background: Weight loss beyond 6 months following laparoscopic adjustable gastric banding (LAGB) is associated with a preferential mobilization of visceral adipose tissue and an improvement in insulin sensitivity in insulin resistant subjects. Because the rate of weight loss is greatest in the first 3 months after LAGB, we investigated the impact of LAGB on changes in regional lipid deposition and insulin sensitivity over this period. Methods: 10 female obese non-diabetic subjects underwent magnetic resonance (MR) imaging and spectroscopy before and 12 weeks after LAGB (using the Swedish band), for the quantification of abdominal subcutaneous and visceral adipose tissue areas and intrahepatic lipid. Fasting blood free fatty acids were analyzed. Insulin sensitivity was monitored by fasting insulin and homeostasis model assessment (HOMA). Results: Median weight loss 12 weeks after gastric banding was 9.5 kg [interquartile range (IQR): −16.5 to −6]. There were significant reductions in median abdominal subcutaneous (−20% [IQR: −24 to −13]) and visceral (−15% [IQR: −49 to −8]) adipose tissue depots as well as plasma free fatty acids (−34% [IQR: −79 to −8]). The amount of weight lost was directly proportional to the initial BMI (r=0.778; P=0.008). Visceral fat loss was proportional to initial visceral adiposity (r=0.80, P=0.01). There was no significant improvement in insulin sensitivity. Conclusion: Significant fat loss occurs 3 months after LAGB. The absence of a concurrent improvement in insulin sensitivity may reflect the relatively small reduction in visceral adipose tissue at this stage. Improvement in insulin sensitivity beyond 3 months after LAGB may be due to the continued loss of visceral adipose tissue.

Abdominal adiposity and liver fat content 3 and 12 months after gastric banding surgery

Weight loss after laparoscopic adjustable gastric banding surgery (LAGB) is associated with mobilization of adipose tissue from a variety of depots. We sought to evaluate and relate abdominal and hepatic lipid deposition in an obese female population 3 and 12 months after LAGB. We related changes in these depots to markers of insulin sensitivity. Eighteen female obese subjects underwent magnetic resonance imaging and spectroscopy before and 3 and 12 months after LAGB for the quantification of abdominal subcutaneous (ABSAT) and visceral (VAT) adipose tissue areas and liver fat content (LFAT). Fasting blood free fatty acids (FFA) were analyzed. Insulin sensitivity was assessed by the homeostasis model assessment of insulin resistance index (HOMA-R). Mean weight loss 3 and 12 months after LAGB was 9.8 +/- 1.1 kg and 20.0 +/- 2.2 kg, respectively. Postoperatively, VAT area loss exceeded ABSAT area loss in the cohort as a whole and when divided according to preoperative liver fat stores. Three months after LAGB, reductions had occurred in VAT and ABSAT areas (both P < .01) and in FFA (P < .05). Twelve months after LAGB, further significant reductions (P < .01) occurred in VAT and ABSAT areas but not in FFA. No significant reduction occurred in LFAT at either time point in the group as a whole. In those with preoperative hepatic steatosis (LFAT > approximately 5%, n = 7), LFAT fell by 42% (P = .036) 3 months after LAGB, with a total reduction of 50% (P = .027 cf baseline) occurring by 12 months. There was an improvement in HOMA-R at 12 months (1.9 +/- 0.3 cf 2.9 +/- 0.5 at baseline, P = .04) but not 3 months (2.7 +/- 0.4). Preoperatively, LFAT related significantly to VAT area (r = 0.67, P = .003) and HOMA-R (r = 0.497, P = .04) but not ABSAT area. Postoperatively at both 3 and 12 months, LFAT continued to relate to VAT area (r = 0.63, P < .01 at both time points) but not HOMA-R. The changes in LFAT and VAT area were unrelated postoperatively. Abdominal adipose tissue loss was greater from the visceral than subcutaneous depots, suggesting that insulin sensitivity may not be an important determinant of selective lipid depot loss. The lack of a significant change in liver fat in the group as a whole may relate to low preoperative liver fat stores and to high postoperative dietary fat intakes. Preoperative liver fat stores did not influence insulin sensitivity or abdominal lipid changes during weight loss. Liver fat content and VAT area interrelated more closely than either related to ABSAT area, suggesting differing regulatory pathways for fat mobilization from ABSAT and VAT depots but possibly similar pathways for storage and mobilization of fat in the liver and viscerally.