Paul E. O’Brien

Preoxygenation Is More Effective in the 25° Head-up Position Than in the Supine Position in Severely Obese Patients: A Randomized Controlled Study

Background:Class III obese patients have altered respiratory mechanics, which are further impaired in the supine position. The authors explored the hypothesis that preoxygenation in the 25° head-up position allows a greater safety margin for induction of anesthesia than the supine position. Methods:A randomized controlled trial measured oxygen saturation and the desaturation safety period after 3 min of preoxygenation in 42 consecutive (male:female 13:29) severely obese (body mass index > 40 kg/m2) patients who were undergoing laparoscopic adjustable gastric band surgery and were randomly assigned to the supine position or the 25° head-up position. Serial arterial blood gases were taken before and after preoxygenation and 90 s after induction. After induction, ventilation was delayed until blood oxygen saturation reached 92%, and this desaturation safety period was recorded. Results:The mean body mass indexes for the supine and 25° head-up groups were 47.3 and 44.9 kg/m2, respectively (P = 0.18). The group randomly assigned to the 25° head-up position achieved higher preinduction oxygen tensions (442 ± 104 vs. 360 ± 99 mmHg; P = 0.012) and took longer to reach an oxygen saturation of 92% (201 ± 55 vs. 155 ± 69 s; P = 0.023). There was a strong positive correlation between the induction oxygen tension achieved and the time to reach an oxygen saturation of 92% (r = 0.51, P = 0.001). There were no adverse events associated with the study. Conclusion:Preoxygenation in the 25° head-up position achieves 23% higher oxygen tensions, allowing a clinically significant increase in the desaturation safety period—greater time for intubation and airway control. Induction in the 25° head-up position may provide a greater safety margin for airway control.

Changes in comorbidities and improvements in quality of life after LAP-BAND placement.

Possibly the most important outcomes of bariatric surgery involve changes in obesity-related illness, quality of life (QOL), and psychologic well-being. Dramatic improvement or resolution of serious medical comorbidity accompanies the weight loss following laparoscopic adjustable gastric banding with the LAP-BAND (INAMED Health, Santa Barbara, CA). There are major improvements in the conditions of the metabolic syndrome, which is characterized by impaired glucose tolerance, dyslipidemia, and hypertension. Improvement in insulin sensitivity and pancreatic beta-cell function associated with weight loss induces remission in the majority of type 2 diabetics and reduces the risk of others developing type 2 diabetes. Improvement in dyslipidemia is characterized by raised high-density lipoprotein cholesterol and lower triglyceride concentrations. Together with lower blood pressure, these changes provide a substantial reduction in cardiovascular risk. Other medical conditions caused or aggravated by obesity are also significantly improved, including sleep apnea, daytime sleepiness, asthma, and gastroesophageal reflux. Weight loss is associated with improved fertility and more favorable pregnancy outcomes. All aspects of QOL improve substantially, especially physical disability, and post-weight-loss QOL measures approximate those of the general population. There are also major improvements in body image and reduction in depressive illness. These changes provide perhaps the most compelling data regarding the value of LAP-BAND surgery and underlie the great satisfaction experienced by patients.

Weight loss and early and late complications--the international experience.

Following its introduction in 1993, the LAP-BAND (INAMED Health, Santa Barbara, CA) has been used extensively across the world for the treatment of obesity, and data on safety and effectiveness are now available. This review draws on the literature and our own clinical patient base to provide an overview of the early and late problems associated with LAP-BAND placement and its effects on weight loss. It has proved to be a remarkably safe procedure. A report analyzing international data on laparoscopic adjustable gastric bands identified 3 deaths in 5,827 patients (approximately 1 in 2,000). In our series of 1,120 patients, there have been no deaths and no life-threatening perioperative complications. Significant early complications occurred in 17 (1.5%) of our patients; late problems have been more common, particularly during our early experience. Prolapse of the stomach through the band occurred in 125 (25%) of our first 500 patients but has occurred in only 28 (4.7%) of our last 600 patients. Erosion of the band into the stomach occurred in 34 patients (3%); all occurred in the first 500 patients. No erosions have occurred in the last 600 patients. Both problems are treated laparoscopically by removal and replacement. Combined international data show that weight loss after LAP-BAND placement is characterized by steady progressive weight loss over a 2- to 3-year period, followed by stable weight out to 6 years. This pattern reflects the benefit of adjustability. For the international series, the percent excess weight loss (%EWL) at 2 years has been between 52% and 65%. In our series, %EWL at 5 years and 6 years was 54% and 57%, respectively. The LAP-BAND is proving to be extremely safe, able to facilitate good weight loss, and able to maintain weight loss over time.

The extent of the problem of obesity.

The prevalence of obesity is increasing worldwide. In the United States, in 1999, 27% of adults had a body mass index >30 kg/m(2), almost double the prevalence of 20 years earlier. The estimated mortality from obesity-related diseases in the United States is approximately 300,000 annually and growing. In the future, mortality related to obesity is expected to exceed that of smoking. Numerous diseases are caused or made worse by obesity. These include type 2 diabetes; hypertension; dyslipidemia; ischemic heart disease; stroke; obstructive sleep apnea; asthma; nonalcoholic steatohepatitis; gastroesophageal reflux disease; degenerative joint disease of the back, hips, knees, and feet; infertility and polycystic ovary syndrome; various malignancies; and depression. Type 2 diabetes is perhaps the most visible obesity-related problem. Present in at least 14 million Americans, it leads to serious complications and premature death. It is largely caused by obesity, and is generally cured by weight loss. The quality of life of the obese is markedly reduced, and the costs to health care systems are great. Preventive programs have yet to affect the rising prevalence. An effective solution is needed.

Patient management after LAP-BAND placement.

Severe obesity is a chronic disease requiring continuing care. Optimal outcomes of laparoscopic adjustable gastric banding using the LAP-BAND (INAMED Health, Santa Barbara, CA) depend on accurate placement of the band and excellent postplacement care, which requires a long-term commitment from both the patient and the bariatric surgical team. Adjustability is a key feature of the LAP-BAND system, and knowing when and how much to adjust requires careful judgment. Two methods of approaching the art of adjustment are described: the office adjustment and the radiologic adjustment. A properly placed and adjusted band produces prolonged satiety after a small meal, facilitating a major reduction in dietary intake leading to weight loss. Healthy food choices, increased activity and exercise, and the behavioral changes necessary to achieve these are essential elements of all weight loss programs. The LAP-BAND program is no exception. Follow-up requires monitoring of the comorbidities of obesity and metabolic and nutritional status. Communication and collaboration with the patients primary care provider are important. All of the elements above are necessary to provide the comprehensive care that contributes to optimal patient outcomes.

Selecting the optimal patient for LAP-BAND placement

Optimal patient selection for laparoscopic adjustable gastric banding with the LAP-BAND (INAMED Health, Santa Barbara, CA) enables maximization of results for patients most suited to the procedure and avoidance of unsatisfactory outcomes for inappropriate candidates. We have investigated potential predictors of outcomes in our patients to look for associations with weight loss. We have also reviewed published data for additional predictors. This analysis has revealed a number of conditions associated with a significantly lower percent excess weight loss (%EWL) than experienced in the overall group. These include increasing age, increasing body mass index (BMI), hyperinsulinemia, insulin resistance, type 2 diabetes, and polycystic ovary syndrome. There was also less weight loss if the SF-36 quality-of-life measure showed a poor physical activity score, high pain score, or poor general health score. However, in all these conditions, the effect was small in comparison with the benefits achieved by these patients, and was judged insufficient to preclude this approach to treatment of their obesity. A number of conditions were found to have no relation to weight loss after LAP-BAND placement. These included sex, presence of mental illness, most comorbidities except those linked to insulin resistance, previous bariatric surgery, and sweet-eating behavior. The value of psychologic assessment to predict outcomes could not be established. The superobese (BMI >50) achieved a lower %EWL at 1 year after LAP-BAND placement compared with those with BMI <50, but there were no differences at the 2-, 3-, and 4-year follow-ups.

Systematic Review of Erosion after Laparoscopic Adjustable Gastric Banding

Erosion of the laparoscopic adjustable gastric band (LAGB) into the lumen of the stomach is a recognised complication of this procedure. We undertook a systematic literature review of the incidence, clinical features and management of erosions occurring after LAGB. A systematic search of relevant medical databases for full-text original articles looking for LAGB patients and reported erosions was conducted. We focussed on incidence, aetiology, clinical presentation, treatment, complications and weight loss. Twenty-five studies of LAGB reported 231 erosions in 15,775 patients (overall incidence of 1.46%). The mean number of patients per study was 631 (±486), and the mean follow-up was 3.73 (±2.4) years. In four reports involving less than 100 patients, there were 27 erosions in a total of 270 patients (10%) compared with 180 erosions in 12,978 patients (1.386%) in the remaining 21 reports. Multiple regression analysis showed that erosion rate was significantly predicted by number of patients and number of years of surgeon experience (r2 = 0.186). Treatment was most commonly by removal of the band, repair of the stomach and later, band replacement. Other options were removal alone or conversion to another procedure. Weight loss was retained after treatment of the erosion with a mean weight loss at final follow-up of 50.34 ± 3.9 percent excess weight loss. Incidence of erosion after gastric banding is relatively low and can be related to surgeon experience. The most common treatment described in the literature is removal of the eroded band with delayed replacement. Replacement of the band is associated with maintenance of weight loss.

Obesity and the White Blood Cell Count: Changes with Sustained Weight Loss

Background: Obesity is a chronic inflammatory condition, and elevated white blood cell counts (WBC) have widely recognized associations with inflammatory conditions. The authors explored the relationship between the WBC and degree of obesity, basic anthropometry, and clinical and biochemical markers of the metabolic syndrome at baseline, and with weight loss following Lap-Band® surgery. Methods: 477 patients with complete biochemical and clinical data at baseline and at 2 years were selected for analysis. Paired analysis assessed the change in WBC at 2 years, and stepwise linear regression assessed factors independently associated with baseline counts and any change at 2 years. Results: Mean ± SD weight loss at 2 years was 29.3 ± 16.2 kg. There were significant decreases in total WBC (−12.2%), and major components, neutrophils (11.7%) and lymphocytes (6.9%), at 2 years (P<0.001 for all). Baseline WBC, neutrophils and lymphocyte counts increased with increasing BMI and decreased with age. Insulin levels were independently positively associated with higher neutrophil counts and triglycerides with higher lymphocyte counts. Age, gender, BMI and components of the metabolic syndrome when modeled together accounted for <10% of the variance of baseline counts. Higher BMI predicted a greater fall in the neutrophil counts at 2 years. Change in BMI at 2 years was the only independent predictor of the change in both neutrophils and lymphocytes, but accounted for <10% of the variance of change. Conclusion: BMI contributes to both baseline and weight loss WBC. However, crude WBC counts are influenced in minor ways by obesity markers and have limited value as clinical markers.

Characterization of an animal model of hepatic metastasis

The experimental study of possible therapies for control of the growth of liver metastases requires the availability of a model which is technically feasible and appears to exhibit growth characteristics similar to human tumours. We report on the development of an intrasplenic injection model of liver metastases, and describe the histology, growth pattern and blood flow demonstrated by light microscopy, stereology and laser Doppler flowmetry. The hepatic metastases were induced in mice by intrasplenic injection of dimethylhydrazine (DMH) induced primary colonic carcinoma cells (106 cells in 1 mL). The growth and development of metastases was studied over a period of 3 weeks at predetermined time points. Tumour cells were visible in the hepatic sinusoids by day 7 by light microscopy. Macroscopically visible tumours with a diameter of 0.18 ± 0.02 cm (mean ± s.d.) were seen by day 10. By this time the tumours had derived a blood supply from the hepatic sinusoids adjacent to the tumour periphery. With further vascularization the tumours reached a diameter of 0.96 ± 0.50 cm by day 22. Metastatic growth was quantitated by stereological analysis of tumour volume in relation to non‐diseased hepatic tissue. Normal mouse liver had a mean volume of 1.13 ± 0.14 cm3. Tumour growth occurred in three phases. During the initial slow phase the volume of metastases increased from 0.03 ± 0.02 cm3 at day 10 to 0.22 ± 0.24 cm3 by day 16. Rapid tumour growth, occurring over the next 3 days, constituted the intermediate phase with metastatic volume reaching 1.21 ± 0.74 cm3 by day 19 (P= 0.0003 compared with day 16). This growth was followed by a plateau phase when the metastatic volume was 1.40 ± 0.55 cm3 at day 22. The volume of total liver and of tumour necrosis followed a similar growth pattern. A necrotic tumour volume of 0.004 ± 0.006 cm3 first seen on day 10 increased to 0.05 ± 0.06 cm3 by day 16, and to 0.25 ± 0.20 cm3 by day 22 (P=0.0022 compared with day 16). The blood flow in metastases measured by laser Doppler flowmetry was lower compared to the non‐diseased liver. Tumour blood flow, expressed as a percentage of normal liver blood flow, was 63.31 ± 26.28% at day 10 and diminished to 27.91 ± 8.99% by day 22, with an increase in tumour size and age. The decrease in flow was significant between days 13 and 16 (P= 0.0015). This intrasplenic mouse model of metastases is reproducible and should prove useful in the study of treatment of hepatic metastases.

Tyk2 and Stat3 Regulate Brown Adipose Tissue Differentiation and Obesity

Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT). Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high-fat diet and in obese humans. Expression of Tyk2 or the constitutively active form of the transcription factor Stat3 (CAStat3) restores differentiation in Tyk2(-/-) brown preadipocytes. Furthermore, Tyk2(-/-) mice expressing CAStat3 transgene in BAT also show improved BAT development, normal levels of insulin, and significantly lower body weights. Stat3 binds to PRDM16, a master regulator of BAT differentiation, and enhances the stability of PRDM16 protein. These results define Tyk2 and Stat3 as critical determinants of brown fat lineage and suggest that altered levels of Tyk2 are associated with obesity in both rodents and humans.