Marc Bessler

Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial.

IMPORTANCE Controlling glycemia, blood pressure, and cholesterol is important for patients with diabetes. How best to achieve this goal is unknown. OBJECTIVE To compare Roux-en-Y gastric bypass with lifestyle and intensive medical management to achieve control of comorbid risk factors. DESIGN, SETTING, AND PARTICIPANTS A 12-month, 2-group unblinded randomized trial at 4 teaching hospitals in the United States and Taiwan involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher, body mass index (BMI) between 30.0 and 39.9, C peptide level of more than 1.0 ng/mL, and type 2 diabetes for at least 6 months. The study began in April 2008. INTERVENTIONS Lifestyle-intensive medical management intervention and Roux-en-Y gastric bypass surgery. Medications for hyperglycemia, hypertension, and dyslipidemia were prescribed according to protocol and surgical techniques that were standardized. MAIN OUTCOMES AND MEASURES Composite goal of HbA1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg. RESULTS All 120 patients received the intensive lifestyle-medical management protocol and 60 were randomly assigned to undergo Roux-en-Y gastric bypass. After 12-months, 28 participants (49%; 95% CI, 36%-63%) in the gastric bypass group and 11 (19%; 95% CI, 10%-32%) in the lifestyle-medical management group achieved the primary end points (odds ratio [OR], 4.8; 95% CI, 1.9-11.7). Participants in the gastric bypass group required 3.0 fewer medications (mean, 1.7 vs 4.8; 95% CI for the difference, 2.3-3.6) and lost 26.1% vs 7.9% of their initial body weigh compared with the lifestyle-medical management group (difference, 17.5%; 95% CI, 14.2%-20.7%). Regression analyses indicated that achieving the composite end point was primarily attributable to weight loss. There were 22 serious adverse events in the gastric bypass group, including 1 cardiovascular event, and 15 in the lifestyle-medical management group. There were 4 perioperative complications and 6 late postoperative complications. The gastric bypass group experienced more nutritional deficiency than the lifestyle-medical management group. CONCLUSIONS AND RELEVANCE In mild to moderately obese patients with type 2 diabetes, adding gastric bypass surgery to lifestyle and medical management was associated with a greater likelihood of achieving the composite goal. Potential benefits of adding gastric bypass surgery to the best lifestyle and medical management strategies of diabetes must be weighed against the risk of serious adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00641251.

Prospective Study of Gut Hormone and Metabolic Changes After Adjustable Gastric Banding and Roux-en-Y Gastric Bypass

Objective:The objective of this study was to quantify hormones that regulate energy and glucose homeostasis to establish possible mechanisms for the greater efficacy of Roux-en-Y gastric bypass (RYGB) compared with laparoscopic adjustable gastric banding (LAGB) in achieving weight loss and improved insulin sensitivity.Design:Longitudinal study of patients undergoing LAGB (n=15) and RYGB (n=28) who were studied before surgery and at 2, 12, 26 and 52 weeks afterwards.Measurements:Fasting blood samples were drawn at each visit. Postprandial blood samples were also obtained before surgery and at 26 and 52 weeks. Samples were assayed for peptide YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, leptin, thyrotropic hormone, free T4 and free T3.Results:At 1 year there was greater weight loss in RYGB compared with LAGB patients (30 vs 15%), but final body mass index was similar (34 vs 33 kg m−2). At week 52, area under the curve (AUC) for PYY in RYGB subjects was greater than LAGB (P<0.01). GLP-1 levels at 30 min after meal were threefold greater after RYGB compared with LAGB (P<0.001). Conversely, ghrelin AUC increased after LAGB at week 52 (P<0.05) but tended to decrease after RYGB. Fasting glucose, insulin, and leptin and homeostasis model of assessment (HOMA-IR) decreased in both groups over time but were significantly lower at week 52 after RYGB compared with LAGB. The change in leptin correlated significantly with weight loss in LAGB (r=0.86) and RYGB (r=0.77), however, HOMA-IR correlated significantly with weight loss only in LAGB (r=0.78), and not RYGB (r=0.15). There was a significant decrease in free T3 (P<0.01) after RYGB.Conclusions:Differences in levels of gut hormones may play a role in promoting greater weight loss and insulin sensitivity after RYGB compared with LAGB, however, weight loss may be limited by decreases in free T3 and leptin.

Re-emergence of diabetes after gastric bypass in patients with mid- to long-term follow-up.

BACKGROUND Studies have shown that type 2 diabetes (T2DM) improves or resolves shortly after Roux-en-Y gastric bypass (RYGB). Few data are available on T2DM recurrence or the effect of weight regain on T2DM status. METHODS A review of 42 RYGB patients with T2DM and >or=3 years of follow-up and laboratory data was performed. Postoperative weight loss and T2DM status was assessed. Recurrence or worsening was defined as hemoglobin A1c >6.0% and fasting glucose >124 mg/dL and/or medication required after remission or improvement. Patients whose T2DM recurred or worsened were compared with those whose did not, and patients whose T2DM improved were compared with those whose T2DM resolved. RESULTS T2DM had either resolved or improved in all patients (64% and 36%, respectively); 24% (10) recurred or worsened. The patients with recurrence or worsening had had a lower preoperative body mass index than those without recurrence or worsening (47.9 versus 52.9 kg/m2; P = .05), regained a greater percentage of their lost weight (37.7% versus 15.4%; P = .002), had a greater weight loss failure rate (63% versus 14%; P = .03), and had greater postoperative glucose levels (138 versus 102 mg/dL; P = .0002). Patients who required insulin or oral medication before RYGB were more likely to experience improvement rather than resolution (92% versus 8%, P <or=.0001; and 85% versus 15%; P = .0006, respectively). CONCLUSION Our results have shown that beyond 3 years after RYGB, the incidence of T2DM recurrence or worsening in patients with initial resolution or improvement was significant. In our patients, a greater likelihood of recurrence or worsening of T2DM was associated with a lower preoperative body mass index. Before widespread acceptance of bariatric surgery as a definitive treatment for those with T2DM can be achieved, additional study of this recurrence phenomenon is indicated.

Differential Effects of Gastric Bypass and Banding on Circulating Gut Hormone and Leptin Levels

Objective: To quantify plasma concentrations of hormones that regulate energy homeostasis in order to establish possible mechanisms for greater weight loss after Roux‐en‐Y gastric bypass (RYGBP) compared with gastric banding (BND).

The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss.

CONTEXT Bariatric surgery is common and may be associated with deleterious effects on the skeleton. OBJECTIVE Our objective was to assess bone metabolism and bone mineral density (BMD) after Roux-en-Y gastric bypass. DESIGN AND SETTING We conducted a 1-yr prospective longitudinal study at a university hospital bariatric surgery practice and metabolic bone disease unit. PARTICIPANTS Participants included 23 obese (mean body mass index 47 kg/m(2)) men and women, aged 20-64 yr. MAIN OUTCOME MEASURES Serum PTH, 25-hydroxyvitamin D, osteocalcin, and urinary N-telopeptide, and BMD were assessed. RESULTS Patients lost 45 +/- 2 kg 1 yr postoperatively (P < 0.01). PTH increased early (3 months, 43-50 pg/ml; P < 0.001) and urinary calcium dropped (161-92 mg/24 h; P < 0.01), despite doubling of calcium intake (1318-2488 mg/d; P < 0.001). Serum 25-hydroxyvitamin D concentrations were unchanged (23-26 ng/ml), although vitamin D intake increased by 260% (658 IU/d at baseline to 1698 IU/d at 12 months; P < 0.05). Markers of bone remodeling rose (P < 0.01 for both urinary N-telopeptide and osteocalcin), whereas BMD decreased at the femoral neck (9.2%, P < 0.005) and at the total hip (8.0%, P < 0.005). These declines were strongly associated with the extent of weight loss (femoral neck: r = 0.90, P < 0.0001; and total hip: r = 0.65, P = 0.02). Lumbar spine and distal radius sites did not change. CONCLUSIONS After Roux-en-Y gastric bypass, there was evidence of calcium and vitamin D malabsorption. Bone turnover increased, and hip bone density rapidly declined. The decline in hip BMD was strongly associated with weight loss itself. Vigilance for nutritional deficiencies and bone loss in patients both before and after bariatric surgery is crucial.

Totally Transumbilical Laparoscopic Cholecystectomy

A recently convened Consortium at the Cleveland Clinic agreed on the term Laparo-Endoscopic Single-Site (LESS) surgery to describe minimally invasive techniques that use a single incision to accomplish laparoscopic procedures. These procedures are done by using either a single port through one fascial incision or multiple ports placed through separate fascial incisions. Because of cost containment issues and the lack of widespread availability of a single port, we currently use multiple reusable ports placed through three separate fascial incisions via a transumbilical incision. As opposed to standard laparoscopic cholecystectomy, a deflecting laparoscope and one articulating instrument are utilized to improve the safety and ease of this procedure. Presented in this video are the steps necessary to perform a LESS cholecystectomy via a transumbilical incision with commercially available instruments.

Very Low–Calorie Diet Mimics the Early Beneficial Effect of Roux-en-Y Gastric Bypass on Insulin Sensitivity and β-Cell Function in Type 2 Diabetic Patients

Marked improvement in glycemic control occurs in patients with type 2 diabetes mellitus shortly after Roux-en-Y gastric bypass surgery (RYGB) and before there is major weight loss. The objective of this study was to determine whether the magnitude of this change is primarily due to caloric restriction or is unique to the surgical procedure. We studied eleven subjects who underwent RYGB and fourteen subjects mean-matched for BMI, HbA1c, and diabetes duration who were admitted to our inpatient research unit and given a very low–calorie diet (VLCD) of 500 kcal/day with a macronutrient content similar to that consumed by patients after RYGB. Frequently sampled intravenous glucose tolerance tests were performed before and after interventions. Both groups lost an equivalent amount of weight over a mean study period of 21 days. Insulin sensitivity, acute insulin secretion after intravenous glucose administration, and β-cell function as determined by disposition index improved to a similar extent in both groups. Likewise, changes in fasting glucose and fructosamine levels were similar. Based on these data, VLCD improves insulin sensitivity and β-cell function just as well as RYGB in the short term.

Better preservation of immune function after laparoscopic-assisted vs . open bowel resection in a murine model

PURPOSE: We evaluated cell-mediated immune function after laparoscopic-assisted and open bowel resection in rats by measuring delayed-type hypersensitivity responses to keyhole limpet hemocyanin (KLH) and phytohemagglutinin (PHA). METHODS: Male Sprague-Dawley rats (n=120) were sensitized to 1 mg of KLH ten days before investigations. Rats were challenged preoperatively, immediately postoperatively, and on postoperative day (POD) 2 with an intradermal injection of 0.3 mg of KLH and 0.2 mg of PHA (at different sites). Averages of two measures of perpendicular diameters (taken 24 and 48 hours postchallenge) were used to calculate the area of induration using the formula for the area of an ellipse, A=(D1/2×D2/2)×π. Anesthesia control animals underwent no procedure (n=40). Open resection group underwent ligation and resection of the cecum (length=2 cm) through a 7 cm midline incision (n=40). In the laparoscopic-assisted resection group, under CO2 pneumoperitoneum (4–6 mmHg), the cecum was identified, dissected free, and exteriorized through a 4 mm port. The cecum was then ligated and resected extracorporeally (n=40). RESULTS: Preoperative responses to both KLH and PHA were the same in all three groups. Furthermore, within each group, postoperative responses were similar. When groups were compared, the anesthesia group responses were significantly greater than the open resection group responses at all time points (P<0.05 for all comparisons). Laparoscopic-assisted resection group responses differed from control at only two of eight postoperative measures. Laparoscopic resection group responses were significantly greater than open resection group responses to challenge with both KLH and PHA on POD1 (P<0.02, for both comparisons) and POD 4 (P<0.05, for both comparisons). CONCLUSIONS: Postoperative cell-mediated immune function is better preserved after laparoscopic-assisted bowel resection than after open resection as assessed by skin antigen testing.

Trocar site recurrence is unlikely to result from aerosolization of tumor cells.

PURPOSE: This study was undertaken to investigate the ability of a high-pressure CO2 environment to aerosolize tumor cells in bothin vitroandin vivo models. (An aerosol is defined as a stable gaseous suspension of insoluble particles.) Also, this study was designed to determine if rapid desufflation is capable of transporting fluid laden with tumor cells. METHODS: The fourin vitro aerosol experiments were performed in an 18.9-l plastic vessel fitted with two 7-mm ports and a compliant latex balloon affixed to the top. After CO2 insufflation, the vessel was desufflated through a sterile soluset containing 25 ml of culture media that was subsequently emptied into a culture dish, incubated for two weeks, and periodicallyassessed for growth. At the bottom of the vessel, one of the following was placed: Study 1 and 2, a suspension of B16 melanoma or colon 26 tumor cells in liquid culture media; Study 3, colon 26 cells in saline solution; Study 4, several pieces of solid colon 26 tumor. In Studies 1 to 3, cell preparations were subjected to the following high-pressure CO2 conditions (pneumo): 1) static pneumo of 15 and 30 mmHg (10 minute dwell); 2) a continuous flow (CF) of CO2 (10 l) while maintaining a pressure of 15 or 30 mmHg in the vessel. In Study 4, only the 30 mmHg static and CF conditions were tested. Between 6 and 12 determinations were performed for each condition and cell preparation.In vivo aerosol experiments consisted of Spraque Dawley rats that received intraperitoneal injections of 10-5 B16 cells in 0.1 ml of liquid media.Two laparoscopic ports were placed in the abdomen, one each for insufflation and desufflation. Study groups were: 1, static CO2 pneumo of 15 mmHg; 2 and 3, continuous CO2 flow (10 l) at a stable pneumo pressure of 5 and 10 mmHg. Desufflation was performedvia the same collecting device and handled in an identical manner to thein vitroexperiments described above. Thein vitro balloon experiment was designed to investigate the ability of desufflation to transport fluid-containing tumor cells; latex balloon model was used. To prevent complete loss of volume on desufflation, a wire coil was placed inside the balloon. Twenty ml of media containing 20×10−6B16 cells was placed in the bottom of the balloon. The balloon was insufflated with 1 to 21 of gas. There were three study groups that differed in the degree to which the cell suspension was agitated before desufflation. Study conditions were as follows: 1) no agitation; 2) moderate agitation to coat the lower walls and coil; 3) maximum agitation to coat the entire balloon. To verify the viability of tumor cells,at the end of eachin vitroandin vivo study, a sample of tumor cells or peritoneal washing was incubated in sterile media. These samples served as positive controls. RESULTS:In vitro aerosol studies consisted of the following. At the end of two weeks of incubation, no tumor growth was noted in any of the 124 test dishes. The 14 control samples all demonstrated tumor growth.In vivo aerosol studies consisted of the following. Zero of 18 experimental dishes grew tumor. All three peritoneal washing samples demonstrated growth.In vitro balloon studies consisted of the following. Zero of 12 test dishes in Groups 1 and 2 demonstrated growth, whereas five of six dishes did so in Group 3 (maximally agitated before desufflation). Again, positive controls all grew tumor cells. SUMMARY: We were unable to demonstrate aerosol formation in any of thein vitroandin vivo studies performed. In the balloon experiment, desufflation-related transport of tumor cells was demonstrated but only when the entire balloon surface was coated with the tumor cell suspension before desufflation. CONCLUSION: Aerosols of tumor cells are not likely to form. Free intraperitoneal tumor cells are most likely found in liquid suspension. Desufflation is a potential means of transport of cell-laden fluid.

Transvaginal natural orifice translumenal endoscopic surgery cholecystectomy: early evolution of the technique.

Introduction:Initial excitement for Natural Orifice Transluminal Endoscopic Surgery (NOTES) has been partly tempered by the reality that a NOTES procedure without laparoscopic or needleoscopic-assistance has not been performed by most groups. After safely performing laparoscopically-assisted transvaginal cholecystectomy in an IACUC-approved porcine model, we embarked on an IRB-approved protocol to ultimately perform a pure NOTES cholecystectomy. Materials and Methods:We describe our experience with performing a true NOTES tansvaginal cholecystectomy after safely accomplishing 3 laparoscopically-assisted hybrid NOTES procedures in humans. To overcome the retracting limitations of currently available endoscopes, we used a 5-mm curved or articulating retractor that was placed into the abdomen via a separate colpotomy in the second and third patient. In a fourth patient, pneumoperitoneum to 15 torr was obtained via a transvaginal trocar placed through a colpotomy made under direct vision and endoscopically placed clips were used for both the cystic duct and artery, thus, obviating the need for any transabdominally placed instruments or needles. Results:This patient was the first patient to undergo a completely NOTES cholecystectomy at our institution and to our knowledge in the United States. She was discharged on the day of surgery and has not suffered any complication after 1 month of follow-up. Conclusion:Pure NOTES transvaginal cholecystectomy without aid of laparoscopic or needleoscopic instruments is feasible and safe in humans. Additional experience with this technique will be required before comparative studies to standard laparoscopy and hybrid techniques are appropriate.