Adiposopathy and bariatric surgery: is 'sick fat' a surgical disease?

OBJECTIVE: To review how bariatric surgery in obese patients may effectively treat adiposopathy (pathogenic adipose tissue or 'sick fat'), and to provide clinicians a rationale as to why bariatric surgery is a potential treatment option for overweight patients with type 2 diabetes, hypertension, and dyslipidaemia. METHODS: A group of clinicians, researchers, and surgeons, all with a background in treating obesity and the adverse metabolic consequences of excessive body fat, reviewed the medical literature regarding the improvement in metabolic disease with bariatric surgery. RESULTS: Bariatric surgery improves metabolic disease through multiple, likely interrelated mechanisms including: (i) initial acute fasting and diminished caloric intake inherent with many gastrointestinal surgical procedures; (ii) favourable alterations in gastrointestinal endocrine and immune responses, especially with bariatric surgeries that reroute nutrient gastrointestinal delivery such as gastric bypass procedures; and (iii) a decrease in adipose tissue mass. Regarding adipose tissue mass, during positive caloric balance, impaired adipogenesis (resulting in limitations in adipocyte number or size) and visceral adiposity are anatomic manifestations of pathogenic adipose tissue (adiposopathy). This may cause adverse adipose tissue endocrine and immune responses that lead to metabolic disease. A decrease in adipocyte size and decrease in visceral adiposity, as often occurs with bariatric surgery, may effectively improve adiposopathy, and thus effectively treat metabolic disease. It is the relationship between bariatric surgery and its effects upon pathogenic adipose tissue that is the focus of this discussion. CONCLUSIONS: In selective obese patients with metabolic disease who are refractory to medical management, adiposopathy is a surgical disease.

Longitudinal changes in pancreatic and adipocyte hormones following Roux-en-Y gastric bypass surgery.

AIMS/HYPOTHESIS: Bariatric surgery is an effective treatment for severe obesity, as in addition to dramatic weight loss, co-morbidities such as type 2 diabetes are frequently resolved. Although altered gastrointestinal peptide hormone secretion and its relationship with post-surgical improvements in insulin sensitivity has been studied, much less is known about long-term changes in pancreatic and adipose tissue-derived hormones. Our objective was to conduct a comprehensive longitudinal investigation of the endocrine changes following Roux-en-Y gastric bypass surgery (RYGBP), focusing on pancreatic and adipocyte hormones and systemic markers of inflammation. METHODS: Nineteen severely obese women (BMI 45.6 +/- 1.6 kg/m(2)) were studied prior to RYGBP, and at 1, 3, 6, and 12 months after RYGBP. Body composition was assessed before surgery and at 1 and 12 months. RESULTS: Pre-surgical adiposity was correlated with circulating adipocyte hormones (leptin, visfatin) and inflammatory molecules (IL-6, high sensitivity C-reactive protein [hsCRP], monocyte chemoattractant protein-1). As expected, RYGBP reduced fat mass and fasting insulin and glucose concentrations. In addition, reductions of fasting pancreatic polypeptide (PP) and glucagon concentrations were observed at 1 and 3 months, respectively. In the 12 months following RYGBP, concentrations of most adipocyte hormones (leptin, acylation-stimulating hormone and visfatin, but not retinol-binding hormone-4) and inflammatory molecules (IL-6, hsCRP and soluble intracellular adhesion molecule-1) were significantly reduced. Reductions of insulin resistance (measured by homeostasis model assessment of insulin resistance) were independently associated with changes of glucagon, visfatin and PP. Pre-surgical HMW adiponectin concentrations independently predicted losses of body weight and fat mass. CONCLUSIONS/INTERPRETATION: These results suggest that pancreatic and adipocyte hormones may contribute to the long-term resolution of insulin resistance after RYGBP.

Genes and networks expressed in perioperative omental adipose tissue are correlated with weight loss from Roux-en-Y gastric bypass.

CONTEXT: Gastric bypass surgery is the most commonly performed bariatric surgical procedure in the United States. Variable weight loss following this relatively standardized intervention has been reported. To date, a method for reliable profiling of patients who will successfully sustain weight loss for the long term has not been established. In addition, the mechanisms of action in accomplishing major weight loss as well as the explanation for the variable weight loss have not been established. OBJECTIVE: To examine whether gene expression in perioperative omental adipose is associated with gastric bypass-induced weight loss. DESIGN: Cross-sectional study of gene expression in perisurgical omental adipose tissues taken/available at the time of operation and total excess weight loss (EWL). SUBJECTS: Fifteen overweight individuals who underwent Roux-en-Y gastric bypass (RYGB) surgery at the University of California Davis Medical Center (BMI: 40.6-72.8 kg/m(2)). MEASUREMENTS: Body weight before and following weight stabilization 18-42 months after surgery. Perioperative omental adipose RNA isolated from 15 subjects was hybridized to Affymetrix HG-U133A chips for 22,283 transcript expression measurements. RESULTS: Downstream analysis identified a set of genes whose expression was significantly correlated with RYGB-induced weight loss. The significant individual genes include acyl-coenzyme A oxidase 1 (ACOX1), phosphodiesterase 3A cGMP-inhibited (PDE3A) and protein kinase, AMP-activated, beta 1 non-catalytic subunit (PRKAB1). Specifically, ACOX1 plays a role in fatty acid metabolism. PDE3A is involved in purine metabolism and hormone-stimulated lipolysis. PRKAB1 is involved in adipocytokine signaling pathway. Gene network analysis revealed that pathways for glycerolipid metabolism, breast cancer and apoptosis were significantly correlated with long-term weight loss. CONCLUSION: This study demonstrates that RNA expression profiles from perioperative adipose tissue are associated with weight loss outcome following RYGB surgery. Our data suggest that EWL could be predicted from preoperative samples, which would allow for informed decisions about whether or not to proceed to surgery.

Esophageal motility disorders after gastric banding.

The long-term effects of gastric banding on esophageal function are not well described. This report describes a 28-year-old woman who developed signs and symptoms of abnormal esophageal motility and lower esophageal sphincter hypotension after gastric banding for morbid obesity. The current literature addressing the effects of gastric banding on esophageal function in light of this case report is discussed.

Serum leptin levels, hepatic leptin receptor transcription, and clinical predictors of non-alcoholic steatohepatitis in obese bariatric surgery patients.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a major cause of liver disease in morbidly obese patients. Clinical predictors of NASH remain elusive, as do molecular mechanisms of pathogenesis. METHODS: A series of 35 morbidly obese patients undergoing bariatric surgery had a liver biopsy performed for standard histologic analysis. In addition, RNA was obtained from liver tissue and analyzed for leptin receptor gene expression. Regression analysis was used to correlate clinical variables, including serum leptin levels and hepatic leptin receptor gene expression, with the presence of histologically confirmed NASH. RESULTS: Of the 35 subjects enrolled, 29% had steatosis only, 60% had NASH, and 11% had normal liver histology. Among the clinical variables studied, only diabetes mellitus was an independent predictor of NASH. There was a trend toward lower levels of mRNA encoding the long form of the leptin receptor in hepatic tissue from patients with NASH compared to those with steatosis only. CONCLUSIONS: Diabetes mellitus is associated with an increased risk of NASH in obese patients. Downregulation of hepatic leptin receptor may play a role in the pathogenesis of NASH.

Circulating concentrations of high-molecular-weight adiponectin are increased following Roux-en-Y gastric bypass surgery.

AIMS/HYPOTHESIS: In addition to weight loss, bariatric surgery for severe obesity dramatically alleviates insulin resistance. In this study, we investigated whether circulating concentrations of the high-molecular-weight (HMW) form of adiponectin are increased following gastric bypass surgery. The HMW form is implicated as the multimer responsible for adiponectin's hepatic insulin-sensitising actions. SUBJECTS AND METHODS: We studied 19 women who were undergoing Roux-en-Y gastric bypass surgery. Studies were conducted prior to, and 1 and 12 months after surgery. RESULTS: One month after surgery, total plasma adiponectin concentrations were unchanged. Nevertheless, increases in both HMW (by 40+/-15%, p=0.006) and the proportion of adiponectin in the HMW form (from 40+/-2 to 50+/-2%, p<0.0001) were observed. At 12 months, total and HMW adiponectin concentrations were increased by 58+/-8% and 118+/-21%, respectively (both p<0.001). The majority (80%) of the increase of total adiponectin was due to an increase of the HMW form. After adjustment for covariates, increases of HMW and total adiponectin at 12 months were correlated with the decrease of fat mass (HMW, p=0.0076; total, p=0.0302). In subjects with improved insulin sensitivity at 12 months after surgery (n=18), the increase of HMW, but not that of total adiponectin, predicted the relative decrease of insulin resistance (HMW: p=0.0044; total: p=0.0775, after adjustment for covariates). CONCLUSIONS/INTERPRETATION: These data suggest that the reduction of fat mass following gastric bypass surgery is an important determinant of the increase of HMW adiponectin concentrations, which in turn is associated with and may contribute to the resulting improvement of insulin sensitivity.

The SAGES Bariatric Surgery Outcome Initiative.

BACKGROUND: The recent initiative for identifying centers of excellence in bariatric surgery calls for documentation of surgical outcomes. The SAGES Outcomes Initiative is a national database introduced in 1999 as a method for surgeons to accumulate and compare their data with summary national data. A bariatric-specific dataset was established later in 2001. The aim of this study was to compare the outcomes of bariatric surgery from the Society of American Gastrointestinal Endoscopic Surgeons' (SAGES) bariatric database with data derived from a national administrative database of academic centers. METHODS: Between 2001 and 2004, 24 surgeons with 1,954 patients participated in the SAGES Bariatric Outcome Initiative, and 97 institutions with 42,847 patients participated in the University HealthSystem Consortium (UHC) database. Only 7 of the 24 surgeons participating in the SAGES Bariatric Outcome Initiative submitted more than 50 cases. The main outcome measures included demographics, comorbidities, type of bariatric procedure, operative time, length of hospital stay, short- and long-term complications, mortality, and weight loss. RESULTS: Both datasets were comparable for gender. Roux-en-Y gastric bypass had been performed for 88% of the patients in the SAGES database and 96% of the patients in the UHC database. Associated comorbidities were similar between the two groups except for a higher rate of hyperlipidemia for the patients in the SAGES database. The SAGES database contains more bariatric-specific information such as body mass index, operative time, blood loss, bariatric-specific complications, long-term complications, and weight loss data than the UHC database. According to the available data, no statistically significant differences exist between the two datasets in terms of perioperative complications and mortality. CONCLUSIONS: The SAGES Bariatric Outcome Initiative provides valuable bariatric-specific data not currently available in an administrative database that may be useful for benchmarking purposes. However, this database is currently underutilized.

Robot-assisted laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Robotic surgery promises to extend the capabilities of the minimally invasive surgeon. The aim of this study was to examine the feasibility of robotic surgery in the setting of laparoscopic gastric bypass. METHODS: The Zeus robotic surgical system was used in 50 laparoscopic gastric bypass procedures. The learning curve was staged to add complexity to the robotic tasks as experience grew. Robotic setup time, robotic operative time, total operative time, and operative outcomes were tracked prospectively. RESULTS: We observed a significant decrease in the robotic setup time. Our robotic learning curve demonstrated decreased operative time, even as more complex tasks were accomplished. Total operative time also decreased significantly over the series. There were no complications in our series that could be attributed to the robotic technique. CONCLUSIONS: Robot-assisted laparoscopic Roux-en-Y gastric bypass is safe. The steadiness and extra degrees of freedom of surgical robotic systems may improve the accuracy of laparoscopic tasks. The learning curve for robot-assisted laparoscopic Roux-en-Y gastric bypass is significant but manageable.

Effects of pneumoperitoneum on intraoperative pulmonary mechanics and gas exchange during laparoscopic gastric bypass.

BACKGROUND: Hypercarbia and elevated intraabdominal pressure resulting from carbon dioxide (CO2) pneumoperitoneum can adversely affect respiratory mechanics. This study examined the changes in mechanical ventilation, CO2 homeostasis, and pulmonary gas exchange in morbidly obese patients undergoing a laparoscopic or open gastric bypass (GBP) procedure. METHODS: In this study, 58 patients with a body mass index (BMI) of 40 to 60 kg/m2 were randomly allocated to laparoscopic ( n = 31) or open ( n = 27) GBP. Minute ventilation was adjusted to maintain a low normal arterial partial pressure of CO2 (PaCO2), low normal end-tidal partial pressure of CO2 (ETCO2), and low airway pressure. Respiratory compliance, ETCO2, peak inspiratory pressure (PIP), total exhaled CO2 per minute (VCO2), and pulse oximetry (SO2) were measured at 30-min intervals. The acid-base balance was determined by arterial blood gas analysis at 1-h intervals. The pulmonary gas exchange was evaluated by calculation of the alveolar dead space-to-tidal volume ratio (V(Dalv)/V(T)) and alveolar-arterial oxygen gradient (PAO2-PaO2). RESULTS: The two groups were similar in age, gender, and BMI. As compared with open GBP, laparoscopic GBP resulted in higher ETCO2, PIP, and VCO2, and a lower respiratory compliance. Arterial blood gas analysis demonstrated higher PaCO2 and lower pH during laparoscopic GBP than during open GBP ( p < 0.05). The V(Dalv)/V(T) ratio and PAO2-PaO2 gradient did not change significantly during laparoscopic GBP. Intraoperative oxygen desaturation (SO2 < 90%) did not develop in any of the patients in either group. CONCLUSIONS: Laparoscopic GBP alters intraoperative pulmonary mechanics and acid-base balance but does not significantly affect pulmonary oxygen exchange. Changes in pulmonary mechanics are well tolerated in morbidly obese patients when proper ventilator adjustments are maintained.

Duplex ultrasound assessment of femoral venous flow during laparoscopic and open gastric bypass.

BACKGROUND: Pneumoperitoneum (PP) and the reverse Trendelenburg (RT) position have been shown to decrease femoral blood flow, resulting in venous stasis. However the effects of PP and RT on femoral venous flow have not been evaluated in morbidly obese patients undergoing laparoscopic gastric bypass (GBP). We analyzed the effects of PP and RT on peak systolic velocity and the cross-sectional area of the femoral vein during laparoscopic and open GBP. We further examined the efficacy of intermittent sequential compression devices in reversing the reduction of femoral peak systolic velocity. METHODS: Thirty patients with a body mass index (BMI) of 40-60 were randomly allocated to under go either laparoscopic (n = 14) or open (n = 16) GBP. A duplex ultrasound examination of the femoral vein was performed at baseline, during PP and combined PP and RT in the laparoscopic group, and at baseline and during RT in the open group. The ultrasound exam was performed first without the use of sequential compression devices and then with the sequential compression devices inflated to 45 mmHg. RESULTS: The two groups were similar in age, sex, BMI, and calf and thigh circumferences. During laparoscopic GBP, PP resulted in a 43% decrease in peak systolic velocity and a 52% increase in the cross-sectional area of the femoral vein; the combination of PP and RT decreased peak systolic velocity to 57% of baseline and increased the femoral cross-sectional area to 121% of baseline. During laparoscopic GBP, the use of sequential compression devices during PP and RT partially reversed the reduction of femoral peak systolic velocity, but femoral peak systolic velocity was still lower than baseline by 38%. During open GBP, RT resulted in a 38% reduction in peak systolic velocity and a 69% increase in the cross-sectional area of the femoral vein; the use of sequential compression devices during RT partially reversed these changes by increasing femoral peak systolic velocity by 26%; however, it was still lower than baseline by 22%. CONCLUSIONS: Pneumoperitoneum and reverse Trendelenburg position during laparoscopic and open GBP are independent factors for the development of venous stasis. Combining the reverse Trendelenburg position with pneumoperitoneum during laparoscopic GBP further reduces femoral peak systolic velocity and hence increases venous stasis. The use of sequential compression devices was partially effective in reversing the reduction of femoral peak systolic velocity, but it did not return femoral peak systolic velocity to baseline levels.

Effect of heated and humidified carbon dioxide gas on core temperature and postoperative pain: a randomized trial.

BACKGROUND: Intraoperative hypothermia is a common event during laparoscopic operations. An external warming blanket has been shown to be effective in preventing hypothermia. It has now been proposed that using heated and humidified insufflation gas can prevent hypothermia and decrease postoperative pain. Therefore, we examined the extent of intraoperative hypothermia in patients undergoing laparoscopic Nissen fundoplication using an upper body warming blanket. We also attempted to determine whether using heated and humidified insufflation gas in addition to an external warming blanket would help to maintain intraoperative core temperature or decrease postoperative pain. METHODS: Twenty patients were randomized to receive either standard carbon dioxide (CO2) gas (control, n = 10) or heated and humidified gas (heated and humidified, n = 10). After the induction of anesthesia, an external warming blanket was placed on all patients in both groups. Intraoperative core temperature and intraabdominal temperature were measured at 15-min intervals. Postoperative pain intensity was assessed using a visual analogue pain scale, and the amount of analgesic consumption was recorded. Volume of gas delivered, number of lens-fogging episodes, intraoperative urine output, and hemodynamic data were also recorded. RESULTS: There was no significant difference between the two groups in age, length of operation, or volume of CO2 gas delivered. Compared with baseline value, mean core temperature increased by 0.4 degrees C in the heated and humidified group and by 0.3 degrees C in the control group at 1.5 h after surgical incision. Intraabdominal temperature increased by 0.2 degrees C in the heated and humidified group but decreased by 0.5 degrees C in the control group at 1.5 h after abdominal insufflation. There was no significant difference between the two groups in visual analog pain scale (5.4 +/- 1.6 control vs 4.5 +/- 2.8 heated and humidified), morphine consumed (27 +/- 26 mg control vs 32 +/- 19 mg heated and humidified), urine output, lens-fogging episodes, or hemodynamic parameters. CONCLUSION: Heated and humidified gas, when used in addition to an external warming blanket, minimized the reduction of intraabdominal temperature but did not alter core temperature or reduce postoperative pain.

Current status of laparoscopic gastric bypass.

Laparoscopic gastric bypass is emerging as a commonly performed procedure for the treatment of morbid obesity. This article discusses the indications for surgery, patient selection, surgical technique, management of complications, and outcomes of laparoscopic gastric bypass.

Cardiac function during laparoscopic vs open gastric bypass.

BACKGROUND: Hypercarbia and increased intraabdominal pressure during prolonged pneumoperitoneum can adversely affect cardiac function. This study compared the intraoperative hemodynamics of morbidly obese patients during laparoscopic and open gastric bypass (GBP). METHODS: Fifty-one patients with a body mass index (BMI) of 40-60 kg/m2 were randomly allocated to undergo laparoscopic (n = 25) or open (n = 26) GBP. Cardiac output (CO), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), heart rate (HR), and mean arterial pressure (MAP) were recorded at baseline, intraoperatively at 30-min intervals, and in the recovery room. Systemic vascular resistance (SVR) and stroke volume (SV) were also calculated. RESULTS: The two groups were similar in terms of age, weight, and BMI. Operative time was longer in the laparoscopic than in the open group (p < 0.05). The HR and MAP increased significantly from baseline intraoperatively, but there was no significant difference between the two groups. In the laparoscopic group, CO was unchanged after insufflation, but it increased by 5.3% at 2.5 h compared to baseline and by 43% compared to baseline in the recovery room. In contrast, during open GBP, CO increased significantly by 25% after surgical incision and remained elevated throughout the operation. CO was higher during open GBP than during laparoscopic GBP at 0.5 h and at 1 h after surgical incision (p < 0.05). During laparoscopic GBP, CVP, MPAP, and SVR increased transiently and PAWP remained unchanged. During open GBP, CVP, MPAP, and PAWP decreased transiently and SVR remained unchanged. There was no significant difference in the amount of intraoperative fluid administered during laparoscopic (5.5 +/- 1.6 L) and open (5.6 +/- 1.7 L) GBP. CONCLUSION: Prolonged pneumoperitoneum during laparoscopic gastric bypass does not impair cardiac function and is well tolerated by morbidly obese patients.

Transforming growth factor-beta1 inhibits macrophage cholesteryl ester accumulation induced by native and oxidized VLDL remnants.

Transforming growth factor beta1 (TGF-beta1) is secreted by various cells, including macrophages, smooth muscle cells, and endothelial cells. TGF-beta1 is present in atherosclerotic lesions, but its role in regulating macrophage foam cell formation is not understood. Hypertriglyceridemic very low density lipoprotein (VLDL) remnants (VLDL-REMs) in their native or oxidized form will induce cholesteryl ester (CE) and triglyceride (TG) accumulation in macrophages. Therefore, we examined whether TGF-beta1 can modulate the macrophage uptake of native or oxidized VLDL-REMs (oxVLDL-REMs). Incubation of J774A.1 macrophages with VLDL-REMs and oxVLDL-REMs compared with control cells increased cellular CE (13- and 21-fold, respectively) and TG mass (21-and 18-fold, respectively). Preincubation with TGF-beta1 before incubation with VLDL-REMs or oxVLDL-REMs significantly decreased CE (73% and 54%, respectively) and TG mass (42% and 41%, respectively). TGF-beta1 inhibited the activity and expression of 2 key components needed for VLDL-REM uptake: lipoprotein lipase and low density lipoprotein receptor. TGF-beta1 inhibited CE mass induced by oxVLDL-REMs in part by decreasing the expression of scavenger receptor type AI/II and CD36. Furthermore, TGF-beta1 enhanced cholesterol efflux through upregulation of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. Thus, TGF-beta1 inhibits macrophage foam cell formation induced by VLDL-REMs or oxVLDL-REMs, which suggests an antiatherogenic role for this cytokine.

Evaluation of core temperature during laparoscopic and open gastric bypass.

BACKGROUND: Intraoperative hypothermia is a common event during open and laparoscopic abdominal surgery. The aim of this study was to compare changes in core temperature between laparoscopic and open gastric bypass (GBP). METHODS: 101 patients with a body mass index (BMI) of 40-60 kg/m2 were randomly assigned to open (n = 50) or laparoscopic (n = 51) GBP. Anesthetic technique was similar for both groups. An external warming blanket and passive airway humidification were used intraoperatively. Core temperature was recorded at preanesthesia, at baseline (after induction) and at 30-min intervals; intra-abdominal temperature was additionally measured at 30-min intervals in a subset of 30 laparoscopic GBP patients. The number of patients who developed intraoperative and postoperative hypothermia (< 36 degrees C) was recorded. Length of operation for both groups and the amount of CO2 gas delivered during laparoscopic operations were also recorded. RESULTS: There was no significant difference between groups with respect to age, gender, mean BMI, and amount of intravenous fluid administered. After induction of anesthesia, core temperature significantly decreased in both groups; 36% of patients in the open group and 37% of patients in the laparoscopic group developed hypothermia. This percentage increased to 46% in the open group and 41% in the laparoscopic group during the operation, and then decreased to 6% in the open group and 8% in the laparoscopic group in the recovery-room. Core temperature increased during the operative procedure to reach 36.5 +/- 0.6 degrees C in the open group and 36.3 +/- 0.5 degrees C in the laparoscopic group at 2.5 hours after surgical incision. Intra-abdominal temperature during laparoscopic GBP was significantly lower than core temperature at all measurement points (p < 0.05). Operative time was longer in the laparoscopic group than in the open group (232 +/- 43 vs 201 +/- 38 min, p < 0.01). Mean volume of gas delivered during laparoscopic GBP was 650 +/- 220 liters. CONCLUSION: Perioperative hypothermia was a common event during both laparoscopic and open GBP. Despite a longer operative time, laparoscopic GBP did not increase the rate of intraoperative hypothermia when efforts were made to minimize intraoperative heat loss.

Increased transplantation of kidneys with multiple renal arteries in the laparoscopic live donor nephrectomy era: surgical technique and surgical and nonsurgical donor and recipient outcomes.

BACKGROUND: For anatomical and technical reasons, many transplant centers restrict laparoscopic live donor nephrectomy (in contrast with open live donor nephrectomy) to left kidneys. HYPOTHESIS: This change in surgical practice increases procurement and transplantation rates of live donor kidneys with multiple renal arteries (RAs), without affecting donor and recipient outcomes. DESIGN AND SETTING: Retrospective review at an academic tertiary care referral center comparing laparoscopically procured single vs multiple-RA kidney grafts (April 1997 to October 2000). PATIENTS: Seventy-nine consecutive left laparoscopic live kidney donors and 78 transplant recipients. MAIN OUTCOME MEASURES: Donor and recipient complications and postoperative length of stay; cold and warm ischemia time; operating time; short-term and long-term graft function; and survival. RESULTS: We noted multiple RAs in 21 (27%) of all kidneys. The proportion of donors with 1 or more perioperative complications was 19% in the single-RA group vs 10% in the multiple-RA group (P was not significant). For the recipients, we noted no significant differences between groups with respect to surgical complications, quality of early and late graft function, rejection rates, graft losses (all immunologic), and graft survival. Cold and warm ischemia time and length of stay were similar for donors and recipients in both groups. Median operating times were significantly longer for the multiple-RA vs single-RA group (difference, 41 minutes for donors and 45 minutes for recipients; P<.02). CONCLUSIONS: While the introduction of laparoscopic live donor nephrectomy has significantly increased the number of grafts with multiple RAs (compared with historical open controls), this change in practice is safe for both donors and recipients from a patient outcome-based perspective. However, from an economic perspective, the longer operating time associated with multiple-RA grafts provides strong added rationale for optimization of surgical instruments and techniques to make right-sided laparoscopic nephrectomy a routine intervention.

Systemic coagulation and fibrinolysis after laparoscopic and open gastric bypass.

HYPOTHESIS: Laparoscopic gastric bypass (GBP) induces a postoperative hypercoagulable state that is similar or reduced compared with open GBP. SETTING: University hospital. PATIENTS: Between May 1999 and June 2000, 70 patients were randomly assigned to laparoscopic (n = 36) or open (n = 34) GBP. Deep venous thrombosis (DVT) prophylaxis consisted of antiembolism stockings and sequential pneumatic compression devices. MAIN OUTCOME MEASURES: Plasminogen, thrombin-antithrombin complex (TAT), prothrombin fragment 1.2 (F1.2), fibrinogen, D-dimer, antithrombin III (AT), and protein C levels were measured at baseline and at 1, 24, 48, and 72 hours postoperatively. A venous duplex examination of both lower extremities was performed preoperatively and between the third and fifth day postoperatively. RESULTS: The 2 groups were similar in age, weight, and body mass index. Plasminogen levels decreased, and TAT, F1.2, and fibrinogen levels increased after laparoscopic and open GBP. There was no significant difference in these levels between groups. D-dimer levels increased in both groups, but the levels were significantly higher after open GBP than after laparoscopic GBP (P<.01). Antithrombin III and protein C levels decreased in both groups. The reduction of AT (at 1 hour) and protein C (at 72 hours) was significantly less after laparoscopic GBP than after open GBP (P<.05). Postoperative venous duplex examination revealed DVT in 1 (2.9%) of 34 patients after open GBP but in none of 36 patients after laparoscopic GBP. One patient developed pulmonary embolism after open GBP. CONCLUSIONS: Laparoscopic GBP induces a hypercoagulable state similar to that of open GBP. Our findings suggest that DVT prophylaxis should be used during laparoscopic GBP as in open GBP.

Laparoscopic versus open gastric bypass: a randomized study of outcomes, quality of life, and costs.

OBJECTIVE: To compare outcomes, quality of life (QOL), and costs of laparoscopic and open gastric bypass (GBP). SUMMARY BACKGROUND DATA: Laparoscopic GBP has been reported to be a safe and effective approach for the treatment of morbid obesity. The authors performed a prospective randomized trial to compare outcomes, QOL, and costs of laparoscopic GBP with those of open GBP. METHODS: From May 1999 to March 2001, 155 patients with a body mass index (BMI) of 40 to 60 kg/m2 were randomly assigned to undergo laparoscopic (n = 79) or open (n = 76) GBP. The two groups were similar in age, sex ratio, mean BMI, and comorbidities. Main outcome measures included operative time, estimated blood loss, length of hospital stay, operative complications, percentage of excess body weight loss, and time to return to activities of daily living and work. Changes in QOL were assessed using the SF-36 Health Survey and the bariatric analysis of reporting outcome system (BAROS). Operative and hospital costs of the two operations were also compared. RESULTS: There were no deaths in either group. Mean operative time was longer for laparoscopic GBP than for open GBP, but operative blood loss was less. Two (2.5%) of the 79 patients in the laparoscopic group required conversion to laparotomy. Median length of hospital stay was shorter for laparoscopic GBP patients (3 vs 4 days). The rate of postoperative anastomotic leak was similar between groups. Wound-related complications such as infection (10.5 vs 1.3%) and incisional hernia (7.9 vs 0%) were more common after open GBP; late anastomotic stricture was less frequent after open GBP (2.6 vs 11.4%). Time to return to activities of daily living and work were shorter after laparoscopic GBP than after open GBP. Weight loss at 1 year was similar between groups. Preoperative SF-36 scores were similar between groups; however, at 1 month after surgery, laparoscopic patients had better physical conditioning, social functioning, general health, and less body pain than open GBP patients. At 6 months, the BAROS outcome was classified as good or better in 97% of laparoscopic GBP patients compared with 82% of open GBP patients. Operative costs were higher for laparoscopic GBP patients, but hospital costs were lower. CONCLUSIONS: Laparoscopic GBP is a safe and cost-effective alternative to open GBP. Despite a longer operative time, patients undergoing laparoscopic GBP benefited from less blood loss, a shorter hospital stay, and faster convalescence. Laparoscopic GBP patients had comparable weight loss at 1 year but a more rapid improvement in QOL than open GBP patients. The higher initial operative costs for laparoscopic GBP were adequately offset by the lower hospital costs.

Lecithin:cholesterol acyl transferase G30S: association with atherosclerosis, hypoalphalipoproteinemia and reduced in vivo enzyme activity.

OBJECTIVES: A 69 yr old male was referred for assessment of a very low plasma HDL cholesterol and apolipoprotein AI concentration. At age 65, he had undergone triple vessel coronary bypass graft surgery. He had a strong family history of early coronary heart disease. We analyzed the molecular basis of his clinical and biochemical abnormalities. DESIGN AND METHODS: We used DNA sequencing to determine whether mutations in LCAT were present. We also evaluated plasma biochemistry and LCAT activity. RESULTS: DNA sequencing revealed that the patient was a heterozygote for the G30S mutation in the gene encoding lecithin:cholesteol acyl transferase (LCAT). His plasma was found to have half-normal LCAT activity. CONCLUSIONS: The findings in this patient suggest that rare dysfunctional mutations in candidate genes, such as LCAT, can contribute to the spectrum of patients ascertained because of low HDL cholesterol.

Quadriceps muscle function and fatigue in women with Addison's disease.

In nine patients with Addison's disease (mean +/- SE: 51 +/- 2 years) receiving conventional steroid treatment, and nine age-matched healthy controls (56 +/- 2 years), we investigated maximum voluntary quadriceps force (MVC) and contractile properties evoked with stimulation and central activation both at rest and during a submaximal intermittent fatigue task. The MVC was similar (-3%), but twitch tension (-27%) and central activation were significantly less (-7%), and tetanic half-relaxation time was approximately 40% slower in the patients. Twitch amplitudes were potentiated by 6% in the patients, but unchanged in the control group. The patients self-terminated a submaximal intermittent fatigue protocol (0.6 duty cycle) at approximately 5 +/- 1 min, whereas the controls stopped when they lost 50% of MVC force ( approximately 10 +/- 1 min). Force loss was similar between groups over the first 5 min of the fatigue task. In the patient group, maximal and submaximal relative integrated electromyogram (IEMG) increased significantly in the first minute of fatigue and remained elevated, whereas the controls exhibited a gradual increase in submaximal IEMG with little change in maximal IEMG. These results indicate that conventionally treated Addison's patients have similar MVC strength, but altered contractile properties and decreased endurance compared with controls.