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Background: Patients undergoing gastric bypass are at greater than ordinary risk for postoperative respiratory insufficiency, presumably related to obstructive sleep apnea (OSA) and patient-controlled analgesia (PCA). This study was proposed to quantify the magnitude of the problem., Methods: Fifteen patients undergoing gastric bypass had oxygen saturation (SpO(2)) recorded continuously, but not displayed, for 24h postoperatively; eight also had arterial blood analysis every 4h. All received narcotic PCA. SpO(2)<90% lasting more than 10 s was reviewed. Results are mean+/-SEM., Results: Mean age was 44+/-4 y, and mean BMI was 48+/-2kg/m(2); 77% had OSA. Every patient had more than one episode with SpO(2)<90% for longer than 30s undetected by routine monitoring; most had multiple episodes. Nadir SpO(2) averaged 75% +/- 8%. Mean longest duration of desaturation below 90% averaged 21+/-15min. Mean PaCO(2) was 37+/-3mm Hg; maximum PaCO(2) was 47mm Hg., Conclusions: Severe and prolonged episodes of hypoxemia were a consistent finding, despite aggressive preoperative diagnosis and treatment of OSA, including use of CPAP postoperatively. Although some postoperative hypoventilation was expected, the degree and frequency of desaturation were surprising. No patient exhibited arterial PaCO(2) evidence of hypoventilation. No patient experienced cardiopulmonary arrest/instability, in spite of severe, repeated episodes of hypoxemia. In no instance was a significant hypoxemic episode suspected or detected. Continuous pulse oximetry monitoring, with an audible alarm set for a saturation less than 90% for 10 s, would have alerted providers to 100% of significant hypoxemic episodes. Our recommendation is routinely monitoring (with alarm capability enabled) every bariatric surgical patient, to prevent such occurrence.

Background: Adrenalectomy rates seem to be increasing in Florida, possibly due to increased availability of laparoscopic adrenalectomy, identification of incidentalomas, and access to care for minorities. We hypothesized that the rate of adrenalectomies in Florida increased from 1998-2005 while characteristics of patients, diagnoses, operations, and operating physicians changed over this period., Methods: Prospectively-collected, mandatory-reported, hospital discharge data for all inpatient adrenalectomies undertaken in Florida from 1998-2005 were obtained along with Florida census and physician certification and education data. Characteristics of adrenalectomy patients, diagnoses, operations, and physicians were analyzed., Results: 1816 adrenalectomies were available for analysis. Yearly rates of adrenalectomy nearly doubled from 1.20 to 2.26 per 100,000 Florida residents (P = .0024). Overall, patient characteristics such as demographics, indications and comorbidities did not change, whereas hospital charges increased and length-of-stay (LOS) significantly decreased (P = .0031 and P < .0001, respectively). There was a non-significant trend toward a yearly increase in physician volume and an inverse relationship between physician volume categories and mean LOS (P < .0001)., Conclusions: The rate of adrenalectomies is increasing in Florida. This increase was not associated with distinct trends in patient characteristics, although a significant decrease in LOS was identified. As these trends continue and adrenalectomy is applied more liberally, indications for adrenalectomy may need to be re-evaluated.

Background: Urinary incontinence is common in obese individuals. We report on the prevalence of urinary incontinence in patients undergoing bariatric surgery and the effect of surgically induced weight loss on urinary incontinence., Methods: The prospectively collected data from 201 consecutive candidates for bariatric surgery were evaluated. The patients were surveyed using a questionnaire regarding the duration of incontinence, stress/urge incontinence symptoms, and incontinence severity before and after undergoing bariatric surgery. Severity was quantified using a validated index developed Data are presented as the mean +/- standard deviation., Results: Of 201 patients, 65 (32%) reported urinary incontinence. Of the 65 patients, 44 women and 1 man (age 49 +/- 11 years, body mass index 48 +/- 7 kg/m(2)) underwent Roux-en-Y gastric bypass (n = 42) or laparoscopic-assisted gastric banding (n = 3). Of the 38 patients who reported mild (2%), moderate (48%), and severe (50%) urinary incontinence preoperatively who had complete follow-up at > or = 6 months postoperatively, 19 (50%) had demonstrated resolution of urinary incontinence and 19 had reported residual slight-moderate (37%) or severe (13%) urinary incontinence. The overall severity score improved from 5.4 +/- 2.3 to 2.3 +/- 2.8 postoperatively (P <.001); the percentage of excess body weight loss was 61% +/- 19%. The patients reported subjective improvement within 4 months postoperatively or after a 50-lb weight loss., Conclusion: Urinary incontinence is prevalent in bariatric surgery patients. Surgically induced weight loss results in improvement or resolution of urinary incontinence in 82% of patients. The findings from this large cohort warrant additional investigation with urodynamic studies.

Protein kinase C-zeta (PKC-zeta) regulates cell death via NF-kappaB; therefore, we tested the hypothesis that PKC-zeta plays a critical role in pancreatitis-induced Kupffer cell apoptosis. Acute pancreatitis was induced in rats by cerulein injection 24 h later, livers were assayed for PKC-zeta, IKKalpha, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, and apoptosis was assessed with Caspase-3 and DNA fragmentation. Kupffer cells from unoperated rats were infected with a PKC-zeta domain-negative adenovirus (AdPKCzeta-DN) to inhibit PKC-zeta, or transfected with pCMVPKC-zeta to overexpress PKC-zeta, and then stimulated with pancreatic elastase; cellular extracts were assayed for PKC-zeta, IKKalpha, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and DNA fragmentation. Cerulein-induced pancreatitis upregulated PKC-zeta protein and activity, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3 and increased DNA fragmentation in rat livers (all p < 0.001 vs control). AdPKCzeta-DN abolished elastase-induced upregulation of PKC-zeta activity, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3 and DNA fragmentation (all p < 0.001 vs infection control), whereas overexpression of PKC-zeta augmented elastase-induced upregulation of IKKbeta, IKKgamma, Fas/FasL, Caspase-3 and DNA fragmentation (p < 0.001 vs control). PKC-zeta plays a critical role in pancreatitis-induced Kupffer cell apoptosis via NF-kappaB and Fas/FasL. The ability of Kupffer cells to autoregulate their stress response by upregulating their death receptor/ligand and key proapoptotic cell signaling systems warrants further investigation.

Objective: To document the effect of anastomotic leaks on morbidity and mortality after Roux-en-Y gastric bypass (RYGB) for obesity., Design: Prospectively collected data on 840 consecutive patients who underwent RYGB between 1998 and 2005. Multivariate logistic regression analysis was used to determine the effect of anastomotic leaks on postoperative morbidity independent of sex, age, preoperative body mass index, access (open vs laparoscopic), calendar year of RYGB, and comorbidities. P < .05 was considered significant., Results: A total of 36 patients (4.3%) developed leaks after RYGB. Patients who developed anastomotic leaks had a significantly higher overall complication rate (61% vs 20%, P < .001), mortality (14% vs 4%, P = .01), and duration of hospital stay (24.5 vs 4.5 days, P < .001) compared with patients who did not develop leaks. In a multivariate logistic regression model, anastomotic leaks increased the likelihood of mortality (odds ratio [OR], 15; 95% confidence interval [CI], 3-80; P = .002) and overall complications (OR, 6; 95% CI, 3-13; P < .001), specifically sepsis (OR, 27; 95% CI, 2-472; P = .02), renal failure (OR, 16; 95% CI, 3-99; P = .003), small-bowel obstruction (OR, 11; 95% CI, 2-68; P = .008), internal hernia (OR, 10; 95% CI, 2-51; P = .008), thromboembolism (OR, 9; 95% CI, 3-27; P < .001), and incisional hernia (OR, 5; 95% CI, 2-13; P = .001)., Conclusions: Anastomotic leaks significantly increase the likelihood of developing additional life-threatening complications after RYGB. Close and aggressive monitoring is recommended for early detection and management of added complications, should they occur.

Objectives: To report contemporary outcomes of gastric bypass for obesity and to assess the relationship between provider volume and outcomes., Background: Certain Florida-based insurers are denying patients access to bariatric surgery because of alleged high morbidity and mortality., Settings and Patients: The prospectively collected and mandatory-reported Florida-wide hospital discharge database was analyzed. Restrictive procedures such as adjustable gastric banding and gastroplasty were excluded., Results: The overall complication and in-hospital mortality rates in 19,174 patients who underwent gastric bypass from 1999 to 2003 were 9.3% (8.9-9.7) and 0.28% (0.21-0.36), respectively. Age and male gender were associated with increased duration of hospital stay (P < 0.001), increased in-hospital complications [age: odds ratio (OR) = 1.11, CI: 1.08-1.13; male: OR = 1.53, CI: 0.36-1.72] and increased in-hospital mortality (age: OR = 1.51, CI: 1.32-1.73; male: CI = 2.66, CI: 1.53-4.63), all P < 0.001. The odds of in-hospital complications significantly increased with diminishing surgeon or hospital procedure volume (surgeon: OR = 2.0, CI: 1.3-3.1; P < 0.001, 1-5 procedures relative to >500 procedures; hospital volume: OR = 2.1, CI: 1.2-3.5; P < 0.001, 1-9 procedures relative to >500 procedures). The percent change of in-hospital mortality in later years of the study was lowest, indicating higher mortality rates, for surgeons or hospitals with fewer (< or =100) compared with higher (> or =500) procedures., Conclusion: Increased utilization of bariatric surgery in Florida is associated with overall favorable short-term outcomes. Older age and male gender were associated with increased morbidity and mortality. Surgeon and hospital procedure volume have an inverse relationship with in-hospital complications and mortality.

Background: Obstructive sleep apnea (OSA) is associated with obesity. Our aim in this study is to report objective improvement of obesity-related OSA and sleep quality after bariatric surgery., Methods: Prospective bariatric patients were referred for polysomnography if they scored >or=6 on the Epworth Sleepiness Scale. The severity of OSA was categorized by the respiratory disturbance index (RDI) as follows: absent, 0 to 5; mild, 6 to 20; moderate, 21 to 40; and severe, <40. Patients were referred for repeat polysomnography 6 to 12 months after bariatric surgery or when weight loss exceeded 75 lbs. Means were compared using paired t tests. Chi-square tests and linear regression models were used to assess associations between clinical parameters and RDI; P<.05 was considered statistically significant., Results: Of 349 patients referred for polysomnography, 289 patients had severe (33%), moderate (18%), and mild (32%) OSA; 17% had no OSA. At a median of 11 months (6 to 42 months) after bariatric surgery, mean body mass index (BMI) was 38 +/- 1 kg/m2 (P<.01 vs 56 +/- 1 kg/m2 preoperatively) and the mean RDI decreased to 15 +/- 2 (P<.01 vs 51 +/- 4 preoperatively) in 101 patients who underwent postoperative polysomnography. In addition, minimum oxygen saturation, sleep efficiency, and rapid eye movement latency improved, and the requirement for continuous positive airway pressure was reduced (P

Background: Improved outcomes of laparoscopic Roux-en-Y gastric bypass (LRYGB) have been demonstrated once pratice has moved beyond the learning curve. However, there is no evidence that experience has a favorable impact on the incidence of leaks. This study evaluated the incidence of staple-line leaks as experience accrued in a university-based bariatric surgery program., Methods: Prospectively collected data on our first 200 patients undergoing LRYGB since July 1998 were analyzed. Linear staplers were used to divide the stomach and to create a side-to-side jejunojejunostomy. A side-to-side cardiojejunostomy was created using a 21-mm circular stapler. Patient characteristics, operative data, and outcomes were evaluated chronologically with comparison of outcomes between quartiles., Results: Staple-line leaks developed in 9 (4.5%) of the first 200 patients undergoing LRYGB. Among the 200 patients were 190 women (95%). The median age of the patients was 48 years (ranges, 24-62 years), and their body mass index was 43 kg/m(2) (ranges, 32-59 kg/m(2)). As surgeons' experience increased over time, there was a significant increase in the weight of patients and the percentage of patients with previous abdominal operations. There also was a significant decrease in conversion rates and operative times. Leaks occurred in six patients at the cardiojejunostomy (3%), in two patients jejunojejunostomy (1%), and in one patient at the excluded stomach (0.5%). Of the 50 leaks that occurred in each quartile, there were in the 3 in the 1st quartile, 1 in the 2nd quartile, 2 in the 3rd quartile, 3 in the 4th quartile. The differences were not significant. There was no correlation between the number of LRYGBs, and the occurrence of a leak (p = 0.59 confidence interval -0.13-0.22)., Conclusions: The incidence of staple-line leaks appears to be independent of the number of LRYGBs performed. These data suggest that surgeons' experience may not eliminate anastomotic complications experienced by patients undergoing LRYGB.

Acute pancreatitis induces liver injury by upregulating Kupffer cell-derived Fas/FasL; on the other hand, acute pancreatitis induces apoptosis of Kupffer cells via NF-kappaB-dependent pathways. The balance between upregulation of Fas/FasL and Fas/FasL-induced apoptosis of its originator cell may determine the severity of pancreatitis-related liver injury. The aim of our study was to determine the role of p65 NF-kappaB/RelA in pancreatitis-induced Kupffer cell apoptosis. Acute pancreatitis was induced in NIH Swiss mice by a choline-deficient ethionine-supplement (CDE) diet. In vitro mouse Kupffer cell line was transfected with p65 siRNA and treated with pancreatic elastase to mimic pancreatitis. CDE pancreatitis upregulated nuclear translocation of p65 NF-kappaB/RelA, Fas/FasL, caspase-3, and DNA fragmentation in mice livers (all P < 0.001). In vitro, pancreatic elastase mimicked CDE-pancreatitis by upregulating nuclear translocation of p65 NF-kappaB/RelA, Fas/FasL, caspase-3, DNA fragmentation, and apoptosis in Kupffer cells (all P < 0.001). Transfection with p65 siRNA attenuated the elastase-induced nuclear translocation of p65 NF-kappaB/RelA, upregulation of Fas/FasL, caspase-3, DNA fragmentation, and apoptosis in Kupffer cells (all P < 0.001). Acute pancreatitis activates p65 NF-kappaB/RelA and induces apoptosis of Kupffer cells. Inhibition of p65NF-kappaB/RelA attenuates elastase-induced upregulation of proapoptotic pathways and apoptosis in Kupffer cells. The ability of Kupffer cells to autoregulate their stress response by inducing self-apoptosis warrants further investigation.

Background: Small bowel obstruction (SBO) is a well-recognized complication of bariatric surgery. Many factors that play a role in the etiology of SBO affect the presentation, timing, and treatment after Roux-en-Y gastric bypass (RYGB). We reviewed our experience with SBO after open and laparoscopic RYGB., Methods: We reviewed prospectively collected data from 784 consecutive patients who had undergone RYGB (458 open and 326 laparoscopic) from July 1998 to March 2005. The operative techniques were standardized, including closure of the mesenteric defects. The follow-up data were taken from clinic visit records and follow-up questionnaires. The mean follow-up period was 16 +/- 1 months (range 1-75). The data presented are the mean +/- SEM., Results: The overall incidence of SBO after RYGB was 3.2%. Thirteen patients developed SBO after laparoscopic RYGB (4%) and 12 patients did so after open RYGB (2.6%, P = NS). Obstruction at the jejunojejunostomy was more common after laparoscopic RYGB (77%, P <.05), and adhesive SBO was more common after open RYGB (50%, P <.05). The incidence of SBO from internal hernia was low, regardless of the operative approach (open 0.7% versus laparoscopic 0.3%). Early SBO resolved with nonoperative treatment in 30% of patients., Conclusion: Understanding the anatomic considerations of RYGB in the development of SBO after open and laparoscopic approach is essential to timely and effective treatment.

Background: Obesity is a major risk factor for postoperative deep venous thrombosis (DVT) and pulmonary embolism (PE). Identifying those patients at the greatest risk for DVT/PE is essential to prevent thromboembolic events among patients undergoing Roux-en-Y gastric bypass (RYGB) for clinically significant obesity. This aim of the study is to identify factors associated with an increased likelihood of developing DVT/PE after RYGB., Methods: Prospectively collected data from 660 consecutive patients who underwent RYGB were reviewed. Patients received perioperative prophylaxis with low molecular weight heparin and sequential compression devices. Diagnosis was based on clinical, radiologic, and/or necropsy findings. Patients with and without postoperative DVT/PE were compared using chi(2) and multivariate logistic regression analysis., Results: A total of 23 patients (3.5%) developed postoperative DVT/PE. Age > 50 years (P = .04), previous DVT/PE (P = .02), history of smoking (P < .01), revisional operation (P = .03), open RYGB (P = .02), and anastomotic leak (P < .0001) significantly increased the likelihood of developing DVT/PE. On the other hand, gender, body mass index > 50 kg/m(2) and history of sleep apnea, hypertension, diabetes, or myocardial infarction did not increase the likelihood of DVT/PE. Multivariate analysis revealed that age > 50 years (P = .04), postoperative anastomotic leak (P < .001), smoking (P < .01), and previous DVT/PE (P < .001) increased the likelihood of postoperative DVT/PE., Conclusions: Age > 50 years, anastomotic leak, smoking, and history of DVT/PE all increase the likelihood of postoperative thromboembolic events in patients undergoing RYGB. Further preoperative screening and/or postoperative prophylaxis may be needed in this subset of high-risk patients.

Introduction: Nuclear factor (NF)-kappaB is a key transcriptional factor for cell survival, inflammation, and stress response. We demonstrated that Kupffer cell-derived FasL plays a central role in pancreatitis-induced hepatocyte injury. The aim of this study was to determine the role of NF-kappaB in regulating death ligand/receptor pathway in Kupffer cells during conditions that mimic acute pancreatitis., Materials and Methods: Tissue cultures of rat Kupffer cells were treated with elastase (1 U/L) to mimic pancreatitis before and after infection with AdIkappaB to block activation of NF-kappaB. Tumor necrosis factor (enzyme-linked immunoassay), Fas/FasL, and caspase-3 (Western), tumor necrosis factor and Fas/FasL mRNA (reverse-transcription polymerase chain reaction), and NF-kappaB DNA binding (electrophoretic mobility shift assay) were determined. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) and DNA fragmentation. Gels were quantified by densitometry. Data (n=3) are mean+/-SEM; student's t test was used for statistical analysis., Results: AdIkappaB infection up-regulated mutated IkappaBalpha that maintained its binding properties to NF-kappaB. Promoter-reporter assay demonstrated that FasL gene promoter was regulated by NF-kappaB. Infection with AdIkappaB attenuated the elastase-induced up-regulation of Fas/FasL (all P<0.01 versus elastase) and NF-kappaB DNA binding but did not affect elastase-induced up-regulation of TNF. AdIkappaB attenuated elastase-induced cleavage of caspase-3, DNA fragmentation and TUNEL staining (all P<0.01 versus elastase)., Conclusions: Inhibition of NF-kappaB DNA binding down-regulates Fas/FasL and attenuates elastase-induced apoptosis; however, it has no effect on TNF production, suggesting that regulation of Fas/FasL and TNF may occur via different pathways. The ability of Kupffer cells to autoregulate their stress response by up-regulating their death ligand/receptor and apoptosis warrants further investigation.

Symptoms of gastroesophageal reflux disease (GERD) are frequent in patients with clinically significant obesity and are reported to improve after Roux-en-Y gastric bypass (RYGB). The purpose of this study is to determine timing and duration of improvement of GERD symptoms in patients undergoing RYGB. Prospectively collected data from patients who underwent RYGB from January 1998 to August 2004 were analyzed. Patients answered a standardized questionnaire pre- and postoperatively inquiring about frequency of GERD symptoms (none, one episode/ week, one episode/day, more than one episode/day) and medication use. Of 606 patients undergoing RYGB, 239 patients (39%) reported GERD symptoms preoperatively (mean age 43 +/- 1 years; body mass index 51 +/- 1 kg/m2). Of these, 89 per cent of patients reported improved at 3 months post-op and 94 per cent of patients 9 months post-op (P < 0.001). Medication usage decreased from 30 per cent to 3 per cent by 3 months and 5 per cent beyond 9 months (P < 0.001). Percentage of excess weight loss was 18 +/- 1 per cent and 75 +/- 2 per cent at 3 and 9 months, respectively. Symptoms of GERD significantly improve and use of antireflux medications is reduced after RYGB independent of weight loss. RYGB may be the treatment of choice for GERD in obese patients.

Background: Bariatric surgeons are increasingly encountering patients with failed weight-loss operations. Conversion from vertical banded gastroplasty (VBG) to Roux-en-Y gastric bypass (RYGB) is the most common revisional operation in our practice. We reviewed our experience in converting from VBG to RYGB using a basic five-step surgical technique., Study Design: We reviewed data on all patients undergoing revisional surgery for failed VBG, defined as patients with body mass index >/=35 kg/m(2), weight gain, poor control of comorbidities, staple-line dehiscence, or band-specific complications. The five basic steps include identification of the band, delineation of the extent of the pouch, division of the stomach, preparation of the Roux limb, and completion of the cardiojejunostomy., Results: We have undertaken 28 conversions from VBG to RYGB. Median age was 51 years (range 27 to 65 years), preoperative body mass index was 40 kg/m(2) (range 20 to 58 kg/m(2)), and 25 patients (89%) were women. Indications for revision were band-related complications (13 patients), staple-line disruption (9 patients), and inadequate weight loss (6 patients). Median operative time was 185 minutes (range 105 to 465 minutes), estimated blood loss was 450 mL (range 100 to 2,500 mL), postoperative complications occurred in 6 patients (21%), and length of hospitalization was 5 days (range 3 to 69 days). Median postoperative body mass index was 32 kg/m(2) (range 20 to 41 kg/m(2)) at a followup time of 16 months (range 1 to 32 months)., Conclusions: The technique described facilitates the operative approach to patients with failed VBG, providing guidelines for safe dissection and division of the gastric pouch for conversion to RYGB. Revisional bariatric operations are technically difficult and are associated with relatively higher complication rates than those reported for primary operations.

Background: Work hour guidelines and core competencies were introduced to improve surgical education and are changing the landscape of surgical training. We sought to examine perceptions and attitudes regarding the impetus and impact associated with these changes., Materials and Methods: Anonymous surveys were distributed to faculty and surgeons-in-training in an Accreditation Council for Graduate Medical Education, university-based, training program., Results: Faculty (F, n = 30) and trainees (T, n = 30) agree that lifestyle expectations and long work hours are the principal issues facing surgical education (F = 80%, T = 56%; P = 0.03). Implementation of ACGME guidelines is perceived as NOT improving patient care or clinical experience (F = 100%, T = 90%; P = 0.03) while reducing operative experience (F = 50%, T = 70%). More faculty (>80%) than trainees (33%) are concerned that ACGME guidelines will diminish patient care experiences. Although most (F = 77%, T = 83%; P = NS) agree that hiring additional providers will improve guideline compliance, many oppose ACGME guideline implementation fearing a loss of professionalism. Although both (F = 50%, T = 47%) admonish deficient interpersonal and communication skills as the major impediment to implementing ACGME guidelines, opinions regarding implementation differ. Most faculty (67%) believe ACGME-imposed deadlines are the most influential reason; however, trainees (57%) believe guidelines should be promptly implemented to address long-awaited changes in work environment and surgical graduate medical education., Conclusions: Although faculty and trainees' perception of the issues surrounding ACGME guidelines converge, perception of changes following implementation is quite divergent. For successful implementation, leadership must address prevailing attitudes and set realistic expectations. These trends have important implications for planning the future of surgical education, unifying multi-generational colleagues, and improving systems-based practice.

Liver injury is a clinical prognostic indicator in acute pancreatitis (AP). We have demonstrated that Kupffer cell-derived FasL mediates liver injury during AP and sought to determine its role in AP-induced hepatocyte apoptosis. AP was induced in National Institutes of Health (NIH) Swiss mice, C57/C57, and Fas-/-, FasL-/- mice by a choline-deficient ethionine-supplement diet. Liver Fas, FasL, p38-mitogen activated phosphokinase (p38-MAPK), poly-ADP ribose polymerase (PARP), and cytochrome C were measured by immunoblotting. Apoptosis was assessed by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA fragmentation (ELISA). AP upregulated liver FasL (4280 +/- 580 vs. 733 +/- 336), Fas (2866 +/- 595 vs. 649 +/- 111), cytochrome C (6980 +/- 237 vs. 903 +/- 156), and PARP (6393 +/- 591 vs. 466 +/- 261) as well as increased TUNEL staining (40 +/- 2 vs. 14 +/- 1) and DNA fragmentation (all P < 0.03 vs. control). In FasL-/- and Fas-/- mice, AP-induced upregulation of p38-MAPK, PARP, and cytochrome C was significantly attenuated (all P < 0.01 compared to C57/C57 control). In addition, AP-induced DNA fragmentation was reduced 60% in Fas-/- and FasL-/- mice (P < 0.01 vs. C57/C57). AP induces apoptosis by transcriptional activation of Fas/FasL. AP-induced apoptosis was significantly reduced in Fas and FasL knockout mice along with downregulation of p38-MAPK, PARP, and cytochrome C, thereby suggesting a central role for Fas/FasL in hepatocyte apoptosis. The manipulation of interactions between Kupffer cell-derived FasL and hepatocytes may have important therapeutic implications.

Hypothesis: Medicare health maintenance organizations (HMOs) do not reduce the cost of colon resections in elderly patients., Design: Review of prospectively collected and mandatory reported Florida hospital discharge data from January 1, 1995, through December 31, 1999. We used the chi(2) test for trend analysis to assess significant change in age, mortality, and complications, and the Kruskal-Wallis test to compare inflation-adjusted hospital charges, comorbidity, length of stay, and secondary procedures., Setting: Administrative database including all community- and university-based surgeons., Patients: All patients 70 years or older who underwent colon resection from 1995 through 1999., Main Outcome Measures: Age, mortality, complications, length of stay, number of comorbidities and secondary procedures, hospital charges, and type of colon resection., Results: The frequency of different colon resections increased by 10% to 30% from 1995 through 1999. Total hospital charges increased during the study period (P<.001), whereas mortality and complications remained unchanged. Length of stay, number of secondary procedures, and comorbidities were the most significant contributors to hospital charges. Despite a significantly shorter hospital stay, Medicare HMO patients had similar hospital charges to those of original Medicare patients., Conclusions: Colon resections can be undertaken in elderly patients with acceptable morbidity. Per diem charges were higher for patients covered by Medicare HMO, despite their having shorter lengths of stay, fewer comorbidities, and fewer secondary procedures.

Background: Liver injury is an important prognostic indicator in acute pancreatitis. We previously demonstrated that Kupffer cell-derived cytokines mediate liver injury. In this work, we sought to characterize the role of Fas Ligand (FasL) in liver injury during acute pancreatitis., Methods: Acute pancreatitis was induced in mice using cerulein; serum FasL, AST, ALT, liver FasL, p38-MAPK, and caspase-3 were measured. FasL mRNA and protein and its receptor (Fas) were determined in rat Kupffer cells treated with elastase (1 U/ml) to mimic acute pancreatitis. Apoptosis was measured by flow cytometry., Results: Cerulein-induced pancreatitis increased serum AST, ALT, and FasL and up-regulated liver FasL (1315 +/- 111 versus 310 +/- 164 pg/ml, P = 0.002 versus sham), while inducing p38-MAPK phosphorylation (P < 0.01 versus sham) and cleavage of caspase-3 (P < 0.04 versus sham); all were attenuated by pretreatment with the Kupffer cell inhibitor, gadolinium (all P < 0.003). In vitro, elastase induced a time-dependent increase in Kupffer cell FasL protein (FasL = 404 +/- 94 versus 170 +/- 40, P = 0.02, versus control), a 100-fold increase in FasL mRNA, and up-regulated Fas (FasL receptor). Gadolinium significantly attenuated the elastase-induced increase in FasL and FasL mRNA (FasL = 230 +/- 20 versus 404 +/- 94, P = 0.01, versus elastase) but had little effect on Fas. Additionally, elastase-primed Kupffer cell media induced apoptosis in hepatocytes (29 +/- 1 versus 16% +/- 1%; versus control, P < 0.001)., Conclusions: Acute pancreatitis induces liver injury and hepatocyte death while up-regulating FasL, p38-MAPK, and caspase-3. Fas is up-regulated within Kupffer cells, suggesting that FasL may autoregulate its production by inducing its originator-cell death. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.

The gastrojejunostomy may be the most technically challenging step when performing laparoscopic Roux-en-Y gastric bypass. Patients who develop anastomotic leaks have increased morbidity and mortality rates. Difficulty in diagnosis is related to nonspecific systemic symptoms and limitations in most radiological studies. Our aim is to evaluate the incidence, etiology, diagnosis, management, and prevention of anastomotic leaks occurring in patients undergoing laparoscopic Roux-en-Y gastric bypass.

Background: Ovarian disease is common in obese women and is usually not screened during routine preoperative evaluation in patients undergoing bariatric surgery. Consequently, surgeons may encounter previously undiagnosed adnexal tumors during bariatric operations. The aim of this study is to report our experience with incidental ovarian tumors in patients during Roux-en-Y gastric bypass (RYGBP)., Methods: Prospectively collected data on all consecutive patients undergoing RYGBP for clinically significant obesity from July 1998 to September 2003 were reviewed for patients with incidental gynecological tumors. Details of operative treatment and outcomes are reported herein., Results: 460 women underwent RYGBP during the study period. 52 (11%) had a previous hysterectomy and/or bilateral oophorectomy and were excluded from the study. 12 ovarian masses, median tumor size 11 cm (range 4-65 cm) were found in 10 women (2.5%) during 6 open and 4 laparoscopic RYGBPs. Mean age was 40+/-9 years and mean BMI was 58+/-12 kg/m(2). Resection of 9 benign cystic lesions and 2 malignant lesions was undertaken. One patient with polycystic ovary syndrome did not undergo resection. The RYGBP was completed in all but 2 patients who, by appearance and intraoperative frozen biopsy, had evidence of malignancy. No additional morbidity resulted from the added gynecological procedure. Based on these results, an algorithm for the treatment of incidental gynecological tumors is suggested., Conclusions: Although infrequent, incidental ovarian tumors may be discovered in patients undergoing bariatric surgery, emphasizing the importance of thorough exploration of the abdominal cavity. Consultation with a gynecologist is warranted in most instances, and treatment should be on a patient-by-patient basis, especially in women of child-bearing age.

Liver injury is an important prognostic indicator during acute pancreatitis. The aim of this study was to determine the role of Fas ligand (FasL) in hepatocyte injury. Liver parenchymal enzymes were measured in cocultures of hepatocytes and Kupffer cells treated with elastase. FasL and FasL mRNA were measured in elastase-treated Kupffer cells. Hepatocytes were treated with FasL and their viability was assessed by monotetrazolium (MTT), apoptosis by flow cytometry, as well as caspase-3 and p38-mitogen-activated protein kinase (MAPK) by immunoblotting. Elastase increased aspartate aminotransferase and lactate dehydrogenase in cocultures of hepatocyte and Kupffer cells (P<0.040). Elastase increased FasL production from Kupffer cells (P=0.02) and upregulated FasL mRNA (FasL/beta-2 microglobulin (BMG): 0.23+/-0.03 vs. 0.11+/-0.003; P=0.04). FasL increased alanine aminotransferase and lactate dehydrogenase (P<0.03) and reduced hepatocyte viability by 45% (P=0.01). FasL increased the number of dually labeled cells with AnnexinV/7AAD (P=0.03) while upregulating cleavage of caspase-3 and the phosphorylation of p38-MAPK. FasL antibody attenuated the FasL-related increase in dually labeled cells (P=0.02), the cleavage of caspase-3, and phosphorylation of p38-MAPK. Pancreatic elastase upregulates FasL within Kupffer cells. FasL induces hepatocyte injury and death and upregulates p38-MAPK and caspase-3 within hepatocytes. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.

Background: Nonalcoholic Steatohepatitis (NASH) commonly occurs in obese patients and predisposes to cirrhosis. Prevalence of NASH in bariatric patients is unknown. Our aim was to determine the role of routine liver biopsy in managing bariatric patients., Methods: Prospective data on patients undergoing Roux-en-Y gastric bypass (RYGBP) was analyzed. One pathologist graded all liver biopsies as mild, moderate or severe steatohepatitis. NASH was defined as steatohepatitis without alcoholic or viral hepatitis. Consecutive liver biopsies were compared to those liver biopsies selected because of grossly fatty livers., Results: 242 patients underwent open and laparoscopic RYGBP from 1998-2001. Routine liver biopsies (68 consecutive patients) and selective liver biopsies (additional 86/174, 49%) were obtained. Findings of cirrhosis on frozen section changed the operation from a distal to a proximal RYGBP. The two groups were similar in age, gender, and BMI. The group with the routine liver biopsies showed a statistically significant larger preponderance of NASH (37% vs 32%). Both groups had a similar prevalence of cirrhosis. Neither BMI nor liver enzymes predicted the presence or severity of NASH., Conclusions: Routine liver biopsy documented significant liver abnormalities in a larger group of patients compared with selective liver biopsies, thereby suggesting that liver appearance is not predictive of NASH. Liver biopsy remains the gold-standard for diagnosing NASH. We recommend routine liver biopsy during bariatric operations to determine the prevalence and natural history of NASH, which will have important implications in directing future therapeutics for obese patients with NASH and for patients undergoing bariatric procedures.

Background: Minimally-invasive parathyroidectomy (MIP) appears to be changing preoperative treatment and referral patterns for sporadic, nonfamilial, non-multiple endocrine neoplasia, primary hyperparathyroidism (PHPT)., Methods: The American Association of Clinical Endocrinologists membership was surveyed by mail (n=1406 members) regarding physician practices and surgical referral patterns for PHPT., Results: Seven hundred eighty-eight respondents (56%) practiced 17.0+/-0.4 years and referred 63%+/-1% of patients with PHPT for operation. Most endocrinologists (90%) used localizing studies before surgical referral (sestamibi, ultrasound scanning, technetium/thallium scanning, magnetic resonance imaging, computed tomography). Respondents identified symptoms, calcium homeostasis, bone density, health status, age, and general anesthesia risk as the most important considerations for surgical referral. Most respondents (79%) indicated that MIP availability would increase the number of patients who were referred for operation (P<.001), although most of the respondents stated that MIP would change the extent and duration of preoperative evaluations (P<.001). Respondents in practice for fewer years were more likely to refer patients for MIP (P<.001) and minimize preoperative evaluation (P<.05). Endocrinologists who had a patient with a complication after traditional parathyroidectomy were more likely to embrace MIP (P<.05)., Conclusions: MIP availability decreases the extent and duration of preoperative evaluation while decreasing the time from diagnosis to referral. MIP also lowers the endocrinologists' surgical referral threshold for PHPT, although it emphasizes the perceived shortcomings of traditional parathyroidectomy that are held by many physicians.

Background: Laparoscopic Roux-en-Y gastric bypass is being undertaken with increasing frequency. We describe a technique for introducing the anvil of the circular stapler using a totally transabdominal approach., Methods: One hundred consecutive patients underwent laparoscopic Roux-en-Y gastric bypass in a university-affiliated teaching hospital., Results: The cardiojejunostomy was constructed in all 100 patients using the circular stapler with no complications. No anastomotic leaks were detected postoperatively., Conclusions: The totally transabdominal approach for introducing the anvil of the circular stapler into the gastric pouch is safe and feasible.

Background: The economic burden of caring for veterans with clinically severe obesity and its comorbidities is straining the Veterans Administration (VA) healthcare system. The authors determined the cost of Roux-en-Y Gastric Bypass (RYGBP) in the VA's single-payor healthcare system., Methods: The records of all 25 patients who underwent RYGBP from May 1999 to October 2001 were reviewed. All obesity-related health-care costs including hospitalizations as well as outpatient visits, medications and home health devices were calculated for 12 months before and after the RYGBP., Results: Age was 52+/-2 yr and preoperative BMI was 52+/-2 kg/m(2); ASA score was III (21 patients) and II (4 patients). Mean follow-up was 18 months. Total cost of care for these patients preoperatively was $10,778+/-2,460/patient (outpatient visits=$5,476+/-682, hospital admissions=$12,221+/-6,062, and home health devices=$1,383+/-349). Postoperative length of stay was 8+/-0.5 days. Cost of the gastric bypass was $8,976+/-497/pt (OR fixed cost=$1,900/patient + ICU and ward=$7,076+/-497/patient). For the first postoperative year, 6 patients had 12 admissions, but routine outpatient visits were significantly reduced from 55+/-6 to 18+/-2 postoperatively (P<0.001). The cost of all care excluding peri-operative charges for 1 year after gastric bypass was $2,840+/-622/patient (P=0.005 vs preop)., Conclusions: Operative treatment of clinically severe obesity reduces obesity-related expenditures and utilization of healthcare resources. The cost of undertaking RYGBP at the VA is offset by reduction of health-care costs within the first year after surgery. These data support allocation of resources to support existing bariatric surgery programs throughout the VA system.

Background: Elderly patients are an increasingly larger group of injured trauma care patients. Comorbidities influence outcome. Little is known of short- and long-term mortality in the elderly who survive initial resuscitation., Methods: Short- and long-term mortality was retrospectively analyzed in 363 consecutively injured patients (Injury severity score >15) surviving more than 3 days after admission to a level 1 trauma center (including 197 patients >60 years). Cardiac morbidity was the focus., Results: Survival to hospital discharge was similar comparing older patients with the entire group. Mortality increased incrementally with age. In older patients, cardiac morbidity was observed in 28% (fatal in 7); 2-year mortality was 36% (older group) and 60% (patients sustaining cardiac complications). Most elderly (80%) were discharged to long-term care., Conclusions: Elderly who survive initial resuscitation are as likely to survive to discharge as younger patients, but long-term survival is significantly lower as age increases. Cardiac morbidity is associated with higher long-term mortality. Most elderly are discharged to long-term care.

Background: We have demonstrated that obstructive sleep apnea (OSA) is prevalent in 60% of patients undergoing bariatric surgery. A study was conducted to determine whether weight loss following bariatric surgery ameliorates OSA., Methods: All 100 consecutive patients with symptoms of OSA were prospectively evaluated by polysomnography before gastric bypass. Preoperative and postoperative scores of Epworth Sleepiness Scale (ESS), Respiratory Disturbance Index (RDI), and other parameters of sleep quality were compared using t-test., Results: Preoperative RDI was 40 +/- 4 (normal 5 events/hour, n = 100). 13 patients had no OSA, 29 had mild OSA, while the remaining 58 patients were treated preoperatively for moderate-severe OSA. At a median of 6 months follow-up, BMI and ESS scores improved (38 +/- 1 vs 54 +/- 1 kg/m2, 6 +/- 1 vs 12 +/- 0.1, P < 0.001, postoperatively vs preoperatively). To date, 11 patients have completed postoperative polysomnography (3-21 months) after losing weight (BMI 40 +/- 2 vs 62 +/- 3 kg/m2, P < 0.001). There was significant improvement in ESS (3 +/- 1 vs 14 +/- 2), minimum O2 saturation (SpO2 86 +/- 2 vs 77 +/- 5), sleep efficiency (85 +/- 2% vs 65 +/- 5%), all P < 0.001, postop vs preop; and RDI (56 +/- 13 vs 23 +/- 7, P = 0.041). Regression analysis demonstrated no correlation between preoperative BMI, ESS score and the severity of OSA; and no correlation between % excess body weight loss and postoperative RDI., Conclusion: Weight loss following gastric bypass results in profound improvement in OSA. The severity of apnea cannot be reliably predicted by preoperative BMI and ESS; therefore, patients with symptoms of OSA should undergo polysomnography.

Background: The training and credentialing of surgeons for laparoscopic bariatric surgery is controversial. We sought to determine if there is an association between surgeons' practice and choice of open or laparoscopic bariatric surgery., Methods: Members of the ASBS were surveyed via email. Associations were tested with Cochran-Mantel-Haenszel or Pearson's chi-square., Results: 104/472 members responded; 65% were in private practice; 47% did 1-5 operations/week, 48% offered open procedures only, and 76% undertook gastric bypass. Respondents believe that laparoscopic procedures: should mimic open ones (77%), are safe (63%), should be evaluated by clinical trials (48%), and that expertise in bariatric surgery is more important than laparoscopic experience. 75% believe that courses and preceptorships are important. Regarding laparoscopic operations, surgeons doing only open procedures believe that: 1) the ASBS should be the main credentialing body; 2) surgeons should do > 25 open before laparoscopic ones; and 3) clinical trials are needed (P < 0.02, all). Surgeons with laparoscopic training or practices believe that laparoscopic surgery is safe and effective (P < 0.002). Both laparoscopic and open surgeons believe bariatric surgeons should be the only surgeons doing laparoscopic bariatric procedures (P < 0.008)., Conclusions: There is consensus that laparoscopic bariatric surgery should be undertaken only by surgeons with strong interest in bariatric surgery. Laparoscopic bariatric surgeons should incorporate lessons learned from open surgery. Both laparoscopic and open bariatric surgeons should seek added expertise via courses and preceptorships. The skepticism of surgeons with 'open' practices could be addressed by clinical trials. The ASBS should maintain its leadership position and foster emerging technologies.

We have demonstrated that Kupffer cell-derived tumor necrosis factor (TNF) mediates pancreatitis-associated liver injury. The aim of this study was to determine the role of p38 mitogen-activated protein kinase (MAPK), extracellular stress-related kinase 1/2 (ERK1/2), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and nuclear factor-kappaB (NF-kappaB) in TNF gene expression within Kupffer cells. TNF and TNF-mRNA were measured in rat livers perfused with elastase. TNF, TNF-mRNA, NF-kappaB activation, and phosphorylated p38-MAPK, SAPK/JNK, and ERK1/2 were determined in Kupffer cells treated with elastase. Elastase increased TNF and upregulated TNF-mRNA in livers (P<0.03) and Kupffer cells (P<0.001). Phosphorylated p38-MAPK, SAPK/JNK, and ERK1/2 and activated NF-kappaB were detected in Kupffer cells at 7 minutes; at 60 minutes, TNF-mRNA peaked and NF-kappaB returned to baseline, whereas all three kinases remained activated. Gadolinium inhibited elastase-induced upregulation of TNF-mRNA (P < 0.001), TNF production (P<0.001), and attenuated SAPK/JNK, as well as ERK1/2, but not p38-MAPK. Both UO126 and SB203580 significantly inhibited elastase-induced upregulation of TNF-mRNA and TNF production (P<0.001), but only UO126 inhibited activation of NF-kappaB. It was concluded that pretranscriptional regulation of TNF gene expression in Kupffer cells follows an orderly activation of p38-MAPK, ERK1/2, and SAPK/JNK that may not converge on NF-kappaB. The seemingly limited duration of NF-kappaB activation may be important in "switching off" the cytokine cascade during acute pancreatitis., (Copyright 2003 The Society for Surgery of the Alimentary Tract, Inc.)