Postoperative hypoxemia: common, undetected, and unsuspected after bariatric surgery.

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.

Current management of adrenal tumors.

PURPOSE OF REVIEW: Adrenal tumors evoke considerable interest and diagnostic challenges. This rare group of tumors includes functional tumors with a gamut of clinical presentations, as well as adrenocortical carcinoma, with its advanced disease at presentation and dismal prognosis posing additional challenge. Increasing detection of incidentalomas adds further interest with the concomitant diagnostic and management dilemmas. RECENT FINDINGS: Significant advances have been made in diagnostic imaging modalities for identifying malignancy risk in adrenal incidentalomas. Considerable progress has occurred in understanding adrenocortical carcinoma pathogenesis from the study of genetics at the germline level in familial carcinomas, as well as at the somatic level by analyzing molecular alterations in sporadic tumors; this research supplies opportunities to develop novel therapeutic agents against a tumor with poor prognosis. SUMMARY: Laparoscopic adrenalectomy has emerged as standard of care in the treatment of functional benign adenomas and nonfunctional tumors larger than 4 cm when adrenocortical carcinoma is not suspected. Open adrenalectomy with en-bloc excision has been the mainstay for primary and recurrent adrenocortical carcinoma due to the lack of effective adjuvant therapy. International consensus conferences have attempted to standardize diagnostic and treatment approaches in the management of adrenal tumors; further research is necessary.

Trends in adrenalectomy rates, indications, and physician volume: A statewide analysis of 1816 adrenalectomies.

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.

Bariatric surgery improves urinary incontinence in morbidly obese individuals.

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.

Morbidity of anastomotic leaks in patients undergoing Roux-en-Y gastric bypass.

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.

Protein kinase C-zeta is critical in pancreatitis-induced apoptosis of Kupffer cells.

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.

A state-wide review of contemporary outcomes of gastric bypass in Florida: does provider volume impact outcomes?

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.

Objective evidence that bariatric surgery improves obesity-related obstructive sleep apnea.

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

Predictive factors of thromboembolic events in patients undergoing Roux-en-Y gastric bypass.

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.

Spectrum and treatment of small bowel obstruction after Roux-en-Y gastric bypass.

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.

The role of p65 NF-kappaB/RelA in pancreatitis-induced Kupffer cell apoptosis.

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.

Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL.

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.

Amelioration of gastroesophageal reflux symptoms following Roux-en-Y gastric bypass for clinically significant obesity.

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.

Operative technique for converting a failed vertical banded gastroplasty to Roux-en-Y gastric bypass.

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.

Realistic expectations and leadership in the era of work hour reform.

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.

Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis.

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.

Failure of Medicare health maintenance organizations to control the cost of colon resections in elderly patients.

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.

Anastomotic leaks after laparoscopic gastric bypass.

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.

Acute pancreatitis induces FasL gene expression and apoptosis in the liver.

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.