Krista Haines

The importance of routine liver biopsy in diagnosing Nonalcoholic Steatohepatitis in bariatric patients

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.

Current Indications for Preoperative Inferior Vena Cava Filter Insertion in Patients Undergoing Surgery for Morbid Obesity

Background: Pulmonary embolus is a potentially lethal complication in patients undergoing surgery for morbid obesity. In a select group of patients at high risk for venous thromboembolic events (VTE), we have chosen to prophylactically insert inferior vena cava filters via a jugular percutaneous approach. We propose guidelines for preoperative insertion of inferior vena cava filters in patients with clinically significant obesity. Methods: All patients who underwent preoperative insertion of inferior vena cava (IVC) filters as prophylaxis for pulmonary emboli were reviewed. Data regarding body mass index (BMI), prior history of venous thromboembolism, current anticoagulant usage, as well as other patient data were compiled and analyzed. Additionally, all operative notes were reviewed, and operative data were analyzed and compared. Results: 14 patients underwent preoperative IVC filter placement before gastric bypass. Mean patient age was 49.1 ± 1.52 years and mean BMI was 56.5 ± 4.45 kg/m2. No complications occurred due to preoperative filter placement, and no pulmonary emboli occurred in this group. Indications for preoperative IVC filter insertion included prior pulmonary embolus (6), prior deep venous thrombosis (7), and lower extremity venous stasis (1). Conclusions: Vena caval filter placement in the preoperative period can be undertaken safely in bariatric patients. We recommend that routine preoperative vena caval filter placement should be undertaken in all bariatric patients with prior pulmonary embolus, prior deep venous thrombosis, evidence of venous stasis, or known hypercoagulable state. Possible roles for IVC filter placement in this patient population are expanding as more data is acquired.

Incidence of bone loss, falls, and fractures after Roux-en-Y gastric bypass for morbid obesity ☆

The objectives of this study were to determine the incidence of and associated risks for falls and fractures after gastric bypass surgery for morbid obesity and to determine the clinical signs of bone loss. The sample consisted of 167 individuals at a mean age of 47 years (SD = 10). Ten participants (6%) reported a decrease in height since surgery, and 33 (20%) reported a decrease in height since they were 20 years old. Eight participants (5%) reported postoperative fractures. Twenty-three participants (13.8%) reported falling once since surgery, and 34 (20.4%) reported falling two or more times since surgery. Twelve participants reported a new diagnosis of osteoporosis postoperatively, and 1 participant reported a new diagnosis of osteopenia. Sixty-seven percent (n = 112) of the participants were never advised to undergo a bone density test postoperatively. The findings from this study suggest that bone loss is a critical issue in this patient population, with 25% (n = 42) reporting a decrease in height, 8% (n = 13) reporting a new diagnosis of osteoporosis or osteopenia, and 5% (n = 8) reporting fractures during a mean postoperative interval of 2.4 years. In addition, risk for skeletal fragility is profound in this cohort of individuals, with 34% (n = 57) indicating a history of one or more falls postoperatively. The results from this study clearly indicate a need for early recognition of bone loss in this population so that timely interventions can be initiated to prevent further loss and subsequent fractures.

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.

Kupffer cell-derived fas ligand plays a role in liver injury and hepatocyte death

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.

Does experience preclude leaks in laparoscopic gastric bypass

BackgroundImproved 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.MethodsProspectively 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.ResultsStaple-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/m2 (ranges, 32–59 kg/m2). 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).ConclusionsThe 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.

The Role of p65 NF-κB/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-kB-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-kB/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-kB/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-kB/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-kB/RelA, upregulation of Fas/FasL, caspase-3, DNA fragmentation, and apoptosis in Kupffer cells (all P<0.001). Acute pancreatitis activates p65 NF-kB/RelA and induces apoptosis of Kupffer cells. Inhibition of p65NF-kB/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.

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.

Management of Incidental Ovarian Tumors in Patients Undergoing 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/m2. 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.

Life-threatening postoperative hypoventilation after bariatric surgery

Life-threatening postoperative hypoventilation after bariatric surgery Scott F. Gallagher, M.D., F.A.C.S.*, Krista L. Haines, M.A.B.M.H., Lynn Osterlund, M.D., Michel Murr, M.D., F.A.C.S., John B. Downs, M.D., F.C.C.M. Department of Surgery, University of South Florida College of Medicine, University of South Florida Health, Tampa, Florida Department Anesthesiology, University of South Florida College of Medicine, University of South Florida Health, Tampa, Florida Received April 7, 2009; revised April 8, 2009; accepted April 8, 2009 Surgery for Obesity and Related Diseases 6 (2010) 102–104