Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.

Acquired jejunoileal diverticulosis and its complications: a review of the literature.

Jejunoileal diverticulosis is a rare entity. Jejunoileal diverticulosis is not a disease that surgeons see often in clinical practice; however, it should remain on the differential diagnosis for any patient with an acute abdomen or gastrointestinal bleeding of unknown origin. It can present with a wide range of clinical scenarios and when patients experience chronic symptoms such as bloating, abdominal pain, nausea, bacterial overgrowth, or malabsorption, medical therapy is successful in most patients. However, when patients present with acute symptoms of bleeding, inflammation, perforation, or obstruction, surgical resection and primary anastomosis is often the treatment of choice. If patients are asymptomatic, they are better left alone, even when discovered incidentally in the operating room. In closing, the possibility of a patient having jejunal diverticular disease should be suspected whenever the symptoms of obscure abdominal pain, anemia, dilated jejunal loops on abdominal radiographs, a history of colonic diverticuli, and a history of acute appendicitis.

Antegrade and retrograde endoscopy for treatment of esophageal stricture.

Total or near-total esophageal stricture results from multiple processes. Traditional treatment with wire cannulation followed by serial dilation is often contraindicated due to poor visualization and the risk of perforation. We seek to demonstrate that combined antegrade and retrograde endoscopy are useful for treatment of total or near-total esophageal strictures. The gastrostomy tube is removed and the tract dilated. A standard endoscope is passed retrograde to the stricture. An antegrade endoscope is advanced until transillumination across the stricture is visualized. A biopsy forceps or needle is used to traverse the stricture in an antegrade fashion. The tract is cannulated with a stiff wire that is then brought out through the gastrostomy site. The stricture is serially dilated. The gastrostomy tube is replaced, and a nasogastric tube is left across the stricture for 3 to 4 weeks. The endoscope is withdrawn and an 18 or 20 Fr gastrostomy tube is left in place. A total of three patients with total esophageal strictures were treated using combined antegrade and retrograde esophagoscopy. All three patients regained the ability to swallow secretions. Importantly, there were no instances of esophageal perforation. This technique has broader application, including combination with minilaparotomy for patients without retrograde access. Further research is needed to determine durability of stricture dilation.

Protracted Hypocalcemia following 3.5 Parathyroidectomy in a Kidney Pancreas Recipient with a History of Robotic-Assisted Roux-en-Y Gastric Bypass.

BACKGROUND: Hypocalcemia is a frequent complication of parathyroidectomy for secondary/tertiary hyperparathyroidism. In patients with a history of prior Roux-en-Y gastric bypass (RYGBP), changes in nutritional absorption make management of hypocalcemia after parathyroidectomy difficult. CASE REPORT: A 41-old-year morbidly obese female with c-peptide negative diabetes mellitus and renal failure had RYGBP. Following significant weight loss she underwent simultaneous pancreas-kidney transplantation. She had excellent transplant graft function but developed tertiary hyperparathyroidism with calciphylaxis. She underwent resection of 3.5 glands leaving a small, physiologic remnant remaining in situ at the left inferior position. She was discharged on postoperative day one in good condition, asymptomatic with serum calcium of 7.6 mg/dL and intact PTH of 12 pg/mL. The patient had to be readmitted on postoperative day #14 for severe hypocalcemia of 5.0 mg/dl and ionized calcium 2.4 mg/dl. She required intravenous calcium infusion to achieve calcium levels of >6.5 mg/dl. Long-term treatment includes 5 g of elemental oral calcium TID, vitamin D, and hydrochlorothiazide. She remains in the long term on high-dose medical therapy with normal serum calcium levels and PTH levels around 100 pg/mL. DISCUSSION: Our patient's protracted hypocalcemia originates from a combination of 3.5 gland parathyroidectomy, altered intestinal anatomy post-RYGBP, and potentially her pancreas transplant causing additional metabolic derangement. Alternative bariatric procedures such as sleeve gastrectomy may be more suitable for patients with renal failure or organ transplants in whom adequate absorption of vitamins, minerals, and drugs such as immunosuppressants is essential.

Effect of gastric bypass operation on Framingham and actual risk of cardiovascular events in class II to III obesity.

BACKGROUND: Obesity is known to be a major risk factor for cardiovascular diseases. There are few studies in the literature assessing the effect of bariatric procedures on longterm risk of cardiovascular events. The aim of this study was to determine the effect of gastric bypass operation on actual and Framingham risk of coronary heart disease (CHD) events in class II to III obesity. STUDY DESIGN: In a cohort of subjects with class II to III obesity, we used the observed change in CHD risk factors and risk models derived from the Framingham data equation to calculate the predicted 10-year absolute and relative risk of CHD after gastric bypass operation. The risk predicted by the Framingham model was then compared with the actual incidence of CHD events of the cohort. RESULTS: Five-hundred patients were included in the study. The 1-year mean excess body weight loss was 68.7% +/- 22%. There was a substantial reduction in prevalence of diabetes from 28% to 6% (p = 0.001). Compared with baseline, the average 10-year absolute risk of cardiac events decreased from 5.4% at baseline to 2.7% at 1 year after operation (p = 0.001). A similar risk reduction was observed in subgroups defined by diabetes status and gender. Gastric bypass decreased absolute risk of cardiac events by a mean of 63% (p = 0.0001) in diabetics and 56% (p = 0.001) in male patients. The cohort actual rate of CHD events was 1% (5 of 500). At the 5-year horizon, this was considerably (p = 0.001) lower than the predicted rate before gastric bypass operation. CONCLUSIONS: Gastric bypass operation is effective in reducing actual and the 10-year Framingham risk of CHD events in individuals with class II to III obesity. The major estimated risk reduction was observed in male patients with type 2 diabetes.

National variations in morbid obesity and bariatric surgery use.

BACKGROUND: Exploring bariatric surgery use provides data on effective treatment allocation. This study analyzed national rates of bariatric surgery use and the burden of morbid obesity by gender, census region, and age. STUDY DESIGN: Patients 18 years of age or older undergoing bariatric surgery were identified from the US 2002 Nationwide Inpatient Sample, and the national morbidly obese population 18 years of age or older was determined using the Centers for Disease Control and Prevention 2002 Behavioral Risk Factor Surveillance System databases. General population data were obtained from 2000 census data. Annual rates of bariatric surgery procedures were determined by gender, age group, and census region (Northeast, Midwest, South, and West). Rate ratios were calculated and significance tested through 95% confidence intervals (95% CI), accounting for the Nationwide Inpatient Sample and Behavioral Risk Factor Surveillance System sampling design. RESULTS: In 2002, a national cohort of 69,490 bariatric surgery patients was identified. Of these patients 85% were women and 76% were ages 18 to 49 years. The prevalence of morbid obesity (body mass index > or = 40 kg/m(2)) in the US in 2002 was 1.8%; 60% of morbidly obese people were women, and 63% were ages 18 to 49 years. The rates of bariatric surgery procedures per 100,000 morbidly obese individuals ranged from a low of 139 in men aged 60 years and older in the Midwest to a high of 5,156 in women ages 40 to 49 years in the Northeast. For both men and women, bariatric surgery rates in the West and Northeast were 1.35 (95% CI 1.31 to 1.40, p < 0.05) to 4.51 (95% CI 4.15 to 4.89, p < 0.05) times higher than in the South, respectively; rates in the Midwest were similar to those in the South. CONCLUSIONS: National estimates suggest that bariatric surgery rates do not parallel the burden of morbid obesity by region or age. Additional evaluation of these differences is necessary for optimal bariatric surgery use.

Percutaneous endoscopic transgastric jejunostomy: a new approach.

A percutaneous transgastric jejunostomy allows long-term simultaneous gastric decompression and jejunal feedings. We have developed a safe and effective bedside technique for placement of a large-bore (22 French) feeding tube while providing gastric drainage with no mortalities and minimal morbidities. We have modified the push technique used for percutaneous gastrostomies and introduced a cut-away sheath that is placed using a modified Seldinger technique. The entire procedure is performed under endoscopic visualization. Our experience with more than 100 successful tube placements has made this method common practice at our institute. This technique is ideal for patients with poor gastric emptying of any etiology. We feel that this technique will have an expanding and important role in the future management of this patient population's nutritional problems.

National analysis of adverse patient safety for events in bariatric surgery.

Identifying risk factors for adverse events after bariatric surgery (BaS) can help define high-risk groups to improve patient safety. We calculated cumulative incidence of adverse events and identified risk factors for these events using validated surgical patient safety indicators (PSIs) developed by the Agency for Healthcare Research and Quality. BaS patients > or =18 years old were identified using the 2002 Nationwide Inpatient Sample. Cumulative incidence at discharge was calculated for accidental puncture or laceration (APL), pulmonary embolus or deep venous thrombosis (PE/DVT), and postoperative respiratory failure (RF). Factors predictive of these PSIs were identified. From 7,853,982 discharges, a national cohort of 69,490 BaS patients was identified. During BaS hospitalization, the cumulative incidences per 1000 discharges of APL, PE/DVT, and RF were 12.6, 3.4, and 7.3, respectively. Risk factors for APL included male gender (odds ratio [OR] 1.6, 95% confidence interval 1.1-2.3, P < 0.05) and age of 40-49 years (OR 1.6 [1.1-2.3], P < 0.05) compared to ages 18-39 years. Patients aged 50-59 years (OR 3.5 [1.6-7.7], P < 0.05) had a higher chance of PE/DVT compared to those 18-39 years. Male gender (OR 1.8 [1.1-2.9], P < 0.05), ages 40-49 (OR 2.1 [1.1-4.2], P < 0.05) and 50-59 (OR 3.8 [2.1-6.9], P < 0.05), a history of chronic lung disease (OR 1.7 [1.1-2.7], P < 0.05), and Medicare coverage compared to private insurance (OR 2.2 [1.2-3.8], P < 0.05) were predictive of RF. This study established national measures for BaS adverse events. Further, risk factors associated with adverse events varied by gender, age, insurance status, and comorbidity. Evaluation of these higher risk BaS groups is needed to improve patient safety.

Liposarcoma of the spermatic cord masquerading as an incarcerated inguinal hernia.

We present a rare case of liposarcoma of the spermatic cord. There are only 61 reports in the literature. The presenting complaint is usually a painless bulge in the inguinal or scrotal region. Our patient presented with a new-onset inguinoscrotal swelling that was misdiagnosed preoperatively as an incarcerated indirect hernia. The treatment for a spermatic cord liposarcoma is radical orchiectomy with high ligation of the cord. Radiation therapy is recommended in addition to surgery in situations with evidence of tumor with propensity for more aggressive behavior (i.e., high-grade tumor, lymphatic invasion, inadequate margin, or recurrence). The current literature, diagnosis, and management of malignant tumors of the spermatic cord are reviewed.

Robotic-assisted Roux-en-Y gastric bypass in a patient with situs inversus.

We report the case of a morbidly obese patient with situs inversus who presented for robotic-assisted Roux-en-Y gastric bypass. To do the procedure, the ports were reversed and the first assistant stood on the opposite side of the table. With these minor modifications to technique, the surgery was successfully performed without confusion over the patient's anatomy. There were no intraoperative complications. The patient's postoperative course was uneventful and he was discharged on postoperative day 3. We believe this is the first reported robotic-assisted Roux-en-Y gastric bypass in a patient with situs inversus.

Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with elevated ghrelin.

OBJECTIVES: We sought to determine: (1) if early weight regain between 1 and 2 years after Roux-en-Y gastric bypass (RYGB) is associated with worsened hepatic and peripheral insulin sensitivity, and (2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB. METHODS: Hepatic and peripheral insulin sensitivity and ghrelin and leptin plasma levels were assessed longitudinally in 45 subjects before RYGB and at 1 month, 6 months, 1 year, and 2 years postoperatively. Weight regain was defined as ≥5% increase in body weight between 1 and 2 years after RYGB. RESULTS: Weight regain occurred in 33% of subjects, with an average increase in body weight of 10 ± 5% (8.5 ± 3.3 kg). Weight regain was not associated with worsening of peripheral or hepatic insulin sensitivity. Subjects with weight regain after RYGB had higher preoperative and postoperative levels of ghrelin compared to those who maintained or lost weight during this time. Conversely, the trajectories of leptin levels corresponded with the trajectories of fat mass in both groups. CONCLUSIONS: Early weight regain after RYGB is not associated with a reversal of improvements in insulin sensitivity. Higher preoperative ghrelin levels might identify patients that are more susceptible to weight regain after RYGB.

Reduction in inflammatory gene expression in skeletal muscle from Roux-en-Y gastric bypass patients randomized to omentectomy.

OBJECTIVES: To examine the effects of Roux-en-Y gastric bypass (RYGB) surgery with and without laparoscopic removal of omental fat (omentectomy) on the temporal gene expression profiles of skeletal muscle. DESIGN: Previously reported were the whole-body metabolic effects of a randomized, single-blinded study in patients receiving RYGB surgery stratified to receive or not receive omentectomy. In this follow up study we report on changes in skeletal muscle gene expression in a subset of 21 patients, for whom biopsies were collected preoperatively and at either 6 months or 12 months postoperatively. METHODOLOGY/PRINCIPAL FINDINGS: RNA isolated from skeletal muscle biopsies of 21 subjects (8 without omentectomy and 13 with omentectomy) taken before RYGB or at 6 and 12 months postoperatively were subjected to gene expression profiling via Exon 1.0 S/T Array and Taqman Low Density Array. Robust Multichip Analysis and gene enrichment data analysis revealed 84 genes with at least a 4-fold expression difference after surgery. At 6 and 12 months the RYGB with omentectomy group displayed a greater reduction in the expression of genes associated with skeletal muscle inflammation (ANKRD1, CDR1, CH25H, CXCL2, CX3CR1, IL8, LBP, NFIL3, SELE, SOCS3, TNFAIP3, and ZFP36) relative to the RYGB non-omentectomy group. Expressions of IL6 and CCL2 were decreased at all postoperative time points. There was differential expression of genes driving protein turnover (IGFN1, FBXW10) in both groups over time and increased expression of PAAF1 in the non-omentectomy group at 12 months. Evidence for the activation of skeletal muscle satellite cells was inferred from the up-regulation of HOXC10. The elevated post-operative expression of 22 small nucleolar RNAs and the decreased expression of the transcription factors JUNB, FOS, FOSB, ATF3 MYC, EGR1 as well as the orphan nuclear receptors NR4A1, NR4A2, NR4A3 suggest dramatic reorganizations at both the cellular and genetic levels. CONCLUSIONS/SIGNIFICANCE: These data indicate that RYGB reduces skeletal muscle inflammation, and removal of omental fat further amplifies this response. TRIAL REGISTRATION: ClinicalTrials.gov NCT00212160.

Inpatient mortality and length of stay comparison of percutaneous endoscopic gastrostomy and percutaneous endoscopic gastrojejunostomy.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic gastrojejunostomy (PEGJ) are endoscopic procedures often performed by surgeons. No recent population-based study has compared inpatient mortality or length of stay between patients who undergo PEG or PEGJ placement during their hospitalization. METHODS: Patients undergoing inpatient PEG or PEGJ placement and who were at least 18 years old were identified from the 2006 Nationwide Inpatient Sample (NIS) database. Baseline characteristics of each group were compared, and outcomes of risk-adjusted inpatient mortality and length of stay were determined. Means were compared from using a complex sample t-test, and proportions were compared from using a complex sample chi-square test, with an alpha level of 0.05 for significance. Bivariate logistic regression was used to evaluate PEG or PEGJ placement as a risk factor for mortality. RESULTS: In the 2006 NIS, 187,597 discharges were identified, during which a PEG or PEGJ was placed. Ninety-six percent (179,587) of patients underwent PEG placement, and 4% (8010) had PEGJ tubes placed. Fifty-one percent were men, with the mean age for PEG and PEGJ placement of 71.3 +/- 0.3 (mean +/- standard error) and 64.8 +/- 0.8 years (P < 0.05). In the PEG group, 86% of admissions were nonelective, compared to 79% in the PEGJ group (P < 0.05). The primary discharge diagnoses for both groups of patients included acute cerebrovascular disease, aspiration pneumonitis, septicemia, respiratory failure, and intracranial injury. PEG patients had a higher cumulative incidence of congestive heart failure, chronic lung disease, and diabetes. Crude in-hospital mortality for death was 11% for both PEG and PEGJ patients. No difference in mortality was observed in risk-adjusted analyses accounting for patient severity. Mean length of stay was similar for both groups (PEG 20.9 +/- 0.4 days; PEGJ 22.5 +/- 1.1 days). Neither PEG nor PEGJ was identified as a risk factor for inpatient mortality. CONCLUSIONS: Comparative analyses of patients undergoing PEG versus PEGJ revealed no detectable difference between inpatient mortality and hospital length of stay in this large observational study. Both procedures can be performed safely in high-risk populations, with no increased mortality or length of stay incurred by jejunal feeding access. However, further analysis is required to compare more specific short-term outcomes between these populations as well as their respective cost-effectiveness.

Intraband pressure measurements describe a pattern of weight loss for patients with adjustable gastric bands.

BACKGROUND: Individuals with adjustable gastric bands experience plateaus in weight loss. Patients commonly attribute this to a "loosening" of their band with time. We sought to elucidate a physiologic mechanism for this pattern in patient behavior and describe the feasibility of a pressure-based adjustment algorithm for adjustable gastric bands. METHODS: Following IRB protocol, 100 consecutive patients undergoing placement of the Lap-Band (Inamed) were enrolled and followed prospectively for 12 months. Intraband pressure measurements at band volumes 0 to 4 mL were recorded intraoperatively and at each subsequent band adjustment. Band adjustments were made using the currently accepted volume-based postoperative protocol. RESULTS: Seventy-nine patients were included in analysis. Mean percent excess weight loss for the study cohort was 36 +/- 17% at a median followup of 347 days. During the time between adjustments, there was a statistically significant decrease (p < 0.001) in intraband pressure without a corresponding decrease in band volume. This was a result of a substantial change in the pressure-volume relationship of the Lap-Band. As time progressed, the Lap-Band developed less intraband pressure per unit volume. This change was not a result of changes in the elastic properties of the band material itself. CONCLUSIONS: Between adjustments, Lap-Band patients experience gradual loss of satiety and a loosening of their band, despite stable band volume. Their experience is substantiated by degradation in their intraband pressures with time. We have demonstrated that intraband pressures correlate with the patient's clinical history and have thereby established the foundation for a pressure-based adjustment protocol.

Risk factors for post-operative mortality in bariatric surgery.

BACKGROUND: Appropriate patient selection is crucial to the success of bariatric surgery (BaS). The objective of this study was to identify risk factors for increased post-operative mortality in patients undergoing BaS using a nationally representative sample. MATERIALS AND METHODS: BaS patients > or = 18 years old in the United States were identified from the 2001 Nationwide Inpatient Sample (NIS). The effect of gender, age, insurance status, and need for re-operation on post-operative mortality was examined using a multivariate logistic regression model. RESULTS: A national cohort of 54,878 patients was identified with age 41 +/- 0.2 years (mean +/- SE), 84% women, length of stay (LOS) 3.9 +/- 0.2 days, and overall mortality of 4 per 1,000 BaS patients. Mean LOS of those who died was 17.6 +/- 3.7 days. Adjusting for comorbidities and demographics, men had increased likelihood of death [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.3, P < 0.05]. Compared to younger patients, those aged above 39 years had over two-fold risk of death [ages 40-49: OR 2.6, 95% CI 1.1-6.5, P < 0.05; ages 50-59: OR 4.3, 95% CI 1.7-11, P < 0.05]. Medicaid patients [OR 4.7, 95% CI 1.2-13, P < 0.05 compared to privately insured] and those requiring re-operation [OR 22, 95% CI 5.4-88, P < 0.05] had higher odds of dying. CONCLUSION: Based on national data, risk factors for increased post-operative mortality in BaS patients include male gender, age > 39 years, Medicaid insured, and need for re-operation. These data can assist in optimizing BaS patient outcomes.