CCL20 is up-regulated in non-alcoholic fatty liver disease fibrosis and is produced by hepatic stellate cells in response to fatty acid loading.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood. METHODS: Gene expression profiling using microarray, PCR array, and RNA sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity. Patients were grouped based on histological findings including normal liver histology with no steatosis, lobular inflammation, or fibrosis, and grades 1, 2, 3, and 4 fibrosis with coexistent steatosis and lobular inflammation. Validation of expression was conducted using quantitative PCR. Serum analysis was performed using ELISA. Expression analysis of hepatocytes and hepatic stellate cells in response to lipid loading were conducted in vitro using quantitative PCR and ELISA. RESULTS: Three orthogonal methods to profile human liver biopsy RNA each identified the chemokine CCL20 (CC chemokine ligand 20 or MIP-3 alpha) gene as one of the most up-regulated transcripts in NAFLD fibrosis relative to normal histology, validated in a replication group. CCL20 protein levels in serum measured in 224 NAFLD patients were increased in severe fibrosis (p < 0.001), with moderate correlation of hepatic transcript levels and serum levels. Expression of CCL20, but not its cognate receptor CC chemokine receptor 6, was significantly (p < 0.001) increased in response to fatty acid loading in LX-2 hepatic stellate cells, with relative increases greater than those in HepG2 hepatocyte cells. CONCLUSIONS: These results suggest that expression of CCL20, an important inflammatory mediator, is increased in NAFLD fibrosis. CCL20 serves as a chemoattractant molecule for immature dendritic cells, which have been shown to produce many of the inflammatory molecules that mediate liver fibrosis. These data also point to hepatic stellate cells as a key cell type that may respond to lipid loading of the liver.

Preoperative use of incretins is associated with increased diabetes remission after RYGB surgery among patients taking insulin: a retrospective cohort analysis.

OBJECTIVE: The main goal of this study was to determine the effects of incretins on type 2 diabetes (T2D) remission after Roux-en-Y gastric bypass (RYGB) surgery for patients taking insulin. BACKGROUND: Type 2 diabetes is a chronic disease with potentially debilitating consequences. RYGB surgery is one of the few interventions that can remit T2D. Preoperative use of insulin, however, predisposes to significantly lower T2D remission rates. METHODS: A retrospective cohort of 690 T2D patients with at least 12 months follow-up and available electronic medical records was used to identify 37 T2D patients who were actively using a Glucagon-like peptide 1 (GLP-1) agonist in addition to another antidiabetic medication, during the preoperative period. RESULTS: Here, we report that use of insulin, along with other antidiabetic medications, significantly diminished overall T2D remission rates 14 months after RYGB surgery (9%) compared with patients not taking insulin (56%). Addition of the GLP-1 agonist, however, increased significantly T2D early remission rates (22%), compared with patients not taking the GLP-1 agonist (4%). Moreover, the 6-year remission rates were also significantly higher for the former group of patients. The GLP-1 agonist did not improve the remission rates of diabetic patients not taking insulin as part of their pharmacotherapy. CONCLUSIONS: Preoperative use of antidiabetic medication, coupled with an incretin agonist, could significantly improve the odds of T2D remission after RYGB surgery in patients also using insulin.

Next-generation sequence analysis of genes associated with obesity and nonalcoholic fatty liver disease-related cirrhosis in extreme obesity.

OBJECTIVES: Genome-wide association studies (GWAS) have led to the identification of single nucleotide polymorphisms in or near several loci that are associated with the risk of obesity and nonalcoholic fatty liver disease (NAFLD). We hypothesized that missense variants in GWAS and related candidate genes may underlie cases of extreme obesity and NAFLD-related cirrhosis, an extreme manifestation of NAFLD. METHODS: We performed whole-exome sequencing on 6 Caucasian patients with extreme obesity [mean body mass index (BMI) 84.4] and 4 obese Caucasian patients (mean BMI 57.0) with NAFLD-related cirrhosis. RESULTS: Sequence analysis was performed on 24 replicated GWAS and selected candidate obesity genes and 5 loci associated with NAFLD. No missense variants were identified in 19 of the 29 genes analyzed, although all patients carried at least 2 missense variants in the remaining genes without excess homozygosity. One patient with extreme obesity carried 2 novel damaging mutations in BBS1 and was homozygous for benign and damaging MC3R variants. In addition, 1 patient with NAFLD-related cirrhosis was compound heterozygous for rare damaging mutations in PNPLA3. CONCLUSIONS: These results indicate that analyzing candidate loci previously identified by GWAS analyses using whole-exome sequencing is an effective strategy to identify potentially causative missense variants underlying extreme obesity and NAFLD-related cirrhosis.

An electronic health record-enabled obesity database.

BACKGROUND: The effectiveness of weight loss therapies is commonly measured using body mass index and other obesity-related variables. Although these data are often stored in electronic health records (EHRs) and potentially very accessible, few studies on obesity and weight loss have used data derived from EHRs. We developed processes for obtaining data from the EHR in order to construct a database on patients undergoing Roux-en-Y gastric bypass (RYGB) surgery. METHODS: Clinical data obtained as part of standard of care in a bariatric surgery program at an integrated health delivery system were extracted from the EHR and deposited into a data warehouse. Data files were extracted, cleaned, and stored in research datasets. To illustrate the utility of the data, Kaplan-Meier analysis was used to estimate length of post-operative follow-up. RESULTS: Demographic, laboratory, medication, co-morbidity, and survey data were obtained from 2028 patients who had undergone RYGB at the same institution since 2004. Pre-and post-operative diagnostic and prescribing information were available on all patients, while survey laboratory data were available on a majority of patients. The number of patients with post-operative laboratory test results varied by test. Based on Kaplan-Meier estimates, over 74% of patients had post-operative weight data available at 4 years. CONCLUSION: A variety of EHR-derived data related to obesity can be efficiently obtained and used to study important outcomes following RYGB.

Downregulation of PAR-4, a pro-apoptotic gene, in pancreatic tumors harboring K-ras mutation.

Oncogenic ras is known to inhibit cell death and growth inhibitory genes and activate prosurvival genes. Proapoptotic gene PAR-4, has been found to be downregulated by oncogenic ras. Since pancreatic tumors harbor a high incidence of K-ras point mutations, we hypothesized that oncogenic K-ras might influence the function and expression of PAR-4. PAR-4 expression levels were analyzed in 4 established pancreatic tumor cell lines, 10 normal pancreatic tissues, 44 frozen tumor tissues and 25 paraffin-embedded pancreatic adenocarcinoma samples by Real Time RT-PCR, Western blot analysis and immunohistochemistry. K-ras mutational status was analyzed by allele-specific oligonucleotide-hybridization. Expression levels of PAR-4 were correlated with the K-ras mutational status and clinical characteristics. Further, modulation of endogenous PAR-4 was tested by transiently expressing oncogenic ras in a wild-type K-ras pancreatic cancer cell line, BxPC-3. Three cell lines with K-ras mutations showed low levels of PAR-4 when compared to a normal pancreatic tissue. Of 44 frozen tumors, 16 showed appreciable upregulation of Par mRNA and 27 showed significant downregulation of PAR-4 mRNA when compared to normal pancreatic tissue and 1 had levels equivalent to normal pancreatic tissue. Of 25 paraffin-embedded tumors, 9 showed downregulation of PAR-4 protein and this downregulation of PAR-4 correlated significantly with K-ras mutational status (p < 0.00002). In addition, the presence of PAR-4 mRNA or protein expression in pancreatic tumors correlated with prolonged survival. Transient overexpression of oncogenic ras in wild-type K-ras BxPC-3 cells significantly downregulated the endogenous PAR-4 protein levels and conferred accelerated growth. Thus, downregulation or loss of PAR-4 expression by oncogenic ras may provide a selective survival advantage for pancreatic tumors, through inhibition of proapoptotic pathway mediated by PAR-4.

Outcomes of preoperative weight loss in high-risk patients undergoing gastric bypass surgery.

HYPOTHESIS: Modest, preoperative weight loss will improve perioperative outcomes among high-risk, morbidly obese patients undergoing Roux-en-Y gastric bypass. DESIGN: A prospective, longitudinal assessment of characteristics and outcomes of gastric bypass patients. SETTING: All patients undergoing open or laparoscopic Roux-en-Y gastric bypass surgery for morbid obesity or its comorbid medical problems at Geisinger Medical Center in Danville, Pennsylvania, during a 3-year period from May 31, 2002, to February 24, 2006, were included in this analysis. Patients were required to participate in a standardized multidisciplinary preoperative program that encompasses medical, psychological, nutritional, and surgical interventions and education. In addition, patients were encouraged to achieve a 10% loss of excess body weight prior to surgical intervention. RESULTS: Of the 884 subjects, 425 (48%) lost more than 10% of their excess body weight prior to the operation. After surgery (mean follow-up, 12 months), this group was more likely to achieve 70% loss of excess body weight (P < .001). Those who lost more than 5% of excess body weight prior to surgery were statistically less likely to have a length of stay of greater than 4 days (P = .03). CONCLUSIONS: This study shows that high-risk morbidly obese candidates for bariatric surgery who are able to achieve a loss of 5% to 10% excess body weight prior to surgery have a higher probability of a shorter length of hospital stay and more rapid postoperative weight loss.

Outcomes among elderly bariatric patients at a high-volume center.

BACKGROUND: Bariatric surgery in elderly patients remains controversial. With a growing morbidly obese elderly population, management strategies and treatment outcomes need to be evaluated. METHODS: We reviewed all bariatric cases from 2001 to 2005 at a single institution. The preoperative factors (body mass index, smoking status, co-morbid conditions, number of medications) and surgical information (operation and length of stay) were recorded. Patients >60 years old who had undergone Roux-en-Y gastric bypass (RYGB) were followed up, and their surgical outcomes were analyzed (reduction in medications, resolution of diabetes mellitus and hypertension, percentage of excess body weight loss, complications, and mortality). RESULTS: Of 1065 patients, 76 (7.1%) were aged > or =60 years. Of these 76 patients, 61 (5.7%) underwent RYGB. The other 989 patients (92.9%) were <60 years old, and 952 of these underwent RYGB. In the older group, the mean number of co-morbid conditions was 10 +/- 3.3, 70.5% had diabetes, and 83.6% had hypertension. In the younger group, the mean number of co-morbidities was 4.7 +/- 2.3. The mean number of preoperative medications was 10 +/- 4.5 in the older group compared with 6.0 +/- 4.3 in the younger group. The mean length of stay was 2.9 days in both groups. Postoperatively, medications were reduced by nearly 50% in both groups. Diabetes and hypertension resolved or improved significantly in both groups. The mean percentage of excess body weight loss was lower in the older patients (54.9% versus 60.1%; P = .09). The 90-day operative mortality rate was 1.64% in the older group versus 0.53% for the younger group (P = NS). CONCLUSION: Our data support the use of RYGB in older patients in programs prepared to comprehensively manage the medical co-morbidities. Although the percentage of excess body weight loss was less, the mortality was acceptable despite the greater number of co-morbidities. Both diabetes and hypertension were more common in this population, with trends toward better improvement after RYGB than in younger patients.

All-Cause and Specific-Cause Mortality Risk After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes.

OBJECTIVE: This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status. RESEARCH DESIGN AND METHODS: RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes. RESULTS: Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025), than control subjects without diabetes. CONCLUSIONS: All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

Obesity disease burden and surgical risk.

BACKGROUND: The rapid national expansion in bariatric surgical procedures has been accompanied by recent reports of significant complication rates. This has resulted in increased public scrutiny of bariatric surgery outcomes, restrictions on patient eligibility criteria by payors, and credentialing requirements for providers. This focus on outcomes has resulted in interest in bariatric risk analysis. METHODS: During an 8-year period, 1210 patients were evaluated for bariatric surgery. Clinical information was recorded prospectively. Co-morbid medical conditions were analyzed according to proven surgical risk factors: age, body mass index (BMI), and male gender. RESULTS: The prevalence of many co-morbid conditions and the total number of co-morbid conditions correlate highly with increasing age, increasing BMI, and male gender. CONCLUSION: The established surgical risk factors, age, BMI, and male gender, are markers for a sicker patient population, as evidenced by a greater obesity disease burden.

Nutrient Transporter Expression in the Jejunum in Relation to Body Mass Index in Patients Undergoing Bariatric Surgery.

Nutrient tranters (NT) facilitate nutrient absorption and contribute to the regulation of circulating nutrients. In this cross-sectional study, we determined the associations between the level of obesity; mRNA abundance for NTs; and serum concentrations of amino acids, short-chain fatty acids, and glucose in patients with morbid obesity undergoing a Roux-en-Y gastric bypass. Proximal jejunal samples were obtained at the time of surgery from 42 patients (90% female, age = 42.6 ± 11.9 years, pre-operative body mass index (BMI) = 55.5 ± 11.3 kg/m²) undergoing a Roux-en-Y gastric bypass. RNA was extracted from the jejunal mucosa and quantitative real-time-PCR was performed for the NTs studied. BMI negatively correlated with jejunal mRNA abundance of the amino acid NTs TauT (r = -0.625, p < 0.0001), ASCT2 (r = -0.320, p = 0.039), LAT1 (r = -0.304, p = 0.05). BMI positively correlated with jejunal mRNA abundance of the lactate/short-chain fatty acid NT SMCT1 (r = 0.543, p = 0.0002). Serum concentrations of the short-chain fatty acids, butyric, valeric, and isocaproic acid correlated positively with BMI (n = 30) (r = 0.45, r = 0.44, r = 0.36, p ≤ 0.05; respectively). Lower jejunal mRNA abundance for the amino acid NTs TauT, ASCT2, and LAT1 could protect against further obesity-related elevations in circulating amino acids. The positive correlation between BMI and the jejunal mRNA abundance of the high-affinity short-chain fatty acid/monocarboxylate transporter SMCT1 is intriguing and requires further investigation.

Feasibility and impact of an evidence-based program for gastric bypass surgery.

BACKGROUND: Health care in the United States is expensive and quality is variable. The aim of this study was to investigate whether our integrated health system, composed of academic hospitals, a practice plan, and a managed care payer, could reliably implement an evidence-based program for gastric bypass surgery. A secondary aim was to evaluate the impact of the program on clinical outcomes. STUDY DESIGN: A standardized program for delivery of clinical best-practice elements for patients undergoing initial open or laparoscopic Roux-en-Y gastric bypass was implemented in 2008. Best-practice elements were embedded into the workflow. The best-practice elements were refined after reviewing failures observed during the early implementation period. The study period was divided into 3 groups: group α = year preceding program implementation (control), group ß = first year of implementation (unreliable), and group Ω = 2nd to 4th years of implementation (reliable). Outcomes data were collected for all patients who had undergone Roux-en-Y gastric bypass between May 2008 and April 2012 and were compared with a control group from the preceding year using multiple logistic regression analysis. RESULTS: Two thousand and sixty-one patients were studied, with no significant demographic differences between study groups. Best-practice elements delivery was 40% in group ß, but was >90% for group Ω (p < 0.001). Length of stay for group α was 3.5 days and improved to 2.2 days (p < 0.001) for group Ω. Complications and readmission rates improved considerably with reliable delivery of best-practice elements. CONCLUSIONS: Standardization of evidence-based care delivery for Roux-en-Y gastric bypass was feasible and reliable delivery of this pathway improved clinical outcomes.

Utility of Ultrasound, Transaminases, and Visual Inspection to Assess Nonalcoholic Fatty Liver Disease in Bariatric Surgery Patients.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common in adults with extreme obesity and can impact long-term health and survival. Liver biopsy is the only accurate test for diagnosis and staging, but is invasive and costly. Non-invasive testing offers an attractive alternate, but the overall accuracy remains a significant issue. This study was conducted to determine the accuracy and clinical utility of pre-operative ultrasound and liver transaminase levels, as well as intra-operative hepatic visual inspection, for assessing presence of NAFLD as confirmed by hepatic histology. METHODS: Data was collected prospectively from 580 morbidly obese adult patients who underwent Roux-en-Y gastric bypass surgery with intraoperative wedge biopsy between January 2004 and February 2009. Complete data for ultrasound, ALT and AST levels, and documented visual inspection was available for 513 patients. RESULTS: The prevalence of NAFLD was 69 % and that of NASH was 32 %. The individual non-invasive clinical assessments demonstrated low sensitivity, specificity, and accuracy for detecting the presence of steatosis, steatohepatitis, or fibrosis. The combination of normal or abnormal results for all tests improved predictive utility. Abnormal tests with all three assessments had a sensitivity of 95-98 % and a specificity of 28-48 % for major histologic findings in NAFLD/NASH. Normal tests with all three assessments had a sensitivity of 12-22 % and a specificity of 89-97 % for major histologic findings in NAFLD/NASH. CONCLUSIONS: Although individual clinical tests for NAFLD have limited accuracy, the use of combined clinical tests may prove useful.

Same-day combined endoscopic retrograde cholangiopancreatography and cholecystectomy: Achievable and minimizes costs.

BACKGROUND: It is estimated that choledocholithiasis is present in 5% to 20% of patients at the time of laparoscopic cholecystectomy (LC). Several European studies have found decreased length of stay (LOS) when performing LC and intraoperative endoscopic retrograde cholangiopancreatography (ERCP) on the same day for choledocholithiasis. In the United States, common bile duct stones are usually managed preoperatively and typically on a day separate from the day LC was performed. Our aim was to evaluate LOS and total hospital cost for separate-day versus same-day ERCP/cholecystectomy. METHODS: This was a retrospective study of patients undergoing ERCP and cholecystectomy during the same admission for the management of choledocholithiasis from 2010 to 2014 at Geisinger Medical Center. The separate-day group underwent ERCP at least 1 day before cholecystectomy and often underwent two separate anesthesia events, while the same-day group had ERCP and cholecystectomy performed on the same day under one general anesthesia event. The primary outcome measured was LOS. RESULTS: The study population included 240 patients. There were 175 patients in the separate-day group and 65 patients in the same-day group. Median age was similar between the two groups. The separate-day group had a median of one minor comorbidity compared with zero within the same-day group using the Charlson Comorbidity Index. Overall, LOS for the separate-day group was 5 days compared with 3 days in the same-day group (p < 0.0001). There was no difference in conversion rates to open cholecystectomy between the two groups (14% in the separate-day vs. 12% in the same-day group). Total median hospital cost for the separate-day group was $102,537 compared with $90,269 in the same-day group (p < 0.0001). CONCLUSION: Same-day ERCP and cholecystectomy is feasible and minimizes costs. Same-day procedures decreased hospital LOS by 2 days and had approximately $12,000 in cost savings. Future goals include a multidisciplinary protocol to study outcomes in larger numbers. LEVEL OF EVIDENCE: Therapeutic study, level IV. Economic study, level III.

Perturbations of fibroblast growth factors 19 and 21 in type 2 diabetes.

Fibroblast growth factors 19 and 21 (FGF19 and FGF21) have been implicated, independently, in type 2 diabetes (T2D) but it is not known if their circulating levels correlate with each other or whether the associated hepatic signaling mechanisms that play a role in glucose metabolism are dysregulated in diabetes. We used a cross-sectional, case/control, experimental design involving Class III obese patients undergoing Roux-en-Y bariatric surgery (RYGB), and measured FGF19 and FGF21 serum levels and hepatic gene expression (mRNA) in perioperative liver wedge biopsies. We found that T2D patients had lower FGF19 and higher FGF21 serum levels. The latter was corroborated transcriptionally, whereby, FGF21, as well as CYP7A1, ß-Klotho, FGFR4, HNF4α, and glycogen synthase, but not of SHP or FXR mRNA levels in liver biopsies were higher in T2D patients that did not remit diabetes after RYGB surgery, compared to T2D patients that remitted diabetes after RYGB surgery or did not have diabetes. In a Phenome-wide association analysis using 205 clinical variables, higher FGF21 serum levels were associated with higher glucose levels and various cardiometabolic disease phenotypes. When serum levels of FGF19 were < 200 mg/mL and FGF21 > 500 mg/mL, 91% of patients had diabetes. These data suggest that FGF19/FGF21 circulating levels and hepatic gene expression of the associated signaling pathway are significantly dysregulated in type 2 diabetes.

Bariatric surgery: shedding the monetary weight of prescription costs in the managed care arena.

BACKGROUND: Prescription costs for treatment of comorbidities associated with morbid obesity is a considerable annual health-care expenditure. This study addressed the effect of Roux-en-Y gastric bypass (RYGBP) on diabetic and anti-hypertensive pharmaceutical utilization and cost savings at our institution. METHODS: Retrospective data from the electronic database of 51 consecutive patients, who underwent RYGBP from March 2001 to May 2002 were studied. Patients had BMI >40 associated with obesity-related diabetes and hypertension. Prescription medications utilized by this cohort were reviewed preoperatively and at 3- and 9-month intervals postoperatively. Significance was analyzed by paired t-test. RESULTS: Prevalence of diabetes and hypertension was 55.7% (29/53) and 44.3% (24/53) respectively, and 34% (18/53) patients had both co-morbidities. Preoperatively, patients were on an average of 2.44 +/- 1.86 medications at a cost of 187.24 USD +/- 237.41 USD per month. Postoperatively, the mean number of medications was reduced to 0.56 +/- 0.81 agents (P<0.001) at a monthly cost of 42.53 USD +/- 116.60 (P<0.001). CONCLUSIONS: RYGBP can decrease the prescription medication requirements, resulting in significant cost-savings in the treatment of obesity-related hypertension and diabetes. This study found a 77.3% reduction in total cost of diabetic and anti-hypertensive medications.

Laparoscopic cholecystectomy for elderly patients: gold standard for golden years?

HYPOTHESIS: Laparoscopic cholecystectomy (LC) has known physiological benefits and positive socioeconomic effects over the open procedure. Although recent studies have questioned the technique's efficacy in elderly patients (>65 years), we hypothesize that LC is safe and efficacious in that patient group. METHODS: Five thousand eight hundred eighty-four consecutive patients (mean age, 40 years; 26% male) underwent an attempted LC (conversion rate, 5.2%) from 1991 to 2001 at a teaching institution. Of these, 395 patients (6.7%) were older than 65 years. Analysis included patient age, sex, American Society of Anesthesiologists classification, conversion rate, morbidity, mortality, and assessment of results over time. RESULTS: Elderly patients were predominantly male (64%). Septuagenarians had a 40% incidence of complicated gallstone disease, such as acute cholecystitis, choledocholithiasis, or biliary pancreatitis, and octogenarians had a 55% incidence. Overall mortality was 1.4%. The conversion rate was 17% for the first 5 years of the study period and 7% for the second half. The conversion rate was 22% for patients with complicated disease and 2.5% for patients with chronic cholecystitis. Average hospital stay decreased from 10.2 days to 4.6 days during the first and second half of the study period, respectively. CONCLUSIONS: The results of LC in patients aged 65 to 69 years are comparable with those previously reported in younger patients. Patients older than 70 years had a 2-fold increase in complicated biliary tract disease and conversion rates, but a low mortality rate (2%) compared with results of other authors (12%), despite an increase in American Society of Anesthesiologists classification. Increased technical experience with LC favorably affected outcomes over time. Early diagnosis and treatment prior to onset of complications are necessary for further improvement in the outcomes of elderly patients undergoing LC.

Intraoperative parathyroid hormone assay: an accurate predictor of symptomatic hypocalcemia following thyroidectomy.

HYPOTHESIS: Intraoperative parathyroid hormone (IOPTH) assay is useful for predicting symptomatic hypocalcemia following total thyroidectomy. DESIGN: A prospective study of 30 patients undergoing total thyroidectomy with IOPTH levels obtained following skin closure and ionized calcium (Ca2+) levels obtained 6 hours postoperatively and on postoperative day 1. All patients were evaluated for symptoms of hypocalcemia. SETTING: University teaching hospital. MAIN OUTCOME MEASURES: Patients who developed symptomatic hypocalcemia were compared with asymptomatic patients in regard to age, diagnosis, thyroid weight, thyrotropin level, Ca2+ level, parathyroid status, and IOPTH level. RESULTS: The onset of symptomatic hypocalcemia ranged from 8 to 48 hours postoperatively (n = 10). One patient required readmission. Of 10 patients with symptoms, 5 developed tetany. There were no significant differences in age, diagnosis, thyroid weight, thyrotropin level, or the number of parathyroid glands preserved in patients with or without symptomatic hypocalcemia. All patients with an IOPTH level of less than 10 pg/mL (1.1 pmol/L) had symptoms (n = 8). The mean +/- SD IOPTH level (7.6 +/- 12.0 pg/mL [0.8 +/- 1.3 pmol/L]) in patients who developed symptomatic hypocalcemia was significantly lower than the mean IOPTH level (55.7 +/- 31.8 pg/mL [5.9 +/- 3.3 pmol/L]) in patients without symptoms (P =.001). The 6-hour and postoperative day 1 Ca2+ levels were significantly lower in patients with symptomatic hypocalcemia (P =.19 and P =.13, respectively). An IOPTH level of less than 10 pg/mL is 80% sensitive and 100% specific for the development of symptomatic hypocalcemia. CONCLUSION: The incorporation of the IOPTH assay in the management of thyroid disease is recommended to prevent and prospectively treat symptomatic hypocalcemia, thereby reducing readmissions following thyroidectomy.

Reasons for conversion from laparoscopic to open cholecystectomy: a 10-year review.

Laparoscopic cholecystectomy is now considered the "gold standard" operation for patients with gallstone disease. A number of patients require conversion to an open cholecystectomy for the safe completion of the procedure. This study investigates how the etiology and incidence of conversion from laparoscopic to open cholecystectomy has changed over time. All 5884 patients undergoing laparoscopic cholecystectomy between March 1991 and June 2001 were prospectively collected in a database. A total of 310 patients (5.2%) had had their cholecystectomies converted to an open procedure. The mortality rate for these patients was 0.7%. Causes for conversion were inability to correctly identify anatomy (50%), "other" indications (16%), bleeding (14%), suspected choledocholithiasis (11%), and suspected bile duct injury (8%). After an initial learning curve in thin patients with symptomatic cholelithiasis, inclusion of patients with acute cholecystitis, morbid obesity, or a prior celiotomy resulted in a peak conversion rate of 11% by 1994. From 1994 to the first half of 2001, the conversion rate has declined significantly for all patients (10% to 1%), as well as for patients with acute cholecystitis (26% to 1%). Although unclear anatomy secondary to inflammation remains the most common reason for conversion, the impact of acute cholecystitis on the operative outcome has decreased with time.

Is thyroid frozen section too much for too little?

BACKGROUND: The role of frozen section (FS) in thyroid disease is controversial. The goal of this study was to identify a cohort of patients who may or may not benefit from FS. METHODS: Two hundred thirty-one patients who underwent thyroidectomy were evaluated in regard to fine-needle aspiration (FNA), FS, and the extent of surgery. RESULTS: In all, 155 patients underwent FNA, 140 patients underwent FS, and 103 patients had both. A final diagnosis of malignancy was obtained in 47 of 231 patients. FNA had a sensitivity of 50% and a specificity of 99%, and FS had a sensitivity of 50% and a specificity of 100% for diagnosing malignancy. Accounting for the clinical findings and FNA results, FS results altered the extent of thyroidectomy in 1 of 103 patients. CONCLUSIONS: The increased costs for the operative time and the pathologists needed to obtain routine FS are not supported with any substantial benefit in patient outcome.