Quantifying Carcinoembryonic Antigen-like Cell Adhesion Molecule-Targeted Liposome Delivery Using Imaging Flow Cytometry.

Carcinoembryonic antigen-like cell adhesion molecules (CEACAMs) are human cell-surface proteins that can exhibit increased expression on tumor cells and are thus a potential target for novel tumor-seeking therapeutic delivery methods. We hypothesize that engineered nanoparticles containing a known interaction partner of CEACAM, Neisseria gonorrhoeae outer membrane protein Opa, can be used to deliver cargo to specific cellular targets. In this study, the cell association and uptake of protein-free liposomes and Opa proteoliposomes into CEACAM-expressing cells were measured using imaging flow cytometry. A size-dependent internalization of liposomes into HeLa cells was observed through endocytic pathways. Opa-dependent, CEACAM1-mediated uptake of liposomes into HeLa cells was observed, with limited colocalization with endosomal and lysosomal trafficking compartments. Given the overexpression of CEACAM1 on several distinct cancers and interest in using CEACAM1 as a component in treatment strategies, these results support further pursuit of investigating Opa-dependent specificity and the internalization mechanism for therapeutic delivery.

Asymptomatic Cholelithiasis and Bariatric Surgery: a Comprehensive Long-Term Analysis of the Risks of Biliary Disease in Patients Undergoing Primary Roux-en-Y Gastric Bypass.

PURPOSE: Currently, there is little consensus on management of the in situ gallbladder of patients undergoing gastric bypass. Our aim was to evaluate outcomes of selective concomitant cholecystectomy (CCY) and long-term biliary outcomes after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We performed a retrospective analysis of patients undergoing laparoscopic RYGB (LRYGB) between 2008 and 2018. Chi-square, Fisher's exact, or Wilcoxon rank-sum tests were used to compare outcomes. Concomitant CCY was performed on a selective basis. RESULTS: Three thousand and four patients underwent a RYGB (LRYGB n = 2458, open RYGB n = 546). Fifty-two percent (n = 1670) of patients had undergone CCY at any stage. Thirty-one percent of patients (n = 933) had CCY prior to RYGB, 13% (n = 403) had a concomitant CCY and 13% (n = 214) of the remainder required interval CCY. In the LRYGB subgroup, 29.9% (n = 735) had a prior CCY; 12.9% (n = 202) of those with an in situ gallbladder required interval CCY. Those who underwent concomitant CCY/LRYGB (n = 328) were compared with LRYGB alone (n = 1231). The concomitant CCY group was significantly older and had higher percentage of females, higher preoperative BMI, higher Charlson Comorbidity Index, and a higher medication count. There was no significant difference in BMI nadir, length of stay, complications, or mortality. Interval CCY had a higher incidence of CCY-related complications. CONCLUSION: Our study suggests a higher percentage of bariatric patients with in situ gallbladders will undergo interval CCY than documented in recently published guidelines. Concomitant CCY can be performed without an increase in length of stay or complications. Interval CCY may be associated with a higher complication rate.

The Longitudinal Efficiency of Robotic Surgery: an MBSAQIP Propensity Matched 4-Year Comparison of Robotic and Laparoscopic Bariatric Surgery.

BACKGROUND: The objective of this study was to examine the MBSAQIP database to assess efficiency trends and perioperative outcomes in robotic bariatric surgery. METHODS: Robotic (RA) and laparoscopic (L) sleeve gastrectomy (SG) and gastric bypass (RYGB) were compared using the 2015-2018 MBSAQIP Participant Use Data Files. Patients were propensity matched 1:1 based on sex, body mass index, assistant, and previous obesity or foregut surgery. A total of 93,802 patients were included. RESULTS: Median operative times were significantly longer for both RA-SG (89 vs. 62 min; p < 0.0001) and RA-RYGB (141 vs. 105 min; p < 0.0001) compared with laparoscopic. Over the 4-year period, the difference in operative times (OR delta) between RA-SG and L-SG was unchanged while the difference in operative times between RA-RYGB and L-RYGB increased. Both robotic groups were significantly more likely to be readmitted (RA-SG p = 0.001, RA-RYGB p = 0.006). Robotic SG was more likely to have a reintervention (p = 0.018) and extended length of stay (LOS) (> 4 days) compared with laparoscopic (p = < 0.0002). No significant differences were noted in morbidity and mortality by approach. CONCLUSIONS: Operative times were 30% longer for RA-SG and 25% longer for RA-RYGB when compared with laparoscopic. There was no significant improvement in OR delta for either RA-SG or RA-RYGB over the four years. Readmission rates were higher for both RA-SG and RA-RYGB. Robotic SG had a greater percentage of patients with extended LOS compared with laparoscopic. No evidence of improved efficiency for robotic bariatric surgery as defined by operative time or clinical outcomes was identified.

Comparison of short-term outcomes following Roux-en-Y gastric bypass in male and female patients using the MBSAQIP database.

BACKGROUND: Male sex has long been identified as a risk factor for adverse outcomes, including mortality, after Roux-en-Y gastric bypass (RYGB). OBJECTIVES: The objective of this study was to compare short-term outcomes of patients undergoing laparoscopic RYGB based on biologic sex. SETTING: Geisinger Medical Center, Danville, PA. METHODS: Patients undergoing RYGB in the 2015, 2016, and 2017 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database were propensity matched 1:1 to compare 30-day outcomes between male and female sex. RESULTS: A total 47,906 patients were included (23,953 men/23,953 women). The overall complication rate was higher in female patients (11.5% versus 10.2%; P < .001) with no difference in mortality related to RYGB at 30 days. No significant differences were seen between sexes for organ space surgical site infection or septic shock. Women had significantly more superficial surgical site infections (P = .002), urinary tract infections (P < .001), readmissions (P < .001), and reinterventions (P < .001). Men had significantly more episodes of unplanned intubation (P = .008), extended ventilator use (P = .01), progressive renal insufficiency (P = .01), acute renal failure (P = .008), cardiac arrest (P = .005), intensive care unit admission (P < .001), all-cause 30-day mortality (P = .038), and inpatient mortality rate (P < .001). CONCLUSIONS: Male sex has been identified as a risk factor for adverse events and mortality after RYGB in several risk models. This study demonstrates an overall increased risk of both all-cause mortality and inpatient mortality. The study, however, did not demonstrate a difference in bariatric-related mortality. The prevalence of both major and minor complications was mixed between sexes, while women had a higher overall complication rate after RYGB. The abundance of data available within the MBSAQIP Participant Use Data File facilitates the creation of tools like risk models for bariatric surgery, such as the MBSAQIP Risk calculator.

Bariatric surgery is safe and effective in Medicare patients regardless of age: an analysis of primary gastric bypass and sleeve gastrectomy outcomes.

BACKGROUND: Numerous studies have shown that bariatric surgery in older patients is safe and effective. However, both the Agency for Healthcare Research and Quality (AHRQ) and a Medicare Evidence Advisory Committee (MEDCAC) have cited gaps in the evidence for outcomes in Medicare patients undergoing bariatric surgery. These gaps are predominantly in the safety and outcomes evidence in Medicare patients younger than 65 years old (Centers for Medicare and Medicaid Services [CMS] < 65). OBJECTIVES: The aim of our study was to review both the safety and efficacy of gastric bypass (RYGB) and sleeve gastrectomy (SG) in Medicare patients compared with other payers. SETTING: A single academic medical center. METHODS: A prospectively maintained database of 3300 patients who underwent bariatric surgery between January 2007 and December 2017 was utilized. The outcomes of Medicare patients undergoing RYGB and SG were analyzed and compared to those of similar patients covered by Medicaid or Commercial insurers. RESULTS: There were too few patients with commercial insurance older than 65 to compare to those with Medicare (CMS ≥ 65). Mortality at 90 days for CMS ≥ 65 was 1.3% and the overall complication rate was 20.1% (minor 15.6%; major 7.1%). Total weight loss (TWL) at 6 months and 1, 2, and 3 years was 25.3%, 30.0%, 29.9%, and 29.4% respectively. For any time after surgery, 23% of CMS ≥ 65 had complete remission of diabetes and 45% had partial remission. Demographic analysis of CMS < 65 found Medicare patients were significantly older with more diabetes, hypertension and hyperlipidemia than those with commercial payers. Mortality at 90 days for CMS < 65 was 0.6% and the overall complication rate was 18.3% (minor 14.3%; major 4.7%). Mortality was not significantly different between payers. After adjustment for baseline differences and comparing to the Medicare group, the commercial group was less likely to have minor complications (P = .019), any complications (P = .007), and extended length of stay (P < .001). The TWL for the entire cohort age <65 at 6 months and 1, 2, and 3 years was 28.1%, 34.1%, 34.1%, and 31.8% respectively. After adjusting for differences, there was no significant difference in TWL between payers. For any time after surgery, complete remission of diabetes was 45% in CMS < 65 patients and partial remission was 59%. The comparison of remission between groups was then adjusted for DiaRem score and surgery type. CMS < 65 patients had significantly less partial remission of diabetes than commercial patients (P = .034) but no difference in complete remission. CONCLUSIONS: RYGB and SG are both safe and effective in Medicare patients of all ages. CMS ≥ 65 have acceptable mortality and complication rates with TWL and diabetes remission similar to younger patients. CMS < 65 patients are older than those with commercial insurance with more comorbid disease. While they have longer hospital stays after bariatric surgery, their weight loss and complete remission of diabetes are no different than patients with Medicaid or commercial insurance. This study helps fill an important evidence gap in bariatric surgical patients raised by both Agency for Healthcare Research and Quality, and a Medicare Evidence Advisory Committee.