Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells.

OBJECTIVES: Obesity, a risk factor for pancreatic adenocarcinoma (PDAC), is often accompanied by a systemic increase in lipopolysaccharide (LPS; metabolic endotoxemia), which is thought to mediate obesity-associated inflammation. However, the direct effects of LPS on PDAC cells are poorly understood. METHODS: The expression of toll-like receptor 4, the receptor for LPS, was confirmed in PDAC cell lines. AsPC-1 and PANC-1 cells were exposed to LPS, and differential gene expression was determined by RNA sequencing. The activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by LPS in PDAC cells was assessed by Western blotting. RESULTS: The expression of toll-like receptor 4 was confirmed in all PDAC cell lines. The exposure to LPS led to differential expression of 3083 genes (426 ≥5-fold) in AsPC-1 and 2584 genes (339 ≥5-fold) in PANC-1. A top canonical pathway affected by LPS in both cell lines was PI3K/Akt/mTOR. Western blotting confirmed activation of this pathway as measured by phosphorylation of the ribosomal protein S6 and Akt. CONCLUSIONS: The exposure of PDAC cells to LPS led to differential gene expression. A top canonical pathway was PI3K/Akt/mTOR, a known oncogenic driver. Our findings provided evidence that LPS can directly induce differential gene expression in PDAC cells.

Underrepresentation of pediatric operations in the relative value unit updating process.

BACKGROUND: The Relative Value Unit (RVU) system was designed and implemented by Medicare to standardize physician payments for a given service. Because Medicare primarily cares for older adults, RVU assignments and updates may not consider pediatric-specific procedures, despite the fact that private insurers and Medicaid often base their payments on these RVU valuations. METHODS: The CPT codes of index pediatric operations were retrieved from the ACGME. We categorized these procedures into "Peds-specific" (eg, Ladd Procedure) versus those that could be performed in both children and adults, or "Non-specific" (eg, fundoplication). We merged these codes with RVU information from publicly available CMS files and the Resource-based Relative Value Scale Data Manager. Variables included were the date of last RVU update and the vignette used by survey respondents when asked to update the RVU valuation. RESULTS: Among 85 procedures, nearly three-quarters were Peds-specific (74%), with the remainder Non-specific. Approximately half of the 85 procedures (52%) had never been updated. Compared to Non-specific CPT codes, Peds-specific CPT codes were less likely to have been updated (38% vs. 91%, p < 0.001) and, among those that were updated, were updated more remotely (median year 2000 vs. 2005, p = 0.02). Among updated Non-specific CPT codes, the vignette written to justify the valuation was based on an adult patient in 85% of cases. CONCLUSIONS: Peds-specific surgical CPT codes have either never been updated or have not been updated in decades. Procedures performed in both children and adults have been updated more often and more recently, but the vignette on which this valuation is based on is typically an adult patient. In order to remain relevant and reimburse pediatric surgeons accurately, the RVUs for pediatric procedures need to also be prioritized for revision and updating.

Assessing Knowledge and Perceptions of Colorectal Cancer Screening in Armenia.

BACKGROUND: Armenia has a high incidence of and mortality from colorectal cancer (CRC). No organized screening programs for CRC exist in Armenia. This study seeks to evaluate knowledge of and attitudes toward CRC and screening programs in Armenia. METHODS: Adults aged 40-64 y were administered a survey using convenience sampling throughout polyclinics in Yerevan city. Survey questions were based on the Health Belief Model and were translated and modified for local relevance. RESULTS: A total of 368 surveys were completed. Eighty-four percent had knowledge of CRC, 91% believed that early detection leads to improved outcomes, but only 22% had knowledge of screening. Women were more likely to have knowledge of CRC (odds ratio 2.19, P < 0.05). Although 19% have personally worried about having CRC, only 7% admitted to discussing their worries with a provider and 76% were willing to undergo screening if recommended by their doctor. Seventy-eight percent of respondents would only undergo screening if free or less than ~$20 USD. CONCLUSIONS: Self-reported knowledge of CRC is high, whereas knowledge of screening remains low in Armenia. There is a willingness to undergo screening if recommended by a health care professional; however, this willingness is cost-sensitive. Interventions aimed at (1) increasing awareness of the disease and screening tests, (2) improving physician counseling, and (3) reducing financial barriers to screening should be considered along with the implementation of a national screening program in Armenia.

The impact of removing global periods on pediatric surgeon reimbursement.

PURPOSE: CMS has proposed removing postoperative care from the global periods for surgical procedures and instead requiring surgeons to bill for postoperative visits using evaluation & management (E&M) codes. This policy may alter reimbursement to pediatric surgeons. METHODS: To assess the impact of this policy, NSQIP-pediatric data were used to calculate median LOS for high-volume procedures with 10 or 90 day global periods. We then merged these data with CMS physician work time and RVU files. A CMS LOS variable was created by counting the number of hospital-based E&M codes built into the global period based on the fact that if global periods are removed, surgeons may only bill one E&M code per postoperative day. We then compared the CMS and NSQIP LOS values. RESULTS: The dataset included 201 CPT codes with NSQIP LOS estimates derived from a median of 137 operations. Twenty-nine procedures (14.4%) had higher, 24 (16.9%) had the same, and 138 (68.7%) had lower NSQIP median LOS than current CMS values. On average, NSQIP values were 40.0% (95% confidence interval [95CI] -50.0, -29.9%) lower than CMS values. Based on a daily average work RVU per postoperative E&M code of 1.09 (95% CI 1.05, 1.12), and $35.78 per RVU (2017 rate), surgeons in this sample would experience a cumulative annual reduction in reimbursement of approximately $3.4 M following the policy change. CONCLUSIONS: Most pediatric surgical procedures have RVU valuations that include more hospital-based E&M codes than the current median number of postoperative days. Holding all else equal, the removal of global periods would therefore reduce reimbursement for pediatric surgeons. The downstream effects of this policy change, such as the impact on the quality of clinical care, are uncertain and warrant further investigation. TYPE OF STUDY: Clinical research paper. LEVEL OF EVIDENCE: Level II.

Postoperative Physician Phone Calls as a Method to Decrease Urgent Care and Emergency Department Returns After Ambulatory General Surgery.

Unplanned returns after ambulatory surgery pose a burden to patients and health care providers alike. We hypothesized that a postoperative phone call by a physician would decrease avoidable returns to urgent care (UC) or the emergency department (ED) in the week after anorectal (AR), laparoscopic cholecystectomy (LC), inguinal hernia repair (IHR), and umbilical hernia repair (UHR) operations. A retrospective analysis from 1/2011 to 12/2015 across 14 Kaiser hospitals was conducted to determine baseline UC/ED return rates of patients pre-call. Between 10/2017 and 06/2019, physicians placed phone calls to patients within postoperative days (PODs) 1-4. The cohorts were compared using chi-squared analysis with significance determined at P < .05. In total, 276 patients received a call, with the majority placed on PODs 1-3. There were no statistically significant differences in return rates between the pre- and post-call groups. All of the AR, 50.0% of LC, 66.7% of IHR, and 50.0% of UHR patients returned prior to phone call placement. Our data indicate that a physician phone call does not help in decreasing UC/ED returns. However, it is noteworthy that many of the returns occurred pre-call placement. Future directions should be aimed at placing earlier postoperative phone calls.

Differences in Outcomes Based on Sex for Pediatric Patients Undergoing Pyloromyotomy.

BACKGROUND: Males and females are known to have varied responses to medical interventions. Our study aimed to determine the effect of sex on surgical outcomes after pyloromyotomy. MATERIALS AND METHODS: Using the Kids' Inpatient Database for the years 2003-2012, we performed a serial, cross-sectional analysis of a nationally representative sample of all patients aged <1 y who underwent pyloromyotomy for hypertrophic pyloric stenosis. The primary predictor of interest was sex. Outcomes included mortality, in-hospital complications, cost, and length of stay. Regression models were adjusted by race, age group, comorbidity, complications, and whether operation was performed on the day of admission with region and year fixed effects. RESULTS: Of 48,834 weighted operations, 81.8% were in males and 18.2% were in females. The most common reported race was white (47.3%) and most of the patients were ≥29 days old (72.5%). There was no difference in the odds of postoperative complications, but females had a significantly longer length of stay (incidence rate ratio, 1.28; 95% confidence interval [95% CI], 1.18-1.39; P ≤ 0.01), higher cost (5%, 95% CI, 1.02-1.08; P ≤ 0.01), and higher odds of mortality (odds ratio, 3.26; 95% CI, 1.52-6.98; P ≤ 0.01). CONCLUSIONS: Our study demonstrated that females had worse outcomes after pyloromyotomy compared with males. These findings are striking and are important to consider when treating either sex to help set physician and family expectations perioperatively. Further studies are needed to determine why such differences exist and to develop targeted treatment strategies for both females and males with pyloric stenosis.

The contemporary appendectomy for acute uncomplicated appendicitis in children.

BACKGROUND: National, procedure-specific clinical registries are increasingly available in surgery, although data about children have lagged behind. Data related to the surgical management of appendicitis in children have become available recently and can be used to inform patient and family expectations and to identify clinical areas in need of ongoing improvement. METHODS: Cases of acute, uncomplicated appendicitis in children (<18 years of age) were extracted from the 2017 pediatric appendectomy-targeted file of the American College of Surgeons National Surgical Quality Improvement Program. Epidemiologic data were generated across 5 domains: (1) patient characteristics/severity, (2) preoperative imaging patterns, (3) characteristics of the operation, (4) pathologic outcomes, and (5) postoperative morbidity and mortality. RESULTS: The final sample included 9,507 appendectomies for acute, uncomplicated appendicitis performed at 106 hospitals. The population was predominantly male (60.6%), involving children 6 to 12 years of age (55.3%). Only 2.9% of patients did not have imaging before their appendectomy. Overall, 38.2% received a computed tomography; however, patients transferred with imaging received computed tomography at 3.8 times the rate of those with only local (ie, operating hospital) imaging. Laparoscopy was used in 94.6% of cases, with 1.1% converted to open. Negative appendectomy and complication rates were 3.3% and 2.1%, respectively. Children ≤5 years of age had 2.3 greater odds of negative appendectomy than children 6 to 17 years of age. CONCLUSION: Children undergoing operation for acute, uncomplicated appendicitis have excellent clinical outcomes, although children ≤5 years of age have an increased risk of negative appendectomy. Despite guidelines against their use, more than one-third of children received a computed tomography before operation, driven predominantly by transferring hospitals.

Emerging Evidence for the Clinical Relevance of Pancreatic Cancer Exosomes.

The last 5 years have seen a dramatic increased interest in the field of exosome biology. Although much is unknown about the role of exosomes in human health and disease, disparate scientific disciplines are recognizing the highly conserved role that exosomes play in fundamental biological processes. Recently, there have been intriguing discoveries defining the role of exosomes in cancer biology. We performed a structured review of the English-language literature using the PubMed database searching for articles relating to exosomes and pancreatic ductal adenocarcinoma (PDAC). Articles were screened for relevance and content to judge for inclusion. Evidence implicates exosomes in the pathogenesis, local progression, metastasis, immune evasion, and intercellular communication of PDAC. Basic science discoveries in exosome biology have the potential to change the clinical management of PDAC, where, despite advances in early detection, diagnosis, staging, chemotherapy, and surgery, survival rates have been stagnant for decades and PDAC remains the most deadly human gastrointestinal malignancy.

Antibiotic stewardship in the newborn surgical patient: A quality improvement project in the neonatal intensive care unit.

BACKGROUND: There is significant diversity in the utilization of antibiotics for neonates undergoing surgical procedures. Our institution standardized antibiotic administration for surgical neonates, in which no empiric antibiotics were given to infants with surgical conditions postnatally, and antibiotics are given no more than 72 hours perioperatively. METHODS: We compared the time periods before and after implementation of antibiotic protocol in an institution review board-approved, retrospective review of neonates with congenital surgical conditions who underwent surgical correction within 30 days after birth. Surgical site infection at 30 days was the primary outcome, and development of hospital-acquired infections or multidrug-resistant organism were secondary outcomes. RESULTS: One hundred forty-eight infants underwent surgical procedures pre-protocol, and 127 underwent procedures post-protocol implementation. Surgical site infection rates were similar pre- and post-protocol, 14% and 9% respectively, (P = .21.) The incidence of hospital-acquired infections (13.7% vs 8.7%, P = .205) and multidrug-resistant organism (4.7% vs 1.6%, P = .143) was similar between the 2 periods. CONCLUSION: Elimination of empiric postnatal antibiotics did not statistically change rates of surgical site infection, hospital-acquired infections, or multidrug-resistant organisms. Limiting the duration of perioperative antibiotic prophylaxis to no more than 72 hours after surgery did not increase the rate of surgical site infection, hospital-acquired infections, or multidrug-resistant organism. Median antibiotic days were decreased with antibiotic standardization for surgical neonates.

Infectious outcomes of gastroschisis patients with intraoperative hypothermia.

BACKGROUND: Perioperative hypothermia decreases nutrient and oxygen delivery to tissues and, in adult studies, increases the risk of infectious complications (ICs). Gastroschisis (GS) places newborns at risk for hypothermia by nature of exposed viscera and excessive heat loss. Although hypothermia is a known cause of mortality in GS, the rate of ICs in this at-risk cohort has not yet been delineated. MATERIALS AND METHODS: A retrospective cohort study was performed at our single tertiary-referral hospital, evaluating patient and operative characteristics of all GS infants who underwent operative closure. Intraoperative temperatures were recorded, defining hypothermia as mild (35.5°C-35.9°C), moderate (35.0°C-35.4°C), or severe (<35°C). Temperature nadirs, procedural and anesthesia duration were observed. The primary outcome was 30-d surgical site infections. Secondary measures included other ICs. RESULTS: Among 43 GS neonates, 21 (48.8%) had intraoperative hypothermia, classified as mild in 2 (4.7%), moderate in 8 (18.6%), and severe in 11 (25.6%). Nineteen ICs occurred in 35.9% of patients, including 10 (23.3%) surgical site infections. There was no association between hypothermia and ICs. Patient and operative characteristics were similar between normothermic and hypothermic groups, except that normothermic infants were more likely to have silos placed with delayed closure than hypothermic patients (63.6% versus 23.8%, P = 0.01). CONCLUSIONS: Infants with GS are at high risk for hypothermia and ICs, though newborns with silos were less subject to temperature lability. A multiinstitutional study with greater power is needed to further investigate the relationship between perioperative hypothermia and surgical ICs.

Postoperative Complications of Laparoscopic Cholecystectomy for Acute Cholecystitis: A Comparison to the ACS-NSQIP Risk Calculator and the Tokyo Guidelines.

BACKGROUND: We compared observed postoperative outcomes from laparoscopic cholecystectomy performed for acute cholecystitis (AC) to outcomes predicted by the ACS-NSQIP risk calculator.We also noted and compared any differences in observed outcomes across the different Tokyo Guidelines (TG) levels of AC severity.We hypothesized that ACS-NSQIP would accurately predict complications and length of stay (LOS) and that increased TG severity levels would correlate with more complications, increased conversion to open surgery, and longer LOS. METHODS: A review of all patients who underwent laparoscopic cholecystectomy for acute cholecystitis over eighteen months was performed. RESULTS: ACS-NSQIP predicted a complication rate of 4.6% (11% found) and LOS of 0.73 days (2.5 found), p < 0.05. Increased TG severity had LOS of 1.89, 2.75, and 5.33, respectively, p < 0.05. The complication numbers and conversion to open cholecystectomy were insignificant between the TG classes. CONCLUSION: ACS-NSQIP did not accurately predict complications or LOS. TG classifications did not show a significant difference in complications or conversion to open surgery, but positively correlated with LOS. ACS-NSQIP may not accurately predict patient outcomes and the TG, originally created with the purpose of differentiating levels of inflammation and severity, may only be useful for predicting LOS.

Gastrojejunostomy Tube Bowel Perforations in Low-Weight Infants.

This is a case series in which 3 infants with gastrojejunostomy tube (GJT) insertion developed delayed perforation secondary to pressure necrosis. A review of all patients who underwent a GJT placement in 2013 was performed. Three of these patients developed surgically confirmed perforation secondary to pressure necrosis during this time period; no patients developed perforation at the time of GJT insertion. The indications for GJT insertion for all 3 patients were severe gastroesophageal reflux disease; 2 patients also had recurrent aspiration. The patients were between 9 weeks and 10 months of age at the time of GJT insertion. The site of perforation for all 3 cases occurred just distal to the ligament of Treitz between 48 and 72 hours following insertion. Given our 3 cases of perforation in patients weighing <10 kg, there may be a higher risk of perforation in low-weight patients.