Deductible Status in the Pediatric Population: A Barrier to Appropriate Care?

OBJECTIVE: The objective of this study is to evaluate the impact of high-deductible health plans on elective surgery (tonsillectomy) in the pediatric population. STUDY DESIGN: Cross-sectional study. SETTING: Health claims database from a third-party payer. METHODS: Data were reviewed for children up to 18 years of age who underwent tonsillectomy or arm fracture repair (nonelective control) from 2016 to 2019. Incidence of surgery by health plan deductible (high, low, or government insured) and met or unmet status of deductibles were compared. RESULTS: A total of 10,047 tonsillectomy claims and 9903 arm fracture repair claims met inclusion and exclusion criteria. The incidence of tonsillectomy was significantly different across deductible plan types. Patients with met deductibles were more likely to undergo tonsillectomy. In patients with deductibles ≥$4000, a 1.75-fold increase in tonsillectomy was observed in those who had met their deductible as compared with those who had not. These findings were not observed in controls (nonelective arm fracture). For those with met deductibles, those with high deductibles were much more likely to undergo tonsillectomy than those with low, moderate, and government deductibles. Unmet high deductibles were least likely to undergo tonsillectomy. CONCLUSIONS: Health insurance plan type influences the incidence of pediatric elective surgery such as tonsillectomy but not procedures such as nonelective repair of arm fracture. High deductibles may discourage elective surgery for those deductibles that are unmet, risking inappropriate care of vulnerable pediatric patients. However, meeting the deductible may increase incidence, raising the question of overutilization.

Implementation of a Quality Improvement Initiative to Decrease Opioid Prescribing in General Surgery.

BACKGROUND: There is increasing need to avoid excess opioid prescribing after surgery. We prospectively assessed overprescription in our hospital system and used these data to design a quality improvement intervention to reduce overprescription. MATERIALS AND METHODS: Beginning in January 2017, an e-mail-based survey to assess the quantity of opioids used postoperatively as well as patient-reported pain control was sent to all surgical patients in a 23-hospital system. In January 2018, as a quality improvement initiative, guidelines were given to surgeons based on patient consumption data. Prescription and consumption were then tracked prospectively. Wilcoxon signed-rank, analysis of variance, and Cuzick trend tests were used to assess for overprescription and changes over time in opioid prescribing and consumption. RESULTS: We included 2239 patients in our cohort. The amount prescribed (median [IQR]: 30 [24-45] versus 18 [12-30], P < 0.001) and consumed (median [IQR]: 12 [7-20] versus 8 [3-15], P < 0.001) each decreased between the first and last quarter studied. Academic hospitals prescribed fewer opioids than nonacademic hospitals (median [IQR]: 24[15-40] versus median [IQR]: 30 [20-45], P < 0.001). There was no difference in the quantity of opioids consumed between patients treated at academic and nonacademic facilities (median [IQR]: 10[3-19] versus 10.5 [4-20], P = 0.08). Patients consumed a median of 42% of the opioids prescribed, and there was no significant trend in the percent consumed over time (P = 0.8). CONCLUSIONS: Patients used far fewer opioids than prescribed after common adult general surgery procedures. When surgeons were provided with patient consumption data, the number of opioids prescribed decreased significantly.

Laparoscopic Repair of Paraesophageal Hernias with a Falciform Ligament Buttress.

BACKGROUND: Buttressing the crura in paraesophageal hernia (PEH) repairs with synthetic mesh may be associated with erosions and dysphagia, while biologic buttresses are expensive and do not decrease long-term recurrence rates. This study documents outcomes following laparoscopic PEH repairs using the falciform ligament as a buttress. METHODS: This is a prospective study of laparoscopic PEH repairs with a falciform ligament buttress. Preoperatively and at 6 months follow-up, medications, radiologic studies and symptom scores were recorded. Patients included had a hiatal defect greater than 5 cm, while recurrent PEH or prior gastric surgery patients were excluded. RESULTS: Thirty-four patients were included with a mean age of 61 years, and 33 patients completed postoperative evaluation with a mean follow-up of 7.1 months. The mean symptom severity decreased from 11.24 ± 1.71 to 3.24 ± 0.84, mean symptom frequency decreased from 11.62 ± 1.70 to 3.45 ± 0.85, and mean total symptom score decreased from 22.85 ± 3.40 to 6.69 ± 1.69 (p < 0.0001). Three patients had recurrences on the upper gastrointestinal (UGI) series. Only one required reoperation. CONCLUSIONS: Laparoscopic PEH repair with a falciform ligament buttress is a viable option. Ongoing follow-up will demonstrate the utility of this approach to decrease morbidity and recurrence rates for paraesophageal hernia repairs.

Follow-up after gastric electrical stimulation for gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) is used to treat medically refractory gastroparesis. However, there are few large series with outcomes beyond 12 months. This study reports surgical outcomes of GES for patients up to 8 years receiving treatment from a single institution. STUDY DESIGN: A prospective database was reviewed from 2003 to 2013 for patients undergoing GES. Baseline patient characteristics were recorded, including age, sex, cause of gastroparesis, gastric emptying, and Hgb A1C. Outcomes variables included nutrition supplementation, additional operations, 30-day morbidity, and mortality. Pre- and postoperative pain and function scores are analyzed over time using generalized estimating equations. Patient outcomes in terms of reoperation rates and types of operations are also reviewed. RESULTS: Seventy-nine patients underwent GES with a mean ± SD age of 43 ± 11 years and a BMI of 27 ± 8 kg/m(2). Symptom scores were available for 60 patients: 60 patients at baseline, 52 patients at 1 year, 14 patients during years 2 to 3, and 18 patients during years 4 to 8. Symptom scores decreased considerably in all categories. At 1-year follow-up, 44% and 31% of patients had at least a 25% reduction in symptom distress for functional and pain symptoms, respectively. Preoperatively, 9 patients required nutrition supplementation. After implantation, 34 (43%) patients underwent additional operations, with a mean of 2.15 operations per patient. Generator-related causes were the most common indication for reoperation, including battery exchanges and relocation. Other operations included 8 gastrectomies and 7 median arcuate ligament releases. Postoperatively, 4 patients required supplemental nutrition. There were no 30-day mortalities, but 11 patients died during the study period. CONCLUSIONS: Gastric electrical stimulation was significantly associated with reductions in both functional and pain-related symptoms of gastroparesis. Patients who undergo GES have a high likelihood of additional surgery.

Celiac artery compression after a gastric bypass.

Median arcuate ligament (MAL) syndrome or celiac artery compression occurs secondary to diaphragmatic compression of the celiac artery and the corresponding neural structures of the celiac plexus. Typically, patients present with postprandial abdominal pain, nausea, vomiting, and weight loss. Diagnostically, various radiologic studies are used to document impingement of the celiac artery including ultrasound, computed tomography, aortograms, and magnetic resonance imaging. Historically, open approaches to the aorta and the celiac artery are performed to release the MAL and relieve compression of the celiac artery and the plexus. Laparoscopic approaches are now utilized to divide the MAL. This study describes a patient who underwent a successful laparoscopic Roux-en-Y gastric bypass and lost 100 lbs over a 2-year postoperative period. Subsequently, the patient developed postprandial abdominal pain associated with nausea. She underwent a computed tomogram that diagnosed celiac compression and then a dynamic ultrasound that showed elevated velocities with deep expiration. Ultimately, a laparoscopic MAL release with division of the celiac plexus was performed. At 10 months postoperatively, the patient remains asymptomatic. To our knowledge, this report documents a rare case of CAC after Roux-en-Y gastric bypass. On the basis of this report, CAC should be considered in the differential diagnosis of postprandial abdominal pain in patients after bariatric surgery.

A novel single agent for nutritional supplementation following Roux-en-Y gastric bypass.

BACKGROUND: Duodenal bypass and intestinal malabsorption from Roux-en-Y gastric bypass (RYGB) can exacerbate known nutritional deficiencies of morbidly obese patients and worsen symptoms. Preventatively, most bariatric patients use postoperative nutritional supplementation. This study evaluated Nuvista(®) (Nutricia North America, Rockville, MD) and its potential as an adequate single nutritional supplement. SUBJECTS AND METHODS: From October 2009 to June 2010, 25 patients enrolled in a prospective, consecutive pilot study. Each underwent laparoscopic RYGB. The study group consumed two packs of Nuvista daily. The control group received standard nutritional supplements. Both groups had the same postoperative diet. Laboratory and demographics were compared at baseline and 12 months. Statistical analysis included paired t test, and a value of P<.05 was significant. RESULTS: The study and control groups (16 and 9 patients, respectively) had statistically similar demographic profiles. Both groups had preoperative elevations of hemoglobin A1c (HbA1c) (6.2% and 6.2%, respectively), low-density lipoprotein (LDL) (108.2 mg/dL and 199.2 mg/dL, respectively), and high-density lipoprotein (HDL) (55.1 mg/dL and 48.0 mg/dL, respectively) and deficiencies in vitamin D with respective mean values of 20.6 ng/mL and 22.7 ng/mL (normal range, 30-100 ng/mL). Postoperatively, the study group had significant increases in phosphorus (P=.02), iron (P=.03), vitamin D (P=.05), zinc (P=.01), and HDL (P≤.01) and significant decreases in body mass index (BMI) (P≤.01), creatinine (P=.02), HbA1c (P=.01), triglycerides (P≤.01), and LDL (P≤.01). The control group had a significant increase in HDL (P=.01) and significant decreases in BMI (P≤.01), hemoglobin (P=.01), creatinine (P≤.01), albumin (P=.05), HbA1c (P=.05), zinc (P≤.01), triglycerides (P=.03), and LDL (P=.01). No change in mean parathyroid hormone value was seen. CONCLUSIONS: Nuvista can provide adequate supplementation to bariatric patients 12 months after RYGB. Lifelong biochemical follow-up is necessary to personalize the diet and nutritional supplementation to compensate for the pathophysiologic changes of the gastric bypass.

Serum blood urea nitrogen and serum albumin on the first postoperative day predict pancreatic fistula and major complications after pancreaticoduodenectomy.

INTRODUCTION: Pancreaticoduodenectomy (PD) has a high morbidity rate. Previous work has shown that hypoalbuminemia on postoperative day 1 (POD) to be contributory to post-esophagectomy complications. We set out to determine the impact of blood urea nitrogen (BUN) and albumin on POD 1 for patients undergoing PD. METHODS: We examined 446 consecutive patients who underwent PD at the Thomas Jefferson University Hospital between January 1, 2000 and December 31, 2008. Complications were graded using the Clavien scale. We examined the incidence of complications based on POD 1 albumin <2.5 versus ≥2.5 mg/dl, as well as POD 1 BUN <10 vs. ≥10 g/dL. RESULTS: Patients with a BUN <10 had a significantly decreased risk of any complication (p < 0.001), serious complication (p < 0.001), and pancreatic fistula (p = 0.011). On multivariate analysis, BUN ≥ 10 was the most significant predictor of grade III or above complication (p = 0.0019, hazard ration (HR) = 2.7) and pancreatic fistula (p = 0.016, HR = 2.6). POD 1 albumin <2.5 mg/dl was also an independent predictor of serious complication (p = 0.01, HR = 2.3). Patients with both risk factors had a 31 % chance of developing serious complications and 18.5 % risk of developing pancreatic fistula, while those patients with neither risk factor had a 6.5 and 3.6 % risk, respectively. CONCLUSION: Serum albumin and BUN on POD 1 are important predictors of perioperative morbidity following PD. These low-cost and easily accessible tests can be used as a prognostic tool to predict adverse surgical outcomes.

The economic costs of obesity and the impact of bariatric surgery.

The obesity epidemic has far-reaching implications for the economic and health care future in the United States. Treatments that show reduction in health care costs over time should be approved and made available to as many patients as possible. It is our opinion that bariatric surgery meets this criterion. However, bariatric surgery cannot provide the impact necessary for reduction in health care and economic costs on a national scale. The obesity epidemic must be addressed by policy efforts at the local, state, and national levels. As experts on obesity, bariatric surgeons must be prepared to guide and inform these efforts.

pp32 (ANP32A) expression inhibits pancreatic cancer cell growth and induces gemcitabine resistance by disrupting HuR binding to mRNAs.

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy.

CanScript, an 18-Base pair DNA sequence, boosts tumor cell-specific promoter activity: implications for targeted gene therapy.

Gene therapy protocols for the treatment of cancer often employ gene promoter sequences that are known to be over-expressed in specific tumor cell types relative to normal cells. These promoters, while specific, are often weakly active. It would be desirable to increase the activity of such promoters, while at the same time retain specificity, so that the therapeutic gene is more robustly expressed. Using a luciferase reporter DNA construct in both in vitro cell transfection assays and in vivo mouse tumor models, we have determined that in the absence of any other DNA sequence, a previously identified 18-base pair enhancer sequence called CanScript, lying upstream of the MSLN gene, has ~25% of the promoter activity of CAG, a very strong non-specific promoter/enhancer, in tumor cells in which MSLN is highly expressed. Furthermore, tandem repeat copies of CanScript enhance transcription in a dose-dependent manner and, when coupled with promoter sequences that are active in tumor cells, increase promoter activity. These findings suggest that the incorporation of CanScript into gene constructs may have application in enhancing activity of promoters used in cancer-targeting gene therapy strategies, thereby improving therapeutic efficacy.

HuR status is a powerful marker for prognosis and response to gemcitabine-based chemotherapy for resected pancreatic ductal adenocarcinoma patients.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a devastating disease that killed nearly 38,000 people in the United States this past year. OBJECTIVE: Treatment of PDA typically includes surgery and/or chemotherapy with gemcitabine. No reliable biomarker exists for prognosis or response to chemotherapy. Two previously proposed prognostic markers, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), are regulated by Hu protein antigen R (HuR), an mRNA binding protein that we have previously demonstrated to be a promising predictive marker of gemcitabine response. This study was designed to evaluate the clinical utility of HuR, COX-2, and VEGF as potential prognostic and predictive biomarkers for PDA. METHODS: A tissue microarray of 53 PDA specimens from patients who underwent potentially curative pancreatic resection was analyzed. HuR, COX-2, and VEGF status were correlated with clinicopathologic and survival data. We also performed ribonucleoprotein immunoprecipitation assays using an HuR antibody to assess VEGF and COX-2 mRNA binding to HuR in pancreatic cancer cells. RESULTS: Roughly 50% (27/53) of patients had high cytoplasmic HuR expression. These patients had worse pathologic features as assessed by T staging (P = 0.005). Only cytoplasmic HuR status correlated with tumor T staging, whereas VEGF (P = 1.0) and COX-2 (P = 0.39) expression did not correlate with T staging. Additionally, HuR status was an unprecedented positive predictive marker for overall survival in patients treated with gemcitabine, pushing median survival over 45 months in the high cytoplasmic HuR expressing patient population compared with less than 23 months in the low cytoplasmic HuR expressing patient group (P = 0.033 for log-rank test and P = 0.04 in a Cox regression model) for the low versus high cytoplasmic HuR expressing group. We also validated that mRNA transcripts for both VEGF and the gemcitabine metabolizing enzyme, deoxycytidine kinase, are specifically bound by HuR in pancreatic cancer cells. CONCLUSIONS: HuR is a useful prognostic biomarker for PDA patients as indicated by its association with higher tumor T stage. Additionally, HuR status is a robust predictor of outcome for patients with resected PDA in the setting of adjuvant gemcitabine therapy. Finally, HuR binds to VEGF mRNA implying that HuR, in part, regulates VEGF expression in PDA. This study supports the notion that HuR status should be used by clinicians for the individualized treatment of PDA in the future.

Identifying pancreatic cancer patients for targeted treatment: the challenges and limitations of the current selection process and vision for the future.

Recent preclinical data have demonstrated that pancreatic adenocarcinoma (PDA) cells with defects in the Fanconi anemia/BRCA2 pathway are hypersensitive to interstrand crosslinking agents. The challenge is to efficiently identify patients who will benefit from these therapies. Patients were chosen for this study by evaluating personal history, ethnic background and family history of pancreatic malignancy. Molecular assays were performed on tissue samples. Patient A developed PDA in the context of a known BRCA2 frameshift mutation (2157delG), suspected because of her personal and multigenerational family history of breast cancer. She was treated with surgical resection, and targeted chemotherapy. Patient A continues to be disease free 32 months after her diagnosis and treatment. Patient B developed PDA in the context of a strong family history of PDA and Ashkenazi Jewish heritage. Genetic analysis on critical DNA repair genes revealed no alterations. This patient did not receive a tailored treatment regimen. This study highlights the challenge of treating PDA patients and selecting those eligible for targeted therapy. The current targeted treatment options for PDA are reviewed. A new multidisciplinary approach for stratifying PDA patients for promising targeted adjuvant therapy and familial risk counseling is proposed.