Citations

ABSTRACTObjectives:The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.Methods:Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.Results:Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2‐CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2‐CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2‐CO vs 1% INSPPIRE cohorts, P = 0.011).Conclusions:Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.

442 Background: Neutrophil to lymphocyte ratio (NLR) has been used as an inflammation-based prognostic marker for various malignancies. The aim of our study was to determine whether NLR can independently predict the overall survival in patients with metastatic gallbladder cancer (GBC). Methods: We identified patients diagnosed with GBC who were treated at Mayo Clinic between the years 2000 and 2016. Patients who had nonmetastatic GBC were excluded along with the patients who did not have data for neutrophils and lymphocytes. Optimal cutoff point for NLR was identified by plotting martingale residuals against NLR and patients were divided into two groups, ≥ 5 or < 5. Demographic, follow-up data and outcomes were collected by retrospective review of electronic medical records. Fisher’s exact test was used to compare categorical variables, while The Mann- Whitney U test was used to compare continuous variables. Kaplan-Meier curves were plotted for NLR ≥ 5 and NLR < 5 and overall survival (OS) between the two groups were compared using log rank test. Multivariate survival analysis was performed using Cox-proportional hazard regression. Results: A total of 231 patients met our inclusion criteria, of which, 138 (60%) had NLR < 5 and 93 (40%) had NLR ≥ 5. Patients with NLR ≥ 5 were more likely to be older and have poor performance score, lower albumin level, higher alkaline phosphatase level, and higher platelet count. There were no significant differences noted in gender, race and administration of chemotherapy between the two groups. In univariate analysis, patients with NLR ≥ 5 at presentation had a significantly worse OS compared to those with NLR < 5 (Median survival: 3.6 vs. 8.8 months, p < 0.001). In multivariate analysis, adjusting for age, ECOG status, albumin, ALP, AST, ALT, bilirubin, platelet count and administration of chemotherapy, NLR of ≥ 5 was associated with a worse OS compared to NLR < 5 (HR: 1.70, 95% CI:1.20 – 2.39. p < 0.05). Conclusions: Our study demonstrates that NLR ≥ 5 is an independent predictor of poor prognosis in patients with metastatic gallbladder cancer.

433 Background: Current staging systems for gallbladder cancer (GBC) are inadequate, as they are based on surgical pathology, and therefore are not relevant for unresectable patients and patients undergoing neoadjuvant chemotherapy. Methods: Patients with a confirmed diagnosis of GBC who were seen at Mayo Clinic between the years 2000 and 2016 were included in this analysis. Data on demographic and tumor characteristics and outcomes were collected by retrospective review of electronic medical records. A model predictive of overall survival was developed using Cox proportional hazard regression analysis. Harrel’s C-statistic was calculated to evaluate the predictive accuracy of the model and compared with the TNM staging system. Results: A total of 523 patients were included in the final analysis, with a median age of diagnosis of 68 years. The median duration of follow up of the entire cohort was 12 months. In multivariate analysis, factors predictive of poorer overall survival were: ages 65-74 years (HR : 1.80, 95% CI: 1.33–2.43) and ages 75+ years (HR: 2.93, 95% CI: 2.12–4.06) compared to age <55 years; tumor size ≥ 5 cm by imaging (HR: 1.24, 95% CI: 1.01–1.55); nodal involvement by imaging (HR:1.61, 95% CI: 1.23–2.10); involvement of distant organs by imaging (HR: 2.85, 95% CI: 2.16–3.75); ECOG performance score of 2 or higher (HR: 1.78, 95% CI: 1.36–2.32) compared to ECOG 0-1; albumin level <3.5 g/dL (HR: 1.40, 95% CI: 1.08–1.81); and alkaline Phosphatase level ≥ 200 IU/L (HR: 1.49, 95% CI: 1.21–1.84). Using these seven predictive factors of survival we created a four-tier staging system. The median survivals of Stages I, II, III and IV created in our novel system were 64, 34, 20 and 7 months with corresponding hazard ratios of 1, 1.5, 2.5 and 8.5 respectively. The C-statistic for this novel staging system was 0.68 compared to C-statistic of 0.69 for the TNM staging system, indicating similar performance in predicting survival. Conclusions: We have created a novel clinically-based staging system for patients with GBC based on nonoperative information at the time of diagnosis which performs on par with the current surgical pathology based TNM staging system.

426 Background: Small bowel adenocarcinoma is a rare malignancy affecting approximately 2,000 patients per year. There is a paucity of evidence prognosticating patients with small bowel adenocarcinoma. We aimed to evaluate multiple factors in patients with resected small bowel adenocarcinoma to determine any association with survival outcomes. Methods: Ninety three patients who underwent resection for stage I-III small bowel adenocarcinoma were retrospectively identified utilizing the pathology database at a single tertiary referral institution. All patients had complete follow up data and were included in the survival analysis. JMP software was used for statistical analysis. Overall survival was performed utilizing Kaplan-Meier method, and log-rank tests were used for statistical comparisons. Cox proportional hazards were performed to control for age, gender, location of tumor, tumor size, tumor stage, and adjuvant therapy. Sensitivity analysis was performed to establish best cutoff points for continuous variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65 years (range 32-90). 61% were male. Median tumor size was 4.5 cm. There were 20, 36, and 37 patients with stage I, stage II, and stage III disease, respectively. Median overall survival (OS) was 151 months, 104 months, and 44 months for stages I, II, and III disease. In a multivariate analysis, independent predictor factors included presurgical lymphocyte to monocyte ratio (LMR) > 4.0, with a Hazard Ratio (HR) 0.13 (95% CI 0.007-0.69, p = 0.01), presurgical neutrophil to lymphocyte ratio (NLR) < 8.0, HR 0.39 (95% CI 0.17-0.96, p = 0.04), and tumor size < 7.5 cm, HR 0.22 (95% CI 0.07-0.85, p = 0.03). Stage, age, T stage, and N stage influenced overall survival in univariate analysis, but were not statistically significant on multivariate analysis. Conclusions: LMR and NLR independently predict survival in patients with resected small bowel adenocarcinoma.

393 Background: Clinicopathological features and the outcomes of patients with fibrolamellar hepatocellular carcinoma (FLHCC) are not clearly defined. Methods: Data were collected by retrospective chart review on 42 patients with FLHCC treated between 1990 and 2017 at the Mayo Clinic. Clinicopathological characteristics, response to treatment, recurrence pattern and survival were analyzed. Results: Of 42 patients (17 males and 25 females; median age at diagnosis 22 years, range 15 to 39), 10 patients (23%) had stage I disease and 32 patients (77%) had stage II to IVB disease. All 10 patients with stage I disease and 21 of 32 patients with stage II-IVB disease underwent resection at presentation. In stage I patient group, 6 patients experienced recurrence with a median time to recurrence of 30.5 months, resulting in a 5 year overall survival (OS) of 86%. Patients with stage II to IVB disease who underwent resection (n=21) at presentation had a median OS of 32.5 months and 5 year OS of 44%. In the upfront surgery group, 71% of the patients experienced recurrent disease. The median OS of patients with unresectable disease (n=11) was 10 months. Systemic therapy was given to 17 patients which included sorafenib, FOLFOX (5-fluorouracil/leucovorin and oxaliplatin), gemcitabine plus oxaliplatin, single agent adriamycin or gemcitabine, capecitabine plus interferon alfa, gemcitabine plus cisplatin, cisplatin plus adriamycin and nivolumab . Sorafenib was given to 9 patients and 4 patients achieved stable disease (SD) with duration ranging from 5 months to 5 years. One programmed cell death receptor positive-1 patient had a durable complete response after 2 months of therapy with nivolumab. Conclusions: In FLHCC, surgical resection was associated with prolonged OS. However, recurrences were common after the surgery. Limited benefit was derived from the systemic treatment. In rare cases, therapy with a checkpoint inhibitor may provide a viable treatment option.

322 Background: The role of perioperative systemic therapy (PST) is unclear in the management of localized pancreatic neuroendocrine tumor (pNET). We aim to evaluate the benefit of PST compared to surgical resection alone in localized pNET. Methods: We identified patients with stage I–III pNET who underwent curative-intent surgical resection in National Cancer Database from 2006 to 2014. Patients who underwent PST and surgical resection were matched with patients who received surgery alone by propensity score at 1:1 ratio with nearest neighbor method. Factors predicting the use of PST were identified from logistic regression. Survival was estimated with Kaplan-Meier method and compared with Cox proportional hazards regression. Results: 4919 patients were included in this study with median age of 60 years. 1397 (28%) patients had pNET at the head of pancreas. 2708 (55%) patients had pNET at pancreas body and tail. 334 (6.8%) patients received PST. Factors associated with significant more use of PST compared to surgery alone were age < 65 years, low income, community medical facilities, grade 3/4 tumor, tumor at the head of pancreas, T3-4 tumor and N1 tumor. 310 patients in PST group were matched with 310 patients in surgery alone group, with no significant difference for all covariates after match. For those in PST group, 64 (21%) patients received neoadjuvant systemic therapy, 173 (56%) patients received adjuvant systemic therapy, 7 (2.3%) patients received both, and 66 (21%) patients received PST without clear sequence. In the matched cohort, PST group had significantly shorter overall survival (OS) compared to surgery alone group (median OS 91.1 months versus not reached, p = 0.04). This finding was confirmed by multivariable Cox proportional hazards regression in unmatched cohort with HR 1.5 (95% CI 1.2 – 1.9, p = 0.002). Subgroup analysis in patients with grade 3/4 tumor demonstrated PST group has a trend of shorter OS compared to surgery alone group (median OS 34.1 versus 54.4 months, p = 0.1). Conclusions: PST compared to surgery alone is associated with worse OS in patients with localized pNET. This finding suggests that we may use PST in localized pNET with caution in the absence of solid clinical trial data.

243 Background: The risk factors for gallbladder cancer (GBC) are poorly understood and preventive therapeutic options have not been identified. The use of aspirin (ASA) and/or statin has been associated with reduced risk of several gastrointestinal cancers. In this study, we explore if the use of ASA or statin is associated with a reduced risk of GBC. Methods: We identified patients with GBC diagnosed between the years 2000 and 2016 at Mayo Clinic. We identified matched controls in 2:1 fashion for age, gender and country of residence from patients who underwent cholecystectomy at Mayo Clinic. We collected information on co-morbidities and use of statins or ASA by retrospective chart review. We compared baseline characteristics between cases and controls using Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables. We used binomial logistic regression to calculate the odds ratio (OR) and 95% confidence intervals (CI) to estimate the association of ASA or statin use with GBC. The logistic regression model included history of cholelithiasis, diabetes, hypercholesterolemia (HCL), hypertension (HTN), hyperthyroidism, hypothyroidism, primary sclerosing cholangitis (PSC), inflammatory bowel disease (IBD), cirrhosis and statin or ASA use as covariates. Results: 633 cases and 1,266 controls were included in our final analysis. The median age at diagnosis of cases and controls was 67 years. The control group had a significantly (p < 0.05) higher proportion of patients with cholelithiasis, HCL, HTN, hypothyroidism and liver cirrhosis compared to the cases. The case group,contrarily, had a significantly higher proportion of patients with PSC and IBD. In univariate analysis, ASA (OR: 0.41; 95% CI: 0.33-0.52) or statin (OR: 0.48; 95% CI: 0.38-0.60) use was associated with a lower risk of GBC (p < 0.001). However, in multivariate analysis, ASA use was associated with a lower risk of GBC (OR: 0.52; 95% CI: 0.41-0.67, p < 0.001) whereas statin use was not (OR: 0.76; 95% CI: 0.56-1.03, p = 0.08). Conclusions: Our study demonstrates that aspirin use is associated with a reduced risk of GBC, whereas statin use is not. Further studies on GBC are needed to confirm these results and to elucidate mechanisms that explain the risk reduction with aspirin.

ABSTRACT Background and purpose: The use of pulmonary ultrasound (US) in the critical care setting has been increasing over the past 2 decades. The use of advanced practice providers (APPs) in the critical care setting is also increasing. Limited data exist regarding the clinical and educational impact of a formal pulmonary US training course for APPs working in critical care settings. Methods: A preimplementation and postimplementation comparative design focused on the development and implementation of a formal pulmonary US course for novice critical care APPs. Conclusions: Eleven APPs underwent formal pulmonary US training. There was a significant increase in pulmonary US knowledge after the course, with pretest median of 13 and posttest median of 22 (p < .001; maximum score = 23). Presurvey and postsurvey comparison showed overall increase in skill and clinical use of pulmonary US. After the course, participating APPs reported a greater frequency of clinical decision-making based on US examination as measured by presurvey and postsurvey results. Implications for practice: Implementation of a formal pulmonary US course for critical care APPs improved pulmonary US knowledge, skill, and utilization, and impacted clinical decision-making and should be a highly recommended addition to the practice setting.