bluuebunny/crossref_metadata_2025_split huggingface dataset:
51 Eosinophilic Pancreatitis as a Benign Mimicker of Pancreatic Neoplasm: A Systematic Review
Authors: Kuftinec Gabriela , Barkin Jodie A. , Nemeth Zsuzasanna , Barkin Jamie S. 
Published: October 2019

INTRODUCTION:
Eosinophilic pancreatitis (EP) is a rare form of pancreatitis characterized by diffuse infiltration of the pancreas with eosinophils & elevated serum immunoglobulin E levels. Diagnosis is clinically difficult as endoscopic/radiographic findings often mimic neoplasm, leading to surgical resection. The aim of this review is to chronicle all cases of EP, describe clinical & radiographic presentation & outcome.

METHODS:
A systematic search was performed with an experienced librarian of PubMed, Embase & Scopus for search terms of “Eosinophilic Pancreatitis” from 1975–4/19/2019. We included all case reports, series, cohorts & randomized studies with diagnosis of EP. Exclusion criteria were articles with other attributable pancreatitis etiology, fetal EP cases, or non-English language. All articles were reviewed by 2 authors. Data was collected on clinical & radiographic findings, comorbidities & outcome.

RESULTS:
The search yielded 1379 results of which 18 case reports/series of 23 total patients were included. 17/23 (73.9%) were men, mean age 43.6 ± 17.0 years (range 14–74). Most common symptoms at presentation were abdominal pain (18/23), jaundice (9/23), weight loss (6/23), nausea/vomiting (6/23), & recurrent acute pancreatitis (2/23). Comorbidities included Diabetes Mellitus (2/23) & asthma/allergies (4/23). Imaging revealed abnormalities (mass, hypodensity, or enlargement) located in the pancreatic head (13/23), body (2/23) & tail (3/23). A pancreatic mass was most commonly found (11/23), followed by pancreatic enlargement (8/23), pancreatic duct dilatation (5/23) & bile duct dilatation (8/23). 4/23 patients had a pseudocyst; none had necrosis. Pathology showed prominent eosinophilic infiltrate in all cases, with 5/23 having few lymphocytes & 9/23 with diffuse inflammatory infiltrates. 16/23 patients underwent surgical resection with EP diagnosis made post-operatively. 5/23 patients had complications (4/23 resolved with steroids; 1 died from systemic hypereosinophilia with renal failure & chylothorax).

CONCLUSION:
EP presents more commonly in men in a 3:1 ratio in the 5th decade. EP should be considered in patients with abdominal pain, jaundice, & weight loss with imaging of a pancreatic mass or enlargement, or ductal dilation. EP masquerades as malignancy; however, diagnostic clues to EP include peripheral eosinophilia & presence of diabetes or asthma/allergies. Awareness of EP may allow for potential non-operative diagnosis, avoidance of surgery, & appropriate medical therapy.
62 Surveillance of High-Risk Individuals for Pancreatic Cancer With EUS and MRI: A Meta-Analysis
Authors: Kogekar Nina , Diaz Kelly E. , Weinberg Alan D. , Lucas Aimee 
Published: October 2019

INTRODUCTION:
Early detection of pancreatic cancer is of interest given the significant morbidity and mortality of this disease. The International Cancer of the Pancreas Screening (CAPS) Consortium guidelines recommend surveillance of high-risk individuals (HRI) with a history of familial pancreatic cancer or carriers of genetic cancer syndrome mutations. Surveillance is typically performed with endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI). The aim of this study is to assess the yield of pancreatic cancer surveillance programs of HRI and compare the yield of EUS and MRI.

METHODS:
The MEDLINE and Embase (Ovid) databases were searched for prospective studies published up to April 11, 2019 using EUS and/or MRI to screen HRI for pancreatic cancer. Baseline detection of focal pancreatic abnormalities, cystic lesions, solid lesions, high-risk lesions (defined as pancreatic intraepithelial neoplasia grade 3, intrapapillary mucinous neoplasia with high grade dysplasia, or T1N0M0 adenocarcinoma), and pancreatic adenocarcinoma were recorded, as were surgeries performed. Weighted pooled detection rates of outcomes were calculated and were compared between EUS and MRI using random effects modeling.

RESULTS:
A total of 1109 studies were reviewed and 24 were included in analysis, representing 2112 patients who underwent screening. The weighted pooled rate of focal pancreatic abnormalities detected on baseline screen by EUS (0.34, 95% CI 0.30–0.37) was significantly higher (P = 0.006) than by MRI (0.31, 95% CI 0.28–0.33). There were no significant differences between EUS and MRI for detection of other outcomes, including cysts, high-risk lesions, or pancreatic cancer (Table 1). The overall weighted pooled detection rate of high-risk lesions on baseline screening (regardless of imaging modality) was 0.0090 (95% CI 0.0022–0.016), corresponding to a number-needed-to-screen (NNS) of 111 patients to detect one high-risk lesion. The overall weighted pooled detection rate for pancreatic adenocarcinoma was 0.012 (95% CI 0.0051–0.018) and the surgery rate was 0.054 (95% CI 0.045–0.063) (Table 2).

CONCLUSION:
Surveillance programs are successful in detecting high-risk precursor lesions with a NNS compatible with existing screening and surveillance programs. No differences between EUS and MRI were noted in the detection rate of high-risk lesions or pancreatic cancer, which supports the use of either imaging study in surveillance programs.
84 The Role of the GNAS Oncogene in the Immune Microenvironment of Intraductal Papillary Mucinous Neoplasm
Authors: Hernandez-Barco Yasmin G. , Ferrer Christina , Ngo Kenneth , Schiferle Erik , Patra Krushna , Fernandez-Del Castillo C. , Mino-Kenudson Mari , Mostoslavsky Raul , Demehri Shadmehr , Bardeesy Nabeel 
Published: October 2019

INTRODUCTION:
Pancreatic ductal adenocarcinoma (PDA) arises from two main precursor lesions, pancreatic intraepithelial neoplasia (PanIN), and intraductal papillary mucinous neoplasia (IPMN). Extensive studies of The PanIN-to-PDA sequence has identified the immunosuppressive microenvironment and recruitment of pro-tumorigenic inflammatory cells as a key hallmark, whereas the immune microenvironment of IPMN remains unexplored. This proposal aims to test the core hypothesis that GNAS-driven IPMN precursor lesions display a distinct inflammatory program that contributes to tumor initiation and progression.

METHODS:
We developed novel genetically engineered mouse models (GEMMs) harboring combinations of the most frequent mutations found in human IPMN of benign and malignant disease. We also utilized genetically characterized and carefully demographically annotated human tissues and perform immunological characterization by immunofluorescence, immunohistochemistry and flow cytometry. We also performed cytokine arrays and early functional studies from the preliminary data generated from this characterization.

RESULTS:
We identified that GNAS-mutant tumors are replete with T-cells and dendritic cells, as compared to the virtual absence of these cell types in “classic” PanIN-PDA (3.0 ± 0.6 vs. 81.4 ± 25.4, P < 0.03) (Figure 1). With the switching off of GNAS, there is an influx of CD8+ T cells 7.2 ± 1.9 vs. 25.4 ± 4.9 (P < 0.004) and loss of CD206+ macrophages 62.6 ± 10.7 vs. 22.9 ± 6.8, P < 0.02 (Figure 2). We observe that GNAS is a potent regulator of these differences through immunomodulatory cytokines, IL33, Arg1; along with the upregulation of CD105 and Reg3G. The human-relevance of our findings is supported by our initial pilot studies of human pancreatic tumor specimens. These early studies indicated that IPMNs with GNAS mutations (alone or in combination with KRAS) have increased CD3+ and CD4+ T cell infiltrate compared to those lacking GNAS mutations, consistent with our murine data (Figure 3).

CONCLUSION:
GNAS mutant IPMNs display a distinct immune infiltrate as compared to classic PanIN-PDA lesions, suggesting that these tumors will likely be amenable to immunopreventative and immunotherapeutic strategies. These studies will link immune dynamics to tumor growth, which is profoundly induced in GNAS-mutant IPMN. Deciphering the interplay between the evolving neoplastic cells and immune system underlying these cystic tumors can inform the development of strategies to prevent or treat GNAS-mutant IPMN.
88 Racial and Gender Disparities Among Obese Patients With Pancreatic Cancer: A Trend Analysis From 2004–2018 in the United States
Authors: Twohig Patrick , Butt Muhammad , Gardner Timothy , Sandhu Sonia , Sandhu Dalbir S. 
Published: October 2019

INTRODUCTION:
Obesity increases the risk of pancreatic cancer by up to 50%. Epidemiologic studies indicate that disparities exist in obesity trends across different demographics in the United States. This is suspected to be from modifiable risk factors, comorbidities, and differences in the gut microbiome, along with social determinants of health such as a lack of access to high-volume treatment centers. Our aim is to determine if variation exists in the demographic of obese pancreatic cancer patients over the last 15 years.

METHODS:
We performed a retrospective analysis in the IBM Explorys database (1999–2018), a pooled, de-identified clinical database of unique patient records from 26 health care networks and 300 hospitals across the United States. At the time of analysis there were 63,744,040 patients, of which 9,620 were adults (>18 years old) with both pancreatic cancer and obesity (BMI >30). Patient populations were identified using SNOMED and ICD codes. Cochrane-Armitage testing was performed to analyze trends in obesity among pancreatic cancer patients between 2004–2018. Subgroup analysis for gender, age, race, and mortality rate were assessed.

RESULTS:
The percentage of obese patients with pancreatic cancer increased over the 15-year period (2.5% to 8.5%); P = <0.0001). Rates of obesity among pancreatic cancer patients increased among females (P = 0.0004), individuals under age 65 years (P = 0.0002), and all-races, but especially for African Americans (P = 0.0007) and those in minority groups.

CONCLUSION:
Pancreatic cancer is becoming more common among patients who are obese, younger, female, and not Caucasian. African Americans have been shown to have a higher incidence and mortality from pancreatic cancer. This disparity has been attributed to lifestyle habits, co-morbidities including obesity, and a lack of access to high-volume treatment centers. However, differences in gene expression also increase the risk. Although these could be therapeutic targets, low minority enrollment in research studies is a barrier to progress. This is the first study to assess demographic trends in obese pancreatic cancer patients over the last 15 years. Awareness of disparities in pancreatic cancer and applying more precise population approaches to those at increased risk are essential to improving future outcomes. An integrated approach should include increased health care access and recruitment in research studies for minority groups.
133 Impact of Clostridium difficile Infection in Patients With Ulcerative Colitis and Crohn's Disease: A Comparative Analysis
Authors: Khan Ahmad , Sohail Abdullah , Berry Davis B. , Gupta Kamesh , Goyal Hemant 
Published: October 2019

INTRODUCTION:
Patients with Inflammatory bowel disease (IBD) are at increased risk of acquiring Clostridium difficile infection (CDI) that leads to an increased in morbidity and mortality. The aim of our study is to compare the outcomes of CDI on in-hospital mortality and resource utilization among adult hospitalized patients with Ulcerative colitis (UC) and Crohn's disease (CD) without CDI in the USA.

METHODS:
A retrospective cohort analysis using the 2004–2014 Nationwide Inpatient Sample is performed. Adult hospitalized patients with IBD (subgrouped into UC and CD) with CDI were identified using validated ICD-9 codes. Outcomes include in-patient mortality, hospital charges, and length of stay (LOS) among two groups. Confounding factors such as age, sex, ethnicity, insurance status, hospital characteristics, and CDI are adjusted with univariate and multivariate regression models.

RESULTS:
Out of total 514,889 UC patient's hospitalizations, 24,783 (4.81%) discharges were related to CDI with mean age 60 ± 3 years and 60% female population. In comparison to that, out of 878,896 CD hospitalizations, 13,120 (1.49%) were related to CDI (see Table 1). In terms of outcomes, patients with UC + CDI had increased mortality (adjusted OR 3.003, 95% CI 2.65–3.39), P = 0.00 and LOS (8.0 days vs 6.5 days) and mean total charges difference of $16,739.33 as compared to UC patients without CDI. However, in contrast to CD patients with CDI, there was no significant difference in mortality (adjusted OR 0.60, 95% CI 0.40–0.90, P = 0.021), mean LOS (6.57 days vs 6.15 days) and total hospitalization charges ($34,137.16 VS $33,020.09) in comparison to CD patients without CDI.

CONCLUSION:
Our study results provide important insight on the effect of CDI on the outcome in patients with IBD. Surprisingly, we found that among US adults with UC and CD-related hospitalizations, CDI is associated with significantly subgrouped in-hospital mortality and healthcare utilization only in patients with UC and CDI infection did not appear to affect the outcomes in the CD-related hospitalizations.
179 Cost-Effectiveness Analysis of Starting a Fecal Microbiota Transplantation (FMT) Unit for the Treatment of Recurrent C. difficile Infection Compared With Antibiotic Therapy
Authors: Shaffer Seth , Rubin David T. , Targownik Laura , Singh Harminder , Witt Julia , Kao Dina , Lee Christine , Bernstein Charles 
Published: October 2019

INTRODUCTION:
Despite the proven efficacy of FMT in recurrent Clostridioides difficile infection (CDI), many hospitals and health regions have yet to establish a program for its use. We assessed the cost effectiveness of FMT (including start-up costs) for recurrent CDI (rCDI) to determine how many patients would need to be treated to make this approach cost effective for a centre.

METHODS:
We conducted a decision-analytic model comparing six separate strategies for the management of the third recurrence of CDI: each FMT modality (via capsule, enema (Figure 1), or colonoscopy) versus vancomycin, fidaxomicin, and a combined antibiotic model of vancomycin followed by fidaxomicin. At the end of the decision tree, the patient would be in one of 4 health conditions: healthy, mild-to-moderate CDI, post-colectomy, or death. Costs for a FMT start up centre (preparation of donor material, screening costs, etc. Table 1) were calculated over 10 years, and discounted at 5%/year. Our primary outcome was to estimate how many patients would have to be treated with FMT on an annual basis to make a FMT centre cost-effective (WTP of $50,000/QALY) versus antibiotic therapy for the treatment of rCDI.

RESULTS:
To make any of the FMT modalities cost-effective compared with vancomycin treatment, 26 patients would have to be treated with FMT via enema annually, 32 via capsule, and 31 via colonoscopy (Figure 2). In our base case analysis of all three FMT modalities treating 40 patients/year compared with vancomycin, FMT via enema was the most cost-effective strategy with an incremental cost-effectiveness rate (ICER) of $21,366.03, followed by ICERs of $37,911.01, and $37,743.24 via capsule and colonoscopy, respectively. Treatment with fidaxomicin in these patients was both more expensive and less effective than FMT, as it was dominated by all 3 FMT modalities. When patients were initially treated with vancomycin followed by fidaxomicin if they failed vancomycin, FMT via enema dominated.

CONCLUSION:
FMT, including start-up and ongoing costs, is cost-effective compared to conventional antibiotics in the treatment of recurrent CDI. Only 26 patients are required to be treated each year with FMT via enema for it to be a cost-effective strategy for rCDI. In healthcare regions where FMT is not currently a therapeutic option, this analysis suggests that despite its higher initial costs, starting up a FMT unit will lead to healthcare savings over time.
189 Colon Ischemia Is Associated With a Low Rate of Subsequent C. difficile-Associated Diarrhea
Authors: Zheng Kevin , Gnanapandithan Karthik , Feuerstadt Paul , Brandt Lawrence , Aroniadis Olga 
Published: October 2019

INTRODUCTION:
Studies suggest an association between colon ischemia (CI) and C. difficile-associated diarrhea (CDAD). It is unclear, however, if CI disease severity, attendant antibiotic use, or both are risk factors for CDAD. The aim of our study was to answer these questions.

METHODS:
A retrospective cohort study was performed on patients admitted to Montefiore Medical Center and Yale New Haven Hospital between 2005 and 2017 with a diagnosis of biopsy-proven CI. Patients who developed CDAD within 90 days of diagnosis of CI were identified. Various epidemiological factors were included (e.g., demographics, medical history, medication exposures, outcome, etc.). CDAD was defined by diarrhea and a positive C. difficile toxin assay. Patients with prior CDAD diagnosed within 90 days before admission for CI were excluded. Severity of CI was defined according to ACG Clinical Guideline recommendations. Bivariate analyses were performed to compare incidence of CDAD between groups with mild, moderate, and severe CI. Additionally, bivariate analyses were performed to compare epidemiological factors between cohorts with and without CDAD.

RESULTS:
Of 853 patients with biopsy-proven CI, 16 (1.9%) acquired CDAD within 90 days. There was a trend for those who developed CDAD to be older than those who did not (75 [64,82] vs 70 [61,80] years, respectively; P = 0.37; Table 1). Severity of CI was not significantly associated with incidence of CDAD (mild: 0%; moderate: 1.5%; severe: 2.1%; P = 0.63). Antibiotic use was more common in patients who developed CDAD than in those who did not (80% vs 69.3%), however, this finding was not statistically significant (P = 0.57; Table 1). Demographic data, ICU admission, length of stay, inpatient PPI use, and colectomy for CI were not significantly associated with CDAD development (Table 1).

CONCLUSION:
Typically, antibiotic use is strongly associated with CDAD but the similar incidence of CDAD between those who did and did not receive antibiotics in our cohort remains unexplained. One possible explanation is that the unique type of injury and healing of the colon wall in CI along with other factors play an important role independent of antibiotic use. The low CDAD incidence might reflect a compromised immune epithelial barrier, allowing more serologically-driven antibodies access to the bowel lumen, thereby minimizing CDAD development by (neutralizing) toxin A and B. Larger studies are needed to better understand the relationship between CDAD and CI.
194 Cadazolid vs. Vancomycin for Treatment of Clostridioides difficile Infection: Systematic Review With Meta-Analysis
Authors: Aziz Muhammad , Weissman Simcha , Fatima Rawish , Alshati Ali , Malik Fahad , Rajani Sabih , Eid Albert , Nawras Ali 
Published: October 2019

INTRODUCTION:
Current guidelines recommend the use of vancomycin for the initial treatment of Clostridioides difficile infection (CDI). Cadazolid, an experimental drug, has been utilized and compared in several studies with varying results.

METHODS:
A systematic literature search was performed using the following electronic databases [Medline, Google Scholar, and Cochrane] for eligible studies. Randomized controlled trials (RCTs) comparing cadazolid with vancomycin for CDI treatment were included. Demographic variables and outcomes (CDI resolution, CDI recurrence, adverse events) were collected.

RESULTS:
Two studies with three RCTs met the inclusion criteria with a total of 1283 patients with CDI who received either cadazolid 250 mg twice daily (624 patients) or vancomycin 125 mg four times daily (659 patients). Clinical cure rate at the end of treatment was not statistically significant (pooled odds ratio (OR) = 0.82; 95% confidence interval (CI) = 0.61 to 1.11; P = 0.20; I2 = 0%). Sustained clinical response at clinical follow-up was also not significantly different (pooled OR = 1.14; 95% CI = 0.91 to 1.43; P = 0.27; I2 = 0%). Cadazolid had a lower recurrence rate than vancomycin (pooled OR = 0.71; 95% CI = 0.52 to 0.98; P = 0.04; I2 = 13%).

CONCLUSION:
To our knowledge, this is the first systematic review and meta-analysis comparing the efficacy, recurrence rates, and safety profile of cadazolid and vancomycin, for the treatment of CDI. Our results indicate that cadazolid did not differ significantly from vancomycin in terms of achieving a higher clinical cure rate, sustained clinical response rate, or fewer adverse effects. However, cadazolid was associated with a lower rate of recurrences than vancomycin. Clostridioides difficile is a challenging pathogen to treat from a clinical perspective. In the last two decades, there has been a dramatic increase in both the incidence and severity of CDI. Hence, while cadazolid and vancomycin are generally safe and well tolerated, cadazolid had a lower CDI recurrence rate than vancomycin thus meriting its further evaluation.
203 Outcomes of Colon Self-Expandable Metal Stents Placed for Malignant and Benign Obstruction at a Tertiary Care Academic Center
Authors: Johannes Andrew , Benson Mark , Akhter Ahmed , Nelsen Eric , Pfau Patrick , Soni Anurag , Reichelderfer Mark , Gopal Deepak 
Published: October 2019

INTRODUCTION:
Endoscopically placed self-expandable metal stent (SEMS) is a minimally invasive treatment for the management of colonic obstruction. SEMS are increasingly being used in benign strictures as a bridge to one step surgery, to avoid ileostomy. There is limited data regarding efficacy, complications and outcomes in benign disease. The aim of this study was to review long- and short-term clinical success of SEMS use for colonic obstruction at our center.

METHODS:
We retrospectively reviewed all the patients who underwent colonic SEMS placement over a fourteen-year period (August 2004 through November 2018) at our academic center. Demographics including age, gender, indication (malignant and benign), technical success, clinical success, complications (perforation, stent migration), mortality, and outcomes were recorded.

RESULTS:
Fifty-six patients underwent colon SEMS over a 14-year period. Forty-eight cases were for malignant indications, 8 were for benign conditions. The benign strictures included post-surgical anastomotic narrowing's (n = 2), extrinsic fibroid compression (n = 1) and diverticular disease (n = 5). Thirty-eight of the malignant cases were due to intrinsic obstruction from primary or recurrent colon cancer; 10 were from extrinsic compression. Fifty strictures occurred on the left side, 6 occurred on the right. The total malignant case (n = 48) procedural success rate was 96% vs. 100% for benign cases (P = 1.0, NS). Overall complication rate was 3.6%: No complications were observed in the malignant group vs. 2 of 8 (25%) for benign obstruction (1-perforation, 1-stent migration) (P = 0.02). When stratifying complications of perforation and stent migration there was no significant difference between the two groups (P = 0.14, NS).

CONCLUSION:
Colon SEMS remains a worthwhile option for colonic obstruction related to malignancy and has a high procedural and clinical success rate. Benign indications for SEMS placement appear to have similar success to malignant. While there appears to be a higher overall complication rate in benign cases, it is limited by sample size. When evaluating for perforation alone there does not appear to be any significant difference between the two groups. SEMS placement may be a practical option for indications other that malignant obstruction. Interventional endoscopists should be aware and discuss the risk for complications in setting of benign conditions. Indications in these cases should be discussed in a multi-disciplinary fashion with colorectal surgery.