Pancreatic Cyst Size Measurement on Magnetic Resonance Imaging Compared to Pathology.

BACKGROUND: While multiple cyst features are evaluated for stratifying pancreatic intraductal papillary mucinous neoplasms (IPMN), cyst size is an important factor that can influence treatment strategies. When magnetic resonance imaging (MRI) is used to evaluate IPMNs, no universally accepted sequence provides optimal size measurements. T2-weighted coronal/axial have been suggested as primary measurement sequences; however, it remains unknown how well these and maximum all-sequence diameter measurements correlate with pathology size. This study aims to compare agreement and bias between IPMN long-axis measurements on seven commonly obtained MRI sequences with pathologic size measurements. METHODS: This retrospective cohort included surgically resected IPMN cases with preoperative MRI exams. Long-axis diameter tumor measurements and the presence of worrisome features and/orhigh-risk stigmata were noted on all seven MRI sequences. MRI size and pathology agreement and MRI inter-observer agreement involved concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC), respectively. The presence of worrisome features and high-risk stigmata were compared to the tumor grade using kappa analysis. The Bland-Altman analysis assessed the systematic bias between MRI-size and pathology. RESULTS: In 52 patients (age 68 ± 13 years, 22 males), MRI sequences produced mean long-axis tumor measurements from 2.45-2.65 cm. The maximum MRI lesion size had a strong agreement with pathology (CCC = 0.82 (95% CI: 0.71-0.89)). The maximum IPMN size was typically observed on the axial T1 arterial post-contrast and MRCP coronal series and overestimated size versus pathology with bias +0.34 cm. The radiologist interobserver agreement reached ICCs 0.74 to 0.91 on the MRI sequences. CONCLUSION: The maximum MRI IPMN size strongly correlated with but tended to overestimate the length compared to the pathology, potentially related to formalin tissue shrinkage during tissue processing.

A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

A pilot study to evaluate tissue- and plasma-based DNA driver mutations in a cohort of patients with pancreatic intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to pancreatic ductal adenocarcinoma that are challenging to manage due to limited imaging, cytologic, and molecular markers that accurately classify lesions, grade of dysplasia, or focus of invasion preoperatively. The objective of this pilot study was to determine the frequency and type of DNA mutations in a cohort of surgically resected, pathologically confirmed IPMN, and to determine if concordant mutations are detectable in paired pretreatment plasma samples. Formalin-fixed paraffin-embedded (FFPE) tissue from 46 surgically resected IPMNs (31 low-grade, 15 high-grade) and paired plasma from a subset of 15 IPMN cases (10 low-grade, 5 high-grade) were subjected to targeted mutation analysis using a QIAseq Targeted DNA Custom Panel. Common driver mutations were detected in FFPE from 44 of 46 (95.6%) IPMN cases spanning all grades; the most common DNA mutations included: KRAS (80%), RNF43 (24%), and GNAS (43%). Of note, we observed a significant increase in the frequency of RNF43 mutations from low-grade to high-grade IPMNs associated or concomitant with invasive carcinoma (trend test, P = 0.01). Among the subset of cases with paired plasma, driver mutations identified in the IPMNs were not detected in circulation. Overall, our results indicate that mutational burden for IPMNs is a common occurrence, even in low-grade IPMNs. Furthermore, although blood-based biopsies are an attractive, noninvasive method for detecting somatic DNA mutations, the QIAseq panel was not sensitive enough to detect driver mutations that existed in IPMN tissue using paired plasma in the volume we were able to retrieve for this retrospective study.

Prophylactic Perioperative Antibiotics in Open Pancreaticoduodenectomy: When Less Is More and When It Is Not. A National Surgical Quality Improvement Program Propensity-Matched Analysis.

INTRODUCTION: We hypothesized that first-generation cephalosporins (G1CEP) provide adequate antimicrobial coverage for pancreaticoduodenectomy (PD) when no biliary stent is present but might be inferior to second-generation cephalosporins or broad-spectrum antibiotics (G2CEP/BS) in decreasing surgical-site infection (SSI) rates when a biliary stent is present. METHODS: The National Surgical Quality Improvement Program 2014-2019 was used to select patients who underwent elective open PD. We divided the population into no-stent versus stent groups based on the status of biliary drainage and then divided each group into G1CEP versus G2CEP/BS subgroups based on the choice of perioperative antibiotics. We matched the subgroups per a propensity score match and analyzed postoperative outcomes. RESULTS: Six thousand two hundred forty five cases of 39,779 were selected; 2821 in the no-stent (45.2%) versus 3424 (54.8%) in the stent group. G1CEP were the antibiotics of choice in 2653 (42.5%) versus G2CEP/BS in 3592 (57.5%) cases. In the no-stent group, we matched 1129 patients between G1CEP and G2CEP/BS. There was no difference in SSI-specific complications (20.3% versus 21.0%; P = 0.677), general infectious complications (25.7% versus 26.9%; P = 0.503), PD-specific complications, overall morbidity, length of stay, or mortality. In the stent group, we matched 1244 pairs. G2CEP/BS had fewer SSI-specific complications (19.9% versus 26.6%; P < 0.001), collections requiring drainage (9.6% versus 12.9%; P = 0.011), and general infectious complications (28.5% versus 34.1%; P = 0.002) but no difference in overall morbidity, mortality, length of stay, and readmission rates. CONCLUSIONS: G2CEP/BS are associated with reduced rates of SSI-specific and infectious complications in stented patients undergoing open elective PD. In patients without prior biliary drainage, G1CEP seems to provide adequate antimicrobial coverage.

The Role of Endoscopic Ultrasonography in the Diagnosis and Staging of Pancreatic Cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death and the second gastrointestinal cancer-related death in the United States. Early detection and accurate diagnosis and staging of pancreatic cancer are paramount in guiding treatment plans, as surgical resection can provide the only potential cure for this disease. The overall prognosis of pancreatic cancer is poor even in patients with resectable disease. The 5-year survival after surgical resection is ~10% in node-positive disease compared to ~30% in node-negative disease. The advancement of imaging studies and the multidisciplinary approach involving radiologists, gastroenterologists, advanced endoscopists, medical, radiation, and surgical oncologists have a major impact on the management of pancreatic cancer. Endoscopic ultrasonography is essential in the diagnosis by obtaining tissue (FNA or FNB) and in the loco-regional staging of the disease. The advancement in EUS techniques has made this modality a critical adjunct in the management process of pancreatic cancer. In this review article, we provide an overall description of the role of endoscopic ultrasonography in the diagnosis and staging of pancreatic cancer.

Endoscopic cryotherapy: Indications, techniques, and outcomes involving the gastrointestinal tract.

Endoscopic cryotherapy is a technique utilized for the ablation of target tissue within the gastrointestinal tract. A cryotherapy system utilizes the endoscopic application of cryogen such as liquid nitrogen, carbon dioxide or liquid nitrous oxide. This leads to disruption of cell membranes, apoptosis, and thrombosis of local blood vessels within the target tissue. Several trials utilizing cryotherapy for Barrett's esophagus (BE) with variable dysplasia, gastric antral vascular ectasia (GAVE), esophageal carcinoma, radiation proctitis, and metastatic esophageal carcinomas have shown safety and efficacy. More recently, liquid nitrogen cryotherapy (cryodilation) was shown to be safe and effective for the treatment of a benign esophageal stricture which was refractory to dilations, steroid injections, and stenting. Moreover, liquid nitrogen cryotherapy is associated with less post procedure pain as compared to radiofrequency ablation in BE with comparable ablation rates. In patients with GAVE, cryotherapy was found to be less tedious as compared to argon plasma coagulation. Adverse events from cryotherapy most commonly include chest pain, esophageal strictures, and bleeding. Gastric perforations did occur as well, but less often. In summary, endoscopic cryotherapy is a promising and growing field, which was first demonstrated in BE, but the use now spans for several other disease processes. Larger randomized controlled trials are needed before its role can be established for these different diseases.

Malignant colon polyps: predicting lymph node metastasis following endoscopic excision.

AIM: The risk of lymph node metastasis (LNM) of malignant colon polyps (MCPs) is partly estimated by histologic features of the sampled polyp. However, the routinely available histologic data is limited to tumor grade and status of lymphovascular invasion (LVI). METHODS: The NCDB for colon cancer 2004-2018 was utilized. Patients with pT1Nx adenocarcinoma arising in a polyp and undergoing partial colectomy with ≥ 12 retrieved nodes were selected. NCDB 2004-2017 was used as a training cohort to develop two scoring systems based on a multivariable regression for predictors of LNM including clinical characteristics, grade, and LVI: a nomogram scoring system (NSS) and a simplified scoring system (SSS). These models were internally validated using NCDB 2018 to calculate precision metrics for each model. RESULTS: Six thousand sixty-nine patients were selected in the training cohort. 64.5% of MCPs were in the sigmoid, and LNM rate was 11.2%. Multivariable regression identified younger age, females, hindgut location, higher grade, and LVI as significant predictors of LNM. LNM risk was 1.2% when all unfavorable predictors were absent and exceeded 10% when NSS > 70 or SSS ≥ 3. In the 2018 validation cohort, 723 patients were scored per NSS and SSS, and the negative predictive value for both was 96%. CONCLUSION: Estimating LNM risk in MCPs by applying clinical characteristics along with limited histologic data can help inform decision-making when considering formal oncologic resection. The NSS and SSS demonstrated comparable predictability of LNM among pT1Nx MCPs. The models require external validation and may be strengthened by incorporating additional endoscopic and pathologic characteristics.

A Case of Esophageal Squamous Cell Carcinoma Metastasized to the Colonic Anastomotic Site of Right Hemicolectomy.

A 73-year-old woman with a history of right hemicolectomy for advanced ascending colon cancer 14 years earlier was referred to our facility for a 2-month history of solid food dysphagia. An esophagogastroduodenoscopy revealed a 7-cm fungating and ulcerated mass in the middle to lower esophagus. The biopsy from the esophageal mass showed a moderately to poorly differentiated squamous cell carcinoma. A colonoscopy showed an end-to-end ileocolonic anastomosis with a 7-mm ulceration in the transverse colon. The biopsy of the ulceration at the anastomotic site showed a moderately to poorly differentiated squamous cell carcinoma with a morphology similar to that of the esophageal mass, rendering the diagnosis of metastatic esophageal squamous cell carcinoma. Colonic metastasis from esophageal squamous cell carcinoma, especially at the anastomotic site, is extremely rare. Although surgical trauma may not have contributed to the anastomotic site metastasis, given the distant timeline, its role in the pathogenesis of metastasis cannot be completely ruled out.

Choice of sedation in endoscopic retrograde cholangiopancreatography: is monitored anesthesia care as safe as general anesthesia? A systematic review and meta-analysis.

BACKGROUND: Monitored anesthesia care (MAC) and general anesthesia (GA) are the 2 most common methods of sedation used for endoscopic retrograde cholangiopancreatography (ERCP). We performed a systematic review and meta-analysis to compare the overall safety between MAC vs. GA in ERCP. METHODS: We conducted a comprehensive search of electronic databases to identify studies reporting the use of MAC or GA as a choice of sedation for ERCP. The primary outcome was to compare the overall rate of sedation-related adverse events in MAC vs. GA groups. The secondary endpoint was to investigate the total duration of the procedure, recovery time, ERCP cannulation rates, and conversion rate of MAC to GA. The meta-analysis was performed using a Der Simonian and Laird random-effects model. RESULTS: A total of 21 studies reporting on 11,592 patients were included. The overall sedation-related side-effects were similar in the GA (12.76%, 95% confidence interval [CI] 5.80-21.73; I2=95%) and MAC (12.08%, 95%CI 5.38-20.89; I2=99%) groups (P=0.956). Hypoxia, arrhythmias, hypotension, aspiration and other sedation-related side-effects were similar between the 2 groups. The mean duration of the procedure was longer in the MAC group, but the mean recovery time was shorter. Significant heterogeneity was noted in our meta-analysis. CONCLUSIONS: In our meta-analysis, the overall sedation-related side-effects were similar between the MAC and GA groups. MAC could be used as a safer alternative to GA when performing ERCP. However, large multicenter randomized control trials are needed to further validate our findings.

The Florida Pancreas Collaborative Next-Generation Biobank: Infrastructure to Reduce Disparities and Improve Survival for a Diverse Cohort of Patients with Pancreatic Cancer.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

A narrative review of Barrett's esophagus in 2020, molecular and clinical update.

Barrett's esophagus (BE) is a condition resulting from an acquired metaplastic epithelial change in the esophagus in response to gastroesophageal reflux. BE is the only known precursor lesion to esophageal adenocarcinoma, and can progress from non-dysplastic BE (NDBE) to low grade dysplasia (LGD) and high grade dysplasia (HGD), and ultimately invasive carcinoma. Although the risk of developing esophageal adenocarcinoma (EAC) in NBDE is less than 0.5% per year, there has been a rising incidence of EAC in Western countries, which continue to drive efforts to optimize screening and surveillance methods. The current gold standard for diagnosis is esophagogastroduodenoscopy (EGD), and there has been significant interest in alternative, minimally invasive methods for screening which would be more readily accessible in the primary care setting. Surveillance endoscopy in 3-5 years is recommended for NDBE given the low progression to EAC. The mainstay of treatment for LGD and HGD is endoscopic eradication therapy (EET). Visible lesions are treated with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Radiofrequency ablation (RFA) is considered first line therapy for flat dysplastic BE and cryotherapy has shown promising results as an alternate form of treatment for of dysplasia. The molecular progression of BE to EAC is a complex process involving multiple pathways involving genetic and epigenetic modifications. Genomic studies have further led to the understanding of the complex molecular landscape that occurs early and late in the disease process. Promising biomarker panels have been investigated to help with the diagnosis of BE as well as aid in the risk stratification of BE during surveillance. In addition, clinical prediction models have been developed to categorize BE patients in low, intermediate, and high risk for progression to HGD and EAC. Further clinical and translational research is needed to help refine markers and techniques in diagnosis, screening, and surveillance.

Is Preoperative G-Tube Use Safe for Esophageal Cancer Patients?

Objective: Gastrostomy tubes (g-tubes) have been used with caution prior to esophageal resection due to the risks of inoculation metastasis and of injury to the gastric conduit used for reconstruction. In this study, we aim to evaluate the safety of preoperative g-tube placement by comparing outcomes in patients undergoing esophageal resection with and without prior g-tube use.Method: We retrospectively reviewed our institution's database of 1113 esophagectomies performed between 1994 and 2018. We included only patients who received neoadjuvant therapy and identified 65 patients who received preoperative nutritional support through a g-tube (GT+) and 657 who did not (GT-). Demographics, postoperative complications, survival, and cancer recurrence rates were compared between GT + and GT- using Chi-squared and Kaplan-Meier survival analyses.Results: Seven-hundred twenty-two patients (122 female, 600 male) with a median age of 63.2 (28.2-86.3) met our inclusion criteria. Between GT+ (n = 65) and GT- (n = 657), there were no significant differences in anastomotic leak rates (11.5% vs 10.9%; p = 0.901), postoperative mortality (3.1% vs 3.9%; p = 0.765), or overall complications (63.1% vs 65.1%; p = 0.746). GT + was associated with a significantly lower overall survival compared to GT- (32.5 m vs 92.9 m; p = 0.003), and tumor recurrence rates were similar (30.6% vs 31.8%; p = 0.851). There were no cases documenting damage to the gastric conduit caused by prior g-tube placement.Conclusions: G-tube usage was not associated with increased tumor recurrence, anastomotic leak rates, or overall complication rates in this study. Our data suggest that g-tube usage is safe for patients with esophageal cancer requiring preoperative nutrition.

Common GI Drug Interactions in the Elderly.

OPINION STATEMENT: The careful review of drug-drug interactions is vital to the safe prescribing of medications for chronic medical conditions. The elderly population suffers from multiple medical problems, and polypharmacy leads to further morbidity in this vulnerable group of patients. We discuss gastrointestinal conditions such as GERD, peptic ulcer disease, gastroparesis, diarrhea, constipation, irritable bowel syndrome, inflammatory bowel disease, chronic liver disease and the commonly used medications in these conditions. Treatment options must be individualized and tailored to accommodate the underlying pharmacokinetics and known drug-drug interactions. The indication for the use of a therapeutic agent in the elderly and the duration of use must be frequently readdressed to help prevent polypharmacy and adverse drug reactions. Medications should be started at a low dose with careful titration to achieve a clinical response to prevent toxicity. The aim of this article is to increase awareness of important drug-drug interactions of commonly prescribed gastrointestinal medications in the elderly.

Environmental influences on the onset and clinical course of Crohn's disease-part 1: an overview of external risk factors.

The pathogenesis of Crohn's disease (CD) involves host, genetic, and environmental factors. These factors result in disturbances in the innate and adaptive immune systems and composition of the intestinal microbiota. Epidemiologic and migration studies support an environmental component in the development of CD. Environmental risk factors include childhood hygiene, air pollution, breastfeeding, smoking, diet, stress, exercise, seasonal variation, and appendectomy. This review, part 1 of a 2-part series, provides an overview of these external contributors to the development or exacerbation of CD. Part 2, which will be published in a subsequent issue, will discuss the influences of infections, vaccinations, and medications (including antibiotics, nonsteroidal anti-inflammatory agents, and oral contraceptives) on CD.

Environmental influences on the onset and clinical course of Crohn's disease-part 2: infections and medication use.

The pathogenesis of Crohn's disease (CD) involves host, genetic, and environmental factors. These factors result in disturbances in the innate and adaptive immune systems and composition of the intestinal microbiota. Epidemiologic and migration studies support an environmental component in the development of CD. Environmental risk factors include childhood hygiene, air pollution, breastfeeding, smoking, diet, stress, exercise, seasonal variation, appendectomy, medications, and infections. This 2-part series provides an overview of these external contributors to the development or exacerbation of CD. Part 1, which was published in a previous issue, focused on childhood factors, perinatal influences, and lifestyle choices. Part 2, presented here, details the effects of infections, antibiotics, nonsteroidal anti-inflammatory drugs, and oral contraceptives.

Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity.

Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown. Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO(*)). Here we show that aldosterone (10(-9)-;10(-7) mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO(*) levels-similar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMP-response element modulator (CREM) to inhibit cyclic AMP-response element binding protein (CREB)-mediated G6PD transcription. In vivo, infusion of aldosterone decreased vascular G6PD expression and impaired vascular reactivity. These effects were abrogated by spironolactone or vascular gene transfer of G6pd. These findings demonstrate that aldosterone induces a G6PD-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6PD activity.