Magnetic Resonance Imaging-Based Assessment of Pancreatic Fat Strongly Correlates With Histology-Based Assessment of Pancreas Composition.

OBJECTIVE: The aim of the study is to assess the relationship between magnetic resonance imaging (MRI)-based estimation of pancreatic fat and histology-based measurement of pancreatic composition. MATERIALS AND METHODS: In this retrospective study, MRI was used to noninvasively estimate pancreatic fat content in preoperative images from high-risk individuals and disease controls having normal pancreata. A deep learning algorithm was used to label 11 tissue components at micron resolution in subsequent pancreatectomy histology. A linear model was used to determine correlation between histologic tissue composition and MRI fat estimation. RESULTS: Twenty-seven patients (mean age 64.0 ± 12.0 years [standard deviation], 15 women) were evaluated. The fat content measured by MRI ranged from 0% to 36.9%. Intrapancreatic histologic tissue fat content ranged from 0.8% to 38.3%. MRI pancreatic fat estimation positively correlated with microanatomical composition of fat (r = 0.90, 0.83 to 0.95], P < 0.001); as well as with pancreatic cancer precursor ( r = 0.65, P < 0.001); and collagen ( r = 0.46, P < 0.001) content, and negatively correlated with pancreatic acinar ( r = -0.85, P < 0.001) content. CONCLUSIONS: Pancreatic fat content, measurable by MRI, correlates to acinar content, stromal content (fibrosis), and presence of neoplastic precursors of cancer.

A Department-Sponsored, Hospital-Based Pathology Education Symposium Is a Cost-Effective Method to Provide Laboratory Staff With Highly Rated Continuing Education Experiences.

CONTEXT.­: Continuing education improves the quality of medical care and is a required part of most health care professions. Although a variety of educational modules are available online or at external conferences, completion of these activities can be expensive and time-consuming. In addition, externally produced modules may have limited applicability to a local practice. OBJECTIVE.­: To assess the ability of an economically efficient, locally produced, department-wide pathology educational seminar to efficiently meet education requirements for a large number of employees in a large health system. DESIGN.­: A multiday continuing education symposium was produced annually from 2013 through 2019 at no cost to participants. Metrics related to attendance, number of educational sessions available for registration, and participant satisfaction were tabulated, trended, and compared with similar metrics tabulated from an external continuing education conference that was offered from 2011 through 2012. RESULTS.­: The production of an internal, hospital-based educational symposium increased employee attendance (mean of 635 attendees per year versus 247 at the external program; P < .001) while reducing mean annual cost per attendee ($51 versus $140, P < .001). The number of sessions produced for the internal symposium was 39 per year on average, compared with 12 per year at the external program. Technical staff, residents, fellows, and faculty all contributed to internal educational programming, helping to build a team culture in the department. Overall employee satisfaction was 96.2%. CONCLUSIONS.­: An internal educational pathology symposium led to cost-efficient distribution of continuing education credits to a large number of technical staff, with a high degree of reported employee satisfaction.

Amsterdam International Consensus Meeting: tumor response scoring in the pathology assessment of resected pancreatic cancer after neoadjuvant therapy.

Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including "minimal" or "extensive" with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the "Materials and methods" section.

The "Race" Toward Diversity, Inclusion, and Equity in Pathology: The Johns Hopkins Experience.

With 3.8% black trainees in 2012, pathology had significantly fewer trainees from groups underrepresented in medicine compared to other specialties. To address this, faculty in the Johns Hopkins Department of Pathology established an outreach program and funded rotation for students underrepresented in medicine and from disadvantaged groups. The aims were to increase exposure to the field and improve diversity, inclusion, and equity in pathology. A 1-month rotation for students underrepresented in medicine was established in 2013. Rotation schedules tailored to each rotator's interests included resident conferences and individual faculty meetings. In 2016, a proactive outreach program was established. Faculty visited historically black medical schools and underrepresented in medicine student groups at other institutions, where they gave a "Careers in Pathology" presentation targeted to second- and third-year medical students. Faculty also attended underrepresented in medicine student conferences and participated in high school student programs to further expand the underrepresented in medicine pipeline into medicine and pathology. Since 2016, fourteen outreach presentations have been delivered. The number of rotators increased from 1 in 2013 to 18 in July 2019. Rotators self-identified as African, African American, Hispanic, and Native American. Most were second- to fourth-year medical students, and 1 was a pathology resident. Six rotators are currently pathology residents, and others are strongly considering applying to pathology. The outreach efforts account for the success of our rotation, which, in turn, has had a positive impact on interest in pathology. However, we recognize barriers to retention and intend to incorporate additional professional development activities to further address equity.

Are pancreatic IPMN volumes measured on MRI images more reproducible than diameters? An assessment in a large single-institution cohort.

OBJECTIVES: To assess reproducibility of volume and diameter measurement of intraductal papillary mucinous neoplasms (IPMNs) on MRI images. METHODS: Three readers measured the diameters and volumes of 164 IPMNs on axial T2-weighted images and coronal thin-slice navigator heavily T2-weighted images using manual and semiautomatic techniques. Interobserver reproducibility and variability were assessed. RESULTS: Interobserver intraclass correlation coefficients (ICCs) for the largest diameter measured using manual and semiautomatic techniques were 0.979 and 0.909 in the axial plane, and 0.969 and 0.961 in the coronal plane, respectively. Interobserver ICCs for the volume measurements were 0.973 and 0.970 in axial and coronal planes, respectively. The highest intraobserver reproducibility was noted for coronal manual measurements (ICC 0.981) followed by axial manual measurements (ICC 0.969). For the diameter measurements, Bland-Altman analysis revealed the lowest interobserver variability for manual axial measurements with an average range of 95% limits of agreement (LOA) of 0.68 cm. Axial and coronal volume measurements showed similar 95% LOA ranges (8.9 cm3 and 9.4 cm3, respectively). CONCLUSIONS: Volume and diameter measurements on axial and coronal images show good interobserver and intraobserver reproducibility. The single largest diameter measured manually on axial images showed the highest reproducibility and lowest variability. The 95% LOA may help define reproducible size changes in these lesions using measurements from different readers. KEY POINTS: • MRI measurements by different radiologists can be used for IPMN follow-up. • Both diameter and volume measurements demonstrate excellent interobserver and intraobserver reproducibility. • Manual axial measurements show the highest interobserver reproducibility in determining size. • Axial and coronal volume measurements show similar limits of agreement. • Manual axial measurements show the lowest variability in agreement range.

Detection and localization of surgically resectable cancers with a multi-analyte blood test.

Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

Autoimmune pancreatitis: current diagnostic criteria are suboptimal.

BACKGROUND AND AIMS: The preoperative diagnosis of autoimmune pancreatitis (AIP) is difficult, given its similar clinical presentation to pancreatic cancer. The aims of the study are to describe our center's experience with AIP and apply the Japanese AIP diagnostic criteria to a cohort of patients with histologically-proven AIP in order to assess their performance characteristics. METHODS: A prospective pathology database was queried for AIP patients who were evaluated and/or treated at Johns Hopkins Hospital from 2002 to 2009. AIP histology was defined by the presence of lymphoplasmacytic infiltration, periductal inflammation, fibrosis, and periphlebitis. Imaging, clinical, and biochemical data were analyzed. RESULTS: Thirty patients had pancreatic resection with pathological confirmation of AIP. Imaging revealed pancreatic mass (45%), focal prominence without mass lesion (24%), diffuse enlargement (17%), and normal pancreas (14%). Twenty-four patients underwent an endoscopic retrograde cholangiopancreatography and/or magnetic resonance cholangiopancreatography, and 4/24 (17%) had pancreatic ductal narrowing or irregularity. Extrapancreaticobiliary organ involvement was found in 6% (n = 2) of patients. Biliary strictures were present in 87% of patients. Of 16 patients who underwent preoperative tissue biopsy, 10 had non-diagnostic pathology, five had cellular atypia, and one had AIP. Serum immunoglobulin G4 (IgG4) levels were elevated in 12 of 29 (41%) patients. Three (10%) patients had evidence of extrapancreatic manifestations of AIP. When applying the Japanese criteria to the 27 patients who had serum IgG4 measurement, preoperative biopsy, and cross-sectional abdominal imaging, only 44% of the patients would have been diagnosed accurately. CONCLUSIONS: When applied to a highly-selected single-center referral population in the USA, current Japanese guidelines for the diagnosis of AIP are found to have suboptimal sensitivity.

Assessment of "gene-environment" interaction in cases of familial and sporadic pancreatic cancer.

INTRODUCTION: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. This study characterizes one of the largest national registries of familial PC (FPC) and sporadic PC (SPC), focusing on demographics, clinical factors, self-reported environmental and occupational lifetime exposures, and survival status. BACKGROUND: Reported risk factors for PC include advancing age, a family history of PC, high-risk inherited syndromes, cigarette, cigar, and pipe smoking, exposure to occupational and environmental carcinogens, African-American race, high fat/high cholesterol diet, obesity, chronic pancreatitis, and diabetes mellitus. PATIENTS AND METHODS: This retrospective cross-sectional, case-only analysis includes cases of FPC (n = 569) and SPC (n = 689) from the Johns Hopkins National Familial Pancreas Tumor Registry (NFPTR) enrolled between 1994 and 2005. RESULTS: FPC smokers with environmental tobacco smoke (ETS) exposure were diagnosed at a significantly younger mean age (63.7 years) as compared to FPC non-smokers without ETS exposure (66.6 years; p = 0.05). Non-smoker ETS-exposed cases were diagnosed with PC at a significantly younger mean age (64.0 years) compared to non-smoker non-ETS-exposed cases (66.5 years) (p < 0.0004). The mean age at diagnosis for Ashkenazi Jewish SPC subjects was significantly younger (by 2.1 years) than Ashkenazi Jewish FPC cases (p = 0.05). In addition, Ashkenazi Jewish FPC subjects who smoked were diagnosed 5.9 years earlier than Ashkenazi Jewish FPC non-smokers (p = 0.05). The median length of survival for unresected FPC cases was significantly shorter (168 days) as compared to unresected SPC cases (200 days) (p = 0.04). Survival was improved in resected cases, 713 days for FPC cases and 727 days for SPC cases, but was not significantly different between the groups (p = 0.4). Mild to moderate multiplicative interaction was found between a family history of PC and exposure to asbestos, environmental radon, and environmental tobacco smoke (ETS), as evidenced by odds ratios >1.0. CONCLUSIONS: These are the first data to show that occupational and environmental exposures may act synergistically with inherited or acquired genetic polymorphisms, resulting in earlier occurrence of PC. Exposure to cigarette smoking and ETS exposure in non-smokers when younger than 21 years of age are associated with a younger mean age of diagnosis in FPC and SPC cases and Ashkenazi Jewish smokers, when compared to non-exposed cases. Risk prediction models which take into account environmental exposures as well as family history may more accurately predict the risk of PC. High-risk individuals will likely benefit from early identification of pre-malignant lesions and molecular profiling, as methods of early detection, prevention, and personalized therapy.

PancPRO: risk assessment for individuals with a family history of pancreatic cancer.

PURPOSE: The rapid fatality of pancreatic cancer is, in large part, the result of an advanced stage of diagnosis for the majority of patients. Identification of individuals at high risk of developing pancreatic cancer is a first step towards the early detection of this disease. Individuals who may harbor a major pancreatic cancer susceptibility gene are one such high-risk group. The goal of this study was to develop and validate PancPRO, a Mendelian model for pancreatic cancer risk prediction in individuals with familial pancreatic cancer, to identify high-risk individuals. METHODS: PancPRO was built by extending the Bayesian modeling framework developed for BRCAPRO, trained using published data, and validated using independent prospective data on 961 families enrolled onto the National Familial Pancreas Tumor Registry, including 26 individuals who developed incident pancreatic cancer during follow-up. RESULTS: We developed a risk prediction model, PancPRO, and free software for the estimation of pancreatic cancer susceptibility gene carrier probabilities and absolute pancreatic cancer risk. Model validation demonstrated an observed to predicted pancreatic cancer ratio of 0.83 (95% CI, 0.52 to 1.20) and high discriminatory ability, with an area under the receiver operating characteristic curve of 0.75 (95% CI, 0.68 to 0.81) for PancPRO. CONCLUSION: PancPRO is the first risk prediction model for pancreatic cancer. When we validated our model using the largest registry of familial pancreatic cancer, our model provided accurate risk assessment. Our findings highlight the importance of detailed family history for clinical cancer risk assessment and demonstrate that accurate genetic risk assessment is possible even when the causative genes are not known.

Linkage analysis of chromosome 4 in families with familial pancreatic cancer.

BACKGROUND: Approximately 10% of pancreatic ductal adenocarcinomas have a familial basis. While a small portion of this familial clustering can be explained by inherited mutations in known genes (BRCA2, p16/CDKN2A, PRSS1, and STK11), the genetic basis for the majority of this familial clustering remains unknown. In addition, a pancreatic cancer susceptibility locus has been reported to be linked to chromosome 4q32-34 in a single family having a high penetrance of early-onset pancreatic ductal adenocarcinoma and pancreatic insufficiency. The goal of this study is to determine if linkage to chromosome 4q exists in our series of well-characterized families with idiopathic familial pancreatic cancer enrolled in the Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE). METHODS: Parametric and nonparametric linkage analyses were performed using 21 microsatellite markers on chromosome 4 on affected individuals with pancreatic cancer from 42 familial pancreatic cancer kindreds. RESULTS: Markov Chain Monte Carlo parametric and nonparametric linkage analyses using SIMWALK2 as well as nonparametric linkage analysis using MERLIN did not provide strong evidence of linkage in this region (LOD < 1.0). Only one family provided a multipoint LOD score of >0.5 adjacent to the reported region. CONCLUSIONS: Our results do not support linkage to the 4q32-34 region in the majority of our familial pancreatic cancer kindreds. However, because multiple pancreatic cancer susceptibility genes are likely to exist, it is possible that a subset of the families in this study may be linked to this region.

Assessment of celecoxib pharmacodynamics in pancreatic cancer.

Cyclooxygenase-2 (COX-2) inhibitors are being developed as chemopreventive and anticancer agents. This study aimed to determine the biological effect of the COX-2 inhibitor celecoxib in pancreatic cancer as an early step to the further development of the agent in this disease. Eight patients scheduled for resection of an infiltrating adenocarcinoma of the pancreas were randomized to receive celecoxib at a dose of 400 mg twice daily or placebo for 5 to 15 days before the surgery. In addition, carcinomas from nine additional patients were xenografted in nude mice, expanded, and treated with vehicle or celecoxib for 28 days. Celecoxib markedly decreased the intra-tumor levels of prostaglandin E2 in patient carcinomas and in the heterotransplanted xenografts. However, this effect did not result in inhibition of cell proliferation or microvessel density (as assessed by Ki67 and CD31 staining). In addition, a panel of markers, including bcl-2, COX-1, COX-2, and VEGF, did not change with treatment in a significant manner. Furthermore, there was no evidence of antitumor effects in the xenografted carcinomas. In summary, celecoxib efficiently inhibited the synthesis of prostaglandin E2 both in pancreatic cancer surgical specimens and in xenografted carcinomas but did not exert evident antitumor, antiproliferative, or antiangiogenic effect as a single agent. The direct pancreatic cancer xenograft model proved to be a valuable tool for drug evaluation and biological studies and showed similar results to those observed in resected pancreatic cancer specimens.

Spiritual issues of family members in a pancreatic cancer chat room.

PURPOSE/OBJECTIVES: To describe spiritual issues addressed by users of a pancreatic cancer informational Web site. DESIGN: Qualitative, descriptive. SETTING: The patient and family chat room of Johns Hopkins Hospital's pancreatic cancer Web site. SAMPLE: 600 postings on the pancreatic cancer Web site. METHODS: Identification of categories and themes in Web postings using the constant comparison method of content analysis. MAIN RESEARCH VARIABLES: Spirituality, relationship of the person posting a message (poster) to the person with cancer. FINDINGS: Relationship of the poster to the person with pancreatic cancer was explicit in 68% (n = 410) of the 600 postings, and 83% of those 410 postings indicated that the poster was a family member. Issues of spirituality appeared in 19% (n = 114) of the 600 postings and addressed four themes: spiritual convergence, reframing suffering, hope, and acceptance of the power of God and eternal life. Six percent of postings were by family members reporting on the death of their loved ones, suggesting that the site also served a bereavement function. CONCLUSIONS: Family members of patients with pancreatic cancer sought and received spiritual comfort in a variety of forms in an Internet-based cancer chat room. IMPLICATIONS FOR NURSING: Nurse developers of cancer information Web sites should periodically assess how the sites are being used and apply the information to the refinement of the sites to better meet user needs. Further study is needed to develop and evaluate cancer Web sites as an evolving medium for providing spiritual support to family members of patients with life-threatening forms of cancer.

The effect of a Frequently Asked Questions module on a pancreatic cancer Web site patient/family chat room.

The Internet provides access to health information and a supportive community with similar illness concerns. Securing accurate information about treatment and prognosis is important to those with pancreatic cancer given its high mortality and short survival. The purpose of this descriptive-comparative study was to determine the effect of a Frequently Asked Questions (FAQ) module on postings in the chat room of a pancreatic cancer Web site. Six hundred postings were analyzed. Three themes were isolated: information seeking, giving, or both; support seeking, giving, or both; and reporting status or death. Information included treatments, nutrition, prognosis, end-of-life care, cost of care, symptoms, and support (social, emotional, spiritual, or physical). A greater proportion of postings sought information after the FAQ module was added, although questions about medical treatment decreased, whereas questions about prognosis and end-of-life care nearly doubled. There was no difference in the proportion of postings addressing support. Medical treatment was the most common treatment reported and pain was the most common symptom reported. This study supported the addition of a FAQ module to a pancreatic cancer Web site and revealed the need for information regarding pain management and care giving at the end of life.