BACKGROUND:The United States notoriously has one of the highest rates of incarceration in the world, yet scant attention to the health care needs of those incarcerated exists within laboratory medicine and pathology training and education. This article explores health disparities among incarcerated and released individuals regarding diagnostic laboratory testing and pathology services. METHODS:A literature search was conducted for articles published between 2002 and 2023 using keywords including "healthcare," "incarcerated," "laboratory services," "pathology services," and "health insurance for prisoners." Central themes were extracted and discussed to reveal the realities of health care during and after release from incarceration. Excluded from the analysis were articles about the immediate or extended family of incarcerated persons. RESULTS:Incarcerated individuals have an increased risk for the development and exacerbation of communicable and noncommunicable diseases and mental health disorders, which results in exceedingly high morbidity and mortality rates. CONCLUSION:Policy changes are needed to mitigate disparities and improve health outcomes for incarcerated and released persons. Central to these disparities is decreased access to laboratory and pathology services, impeded by inadequate health care funding for these carceral institutions. Providing additional funding to the carceral system's health care budget is necessary to improve access to pathology and laboratory services.

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Supplementary Table 1 - PDF file 74K, Prevalence of serrated lesion subtypes with mutant BRAF, CIMP-high, and methylated MLH1: Group Health Enrollees 1998-2007

Supplementary Data from A Genetic Expression Profile Associated with Oral Cancer Identifies a Group of Patients at High Risk of Poor Survival

Supplementary Figure S1; Supplementary Tables S1-S4.

The fields of pathology and laboratory medicine have a long-standing pipeline problem. Most students do not have medical laboratory sciences or pathology on their list of possible future careers, partly because their exposure to those fields as careers is extremely limited. Confounding this problem are the incorrect and contradictory impressions that pathology might be an “inferior” specialty within medicine (due to lack of direct patient contact), chosen by only those with poor communication skills or those who are not doing well academically. Others believe incorrectly that pathology requires only the highest level of scientific knowledge and skills, such that students who are not in the top tiers of their basic science courses need not apply.

Our aims were to assess performance of duodenal intraepithelial lymphocyte counting for diagnosis of Helicobacter pylori (H. pylori) gastritis, and effects of eradication therapy on intraepithelial lymphocytosis. Paired duodenal and gastric biopsies from subjects with a pathologic diagnosis of H. pylori gastritis were reviewed. Higher duodenal intraepithelial lymphocyte counts were observed in 40 subjects with H. pylori gastritis (26 ± 5 per villus) than 52 subjects negative for H. pylori (12 ± 2 per villus). After successful eradication therapy, duodenal lymphocytes were indistinguishable from H. pylori–negative subjects, whereas they remained elevated after failed eradication therapy. This study confirms previous reports of increased duodenal intraepithelial lymphocytes in patients with concurrent Helicobacter pylori gastritis. Intraepithelial lymphocyte counts of > 15 per villus or > 10 per 100 enterocytes were predictive of infection. Duodenal lymphocytosis decreases significantly after successful eradication therapy but remains elevated when treatment fails.

Objectives: To WA the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer. Materials and Methods: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay. Ridge-penalized Cox regressions were applied to samples randomly split into discovery and validation sets to build models and evaluate the performance of the 13-gene signature in predicting 2-year oral cavity cancer-specific survival overall and separately for patients with early and late stage disease. Results: Among AJCC stage I/II patients, including the 13-gene signature in the model resulted in substantial improvement in the prediction of 2-year oral cavity cancer-specific survival. For models containing age and sex with and without the 13-gene signature score, the areas under the Receiver Operating Characteristic Curve (AUC) and partial AUC were 0.700 vs. 0.537 (p < 0.001), and 0.046 vs. 0.018 (p < 0.001), respectively. Improvement in predicting prognosis for AJCC stage III/IV disease also was observed, but to a lesser extent. Conclusions: If confirmed using tumor samples from a larger number of early stage oral cavity cancer patients, the 13-gene signature may inform personalized treatment of early stage HPV-negative and p16-negative oral cavity cancer patients.

Purpose: Molecular characteristics, including BRAF mutation, MLH1 methylation, and CpG island methylator phenotype (CIMP), help identify aggressive subtypes of colorectal cancer (CRC), but their role is unclear for precursor lesions, especially in serrated polyps. Hyperplastic polyps (HPs) are serrated polyps that were considered to have no malignant potential, but a subset of HPs has been reclassified as sessile serrated polyps/adenomas (SSP/As), and SSP/As are now considered CRC precursors. In this study, we evaluated the association between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia. Methods: Study subjects included Kaiser Permanente Washington members who were 20-75 years old, received an index colonoscopy between 1/1/98-12/31/07 with a diagnosis of HPs or SSP/As and were free of synchronous conventional adenomas, inflammatory bowel disease, familial CRC syndromes, and prior or prevalent CRC. All eligible participants received ≥1 subsequent endoscopy or a CRC diagnosis before 1/1/13. These subsequent endoscopy pathology reports and clinical biopsies were reviewed for advanced colorectal neoplasia, defined as CRC, conventional adenomas ≥10 mm, with ≥20% villous components, with high-grade dysplasia, or SSP/As with nuclear dysplasia. Incident CRC cases were also identified through linkage to the SEER registry. Polyps from index colonoscopies were assayed for BRAF mutation (V600E), MLH1 methylation, and CIMP (using an 8-marker panel). We used generalized estimating equations with a binomial distribution, logit link, and independent correlation structure to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing subgroups of serrated polyps with different molecular characteristics. Results: We included 733 subsequent endoscopies among 553 individuals with index serrated polyps (420 HPs and 133 SSP/As). The prevalence of BRAF mutation, MLH1 methylation, and CIMP-high among index serrated polyps were 51%, 2%, and 4% respectively. Compared to those without MLH1 methylation, those with MLH1methylated serrated lesions were more likely to have advanced colorectal neoplasia at a subsequent endoscopy, but the association was not statistically significant (adjusted OR = 1.95; 95% CI: 0.46-8.35). When restricted to index SSP/As, we observed a stronger association with MLH1 methylation (adjusted OR = 4.66, 95% CI: 1.06-20.51). BRAF and CIMP were also not statistically significantly associated with advanced colorectal neoplasia, even among those with SSP/As at the index colonoscopy. Conclusion: There was no association between the molecular characteristics of serrated polyps and subsequent advanced colorectal neoplasia. However, among index SSP/As, we observed a strong association between MLH1 methylation and subsequent advanced neoplasia. Citation Format: Xinwei Hua, Polly Newcomb, Jessica Chubak, Rachel Malen, Rebecca Ziebell, Aruna Kamineni, Lee-Ching Zhu, Melissa Upton, Hana Newman, Sheetal Hardikar, Andrea Burnett-Hartman. Association between molecular characteristics of serrated polyps and subsequent advanced colorectal neoplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3310.

BackgroundTreatment of Helicobacter pylori infection is often empiric; however, current guidelines for management of Helicobacter pylori infection advise against the use of standard triple therapy (clarithromycin, amoxicillin, and proton-pump inhibitor) when clarithromycin resistance exceeds 20%. We developed and tested a new culture-free assay to detect clarithromycin resistance-conferring mutations to determine the prevalence of H.pylori clarithromycin resistance in patients from the United States Pacific Northwest. Materials and MethodsDroplet digital PCR (ddPCR) was used to detect the H.pylori 23S rRNA gene, and resistance-conferring mutations, in archived, formalin-fixed, paraffin-embedded (FFPE) gastric tissue and to retrospectively determine the prevalence of clarithromycin-resistant H.pylori among 110 patients at an academic medical center in the Northwest United States between 2012 and 2014. ResultsOf 102 patients with the H.pylori 23S rRNA gene detected by the ddPCR assay, 45 (44%) had clarithromycin resistance mutations. Thirty-three of the 45 patients with clarithromycin resistance mutations had a mix of wild-type and resistance alleles. Prevalence of clarithromycin resistance mutations differed among racial groups and was highest among Asians, with mutations detected in 14 (67%) of the 21 patient samples. ConclusionsThe prevalence of clarithromycin resistance detected in this region exceeds 20%, indicating that standard triple therapy should not be the first-line antibiotic treatment for H.pylori infection. Culture-free assays for detecting clarithromycin resistance mutations can be performed on archived tissue samples and will aid in informing tailored treatment for effective H.pylori eradication.

Short telomeres have been associated with increased risk of many cancers, particularly cancers of the gastrointestinal tract including esophagus and stomach. However, the association between telomere length (TL) and colorectal cancer and its precursors, colorectal polyps, is not clear.

Importance Global health systems are shifting toward value-based care in an effort to drive better outcomes in the setting of rising health care costs. This shift requires a common definition of value, starting with the outcomes that matter most to patients. Objective The International Consortium for Health Outcomes Measurement (ICHOM), a nonprofit initiative, was formed to define standard sets of outcomes by medical condition. In this article, we report the efforts of ICHOM’s working group in colorectal cancer. Evidence Review The working group was composed of multidisciplinary oncology specialists in medicine, surgery, radiation therapy, palliative care, nursing, and pathology, along with patient representatives. Through a modified Delphi process during 8 months (July 8, 2015 to February 29, 2016), ICHOM led the working group to a consensus on a final recommended standard set. The process was supported by a systematic PubMed literature review (1042 randomized clinical trials and guidelines from June 3, 2005, to June 3, 2015), a patient focus group (11 patients with early and metastatic colorectal cancer convened during a teleconference in August 2015), and a patient validation survey (among 276 patients with and survivors of colorectal cancer between October 15, 2015, and November 4, 2015). Findings After consolidating findings of the literature review and focus group meeting, a list of 40 outcomes was presented to the WG and underwent voting. The final recommendation includes outcomes in the following categories: survival and disease control, disutility of care, degree of health, and quality of death. Selected case-mix factors were recommended to be collected at baseline to facilitate comparison of results across treatments and health care professionals. Conclusions A standardized set of patient-centered outcome measures to inform value-based health care in colorectal cancer was developed. Pilot efforts are under way to measure the standard set among members of the working group.

Orthotopic liver transplantation is the best option for patients with carefully selected unresectable disease because of underlying liver dysfunction. The 5-year survival rate after orthotopic liver transplantation for early detected hepatocellular carcinoma (HCC) is high, and a similar or even higher rate is reported in those with radiologically undetected HCC. This study evaluated and compared the histologic features of pretransplant radiologically undetected (14 patients, 25 tumors) versus detected (36 patients, 45 tumors) HCCs. Tumor size, tumor differentiation, number of unpaired arteries, mitotic count per 10 high-power fields, CD34 immunostain to assess microvessel density, and Ki67 immunostain were compared with the Liver Imaging Reporting and Data System score, which was retrospectively assigned to each tumor in both groups. The Liver Imaging Reporting and Data System score was significantly higher in the HCC detected group (P<0.001). The vast majority of the undetected HCCs (88%) was <2 cm in size. Only 12% of the undetected HCCs were ≥2 cm, whereas 51% of the detected HCCs were ≥2 cm in size. Higher rate of moderate to poor tumor differentiation was noted in the detected HCCs compared with the undetected group (89% vs. 60%; P=0.004). No statistically significant difference in the number and distribution of unpaired arteries, or mitotic count was observed in 2 groups (although fewer unpaired arteries were identified in the undetected group). The detected HCCs had a higher rate of 2+ CD34 staining compared with the undetected HCCs (68% vs. 27%; P=0.002), whereas the opposite was observed for 1+ CD34 staining (59% undetected HCCs vs. 17% detected HCCs; P=0.002). Ki67 proliferative index was not statistically different between the 2 groups (120.8/1000 cells detected HCCs vs. 81.8/1000 cells undetected HCCs; P=0.36). The factors associated with failing to detect HCCs pretransplant by radiologic studies include small tumor size (<2 cm), low-grade histologic differentiation, and low microvessel density (low CD34 staining). A significant association between the number and distribution of unpaired arteries and HCC detection has not been established by our study.

Oral contraceptives (OC) are associated with a decreased risk of colorectal cancers; however, a recent study reported an increased risk of small colorectal adenomas associated with OC use. To determine if these results were replicable in a different study population, we investigated the relationship between OC use and other reproductive factors and risk of colorectal polyps in a case–control study in western Washington.

Juvenile polyps involving the stomach are uncommon. Massive gastric juvenile polyposis is even rarer.We describe the clinicopathologic features of nine cases of massive gastric juvenile polyposis.All patients had anemia; four had hypoalbuminemia. The polyps were composed predominantly of dilated crypts lined by columnar epithelium and abundant edematous stroma with mixed inflammatory infiltrates. One patient had a poorly differentiated adenocarcinoma, arising in juvenile polyp-associated intraepithelial neoplasia. A second patient had a well-differentiated intramucosal adenocarcinoma arising in a juvenile polyp with high-grade dysplasia. Three of our cases had polyposis restricted to the stomach. Six (66.6%) had loss of SMAD4 immunoreactivity, making them subject to severe bleeding and hypoproteinemia, as well as developing severe dysplasia or adenocarcinoma.SMAD4 immunohistochemstry is a helpful ancillary diagnostic test in cases of suspected juvenile polyposis syndrome involving the stomach.

Oral squamous cell carcinoma (OSCC) is the most commonly diagnosed type of head and neck cancer, accounting for similar to 300,000 new cases worldwide annually. Carbonic anhydrase IX (CAIX) and Ki-67 have been associated with reduced disease-specific survival (DSS) in patients with OSCC. We previously proposed a combined CAIX and Ki-67 signature of 'functional hypoxia' and sought to replicate this association in a larger independent cohort of patients with OSCC at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle. The study population included patients with incident primary OSCC treated at the University of Washington Medical Center and the Harborview Medical Center in Seattle between December 2003 and February 2012. Archived tumor blocks were obtained with tissue samples from 189 patients, and triplicate 0.6 mm cores were assembled into tissue microarrays (TMAs). Fluorescence immunohistochemistry and AQUAnalysis (TM) were used to quantify the expression of tumoral CAIX (tCAIX) and stromal CAIX (sCAIX) and tumoral Ki-67 for each TMA core. Hazard ratios for DSS were calculated using Cox proportional hazards analysis. High tCAIX and sCAIX expression levels were associated with reduced DSS (aHR=1.003, 95% CI: 1.00-1.01 and aHR=1.010, 95% CI: 1.001-1.019, per AQUA score unit, respectively). Ki-67 expression was not associated with survival (aHR=1.01, 95% CI: 0.99-1.02) in the FHCRC cohort. DSS for patients with high sCAIX and low Ki-67 did not differ from that of other patient groups. Elevated tCAIX was associated with reduced DSS as a continuous and as a dichotomized (75%) variable. sCAIX was associated with DSS as a continuous variable but not when dichotomized (75%). However, the previously proposed 'functional hypoxia' signature was not replicated in the current FHCRC study. The failure to replicate our prior observation of poorer survival in patients with combined high sCAIX and low tumoral Ki-67 was likely due to the absence of an association between tumoral Ki-67 and DSS in this cohort. However, the association between DSS and tCAIX and sCAIX supports a role for CAIX in OSCC clinical outcomes.

OBJECTIVES:The aim of this study was to evaluate the concordance in grade assignment for gastroenteropancreatic neuroendocrine tumors using mitotic count (MC), Ki-67 proliferative index (KPI), and phosphohistone H3 count (PHH3C).METHODS:Resected gastroenteropancreatic neuroendocrine tumors were graded based on MC, KPI, and PHH3C. Concordance was determined using a weighted κ statistic. Median survival across each grade category was determined using Kaplan-Meier methods.RESULTS:Of the 110 patients, the majority had gastrointestinal primaries and grade 1 or 2 tumors. Rates of discordance in grade assignment were 29% of cases for KPI versus MC (κW = 0.26), 32% for PHH3C versus MC (κW = 0.34), and 32% for PHH3C versus KPI (κW = 0.37). There was fair agreement between grading by KPI and MC. Relative to grade by KPI and MC, PHH3C tended to upgrade tumors. The proportion alive at 3 and 5 years was not significantly different for patients with grade 1 versus grade 2 tumors.CONCLUSIONS:The concordance between KPI and MC was fair. Phosphohistone H3 count tended to upgrade tumors using the cutoffs established by MC. Grade 1 and grade 2 tumors were associated with similar survival regardless of grading method. The overall relevance of the current cutoff values used in grading neuroendocrine tumors may need to be revisited.

Abstract Background: Recent research suggests that in addition to advanced adenomas, sessile serrated polyps (SSPs) may be important precursors for proximal colon cancer. In this study, we conducted the first large cohort study to evaluate the risk of colorectal cancer (CRC) in patients diagnosed with SSPs through usual care. Methods: The University of Washington Medical Center (UWMC) uses a comprehensive electronic medical records (EMR) system to track patient demographics and health-related information, including diagnoses and procedures for all patients. We used procedure codes to identify a cohort of patients receiving colonoscopies at UWMC from 2003-2013. Natural language processing of text in the final diagnosis section of the pathology report was used to characterize the type of polyps present at each colonoscopy procedure, including non-advanced conventional adenomas, advanced conventional adenomas (defined as having villous histology, high-grade dysplasia, or a diameter ≥ 10 mm), and sessile serrated polyps. These colonoscopy records were then linked to the Puget Sound Surveillance, Epidemiology, and End Results Cancer Registry (SEER) and subsequent EMR data to identify incident CRCs occurring through December 31, 2014 within this cohort. Those who lived outside of the SEER catchment area or who had prior colectomy, inflammatory bowel disease, or CRC were excluded from analyses. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the risk of CRC in each polyp group to those who were polyp-free at an index colonoscopy. HR estimates were adjusted for age, sex, race/ethnicity, smoking status, and body mass index. Results: From 2003 through 2013, 32,136 colonoscopies were performed at UWMC, and 17,424 colonoscopies from 14,846 patients met the study inclusion criteria. Of these patients, 8,908 were polyp-free, 4,145 had only non-advanced conventional adenomas, 927 had advanced conventional adenomas and no SSPs, 314 had ≥1 SSP and ≥1 conventional adenoma, and 552 had SSPs and no conventional adenomas at an index colonoscopy. Median follow-up time in the study cohort was 5.8 years, and 66 incident colorectal cancers occurred during the follow-up period. The risk of incident CRC in those with advanced conventional adenomas at their index colonoscopy was significantly higher than those who were polyp-free (HR=3.9; CI: 1.9-7.7). However, there was not a statistically significant difference in the risk of incident CRC between those who were polyp-free at their index colonoscopy and those who had only non-advanced conventional adenomas (HR=1.5; CI: 0.8-2.6), SSPs with conventional adenomas (HR=2.0; CI: 0.5-8.7), or SSPs without conventional adenomas (HR=1.3; CI: 0.3-5.5). Discussion: Despite recent evidence from cross-sectional studies suggesting that SSPs are high-risk precursors for a subset of colorectal cancers, our results indicate that the risk of CRC in patients with clinically-diagnosed SSPs is similar to the risk of CRC in those with non-advanced adenomas. Additional longitudinal studies of SSPs diagnosed through usual care are needed to inform guidelines for the surveillance of patients with SSPs. This abstract is also being presented as Poster B01. Citation Format: Andrea Burnett-Hartman, Polly A. Newcomb, Chan X. Zeng, Yingye Zheng, John M. Inadomi, Christine Fong, Melissa P. Upton, William M. Grady. Using medical informatics to evaluate the risk of colorectal cancer in patients with clinically diagnosed sessile serrated polyps. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr PR05.