Rates of Downstream Procedures and Complications Associated With Lung Cancer Screening in Routine Clinical Practice : A Retrospective Cohort Study.

BACKGROUND: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) reduces lung cancer mortality but can lead to downstream procedures, complications, and other potential harms. Estimates of these events outside NLST (National Lung Screening Trial) have been variable and lacked evaluation by screening result, which allows more direct comparison with trials. OBJECTIVE: To identify rates of downstream procedures and complications associated with LCS. DESIGN: Retrospective cohort study. SETTING: 5 U.S. health care systems. PATIENTS: Individuals who completed a baseline LDCT scan for LCS between 2014 and 2018. MEASUREMENTS: Outcomes included downstream imaging, invasive diagnostic procedures, and procedural complications. For each, absolute rates were calculated overall and stratified by screening result and by lung cancer detection, and positive and negative predictive values were calculated. RESULTS: Among the 9266 screened patients, 1472 (15.9%) had a baseline LDCT scan showing abnormalities, of whom 140 (9.5%) were diagnosed with lung cancer within 12 months (positive predictive value, 9.5% [95% CI, 8.0% to 11.0%]; negative predictive value, 99.8% [CI, 99.7% to 99.9%]; sensitivity, 92.7% [CI, 88.6% to 96.9%]; specificity, 84.4% [CI, 83.7% to 85.2%]). Absolute rates of downstream imaging and invasive procedures in screened patients were 31.9% and 2.8%, respectively. In patients undergoing invasive procedures after abnormal findings, complication rates were substantially higher than those in NLST (30.6% vs. 17.7% for any complication; 20.6% vs. 9.4% for major complications). LIMITATION: Assessment of outcomes was retrospective and was based on procedural coding. CONCLUSION: The results indicate substantially higher rates of downstream procedures and complications associated with LCS in practice than observed in NLST. Diagnostic management likely needs to be assessed and improved to ensure that screening benefits outweigh potential harms. PRIMARY FUNDING SOURCE: National Cancer Institute and Gordon and Betty Moore Foundation.

Uptake of Lung Cancer Screening CT After a Provider Order for Screening in the PROSPR-Lung Consortium.

BACKGROUND: Uptake of lung cancer screening (LCS) has been slow with less than 20% of eligible people who currently or formerly smoked reported to have undergone a screening CT. OBJECTIVE: To determine individual-, health system-, and neighborhood-level factors associated with LCS uptake after a provider order for screening. DESIGN AND SUBJECTS: We conducted an observational cohort study of screening-eligible patients within the Population-based Research to Optimize the Screening Process (PROSPR)-Lung Consortium who received a radiology referral/order for a baseline low-dose screening CT (LDCT) from a healthcare provider between January 1, 2015, and June 30, 2019. MAIN MEASURES: The primary outcome is screening uptake, defined as LCS-LDCT completion within 90 days of the screening order date. KEY RESULTS: During the study period, 18,294 patients received their first order for LCS-LDCT. Orders more than doubled from the beginning to the end of the study period. Overall, 60% of patients completed screening after receiving their first LCS-LDCT order. Across health systems, uptake varied from 41 to 87%. In both univariate and multivariable analyses, older age, male sex, former smoking status, COPD, and receiving care in a centralized LCS program were positively associated with completing LCS-LDCT. Unknown insurance status, other or unknown race, and lower neighborhood socioeconomic status, as measured by the Yost Index, were negatively associated with screening uptake. CONCLUSIONS: Overall, 40% of patients referred for LCS did not complete a LDCT within 90 days, highlighting a substantial gap in the lung screening care pathway, particularly in decentralized screening programs.

The Kaiser Permanente Research Bank Cancer Cohort: a collaborative resource to improve cancer care and survivorship.

BACKGROUND: The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and surveys linked to electronic health records (EHR) from approximately 400,000 adult KP members. Within the KPRB, we developed a Cancer Cohort to address issues related to cancer survival, and to understand how genetic, lifestyle and environmental factors impact cancer treatment, treatment sequelae, and prognosis. We describe the Cancer Cohort design and implementation, describe cohort characteristics after 5 years of enrollment, and discuss future directions. METHODS: Cancer cases are identified using rapid case ascertainment algorithms, linkage to regional or central tumor registries, and direct outreach to KP members with a history of cancer. Enrollment is primarily through email invitation. Participants complete a consent form, survey, and donate a blood or saliva sample. All cancer types are included. RESULTS: As of December 31, 2020, the cohort included 65,225 cases (56% female, 44% male) verified in tumor registries. The largest group was diagnosed between 60 and 69 years of age (31%) and are non-Hispanic White (83%); however, 10,076 (16%) were diagnosed at ages 18-49 years, 4208 (7%) are Hispanic, 3393 (5%) are Asian, and 2389 (4%) are Black. The median survival time is 14 years. Biospecimens are available on 98% of the cohort. CONCLUSIONS: The KPRB Cancer Cohort is designed to improve our understanding of treatment efficacy and factors that contribute to long-term cancer survival. The cohort's diversity - with respect to age, race/ethnicity and geographic location - will facilitate research on factors that contribute to cancer survival disparities.

Percentage Up to Date With Chest Computed Tomography Among Those Eligible for Lung Cancer Screening.

INTRODUCTION: Authors aimed to calculate the percentage up-to-date with testing in the context of lung cancer screening across 5 healthcare systems and evaluate differences according to patient and health system characteristics. METHODS: Lung cancer screening‒eligible individuals receiving care within the five systems in the Population-based Research to Optimize the Screening Process Lung consortium from October 1, 2018 to September 30, 2019 were included in analyses. Data collection was completed on June 15, 2021; final analyses were completed on April 1, 2022. Chest computed tomography scans and patient characteristics were obtained through electronic health records and used to calculate the percentage completing a chest computed tomography scan in the previous 12 months (considered up-to-date). The association of patient and healthcare system factors with being up-to-date was evaluated with adjusted prevalence ratios and 95% CIs using log-binomial regression models. RESULTS: There were 29,417 individuals eligible for lung cancer screening as of September 30, 2019; 8,333 (28.3%) were up-to-date with testing. Those aged 65-74 years (prevalence ratio=1.19; CI=1.15, 1.24, versus ages 55-64), those with chronic obstructive pulmonary disease (prevalence ratio=2.05; CI=1.98, 2.13), and those in higher SES census tracts (prevalence ratio=1.22; CI=1.16, 1.30, highest quintile versus lowest) were more likely to be up-to-date. Currently smoking (prevalence ratio=0.91; CI=0.88, 0.95), having a BMI ≥30 kg/m2 (prevalence ratio=0.83; CI=0.77, 0.88), identifying as Native Hawaiian or other Pacific Islander (prevalence ratio=0.79; CI=0.68, 0.92), and having a decentralized lung cancer screening program (prevalence ratio=0.77; CI=0.74, 0.80) were inversely associated with being up-to-date. CONCLUSIONS: The percentage up-to-date with testing among those eligible for lung cancer screening is well below up-to-date estimates for other types of cancer screening, and disparities in lung cancer screening participation remain.

Smoking status and the association between patient-level factors and survival among lung cancer patients.

BACKGROUND: Declines in the prevalence of cigarette smoking, advances in targeted therapies, and implementation of lung cancer screening have changed the clinical landscape for lung cancer. The proportion of lung cancer deaths is increasing in those who have never smoked cigarettes. To better understand contemporary patterns in survival among patients with lung cancer, a comprehensive evaluation of factors associated with survival, including differential associations by smoking status, is needed. METHODS: Patients diagnosed with lung cancer between January 1, 2010, and September 30, 2019, were identified. We estimated all-cause and lung cancer-specific median, 5-year, and multivariable restricted mean survival time (RMST) to identify demographic, socioeconomic, and clinical factors associated with survival, overall and stratified by smoking status (never, former, and current). RESULTS: Analyses included 6813 patients with lung cancer: 13.9% never smoked, 54.2% formerly smoked, and 31.9% currently smoked. All-cause RMST through 5 years for those who never, formerly, and currently smoked was 32.1, 25.9, and 23.3 months, respectively. Lung cancer-specific RMST was 36.3 months, 30.3 months, and 26.0 months, respectively. Across most models, female sex, younger age, higher socioeconomic measures, first-course surgery, histology, and body mass index were positively associated, and higher stage was inversely associated with survival. Relative to White patients, Black patients had increased survival among those who formerly smoked. CONCLUSIONS: We identify actionable factors associated with survival between those who never, formerly, and currently smoked cigarettes. These findings illuminate opportunities to address underlying mechanisms driving lung cancer progression, including use of first-course treatment, and enhanced implementation of tailored smoking cessation interventions for individuals diagnosed with cancer.

Uptake of novel systemic therapy: Real world patterns among adults with advanced non-small cell lung cancer.

INTRODUCTION/BACKGROUND: Systemic treatment for advanced non-small cell lung cancer (NSCLC) is shifting from platinum-based chemotherapy to immunotherapy and targeted therapies associated with improved survival in clinical trials. As new therapies are approved for use, examining variations in use for treating patients in community practice can generate additional evidence as to the magnitude of their benefit. PATIENTS AND METHODS: We identified 1,442 patients diagnosed with de novo stage IV NSCLC between 3/1/2012 and 12/31/2020. Patient characteristics and treatment patterns are described overall and by type of first- and second-line systemic therapy received. Prevalence ratios estimate the association of patient and tumor characteristics with receipt of first-line therapy. RESULTS: Within 180 days of diagnosis, 949 (66%) patients received first-line systemic therapy, increasing from 53% in 2012 to 71% in 2020 (p = 0.0004). The proportion of patients receiving first-line immunotherapy+/-chemotherapy (IMO) increased from 14%-66% (p<0.0001). Overall, 380 (26%) patients received both first- and second-line treatment, varying by year between 16%-36% (p = 0.18). The proportion of patients receiving second-line IMO increased from 13%-37% (p<0.0001). Older age and current smoking status were inversely associated with receipt of first-line therapy. Higher BMI, receipt of radiation, and diagnosis year were positively associated with receipt of first-line therapy. No association was found for race, ethnicity, or socioeconomic status. CONCLUSION: The proportion of advanced NSCLC patients receiving first- and second-line treatment increased over time, particularly for IMO treatments. Additional research is needed to better understand the impact of these therapies on patient outcomes, including short-term, long-term, and financial toxicities. MICROABSTRACT: Systemic treatment for non-small cell lung cancer (NSCLC) is shifting from platinum-based therapies to immunotherapy and targeted therapies. Using de novo stage IV NSCLC patients identified from 4 healthcare systems, we examine trends in systemic therapy. We saw an increase in the portion of patients receiving any systemic therapy and a sharp increase in the proportion of patients receiving immunotherapy.

Development of an Electronic Health Record-Based Algorithm for Predicting Lung Cancer Screening Eligibility in the Population-Based Research to Optimize the Screening Process Lung Research Consortium.

PURPOSE: Lung cancer screening (LCS) guidelines in the United States recommend LCS for those age 50-80 years with at least 20 pack-years smoking history who currently smoke or quit within the last 15 years. We tested the performance of simple smoking-related criteria derived from electronic health record (EHR) data and developed and tested the performance of a multivariable model in predicting LCS eligibility. METHODS: Analyses were completed within the Population-based Research to Optimize the Screening Process Lung Consortium (PROSPR-Lung). In our primary validity analyses, the reference standard LCS eligibility was based on self-reported smoking data collected via survey. Within one PROSPR-Lung health system, we used a training data set and penalized multivariable logistic regression using the Least Absolute Shrinkage and Selection Operator to select EHR-based variables into the prediction model including demographics, smoking history, diagnoses, and prescription medications. A separate test data set assessed model performance. We also conducted external validation analysis in a separate health system and reported AUC, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy metrics associated with the Youden Index. RESULTS: There were 14,214 individuals with survey data to assess LCS eligibility in primary analyses. The overall performance for assigning LCS eligibility status as measured by the AUC values at the two health systems was 0.940 and 0.938. At the Youden Index cutoff value, performance metrics were as follows: accuracy, 0.855 and 0.895; sensitivity, 0.886 and 0.920; specificity, 0.896 and 0.850; PPV, 0.357 and 0.444; and NPV, 0.988 and 0.992. CONCLUSION: Our results suggest that health systems can use an EHR-derived multivariable prediction model to aid in the identification of those who may be eligible for LCS.

Community-based Lung Cancer Screening Results in Relation to Patient and Radiologist Characteristics: The PROSPR Consortium.

Rationale: Lung-RADS classification was developed to standardize reporting and management of lung cancer screening using low-dose computed tomographic (LDCT) imaging. Although variation in Lung-RADS distribution between healthcare systems has been reported, it is unclear if this is explained by patient characteristics, radiologist experience with lung cancer screening, or other factors. Objectives: Our objective was to determine if patient or radiologist factors are associated with Lung-RADS score. Methods: In the Population-based Research to Optimize the Screening Process (PROSPR) Lung consortium, we conducted a study of patients who received their first screening LDCT imaging at one of the five healthcare systems in the PROSPR Lung Research Center from May 1, 2014, through December 31, 2017. Data on LDCT scans, patient factors, and radiologist characteristics were obtained via electronic health records. LDCT scan findings were categorized using Lung-RADS (negative [1], benign [2], probably benign [3], or suspicious [4]). We used generalized estimating equations with a multinomial distribution to compare the odds of Lung-RADS 3, and separately Lung-RADS 4, versus Lung-RADS 1 or 2 and estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between Lung-RADS assignment and patient and radiologist characteristics. Results: Analyses included 8,556 patients; 24% were assigned Lung-RADS 1, 60% Lung-RADS 2, 10% Lung-RADS 3, and 5% Lung-RADS 4. Age was positively associated with Lung-RADS 3 (OR, 1.02; 95% CI, 1.01-1.03) and 4 (OR, 1.03; 95% CI, 1.01-1.05); chronic obstructive pulmonary disease (COPD) was positively associated with Lung-RADS 4 (OR, 1.78; 95% CI, 1.45-2.20); obesity was inversely associated with Lung-RADS 3 (OR, 0.70; 95% CI, 0.58-0.84) and 4 (OR, 0.58; 95% CI, 0.45-0.75). There was no association between sex, race, ethnicity, education, or smoking status and Lung-RADS assignment. Radiologist volume of interpreting screening LDCT scans, years in practice, and thoracic specialty were also not associated with Lung-RADS assignment. Conclusions: Healthcare systems that are comprised of patients with an older age distribution or higher levels of COPD will have a greater proportion of screening LDCT scans with Lung-RADS 3 or 4 findings and should plan for additional resources to support appropriate and timely management of noted positive findings.

Reusing a prepaid health plan's fecal immunochemical tests for microbiome associations with colorectal adenoma.

An altered colonic microbiota probably increases colorectal adenoma (CRA) and cancer (CRC) risk, but large, unbiased fecal collections are needed to examine the relationship of gut microbiota diversity and composition to colorectal carcinogenesis. This study assessed whether fecal immunochemical tests (FITs) from CRA/CRC screening may fulfill this requirement. Using FIT, self-collected by members of Kaiser Permanente Hawaii (KPH), as well as interspersed quality control (QC) specimens, DNA was extracted and amplified to generate 16S rRNA microbiome profiles rarified at 10,000 reads. CRA/CRC were diagnosed by colonoscopy and histopathology. Covariates were from electronic KPH records. Of 921 participants' FIT devices, 538 (58%) yielded at least 10,000 rRNA reads and 1016 species-level variants mapped to 46 genera. Of the 538 evaluable participants, 63 (11.7%) were FIT-negative per protocol, and they were considered negative for CRA/CRC. Of the 475 FIT + participants, colonoscopy and pathologic review revealed that 8 (1.7%) had CRC, 71 (14.9%) had high-risk CRA, 107 (22.5%) had low-risk CRA, and 289 (60.8%) did not have CRA/CRC. Men were 2.27-fold [95% confidence interval (CI) 1.32-3.91] more likely than women to be FIT+ . Men also had 1.96-fold (CI 1.24-3.07) higher odds of low-risk CRA, with similar trends for high-risk CRA and CRC. CRA/CRC were not associated with overweight, obesity, diabetes, or antibiotic prescriptions in this study. QC analysis across 24 batches of FIT devices revealed QC outliers in four batches. With or without exclusion of the four QC-outlier batches, as well as lenient (1000-read) rarefaction, CRA/CRC had no consistent, statistically significant associations with fecal microbiome alpha diversity, beta diversity or genera relative abundance. CRA/CRC had expected associations with male sex but not with microbiome metrics. Fecal microbiome profiling using DNA extracted from at-home collected, re-used FIT devices is feasible, albeit with substantial challenges. Using FITs for prospective microbiome studies of CRA/CRC risk should consider the impact of the current findings on statistical power and requisite sample sizes.

Racial Disparities in Adherence to Annual Lung Cancer Screening and Recommended Follow-Up Care: A Multicenter Cohort Study.

Rationale: Black patients receive recommended lung cancer screening (LCS) follow-up care less frequently than White patients, but it is unknown if this racial disparity persists across both decentralized and centralized LCS programs. Objectives: To determine adherence to American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) recommendations among individuals undergoing LCS at either decentralized or centralized programs and to evaluate the association of race with LCS adherence. Methods: We performed a multicenter retrospective cohort study of patients receiving LCS at five heterogeneous U.S. healthcare systems. We calculated adherence to annual LCS among patients with a negative baseline screen (Lung-RADS 1 or 2) and recommended follow-up care among those with a positive baseline screen (Lung-RADS 3, 4A, 4B, or 4X) stratified by type of LCS program and evaluated the association between race and adherence using multivariable modified Poisson regression. Results: Of the 6,134 total individuals receiving LCS, 5,142 (83.8%) had negative baseline screens, and 992 (16.2%) had positive baseline screens. Adherence to both annual LCS (34.8% vs. 76.1%; P < 0.001) and recommended follow-up care (63.9% vs. 74.6%; P < 0.001) was lower at decentralized compared with centralized programs. Among individuals with negative baseline screens, a racial disparity in adherence was observed only at decentralized screening programs (interaction term, P < 0.001). At decentralized programs, Black race was associated with 27% reduced adherence to annual LCS (adjusted relative risk [aRR], 0.73; 95% confidence interval [CI], 0.63-0.84), whereas at centralized programs, no effect by race was observed (aRR, 0.98; 95% CI, 0.91-1.05). In contrast, among those with positive baseline screens, there was no significant difference by race for adherence to recommended follow-up care by type of LCS program (decentralized aRR, 0.95; 95% CI, 0.81-1.11; centralized aRR, 0.81; 95% CI, 0.71-0.93; interaction term, P = 0.176). Conclusions: In this large multicenter study of individuals screened for lung cancer, adherence to both annual LCS and recommended follow-up care was greater at centralized screening programs. Black patients were less likely to receive annual LCS than White patients at decentralized compared with centralized LCS programs. Our results highlight the need for further study of healthcare system-level mechanisms to optimize longitudinal LCS care.

Evaluation of Population-Level Changes Associated With the 2021 US Preventive Services Task Force Lung Cancer Screening Recommendations in Community-Based Health Care Systems.

Importance: The US Preventive Services Task Force (USPSTF) released updated lung cancer screening recommendations in 2021, lowering the screening age from 55 to 50 years and smoking history from 30 to 20 pack-years. These changes are expected to expand screening access to women and racial and ethnic minority groups. Objective: To estimate the population-level changes associated with the 2021 USPSTF expansion of lung cancer screening eligibility by sex, race and ethnicity, sociodemographic factors, and comorbidities in 5 community-based health care systems. Design, Setting, and Participants: This cohort study analyzed data of patients who received care from any of 5 community-based health care systems (which are members of the Population-based Research to Optimize the Screening Process Lung Consortium, a collaboration that conducts research to better understand how to improve the cancer screening processes in community health care settings) from January 1, 2010, through September 30, 2019. Individuals who had complete smoking history and were engaged with the health care system for 12 or more continuous months were included. Those who had never smoked or who had unknown smoking history were excluded. Exposures: Electronic health record-derived age, sex, race and ethnicity, socioeconomic status (SES), comorbidities, and smoking history. Main Outcomes and Measures: Differences in the proportion of the newly eligible population by age, sex, race and ethnicity, Charlson Comorbidity Index, chronic obstructive pulmonary disease diagnosis, and SES as well as lung cancer diagnoses under the 2013 recommendations vs the expected cases under the 2021 recommendations were evaluated using χ2 tests. Results: As of September 2019, there were 341 163 individuals aged 50 to 80 years who currently or previously smoked. Among these, 34 528 had electronic health record data that captured pack-year and quit-date information and were eligible for lung cancer screening according to the 2013 USPSTF recommendations. The 2021 USPSTF recommendations expanded screening eligibility to 18 533 individuals, representing a 53.7% increase. Compared with the 2013 cohort, the newly eligible 2021 population included 5833 individuals (31.5%) aged 50 to 54 years, a larger proportion of women (52.0% [n = 9631]), and more racial or ethnic minority groups. The relative increases in the proportion of newly eligible individuals were 60.6% for Asian, Native Hawaiian, or Pacific Islander; 67.4% for Hispanic; 69.7% for non-Hispanic Black; and 49.0% for non-Hispanic White groups. The relative increase for women was 13.8% higher than for men (61.2% vs 47.4%), and those with a lower comorbidity burden and lower SES had higher relative increases (eg, 68.7% for a Charlson Comorbidity Index score of 0; 61.1% for lowest SES). The 2021 recommendations were associated with an estimated 30% increase in incident lung cancer diagnoses compared with the 2013 recommendations. Conclusions and Relevance: This cohort study suggests that, in diverse health care systems, adopting the 2021 USPSTF recommendations will increase the number of women, racial and ethnic minority groups, and individuals with lower SES who are eligible for lung cancer screening, thus helping to minimize the barriers to screening access for individuals with high risk for lung cancer.

Clinical Molecular Marker Testing Data Capture to Promote Precision Medicine Research Within the Cancer Research Network.

PURPOSE: To evaluate health care systems for the availability of population-level data on the frequency of use and results of clinical molecular marker tests to inform precision cancer care. METHODS: We assessed cancer-related molecular marker test data availability across 12 US health care systems in the Cancer Research Network. Overall, these systems provide care to a diverse population of more than 12 million people in the United States. We performed qualitative analyses of test data availability for five blood-based protein, nine germline, and 14 tissue-based tumor marker tests in each health care system's electronic health record and tumor registry using key informants, test code lists, and manual review of data types and output. We then performed quantitative analyses to estimate the proportion of patients with cancer with test utilization data and results for specific molecular marker tests. RESULTS: Health systems were able to systematically capture population-level data on all five blood protein markers, six of 14 tissue-based tumor markers, and none of the nine germline markers. Successful, systematic data capture was achievable for tests with electronic data feeds for test results (blood protein markers) or through prior manual abstraction by tumor registrars (select tumor-based markers). For test results stored in scanned image files (particularly germline and tumor marker tests), information on which test was performed and test results was not readily accessible in an electronic format. CONCLUSION: Even in health care systems with sophisticated electronic health records, there were few codified data elements available for evaluating precision cancer medicine test use and results at the population level. Health care organizations should establish standards for electronic reporting of precision medicine tests to expedite cancer research and facilitate the implementation of precision medicine approaches.

Serous carcinomatous component championed by heparin-binding EGF-like growth factor (HB-EGF) predisposing to metastasis and recurrence in stage I uterine malignant mixed mullerian tumor.

The stage I uterine malignant mixed mullerian tumor (MMMT) shows different potential for progression. We reason that MMMTs with high-grade carcinomatous component and positivity for HB-EGF are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18 (33%) in stage I disease. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component (83% [5/6] versus 17% [1/12], P = .0015) and HB-EGF expression (100% [6/6] versus 50% [6/12], P=.0339) were significantly different between groups with RM and without RM. The presence of serous carcinoma in all stages was 83% (5/6) in stage I with RM, 8% (1/12) in stage I without RM, 20% (1/5) in stage II, 36.4% (8/22) in stage III and 64.7% (11/17) in stage IV; this was paralleled by HB-EGF expression of 100% (6/6), 50% (6/12), 40% (2/5), 50% (11/22) and 71% (12/17) with a correlation coefficient r=0.9131 (P=.027). HB-EGF and integrin-α5 were highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, P=.025 for HB-EGF; and 61.5%/42.9%/20.0%, P=.021 for integrin-α5). The EGFR positivity was comparable among the three subtypes (48.1%, 47.6% and 26.7%, P=.326). This study indicates that serous carcinomatous component championed by expression of HB-EGF predisposes to recurrence/metastasis in stage I MMMT. This process might involve integrin-α5 and does not seem to require overexpression of EGFR. Further study is required.

Real-Time Polymerase Chain Reaction Detection of Angiostrongylus cantonensis DNA in Cerebrospinal Fluid from Patients with Eosinophilic Meningitis.

Angiostrongylus cantonensis is the most common infectious cause of eosinophilic meningitis. Timely diagnosis of these infections is difficult, partly because reliable laboratory diagnostic methods are unavailable. The aim of this study was to evaluate the usefulness of a real-time polymerase chain reaction (PCR) assay for the detection of A. cantonensis DNA in human cerebrospinal fluid (CSF) specimens. A total of 49 CSF specimens from 33 patients with eosinophilic meningitis were included: A. cantonensis DNA was detected in 32 CSF specimens, from 22 patients. Four patients had intermittently positive and negative real-time PCR results on subsequent samples, indicating that the level of A. cantonensis DNA present in CSF may fluctuate during the course of the illness. Immunodiagnosis and/or supplemental PCR testing supported the real-time PCR findings for 30 patients. On the basis of these observations, this real-time PCR assay can be useful to detect A. cantonensis in the CSF from patients with eosinophilic meningitis.

Insulinoma, a rare neuroendocrine tumor: a case report.

We report a case of Insulinoma, a rare neuroendocrine tumor with an incidence of approximately four per 5 million. This case demonstrates the characteristic clinical, biochemical and histological features of an insulinoma, a rare benign neuroendocrine tumor where early recognition is important to ensure proper surgical treatment and prevent serious adverse consequences.

Axillary metaplastic breast carcinoma with ipsilateral pectoral invasive ductal carcinoma: an unusual presentation.

We report a case of axillary metaplastic breast carcinoma (MBC) with triple negative (ER-/PR-/Her2-) phenotype, concurrent with multifocal invasive ductal carcinoma (IDC) of ipsilateral pectoral breast (ER+/PR+/Her2-) in a 60-year-old woman. The two tumors demonstrate different morphology, immunophenotype, and opposite response to neoadjuvant chemotherapy of paclitaxol, adriamycin, and cyclophosphamide. Methylation analysis of human androgen receptor (HUMARA) on X-chromosome identified monoclonal pattern of X-chromosome inactivation in MBC and mosaic pattern in the IDC. Stem cell origin of MBC is suggested in this case. Clinicopathological features, imaging findings, biological markers, chemoradiation management, and prognosis of MBC are reviewed in comparison to invasive ductal carcinoma. Our case and literature review suggest that traditional chemotherapy applicable to IDC is less effective towards MBC. However, new chemotherapy protocols targeting stem cell and multimodality management of MBC are promising. Recognition of unusual presentation of MBC will help tailor therapy towards tumor with worse prognosis.