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Purpose To analyze the effect of a patient’s renal failure status on acute outcomes after lower extremity endovascular interventions for peripheral artery disease. Materials and Methods A retrospective analysis of the American College of Surgery National Surgical Quality Improvement Program database from 2014 to 2017 was conducted. Patients were included based on current procedural terminology codes. They were divided into renal failure cohorts. Six thousand seven hundred and sixty-five patients were included in the analysis, 11.0% of whom had renal failure. A univariate analysis was performed using chi-squared test or Fischer’s exact test as appropriate. Multivariate logistic regression models were constructed, while controlling for relevant patient factors, to identify the effect of renal failure on several outcomes of interest after the intervention. A sensitivity analysis was performed with a propensity score-matched cohort. Results Patients with renal failure were more likely to have infrapopliteal interventions (38.0% vs 20.9%), critical limb ischemia with tissue loss (73.5% vs 38.9%), diabetes (70.9% vs 52.3%), preoperative wound infection (59.2% vs 30.7%), mortality (5.1% vs 1.3%), prolonged hospital stay (68.5% vs 46.5%), transfusion after the intervention (13.3% vs 9.1%), reoperation (18.3% vs 9.5%), and readmission (24.9% vs 12.6%), compared to patients without renal failure. The multivariate analysis found renal failure to be significant for mortality (odds ratio [OR] = 4.11, 95% confidence interval [CI] = 2.71–6.24), any complication (OR = 2.03, 95% CI = 1.72–2.39), extended length of stay (OR = 1.53, 95% CI = 1.28–1.83), sepsis (OR = 2.37, 95% CI = 1.60–3.51), readmission (OR = 1.89, 95% CI = 1.57–2.29), reoperation (OR = 1.84, 95% CI = 1.48–2.27), major adverse cardiovascular event (OR = 3.50, 95% CI = 2.54–4.84), and major adverse limb event (OR = 1.97, 95% CI = 1.55–2.51). P value was Conclusions Renal failure before the intervention places patients at a significantly elevated risk of morbidity and mortality following endovascular revascularization procedures for peripheral artery disease.

A radiology research interest group of medical students, with the necessary infrastructure and resident leadership, may create a productive environment for research and career development for all p...

Background Angiotensin-converting enzyme 2, a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates its highest surface expression in the lung, small bowel, and vasculature, suggesting abdominal viscera may be susceptible to injury. Purpose To report abdominal imaging findings in patients with coronavirus disease 2019. Materials and Methods In this retrospective cross-sectional study, patients consecutively admitted to a single quaternary care center from March 27 to April 10, 2020, who tested positive for SARS-CoV-2 were included. Abdominal imaging studies performed in these patients were reviewed, and salient findings were recorded. Medical records were reviewed for clinical data. Univariable analysis and logistic regression were performed. Results A total of 412 patients (average age, 57 years; range, 18 to >90 years; 241 men, 171 women) were evaluated. A total of 224 abdominal imaging studies were performed (radiography, n = 137; US, n = 44; CT, n = 42; MRI, n = 1) in 134 patients (33%). Abdominal imaging was associated with age (odds ratio [OR], 1.03 per year of increase; P = .001) and intensive care unit (ICU) admission (OR, 17.3; P < .001). Bowel-wall abnormalities were seen on 31% of CT images (13 of 42) and were associated with ICU admission (OR, 15.5; P = .01). Bowel findings included pneumatosis or portal venous gas, seen on 20% of CT images obtained in patients in the ICU (four of 20). Surgical correlation (n = 4) revealed unusual yellow discoloration of the bowel (n = 3) and bowel infarction (n = 2). Pathologic findings revealed ischemic enteritis with patchy necrosis and fibrin thrombi in arterioles (n = 2). Right upper quadrant US examinations were mostly performed because of liver laboratory findings (87%, 32 of 37), and 54% (20 of 37) revealed a dilated sludge-filled gallbladder, suggestive of bile stasis. Patients with a cholecystostomy tube placed (n = 4) had negative bacterial cultures. Conclusion Bowel abnormalities and gallbladder bile stasis were common findings on abdominal images of patients with coronavirus disease 2019. Patients who underwent laparotomy often had ischemia, possibly due to small-vessel thrombosis. © RSNA, 2020.

To identify the variables associated with patient discharge disposition to optimize postprocedural care and discharge planning following lower extremity arterial interventions for peripheral artery disease (PAD).The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program database was queried using current procedural terminology codes for endovascular infrainguinal interventions for PAD. The main outcome variable of interest was nonhome discharge. Covariates included patient sociodemographic variables, age quartile (upper quartile, ≥77 years), comorbidities (diabetes, renal disease, bleeding disorder, congestive heart failure [CHF], and chronic obstructive pulmonary disease), presence of an open wound before a procedure, type of procedure, operative time, symptom severity, American Society of Anesthesiologists class, and baseline functional status. Univariate analysis and multivariate logistic regression were performed on Stata/SE 15.1.A total of 3,190 patients met the inclusion criteria, of whom 664 (20.8%) had nonhome discharge. Multivariate regression revealed that age (odds ratio [OR], 1.9 for the upper age quartile [77 years]; 95% confidence interval [CI], 1.46-2.50), operative time (OR, 1.2 per increase in quartile; 95% CI, 1.09-1.30), preoperative wound (OR, 1.5; 95% CI, 1.24-1.90), renal failure (OR, 1.7; 95% CI, 1.30-2.14), CHF (OR, 2.2; 95% CI, 1.51-3.24), symptom severity (OR, 1.7; 95% CI, 1.46-1.98), and independent functional status (OR, 0.74; 95% CI, 0.59-0.92; P = .007) were associated with nonhome discharge. All P values were ≤.001 unless otherwise stated.Prolonged procedural time, the presence of preprocedural wound and patient comorbidities, symptomatology, and baseline functional status may be used to identify patients who will require a nonhome discharge and early discharge planning.

Immunotherapy has revolutionized the contemporary oncology landscape, with durable responses possible across a range of cancer types. However, the majority of cancer patients do not respond to immunotherapy due to numerous immunosuppressive barriers. Efforts to overcome these barriers and increase systemic immunotherapy efficacy have sparked interest in the local intratumoral delivery of immune stimulants to activate the local immune response and subsequently drive systemic tumor immunity. While clinical evaluation of many therapeutic candidates is ongoing, development is hindered by a lack of imaging confirmation of local delivery, insufficient intratumoral drug distribution, and a need for repeated injections. The use of polymeric drug delivery systems, which have been widely used as platforms for both image guidance and controlled drug release, holds promise for delivery of intratumoral immunoadjuvants and the development of an in situ cancer vaccine for patients with metastatic cancer. In this review, we explore the current state of the field for intratumoral delivery and methods for optimizing controlled drug release, as well as practical considerations for drug delivery design to be optimized for clinical image guided delivery particularly by CT and ultrasound.

To assess the utility of the radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines (RENAL) nephrometry scoring system at predicting adverse events and outcomes in percutaneous microwave ablation (MWA) of renal tumors.A retrospective review of 116 patients who underwent MWA from 2004 to 2018 at 2 large university hospitals was conducted. Patient demographics and tumor characteristics were collected. The RENAL nephrometry scores were calculated, and procedure-related adverse events were stratified into minor and major (the Society of Interventional Radiology classification of class C or higher). Technical and oncologic outcomes were based on follow-up magnetic resonance imaging and computed tomography scans after ablation.The mean RENAL score was 6.6 (range, 4-11), and the mean tumor size was 24 mm. Follow-up ranged between 16 and 161 weeks (median, 50 weeks; mean, 65 weeks). Oncologic control was achieved in 96% (n = 111) of patients. The major and minor adverse event rates were 8.6% (n = 10) and 17% (n = 19), respectively. The mean RENAL score for patients with recurrent and/or residual tumor (8.2 ± 2.7) was higher than that for patients without disease recurrence (6.5 ± 3.5, P = .05). However, in a multivariate analysis, the RENAL score was not found to be an independent predictor of oncologic outcomes (odds ratio, 1.548; P = .092).The RENAL nephrometry score has minimal utility for predicting outcomes and adverse events in MWA of renal tumors. The inconsistent nature of RENAL nephrometry scoring in percutaneous ablation procedures underscores the need for an ablation-specific risk stratification system.

BACKGROUND. Previous studies compared CT findings of COVID-19 pneumonia with those of other infections; however, to our knowledge, no studies to date have included noninfectious organizing pneumonia (OP) for comparison. OBJECTIVE. The objectives of this study were to compare chest CT features of COVID-19, influenza, and OP using a multireader design and to assess the performance of radiologists in distinguishing between these conditions. METHODS. This retrospective study included 150 chest CT examinations in 150 patients (mean [± SD] age, 58 ± 16 years) with a diagnosis of COVID-19, influenza, or non-infectious OP (50 randomly selected abnormal CT examinations per diagnosis). Six thoracic radiologists independently assessed CT examinations for 14 individual CT findings and for Radiological Society of North America (RSNA) COVID-19 category and recorded a favored diagnosis. The CT characteristics of the three diagnoses were compared using random-effects models; the diagnostic performance of the readers was assessed. RESULTS. COVID-19 pneumonia was significantly different (p < .05) from influenza pneumonia for seven of 14 chest CT findings, although it was different (p < .05) from OP for four of 14 findings (central or diffuse distribution was seen in 10% and 7% of COVID-19 cases, respectively, vs 20% and 21% of OP cases, respectively; unilateral distribution was seen in 1% of COVID-19 cases vs 7% of OP cases; non-tree-in-bud nodules was seen in 32% of COVID-19 cases vs 53% of OP cases; tree-in-bud nodules were seen in 6% of COVID-19 cases vs 14% of OP cases). A total of 70% of cases of COVID-19, 33% of influenza cases, and 47% of OP cases had typical findings according to RSNA COVID-19 category assessment (p < .001). The mean percentage of correct favored diagnoses compared with actual diagnoses was 44% for COVID-19, 29% for influenza, and 39% for OP. The mean diagnostic accuracy of favored diagnoses was 70% for COVID-19 pneumonia and 68% for both influenza and OP. CONCLUSION. CT findings of COVID-19 substantially overlap with those of influenza and, to a greater extent, those of OP. The diagnostic accuracy of the radiologists was low in a study sample that contained equal proportions of these three types of pneumonia. CLINICAL IMPACT. Recognized challenges in diagnosing COVID-19 by CT are furthered by the strong overlap observed between the appearances of COVID-19 and OP on CT. This challenge may be particularly evident in clinical settings in which there are substantial proportions of patients with potential causes of OP such as ongoing cancer therapy or autoimmune conditions.

The COVID-19 pandemic has led to delays in cancer diagnosis, in part due to postponement of cancer screening. We used Google Trends data to assess public attention to cancer screening during the first peak of the COVID-19 pandemic. Search volume for terms related to established cancer screening tests (“colonoscopy,” “mammogram,” “lung cancer screening,” and “pap smear”) showed a marked decrease of up to 76% compared to the pre-pandemic period, a significantly greater drop than for search volume for terms denoting common chronic diseases. Maintaining awareness of cancer screening during future public health crises may decrease delays in cancer diagnosis.

The COVID-19 pandemic has challenged the capacity of interventional radiology departments worldwide to effectively treat COVID-19 and non-COVID-19 patients while preventing disease transmission among patients and healthcare workers. In this review, we describe the various data driven infection control measures implemented by the interventional radiology department of a large tertiary care center in the United States including the use and novel re-use of personal protective equipment, COVID-19 testing strategies, modifications in procedural workflows and the leveraging of telehealth visits. Herein, we provide effective triage, procedural, and management algorithms that may guide other interventional radiology departments during the ongoing COVID-19 pandemic and in future infectious disease outbreaks.

To determine the pathologic response of computed tomography-guided percutaneous microwave ablation as bridging therapy for patients with hepatocellular carcinoma awaiting liver transplant, and its subsequent effect on survival.A single-center retrospective analysis was conducted on 62 patients (M:F = 50:12) with mean age of 59.6 years ± 7.2 months (SD). Sixty-four total MWA procedures were performed for hepatocellular carcinomas within Milan criteria as bridging therapy to subsequent orthotopic liver transplant between August 2014 and September 2018. The pathology reports of the explanted livers were reviewed to assess for residual disease. Residual disease was categorized as complete or incomplete necrosis. Patient demographics, tumor/procedural characteristics, and laboratory values were evaluated. Survival from time of ablation and time of transplantation were recorded and compared between cohorts using log rank tests.The mean tumor size was 2.4 cm ± 0.7 cm (SD), (range = 1-4.6 cm). 32 (50%) cases required hydrodissection. Histopathologic necrosis was seen in 66% of cases at time of liver transplantation. Median time to liver transplant post-MWA was 12.6 months. [IQR = 8.6-14.8 months]. The median survival from ablation was 60.8 months [IQR = 45.5-73.7 months], and the median survival from transplant was 49.3 months [IQR = 33.7-60.1 months]. There was no significant difference in survival for patients with complete versus incomplete necrosis from ablation or liver transplant (p = 0.49, p = 0.46, respectively).Computed tomography-guided percutaneous microwave ablation is an effective bridge to orthotopic liver transplantation for patients with hepatocellular carcinoma.Level 3, non-randomized controlled cohort study/follow-up study.

Rationale and Objectives While affiliated imaging centers play an important role in healthcare systems, little is known of how their operations are impacted by the COVID-19 pandemic. Our goal was to investigate imaging volume trends during the pandemic at our large academic hospital compared to the affiliated imaging centers. Materials and Methods This was a descriptive retrospective study of imaging volume from an academic hospital (main hospital campus) and its affiliated imaging centers from January 1 through May 21, 2020. Imaging volume assessment was separated into prestate of emergency (SOE) period (before SOE in Massachusetts on March 10, 2020), “post-SOE” period (time after “nonessential” services closure on March 24, 2020), and “transition” period (between pre-SOE and post-SOE). Results Imaging volume began to decrease on March 11, 2020, after hospital policy to delay nonessential studies. The average weekly imaging volume during the post-SOE period declined by 54% at the main hospital campus and 64% at the affiliated imaging centers. The rate of imaging volume recovery was slower for affiliated imaging centers (slope = 6.95 for weekdays) compared to main hospital campus (slope = 7.18 for weekdays). CT, radiography, and ultrasound exhibited the lowest volume loss, with weekly volume decrease of 41%, 49%, and 53%, respectively, at the main hospital campus, and 43%, 61%, and 60%, respectively, at affiliated imaging centers. Mammography had the greatest volume loss of 92% at both the main hospital campus and affiliated imaging centers. Conclusion Affiliated imaging center volume decreased to a greater degree than the main hospital campus and showed a slower rate of recovery. Furthermore, the trend in imaging volume and recovery were temporally related to public health announcements and COVID-19 cases.

The purpose of this article was to report the utility of computed tomography (CT) for detecting unsuspected cases of Coronavirus disease 2019 (COVID-19) and the utility of the Radiological Society of North America (RSNA)/Society of Thoracic Radiology (STR)/American College of Radiology (ACR) consensus guidelines for COVID-19 reporting.A total of 22 patients of the 156 reverse transcriptase polymerase chain reaction confirmed COVID-19 patients who were hospitalized between March 27, 2020 and March 31, 2020 at our quaternary care academic medical center and who underwent CT imaging within 1 week of admission were included in this retrospective study. Demographics and clinical data were extracted from the electronic medical record system. Two thoracic radiologists independently categorized each CT study on the basis of RSNA/STR/ACR consensus guidelines. Disagreement in categorization was resolved by consensus discussion with a third thoracic radiologist.At the time of imaging, 16 patients (73%) were suspected of COVID-19, and 6 patients (27%) were not. Common symptoms at presentation were fever (73%), cough (77%), and gastrointestinal symptoms (59%). An overall 63% of suspected COVID-19 patients exhibited shortness of breath, whereas 0 unsuspected COVID-19 patients did (P=0.02). On the basis of the RSNA consensus guidelines, 68%, 18%, 9%, and 5% of studies were categorized as "typical appearance," "indeterminate appearance," "atypical appearance," and "negative for pneumonia," respectively. There was no difference of category distribution between suspected and unsuspected COVID-19 patients (P=0.20), with "typical appearance" being the most prevalent in both (69% vs. 67%, respectively).It is important to recognize imaging features of COVID-19 pneumonia even in unsuspected patients. Implementation of the RSNA/STR/ACR consensus guidelines may increase consistency of reporting and convey the level of suspicion for COVID-19 to other health care providers, with "typical appearance" especially warranting further attention.

Aim: CaCO3 nanoparticles (nano-CaCO3) can neutralize the acidic pHe of solid tumors, but the lack of intrinsic imaging signal precludes noninvasive monitoring of pH-perturbation in tumor microenvironment. We aim to develop a theranostic version of nano-CaCO3 to noninvasively monitor pH modulation and subsequent tumor response. Materials & methods: We synthesized ferromagnetic core coated with CaCO3 (magnetite CaCO3). Magnetic resonance imaging (MRI) was used to determine the biodistribution and pH modulation using murine fibrosarcoma and breast cancer models. Results: Magnetite CaCO3-MRI imaging showed that nano-CaCO3 rapidly raised tumor pHe, followed by excessive tumor-associated acid production after its clearance. Continuous nano-CaCO3 infusion could inhibit metastasis. Conclusion: Nano-CaCO3 exposure induces tumor metabolic reprogramming that could account for the failure of previous intermittent pH-modulation strategies to achieve sustainable therapeutic effect.

Enhanced glycolysis and poor perfusion in most solid malignant tumors create an acidic extracellular environment, which enhances tumor growth, invasion, and metastasis. Complex molecular systems have been explored for imaging and treating these tumors. Here, we report the development of a small molecule, LS662, that emits near-infrared (NIR) fluorescence upon protonation by the extracellular acidic pH environment of diverse solid tumors. Protonation of LS662 induces selective internalization into tumor cells and retention in the tumor microenvironment. Noninvasive NIR imaging demonstrates selective retention of the pH sensor in diverse tumors, and two-photon microscopy of ex vivo tumors reveals significant retention of LS662 in tumor cells and the acid tumor microenvironment. Passive and active internalization processes combine to enhance NIR fluorescence in tumors over time. The low background fluorescence allows tumors to be detected with high sensitivity, as well as dead or dying cells to be delineated from healthy cells. In addition to demonstrating the feasibility of using small molecule pH sensors to image multiple aggressive solid tumor types via a protonation-induced internalization and retention pathway, the study reveals the potential of using LS662 to monitor treatment response and tumor-targeted drug delivery.

Introduction Owing to its capacity to perform remote assessments, telemedicine is rising as a new force in chronic obstructive pulmonary disease (COPD) management. We conducted an eight month randomised-controlled-trial to study the effect of an automated telemedicine intervention on patients’ time-to-hospitalisation. Methods A total of 168 patients with a diagnosis of COPD in the past 24 months were enrolled to receive the intervention at a primary care clinic. The treatment group received daily phone messages from an automated system asking them to report if they were breathing better than, worse than, or the same as the day prior. Patients reported their breathing status by responding to the text message or call. If a patient reported breathing worse, an alert was sent directly to that patient’s provider within the clinic. The control group received the same daily phone messages as the treatment group. However, no proactive breathing alerts were ever generated to the provider for these subjects. The primary outcome was the subjects’ time-to-first-COPD-related hospitalisation following the start of messages. Results The treatment group’s time-to-hospitalisation was significantly different than the control group’s with a hazard ratio of 2.36 (95% confidence interval 1.02–5.45, p = 0.0443). The number needed-to-treat ratio was 8.62. Subject engagement consistently ranged between 60% and 75%. The treatment group received both proactive monitoring and follow-up care from the providers. Discussion Active monitoring with provider feedback enables the detection of exacerbation events early enough for subjects to avoid admissions. The use of non-smartphone interventions reduces barriers to care presented by more complicated and expensive technologies. This intervention represents a simple, innovative, and inexpensive tool for improved COPD management.

Comorbidities and socioeconomic barriers often limit patient adherence and self-management with hemodialysis. Missed sessions, often associated with communication barriers, can result in emergency dialysis and avoidable hospitalizations. This proof of concept study explored using a novel digital-messaging platform, EpxDialysis, to improve patient-to-dialysis center communication via widely available text messaging and telephone technology. A randomized controlled trial was conducted through Washington University-affiliated hemodialysis centers involving ESRD patients with poor attendance, defined as missing 2–6 sessions over the preceding 12 weeks. A cross-over study design evaluated appointment adherence between intervention and control groups. Comparing nonadherence rates eight weeks prior to enrollment, median appointment adherence after using the system increased by 75%, and median number of unintended hospitalization days fell by 31%. A conservative cost-benefit analysis of EpxDialysis demonstrates a 1:36 savings ratio from appointment adherence. EpxDialysis is a low-risk, cost-effective, intervention for increasing hemodialysis adherence in high-risk patients, especially at centers caring for vulnerable and low-income patients.

Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer.

Background: The bone-forming metastases of prostate cancer result from complex stromal–epithelial interactions within the tumour microenvironment. Autocrine–paracrine signalling pathways between prostate cancer epithelial cells, osteoblasts, and osteoclasts stimulate aberrant bone remodelling, and the activity of these three cell populations can be quantitatively measured using prostate-specific antigen (PSA), bone-specific alkaline phosphatase (BAP) and urine N-telopeptide (uNTx), respectively. The purpose of the present study was to test the hypothesis that serial measurements of BAP and uNTx during therapy would facilitate monitoring of disease activity and predict the overall survival (OS) in patients with metastatic prostate cancer receiving therapy. Methods: Radionuclide bone scan, PSA, BAP, and uNTx data were retrospectively analysed from three clinical trials in patients with metastatic prostate cancer conducted at our institution. Qualitative changes in bone scans and quantitative changes in PSA, BAP, and uNTx concentrations during therapy were correlated with OS. Results: Baseline levels of BAP, but not PSA, were prognostic for OS in both androgen-dependent and castrate-resistant disease. A reduction in PSA, BAP, uNTx, or BAP/uNTx on therapy was predictive of improved OS in both patient groups. Conversely, an increase in PSA, or BAP on therapy was predictive of worse OS in both patient groups. Baseline number of lesions and response on bone scan during therapy were neither prognostic nor predictive of OS in either patient group. Conclusion: These observations support the concept that serial measurements of bone turnover metabolites during therapy function as clinically informative predictive biomarkers in patients with advanced prostate cancer and skeletal metastases. PSA measurements and bone scans remain essential to monitor the overall disease activity and determine the anatomic distribution of skeletal metastases.

At Washington University, students and faculty have addressed challenges surrounding biomedical innovation and training through a novel and low-cost platform.

A small subset of young men die from seminoma. Studying these high risk, clinically atypical seminomas (CASs)-aggressive tumors with visceral metastases and chemotherapy resistance-may provide clues to the nature of drug resistance and the origin of testicular cancers. We explored the possibility that these seminomas are a unique clinical and biologic entity with intrinsic yolk sac tumor (YST) features.We assayed available archived tissue samples (n = 22) for chemotherapy-resistance markers found in YSTs. Specifically, we analyzed tissues and clinical histories from patients with CASs (those who had visceral metastases and recurrent disease), classical seminomas, and mixed germ-cell tumors containing YST. By using immunohistochemical testing, we evaluated the expression of bone morphogenetic protein 2, alpha fetoprotein, and glutathione S-transferase (pi) [GST (pi)].GST (pi) expression significantly predicted for overall survival (p = .036). In addition, according to the results of GST (pi) immunohistochemical staining, the CASs appeared to resemble YSTs more than they did classical seminomas (p = 0.043). Less-advanced tumors, both those that expressed GST (pi) and those that were negative for GST (pi), were more amenable to local therapies, and the patients who had those tumors had better clinical outcomes.Results from this exploratory study suggest that certain CASs that express GST (pi) are more similar to YST than they are to classical seminomas, and that GST (pi) expression may be able to be used as a prognosticator of disease-specific survival. Such CASs thus may have a unique biologic origin that differs from that of classical seminomas. Additional studies are needed to determine the natural history and therapeutic implications of these CASs.

Introduction A major question concerning cancer is its cells of origin. We hypothesized that distinct cancer subtypes arise from unique cancer-initiating cells. By performing a microarray meta-analysis of seminomas and spermatogonial stem cells, we investigated a putative cell of origin for seminoma. Materials and Methods We obtained published microarray data for 6 human adult germ cell lines, 16 embryonic stem cell lines, 3 normal testicular tissue samples, and 40 seminomas from the Gene Expression Omnibus database. By assessing correlations between various tissue microarrays, we determined the number of transitional events and the distance between seminomas and human spermatogonial stem cells. Results Our meta-analysis showed that spermatogonial stem cells correlated similarly with seminoma (95% CI of Spearman ρ, 0.33-0.44) and with normal somatic testicular tissue cells (95% CI, 0.39-0.40), which suggests parallel paths of cellular origins. Conclusion Analysis of our results suggests that a unique cancer subtype, namely seminoma, may have originated from an undifferentiated cell with stemness features rather than from a differentiated cell that acquired stemness features.

Background: Patients with prostate cancer tend to die from bone metastases. Until now, no evidence has shown that Paget's disease of bone (PDB) affects the progression of bone metastasis or overall survival of patients with prostate cancer. Methods: We searched our patient database for men who had presented with prostate cancer and PDB between June 1993 and March 2009, and identified best-matched control patients according to stage, grade, age, date of diagnosis, treatment, and race. Results: Among 1346 consecutive patients with prostate cancer diagnosed before 2008, 15 were confirmed to have comorbid PDB. Twenty-six more were identified from the institutional billing search. Including the 41 best-matched controls, our total study population was 82 patients. In the Kaplan–Meier analysis, we estimated median times from diagnosis of prostate cancer to bone metastasis to be 21.5 years for those with PDB and 9.4 years for those without PDB (P=0.044). Median overall survival times were 11.8 and 9.2 years for the two groups, respectively (P=0.008). Conclusion: For the first time, we have obtained evidence that patients with prostate cancer and PDB have delayed time to bone metastases and improved overall survival than do patients with prostate cancer alone.

Objectives Certain patients with seminoma and clinically atypical phenotypes—visceral metastases, elevated levels of β human chorionic gonadotropin (βHCG), and/or recurrent disease—have a poor prognosis. The primary goal of this pilot study was to characterize the clinical characteristics and treatment profile of these rare patients. We also wished to test whether these tumors expressed any specific biomarkers that might distinguish them as a unique subtype of seminoma. Materials and methods We retrospectively identified 25 patients with a history of seminoma plus visceral metastases, βHCG levels >200 mU/ml, and/or recurrent disease. We reviewed these patients' histories for treatment efficacy and clinical outcome. Tissue samples were available from 6 of those patients, and we studied them for expression of the markers OCT 3/4, PLAP, CD30, TRA-1-60, c-kit, and gp200. We compared our results with the expression of those markers in tissue samples from mixed seminoma/embryonal carcinomas and classic seminomas. Results Our analysis suggested that certain chemotherapeutic regimens (such as ifosfamide, paclitaxel, and cisplatin) are efficacious for the treatment of patients with these atypical seminomas. Further, specimens from the atypical seminomas generally had staining profiles that resembled those of classic seminomas and the seminoma components in mixed germ-cell tumors, but the profiles differed from those of the embryonal carcinoma components in the same mixed germ-cell tumors. Conclusions Although these atypical seminomas tend to be resistant to chemotherapy, they may still respond to certain chemotherapeutic regimens. Our pilot immunohistochemical study also suggested that the unique phenotypes associated with these atypical seminomas do not result from any relationship with embryonal carcinomas. More study is needed to confirm these initial findings.