Metastatic seminoma and grade 1 follicular lymphoma presenting concurrently in a supraclavicular lymph node: a case report

An asymptomatic 67-year-old man presented with a left supraclavicular lymph node that enlarged over a 2-month period which was biopsied. Pathologic features were consistent with involvement by metastatic seminoma and follicular lymphoma, follicular pattern, grade 1 (of 3). Staging Positron Emission Tomography/Computed Tomography scans indicated several areas of enlarged lymph nodes. The patient completed chemotherapy with bleomycin, etoposide, and cisplatin chemotherapy. This is the first reported case of metastatic seminoma and follicular lymphoma occurring in the same lymph node. No obvious pathophysiologic link exists between these two malignancies and there are no shared common risk factors. Given the natural history of these two malignancies, if this patient develops recurrent lymphadenopathy, it will be difficult to identify whether the enlarged lymph nodes represent recurrent seminoma or follicular lymphoma without a biopsy of each pathologically enlarged node. Similarly, Fluorodeoxyglucose- Positron Emission Tomography is known to be active in both seminoma and follicular lymphoma, making this scan non-specific in this patient. Finally, this patient had no baseline elevation in any germ cell tumor marker. Thus, serum tumor markers cannot be relied upon as surrogates for response to chemotherapy or as identifiers of relapsed seminoma

Evolving Patterns of Metastasis in Renal Cell Carcinoma: Do We Need to Perform Routine Bone Imaging?

Advance diagnostic and treatment modalities have improved outcomes for renal cell carcinoma (RCC) patients, but the prognosis for those with metastatic disease (mRCC) remains poor. As given metastatic distribution is critical in guiding treatment decisions for mRCC patients, we evaluated evolving metastatic patterns to assess if our current practice standards effectively address patient needs. A systematic literature review was performed to identify all publicly available prospective clinical trials in metastatic renal cell carcinoma (mRCC) from 1990 to 2018. A total of 16,899 mRCC patients from 127 qualified phase I–III clinical trials with metastatic site documentations were included for analysis for incidence of metastases to lung, liver, bone, and lymph nodes (LNs) over time. Studies were categorized into three treatment eras based on the timing of regulatory approval: Cytokine Era (1990-2004), vascular endothelial growth factor/tyrosine kinase inhibitor (TKI) Era (2005-2016), and immune checkpoint inhibitor/TKI Era (ICI-TKI, 2017-2018) and also classified as first-line only (FLO) or second-line and beyond (SLB). Overall, an increase in the incidence of bone and LNs metastases in FLO and SLB, and lung metastases in FLO, was seen over the three treatment eras. Generally, the burden of disease is higher in SLB when compared with FLO. Importantly, in the ICI-TKI era, the incidences of bone metastasis are 28% in FLO and 29% in SLB settings. The disease burden in patients with mRCC has increased steadily over the past three decades. Given the unexpectedly high rate of bone metastasis, routine dedicated bone imaging should be considered in all patients with mRCC

Intraoperative evaluation of mitral valve regurgitation and repair by transesophageal echocardiography: Incidence and significance of systolic anterior motion

AbstractObjectives. This study was designed to delineate the utility and results of intraoperative transesophageal echocardiography in the evaluation of patients undergoing mural valve repair for mitral regurgitation.Background. Mitral valve reconstruction offers many advantages over prosthetic valve replacement. Intraoperative assessment of valve competence after repair is vital to the effectiveness of this procedure.Methods. Intraoperative transesophageal echocardiography was performed in 143 patients undergoing mitral valve repair over a period of 23 months, Before and after repair, the functional morphology of the mitral apparatus was defined by twodimensional echocardiography; Doppler color flow imaging was used to clarify the mechanism of mitral regurgitation and to semiquantitate its severity.Results. There was significant improvement in the mean mitral regurgitation grade by composite intraoperative transesophageal echocardiography after valve repair (3.6 ± 0.8 to 0.7 ± 0.7; p < 0.00001). Excellent results from initial repair with grade ≤ 1 residual mitral regurgitation were observed in 88.1% of patients. Significant residual mitral regurgitation (grade ≥ 3) was identified in 11 patients (7.7%); 5 underwent prosthetic valve replacement, 5 had revision of the initial repair and 1 patient had observation only. Of the 100 patients with a myxomatous mitral valve, the risk of grade ≥ 3 mitral regurgitation after initial repair was 1.7% in patients with isolated posterior leaflet disease compared with 22.5% in patients with anterior or bileaflet disease.Severe systolic anterior motion of the mitral apparatus causing grade 2 to 4 mitral regurgitation was present in 13 patients (9.1%) after cardiopulmonary bypass. In 8 patients (5.6%), systolic anterior motion resolved immediately with correction of hyperdynamic hemodynamic status, resulting in grade ≤ 1 residual mitral regurgitation without further operative intervention.Transthoracic echocardiography before hospital discharge demonstrated grade ≤ 1 residual mitral regurgitation in 86.4% of 132 patients studied. A significant discrepancy (> 1 grade) in residual mitral regurgitation by predischarge transthoracic versus intraoperative transesophageal echocardiography was noted in 17 patients (12.9%).Conclusions. Transesophageal echocardiography is a valuable adjunct in the intraoperative assessment of mitral valve repair

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma.

Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly

What Predicts Hospital Admissions in Community-Dwelling People With Parkinsonism?

Objectives: Previous studies have looked at the reasons for hospital admission in people with parkinsonism (PwP), yet few have looked at factors that precipitate admission. Methods: People with parkinsonism with a diagnosis of idiopathic Parkinson disease of Hoehn and Yahr stage III-V and those with Parkinson plus syndromes were assessed for motor and nonmotor symptoms, quality of life, and functional performance. Logistic regression was used to investigate predictors of hospital admission over the subsequent 2 years. Results: Overall, 162 patients consented to be part of the study. Seventy-one PwP (43.8%) had at least 1 hospital admission, and 17 (10.5%) patients had 3 or more admissions to hospital. Poorer cognition, more nonmotor symptoms, poorer quality of life, slower timed-up-and-go test scores, and abnormal swallow predicted a subsequent hospital admission. Discussion: Our study emphasizes the importance of nonmotor symptoms in predicting admission. A cost–benefit analysis of early intervention to prevent admission should be considered

Early-Onset Progressive Retinal Atrophy Associated with an IQCB1 Variant in African Black-Footed Cats (Felis nigripes)

African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management

Sixty Years of CA: A Cancer Journal for Clinicians

The first issue of CA: A Cancer Journal for Clinicians was published in November of 1950. On the 60th anniversary of that date, we briefly review several seminal contributions to oncology and cancer control published in our journal during its first decade. CA Cancer J Clin 2010. © 2010 American Cancer Society, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78301/1/20088_ftp.pd

Analysis of the 10q11 Cancer Risk Locus Implicates MSMB and NCOA4 in Human Prostate Tumorigenesis

Genome-wide association studies (GWAS) have established a variant, rs10993994, on chromosome 10q11 as being associated with prostate cancer risk. Since the variant is located outside of a protein-coding region, the target genes driving tumorigenesis are not readily apparent. Two genes nearest to this variant, MSMB and NCOA4, are strong candidates for mediating the effects of rs109939934. In a cohort of 180 individuals, we demonstrate that the rs10993994 risk allele is associated with decreased expression of two MSMB isoforms in histologically normal and malignant prostate tissue. In addition, the risk allele is associated with increased expression of five NCOA4 isoforms in histologically normal prostate tissue only. No consistent association with either gene is observed in breast or colon tissue. In conjunction with these findings, suppression of MSMB expression or NCOA4 overexpression promotes anchorage-independent growth of prostate epithelial cells, but not growth of breast epithelial cells. These data suggest that germline variation at chromosome 10q11 contributes to prostate cancer risk by influencing expression of at least two genes. More broadly, the findings demonstrate that disease risk alleles may influence multiple genes, and associations between genotype and expression may only be observed in the context of specific tissue and disease states

An audio personal health library of clinic visit recordings for patients and their caregivers (HealthPAL): User-centered design approach

Background: Providing digital recordings of clinic visits to patients has emerged as a strategy to promote patient and family engagement in care. With advances in natural language processing, an opportunity exists to maximize the value of visit recordings for patients by automatically tagging key visit information (eg, medications, tests, and imaging) and linkages to trustworthy web-based resources curated in an audio-based personal health library. Objective: This study aims to report on the user-centered development of HealthPAL, an audio personal health library. Methods: Our user-centered design and usability evaluation approach incorporated iterative rounds of video-recorded sessions from 2016 to 2019. We recruited participants from a range of community settings to represent older patient and caregiver perspectives. In the first round, we used paper prototypes and focused on feature envisionment. We moved to low-fidelity and high-fidelity versions of the HealthPAL in later rounds, which focused on functionality and use; all sessions included a debriefing interview. Participants listened to a deidentified, standardized primary care visit recording before completing a series of tasks (eg, finding where a medication was discussed in the recording). In the final round, we recorded the patients\u27 primary care clinic visits for use in the session. Findings from each round informed the agile software development process. Task completion and critical incidents were recorded in each round, and the System Usability Scale was completed by participants using the digital prototype in later rounds. Results: We completed 5 rounds of usability sessions with 40 participants, of whom 25 (63%) were women with a median age of 68 years (range 23-89). Feedback from sessions resulted in color-coding and highlighting of information tags, a more prominent play button, clearer structure to move between one\u27s own recordings and others\u27 recordings, the ability to filter recording content by the topic discussed and descriptions, 10-second forward and rewind controls, and a help link and search bar. Perceived usability increased over the rounds, with a median System Usability Scale of 78.2 (range 20-100) in the final round. Participants were overwhelmingly positive about the concept of accessing a curated audio recording of a clinic visit. Some participants reported concerns about privacy and the computer-based skills necessary to access recordings. Conclusions: To our knowledge, HealthPAL is the first patient-centered app designed to allow patients and their caregivers to access easy-to-navigate recordings of clinic visits, with key concepts tagged and hyperlinks to further information provided. The HealthPAL user interface has been rigorously co-designed with older adult patients and their caregivers and is now ready for further field testing. The successful development and use of HealthPAL may help improve the ability of patients to manage their own care, especially older adult patients who have to navigate complex treatment plans

NCoR Repression of LXRs Restricts Macrophage Biosynthesis of Insulin-Sensitizing Omega 3 Fatty Acids

SummaryMacrophage-mediated inflammation is a major contributor to obesity-associated insulin resistance. The corepressor NCoR interacts with inflammatory pathway genes in macrophages, suggesting that its removal would result in increased activity of inflammatory responses. Surprisingly, we find that macrophage-specific deletion of NCoR instead results in an anti-inflammatory phenotype along with robust systemic insulin sensitization in obese mice. We present evidence that derepression of LXRs contributes to this paradoxical anti-inflammatory phenotype by causing increased expression of genes that direct biosynthesis of palmitoleic acid and ω3 fatty acids. Remarkably, the increased ω3 fatty acid levels primarily inhibit NF-κB-dependent inflammatory responses by uncoupling NF-κB binding and enhancer/promoter histone acetylation from subsequent steps required for proinflammatory gene activation. This provides a mechanism for the in vivo anti-inflammatory insulin-sensitive phenotype observed in mice with macrophage-specific deletion of NCoR. Therapeutic methods to harness this mechanism could lead to a new approach to insulin-sensitizing therapies