Site of metastatic recurrence impacts prognosis in patients with high-grade upper tract urothelial carcinoma

PurposeMetastatic recurrence occurs in over 25% of upper tract urothelial carcinoma patients treated with radical nephroureterectomy. While metastatic recurrence suggests poor prognosis, the impact of the specific site of recurrence on prognosis is not well documented.Materials and methodsWe retrospectively analyzed 188 patients who underwent radical nephroureterectomy for high-grade, node-negative upper tract urothelial carcinoma at our institution from 2003 to 2018 without receiving neoadjuvant or adjuvant chemotherapy. Competing-risks survival analysis was performed to evaluate the cumulative incidence and predictors of metastatic recurrence. The Kaplan-Meier method and log-rank test were used to estimate and compare recurrence site-specific survival probabilities following metastatic recurrence. Cox regression analyses were performed to assess site-specific prognoses.ResultsOf the 188 patients, 47 (25%) developed metastatic recurrence over a median follow-up of 30 months (interquartile range: 10.5–58.5 months). The 1- and 2-year cumulative incidences of metastatic recurrence were 13.6% and 23.6%, respectively. On multivariable analysis, lymphovascular invasion was significantly predictive of metastatic recurrence (subhazard ratio: 2.6, P = 0.01). Of the 47 patients who developed recurrence, 38 (80.9%) died over a median follow-up of 10 months (interquartile range: 5–20 months). Metastatic recurrence was most common in the lungs (n= 13, 28%) and at multiple sites (n= 14, 30%). Median time to recurrence was shorter for recurrences at multiple sites (6.5 months) and those in the liver (13 months) and bone (18 months) compared to other sites. Patients who recurred in the liver (hazard ratio: 6.3, P = 0.007), bone (hazard ratio: 4.9, P = 0.02), and multiple sites (hazard ratio: 4.6, P = 0.01) had significantly worse prognosis compared to those who recurred in lymph nodes. Statistical significance persisted after adjusting for treatment with salvage therapy.ConclusionsA significant proportion of high-grade upper tract urothelial carcinoma patients recur systemically after radical nephroureterectomy. Lymphovascular invasion is a predictor of metastatic recurrence and may inform decisions regarding perioperative chemotherapy. Hepatic and osseous recurrences have relatively quicker onset and less favorable prognosis compared to other sites. These findings may benefit future efforts to develop recurrence site-specific treatment plans and highlight the necessity of subsequent endeavors to explore the genetic associations of recurrence in upper tract urothelial carcinoma.     

The anatomy of the anterior inferior tibiofibular ligament and its relationship with the Wagstaffe fracture

BackgroundOur aim in this study was to identify the fibular footprint of the Anterior Inferior Tibiofibular Ligament (AITFL) and its relation to Wagstaffe fracture fragment size.MethodsWe examined 25 cadaveric lower limbs which were carefully dissected to identify the lateral ankle ligaments. The AITFL anatomy was compared to 40 Wagstaffe fractures identified from our ankle fracture database.ResultsThe AITFL origin was from the anterior fibular tubercle with an average length of 21.61 mm (95% CI 20.22, 22.99). The average distance of the distal aspect of the AITFL footprint to the distal fibula margin was 11.60 mm (95% CI 10.49, 12.71). In the ankle fractures analyzed, the average length of the Wagstaffe fragment was 17.88 mm (95% CI 16.21, 19.54). The average distance from the distal tip of the fibula to the Wagstaffe fracture fragment was 21.40 mm (95% CI 19.78, 23.01).In total there were 22 syndesmosis injuries. There was no statistical difference in Wagstaffe fragment size between stable and unstable groups.ConclusionThe AITFL fibular origin was both larger and more distal than the Wagstaffe fracture fragments seen in our institution. Therefore, this suggests that a ligamentous failure will also have to occur to result in syndesmotic instability. The size of fracture fragment also did not confer to syndesmotic instability on testing.Level of Evidence - 3     

Multifocal Parotid Oncocytic Cystadenomatosis: A Rare Process that Can Mimic Malignancy

Multifocal cystic oncocytosis (MCO) is a rare, benign process accounting for approximately 0.1% of salivary gland lesions. Salivary oncocytosis is characterized by multiple unencapsulated solid nodules of oncocytic cells derived from transformed striated ducts. MCO is a variant of salivary oncocytosis which manifests as cystically dilated striated ducts. It is difficult to obtain a definitive preoperative diagnosis of MCO; therefore, these lesions are commonly treated with surgery. We report the unique case of a 66-year-old male who previously underwent a superficial left parotidectomy for a pleomorphic adenoma. Four years later, he presented with clinical and radiographic suspicion of a multifocal recurrent pleomorphic adenoma. The patient subsequently underwent a revision parotidectomy. However, final pathology confirmed a diagnosis of MCO. Although MCO is commonly treated with surgery due to lack of a definitive preoperative diagnosis, surgery is unnecessary outside of diagnostic, functional or cosmetic considerations. Thus, if a patient with parotid oncocytosis treated by superficial parotidectomy develops disease re-manifestation in the residual deep lobe, further surgery is not indicated. There is no risk of malignant progression in this process. We report on this unusual entity as it may mimic salivary malignancy or, as in this case, recurrence of benign disease.     

The Self-Identification,LGBTQ+ Identity Development,and Attraction and Behavior of Asexual Youth: Potential Implications for Sexual Health and Internet-Based Service Provision

While often included in the spectrum of sexual minority identities, asexuality receives comparatively little attention. Awareness and understanding remains limited, and knowledge has been generated primarily from adult populations. This paper employs a sample of 711 self-identified asexual youth (aged 14–24, M?=?17.43 years) who identified as members of the LGBTQ+?community to consider the implications of a number of different areas for service provision. Two-thirds (66.8%) of participants identified as gender minorities within the spectrum of transgender and non-binary identities. Findings include aspects of participants’ LGBTQ+?developmental processes, including that only 14.3% had disclosed their LGBTQ+?status to everyone in their lives. However, just 2.4% had disclosed to no one. Their attraction and sexual activity were also explored, with 27.1% having never experienced any kind of romantic or sexual attraction and 20.6% having ever been sexually active. Findings regarding participants’ accessing of LGBTQ+?health information and engagement in a range of offline and online LGBTQ+?community activities are also provided. Participants acquired more health information online than offline—including sexual health information. Recommendations for service provision, particularly implications for sexual health and Internet-based services, are discussed.

     

How do women interpret abortion information they find online?

ObjectiveWe sought to assess how women interpret the information they find online about the overall safety and risk of infertility associated with abortion and cesarean delivery (CD).MethodsWe conducted an exploratory, prospective study tracking the internet searches of 100 reproductive-aged individuals who identify as women. We directed participants to search for information about either (1) whether surgical abortion or CD is safe or (2) the risk of infertility following surgical abortion or CD. Our data collection had 3 phases: baseline survey, directed internet search, and a postsearch survey. We analyzed participants’ pre- and postsurvey responses using bivariate tests and analyzed within-subject changes. We evaluated the sites they visited based on expert ratings of site content based on trustworthiness and slant.ResultsWomen perceived abortion as safer and less likely to cause infertility after their web searches than before (70% perceived abortion in the United States as very/completely safe presearch vs 92% postsearch; p < 0.02). Women's perceptions about CD did not change. Participants sought information from web pages that experts largely deemed trustworthy and lacking in slant.ConclusionsWomen's perceptions about abortion safety and risk can be influenced by information they find online; perceptions about CD safety and risk may be less influenced by online information.ImplicationsDisseminating high quality, user-friendly abortion information on highly ranked and easily findable websites can help women find evidence-based information and influence knowledge about abortion.     

Hepatitis and HIV Risk among Drug-Using Men Who Have Sex with Men: Demonstration of Hart's Law of Inverse Access and Application to HIV

Objectives: The first 215 drug-using men who have sex with men (DU-MSM) evaluated for possible participation in a controlled behavioral intervention study were tested for Hart's law of inverse access, which predicts that access to prevention resources varies inversely to need. Methods: Hepatitis B vaccination, mental health, and substance abuse treatment were used to measure health resource use; hepatitis B (HBV) and HIV infections and unsafe sex measured preventive care needs. Socioeconomic status indicators included education, ethnicity, and income. Results: HBV-vaccinated men were more likely to be white and college educated. HBV-infected men were more likely to be black, older, HIV-positive, and have higher rates of substance use with sex. When stratified according to socioeconomic status indicators, levels of HBV vaccination were inverse to the rates of HBV and HIV infection. This relationship was not found for psychosocial treatment utilization. Conclusions: Demonstration of Hart's law among high-risk DU-MSM has important implications for future HIV prevention efforts among high-risk individuals. Combining HIV, hepatitis, and substance abuse prevention in primary care and substance abuse treatment settings is discussed.     

Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in an NMDA, AMPA/kainate, and metabotropic glutamate receptor-dependent manner.

Previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) enhances cocaine self-administration in a D(1) dopamine receptor-dependent manner. The present study examined the contribution of VTA NMDA, AMPA/kainate, and metabotropic glutamate (mGlu) receptors to this effect. Rats in different groups received three intra-VTA injections, one every third day, of either saline (0.5 microl/side), AMPH (2.5 microg/0.5 microl/side), AMPH+CPP (NMDA receptor antagonist; 10 microM or 100 microM/0.5 microl/side), AMPH+CNQX (AMPA/kainate receptor antagonist; 0.3 mM or 1 mM/0.5 microl/side), AMPH+MCPG (mGlu receptor antagonist; 0.5 mM or 50 mM/0.5 microl/side), or the glutamate receptor antagonists alone. Starting 7-10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) and then tested under a progressive ratio (PR) schedule of reinforcement for 6 consecutive days. As reported previously, VTA AMPH pre-exposed rats worked more and obtained more infusions of cocaine than saline pre-exposed animals. Coadministration of CPP, CNQX, or MCPG with AMPH during pre-exposure dose-dependently blocked this enhancement of cocaine self-administration. Rats pre-exposed to the glutamate receptor antagonists alone did not differ on the test days from the saline pre-exposed controls. These results indicate that, in a manner paralleling the induction of sensitization of the locomotor stimulating effects of AMPH, activation of NMDA, AMPA/kainate, and mGlu receptors during pre-exposure to AMPH in the VTA is necessary for the enhancement of cocaine self-administration to develop.     

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.