The Impact of Systematic Safety Precautions on COVID-19 Risk Exposure and Transmission Rates in Outpatient Healthcare Workers.

We evaluated the impact of safety protocols, including rapid testing and contact tracing, on coronavirus disease 2019 (COVID-19) risk exposure and transmission rates amongst healthcare workers in the outpatient care setting. Over an 11-week period, a total of 254 employees representing 38% of our total workforce had potential COVID-19 exposure and underwent voluntary COVID-19 testing. Data was stratified based on severity of risk exposure and job description. During this period, the probability of a COVID exposure being high risk decreased in Administrative (-93.0%; P < 0.01) and Clinical (-77.0%; P < 0.01) staff; simultaneously, viral transmission rates declined in Administrative (-73.4%; P = 0.03) and Clinical (-69.9%; P = 0.04) staff as well. Systematic safety protocols effectively reduce exposure risk and transmission rates in outpatient healthcare workers and should be ubiquitously adopted.

Pneumoperitoneum with carbon dioxide inhibits macrophage tumor necrosis factor-alpha secretion: source of transitional-cell carcinoma port-site metastasis, with prophylactic irrigation strategies to decrease laparoscopic oncologic risks.

PURPOSE: Peritoneal macrophages play a critical role in maintaining local host resistance to infection and malignancy through the secretion of tumor necrosis factor-alpha (TNF-alpha). We hypothesized that attenuated TNF-alpha secretion, as a result of CO(2) pneumoperitoneum, could alter local immune surveillance, thereby contributing to the development of carcinomatosis and incisional metastasis. We further sought to determine if port-site metastasis could be prevented with prophylactic irrigants. MATERIALS AND METHODS: C57BL/6 mice (n = 50) and the syngenic murine bladder tumor (MBT-2) cell line were used. Experiment 1: Mice were subjected to either CO(2) pneumoperitoneum at 6 mm Hg (n = 10) or a 3-cm midline incision (n = 10). Peritoneal macrophages (1 x 10(6)/animal) were collected and subjected to lipopolysaccharide challenge. TNF-alpha levels were quantified using the Quantikine Mouse TNF-alpha/TNFSF1A Immunoassay. Experiment 2: Peritoneal and port-site metastasis were evaluated 1 week after 1 x 10(6) MBT-2 cells/animal were spilled in an open group (n = 5) and through 5-mm trocars of a pneumoperitoneal group (n = 5). Experiment 3: 1 x 10(6) MBT-2 cells/animal were spilled intraperitoneally through 5-mm trocars of four groups (n = 20). Port sites in each group were then irrigated with either sterile water, mitomycin C (1.0 mg/mL), betadine (10%), or heparin (1000 U/mL). At 1 week, incisional sites were evaluated for gross and microscopic metastasis. In each experiment, Student t-test was used to quantify statistical differences. RESULTS: Peritoneal macrophage TNF-alpha secretion was significantly inhibited in mice subjected to CO(2) pneumoperitoneum v control at 10 and 20 minutes (P = 0.015, P = 0.001, respectively). When 1 x 10(6) MBT-2 cells were spilled, a significantly higher average tumor burden developed in animals subjected to CO(2) pneumoperitoneum than in controls at 1 week (9.2 gm v 3.8 g, P = 0.002). All irrigants prevented the development of port-site metastasis, yet sterile water did so without toxic effect. CONCLUSION: In a syngenic murine model, CO(2) pneumoperitoneum causes inhibition of peritoneal macrophage TNF-alpha secretion. Heavier intraperitoneal and incisional metastasis develops in C57BL/6 mice subjected to CO(2) pneumoperitoneum and a tumor challenge with 1 x 10(6) MBT-2 tumor cells compared with open controls. Inhibition of peritoneal macrophage TNF-alpha secretion may be considered an adverse event contributing to the development of transitional-cell carcinoma (TCC) port-site metastasis, especially if surgical oncologic principles are violated. Irrigating trocar sites and the peritoneal cavity with sterile water at the conclusion of laparoscopic nephroureterectomy and laparoscopic radical cystectomy may offer a safe prophylactic strategy to prevent this unfavorable event. Our murine model presents a novel avenue for the development of adjunct immunomodulatory therapies to perhaps further reduce oncologic risks during laparoscopic management of TCC.

Histologic Changes in Prostate Cancer Detected Subsequent to the 2012 United States Preventive Services Task Force (USPSTF) Prostate Cancer Screening Recommendation.

We report changes in the histopathology of prostate cancer diagnosed in a large urology group practice after the final United States Preventive Services Task Force (USPSTF) Grade D recommendation against prostate-specific antigen screening. All prostate biopsies performed from 2011 through 2015 in a large urology group practice were retrospectively reviewed; 2012 was excluded as a transition year. The changes in biopsy data in years following the USPSTF decision (2013-2015) were then compared with baseline (2011). A total of 10,944 biopsies were evaluated during the study period. Positive biopsy rates rose from 39.1% at baseline to 45.2% in 2015 (P < 0.01) with a marked shift toward more aggressive cancer throughout the study period. The absolute number of patients presenting with Gleason Grade Group 4 or 5 increased from 155/year at baseline to 231, 297, and 285 in 2013, 2014, and 2015, respectively (P < 0.05), unrelated to age or racial changes over time. Black men represented 16% of the cohort. Since the USPSTF recommendation against prostate cancer screening, trends toward a substantial upward grade migration and increased volume of cancers were noted in a cohort of nearly 11,000 patients in a real-world clinical practice. Additionally, continuing reductions in cancer detection in the United States may exacerbate these trends.

Utility of PTEN and ERG immunostaining for distinguishing high-grade PIN from intraductal carcinoma of the prostate on needle biopsy.

Intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified intraductal carcinoma, PIN, or borderline intraductal proliferations more concerning than PIN but falling short of morphologic criteria for intraductal carcinoma. Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated intraductal carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified intraductal carcinoma yet is very rare in high-grade PIN. Borderline intraductal proliferations, especially those with PTEN loss, have a high rate of carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish intraductal carcinoma from high-grade PIN in this setting.

Utilization trends and positive biopsy rates for prostate biopsies in the United States: 2005 to 2011.

This article assesses the positive biopsy rate and core sampling pattern in patients undergoing needle biopsy of the prostate in the United States at a national reference laboratory (NRL) and anatomic pathology laboratories integrated into urology group practices, and analyzes the relationship between positive biopsy rates and the number of specimen vials per biopsy. For the years 2005 to 2011 we collected pathology data from an NRL, including number of urologists and urology practices referring samples, total specimen vials submitted for prostate biopsies, and final pathologic diagnosis for each case. The diagnoses were categorized as benign, malignant, prostatic intraepithelial neoplasia, or atypical small acinar proliferation. Over the same period, similar data were gathered from urology practices with in-house laboratories performing global pathology services (urology practice laboratories; UPLs) as identified by a survey of members of the Large Urology Group Practice Association. For each year studied, positive biopsy rate and number of specimen vials per biopsy were calculated in aggregate and separately for each site of service. From 2005 to 2011, 437,937 biopsies were submitted in > 4.23 million vials (9.4 specimen vials/biopsy); overall positive biopsy rate was 40.3%-this was identical at both the NRL and UPL (P = .97). Nationally, the number of specimen vials per biopsy increased sharply from a mean of 8.8 during 2005 to 2008 to a mean of 10.3 from 2009 to 2011 (difference, 1.5 specimen vials/biopsy; P = .03). For the most recent 3-year period (2009-2011), the difference of 0.6 specimen vials per biopsy between the NRL (10.0) and UPL (10.6) was not significant (P = 0.08). Positive biopsy rate correlated strongly (P < .01) with number of specimen vials per biopsy. The positive prostate biopsy rate is 40.3% and is identical across sites of service. Although there was a national trend toward increased specimen vials per biopsy from 2005 to 2011, from 2009 to 2011 there was no significant difference in specimen vials per biopsy across sites of service. Increased cancer detection rate correlated significantly with increased number of specimens examined. Segregation of prostate biopsy cores into 10 to 12 unique specimen vials has been widely adopted by urologists across sites of service.

Indole-3-carbinol prevents PTEN loss in cervical cancer in vivo.

Indole-3-carbinol (I3C) is a phytochemical (derived from broccoli, cabbage, and other cruciferous vegetables) with proven anticancer efficacy including the reduction of cervical intraepithelial neoplasia (CIN) and its progression to cervical cancer. In a breast cancer cell line, I3C inhibited cell adhesion, spreading, and invasion associated with an upregulation of the tumor suppressor gene PTEN, suggesting that PTEN is important in inhibition of late stages in the development of cancer. The goal of this study was to determine the expression of PTEN during the development of cervical cancer and whether I3C affected expression of PTEN in vivo. We show diminished PTEN expression during the progression from low-grade to high-grade cervical dysplasia in humans and in a mouse model for cervical cancer, the K14HPV16 transgenic mice promoted with estrogen. The implication is that loss of PTEN function is required for this transition. Additionally, dietary I3C increased PTEN expression in the cervical epithelium of the transgenic mouse, an observation that suggests PTEN upregulation by I3C is one mechanism by which I3C inhibits development of cervical cancer.

Epithelioid angiomyolipoma of the ovary: a case report and literature review.

Angiomyolipoma (AML) is a benign mesenchymal neoplasm that mainly occurs in the kidney either sporadically or in patients with tuberous sclerosis complex (TSC). Extrarenal AML is uncommon. We describe a 39-year-old female with a history of TSC and bilateral multicentric renal AML who presented with a persistent cystic ovarian mass that fluctuated in size during 2 years of ultrasonographic observation before its removal by salpingo-oophorectomy. The 4.5-cm mass was solid and cystic and tan-yellow. Microscopic examination showed an admixture of epithelioid cells, smooth muscle bundles, large thick-walled blood vessels, and mature adipose tissue. The epithelioid cells had abundant eosinophilic cytoplasm and many had bizarre atypical nuclei including multinucleated forms. Mitoses were rare. Typical smooth muscle cells and the epithelioid cells were strongly immunoreactive for HMB-45. To our knowledge, this represents the first report of an AML arising in the ovary. The differential with other oxyphilic tumors of the ovary is discussed.