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Epithelioid hemangioendothelioma (EHE) is a difficult to treat vascular sarcoma defined by TAZ-CAMTA1 (TC) or YAP-TFE3 (YT) fusion proteins. Human cell lines needed to further understand the pathogenesis of EHE have been lacking. Herein, we describe a method to generate EHE extended primary cell cultures. An integrated multi –omic and functional approach was used to characterize these cultures. The cell cultures, relatively homogenous by single cell RNA-Seq, demonstrated established characteristics of EHE including increased proliferation, anchorage independent growth, as well as the overall gene expression profile and secondary genetic alterations seen in EHE. Whole genome sequencing (WGS) identified links to epigenetic modifying complexes, metabolic processes, and pointed to the importance of the extracellular matrix (ECM) in these tumors. Bulk RNA-Seq demonstrated upregulation of pathways including PI3K-Akt signaling, ECM/ECM receptor interaction, and the Hippo signaling pathway. Development of these extended primary cell cultures allowed for single-cell profiling which demonstrated different cell compartments within the cultures. Furthermore, the cultures served as a therapeutic platform to test the efficacy of TEAD inhibitors in vitro. Overall, the development of primary EHE cell cultures will aid in the mechanistic understanding of this sarcoma and serve as a model system to test new therapeutic approaches.

We describe the novel occurrence of a adenocarcinoma involving the trachea, with distinct solid and glandular components, in a 34-year-old patient. We illustrate its morphological and immunophenotypic features and describe the molecular finding of an EWSR1::BEND2 gene fusion detected by next-generation sequencing (NGS). We discuss the findings in comparison to BEND2-fusion associated neoplasms reported in the head and neck region in the literature to date.

Mismatch repair (MMR) deficiency in colorectal cancer (CRC) should prompt consideration of genetic counseling (GC) as a Lynch syndrome (LS) diagnosis may have several implications for the patient and family. The study aims were to examine how routine MMR testing influences the rate of GC and surgical resection extent. A single-institution retrospective review was performed on CRC specimens (including colonoscopic biopsies) routinely screened for MMR deficiency from 2012 to 2018. MLH1-deficient cancers with mutated BRAF or MLH1-promoter hypermethylation were excluded. MMR deficiency was identified in 295 of 1139 CRC specimens. After exclusions, 57 patients remained. Forty-two patients (74%) were identified preoperatively, and 35 (83%) were referred to GC: 16 were seen preoperatively, 9 postoperatively. Eight patients were diagnosed with Lynch syndrome (LS) preoperatively: 2 had no resection, 2 underwent segmental resection and 4 underwent extended resection. Most MMR–deficient patients were identified and referred to GC preoperatively, though not all were seen. Of the preoperatively diagnosed LS patients, half underwent extended resection. Barriers to GC and decision-making around resection extent bears further study. •Colorectal cancer specimens are routinely tested for mismatch repair deficiency.•Most MMR deficiencies were identified on colonoscopic biopsy preoperatively.•Though most patients were recommended to see genetic counseling (GC), many did not.•Patients diagnosed with Lynch syndrome were likely to undergo an extended resection.

The Victorian legislation prohibits sex workers from working when they have visible anogenital herpes or warts. The aim of this study was to determine the proportion of asymptomatic female sex workers (FSW) diagnosed with anogenital herpes or warts by genital examination. We analysed all computerised medical records of consultations with FSW at the Melbourne Sexual Health Centre (MSHC) in 2018. All asymptomatic sex workers were offered screening sexually transmitted infections (STIs) and a genital examination to identify visible anogenital herpes or warts at MSHC. FSW consultations were categorised into either 'asymptomatic' or 'symptomatic' based on the presence of symptoms reported by the FSW to the triage nurse. The proportion of asymptomatic FSW diagnosed with visible anogenital herpes or warts during a routine screening examination was calculated. In 2018, 4055 consultations were provided to 1979 FSW. 3406 of these consultations were asymptomatic and all were examined by an experienced clinician for signs of STIs. Of these 3406 asymptomatic consultations, seven FSW (0.21%, 95% CI: 0.08% to 0.42%) were diagnosed with visible anogenital herpes and/or warts following a genital examination. Four were diagnosed with warts (0.12%, 95% CI: 0.03% to 0.30%), two with herpes (0.06%, 95% CI: 0.01% to 0.21%) and one with both herpes and warts (0.03%, 95% CI: 0.001% to 0.16%). Based on these data, approximately 500 asymptomatic FSW would need to be examined to identify one case of anogenital herpes or warts. Genital examinations consume considerable clinical resources, increase the duration of consultations and provide essentially no significant benefit to the mandated testing for gonorrhoea, chlamydia, HIV and syphilis. Our clinic will use self-collected samples and no longer examine FSW who are asymptomatic.

Background. To guide interpretation of gonorrhea tests of cure using nucleic acid amplification testing, this study examined the persistence of Neisseria gonorrhoeae DNA following treatment for pharyngeal and rectal gonorrhea. Methods. Men who had sex with men diagnosed with pharyngeal or rectal gonorrhea underwent swabbing from the pharynx or rectum 7 and 14 days following treatment. Repeat testing for N. gonorrhoeae was undertaken using real-time polymerase chain reaction (PCR) assays targeting the opa gene and porA pseudogene. Results. One hundred pharyngeal and 100 rectal gonorrhea infections in 190 men were included. For pharyngeal gonorrhea, positivity of N. gonorrhoeae DNA on both PCR assays was present at days 7 or 14 in 13% (95% confidence interval [CI], 6.4%–19.6%) and 8% (95% CI, 2.7%–13.3%), respectively. For rectal gonorrhea, DNA positivity was present in 6% (95% CI, 1.4%–10.7%) and 8% (95% CI, 2.7%–13.3%), respectively. Among 200 baseline pharyngeal and rectal isolates, there were 10 with ceftriaxone minimum inhibitory concentration (MIC) ≥0.06 mg/L and azithromycin MIC ≥0.5 mg/L, of which 3 (30%) had DNA detected at day 14; among the 190 isolates with lower ceftriaxone and azithromycin MICs, only 13 (7%) had persistent DNA (odds ratio, 5.8 [95% CI, 1.3–25.4]; P = .019). One man initially infected with N. gonorrhoeae multiantigen sequence type 2400 had type 4244 infection at day 14, indicating reinfection. Conclusions. Pharyngeal and rectal gonorrhea DNA persisted in 8% of men 14 days after treatment. Persistence was associated with elevated ceftriaxone and azithromycin MICs. Persistence can also reflect reinfection.

We performed a retrospective study to investigate the usefulness of immunohistochemical stains for the diagnosis of Helicobacter pylori (HP). We reviewed 200 consecutive gastric biopsy specimens, as well as immunohistochemical stains for HP. Of the biopsy specimens, 32 were positive for HP by immunohistochemical staining; of those, HP was seen on H&E stains in 29 cases (91%). The number of high-power fields required to detect HP on H&E-stained slides ranged from 1 to 25 (mean, 5.75). Combined significant (2+ or 3+) acute and chronic inflammation had a specificity of 98% and a negative predictive value of 97%. Our results show that, in our institution, HP can be seen relatively easily with H&E staining in the majority of cases; however, a small number of cases with significant inflammation can be missed if stains are not used.

Background Extraction of DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is a critical step in molecular oncologic testing. As molecular oncology testing becomes more important for prognostic and therapeutic decision making and tissue specimens become smaller due to earlier detection of suspicious lesions and the use of fine needle aspiration methods for tissue collection, it becomes more challenging for the typical molecular pathology laboratory to obtain reliable test results. We developed a DNA extraction method to obtain sufficient quantity and high quality genomic DNA from limited FFPE tissue for molecular oncology testing using a combination of H&E stained slides, a matrix capture method and the Qiagen DNA column. Methods Three DNA extraction methods were compared: our standard procedure of manually scraping tissue from unstained slides followed by DNA extraction using the QIAamp FFPE column (Qiagen, Valencia, CA), a glue capture method (Pinpoint Solution, Zymo Research Corp, Inc) on H&E stained slides followed by DNA extraction using either the QIAamp column or the column included with the Pinpoint kit (Zymo Research). The DNA extraction protocol was optimized. Statistical analysis was performed using the paired two-sample student’s t-test. Results The combination of the matrix capture method with the QIAamp column gave an equivalent amount of DNA as our standard extraction method using the unstained slides and a 4.6-fold higher DNA yield than using the Zymo column included in the Pinpoint Slide Solution kit. Several molecular tests were performed and DNA purified using the new method gave the same results as for the previous methods. Conclusions Using H&E stained slides allows visual confirmation of tumor cells during microdissection. The Pinpoint solution made removal of specific tissue from the slides easier and reduced the risk of contamination and tissue loss. This DNA extraction method is simple, cost-effective, and blends with our current workflow requiring no additional equipment.

The clinical impact of lymph node dissection extent remains undetermined in the contemporary setting, as reflected in care pattern variations. Despite some series demonstrating a direct relationship between number of lymph nodes identified and detection of nodal involvement, the correlation between lymph node yield and disease control or survival outcomes remains unclear. Patients with clinically localized prostate cancer, pre-RP PSA <30, and pT2-3a/N0 disease at RP were retrospectively identified from two databases for inclusion. Those who received pre- or post-RP radiotherapy or hormone therapy were excluded. Kaplan-Meier method was employed for survival probability estimation. Cox regression models were used to assess bRFS differences between subsets. From 2002 to 2010, 667 eligible patients were identified. The median age was 61 yrs. (range, 43–76), with median PSA 5.6 ng/dL (0.9–28.0). At RP, most patients had pT2c (64%) disease with Gleason Score (GS) ≤6 (43%) or 7 (48%); 218 (33%) patients had positive margins (M+). At median clinical and PSA follow-up of 96 and 87 months, respectively, 146 patients (22%) experienced PSA failure with an estimated bRFS of 81%/76% at 5/8 years. For patients who underwent LND, univariable analysis identified PSA (at diagnosis), higher GS (≥7, at biopsy or RP), intermediate/high risk stratification, M+ as adversely associated with bRFS (all p  < 0.01). A higher number of LNs excised was not associated with improved bRFS for the entire cohort (HR = 0.97, p  = 0.27), nor for any clinical risk stratum, biopsy GS, or RP GS subgroup. This study did not demonstrate an association between LN yield and bRFS in patients with clinically localized pT2-3a/pN0 prostate cancer managed with RP alone, either in the entire population or with substratification by clinical risk stratum or GS.

Background High‐dose cisplatin (Cis) is a preferred systemic agent for concurrent chemoradiation (CRT) in locally advanced head and neck squamous cell cancer (LAHNSCC) patients. As some patients are unable to tolerate Cis, this study compares the toxicity and efficacy of weekly cisplatin‐paclitaxel (CP) regimen with Cis. Methods Patients with LAHNSCC receiving definitive chemoradiation either with Cis (Cisplatin—100 mg/m2 q3w x 3) or CP (Cisplatin—20 mg/m2; Paclitaxel—30 mg/m2qw x7) were included. Results Cis and CP groups were comprised of 114 and 111 subjects, respectively. Complete response for Cis versus CP groups was 88% versus 88%, respectively. Median follow‐up for the study was 58.5 months. After adjusting for potential treatment selection bias, no significant differences were evident between Cis and CP groups for overall survival (hazard ratios [HR] 0.85, 95% CI 0.59‐1.21, P = 0.36), progression free survival (HR 0.88, 95% CI 0.62‐1.24, P = 0.46), locoregional control (HR 0.77, 95% CI 0.52‐1.15, P = 0.21), and distant control (HR 0.87, 95% CI 0.61‐1.23, P = 0.42). Patients in the CP group had less acute and chronic toxicities. Conclusions Weekly CP regimen can serve as an alternative systemic therapy with radiation in patients with LAHNSCC who are not fit for Cis. Concurrent chemoradiation with weekly cisplatin and paclitaxel is tolerable and provide higher compliance rate in patients with locally advanced head and neck squamous cell carcinoma. Outcomes of patients on combination chemotherapy were similar to high‐dose cisplatin.