Change in Management Based on Pathologic Second Opinion Among Bladder Cancer Patients Presenting to a Comprehensive Cancer Center: Implications for Clinical Practice.

OBJECTIVE: To evaluate the incidence and degree of change from a pathologic second opinion of bladder biopsies at a Comprehensive Cancer Center that were initially performed at referring community hospitals. The secondary objective was to determine the impact the potential changes would have on a patient's treatment. MATERIALS AND METHODS: Dedicated genitourinary pathologists reviewed 1191 transurethral biopsies of the bladder and/or prostatic urethra from 2008 to 2013. Major and minor treatment changes were defined as altering recommendations for cystectomy, systemic chemotherapy, or primary cancer diagnosis, and alterations in intravesical regimens, respectively. RESULTS: There were 326/1191 patients (27.4%) with a pathologic change on second opinion: grade (62/1191, 5.2%), stage (115/1191, 9.7%), muscle in the specimen (29/1191, 2.4%), presence or absence of carcinoma in situ (34/1191, 2.9%). Outside pathology did not address the presence or absence of lymphovascular invasion in 620/759 (81.7%) of invasive cases (≥cT1), of which 35/620 (5.6%) had lymphovascular invasion. There were 212 mixed, variant, or nonurothelial histologies detected in 199/1191 (16.7%) patients, with 114/212 (53.7%) resulting in reclassification by our pathologists. Potential treatment alterations accounted for 182/1191 (15.3%) of cases, with 141/1191 (11.8%) imparting major changes. There were 82/1191 (6.8%) changes in recommendation for a radical cystectomy, 38/1191 (3.2%) had a complete change in primary tumor type, and 21/1191 (1.8%) for change in chemotherapy regimen. CONCLUSION: The amount and degree of pathologic changes and its potential impact on treatment emphasize the importance of bladder cancer patients having their histology reviewed by genitourinary-dedicated pathologists. In our cohort, 15.3% of patients could see a treatment alteration, with 11.8% being a major change.

Evaluation and Treatment of Penile Thrombophlebitis (Mondor's Disease).

Superficial penile thrombophlebitis or penile Mondor's disease (PMD) is an underreported condition that causes anxiety and embarrassment in affected men. Patients usually present with a smooth, cord-like induration on the dorsal penile shaft 1-7 days after prolonged or intensive sexual intercourse, but other presentations of disease and triggers for endothelial damage are possible. The condition is typically self-limited with expected spontaneous resolution within 4-8 weeks of initial presentation, and absolute diagnosis is usually not necessary with management including supportive care and pain control. However, when disease course is prolonged or there are concerning risk factors, it may be important to differentiate PMD from other conditions such as Peyronie's disease, hypercoagulability, blood stasis, genitourinary infection, and malignancy. History and physical are often sufficient to distinguish these conditions from PMD, but providers may employ ultrasound to assist with the diagnosis. If PMD does not spontaneously resolve, patients may be considered for thrombectomy, at which point histological analysis can confirm the diagnosis.

The reduction corporoplasty: the answer to the improbable urologic question "can you make my penis smaller?".

INTRODUCTION: Aneurysmal dilatation of the corpora cavernosa can occur because of recurrent priapism in the setting of sickle cell disease. AIM: We present the first case of a successful implementation of the reduction corporoplasty technique for treatment of a phallus that was "too large for intercourse." METHODS: We describe the presentation of a 17-year-old male with a history of sickle cell disease with a phallus "too large for intercourse." Patient reported normal erectile function and response with masturbation but also reported inability to penetrate his partner due to the enlarged and disfigured morphology. He had three priapismic episodes since the age of 10 that progressively led to an aneurysmal morphologic deformity of his phallus. Evaluation included a magnetic resonance imaging, which revealed true aneurysmal dilatation of bilateral corpora cavernosa in the middle and distal portions, and diffusely hyperplastic tunica. MAIN OUTCOME MEASURE: The main outcome measure is the successful management of phallic disfiguration. RESULTS: Reduction corporoplasty was performed, and the patient reported intact erectile function without aneurysmal recurrence. CONCLUSIONS: Patients with significant corporal aneurysmal defects secondary to recurrent priapism can be successfully managed with reduction corporoplasty.

Cardiac hormones target nuclear oncogenes c-Fos and c-Jun in carcinoma cells.

BACKGROUND: c-Fos is a cellular proto-oncogene which dimerizes with c-Jun proto-oncogene to form AP-1 transcription factor, which upregulates transcription of genes involved in proliferation and cancer formation. Four cardiac hormones, that is, long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide (KP) and atrial natriuretic peptide (ANP) with anticancer effects in vivo are potent inhibitors of the Ras-MEK 1/2-ERK 1/2 kinase cascade and signal transducer and activator of transcription-3 (STAT-3) that activate c-Fos and c-Jun. These four cardiac hormones were investigated for their effects on proto-oncogenes c-Fos and c-Jun within the nucleus of cancer cells. MATERIALS AND METHODS: Four cardiac hormones were evaluated for their ability to decrease proto-oncogenes c-Fos and c-Jun, measured by ELISA in extracted nuclei of three human cancer cell lines. RESULTS: Vessel dilator, LANP, KP and ANP over a concentration range of 100 pM-10 µM, maximally decreased c-Fos by 61%, 60%, 61% and 59% in human hepatocellular cancer cells, by 82%, 74%, 78% and 74% in small-cell lung cancer cells, and by 82%, 73%, 78% and 74% in human renal adenocarcinoma cells. c-Jun was maximally reduced by vessel dilator, LANP, KP and ANP by 43%, 31%, 61% and 35% in hepatocellular cancer cells, by 65%, 49%, 59% and 40% in small-cell lung cancer cells, and by 47%, 43%, 57% and 49% in renal cancer cells. CONCLUSION: Four cardiac hormones are potent inhibitors of c-Fos and c-Jun proto-oncogenes within the nucleus of cancer cells.

Paclitaxel and TRAIL synergize to kill paclitaxel-resistant small cell lung cancer cells through a caspase-independent mechanism mediated through AIF.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive form of lung cancer with poor disease outcome. The chemotherapeutic agent paclitaxel (PA) is commonly used as a second-line treatment in SCLC, but response rates are low. MATERIALS AND METHODS: 86M1 SCLC cells were treated in the presence or absence of paclitaxel and TRAIL or the combination for 24 hours. Western blot analysis was utilized to examine protein expression, cell surface protein expression and membrane integrity were elucidated by flow cytometry, and immunofluorescence microscopy was used to demonstrate translocation of proteins to the cell nucleus. RESULTS: Human 86M1 SCLC cells were found to be resistant to PA killing in vitro. This resistance is mediated by up-regulation of pro-survival protein BCL-xl. However, PA also increases surface expression of death receptors 4 and 5 (DR4 and DR5, respectively). The death receptors' ligand increased SCLC killing by PA through an apparent caspase-independent route involving activation/translocation of AIF. CONCLUSION: The addition of TRAIL to PA can potentiate apoptosis in a relatively PA-resistant SCLC line (specifically 86M1 cells). More importantly, we are the first to report an active method of resistance to paclitaxel in SCLC via BCL-xl up-regulation.