A biopsy-integrated algorithm for determining Gleason 6 upgrading risk stratifies risk of active surveillance failure in prostate cancer.

INTRODUCTION: A significant proportion of patients that fail active surveillance (AS) for prostate cancer management do so because of cancer upgrading. A previously validated upgrading nomogram generates a score that predicts risk of biopsy Gleason 6 upgrading following radical prostatectomy in lower-risk populations that are candidates for Active Surveillance (Cancer, 2013). OBJECTIVES: We hypothesize that the upgrading risk (UR) score generated by this nomogram at diagnosis improves the ability to predict patients that will subsequently fail AS. METHODS: To evaluate the nomogram, retrospective data from several institutional cohorts of patients who met AS criteria, group 1 (n = 75) and group 2 (n = 1230), were independently examined. A UR score was generated using the coefficients from the nomogram consisting of PSA density (PSAD), BMI, maximum % core involvement (MCI), and number of positive cores. AS failure was defined as Gleason score (GS) >6, >50 % maximum core involvement, or >2 positive cores on biopsy. Univariate and multivariate Cox proportional-hazards regression models, upgrading risk score, and other clinicopathologic features were each assessed for their ability to predict AS failure. RESULTS: Clinicopathologic parameters were similar in both groups with the exception of mean PSAD (0.13 vs. 0.11, p < 0.01) and follow-up (2.1 vs. 3.2 years, p = 0.2). Most common cause of AS failure was GS > 6 (group 1) compared to >2 positive cores (group 2). On univariate analysis in both populations, features at diagnosis including PSAD and the UR score were significant in predicting AS failure by upgrading (Gleason > 6) and any failure. Multivariate analysis revealed the UR score predicts AS failure by GS upgrading (HR 1.8, 95 % CI 1.12-2.93; p = 0.01) and any failure criteria (HR 1.7, 95 % CI 1.06-2.65); p = 0.02) for group 1. Likewise, the UR score in group 2 predicts AS failure with GS upgrading (HR 1.3, 95 % CI 1.15-1.42; p < 0.0001) and any failure criteria (HR 1.18, 95 % CI 1.18-1.38; p < 0.0001). An ROC generated an AUC of 0.66. Decision curve analysis demonstrated a high net benefit for the UR score across a range of threshold probabilities. Based on these outcomes, at 3 years, patients in the lowest risk quartile have a 15 % risk of AS failure versus a 46 % risk in the highest quartile (p < 0.0001). CONCLUSIONS: The UR score was predictive of pathologic AS failure on multivariate analysis in several AS cohorts. It outperformed single clinicopathologic criteria and may provide a useful adjunct using clinicopathologic data to stratify patients considering AS.

Primary cutaneous adenosquamous carcinoma of the penis: the first characterization of HPV status in this rare and diagnostically challenging entity with review of glandular carcinomas of the penis.

Glandular and pseudoglandular tumors of the penile skin are extremely uncommon and can present diagnostic challenges. Primary adenosquamous carcinoma of the penis is an extremely rare tumor, composed of distinct areas of malignant squamous and glandular cells, making it a diagnostically challenging entity. The World Health Organization (WHO) recognizes several subtypes of squamous cell carcinoma (SCC), each with its own distinctive pathologic appearance, clinical associations and prognosis. Among these variants is the exceedingly uncommon adenosquamous carcinoma (ASC), representing 1%-2% of all SCC of the penis. Recent large studies have interrogated the presence of human papillomavirus (HPV) in malignant penile tumors and have shown specific morphologic patterns and clinical presentations to associate with HPV status. However, given the rarity of the adenosquamous variant of SCC, it has largely been excluded from these studies. The glandular components of these lesions can present a confusing appearance, particularly when a large tumor is represented on a small biopsy. Here we describe a difficult histologic presentation of this rare tumor, with the first published characterization of the HPV status of this subtype. This case represents a distinctly unusual case of metastatic HPV-positive primary cutaneous adenosquamous carcinoma of the penis.

Combination of bupivacaine scalp circuit infiltration with general anesthesia to control the hemodynamic response in craniotomy patients.

BACKGROUND: Sudden and overwhelming increases in blood pressure (BP) and heart rate (HR) during incision of the scalp may give rise to morbidity or mortality in patients with intracranial pathology undergoing neurosurgery. A modification of the method proposed by Labat to abate this circumstantiality was applied in a group of patients receiving craniotomy. The modified method was to combine scalp circuit infiltration of local anesthetic with general anesthesia to control the hemodynamic response to craniotomy. METHODS: Twenty-six patients scheduled to undergo craniotomy were randomly divided into two groups. Patients whose conditions or their current medication that might affect the stability of hemodynamics were excluded. In group A patients (N = 16) 25-30 ml of 0.25% bupivacaine was used for scalp circuit infiltration on the operation side, while in those of group B (N = 10) the same volume of 0.9% normal saline was used. After induction, anesthesia was maintained with 0.6% to 1.2% end-tidal isoflurane (ET-Iso) and 50% N2O in oxygen (N2O:O2 = 2 l/min:2 l/min). The end-tidal CO2 was kept within the range of 25-30 mmHg. BP and HR were recorded every five min before incision and then every two min after incision until one hour after induction. ET-Iso was also recorded every two min throughout a period of sixty min. If the BP and HR increased above 20% of the baseline (10 min before incision), thiopental 2.5 mg/kg and fentanyl 2 micrograms/kg were administered. If hypertension became sustained, the isoflurane concentration was adjusted until an acceptable level was obtained. RESULTS: The mean BP during the surgery was 92 +/- 1 mmHg in group A and 92 +/- 7 mmHg in group B. The difference in BP between incision to 6 min after incision was statistically significant (P < 0.05). The mean HR during surgery was 101 +/- 5 beats/min in group B and 91 +/- 2 beats/min in group A, the difference of which was not statistically significant. All of the patients in group B required a deepened anesthesia to keep the BP and HR within the normal range, but no patient in group A had such need. The average concentration of ET-Iso during the 60 min period was 0.95 +/- 0.12% in group B and 0.41 +/- 0.01% in group A, respectively. The difference was statistically significant (P < 0.05). CONCLUSIONS: Our results showed that scalp circuit infiltration with 0.25% bupivacaine significantly improved the cardiovascular stability and reduced the requirement of isoflurane during craniotomy. The routine use of bupivacaine scalp circuit infiltration in patients undergoing craniotomy should be considered.