A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong, China: what did we learn?

This study aimed to report the outcomes of active surveillance (AS) in the management of low-risk prostate cancer (PCa). It recruited 87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol with local adaptation at SH Ho Urology Centre, Prince of Wales Hospital, Hong Kong, China. We investigated the predictors of disease progression and found that baseline prostate-specific antigen density (PSAD) and the presence of the highest Prostate Imaging-Reporting and Data System (PI-RADS) score 5 lesion on magnetic resonance imaging (MRI) are significantly correlated with disease progression. Moreover, men with PSAD >0.2 ng ml-2 or PI-RADS 4 or 5 lesions had significantly worse upgrading-free survival compared to those with PSAD ≤0.2 ng ml-2 and PI-RADS 2 or 3 lesions. The study concludes that AS is a safe and effective management strategy for selected patients to defer radical treatment and that most disease progression can be detected after the first repeated biopsy. The combination of PSAD >0.2 ng ml-2 and PI-RADS 4 or 5 lesions may serve as a useful predictor of early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

The combined role of MRI prostate and prostate health index in improving detection of significant prostate cancer in a screening population of Chinese men.

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml -1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml -1 . A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml -1 and PHI ≥35, or PSA 10.0-50.0 ng ml -1 . Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml -1 . Among 194 men with PSA 4.0-50.0 ng ml -1 , 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml -1 , additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml -1 , and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml -1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml -1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.

Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine.

OBJECTIVE: Evaluations of upper gastrointestinal toxicity from ketamine abuse are uncommon. This study investigated the clinical pattern of upper gastrointestinal symptoms in patients inhaling ketamine. METHODS: In a cross-sectional study of 611 consecutive patients who were seeking treatment for ketamine uropathy in a tertiary hospital setting between August 2008 and June 2016, their clinical pattern of upper gastrointestinal symptoms was evaluated and compared with a control population of 804 non-users. RESULTS: A total of 168 (27.5%) patients abusing ketamine (mean age 26.3 years, 58.9% female) reported the presence of upper gastrointestinal symptoms. These symptoms were significantly more prevalent in patients inhaling ketamine than in those who were not (27.5% vs 5.2%, P < 0.001). Their mean duration of ketamine abuse before symptom presentation was 5.0 ± 3.1 years. The presenting symptoms included epigastric pain (n = 155, 25.4%), recurrent vomiting (n = 48, 7.9%), anemia (n = 36, 5.9%) and gastrointestinal bleeding (n = 20, 3.3%). Uropathy symptoms were preceded by upper gastrointestinal symptoms for 4.4 ± 3.0 years in 141 (83.9%) patients. Logistic regression showed that elder age (odds ratio [OR] 1.06, P = 0.04), active abuser status (OR 1.60, P = 0.04) and longer duration of ketamine abuse (OR 1.00, P = 0.04) were independent factors associated with upper gastrointestinal toxicity. CONCLUSIONS: Although epigastric symptoms are unusual in the young population, upper gastrointestinal toxicity was highly prevalent in those inhaling ketamine. Enquiries about ketamine abuse are recommended when assessing young patients with epigastric symptoms.

Deletion of EphA4 enhances deafferentation-induced ipsilateral sprouting in auditory brainstem projections.

Axonal selection of ipsilateral and/or contralateral targets is essential for integrating bilateral sensory information and for coordinated movement. The molecular processes that determine ipsilateral and contralateral target choice are not fully understood. We examined this target selection in the developing auditory brainstem. Ventral cochlear nucleus (VCN) axons normally project to the medial nucleus of the trapezoid body (MNTB) only on the contralateral side. However, after unilateral removal of cochlear input in neonates, we found that axons from the unoperated VCN sprout and project to MNTB bilaterally. We found that EphA4 is expressed in the mouse auditory brainstem during development and during a sensitive period for ipsilateral sprouting, so we hypothesized that deletion of the Eph receptor EphA4 would impair target selection in these auditory pathways. Lipophilic dyes were used to evaluate quantitatively the brainstem projections in wild-type and EphA4-null mice. VCN-MNTB projections in EphA4-null mice were strictly contralateral, as in wild-type mice. However, after deafferentation, EphA4-null mice had a significant, threefold increase in the proportion of axons from the intact VCN that sprouted into ipsilateral MNTB compared with wild-type mice. Heterozygous mice had a twofold increase in these projections. These results demonstrate that EphA4 influences auditory brainstem circuitry selectively in response to deafferentation. Although this axon guidance molecule is not by itself necessary for appropriate target choice during normal development, it is a strong determinant of ipsilateral vs. contralateral target choice during deafferentation-induced plasticity.