Prostate­specific antigen density and preoperative MRI findings as predictors of biochemical recurrence in high­risk and very high­risk prostate cancer.

Patients with high-risk prostate cancer after prostatectomy have a particularly high chance of being diagnosed with biochemical recurrence (BCR). Patients with BCR have a greater risk of disease progression and mortality. The present retrospective observational study aimed to clarify the risk factors for the BCR of prostate cancer after radical prostatectomy in patients with high-risk and very high-risk prostate cancer. Patients diagnosed with prostate cancer who received radical prostatectomy in a single center from January 2009 to June 2020 were included in the study. Data from medical records were reviewed and the patients were followed up for ≥6 years. The primary outcome was BCR within 1 year after surgery. A total of 307 patients were included, with 187 in the high-risk group and 120 in the very high-risk group as classified by the National Comprehensive Cancer Network (NCCN) guidelines. Patients in the very high-risk group had a lower BCR-free survival rate compared with those in the high-risk group, with a high risk of BCR even if their PSA levels were initially undetectable after prostatectomy, and a high risk of postoperatively detectable PSA. In patients with undetectable PSA after prostatectomy, BCR was associated with the initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1). Postoperatively detectable PSA was associated with pathologic stage (T3bN0M0 and any N1) In conclusion, preoperative MRI imaging stage and PSA density are predictors for short-term BCR after prostatectomy. NCCN-defined high-risk patients with a high initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1) had a higher risk of BCR when compared with other patients with undetectable PSA, while those with pathologic stage (T3bN0M0 or any N1) displayed a higher risk of postoperatively detectable PSA. These findings may help urologists to identify patients for whom active therapeutic protocols are necessary.

Efficacy of a protocol including heparin ointment for treatment of multikinase inhibitor-induced hand-foot skin reactions.

PURPOSE: The purpose of this study is to evaluate the efficacy of a protocol including topical heparin therapy for hand-foot skin reactions (HFSR) during multikinase (MKI) treatment. METHODS: We prospectively collected 26 patients who had HFSRs during treatment with the MKIs, sunitinib, sorafenib, or axitinib. The age distribution ranged from 46 to 87 years, with a mean of 66 years. The distribution of HFSR severity was 12 patients with grade 1, 12 with grade 2, and 2 with grade 3. A heparin-containing topical ointment treatment, combined with hand-foot shock absorbers and skin moisturizers, was used at the lesion sites. Changes in the grade of HFSR, MKI dosage, and interruptions of MKI therapy were recorded. RESULTS: The results showed that 66.7% of grade 1 patients were cured of disease, 83.3% of grade 2 patients had improved symptoms, and both grade 3 patients (100%) had improved symptoms and were downgraded to grade 2. Four (15.4%) patients required reduction of MKI dosage, but there were no treatment interruptions or dropouts. CONCLUSION: Our protocol is beneficial in promoting resolution of HFSRs induced by MKIs. Further validation in large control studies should be investigated.

The additive erectile recovery effect of brain-derived neurotrophic factor combined with vascular endothelial growth factor in a rat model of neurogenic impotence.

OBJECTIVE: To test the hypothesis that combined intracavernosal injection with vascular endothelial growth factor (VEGF) with adeno-associated virus-mediated brain-derived neurotrophic factor (AAV-BDNF) synergistically facilitates the neural regeneration and erectile function after cavernosal nerve injury. MATERIALS AND METHODS: Forty Sprague-Dawley male rats were randomly divided into five equal groups: eight had a sham operation while 32 had bilateral cavernosal nerve freezing followed by an immediate intracavernosal injection with either phosphate-buffered saline (PBS), VEGF, AAV-BDNF, or AAV-BDNF + VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and samples of the major pelvic ganglia and penile tissue were evaluated histologically. RESULTS: In this animal model of impotence from nerve injury, the recovery of erectile function was greatest in those receiving AAV-BDNF + VEGF; the mean (sd) maximal intracavernosal pressure in this group was 87.2 (20.78) cmH2O, compared with 37.3 (11.39) for VEGF alone and 49.8 (29.58) for AAV-BDNF alone. No erectile dysfunction was identified in the sham group, with a pressure of 100.7 (22.70) cmH2O, while all treatment groups significantly outperformed the PBS (control) group, at 29.3 (13.52) cmH2O. Furthermore, all animals receiving monotherapy or combined treatment had more NADPH-diaphorase-positive nerve fibres than controls but less than in the sham group. CONCLUSION: Bilateral cavernosal nerve freezing causes erectile dysfunction with accompanying neurological changes. Intracavernosal injection with either VEGF or AAV-BDNF alone enhances nerve regeneration, with combined therapy (VEGF and AAV-BDNF) promoting neural and erectile recovery additively.

The effect of vascular endothelial growth factor on a rat model of traumatic arteriogenic erectile dysfunction.

PURPOSE: We tested the hypothesis that intracavernous injection of vascular endothelial growth factor (VEGF) can restore erectile function in a rat model of traumatic arteriogenic erectile dysfunction. MATERIALS AND METHODS: Exploration of bilateral internal iliac arteries was performed in 50, 3-month-old male rats. A total of 44 rats underwent bilateral ligation of the internal iliac arteries and 6 that underwent exploration only served as the sham operated group. Minutes later intracavernous injection of phosphate buffered saline (PBS) plus bovine serum albumin in 16 rats, 2 microg. VEGF plus PBS plus BSA in 12 and 4 microg. VEGF plus PBS plus BSA in 16 was performed. At weeks 1, 2 and 6 about a third of the rats in each group underwent electrostimulation of the cavernous nerves to assess erectile function and were then sacrificed. Penile tissues were collected for histochemical and electron microscopy examinations. RESULTS: No impairment of erectile function was noted in sham operated rats. Immediately after arterial ligation all rats showed little or no erectile response to neurostimulation. In PBS treated rats modest recovery of erectile function was noted at week 6. Significant recovery of erectile function was noted in VEGF treated rats at weeks 1 and 2 in the 4 microg. group only and at week 6 in the 2 and 4 microg. groups. Neuronal nitric oxide synthase staining showed a reduction in neuronal nitric oxide synthase positive nerve fibers in the dorsal or intracavernous nerves at week 1. Moderate recovery of neuronal nitric oxide synthase positive nerve fibers was noted in the 2 and 4microg. VEGF treated groups but not in the PBS treated group. Electron microscopy revealed no pathological change in sham operated rats. In dorsal nerves the atrophy of myelinated and nonmyelinated nerve fibers was noted in ligated plus PBS treated rats. Partial recovery was observed in VEGF treated rats. Scattered atrophic smooth muscle cells were seen in PBS and occasionally in VEGF treated rats but not in the sham operated group. The most dramatic findings in VEGF treated rats were hypertrophy and hyperplasia of the endothelial cells, especially those lining the small capillaries. CONCLUSIONS: Ligation of bilateral internal iliac arteries produced a reliable animal model of traumatic arteriogenic erectile dysfunction. Intracavernous injection of VEGF minutes after arterial ligation facilitated the recovery of erectile function.