Real-world treatment outcomes of patients with penile cancer in the Kyushu-Okinawa area of Japan in the pre-guideline era.

OBJECTIVES: To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. METHODS: We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. RESULTS: A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79-10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11-10.1; P = 0.0319) were identified as independent prognostic factors. CONCLUSIONS: The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.

Direct modelling from GPS data reveals daily-activity-dependency of effective reproduction number in COVID-19 pandemic.

During the COVID-19 pandemic, governments faced difficulties in implementing mobility restriction measures, as no clear quantitative relationship between human mobility and infection spread in large cities is known. We developed a model that enables quantitative estimations of the infection risk for individual places and activities by using smartphone GPS data for the Tokyo metropolitan area. The effective reproduction number is directly calculated from the number of infectious social contacts defined by the square of the population density at each location. The difference in the infection rate of daily activities is considered, where the 'stay-out' activity, staying at someplace neither home nor workplace, is more than 28 times larger than other activities. Also, the contribution to the infection strongly depends on location. We imply that the effective reproduction number is sufficiently suppressed if the highest-risk locations or activities are restricted. We also discuss the effects of the Delta variant and vaccination.

Potential fields and fluctuation-dissipation relations derived from human flow in urban areas modeled by a network of electric circuits.

Owing to the big data the extension of physical laws on nonmaterial has seen numerous successes, and human mobility is one of the scientific frontier topics. Recent GPS technology has made it possible to trace detailed trajectories of millions of people, macroscopic approaches such as the gravity law for human flow between cities and microscopic approaches of individual origin-destination distributions are attracting much attention. However, we need a more general basic model with wide applicability to realize traffic forecasting and urban planning of metropolis fully utilizing the GPS data. Here, based on a novel idea of treating moving people as charged particles, we introduce a method to map macroscopic human flows into currents on an imaginary electric circuit defined over a metropolitan area. Conductance is found to be nearly proportional to the maximum current in each location and synchronized human flows in the morning and evening are well described by the temporal changes of electric potential. Surprisingly, the famous fluctuation-dissipation theorem holds, namely, the variances of currents are proportional to the conductivities akin to an ordinary material.

Preoperative Predictors of Lymph Node Invasion and Biochemical Recurrence in High-risk Prostate Cancer.

Aim: To evaluate the preoperative predictors of pathological lymph node (LN) metastasis and prognostic factors for postoperative biochemical recurrence (BCR) in robot-assisted radical prostatectomy with extended pelvic LN dissection in patients with D'Amico high-risk prostate cancer (PCa). Patients and Methods: Overall, 107 patients with D'Amico high-risk PCa underwent robot-assisted radical prostatectomy with extended pelvic LN dissection without neoadjuvant or adjuvant therapy. BCR was defined as a prostate-specific antigen (PSA) level ≥0.2 ng/ml. Moreover, BCR-free survival rates were determined using Kaplan-Meier analysis. Logistic regression analysis was used to evaluate preoperative predictors of pathological LN metastasis. Cox regression analysis was used to evaluate the effects of preoperative and pathologic variables on BCR. Results: The median follow-up was 21 months, and the 5-year BCR-free survival rate was 59.8%. The positive LN rate was 21.5%. In multivariate analysis, the percentage of positive cores was a significant preoperative predictor of positive LNs. Patients with >50% positive cores (p=0.004) and PSA density (PSAD) >0.5 ng/ml/cc (p=0.005) had a high risk of having ≥3 positive LNs. In multivariate analysis, PSAD >0.5% was a significant preoperative predictor of BCR. Among the postoperative predictors, the number of positive LNs was significantly associated with BCR. Patients with ≥3 positive LNs (n=7) had significantly lower BCR-free survival rates than patients with one or two positive LNs (n=16) (p<0.001). Patients with >50% positive cores and PSAD >0.5 ng/ml/cc had a risk for a high number of positive LNs (≥3) that was strongly associated with shorter BCR-free survival (p<0.001). Conclusion: The percentage of positive cores may be useful as a preoperative predictor of pathological LN metastasis in patients with high-risk PCa. Patients with >50% positive cores and PSAD >0.5 ng/ml/cc were found to have a high risk for ≥3 positive LNs and shorter BCR-free survival.

Universal scaling of human flow remain unchanged during the COVID-19 pandemic.

To prevent the spread of the COVID-19 pandemic, governments in various countries have severely restricted the movement of people. The large amount of detailed human location data obtained from mobile phone users is useful for understanding the change of flow patterns of people under the effect of pandemic. In this paper, we observe the synchronized human flow during the COVID-19 pandemic using Global Positioning System data of about 1 million people obtained from mobile phone users. We apply the drainage basin analysis method which we introduced earlier for characterization of macroscopic human flow patterns to observe the effect of the spreading pandemic. Before the pandemic the afternoon basin size distribution has been approximated by an exponential distribution, however, the distribution of Tokyo and Sapporo, which were most affected by the first wave of COVID-19, deviated significantly from the exponential distribution. On the other hand, during the morning rush hour, the scaling law holds universally, i.e., in all cities, even though the number of moving people in the basin has decreased significantly. The fact that these scaling laws, which are closely related to the three-dimensionality structure of the city and the fractal structure of the transportation network, have not changed indicates that the macroscopic human flow features are determined mainly by the means of transport and the basic structure of cities which are invariant of the pandemic.

Rare case of penile fracture caused by an injury to the crus penis: Delayed repair using the transperineal approach.

INTRODUCTION: Penile fracture is a rare urologic emergency, and its surgical treatment is selected based on the damaged site of the penile corpus cavernosum. Penile fractures at the site of the crus penis are quite rare, and there is controversy regarding the preferred method of surgical repair. CASE PRESENTATION: A 25-year-old Asian man was injured when rolling over in bed. Magnetic resonance imaging showed a tear in the left crus of the penis with a hematoma. Delayed surgery was successfully performed using the transperineal approach. He did not experience pain, dysuria, or erectile dysfunction postoperatively. CONCLUSION: Delayed surgical repair using transperineal approach may be useful for penile fractures associated with penile crus injuries.

[A CASE OF CONGENITAL UNILATERAL ABSENCE OF THE VAS DEFERENS WITH SUSPECTED IPSILATERAL RENAL AGENESIS].

A 5-month-old boy was referred to our department to examine poor development of external genitalia. The patient was diagnosed with micropenis and bilateral impalpable testes, and testosterone replacement therapy was recommended. The testes remained impalpable at 14 months of age; therefore, laparoscopy was performed to explore intra-abdominal testes. The patient was incidentally diagnosed with congenital unilateral absence of the right vas deferens. A renal sonography performed after the operation revealed a high possibility of right renal agenesis. Congenital absence of the vas deferens is associated with a high probability of renal anomalies. It is, therefore, essential to pay careful attention to renal dysfunction.

Universal scaling laws of collective human flow patterns in urban regions.

Detail observation of human locations became available recently by the development of information technology such as mobile phones with GPS (Global Positioning System). We analyzed temporal changes of global human flow patterns in urban regions based on mobile phones' GPS data in 9 large cities in Japan. By applying a new concept of drainage basins in analogous to river flow patterns, we discovered several universal scaling relations. These include, the number of moving people in a drainage basin of diameter L is proportional to [Formula: see text] in the morning rush hour, which is surprisingly different from reasonable intuition of proportionality to the 2 dimensional area, [Formula: see text]. We show that this unexpected 3 dimensional feature is related to the strong attraction of the city center to become a 3 dimensional structure due skyscrapers.

Three cases of brain metastasis from castration-resistant prostate cancer.

Brain metastasis from prostate cancer may be becoming more common and may be associated with occurrence of diffuse systemic metastases.

Isolated left adrenal medullary hyperplasia.

A 44-year-old Japanese man was referred to our hospital for the evaluation of paroxysmal hypertension. 123I-metaiodobenzylguanidine (MIBG) single-photon emission computed tomography (SPECT) revealed specific uptake in the left adrenal gland in addition to high levels of serum and urinary catecholamines although computed tomography and magnetic resonance imaging were not able to detect a definite adrenal mass. Left adrenalectomy was performed and he was diagnosed with adrenal medullary hyperplasia (AMH). A diagnosis of unilateral AMH is important because AMH resection can effectively treat hypertension. .

Stage-specific embryonic antigen-4 is a histological marker reflecting the malignant behavior of prostate cancer.

Stage-specific embryonic antigen-4 (SSEA-4), a specific marker for pluripotent stem cells, plays an important role in the malignant behavior of several cancers. Here, SSEA-4 expression was evaluated by immunohistochemistry using monoclonal antibody RM1 specific to SSEA-4 in 181 and 117 prostate cancer (PC) specimens obtained by biopsy and radical prostatectomy (RP), respectively. The relationships between SSEA-4 expression in cancer cells or the presence of SSEA-4-positive tumor-infiltrating immune cells (TICs) and clinicopathological parameters were analyzed. SSEA-4 expression in cancer cells was significantly associated with Gleason score, local progression, and lymph node and distant metastasis. In RP specimens, high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs were significant predictors of pT3, i.e., invasion and worse biochemical recurrence (BCR) after RP, respectively, in univariate analysis. In contrast, combination of high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs was an independent predictor for pT3 and BCR in multivariate analysis. Biologically this combination was also independently associated with suppression of apoptosis. Thus, the co-expression of SSEA-4 in cancer cells and TICs may have crucial roles in the malignant aggressiveness and prognosis of PC. Invasive potential and suppression of apoptosis may be linked to SSEA-4 expression.

[A Case of Giant Adrenal Endothelial Cyst that was Discovered in Pregnancy and Caused Bleeding Three Years Later].

A 39-year-old woman was referred to our hospital after incidental detection of a hypoechoic abdominal mass on ultrasonography at the 11th week of gestation. Magnetic resonance imaging confirmed a 20 cm cystic lesion just cephalad to the left kidney. The patient delivered in the 40th week of gestation without complications. After 3 years of follow-up, she presented with acute left flank pain. Physical examination revealed pale palpebral conjunctiva and abdominal fullness. Contrast-enhanced computed tomography confirmed a 21 × 17 × 15 cm hemorrhagic cyst arising from the left adrenal gland. Laparoscopic left adrenalectomy was performed. Pathological examination revealed a vascular cyst (endothelial cyst) of the adrenal gland. Surgical intervention is indicated for large adrenal cysts which may cause bleeding into the cavity.

Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer.

Prostate cancer is the most common cancer among men. Green tea consumption is reported to play an important role in the prevention of carcinogenesis in many types of malignancies, including prostate cancer; however, epidemiological studies show conflicting results regarding these anti-cancer effects. In recent years, in addition to prevention, many investigators have shown the efficacy and safety of green tea polyphenols and combination therapies with green tea extracts and anti-cancer agents in in vivo and in vitro studies. Furthermore, numerous studies have revealed the molecular mechanisms of the anti-cancer effects of green tea extracts. We believe that improved understanding of the detailed pathological roles at the molecular level is important to evaluate the prevention and treatment of prostate cancer. Therefore, in this review, we present current knowledge regarding the anti-cancer effects of green tea extracts in the prevention and treatment of prostate cancer, with a particular focus on the molecular mechanisms of action, such as influencing tumor growth, apoptosis, androgen receptor signaling, cell cycle, and various malignant behaviors. Finally, the future direction for the use of green tea extracts as treatment strategies in patients with prostate cancer is introduced.

Successful laparoscopic resection of a paraganglioma immediately behind the inferior vena cava and bilateral renal veins.

INTRODUCTION: Paragangliomas have a rich blood flow and are located around large vessels; thus, resection is often difficult. We herein report a case of a paraganglioma that was located immediately behind the inferior vena cava and bilateral renal veins and successfully resected by laparoscopic surgery. CASE PRESENTATION: A 72-year-old man was incidentally diagnosed with a 7-cm retroperitoneal mass immediately behind the inferior vena cava and bilateral renal veins by computed tomography. The mass was diagnosed as a retroperitoneal paraganglioma. The patient underwent laparoscopic surgery in the left lateral decubitus position. The tumor was dissected completely with no complications. CONCLUSION: Resection of retroperitoneal paragangliomas is often a surgical challenge. The feasibility of the laparoscopic approach to such paragangliomas was demonstrated in the present case.

Influence of prior oral ethinylestradiol use on the efficacy of enzalutamide for the treatment of castration-resistant prostate cancer in men.

OBJECTIVE: To elucidate the effect of prior use of ethinylestradiol on enzalutamide treatment for men with castration-resistant prostate cancer. METHODS: We retrospectively analyzed data from 99 consecutive patients (median age 72 years, range 50-88 years) treated with enzalutamide for castration-resistant prostate cancer between May 2014 and November 2015 after receiving several lines of hormonal therapy. RESULTS: A total of 45 patients were given ethinylestradiol before enzalutamide. The prostate-specific antigen response rate (decline in prostate-specific antigen >50% from baseline) of patients receiving ethinylestradiol and enzalutamide were 51.1% and 41.4%, respectively. Cross-resistance between ethinylestradiol and enzalutamide was clearly observed in the setting of pre-docetaxel. In multivariate analysis, the T stage and number of therapies before enzalutamide were the only significant predictors of prostate-specific antigen response to enzalutamide. However, in patients treated pre-docetaxel use, prior use of ethinylestradiol was a significant predictor of prostate-specific antigen response to enzalutamide, whereas ethinylestradiol did not affect the overall survival of these patients. CONCLUSIONS: Cross-resistance between ethinylestradiol and enzalutamide in the setting of pre-docetaxel therapy seems to be evident. Therefore, ethinylestradiol should be used prudently before enzalutamide in this setting.

Three cases of nonmetastatic prostate cancer treated successfully with primary intermittent androgen deprivation therapy over 10 years.

We report three cases of nonmetastatic prostate cancer treated effectively with long-term primary intermittent androgen deprivation (IAD). IAD is not a standard therapy for patients with nonmetastatic prostate cancer. However, based on our experience, we suggest that IAD is one of useful therapeutic tools under certain patients' condition.

Changes in Lymphangiogenesis and Vascular Endothelial Growth Factor Expression by Neo-Adjuvant Hormonal Therapy in Prostate Cancer Patients.

BACKGROUND: The anti-cancer mechanism of neo-adjuvant hormonal therapy (NHT) is not well understood. Lymphangiogenesis plays an important role in cancer progression and is regulated by a complex mechanism that includes vascular endothelial growth factor (VEGF) signaling. However, there is little information regarding relationship between lymphangiogenesis and androgen deprivation. The aim of this study was to clarify changes in lymphangiogenesis and VEGF expression induced by androgen deprivation in prostate cancer in vivo and in vitro. METHODS: Patients who had undergone a radical prostatectomy were enrolled in the study (NHT, n = 60 and non-NHT, n = 64). Lymph vessels were identified by D2-40 immunoreactivity and lymph vessel density and lymph vessel area (LVD and LVA, respectively) were measured from micrographs. The expression of VEGF-A, -B, -C, and -D was evaluated by immunohistochemistry. The prognostic value of LVD and LVA for biochemical recurrence was also investigated. RESULTS: Mean LVD ± SD was higher in the NHT than in the non-NHT group (11.3 ± 3.0 vs. 7.1 ± 3.4 per high power field; P < 0.001). LVA was larger in the NHT than in the non-NHT group (512.8 ± 174.9 vs. 202.7 ± 72.8 µm2 ; P < 0.001). VEGF-A expression was lower whereas VEGF-C and -D levels were higher in the NHT than in the non-NHT group. VEGF-B expression in specimens with NHT was lower than that in biopsy specimens at diagnosis. These results were confirmed by in vitro studies used androgen-sensitive prostate cancer cell line. LVA was found to be an independent predictor of biochemical recurrence in patients who received NHT. CONCLUSIONS: Our results demonstrate that NHT stimulates lymphangiogenesis via upregulation of VEGF-C and -D, which may increase LVA and affect the outcome of prostate cancer patients. This findings were supported by in vitro data of prostate cancer cell. Prostate 77:255-262, 2017. © 2016 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Comparison Between a Combined Transrectal and Transperineal Approach and a Transrectal Approach for Prostate Rebiopsy.

AIM: To evaluate whether a combination method involving the transrectal (TR) and transperineal (TP) approach can increase the cancer detection rate relative to the TR approach regarding repeat prostate biopsy. PATIENTS AND METHODS: One thousand and nineteen patients underwent initial prostate biopsies and 298 repeat prostate biopsies. All initial biopsies were conducted transrectally. Of the repeat biopsies, 179 (60.1%) were performed using the combined transrectal and transperineal (TR+TP) approach; 113 (37.9%) were carried out transrectally. All biopsies were performed under ultrasound guidance using a 16-gauge core biopsy needle; 651 were diagnosed as prostate cancer; 224 patients underwent radical prostatectomies (RPs). We evaluated the cancer detection rates between the biopsy methods in the repeat biopsy cohort and compared the clinical and pathological features of the RP specimens between the initial and repeat biopsy groups. RESULTS: A median of 12 and 20 cores were obtained in the initial and repeat biopsy patients, respectively. Cancer detection rates regarding biopsies 1, 2, 3, 4 and 5 were 49.2% (551/1,119), 34.7% (75/216), 33.3% (20/60), 26.7% (4/15) and 14.3% (1/7), respectively. There were no significant differences between the TR and the TR+TP approach (32.7% vs. 33.5%). RP specimens diagnosed using repeat biopsies showed more anterior dominant tumors relative to those diagnosed using the initial biopsies (59.5% vs. 35.9%; p<0.001). CONCLUSION: The TR+TP combination approach could not increase cancer detection rates relative to the TR approach in the repeat biopsy cohort. However, 16-gauge needle biopsy demonstrated acceptable cancer detection rates in the comparatively small number of biopsy cores.

Human antigen R is positively associated with malignant aggressiveness via upregulation of cell proliferation, migration, and vascular endothelial growth factors and cyclooxygenase-2 in prostate cancer.

Limited information is available on the pathologic significance of human antigen R (HuR) in prostate cancer (PCa). The main aim of this study was to clarify the relationship between HuR expression and malignant aggressiveness, outcome, and expression of cancer-related molecules in PCa. In vitro proliferation, colony formation, and migration assays were performed on LNCaP and PC-3 cells. HuR expression was knocked down (KD) using small interfering RNA. The relationships between HuR expression and the expression of vascular endothelial growth factors (VEGFs), cyclooxygenase (COX)-2, and heme oxygenase (HO)-1 were investigated in PCa cell lines using Western blotting. On KD of HuR, cell proliferation and migration were suppressed in both LNCaP and PC-3 cells, whereas expression of VEGF-A to -D and COX-2 was suppressed in PC-3 but not in LNCaP cells. In addition, expression of these cancer-related factors was analyzed in 182 hormone-naïve PCa and 23 castration-resistant prostate cancer (CRPC) human tissues in vivo. Cytoplasmic (C)-HuR expression was significantly higher in CRPC > hormone-naïve PCa > nontumoral cells. C-HuR expression was positively associated with Gleason score, T stage, and metastasis, and it was considered to be a useful predictor of biochemical recurrence after radical prostatectomy. C-HuR expression was correlated with COX-2 expression in hormone-naïve PCa, and with the expression of VEGF-A, VEGF-C, and COX-2 in CRPC tissues. Our results demonstrated that HuR plays important roles in determining malignant aggressiveness and outcome in PCa, especially in androgen-independent PCa cells, via the regulation of cell proliferation, migration, and expression of VEGF-A, -C, and COX-2.