High testosterone levels in prostate tissue obtained by needle biopsy correlate with poor-prognosis factors in prostate cancer patients

Background: There is currently no consensus on the correlations between androgen concentrations in prostate tissue and blood and stage and pathological grade of prostate cancer. In this study, we used a newly-developed ultra-sensitive liquid-chromatography tandem mass spectrometry method to measure testosterone (T) and dihydrotestosterone (DHT) concentrations in blood and needle biopsy prostate specimens from patients with prostate cancer.Methods: We analyzed androgen levels in 196 men diagnosed with prostate cancer. All patients had undergone systematic needle biopsy, and an additional needle biopsy from the peripheral zone was conducted for the simultaneous determination of T and DHT. We analyzed the relationships between T and DHT levels in tissue and blood and Gleason score, clinical stage, and percentage of positive biopsy cores, using multivariate analysis. Results: The median T and DHT levels in blood were 3551.0 pg/mL and 330.5 pg/mL, respectively. There was a strong correlation between serum T and DHT. The median T and DHT levels in prostate tissue were 0.5667 pg/mg and 7.0625 pg/mg, respectively. In multivariate analysis, serum prostate-specific antigen and tissue T levels were significantly associated with poor prognosis; high T levels in prostate tissue were significantly related to high Gleason score (p = 0.041), advanced clinical stage (p = 0.002), and a high percentage of positive biopsy cores (p = 0.001). Conclusions: The results of this study indicate that high T levels in prostate tissue are related to high Gleason score, advanced clinical stage, and a high percentage of positive biopsy cores in patients with prostate cancer. T level in needle biopsy specimens may therefore be a useful prognostic factor in prostate cancer patients

The Importance of Time to Prostate-Specific Antigen (PSA) Nadir after Primary Androgen Deprivation Therapy in Hormone-Naïve Prostate Cancer Patients

Prostate-specific antigen (PSA) is currently the most useful biomarker for detection of prostate cancer (PCa). The ability to measure serum PSA levels has affected all aspects of PCa management over the past two decades. The standard initial systemic therapy for advanced PCa is androgen-deprivation therapy (ADT). Although PCa patients with metastatic disease initially respond well to ADT, they often progress to castration-resistant prostate cancer (CRPC), which has a high mortality rate. We have demonstrated that time to PSA nadir (TTN) after primary ADT is an important early predictor of overall survival and progression-free survival for advanced PCa patients. In in vivo experiments, we demonstrated that the presence of fibroblasts in the PCa tumor microenvironment can prolong the period for serum PSA decline after ADT, and enhance the efficacy of ADT. Clarification of the mechanisms that affect TTN after ADT could be useful to guide selection of optimal PCa treatment strategies. In this review, we discuss recent in vitro and in vivo findings concerning the involvement of stromal⁻epithelial interactions in the biological mechanism of TTN after ADT to support the novel concept of “tumor regulating fibroblasts„

Development of Multiphoton Ionization Time-of-Flight Mass Spectrometry for the Detection of Small Emulsion Droplets

A system for measuring small oil droplets in an oil-in-water (O/W) emulsion was developed using multiphoton ionization time-of-flight mass spectrometry. In the present study, a capillary column with an inner diameter of 15 µm was used for sample introduction. Moreover, a compact microscopic system was constructed for observing an emulsion flowing through a capillary column. As a result, the length for sample introduction was shortened, which is preferable for the direct evaluation of an emulsion. Using this system, the minimum diameter of a detectable toluene droplet in an O/W emulsion was decreased to 1.7 µm. The present system could be used to evaluate the local microenvironment and stability of an emulsion

Kock continent ileal urinary reservoirによる尿路変更術20例の検討 : 特に合併症について

1986年8月より1990年7月までに, 20例のKock continent ileal reservoirによる尿路変更術を施行した.術後3ヵ月以内の早期合併症として, 創部感染4例, 尿管回腸吻合部からの尿漏出3例, 輸出脚の脱出, 腸閉塞は各2例, 逆流, 尿管狭窄, 回腸吻合不善, 術後膵炎は各1例づつ認めた.晩期合併症としてpouch内結石形成2例, 輸入脚狭窄1例をみたが, この狭窄はDacron collarの部位に認めた.早期10例と後期10例に分け, 各グループの合併症と手術成績を比較検討した.早期10例のうち8例にのべ14例の合併症を認めたが, 後期10例では4例に減少した.症例が増すにしたがって早期合併症は減少し, 手術成績も後期10例の方が早期10例より良好であった.術後水腎症の検討を行ったところ, 術後1, 2ヵ月目では9例に軽度の水腎症が認められたが, 術後3ヵ月以降は5例と, 正常化する傾向が認められた.pouch内に400～500 ml注入時の最大pouch内圧は37.9±12.2 cmH2O (mean±SD)と, 注入に伴う内圧の著明な上昇は認めなかったFrom August 1986 through July 1990, 20 patients underwent construction of the Kock continent ileal reservoir and were observed for more than three months. The early complications within the first 3 months were wound infection in four patients (20%), leakage at uretero-intestinal anastomosis in three patients (15%), prolapse of efferent limb and ileus in two patients (10%) and reflux, ureteral stenosis, intestinal fistula and postoperative pancreatitis in one patient (5%). The three late complications included stone formation in two patients and stenosis at an afferent limb in one patient. The stenosis occurred at the position of Dacron collar. The patients were divided into two groups and we compared the recent 10 patients with the initial 10 patients on complications and end results. In the initial group, 8 patients (80%) had 14 complications. In the recent group, 4 patients had 4 complications. The early complications have been reduced with the increase of Kock pouch operation. The result of the recent group was better than that of the initial group. Frequency of postoperative hydronephrosis in patients with Kock pouch was investigated. In nine patients (45%) the minimal hydronephrosis occurred within the first two months and in 5 patients (25%) three months after the operation. It had a normalizing tendency. The maximum pouch pressure at the pouch volume of 400 to 500 ml was not significantly high (37.9 +/- 12.2 cmH2O, mean +/- S.D.)

Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers

初発の表在性低悪性度の膀胱癌においては, 増殖状態が再発危険因子である

再発危険因子検索のため, pTa33例とpTl46例の膀胱癌患者にKi-67, c-erbB-2, p53と多薬剤耐性蛋白(MRP)を免疫組織化学的に検討した.その結果, pTl, 広基性, 腫瘍径の大きな腫瘍(>3cm)の再発率は高かった.また, Ki-67, c-erbB-2, p53の過剰発現症例の再発率は, 有意に高かったが, MRP発現と再発とは関連がなかった.多変量解析では, 腫瘍径の大きな腫瘍とKi-67高発現が再発の独立した予後因子であった.腫瘍径が1cm未満の症例の再発は, Ki-67およびp53過剰発現が関連した.Ki-67高発現により, grage2.pTlおよび単発腫瘍において, 再発の高い症例を識別できた.このことより, 増殖関連蛋白を臨床病理因子に加えることにより, 重要な予後を規定する情報となることを示しており, Ki-67高発現が信頼しうる再発予後因子であると考えられたThe current clinicopathologic study for evaluation of superficial bladder cancer still has limitations in predicting the true behavior of recurrence. To determine the high-risk recurrence factors, we studied the influence of Ki-67, c-erbB-2, p53 and multidrug resistance-associated protein (MRP) expression. Samples were obtained from 33 pTa and 46pT1 diagnosed bladder cancer patients with a mean follow-up of 48.7 +/- 30.6 months. The contingency table method, Kaplan-Meier curve and multivariate analysis were used to evaluate the association among the immunohistochemical factors expression, clinicopathologic parameters with tumor recurrence. Stage pT1 tumors, sessile tumors and large tumors (> 3 cm) showed a significantly high recurrence rate (p = 0.0158, p = 0.0162, p = 0.0001 respectively). Tumors with overexpression of Ki-67, c-erbB-2 and p53 were more likely to recur (p = 0.0035, p = 0.0027, p = 0.0076 respectively), MRP expression was not associated with recurrence. Multivariate analysis showed that large tumors and high Ki-67 expression were independent indicators of recurrence. On the other hand, in tumors less than 1 cm, recurrence was significantly correlated with overexpression of Ki-67 and p53. High Ki-67 expression could discriminate higher recurrence cases in grade 2, pT1 and single tumors. The c-erbB-2 overexpression was more frequently associated with recurrence in sessile tumors, large tumors, multiple and grade 1 tumors. The p53 overexpression also predicted a higher risk of recurrence in pTa tumors. These data demonstrated that the use of proliferative related proteins yields significant prognostic information in addition to clinicopathological factors, high Ki-67 expression is a reliable indicator of recurrence. A combination rather than any factor alone could more accurately predict tumor recurrence