Skeletal tissue growth, differentiation and mineralization in the NASA rotating wall vessel

The NASA Rotating Wall Vessel (RWV) is a device that creates a unique environment that supports three-dimensional tissue growth, a heightened level of cell differentiation and randomizes the position of the downward gravitational force on cells. Embryonic bone formation encompasses a cascade of chondrogenic and osteogenic events, which can be altered by changes in gravitational loading. These studies were conducted to determine if the chondrogenic cascade in bone formation would be enhanced or hindered in the unique culture environment of the RWV. Embryonic mouse pre-bone tissues were placed in the RWV at one of four different stages of chondrogenesis, ranging from undifferentiated mesenchyme cells to chondrocytes on the verge of undergoing terminal chondrocyte differentiation. After culture, tissues were analyzed for their size, the amount of alkaline phosphatase (ALP) activity and their ability to form a mineralized matrix. Tissue consisting of cells at the early phase of chondrogenesis grew very little and did not differentiate or mineralize when cultured in the RWV. Some tissues were cultured for short periods in the RWV then cultured in standard culture dishes (SCD). Following this culture regime, the cartilage grew only a small amount, but alkaline phosphatase activity increased, and some mineralized regions formed. The pattern of mineralization was abnormal, with two mineralized zones at each end of the cartilage instead of a single central zone. Tissues that were at the three more advanced stages of chondrogenesis when placed in the RWV showed substantial growth, differentiation and mineralization. Mineralization patterns in these older tissues was normal. Tissues at the oldest stage of chondrogenesis showed more growth and as much or more mineralization as tissue cultured only in SCD. These data suggest that exposure to the RWV at early stages of chondrogenesis severely limits the ability for cartilage growth and yields abnormal downstream morphogenesis. However, at later stages of chondrogenesis, the RWV environment may be beneficial and enhance growth and development. Future studies to characterize intercellular signaling molecules and gene expression activities of chondrocytes in the RWV will be valuable for understanding the mechanism of skeletogenesis.     

Rotating three‐dimensional dynamic culture of adult human bone marrow‐derived cells for tissue engineering of hyaline cartilage

The method of constructing cartilage tissue from bone marrow‐derived cells in vitro is considered a valuable technique for hyaline cartilage regenerative medicine. Using a rotating wall vessel (RWV) bioreactor developed in a NASA space experiment, we attempted to efficiently construct hyaline cartilage tissue from human bone marrow‐derived cells without using a scaffold. Bone marrow aspirates were obtained from the iliac crest of nine patients during orthopedic operation. After their proliferation in monolayer culture, the adherent cells were cultured in the RWV bioreactor with chondrogenic medium for 2 weeks. Cells from the same source were cultured in pellet culture as controls. Histological and immunohistological evaluations (collagen type I and II) and quantification of glycosaminoglycan were performed on formed tissues and compared. The engineered constructs obtained using the RWV bioreactor showed strong features of hyaline cartilage in terms of their morphology as determined by histological and immunohistological evaluations. The glycosaminoglycan contents per µg DNA of the tissues were 10.01 ± 3.49 µg/µg DNA in the case of the RWV bioreactor and 6.27 ± 3.41 µg/µg DNA in the case of the pellet culture, and their difference was significant. The RWV bioreactor could provide an excellent environment for three‐dimensional cartilage tissue architecture that can promote the chondrogenic differentiation of adult human bone marrow‐derived cells. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 517–521, 2009     

Proliferation and differentiation of rat dorsal prostatic epithelial cells in collagen gel matrix culture, focusing upon effects of adipocytes

BACKGROUND: Prostatic epithelial cells organize functional acinus structures under epithelial extracellular matrix and epithelial-stromal cell interactions. Recently, the adipose tissue, which surrounds and even exists within the prostate, has been suggested to affect the differentiation and proliferation of some cell types. Therefore, tissue fragments, which consist mainly of epithelial and fibromuscular stromal cells, were cultured in three-dimensional collagen gel matrix culture with adipocytes. METHODS: Tissue fragments of rat dorsal prostate, including both epithelial and fibromuscular stromal components, were cultured in collagen gel with or without adipocytes. Epithelial cell differentiation was evaluated with the reconstruction of acinus-like structures and with immunohistochemistry of rat dorsal prostate-specific proteins, dorsal protein-1 and probasin. The proliferation was examined by uridine uptake. RESULTS: Under coculture of the fragments and adipocytes, epithelial cells reconstructed more differentiated acinus-like structures surrounded by fibromuscular stromal cells than tissue fragment culture without adipocytes. Dorsal protein-1 and probasin expressions of epithelial cells in this coculture system were the same as in rat prostate in vivo. In the coculture, epithelial cells had a higher proliferation activity. CONCLUSION: These results indicate that adipocytes promote proliferation and differentiation of prostatic epithelial cells. Our new culture model with adipocytes suggests the importance of cell-cell interactions, including those of epithelial cells and adipocytes.     

Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia

BACKGROUND: Local hypoxia may be one of the triggers of embryonic reawakening of the stroma and subsequent hyperplastic growth in the prostate. Using a cell culture model of human prostatic stromal cells, we investigated the effects of hypoxia on activation of hypoxia-inducible factor 1 (HIF 1) and on the production of growth factors. METHODS: Primary prostatic stromal cells were grown in normal and hypoxic (1% O(2)) atmosphere. Activation of HIF 1 was evaluated after different time intervals by Western blot. Induced secretion of growth factors VEGF, FGF-7, TGF-beta, IL 8, and FGF-2 were analyzed by ELISA. To confirm the in vitro findings we also performed immunohistochemistry of HIF 1alpha as well as pro-collagen I, collagens I, III, and IV in the benign tissue of radical prostatectomy specimens. RESULTS: HIF 1 is activated in a time-dependent manner, already starting 1 hr after exposure of stromal cells to hypoxic conditions. Secretion of VEGF, FGF-7, TGF-beta, FGF-2, and IL 8 is increased under hypoxic in vitro conditions in comparison to normoxia. Levels of TGF-beta, VEGF, and IL 8 were rapidly and statistically significantly increased in the supernatant of hypoxic cells. Consistent with the in vitro findings, immunohistochemistry of HIF 1alpha in (benign prostatic hyperplasia) BPH tissue revealed strong HIF 1alpha nuclear staining in hyperplastic areas. No difference was observed in the collagen pattern between hyperplastic and normal prostate tissue. CONCLUSIONS: Prostatic stromal cells respond to hypoxia by upregulation of secretion of several growth factors suggesting that hypoxia can trigger prostatic growth. Therefore, hypoxia might be a key factor contributing to the pathogenesis of BPH.     

Human elastic cartilage engineering from cartilage progenitor cells using rotating wall vessel bioreactor

Transplantation of bioengineered elastic cartilage is considered to be a promising approach for patients with craniofacial defects. We have previously shown that human ear perichondrium harbors a population of cartilage progenitor cells (CPCs). The aim of this study was to examine the use of a rotating wall vessel (RWV) bioreactor for CPCs to engineer 3-D elastic cartilage in vitro. Human CPCs isolated from ear perichondrium were expanded and differentiated into chondrocytes under 2-D culture conditions. Fully differentiated CPCs were seeded into recently developed pC-HAp/ChS (porous material consisted of collagen, hydroxyapatite, and chondroitinsulfate) scaffolds and 3-D cultivated utilizing a RWV bioreactor. 3-D engineered constructs appeared shiny with a yellowish, cartilage-like morphology. The shape of the molded scaffold was maintained after RWV cultivation. Hematoxylin and eosin staining showed engraftment of CPCs inside pC-HAp/ChS. Alcian blue and Elastica Van Gieson staining showed of proteoglycan and elastic fibers, which are unique extracellular matrices of elastic cartilage. Thus, human CPCs formed elastic cartilage-like tissue after 3-D cultivation in a RWV bioreactor. These techniques may assist future efforts to reconstruct complicate structures composed of elastic cartilage in vitro.     

Repair of large osteochondral defects with allogeneic cartilaginous aggregates formed from bone marrow-derived cells using RWV bioreactor.

Our objective was to examine the technique of regenerating cartilage tissue from bone marrow-derived cells by three-dimensional (3D) culture using the rotating wall vessel (RWV) bioreactor. Three-dimensional and cylindrical aggregates of allogeneic cartilage with dimensions of 10 x 5 mm (height x diameter) formed by the RWV bioreactor were transplanted into osteochondral defects of Japanese white rabbits (Group T, n = 15). For the control, some osteochondral defects were left empty (Group C, n = 18). At 4, 8, and 12 weeks postimplantation, the reparative tissues were evaluated macroscopically, histologically, and biochemically. In Group T at as early as 4 weeks, histological observation, especially via safranin-O staining, suggested that the reparative tissues resembled hyaline cartilage. And we observed no fibrous tissues between reparative tissue and adjacent normal tissues. In the deeper portion of the bony compartment, the osseous tissues were well remodeled. At 4 and 8 weeks postimplantation, the mean histological score of Group T was significantly better than that of Group C (p < 0.05). The glycosaminoglycans (GAG)/DNA ratio in both groups increased gradually from 4 to 8 weeks and then decreased from 8 to 12 weeks. We herein report the first successful regeneration of cartilage in osteochondral defects in vivo using allogeneic cartilaginous aggregates derived from bone marrow-derived cells by 3D culture using the RWV bioreactor.     

Prostatic stromal cells derived from benign prostatic hyperplasia specimens possess stem cell like property

INTRODUCTION: The hyper-proliferative activity of stromal smooth muscle (SM) cells is believed to be responsible for the pathogenesis of benign prostatic hyperplasia (BPH). We have observed that those stromal cells can differentiate into unrelated specialized cells. We thus hypothesize that stromal cells derived from adults prostate specimens may contain adult stem cells. To test this hypothesis, human prostate stromal primary cultures were established and used for characterization of their stem cell properties. METHODS: Immunoblotting, immunohistochemistry, RT-PCR, and tissue culture techniques were used to characterize the primary cultured human prostate-derived stromal cells for their stem cell and differentiation properties. The plasticity of these stromal cells was analyzed using cell culture and histology techniques. RESULTS: Primary cultured prostate stromal cells from BPH patient possess polygonal and elongated fibroblast/myofibroblast cellular morphology. They are positive in CD30, CD34, CD44, NSE, CD133, Flt-1, stem cell factor (SCF), and neuron-specific enolase (NSE), but negative in C-Kit, stem cell antigen (SCA), SH2, CD11b. Expression of SM myogenic markers in these cells may be induced by sodium butyrate (NaBu) treatment. Induction to osteogenic and adipogenic differentiation in these cells is also evident. CONCLUSIONS: Our study on primary stromal cells from BPH patients have yielded many interesting findings that these prostate stroma cells possess: (1) mesenchymal stem cell (MSC) markers; (2) strong proliferative potential; and (3) ability to differentiate or transdifferentiate to myogenic, adipogenic, and osteogenic lineages. These cell preparations may serve as a potential tool for studies in prostate adult stem cell research and the regulation of benign prostatic hyperplasia.     

Heat-induced apoptosis in human prostatic stromal cells

OBJECTIVE: To determine whether heat, used in transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia and which causes necrotic lesions within the adenoma, induces apoptosis in benign human prostatic stromal cells. Materials and methods Prostatic stromal cells were cultured from benign human prostatic tissue. The origin of the cells was identified by immunohistochemical staining and transmission electron microscopy. Cell cultures were exposed to moderate hyperthermia (47 degrees C) for 1 h and any apoptosis detected by light microscopy, transmission electron microscopy and the measurement of induced caspase-3-like activity. RESULTS: The cultures contained a mixed population of smooth muscle cells and myofibroblasts. Twenty-four hours after heat exposure, 76% of the cells were apoptotic and the caspase activity had increased, whereas only 14% of the cells were necrotic. CONCLUSION: Moderate hyperthermia induces apoptosis in cultured human prostatic stromal cells.     

Two cases of prostatic stromal tumor of uncertain malignant potential (STUMP) on pathological diagnosis after surgery for benign prostatic hyperplasia

Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare neoplasm characterized by an atypical, unique stromal proliferation of the prostate. Two patients consulted our hospital with the complaint of urinary retardation. We performed holmium laser enucleation of the prostate since by digital rectal examination, magnetic resonance imaging and needle biopsy suggested benign prostatic hyperplasia. The pathologic examination of the surgical specimens revealed prostatic STUMP. Urologic and radiologic examinations have revealed no abnormalities after more than 2 years of follow-up.     

Reconstituted basement membrane promotes morphological and functional differentiation of primary human prostatic epithelial cells.

Prostatic epithelial cells undergo rapid proliferation and lose their ability to synthesize and secrete prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) under standard tissue culture conditions. Herein, we compared the morphology, growth, secretory activity, and intermediate filament expression of human prostatic epithelial cells cultured on either standard tissue culture plastic or reconstituted basement membrane. Epithelial cells grown on plastic exhibited a 10-fold increase in proliferation and a higher percentage of cells in the S-phase of the cell cycle compared to cells cultured on basement membrane. However, cells grown on basement membrane secreted markedly higher levels of PSA and PAP. The basement membrane-induced enhancement of secretory activity was potentiated by dihydrotestosterone (DHT) and prostate stromal cell conditioned medium. Morphological studies showed that cells plated on basement membrane formed organoid-like clusters and maintained several aspects of differentiated epithelium including abundant secretory vesicles, microvilli, and desmosomes with associated cytoskeletal elements. Cultivation of epithelial cells on basement membrane components also suppressed the expression of vimentin, a mesenchymal intermediate filament polypeptide. However, cytokeratin expression was abnormal in cells grown on either surface. These results indicate that the differentiated properties of prostatic epithelial cells are promoted by cultivation on reconstituted basement membrane in the presence of DHT and stromal cell conditioned medium.     

前列腺间质组织成分变化在BPH病程中的意义

目的:探讨良性前列腺增生(BPH)患者前列腺组织是否存在间质成分改变,以及这种改变在BPH病程中的意义。方法:BPH患者手术或穿刺标本43例,尸检正常前列腺标本5例。所有标本行M asson染色显示前列腺间质组织肌纤维和胶原成分。以肌纤维成分与胶原成分比值量化前列腺间质组织成分变化程度。评估前列腺间质成分变化程度与膀胱出口梗阻程度、IPSS评分及药物治疗效果之间的关系。结果:正常前列腺间质组织中肌纤维和胶原成分比例平均为(3.2±0.2)∶1,而BPH患者前列腺间质组织中肌纤维与胶原成分比例平均为1(∶4.7±3.1),两组前列腺间质组织中成分比较差异有统计学意义(P<0.01)。有膀胱出口梗阻的BPH患者前列腺间质组织中肌纤维和胶原成分比例平均为1∶(5.4±3.7),明显低于无膀胱出口梗阻的BPH患者[1∶(2.5±1.1)](P=0.02)。重度前列腺症状的BPH患者前列腺间质组织中肌纤维和胶原成分比例平均为1∶(9.1±2.9),明显低于中度前列腺症状的BPH患者[1∶(5.3±3.4)]和轻度前列腺症状的BPH患者[1∶(2.8±1.7)](P均<0.01)。药物治疗效果差的BPH患者前列腺组织中肌纤维和胶原成分比例平均为1(∶7.6±4.3),明显低于药物治疗效果好的BPH患者[1∶(2.3±1.9)](P<0.01)。结论:BPH患者存在不同程度的间质成分改变。BPH临床症状越明显,药物治疗效果越差,前列腺间质组织中肌纤维成分越低,胶原纤维成分越多。前列腺间质成分的改变可能在BPH发生发展中起重要作用。     

The insulin-like growth factor system in the prostate

Summary The insulin-like growth factor (IGF) system is involved in the regulation of cell growth. The system involves a network of molecules that includes the IGFs themselves (IGF-I and -II), IGF receptors (types I and II), IGF-binding proteins (IGFBP-1 through -6), and IGFBP proteases. Characterization of this complex system in the prostate has recently been initiated. Prostatic cell lines as well as primary cultures of prostatic epithelial and stromal cells have been analyzed for expression of IGFs, receptors, and IGFBPs. Prostatic epithelial cells and, quite likely, stromal cells as well respond to the mitogenic activity of IGFs via the type I IGF receptor. Prostatic stromal cells synthesize and secrete IGF-II; there is evidence that prostatic cell lines also synthesize IGFs, but this has not been confirmed in primary cultures of prostatic epithelial cells. Prostatic stromal and epithelial cells secrete a number of IGFBPs. The biological impact of some of these IGFBPs on the growth of prostatic cells has been examined, and proteolytic cleavage of IGFBP-3 by prostate-specific antigen (PSA) has been demonstrated. Aberrations in several elements of the IGF system have been observed in stromal cells derived from benign prostatic hyperplasia (BPH). The IGF system may therefore have a part in the etiology of BPH as well as in normal and malignant processes in the prostate.     

BPH组织无症状性炎症的模式及临床意义

目的:揭示BPH患者前列腺组织无症状性炎症的模式及临床意义。方法:对40例BPH患者经TURP或开放手术获取的前列腺标本行白细胞共同抗原(LCA)免疫组织化学染色,并对前列腺组织内的炎细胞应用图像分析系统进行扫描,计算炎细胞面积占整个切片面积的百分比。结果:40例患者前列腺组织均有明显的炎细胞浸润,炎症模式分为腺周围型(34/40)、腺型(26/40)和基质型(23/40),约近一半的患者(18/40)在同一张切片上可以同时见到明显的二种甚至三种炎症类型改变。炎细胞面积在前列腺细菌培养阳性者和阴性者之间、术前留置导尿管者和未留置导尿管者之间的差异均无统计学意义(均P>0.05)。结论:BPH患者前列腺组织的炎细胞浸润是非常常见的组织学改变,这种无症状性前列腺炎与BPH关系密切,其临床意义有待进一步确定。     

前列腺组织中EGF、bFGF的表达

目的：研究EGF、bFGF在前列腺组织中的表达。方法：应用mRNA斑点杂交、原位杂交、免疫组织化学及原位杂交与免疫组织化学双染法检测6例正常前列腺（NP）、27例良性前列腺增生症（BPH）前列腺组织中EGF及bFGF的表达。结果：BPH前列腺组织和NP组织中无均无EGF mRNA表达,EGF蛋白表达呈弱阳性,两组间差异无显著性意义（P＞0.05）;NP组织上皮细胞有较多bFGF mRNA表达,但无bFGF翻译,基底基质细胞有少量mRNA及蛋白表达,二者表达水平基本一致;BPH前列腺组织上皮细胞无bFGF mRNA表达,但局灶性增殖上皮细胞细胞膜上有bFGF,基底基质细胞有大量bFGF mRNA转录及蛋白质翻译,以局灶性增殖区最为明显。结论：NP及BPH的前列腺组织中无EGF分泌细胞;bFGF在前列腺基底基质细胞过度表达,以自分泌、旁分泌方式促进了基质和上皮的非均一性增殖。     

Prostatic phyto-oestrogen tissue levels in different Austrian regions

INTRODUCTION: A number of studies suggest that the low incidence of prostate cancer as well as benign prostatic enlargement in Asia depends on the extended consumption of phyto-oestrogens in these parts of the world. In most Asian men, phyto-oestrogen levels are multiple higher compared to Austrian (European) men. The aim of our study was to evaluate, according to the East-West decline, whether there were significant differences within the Austrian population. We compared prostate phyto-oestrogen tissue levels of men living in three different geographical regions of Austria. We further compared men living in rural and urban environments. MATERIAL AND METHODS: Prostatic tissue samples of 103 men undergoing surgery for benign prostatic hyperplasia or prostate cancer were collected and frozen at -40 degrees C. In tissue samples, enterolactone (representative for lignans) and genistein levels (representative for isoflavones) were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared tissue levels of men living in rural and urban environments and different geographical regions of Austria. RESULTS: Prostatic enterolactone tissue levels were similar in men living in an urban (median 19.1 ng/g dry weight, range 1.5-76.4) or rural environment (median 15.7 range 0.6-140.6) p = 0.99. The respective values for genistein were 20.5 ng/g dry weight (range 4.6-47.4) and 9.3 (range 0.1-156.7) p = 0.77. Furthermore, enterolactone (p = 0.1) and genistein (p = 0.65) levels were similar in three different geographic regions in Austria. CONCLUSION: No significant differences regarding genistein and enterolactone were found between our study populations. However, we found a wide variation between individual patients.     

The culture of articular chondrocytes in hydrogel constructs within a bioreactor enhances cell proliferation and matrix synthesis

Bovine and human articular chondrocytes were seeded in 2% alginate constructs and cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte-seeded constructs when compared with static conditions but did not produce enhancement for human cells. There was a significant enhancement of glycosaminoglycans and hydroxyproline synthesis for both bovine and human chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O staining in the peripheral regions of the constructs compared with the central region. There was an overall increase in staining intensity after culture within the RWV compared with static conditions. Type-II collagen was produced by both bovine and human chondrocytes in the peripheral and central regions of the constructs and the staining intensity was enhanced by culture within the RWV. A capsule of flattened cells containing type-I collagen developed around the constructs maintained under static conditions when seeded with either bovine or human chondrocytes, but not when cultured within the RWV bioreactor.     

Mesenchymal Tumors of the Prostate

Prostatic mesenchymal tumors encompass various benign and malignant neoplasms that may derived from the intrinsic prostatic stroma or from associated elements including muscle, connective tissue, blood vessels, and neural structures. The differential diagnosis of these tumors is broad and encompasses prostatic epithelial processes that demonstrate prominent spindle cell morphology, as well as mesenchymal tumors that secondarily involve the prostate. Careful morphologic examination, clinical history, and judicious use of a limited panel of immunohistochemical markers and molecular tests aid in the proper diagnosis of these lesions. This article provides a structured guide for the analysis and diagnosis of both benign and malignant prostatic mesenchymal lesions and highlights key features that distinguish these entities within the differential diagnosis of prostatic spindle cell lesions.     

The characterization of epithelial and stromal subsets of candidate stem/progenitor cells in the human adult prostate

OBJECTIVES: Questions regarding the cell source and mechanisms in the initiation and progression of prostate cancer are today still open for debate. Indeed, our knowledge regarding prostate cell regulation, self-renewal, and cytodifferentiation is presently rather limited. In this study, we investigated these processes in the normal adult human prostate. METHODS: Dynamic expression patterns in prostate stem/progenitor cells, intermediate/transit-amplifying cells, and cell lineages were immunohistochemically identified in an in situ explant renewal model of the human normal/benign adult prostate (n=6). RESULTS: Cells with a basal phenotype proliferated significantly in explant cultures, whereas luminal cells went into apoptosis. Results further show down-regulation in tissue cultures of the basal and hypothetical stem cell marker Bcl-2 in the majority of cells, except in rare putative epithelial stem cells. Investigation of established (AC133) and novel candidate prostate stem/progenitor markers, including the cell surface receptor tyrosine kinase KIT and its ligand stem cell factor (SCF), showed that these rare epithelial cells are AC133(+)/CD133(low)/Bcl-2(high)/cytokeratin(+)/vimentin(-)/KIT(low)/SCF(low). In addition, we report on a stromal population that expresses the mesenchymal marker vimentin and that is AC133(-)/CD133(high)/Bcl-2(-)/cytokeratin(-)/KIT(high)/SCF(high). CONCLUSIONS: We provide evidence for epithelial renewal in response to tissue culture and for basal and epithelial stem/progenitor cell recruitment leading to an expansion of an intermediate luminal precursor phenotype. Data further suggest that SCF regulates prostate epithelial stem/progenitor cells in an autocrine manner and that all or a subset of the identified novel stromal phenotype represents prostate stromal progenitor cells or interstitial pacemaker cells or both.     

良性前列腺增生病人前列腺基质成分含量的变化

目的 :研究良性前列腺增生症 (BPH)不同体积前列腺基质成分含量的变化 ,并探讨前列腺体积对药物治疗的指导意义。　方法 :Masson染色及计算机辅助图像分析法 ,测定 3 0例BPH病人耻骨上切除前列腺基质成分 (平滑肌和结缔组织 )面积百分比 ,并与前列腺体积作相关性分析。　结果 :前列腺平滑肌面积百分比与体积呈显著负相关 (P <0 .0 1) ,前列腺体积 >4 0cm3组平滑肌和总的基质面积百分比 [( 7.5 6± 0 .69) %和 ( 2 5 .68± 1.5 8) % ]比体积 <4 0cm3组 [( 15 .60± 1.2 5 ) %和 ( 3 6.0 8± 2 .62 ) % ]明显减少 (P <0 .0 1)。　结论 :随着前列腺体积增长 ,平滑肌和总的基质含量减少而上皮成分相对增多 ,前列腺体积对BPH药物治疗的选择及提高疗效有参考意义。     

PROSTATIC TUMOR RELAPSE IN PATIENTS WITH SUPERFICIAL BLADDER TUMORS: 15-YEAR OUTCOME

PURPOSE: We assessed the outcome of patients with superficial bladder tumors with relapse in the prostate and defined prognostic variables of survival. MATERIALS AND METHODS: A cohort of 186 men with superficial bladder tumors was followed for 15 years. Tumor relapse in the prostate was classified as noninvasive (prostatic urethra and ducts) or invasive (stroma) with intraurethral or direct prostatic invasion. Bladder tumor stage at the time of prostatic relapse was defined as confined or not confined to the bladder. The end point of the study was disease specific survival. The effects of covariates on survival were estimated on multivariate analysis. RESULTS: Of the 186 patients 72 (39%) had relapse in the prostate after a median followup of 28 months (range 3 to 216), including 45 (62%) with noninvasive prostatic tumor and 27 (38%) with stromal invasion. The survival rate was 82% in patients with prostatic urethra or duct involvement compared to 48% with stromal invasion. Intraurethral stromal invasion was associated with a 75% 15-year survival rate versus 9% for extravesical prostatic stromal invasion. Bladder tumor stage and prostatic stromal invasion were independent prognostic variables of survival. CONCLUSIONS: The prostate is a frequent site of tumor relapse in patients with superficial bladder tumors followed for 15 years. Prostatic relapse may portend tumor invasion in the bladder and stromal invasion in the prostate, which significantly reduce survival.