Increased level of serum leucine-rich-alpha-2-glycoprotein 1 in patients with clear cell renal cell carcinoma.

BACKGROUND: Currently, no useful serum markers exist for clear cell renal cell carcinoma (ccRCC), making early detection challenging as diagnosis relies solely on imaging tests. Radiation exposure is also a concern due to multiple required CT examinations during treatment. Renal cell carcinoma (RCC) histological types include ccRCC and non-clear cell RCC (non-ccRCC); however, treatment response to medications varies which necessitates accurate differentiation between the two. Therefore, we aimed to identify a novel serum marker of RCC. Increased LRG1 expression in the serum has been demonstrated in multiple cancer types. However, the expression of LRG1 expression in the serum and cancer tissues of patients with RCC has not been reported. Since ccRCC is a hypervascular tumor and LRG1 is capable of accelerating angiogenesis, we hypothesized that the LRG1 levels may be related to ccRCC. Therefore, we examined LRG1 expression in sera from patients with RCC. METHODS: Using an enzyme-linked immunosorbent assay, serum levels of leucine-rich-alpha-2-glycoprotein 1 (LRG1) were measured in 64 patients with ccRCC and 22 patients non-ccRCC who underwent radical or partial nephrectomy, as well as in 63 patients without cancer. RESULTS: Median values of serum LRG1 and their inter-quartile ranges were 63.2 (42.8-94.2) µg/mL in ccRCC, 23.4 (17.7-29.6) µg/mL in non-ccRCC, and 36.0 (23.7-56.7) µg/mL in patients without cancer, respectively (ccRCC vs. non-ccRCC or patients without cancer: P < 0.001). C-reactive protein (CRP) levels (P = 0.002), anemia (P = 0.037), hypercalcemia (P = 0.023), and grade (P = 0.031) were independent predictors of serum LRG1 levels in ccRCC. To assess diagnostic performance, the area under the receiver operating characteristic curve of serum LRG1 was utilized to differentiate ccRCC from non-cancer and non-ccRCC, with values of 0.73 (95% CI, 0.64-0.82) and 0.91 (95% CI, 0.82-0.96), respectively. CONCLUSIONS: LRG1 served as a serum marker associated with inflammation, indicated by CRP, anemia, hypercalcemia, and malignant potential in ccRCC. Clinically, serum LRG1 levels may assist in differentiating ccRCC from non-ccRCC with excellent diagnostic accuracy.

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.

Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association.

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition.

Efficacy of Pre-operative 18F-FDG PET/CT in Prognostic Prediction in Patients With Renal Cell Carcinoma.

Background/Aim: This study analyzed the parameters provided by preoperative 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for prognostic prediction of renal cell carcinoma (RCC). Patients and Methods: FDG-PET/CT data from 66 clear cell RCC and 19 non-clear cell RCC cases between January 2015 and October 2018 were reviewed retrospectively. We compared the two groups according to recurrence/metastasis to determine prognosis-influencing factors. Multivariate Cox hazard regression models were constructed to evaluate factors potentially predicting disease-free survival (DFS) after adjustment for confounders. DFS was then compared between groups. Results: Standardized uptake values (SUV) of the PET/CT scan were independent predictors of prognosis after adjusting for confounders. RCC cases were divided into two groups by optimal cut-off values. Differences between DFS percentages in high and low SUV groups were significant. Similar results were obtained in clear cell RCC groups. Conclusion: Increased SUV of the PET/CT scan are significant predictors of worse prognoses in patients with surgically resected RCC.

Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer.

OBJECTIVE: To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. RESULTS: In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥ 8 (p = 0.004), an extent of disease value (EOD) of ≥ 2 (p = 0.004), and a 3-month PSA level > 1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. A 3-month PSA level > 1% of the pretreatment level was an independent predictor of OS (p = 0.004). Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level > 1% of the pretreatment level correlated with a poor prognosis.

A case report of nivolumab-induced myasthenia gravis and myositis in a metastatic renal cell carcinoma patient.

We present a 78-year-old male with renal cell carcinoma who developed myasthenia gravis complicated by myositis after nivolumab administration, which was verified by the presence of antibodies against the acetylcholine receptor. The initial symptom was posterior neck pain, and biochemical examination of blood showed elevated levels of hepatic enzymes and creatine phosphokinase. The level of antibody against the acetylcholine receptor increased 4.1-fold. His condition progressed rapidly resulting in respiratory failure 15 days after conservative therapy.

Concomitant radiotherapy and transarterial chemoembolization reduce skeletal-related events related to bone metastases from renal cell carcinoma.

OBJECTIVES: The purpose of this study was to compare the efficacy of radiotherapy (RT) combined with transcatheter arterial chemoembolization (TACE) with RT alone for the treatment of bone metastases from renal cell carcinoma (RCC). METHODS: We included in this retrospective study 25 RCC patients (28 bone metastases), who were treated with RT at our institution. Patients were divided into two groups: patients treated with RT alone (monotherapy group; n = 17) and those treated with RT combined with TACE (combined therapy group; n = 11). The administered median RT dose was 30 Gy in 10 fractions. Anti-cancer agents used in TACE were cisplatin (median dose, 50 mg) and carboplatin (median dose, 240 mg) for patients with reduced renal function. We evaluated the objective response, post-RT-skeletal-related event (PR-SRE)-free rate, and adverse events associated with treatment for each group. RESULTS: The objective response rates for bone metastases in the monotherapy and combined therapy groups were 33% and 82%, respectively (p = 0.009). The 2-year PR-SRE-free rate in the monotherapy and combined therapy groups was 41.8% and 100%, respectively (p = 0.009). The objective response and PR-SRE-free rates were significantly superior in the combined therapy than in the monotherapy group. There were no significant differences in adverse events or survival between the two groups. CONCLUSION: RT combined with TACE is a promising treatment for bone metastases from RCC, as it results in higher objective response, and PR-SRE-free rates compared with RT alone. KEY POINTS: • Skeletal-related events (SREs) are common in patients with bone metastases from renal cell carcinoma (RCC). • Radiotherapy (RT) provides pain relief in patients with bone metastases from RCC, but rarely achieves objective response. • Combination of RT with transcatheter arterial chemoembolization results in higher objective response and post-RT-SRE-free rates compared with RT alone and is a promising treatment for bone metastases from RCC, as it.

Early occlusion control of the intrapericardial inferior vena cava under femoral-femoral extracorporeal circulation using a technique to prevent pulmonary embolism during nephrectomy for renal cell carcinoma with tumor thrombus: two case reports.

BACKGROUND: Renal cell carcinoma with tumor thrombus extension into the inferior vena cava occurs in approximately 5% of cases. Despite such situations, an aggressive surgical approach is recommended. However, intraoperative prevention of pulmonary embolism by a fragmended tumor thrombus is necessary. To prevent pulmonary embolism, placement of a temporary suprarenal filter has been attempted, however, the precise placement of a temporary filter between the level of the hepatic vein and right atrium is not always easy because of its migration, tilting, and strut fracture. Here we report a method for early occlusion control of the intrapericardial inferior vena cava to prevent pulmonary embolism during nephrectomy in level II or III renal cell carcinoma tumor thrombus. CASE PRESENTATION: Our first case was a 37-year-old Japanese man with left renal cell carcinoma extending into the inferior vena cava below the main hepatic vein (level II) and our second was a 75-year-old Japanese man with right renal cell carcinoma extending into the retrohepatic inferior vena cava at the main hepatic vein (level III). En block resection of the kidney and the tumor thrombus was performed with the aid of partial extracorporeal circulation; the postoperative course of both patients was uneventful. CONCLUSION: Control of intrapericardial inferior vena cava is a feasible method to prevent pulmonary embolism.

[A case of complicated perioperative management of radical nephrectomy in a patient with a drug-eluting stent].

Drug-eluting stents (DES) are commonly used for coronary artery disease and patients with DES require antiplatelet therapy because of the risk of late stent thrombosis. Accordingly problems can occur in the perioperative period due to late thrombosis of a stent after discontinuation of antiplatelet therapy before surgery. A 64-year-old man was diagnosed as having a right renal tumor (T1aN0M0) and his performance status was 4. Three years earlier, a DES had been placed in a coronary artery and he was taking aspirin plus ticlopidine. These drugs were stopped at 7 days before surgery and we started heparin (15,000 U/day). Heparin was continued during and after radical nephrectomy. Although operative blood loss was only 178 ml, the amount of bleeding within 5 hours after surgery was 1,620 ml. The wound was re-opened, but there was no obvious bleeding source, so oozing from the muscle was controlled. His blood pressure dropped and cardiac arrest occurred at 22 hours after re-operation, but he was resuscitated with blood transfusion and the bleeding stopped after the dose of heparin was reduced. Three days after the operation, antiplatelet therapy was re-started and heparin was ceased at 10 days after surgery. The blood clot in the right retroperitoneal space formed an abscess at 28 days after radical nephrectomy. After drainage, the retroperitoneal space was washed twice a day for about 40 days. The wound healed, and he currently has no evidence of recurrence or metastasis and has no cardiac sequelae.

Prostate-specific antigen induces apoptosis of osteoclast precursors: potential role in osteoblastic bone metastases of prostate cancer.

BACKGROUND: Prostate cancer is frequently associated with bone metastases with marked osteoblastic changes and low osteoclastic activity but its mechanism is not well understood. We previously reported that prostate-specific antigen (PSA) stimulated the proliferation and the activation of osteoblasts. In this study, we investigated the effect of PSA on osteoclastogenesis. METHODS: Two human prostate cancer cell lines and PSA were directly injected into human adult bone (HAB) implanted into NOD/SCID mice, followed by morphological analysis. RAW 264.7 cells, murine osteoclast precursor, were treated with PSA. RESULTS: PSA-producing LNCaP and PSA caused a significant decrease of osteoclast precursors and osteoclasts in HAB accompanied by osteoblast proliferation and new bone formation, while PSA-nonproducing PC3 showed increasing osteoclasts with osteolysis. PSA induced apoptosis of RAW 264.7 cells in vitro. PSA-induced apoptosis was dependent of enzymatic activity of PSA and was specific to immature tartrate-resistant acid phosphatase-negative mononuclear RAW 264.7 cells. CONCLUSIONS: PSA plays a crucial role for osteoblastic bone metastasis by promoting both osteoblasts proliferation and apoptosis of osteoclast precursors.

Blockade of paracrine supply of insulin-like growth factors using neutralizing antibodies suppresses the liver metastasis of human colorectal cancers.

Environmental stimuli, such as organ-specific growth factors, can influence the metastatic potential of a tumor. The liver is the main source of insulin-like growth factors (IGFs). The importance of IGF signal in hepatic metastasis has been clarified mainly by IGF-I receptor targeting strategies. This study aims to confirm these precedent reports by novel tool, neutralizing antibodies against IGFs and to show that IGFs are promising therapeutic targets for hepatic metastasis in vivo. Hepatic metastasis was induced by intrasplenic injection of human colorectal cancer cell line, HT29. The antimetastatic effects of three antibodies (anti-mouse IGF-I, anti-mouse IGF-II, and anti-human/mouse IGF-II designated KM1468) were tested singly or in combination in the early phase of metastasis. The dose escalation effect of KM1468 and its survival benefit were examined in the early and late phases of metastasis. The mechanism of IGF neutralization was investigated with immunohistochemistry. Dual neutralization of paracrine IGF-I and IGF-II showed modest additive antimetastatic effects than single neutralization of IGF-I or IGF-II. In any phase of metastasis, neutralization led to significant tumor growth inhibition and longer survival. Dose escalation of KM1468 influenced survival only in the late phase of metastasis. Apoptosis increased significantly in the antibody-treated group compared with the control group (P = 0.0025) In conclusion, IGFs are promising therapeutic targets for hepatic metastases of colorectal cancers. However, the IGF dependency is probably variable in the metastatic process.

Laminin 5 expression protects against anoikis at aerogenous spread and lepidic growth of human lung adenocarcinoma.

Adenocarcinoma of the lung is characterized by frequent aerogenous spread (AE) and advancement along the alveolar wall (BAC growth). To elucidate the mechanism of AE metastasis and BAC growth in human lung adenocarcinoma, we established an in vivo orthotopic animal model and an in vitro culture. Investigation of expression levels of integrins, laminins and Type IV collagens, which are the major regulating molecules for cell attachment and anoikis was carried out and a clear correlation between the expression level of laminin 5 (LN5) and the BAC growth was observed using an orthotopic animal model. Introduction of LN5 cDNA to A549 cells increased anoikis resistance in an expression dependent manner. Cells with LN5 overexpression resisted with anoikis after treatment with PI3K-Akt and ERK inhibitors. The amount of phosphorylated focal adhesion kinase (FAK) was also higher in LN5 overexpressing cells. Major tyrosine residues of the EGF receptor at 1068, 1086 and 1173, except at 1148, remained phosphorylated only in the LN5 overexpressing cells even without EGF stimulation, that indicates the ligand independent activation of EGF receptor. BAC growth ratio and AE was confirmed to be significantly correlated with LN5 expression in surgically resected human lung adenocarcinomas by immunohistochemistry. Our results indicate that the activation of the EGF receptor by overexpressing LN5-integrin-FAK signaling pathway may play a crucial role in BAC growth and AE metastasis in human lung adenocarcinoma.

Growth inhibition of human prostate cancer cells in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice by a ligand-specific antibody to human insulin-like growth factors.

Advanced prostate cancer frequently involves the bone that has the largest content of insulin-like growth factors (IGFs). However, the role of bone-derived IGFs in bone metastasis of prostate cancer has not been studied extensively because of the lack of a reliable animal model. Therefore, we investigated whether a novel antibody directed against human IGF-I and IGF-II (KM1468) could inhibit the development of new bone tumors and the progression of established bone tumors in nonobese diabetic/severe combined immunodeficient mice implanted with human adult bone. We first confirmed that KM1468 bound specifically to human IGF-I, human IGF-II, and mouse IGF-II but not to insulin. It also blocked autophosphorylation of the type I IGF receptor induced by the binding of IGFs in human-type I IGF receptor-overexpressing BALB/c 3T3 cells, and it inhibited the IGF-stimulated growth of MDA PCa 2b cells in vitro. Then mice were injected intraperitoneally with KM1468 once weekly for 4 weeks either immediately or 4 weeks after inoculation of MDA PCa 2b cells. KM1468 markedly and dose-dependently suppressed the development of new bone tumors and the progression of established tumor foci, as determined by histomorphometry, and it also decreased serum prostate-specific antigen levels, compared with the control. This is the first report of an IGF ligand-specific inhibitory antibody that suppresses the growth of human prostate cancer cells in human adult bone. These results indicate that the IGF signaling axis is a potential target for prevention and treatment of bone metastases arising from prostate cancer.

Nuclear beta-catenin accumulation as a prognostic factor in Dukes' D human colorectal cancers.

Beta-catenin is well recognized to play a crucial role as a transcriptional factor during the early step of colorectal carcinogenesis. Some reports concerning the clinical implications of cytoplasmic and/or nuclear beta-catenin accumulation are available, though their results vary. On the other hand, the clinical implication of nuclear accumulation of beta-catenin in Dukes' D colorectal cancers (with distant metastasis) has not been investigated. To assess its value as a prognostic marker in this stage, we selected the cases with synchronous liver metastasis. Thirty-eight surgically resected primary and corresponding metastatic liver tumors were examined immunohistochemically and the relationships between nuclear beta-catenin accumulation and clinicopathological variables were analyzed. Of the 38 primary colorectal cancers analyzed, 11 (29%) showed nuclear accumulation of beta-catenin with cytoplasmic staining. Nuclear accumulation positivity was more frequently associated with lymph node metastasis than being negative [100% (11/11) vs. 67% (18/27), p=0.04]. There was a significant difference in median survival time between the nuclear beta-catenin positive group (1130 days) and the negative group (2102 days: p=0.037). Interestingly, all of the patients (9/9) in the former group had died when the recurrence was in the liver, while 42% (8/19) in the latter group had survived even if the recurrence was in the liver (p=0.03). In conclusion, though these results were obtained in a small series of patients, nuclear accumulation of beta-catenin may be a useful prognostic marker even in Dukes' D colorectal cancers.

Intraosseous growth of human prostate cancer in implanted adult human bone: relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions.

BACKGROUND: More than 80% of patients with advanced prostate cancer have skeletal involvement, but the biology of bone metastasis is poorly understood. This study investigated the in vivo formation and progression of bone metastases under conditions that resembled the human bone environment as closely as possible. METHODS: Adult human bone fragments were implanted subcutaneously into 120 male NOD/SCID mice. Four weeks later, 1 x 10(7) LNCaP prostate cancer cells or phosphate-buffered saline were injected intravenously into 80 or 40 mice, respectively. The implanted bone fragments were removed from 20 to 10 mice in each group at 2, 4, 6, and 8 weeks after injection. RESULTS: LNCaP colonized the bone marrow blood vessels within 2 weeks, and then gradually expanded into the entire medullary cavity. An osteoblastic response often occurred at the edges of metastatic foci (intertrabecular bone metaplasia). In addition, new bone formation was observed adjacent to mature lamellar bone (appositional bone formation). These two processes appeared to occur through different mechanisms, but might similarly cause osteosclerosis. Osteoclasts showed a marked increase in numbers at sites of early tumor invasion, whereas few osteoclasts were observed at sites where tumor invasion was complete. CONCLUSIONS: The predominance of osteoblastic change with resorption may lead to bone remodeling in metastatic lesions, and osteoclasts may play an important role in bone metastasis from prostate cancer.

Matrix metalloproteinase-7 facilitates insulin-like growth factor bioavailability through its proteinase activity on insulin-like growth factor binding protein 3.

Matrix metalloproteinase-7 (MMP-7) secreted by cancer cells has been implicated classically in the basement membrane destruction associated with tumor cell invasion and metastasis. Recent epidemiologic studies have established a correlation between high levels of circulating insulin-like growth factor (IGF) and low levels of IGF binding protein 3 (IGFBP-3), and relative risk of developing colon, breast, prostate, and lung cancer, which are known to produce MMP-7. In this study, IGFBP-3 was assessed as a candidate for the physiologic substrate of MMP-7. MMP-7 proteolysis generated four major fragments (26 kDa, 17 kDa, 15.5 kDa, and 15.5 kDa), and two cleavage sites were identified: one at the site of hydrolysis of the K(144)-I(145) peptide bond and one at the R(95)-L(96) peptide bond. The former site is different from the previously reported site of cleavage of IGFBP-3 by other proteases. Addition of IGFBP-3 inhibited IGF-I-mediated IGF type 1 receptor (IGF-IR) phosphorylation and activation of the downstream molecule Akt in BALB/c 3T3 fibroblasts overexpressing human IGF-IR (3T3-IGF-IR) and in two human colon cancer cell lines (COLO201 and HT29). Coincubation of the IGF-I/IGFBP-3 complex with MMP-7 restored IGF-I-mediated IGF-IR phosphorylation and activation of Akt in these cell lines. The IGF-I signal recovered by MMP-7 protected against apoptosis induced by anoikis in 3T3-IGF-IR cells. These results indicate that MMP-7 proteolysis of IGFBP-3 plays a crucial role in regulating IGF-I bioavailability, thereby promoting cell survival. This mechanism may contribute to the tumorigenesis of MMP-7-producing IGF-IR-expressing tumors in the primary site and to organ-specific metastasis in a paracrine manner.

Influence of hypertension on lower urinary tract symptoms in benign prostatic hyperplasia.

AIM: To clarify the influence of hypertension on lower urinary tract symptoms (LUTS) we examined the relationship between blood pressure, LUTS, and the effect of terazosin on LUTS in patients with benign prostatic hyperplasia (BPH). METHODS: The subjects were patients who had LUTS and BPH. They were treated with terazosin (1 mg, twice-a-day) for 12 weeks. Calculation of the International Prostate Symptom Score (IPSS), measurement of blood pressure, and uroflowmetry were performed before and after 12 weeks of therapy. Patients were divided into a normotensive (NT) group and a hypertensive (HT) group at the time of first examination. RESULTS: The IPSS for urinary frequency and nocturia in BPH-HT patients (n = 21; mean age, 71 years) were significantly higher than those in the BPH-NT patients (n = 21; mean age, 69 years) before the administration of terazosin. The total IPSS the BPH-HT patients was also significantly higher than that of the BPH-NT patients. There were no differences of uroflowmetric parameters between the two groups. After 12 weeks of therapy, systolic and diastolic blood pressure decreased in the BPH-HT patients, but not in the BPH-NT patients. However, the systolic pressure of the BPH-HT patients was still significantly higher than that of the BPH-NT patients. The score for each IPSS parameter decreased in both groups, but the difference of the score between the two groups increased. CONCLUSION: Hypertension may worsen LUTS and may decrease the improvement of symptoms by terazosin.

Osteoprotegerin/osteoclastogenesis inhibitory factor decreases human prostate cancer burden in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice.

Human prostate cancer frequently metastasizes to bone, where it gives rise to osteoblastic bone metastases with an underlying osteoclastic component and subsequent bone pain. However, the importance of osteoclastogenesis in the development of prostate cancer bone lesions in humans is unclear. Osteoprotegerin/osteoclastogenesis inhibitory factor (OCIF) is a member of the tumor necrosis factor receptor family and a novel secreted protein, and it is a negative regulator of osteoclast differentiation, activation, and survival both in vitro and in vivo. In the present study we used a model in which human LNCaP prostate cancer cells that give rise to osteoblastic bone tumors were injected directly into the intramedullary space of human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice to investigate whether the new bone-resorption inhibitor osteoprotegerin/OCIF would inhibit the development of new bone tumors and the progression of established osteoblastic bone tumors. The mice were given consecutive daily s.c. injections of recombinant human OCIF (rhOCIF; 100 micro g/mouse/day) for 2 weeks starting either immediately or 2 weeks after injection of the LNCaP cells. In both protocols, rhOCIF markedly inhibited both the development of bone tumors and the progression of established bone tumor foci quantified by histological examination. Histomorphometrical analysis revealed that rhOCIF markedly reduced the number of osteoclasts and the size of the tumors at the bone sites, but that it had no effect on the local growth of s.c. LNCaP tumors or on LNCaP cell proliferation in culture. These findings demonstrate that osteoclasts play an important role in bone tumor by prostate cancer, and that rhOCIF decreases the LNCaP prostate cancer burden selectively in bone, suppresses the progression of established tumor lesions, and prevents the development of new lesions. These results suggest that inhibition of osteoclastic bone resorption may be an effective therapy for the treatment of prostate cancer that has colonized bone.

[Risk factors for duration of urinary incontinence after radical prostatectomy].

PURPOSE: In this study, we examined risk factors for duration of incontinence after radical prostatectomy at our hospital. MATERIALS AND METHODS: From April 1988 to March 2000, 45 patients with prostate cancer underwent retropubic radical prostatectomy at our hospital. Thirty-eight of 45 patients could be followed up. The patients' age, height, weight, body mass index (BMI), preoperative prostatic specific antigen level, clinical stage, nerve-sparing surgery or none, operation time, bleeding volume, resected prostate weight, cancer positive or negative at surgical margins, postoperative stage, radiation therapy or none, anti-androgen therapy or none, duration of postoperative incontinence, and follow-up period were examined. RESULTS: All patients had postoperative stress incontinence, and no one had urge incontinence. Medians of duration of postoperative incontinence and follow-up period were 5.5 and 12 months, respectively. When the patients were divided into 2 groups by the value of each parameter, postoperative anti-androgen therapy (chi 2 test, p = 0.0429) and high BMI (> or = 25.0 kg/m2, p = 0.0206) were related to the long duration (> or = 5.5 months) of postoperative incontinence. CONCLUSION: These results suggest that common factors are involved in the etiology of prolonged incontinence after radical prostatectomy and genuine stress incontinence in women. Therefore, both body weight control and pelvic floor muscle exercise might be also important for the treatment of incontinence after radical prostatectomy.