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Ra-223 is a therapeutic agent for bone metastatic castration-resistant prostate cancer (mCRPC). We examined the efficacy of a treatment method using Ra-223 together with ethinylestradiol (EE).Patients who received Ra-223 three or more times were included and two groups (with or without EE) were compared retrospectively.Eighteen patients were treated with Ra-223 and EE concomitantly (EstRadium therapy) and 13 patients were treated with Ra-223 alone or Ra-223 and agents other than EE (non-EstRadium therapy). The number of patients with decreased serum prostate-specific antigen level was significantly higher in the EstRadium therapy group than in the non-EstRadium therapy group (p=0.029).The combination of Ra-223 and EE, compared to Ra-223 alone, is an effective treatment option for bone mCRPC patients, in terms of PSA response.

Objectives The effects of human papillomavirus (HPV) infection on male reproductive parameters are currently a matter of controversy. In order to clarify the issue in Japanese infertile men, the prevalence and localization of HPV in semen, sperm parameters, and superoxide dismutase (SOD) activity in seminal plasma were examined in 216 Japanese infertile men. Methods DNA was extracted from liquid-based cytological semen samples. The β-globin gene was amplified by polymerase chain reaction (PCR), and HPV-DNA was amplified using nested PCR with MY09/MY11 as outer primers and GP5+/GP6+ as inner primers. HPV genotyping was performed in the HPV-positive samples. In addition, SOD levels in seminal plasma were analysed quantitatively. In-situ hybridization (ISH) was performed to localize HPV-DNA in sperm from HPV-positive samples. Results Any-risk and high-risk prevalence rates of HPV in semen were 12.5% and 6.9%, respectively. No significant difference in the prevalence of HPV was observed between azoospermic and non-azoospermic subjects. Among non-azoospermic patients, those with HPV detected in semen had significantly lower sperm motility and concentration compared with subjects without HPV detected in semen. SOD levels in seminal plasma were significantly higher in HPV-positive patients compared with HPV-negative patients. ISH analysis of HPV-positive samples revealed that HPV-DNA was localized to the head and mid-piece of sperm. HPV-DNA was present in the sperm of young infertile men. Conclusion HPV infection of sperm was associated with reduced sperm motility and concentration, and resulted in an increase in seminal SOD activity.

Background: The aim of this study was to evaluate the prognosis of patients with T1N0M0 urothelial carcinoma with squamous differentiation (UCSD) or glandular differentiation (UCGD) because it has not been determined whether these variant histologies behave more aggressively than pure urothelial carcinoma (PUC). Patients and Methods: Ninety-nine patients diagnosed with pT1N0M0 bladder cancer and treated conservatively with transurethral resection of bladder tumor at Kanazawa University Hospital between 2007 and 2019 were included in this study. The overall survival, cancer-specific survival (CSS), and recurrence-free survival of the variant histology and PUC groups were evaluated and compared. Results: The variant histology group had significantly lower overall survival (p=0.006) and CSS (p=0.0095) than the PUC group did. Variant histology was found to be an independent prognostic factor in univariate and multivariate analyses for overall survival and CSS. On the other hand, no significant difference in progression-free survival was observed between the two groups (p=0.439). However, the variant histology group had significantly lower overall survival (p=0.004) and CSS (p=0.004) after progression. Conclusion: The prognosis for patients with pT1 bladder cancer with UCSD or UCGD treated conservatively with transurethral resection of bladder tumor was poor. Considering the worse prognosis of these patients after stage progression, early radical cystectomy could be recommended.

Objective Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100 ng/mL and chemokine (CC motif) ligand 2 ≥ 320 pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system. Methods Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker. Results Patients with chemokine (CC motif) ligand 2 ≥ 320 pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2 Conclusions This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.

Background Hypogonadism associated with cancer is reported to cause cachexia and a variety of physical and psychological symptoms. This study aims to evaluate whether androgen replacement therapy can improve cancer‐related symptoms in male advanced cancer patients. Methods An investigator‐initiated, prospective, and randomized controlled study was conducted. Patients with low serum testosterone levels (total or free testosterone levels were

BACKGROUND/AIM To investigate the blood markers for predicting pembrolizumab efficacy in advanced urothelial carcinoma (UC). PATIENTS AND METHODS This study included 91 advanced UC patients. The relationship between prognosis and markers from peripheral blood cell counts, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI=monocytes × neutrophils/lymphocytes), was evaluated. RESULTS Multivariate analysis indicated that pretreatment NLR and the 1-month-change NLR were both significantly associated with overall survival (OS) after pembrolizumab initiation. When the patients were divided into four groups according to calculated cutoffs using Cox proportional hazard model, the pretreatment NLR

Background Our previous report has shown that the flavonoid 2'-hydroxyflavanone (2'-HF) showed inhibition of androgen receptor (AR) activity against androgen-sensitive prostate cancer (PCa) cells, LNCaP, and exhibited antitumor effects against androgen-insensitive PCa cells, PC-3, and DU145. In the present study, we prepared a derivative of 2'-HF, 16MS7F1924, and confirmed the effects of this derivative on PCa cells. Methods The antiproliferation effects of 16MS7F1924 were investigated in PCa cells using LNCaP, PC-3, DU145 and docetaxel-resistant and cabazitaxel-resistant cell lines of PC-3-TxR/CxR and DU145-TxR/CxR. Prostate-specific antigen (PSA) and AR expression level in whole cells and the nucleus were confirmed in LNCaP by reverse transcriptase polymerase chain reaction and Western blot analysis. AR activity in LNCaP cells was confirmed by luciferase assay using PSA promoter-driven reporter. To analyze the antiproliferative effects, cell-based assays using flow cytometry, immunocytochemistry, and TUNEL assay as well as Western blot analysis were employed. Furthermore, PC-3, DU145 and each chemoresistant strain of human PCa cells were subcutaneously xenografted. The antitumor effects of 16MS7F1924 were evaluated in vivo. Results 16MS7F1924 showed antitumor effect on all PCa cells in a dose-dependent manner. 16MS7F1924 reduced the expression of PSA messenger RNA (mRNA) and protein and inhibited AR activity in a dose-dependent manner, while expression of AR protein and mRNA was reduced by 16MS7F1924. 16MS7F1924 induced mitotic catastrophe and apoptosis. Apoptotic cells were increased in a dose-dependent manner, and the apoptosis was mediated through the Akt pathway. Tumor growth was safely and significantly inhibited by both intraperitoneal and oral administration of 16MS7F1924 in vivo. Conclusion 16MS7F1924 had sufficient antitumor activity against androgen-sensitive and cabazitaxel-resistant PCa cells and may be useful as a novel therapeutic agent overcoming hormone- and chemoresistant PCas.

Background/aim Cabazitaxel is recommended as first-line treatment after docetaxel for metastatic castration-resistant prostate cancer. However, the efficacy, adverse events and prognostic factors associated with cabazitaxel are unclear. Patients and methods This single-centre retrospective study including 30 patients with CRPC treated with cabazitaxel between 2014 and 2020 investigated efficacy, outcomes and prognostic factors. Results Fourteen patients had visceral metastases. The median cabazitaxel dose was 20 mg/m2 The prostate-specific antigen response rate, time to prostate-specific antigen response, and overall survival were 13.3%, 3.48 months, and 7.92 months, respectively. The rates of grade 3 or more neutropenia and febrile neutropenia were 20% and 6.7%, respectively. By multivariate analysis, sarcopenia and visceral metastasis at the time of cabazitaxel initiation were independent and significant factors conferring a poor prognosis. Conclusion The early introduction of cabazitaxel, prior to the development of sarcopenia and visceral metastasis, might contribute to improved prognosis in CRPC.

Aim: We investigated whether low plasma free testosterone (FT) levels could predict cardiovascular events (CVE) in Japanese men with coronary risk factors.Methods: Male patients with classical coro...

Objectives To evaluate the safety and efficacy of transvaginal mesh surgery using a polytetrafluoroethylene mesh to treat pelvic organ prolapse. Methods This prospective observational study included women undergoing transvaginal mesh surgery for pelvic organ prolapse that used new polytetrafluoroethylene mesh cut into a shape similar to that of Elevate. We evaluated the subjective and objective outcomes at 3 and 12 months, as well as postoperative complication rates. Results This study included 55 patients. The pelvic organ prolapse quantification scores improved significantly at 3 and 12 months after surgery compared with scores before surgery. In four patients (7.3%), a pelvic examination showed stage 2 objective recurrence without subjective symptoms. Clavien-Dindo grades 2 and 3 perioperative complications were observed in 9.1% and 1.8% of the patients, respectively. Vaginal mesh exposure occurred in one patient (1.8%) at the time of the 3-month follow-up evaluation. The mesh was exposed at the proximal midline of the anterior vaginal wall. Conclusions These findings show the safe and effective use of the polytetrafluoroethylene mesh for transvaginal mesh surgery.

Background Visceral metastasis (VM), an important poor prognostic factor of prostate cancer (PC), is not commonly observed in castration sensitive status but is often observed after castration-resistant progression. However, the site, timing of emergence, and incidence of VM in castration-resistant patients have not yet been fully elucidated. Methods Demographic, surgical, pathological, and follow-up data of PC patients treated at Kanazawa University Hospital between January 2000 and December 2016 were retrospectively analyzed using their medical charts. From this data, risk factors of VM and survival of patients with VM were elucidated. Results Of 1364 patients, 21 (1.5%) had VM at diagnosis. Of 179 (13.1%) castration-resistant patients, 55 experienced emergence of new VM during treatment course. Incidence of new VM, especially nonlung, such as liver and adrenal metastases, increased significantly in proportion with the number of prescribed treatments. Multivariate analysis revealed that T stage, M stage, age, and treatment history with androgen receptor (AR) signaling-targeted agents and/or taxanes significantly increased the risk of VM. Compared with the group with VM at diagnosis, survival after diagnosis of VM following treatment was significantly shorter. Conclusion Although sequential use of new AR signaling-targeted agents and taxanes for castration-resistant PC (CRPC) is a standard treatment strategy, it often results in development of VM. Elucidating the mechanisms of VM are essential to improve survival in patients with CRPC.

A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of ≥ 7 and 273 had a GS of 24, PSA density ≥ 0.24 ng ml−2, positive findings on digital rectal examination, and transrectal with 90.0% sensitivity and 67.4% specificity. In this study, we found that raising the PSA cutoff to 12 ng ml−1 for CSPC in elderly individuals can significantly reduce unnecessary prostate biopsies. Furthermore, CSPC could be efficiently discovered by combining the four supplementary markers in patients with a PSA level of 4–12 ng ml−1. By performing this screening for elderly men over 75 years of age, unnecessary biopsies may be reduced and CSPC may be detected efficiently.

Background/aim This study aimed to assess the efficacy and toxicity of second-line chemotherapy, especially combination chemotherapy, for advanced or metastatic urothelial cancer. Patients and methods This retrospective analysis included patients who received second-line chemotherapy after disease progression during first-line chemotherapy between January 2009 to May 2018. Progression-free survival (PFS), overall survival (OS) and toxicity associated with second-line chemotherapy were assessed. Results In total 25 patients received second-line chemotherapy; 21 patients had combination chemotherapy and 4 had single-agent chemotherapy. Median PFS and OS were 3.6 months (range=0.2-23.5) and 11.9 months (range=0.5-29.0), respectively. Twenty patients (80%) exhibited grade 3 or more severe toxicities. Conclusion PFS and OS benefits of second-line combination chemotherapy corresponded to those of the phase 3 study of pembrolizumab, but adverse events were more severe. Pembrolizumab is potentially a better second-line treatment than combination chemotherapy.

Neuroendocrine prostate cancer (NEPC) is rare and has a poor prognosis; its clinical course and treatment outcomes are also unclear. This study investigated the clinical characteristics, clinical course, and treatment outcomes of patients with NEPC.This retrospective study investigated 14 patients histologically diagnosed with NEPC at Kanazawa University Hospital between 2000 and 2019. Overall survival (OS) and progression-free survival (PFS) were retrospectively analyzed using the Kaplan-Meier method. Additionally, log-rank tests were used to compare survival distributions.We included 14 patients histologically diagnosed with NEPC among 1,845 patients with prostate cancer. Four patients (0.22%) were diagnosed with de novo NEPC, and ten patients were diagnosed with NEPC during treatment. First-line platinum-based therapy's objective response rate (ORR) was 66.7%, and disease control rate was 91.7%; median PFS was 7.5 months. The median OS from NEPC diagnosis was 20.3 months. The median OS of the liver metastasis (-) group was 31.6 months, and that of the (+) group was 9.4 months (p=0.03, hazard ratio=0.24). The median OS of the somatostatin receptor scintigraphy (SRS)-positive group was 31.6 months, and that of the SRS-negative group was 10.6 months (p=0.04, hazard ratio=0.14).Platinum-based chemotherapy is effective to some extent, but the duration of response is not sufficient; therefore, new treatment options are needed. This is the first study to show that SRS findings and the presence of liver metastases might be prognostic predictors of NEPC.

We investigated whether coronavirus disease 2019 (COVID-19) vaccination and its adverse events would cause cancer treatment of patients with urological cancer to be postponed or changed.We collected COVID-19 vaccination information including adverse events from the medical records of 214 patients with urological cancer receiving cancer drug therapy.The cancer types were renal cancer in 40 cases (18.7%), upper urinary tract cancer in 10 cases (4.7%), bladder cancer in 21 cases (9.8%), prostate cancer in 140 cases (65.4%), and others in 3 cases (1.4%). Of the 214 patients, 178 (83.2%) had received the second dose of the vaccine. Out of 180 vaccinated patients, some adverse events were observed in 69 (38.3%). Vaccination rates for males and females were 85.4% (169/198) and 68.8% (11/16), respectively, and were not significantly different (p=0.081). The incidence of adverse events was significantly higher in females [72.7% (8/11)] than in males [36.1% (61/169)]; p=0.015. Treatment was modified in 11 vaccinated patients; postponed or changed at the discretion of the attending physician in 8 cases, skipped at the discretion of the patient in 1 case, and postponed due to side effects of the immune checkpoint inhibitor in 1 case. Treatment for one patient with upper urinary tract cancer on pembrolizumab was postponed for three weeks due to adverse events of the vaccine.Only 0.6% of the adverse events of the vaccine required postponement of treatment, suggesting that vaccination is safe even during cancer drug therapy.

Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.The study included 97 patients with advanced UC whose lesions were classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median age was 73 years. Nineteen patients (20%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The efficacy, safety, and risk factors for prognosis were evaluated for patients with and without measurable lesions.The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8-4.7) and 11.8 months (95% CI: 6.7-17.0), respectively. Twenty-one (22%) patients had no measurable lesions per RECIST. In univariate and multivariate analysis, PS 2-4 and lesions by RECIST were identified as factors associated with short overall survival (OS). The median OS of 18.3 months in patients without lesions by RECIST was significantly longer than the median OS of 6.7 months in patients with lesions by RECIST (p = .012).We demonstrated that good PS 0-1 and no measurable lesions, especially small lesions, by RECIST were favorable prognostic factors in patients with advanced UC treated by pembrolizumab.

Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has been reported to exhibit better postoperative urinary continence compared to conventional RARP (C-RARP) via the anterior approach, but the reasons behind this are unknown. The early postoperative urinary incontinence and anatomical differences were compared between 51 cases each of C-RARP and RS-RARP, which were selected via propensity score matching. Dynamic-MRI was performed before and after surgery to investigate the pelvic anatomical changes under abdominal pressure. The median urine loss ratio in the early postoperative period was 11.0% and 1.0% for C-RARP and RS-RARP, respectively. Postoperative MRI revealed the anterior bladder wall after RS-RARP was fixed in a high position compared to C-RARP. Dynamic-MRI after C-RARP showed cephalocaudal compression of the bladder during abdominal pressure caused expansion of the membranous urethra and the urine flowed out. In RS-RARP cases, the rectum moved forward during abdominal pressure to compress the membranous urethra by closing it from behind, as was observed preoperatively. This was the first study using dynamic-MRI which revealed the importance of a high attachment of the anterior bladder wall for the urethral closure mechanism during abdominal pressure. RS-RARP, which can completely preserve this mechanism, was the least likely to cause stress urinary incontinence.

Background/aim Pelvic drain (PD) placement is commonly performed after robot-assisted radical prostatectomy (RARP), but the need for PD placement is unclear. This study aimed to assess the need for PD placement after RARP. Patients and methods This retrospective study analysed the effect of PD placement on postoperative complications in patients who underwent RARP between 2009 and 2018. All patients prior to October 1, 2016 had a PD placed; those after did not. Results Of the 308 study patients, 231 received a PD (PD group) and 77 did not (ND group). The incidence of ileus, urinary tract infection and anastomotic leak did not differ significantly between the groups; nor did the incidence of asymptomatic and symptomatic lymphocele at 2 weeks and 1 year after surgery. Multivariate analysis showed that lymph node dissection is a predictor of asymptomatic lymphocele development two weeks after surgery. Conclusion PD placement is not necessary after RARP.

Background/aim To evaluate the chronological changes in health-related quality of life and treatment satisfaction after robot-assisted radical prostatectomy (RARP). Patients and methods A total of 196 patients were included, and treatment satisfaction was evaluated using the Expanded Prostate Cancer Index Composite (EPIC) score before and at 1, 3, 6, and 12 months after RARP. Results At 12 months after RARP, 64.8% of patients were satisfied. On the contrary, 4.6% of patients were dissatisfied at 12 months after RARP. In a multivariate analysis, only urinary bother of EPIC was significantly associated with satisfaction at 12 months after RARP (p=0.025, odds ratio=1.029). Conclusion Treatment satisfaction with RARP was generally acceptable from 1 to 12 months after surgery and did not change over time. Urinary bother was associated with satisfaction at 12 months after RARP. Compared with the objective 24-hour pad test, questionnaires answered subjectively were more associated with satisfaction.

To conduct a prospective randomized trial to evaluate the efficacy of a novel prophylactic procedure for inguinal hernia (IH) after transperitoneal robot-assisted radical prostatectomy (RARP).The prophylactic procedure for IH after RARP involved the dissection of the peritoneum ∼5 cm outward from internal inguinal ring (IIR), separating the spermatic cord and vessels from the peritoneum. This was randomly performed on one side (left or right).A total of 148 cases were included, and IH after RARP was observed in 19 (12.8%) cases, with 11 (7.4%) cases in the right side only, 3 (2.0%) in the left side only, and 5 (3.4%) bilaterally. IHs developed in 9 (6.1%) sides that underwent prophylactic procedure and in 15 (10.1%) that did not. Kaplan-Meier curve analysis revealed no significant difference between the preventive and nonpreventive sides (p = 0.197). Based on the observation during laparoscopic hernioplasty, the prophylactic procedure that strengthened the abdominal wall was by adhesion conglutination of the exfoliated peritoneum in the effective side, and IIRs were opened and developed IH in the ineffective sides. Predictive factors for IH after RARP were not found using Cox proportional hazard model.The preventive procedure for IH used in this study reduced the incidence of IH after RARP, but the difference was not significant.

Objective: To examine the association between human papillomavirus (HPV) infection and penile cancer among Japanese patients. Methods: Thirty-four patients with penile cancer were enrolled in this study. DNA was extracted from paraffin-embedded tumor tissue samples, and HPV-DNA tests and genotyping were performed. For all of the samples, in situ hybridization (ISH) was performed to locate HPV-DNA in tumor tissue. Furthermore, expression levels of p16-INK4a, mini-chromosome maintenance protein 7 (mcm-7), HPV-L1, and Ki-67 were analyzed using immunohistochemical methods. Results: HPV and high-risk (HR)-HPV were detected in 14 (41.1%; 95% confidence interval (CI) 24.6–57.7%) and 12 (35.2%; 95% CI 19.2–51.4%) cases, respectively. HPV16 was the most frequently detected HPV type. Among the HR-HPV-positive cases, a punctate HR-HPV-DNA signal pattern was detected by ISH in tumor cell nuclei. P16-INK4a was expressed in 66.7% (95% CI 42.8–90.1%) of HR-HPV-positive cases and was significantly more frequent and stronger in HR-HPV-positive cases than in HPV-negative cases. There was no significant difference in the occurrence or distribution of mcm-7 or Ki-67 expression between HPV-positive and HPV-negative cases. HPV-L1 expression was not observed in any of the cases examined. Conclusions: HPV infection may have had an etiological role in 41% of the examined cases of penile cancer in Japan. Keywords: Penile cancer, Human papillomavirus, p16-INK4a, Mini-chromosome maintenance protein 7, Ki-67

Background/Aim: A peripherally inserted central catheter (PICC) is recommended for the safe administration of anticancer agents. The effectiveness of synthetic polymer-coated and non-coated PICCs was compared. Patients and Methods: Patients with advanced cancers who had indwelling PICCs were reviewed using their medical records. Three types of PICCs were compared in terms of complications and catheter failure. Results: A total of 90 patients were retrospectively analyzed, including 31 with Groshong PICCs, 30 with Argyle PICC kit, and 29 with Argyle PICC kit II. The incidence of catheter failure for Groshong PICC, Argyle PICC kit, and Argyle PICC kit II per 1,000 PICC days was 4.4614, 5.6617, and 0.8658, respectively. Catheter failure-free survival in the Argyle PICC kit II group was significantly better than that in the Argyle PICC kit group (p=0.0339). Conclusion: Argyle PICC kit II, a synthetic polymer-coated PICC, may render longer patency and prevention of catheter failure than non-coated PICCs.

BACKGROUND Coffee inhibits the progression of prostate cancer; however, the direct mechanism through which coffee acts on prostate cancer cells remains unclear. This study aimed to identify the key compounds of coffee that possess anti-cancer effects and to investigate their mechanisms of action. METHODS The anti-proliferation and anti-migration effects of six potentially active types of coffee compounds, including kahweol acetate, cafestol, caffeine, caffeic acid, chlorogenic acid, and trigonelline hydrochloride, were evaluated using LNCaP, LNCaP-SF, PC-3, and DU145 human prostate cancer cells. The synergistic effects of these compounds were also investigated. Apoptosis-related and epithelial-mesenchymal transition-related proteins, androgen receptor in whole cell and in nucleus, and chemokines were assessed. A xenograft study of SCID mice was performed to examine the in vivo effect of coffee compounds. RESULTS Among the evaluated compounds, only kahweol acetate and cafestol inhibited the proliferation and migration of prostate cancer cells in a dose-dependent manner. The combination treatment involving kahweol acetate and cafestol synergistically inhibited proliferation and migration (combination index

We performed test clamp procedure in robot-assisted partial nephrectomy (RAPN) to prevent massive bleeding during tumor resection and to omit dissection of non-feeding arteries around the tumor. We subsequently analyzed the safety and usefulness of the procedure. The Test clamp procedure was performed for 1 to 3 min during renal artery test ischemia prior to the actual ischemia and tumor resection. We confirmed the disappearance of blood flow around the renal tumor using color Doppler ultrasonography. If arterial blood flow around the tumor remained, we surveyed the site for other arteries that needed to be clamped and repeated the test clamp procedure until renal blood flow around the tumor disappeared. We retrospectively analyzed consecutive RAPN cases performed from July 2016 to March 2020 at our institutions and reviewed medical records. The clinical data of the RAPN cases were statistically analyzed. Sixty-four RAPN cases underwent the test clamp procedure, which was categorized as the TEST group. Test clamping was performed safely without any clamping-related complications in all cases. Eleven cases (17%) underwent partial ischemia, which was a significantly higher number than that in the control group. Massive bleeding during tumor resection was more frequent in the control group. Postoperative deterioration of estimated glomerular filtration rate did not differ significantly between both groups. Although further investigation was still necessary, our findings indicate that the test clamp procedure may be a safe and secure procedure to perform in RAPN for both patients and surgeons.

Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P P

Despite improvements in systemic therapy options for renal cancer, it remains one of the most drug-resistant malignancies. Interestingly, reports have shown that kahweol and cafestol, natural diterpenes extracted from coffee beans, exhibit anti-cancer activity. However, the multiple potential pharmacological actions of both have yet to be fully understood. This study therefore investigated the effects of kahweol acetate and cafestol on human renal cancer ACHN and Caki-1 cells. Accordingly, the combination of kahweol acetate and cafestol administration synergistically inhibited cell proliferation and migration by inducing apoptosis and inhibiting epithelial–mesenchymal transition. Mechanistic dissection revealed that kahweol acetate and cafestol inhibited Akt and ERK phosphorylation. Moreover, kahweol acetate and cafestol downregulated the expression of not only C–C chemokine receptors 2, 5, and 6 but also programmed death-ligand 1, indicating their effects on the tumor microenvironment. Thus, kahweol acetate and cafestol may be novel therapeutic candidates for renal cancer considering that they exert multiple pharmacological effects.

Background: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) has different treatment outcomes across institutions, as seen in conventional TURBT. We retrospectively compared the difference in quality between the two types of endoscopic equipment used for PDD-assisted TURBT in our institution. Methods: This study enrolled 205 consecutive patients who underwent PDD-assisted TURBT. Patients were divided into two groups according to the endoscopic equipment used for PDD-assisted TURBT: Group A using the conventionally used endoscopic system and Aladuck LS-DLED and Group S using the Storz PDD system. Cystoscopy findings of white light (WL), fluorescence light (FL), and combination (positive if either WL or FL was positive) were recorded, and diagnostic quality of PDD was compared between both groups. Results: Group A had 105 cases and 336 specimens, while Group S had 100 cases and 361 specimens, with no significant differences between patient characteristics. The tumor sensitivities of WL, FL, and combination in Group A was 71.9%, 77.1%, 90.5%, respectively, while in Group S, these were 71.5%, 92.2%, 96.1%, respectively. Group S had significantly higher sensitivity of FL and combination than Group A, as well as higher detection of carcinoma in situ lesions. Conclusion: Both endoscopic systems had improved sensitivity with PDD-assistance versus WL only, with Group S having higher sensitivity. Differences in the quality of endoscopic equipment may influence the differences in treatment results with PDD-assisted TURBT across institutions.

Background/aim To investigate whether surgical margin (SM) status would affect the biochemical recurrence (BCR) after robot-associated RP (RARP). Patients and methods We evaluated BCR after RARP and the association between pre- and postoperative predictive factors and BCR. Results Positive SM (PSM) was observed in 97 out of 365 enrolled patients. On multivariate analysis, preoperative prostate specific antigen, biopsy Gleason score (GS), clinical stage, GS ≥7 at the PSM and pathological GS ≥7 were predictive factors for BCR. The 5-year BCR-free survival rate was 84.1% in the negative SM (NSM), 87.4% when GS=6 at the PSM, and 47.6% when GS ≥7 at the PSM. There was no statistically significant difference in BCR-free survival between the NSM group and GS=6 at the PSM group (p=0.966). Conclusion It would be desirable to evaluate GS at PSM when PSM is present in a specimen removed by RP.

The aim of this study was to determine the prevalence of collecting system invasion (CSI) on multiphasic CT, validate the pathological findings, and investigate the relationship between CSI and clinical outcomes in patients with renal cell carcinomas (RCC). Patients pathologically diagnosed with RCC between January 2008 and December 2017 were retrospectively enrolled in this study. They were divided into two groups according to the presence of CSI on multiphasic CT images. Patients’ clinical characteristics, radiological findings, and overall survival (OS) and recurrence-free survival (RFS) rates were analyzed and compared between the groups. In addition, the correlation of radiological findings with pathological findings was investigated. Among the included 347 kidneys of 340 patients, CSI was observed in 11 kidneys (3%; 95% confidence interval, 1.3–5.0%). In all the 11 kidneys, the tumors were pathologically diagnosed as clear cell RCC, and in one kidney, the tumor also had sarcomatoid features. When pathological CSI served as the standard of reference, the sensitivity, specificity, and accuracy of CSI on CT were 50%, 99.7%, and 97.1%, respectively. The OS and RFS rates were not significantly different between patients with CSI on CT and those without CSI. This study found that the prevalence of RCC-related CSI was 3%. Because of the low prevalence, we cannot exclude the possibility that CSI on CT would be associated with the OS and RFS. Further studies are needed to determine whether CSI on CT can be an independent prognostic factor for survival in patients with RCC.

Five mg tadalafil was administered once-daily to 48 patients for 6 months. Their International Prostatic Symptoms Score (IPSS), Overactive Bladder Symptoms Score (OABSS), Sexual Health Inventory for Men (SHIM), post-voided residual (PVR) volume, free testosterone (FT) level, prostate-specific antigen level, and highly sensitive C-reactive protein (hsCRP) value obtained before and 6 months after the treatment were analyzed. The treatment significantly improved the IPSS, OABSS, SHIM score, and PVR volume (P0.05), and significantly increased the mean FT level from 6.68 to 7.10 pg/ml ; P0.05. We observed no significant changes in the hsCRP value and PSA level. However, elevated FT values were noted in 25 (52.1%) patients 6 months after the treatment (FT-increased group). Compared with the non-FT-increased group, the FT-increased group had markedly lower baseline FT value and higher prostatic volume. In both groups, IPSS and OABSS improved considerably. Moreover, the PVR volume, SHIM score, and hsCRP value markedly improved in the FT-increased group (P0.05). Thus, 5 mg tadalafil administered oncedaily improved IPSS, OABSS, and erectile function, and increased the FT value, in hypogonadal patients with lower urinary tract symptoms. Furthermore, the hsCRP value declined considerably in patients with posttreatment elevated FT level.

Background/aim Hypertension is a risk factor for occurrence of renal cell carcinoma; however, it remains unclear whether hypertension affects development and prognosis of renal cell carcinoma. This study evaluated the impact of hypertension on the progression of renal cell carcinoma. Patients and methods Renal cell carcinoma patients who were treated from October 2007 to December 2018 at our Institution were retrospectively analyzed. Results Of 462 patients, the number of patients with and without hypertension was 234 (including 227 treated with anti-hypertensive agents) and 228, respectively. The tumor size was significantly smaller in the hypertension group than in the non-hypertension group (median 32 and 45 mm, respectively, p=0.010). The 5-year cancer-specific and metastasis-free survival in the hypertension group were significantly better than those in the non-hypertension group (93.6% and 80.4%, and 84.6% and 73.0%, respectively, p=0.021 and p=0.017). Propensity score matching revealed significantly better metastatic-free survival in the hypertension group than the non-hypertension group (p=0.022). Conclusion Renal cell carcinoma patients with hypertension show better prognosis with low metastasis possibility.

The present study investigated the efficacy of 6 months of testosterone replacement therapy (TRT) on chronic pain syndrome in late-onset hypogonadal (LOH) men. Sixty hypogonadal patients with chronic pain syndrome (31 patients in TRT group and 29 controls) were extracted from a previous randomised controlled study in Japan. Chronic pain was evaluated based on bodily pain (BP) subscale of Short-form (36) Health Survey (SF-36), and patients with a score of 50.0 or less were defined as suffering from chronic pain. SF-36 scores, Aging Male Symptoms (AMS) scale, international prostatic symptoms score (IPSS) and prostate-specific antigen (PSA) levels at baseline and a 6-month visit for the two groups were collected and compared. There were no statistically significant differences in baseline backgrounds between the two groups. Six-month TRT could contribute to significant improvements in BP, mental health of SF-36 and sleep disturbance (AMS question 4). Though the PSA level in the TRT group also significantly elevated at 6 months, the increase was not clinically significant. No significant improvements were evident in any characteristics in the controls. In conclusion, 6-month TRT can improve pain and some aspects of quality of life in LOH men with chronic pain.

To investigate the time course of total testosterone (TT) recovery after cessation of androgen deprivation therapy (ADT) in Japanese patients treated with brachytherapy.In total, 125 patients with prostate cancer received 6 months of neoadjuvant ADT (nADT) followed by low-dose rate (LDR) brachytherapy. TT was measured every 3 months after cessation of nADT, and some predictive factors affecting TT recovery were analyzed.The cumulative incidence rates of TT recovery to normal levels (TT ≥ 3.0 ng/mL) after 12 and 24 months cessation were 49.6% and 81.6%, respectively. The median interval to recover to normal TT was 15 months. In multivariate analysis, the use of a gonadotropin-releasing hormone (GnRH) antagonist as nADT significantly earlier improved to recovery to normal TT level (Approximately one-fifth of patients still had low TT levels 2 years after the cessation of 6 months nADT before LDR brachytherapy. Use of a GnRH agonist, higher BMI, and hypertension were the predictive factors for slower TT recovery to normal TT levels after the cessation of nADT.

Background/aim The best sequential treatment for castration-resistant prostate cancer (CRPC) remains unclear. This study evaluated the therapeutic effects of ethinylestradiol (EE) on CRPC. Patients and methods A total of 80 patients with CRPC, treated with 0.5-1.5 mg/day of EE, were retrospectively assessed. Results The median duration from the initial treatment to the beginning of EE was 48.3 months. A decline in the prostate-specific antigen (PSA) from the baseline was noted in 60 patients (75%) and a >50% PSA decline in 27 patients (34%). The median time of PSA progression, overall survival, and cancer-specific survival after EE were 5.60 months, 24.00 months, and 27.93 months, respectively. Conclusion EE administration for CRPC showed a relatively high PSA response regardless of timing of sequential treatment. The frequency of cardiovascular adverse events was not significantly high. EE administration is a potential treatment option for CRPC.

Objective The present study aimed to investigate human papillomavirus (HPV) prevalence and identify risk factors for HPV detection in urine samples among heterosexual men attending urological clinics. Materials and Methods Spot urine samples including initial stream were collected from 845 participants, and the cell pellets were preserved into liquid-based cytological solution. After DNA extraction from each sample, HPV-DNA amplification and genotyping were performed using Luminex multiplex polymerase chain reaction. Participants completed a questionnaire on their age, education, smoking status, sexuality, age of sexual debut, marital status, and present history of sexually transmitted infections. Results Data from 803 patients were included in the analysis. Overall HPV and high-risk (HR) HPV prevalence in urine samples were 6.2% and 3.1%, respectively. HPV and HR-HPV prevalences were the highest in men with urethritis, and were significantly higher than those without urethritis. HPV detection was the most common in men aged 40–49 years, although significant detection differences were not age-related. Urethritis was an independent risk factor for HPV detection from urine samples, with an odds ratio (OR) of 4.548 (95%CI; 1.802–11.476) (p = 0.001). On the other hand, a sub-analysis excluding men with urethritis demonstrated that prostate cancer was a significant risk factor for HPV detection, with OR of 2.844 (95%CI; 1.046–7.732) (p = 0.0410), whereas was not a significant risk for HR-HPV detection in urine samples. Conclusion Prostate cancer may represent a risk factor for HPV detection in the urine of men without urethritis. Registration of clinical trials The authors did not register to Clinical Trial because this is observational and cross-sectional study.

Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling.

Chyloretroperitoneum is a rare complication of urological surgery. Here we report a case of chyloretroperitoneum that occurred in a 28-year-old man post living-donor transplantation. Twenty-nine days post transplantation, perirenal fluid collection and hydronephrosis were detected and percutaneous drainage was performed. The fluid was chylous and revealed a very high triglyceride concentration (1,197 mg/dL). Total parenteral nutrition and administration of octreotide were performed, but the leakage did not improve. On the contrary, the drainage fluid gradually increased to 1,600 mL/day, and a laparoscopic fenestration was performed owing to a concern about the adverse effects of massive lymph loss. Ascites temporarily appeared but disappeared 3 months post fenestration. To our knowledge, this is the first case report of pelvic chyloretroperitoneum post living-donor transplantation. Furthermore, if chyloretroperitoneum treatment using diet control or octreotide is ineffective, laparoscopic fenestration can be considered as a treatment option.

The present subanalysis of the EARTH study investigates the effects of one year testosterone replacement therapy (TRT) on sleep disturbance among hypogonadal men without obstructive sleep apnea.Sleep disturbance was defined as three or more points in question 4 of the aging males symptoms (AMS) questionnaire. All participants completed the AMS scale, International Prostatic Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) and Short Form 36 (SF-36) health survey at baseline and after 12 months. Sexual symptoms were also evaluated based on three AMS subscores (Q15, 16 and 17).We identified 100 patients with sleep disturbance, of whom 48 (24 each in the TRT and control groups) were ultimately included for analysis. All SF-36 categories , AMS scale, IPSS and SHIM score subdomains were significantly worse in patients with sleep disturbance than in those without disturbance. Statistically significant differences in sleep disturbance, erectile symptoms, sexual desire and some domains of the SF-36 were observed between the TRT and control groups after 12 months.Sleep disturbance may be one of the clinical signs for severe hypogonadism. Moreover, TRT improved sleep conditions, sexual function and quality of life among hypogonadal men with sleep disturbance.

Background The present study investigated human papillomavirus (HPV) prevalence in anal and urine samples, and evaluated cytological findings among human immunodeficiency virus (HIV)-infected Japanese men who have sex with men (MSM). Methods A total of 148 patients were enrolled. Anal and urine samples were collected from each participant, and a HPV-DNA test and genotyping were performed using flow-through hybridization. In addition, anal cytology was evaluated based on Papanicolaou staining. Questionnaires regarding lifestyle habits and sexual behavior were obtained. Results The β-globin gene was positive in 131 (88.5%) anal samples and 139 (94.0%) urine samples. Among the β-globin-positive samples, the HPV prevalence in anal and urine samples was 80.9% and 30.9%, respectively. High-risk HPV (HR-HPV) was detected in 57.3% of anal samples and 20.9% of urine samples. Among 122 adequate cytological samples, anal cytological abnormalities were observed in 99 cases (81.1%). Anal cytological tests revealed that atypical squamous cells of an undetermined significance (ASCUS) were detected in 57 (46.7%) patients, followed by low-grade squamous intraepithelial lesions (SIL) in 35 (28.7%), high-grade SIL in five (4.1%), and atypical squamous cells cannot exclude high-grade SIL (ASC-H) in two (1.6%), respectively. The nadir counts of CD4-positive T-lymphocyte less than 200 μL and anal HR-HPV infection were independent risk factors for anal cytological atypia over ASC-H. Conclusions The present study demonstrated high HPV prevalence in the anus and urine, and showed a high incidence of anal cytological atypia associated with HR-HPV infections among HIV-infected MSM patients.

When advanced prostate cancer recurred during hormonal therapy and became the castration-resistant prostate cancer, "vintage hormonal therapy," such as antiandrogen alternating therapy or estrogen-related hormonal therapy, was widely carried out in Japan until 2013. This vintage hormonal therapy controlled the progression of castration-resistant prostate cancer. When castration-resistant prostate cancer relapses during these therapies, chemotherapy using docetaxel has been carried out subsequently. Since new hormonal therapies using abiraterone acetate and enzalutamide, which improve the prognosis of castration-resistant prostate cancer, became available in Japan from 2014, therapeutic options for castration-resistant prostate cancer have increased. Furthermore, the improvement of the further prognosis is promising by using cabazitaxel for docetaxel-resistant castration-resistant prostate cancer and radium-223 for castration-resistant prostate cancer with bone metastasis. An increase in therapeutic options gives rise to many questions, including best timing to use them and the indication. Furthermore, physicians have to consider the treatment for the recurrence after having carried out chemotherapy. We want to argue the difference in hormonal therapy between Japan and Western countries, and problems when carrying out new treatments, and the importance of imaging in the present review article. © 2017 The Japanese Urological Association., Embargo Period 12 months

Objective: To measure changes in penile length (PL) over time before and after radical prostatectomy (RP), and to investigate the underlying mechanisms for these changes. Patients and Methods: The stretched PL (SPL) of 102 patients was measured before, 10 days after, and at 1, 3, 6, 9, 12, 18 and 24 months after RP. The perpendicular distance from the distal end of the membranous urethra to the midline of the pelvic outlet was measured on mid-sagittal magnetic resonance imaging (MRI) slice at three time points: preoperatively; 10 days after RP; and 12 months after RP. Pre- and postoperative SPLs were compared using paired Student's t-test. Predictors of PL shortening at 10 days and at 12 months after RP were evaluated on univariate and multivariate analyses. Results: The SPL was shortest 10 days after RP (mean PL shortening from preoperative level: 19.9 mm), and gradually recovered thereafter. SPL at 12 months after RP was not significantly different from preoperative SPL. On MRI examination, the distal end of membranous urethra was found to have moved proximally (mean proximal displacement: 3.9 mm) at 10 days after RP, and to have returned to the preoperative position at 12 months after RP. On univariate analysis, only the volume of the removed prostate was a predictor of SPL change at 10 days after surgery; on multivariate analysis, the association was not statistically significant. No predictor of SPL change was found at 12 months after RP. Conclusion: The SPL was shortest at 10 days after RP and gradually recovered thereafter in the present study. Anatomically, the glans and corpus spongiosum surrounding the urethra are an integral structure, and the proximal urethra is drawn into the pelvis during urethrovesical anastomosis. This is the first report showing that slight vertical repositioning of the membranous urethra after RP causes changes in SPL over time. These results can help inform patients about changes in penile appearance after RP. © 2017 BJU International., Embargo Period 12 months

The present study investigated the prevalence of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, M. hominis, and Ureaplasma spp. (biovars 1 and 2) in Japanese HIV-positive men who have sex with men (MSM). One-hundred-and-six Japanese HIV-infected MSM patients were enrolled. Anal and urine samples were collected and DNA testing for each microorganism was performed. Questionnaires regarding lifestyle habits and sexual behavior were administered. The prevalence of N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis, and Ureaplasma spp. in the anus was 5.6%, 8.9%, 4.4%, 5.6%, and 8.9%, respectively. A history of genital warts was an independent risk factor for detection of Mycoplasma spp. and Ureaplasma spp. The prevalence of these microorganisms in the anus of asymptomatic Japanese HIV-positive MSM was relatively high in agreement with previous reports from other countries.

OBJECTIVE To analyze perioperative blood pressure in patients undergoing transurethral resection of bladder tumor with photodynamic diagnosis. METHODS A total of 109 consecutive patients who underwent photodynamic diagnosis-assisted transurethral resection of bladder tumor at Kanazawa University, Kanazawa, Ishikawa, Japan, were included in this study and considered as the photodynamic diagnosis group. Clinical data were collected, and perioperative systolic bladder pressure and vasopressor usage were analyzed. In contrast, consecutive patients who previously underwent conventional transurethral resection of bladder tumor (without the use of oral 5-aminolevulinic acid) were used as the control group. RESULTS The systolic blood pressure before anesthesia, lowest systolic blood pressure from the anesthesia induction to the start of operation and lowest systolic blood pressure during operation were significantly lower in the photodynamic diagnosis group. The rate of vasopressor use was significantly higher in the photodynamic diagnosis group. On multivariate analysis, we found that general anesthesia and regular use of renin-angiotensin system inhibitor were associated with an increased risk of hypotension (lowest systolic blood pressure from the anesthesia induction to the start of operation

Background/aim This study aimed to evaluate the therapeutic effect of enzalutamide (ENZ) or abiraterone acetate (ABI) on bone metastasis in castration-resistant prostate cancer (CRPC), using bone scan index (BSI). Materials and methods Treatment outcomes for 31 patients who had undergone ENZ or ABI treatment were examined for CRPC with bone metastases. Cox proportional-hazards regression models were used to investigate the association between overall survival (OS) and clinical characteristics. Results Median OS after ENZ or ABI treatment was 29 months. Considering the flare phenomenon, BSI in 17 (55%) patients decreased following treatment. In multivariate analysis, low baseline BSI value and a decrease in BSI following treatment were associated with longer OS (hazard ratio [HR]=8.009; p=0.35 and HR=7.025; p=0.045*, respectively). Conclusion Low BSI value before ENZ/ABI treatment and a decrease in BSI following ENZ or ABI treatment are independent predictors of longer OS. BSI could be useful for risk assessment of CRPC patients with bone metastases.

BACKGROUND/AIM To evaluate our initial experience with radium-223 chloride (Ra-223). MATERIALS AND METHODS A total of 26 castration-resistant prostate cancer (CRPC) patients with bone metastases, treated with Ra-223 at our hospital were evaluated. This study aimed to observe adverse events (AEs) and changes in serum markers, and Bone Scan Index (BSI). Additionally, the relationship between these values and OS was investigated. RESULTS The observed AEs mainly included fatigue and nausea. Alkaline phosphatase (ALP) and bone-type alkaline phosphatase (BAP) levels decreased following the treatment; however, those of PSA and 1-CTP tended to increase, regardless of Ra-223 administration. Overall survival (OS) was significantly improved in cases with a baseline BSI value of

Objective: This study investigated the efficacy of 5-year testosterone replacement therapy (TRT) on lipid profile and glucose tolerance in Japanese hypogonadal men.Methods: Fourteen patient...

Metastatic urothelial carcinoma is one of the most fatal urological malignancies. Cisplatin-based systemic chemotherapy is the standard treatment for metastatic urothelial carcinoma, and there is little evidence to support metastasectomy. The aims of the study were to evaluate the efficacy of metastasectomy and to investigate the prognoses of the patients. The study included 436 patients with urothelial carcinoma who were treated at our hospital. Of these, we included and retrospectively analyzed 29 patients who received curative treatment for the primary tumor and had been treated for metastases. Seven of these patients underwent metastasectomy. In a multivariate analysis, a serum C-reactive protein level before treatment for metastasis of