Mechanism of hypertensive crisis during energy device ablation of the adrenal gland: An experimental animal study.

OBJECTIVE: To elucidate the mechanism of hypertensive crisis during energy device ablation of the adrenal gland. METHODS: Electrocoagulation on the adrenal glands of six pigs was carried out with the same energy device (VIO300D) using four methods: (i) monopolar coagulation; (ii) monopolar soft coagulation using IO-advanced ball-type electrodes; (iii) bipolar soft coagulation by pinching; and (iv) bipolar soft coagulation by non-pinching (surface contact) using Bipolar forceps Premium. After electrocoagulation for 5 s, blood pressure and pulse changes were monitored, and adrenal hormones were measured from a central vein. The adrenal glands were removed, and the degree of tissue damage was scored histologically. RESULTS: Hypertensive crisis occurred with electrocoagulation of the adrenal gland by the monopolar coagulation, monopolar soft coagulation and bipolar soft coagulation pinching methods. Blood pressure did not change with the bipolar soft coagulation non-pinching method. Pathologically, tissue damage to the adrenal medulla was associated with elevated blood pressure and adrenaline and noradrenaline release. CONCLUSIONS: Hypertensive crisis caused by energy device ablation to the adrenal gland is caused by the release of catecholamines due to heat damage to the adrenal medulla rather than the type of energy device. Proper use of an energy device that does not cause thermal degeneration of the medulla is required to prevent hypertensive crisis.

Histological and radiological evaluation of thermal denaturation depth using soft coagulation during partial nephrectomy in living pigs.

OBJECTIVES: To evaluate thermal denaturation depth using soft coagulation in kidneys in vivo. METHODS: In experiment 1, nine kidneys from five pigs were cauterized using five soft-coagulation settings at 80 W with effect 7 by VIO300D and one monopolar-coagulation setting. The surface of the kidney was cauterized over a period of 2, 5 and 10 s. The temperature change was measured at depths of 5 and 10 mm. In experiment 2, three kidneys from two pigs were excised in a semicircular shape with a diameter of 5, 10 and 20 mm without clamping the renal artery. Cauterization was carried out until hemostasis was confirmed by soft coagulation at 80 W with effect 7. After completion of the experiments, pathology examinations of the kidneys were carried out. RESULTS: Experiment 1 showed that with proper saline dripping, denaturation spread with increased cauterization time, reaching a depth of 4 mm at 10 s with or without clamps. The depth remained at 2-3 mm at 10 s in the absence or excess of saline. The temperature increased by 15.6°C at a depth of 5 mm and 8.8°C at 10 mm. In experiment 2, the depth was 4.6 mm from the incision surface regardless of the cauterization time or excision size. CONCLUSIONS: These findings suggest that soft coagulation can be useful for preserving renal function and reducing complications in partial nephrectomy.

Cancer detection rate of prebiopsy MRI with subsequent systematic and targeted biopsy are superior to non-targeting systematic biopsy without MRI in biopsy naïve patients: a retrospective cohort study.

BACKGROUND: To determine whether prebiopsy multiparametric magnetic resonance imaging (mpMRI) with subsequent systematic plus targeted biopsies for suspicious lesions improve prostate cancer detection compared with standard non-targeting systematic biopsies without mpMRI in biopsy-naïve patients. METHODS: Patients who underwent their first prostate biopsy due to suspicion of prostate cancer were analyzed retrospectively to compare the biopsy outcomes between patients who received prebiopsy mpMRI (215 patients) and those who did not (281 patients). mpMRI was performed to determine pre-biopsy likelihood of the presence of prostate cancer using a three-point scale (1 = low level of suspicion, 2 = equivocal, and 3 = high level of suspicion). Systematic biopsies were performed in both groups. Targeted biopsies were added for a high level of suspicious lesions on mpMRI. All biopsies were performed by transperineal biopsy technique. After biopsy, Prostate Imaging Reporting and Data System ver. 2 (PIRADS-2) scoring was performed to describe the mpMRI findings and predictive value of PIRADS-2 was evaluated. RESULTS: The detection rate of total and clinically significant prostate cancer was significantly higher in patients who received prebiopsy mpMRI than in those who did not (55.3 and 46.0% vs. 42.0 and 35.2%, respectively; p = 0.004 and p = 0.016). The clinically insignificant prostate cancer detection rate was similar between the two groups (9.3% vs. 6.8%; p = 0.32). Of 86 patients who underwent systematic plus targeted biopsy in the MRI cohort and were diagnosed with prostate cancer, seven patients were detected by addition of targeted biopsy whereas 29 patients were missed by targeted biopsy but detected by systematic biopsy. There was a correlation between the PIRADS-2 and prostate cancer detection rate, and a receiver-operator curve analysis yielded an area under the curve of 0.801 (p <  0.0001). CONCLUSIONS: Prebiopsy mpMRI with subsequent systematic plus targeted biopsies for suspicious lesions can yield a higher cancer detection rate than non-targeting systematic biopsies. PIRADS-2 scoring is useful for predicting the biopsy outcome.

Influence of genetic polymorphisms of multidrug and toxin extrusion protein 1 on its mRNA expression in peripheral blood cells.

This study aimed to determine the effect of multidrug and toxin extrusion protein 1 (MATE1) genetic variants on its transcript expression in peripheral blood cells. Consistent with previous in vitro findings, MATE1 mRNA levels were significantly higher in subjects carrying rs2453579, but not rs2252281, compared to those without either of these promoter variants. In addition, the mRNA levels did not differ between subjects with both variants and those with neither allele. Thus, this study reveals that the influence of MATE1 genetic variants on its mRNA expression can be detected in vivo using peripheral blood.

Temsirolimus induces surfactant lipid accumulation and lung inflammation in mice.

Interstitial lung disease (ILD) is a well-known adverse effect of mammalian target of rapamycin (mTOR) inhibitors. However, it remains unknown how lung toxicities are induced by mTOR inhibitors. Here, we constructed a mouse model of mTOR inhibitor-induced ILD using temsirolimus and examined the pathogenesis of the disease. Male ICR mice were treated with an intraperitoneal injection of different doses of temsirolimus (3 or 30 mg·kg(-1)·wk(-1)) or vehicle. Temsirolimus treatment increased capillary-alveolar permeability and induced neutrophil infiltration and fibrinous exudate into the alveolar space, indicating alveolar epithelial and/or endothelial injury. It also induced macrophage depletion and the accumulation of excessive surfactant phospholipids and cholesterols. Alveolar macrophage depletion is thought to cause surfactant lipid accumulation. To further examine whether temsirolimus has cytotoxic and/or cytostatic effects on alveolar macrophages and alveolar epithelial cells, we performed in vitro experiments. Temsirolimus inhibited cell proliferation and viability in both alveolar macrophage and alveolar epithelial cells. Temsirolimus treatment caused some signs of pulmonary inflammation, including upregulated expression of several proinflammatory cytokines in both bronchoalveolar lavage cells and lung homogenates, and an increase in lymphocytes in the bronchoalveolar lavage fluid. These findings indicate that temsirolimus has the potential to induce alveolar epithelial injury and to deplete alveolar macrophages followed by surfactant lipid accumulation, resulting in pulmonary inflammation. This is the first study to focus on the pathogenesis of mTOR inhibitor-induced ILD using an animal model.

Development of nomogram to non-steroidal antiandrogen sequential alternation in prostate cancer for predictive model.

OBJECTIVES: To clarify clinical predictors for a prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy and to develop a nomogram to predict the prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy in patients with advanced prostate cancer that relapsed after initial combined androgen blockade. We previously reported that combined androgen blockade with an alternative non-steroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial combined androgen blockade. METHODS: We enrolled 161 patients from 14 medical institutions with histologically confirmed prostate cancer who had been treated with combination therapy and in whom cancer progressed after first-line combined androgen blockade therapy. A nomogram for the prostate-specific antigen decrease ≥50% from baseline prostate-specific antigen in response to alternative non-steroidal antiandrogen therapy was developed based on the final logistic regression model. RESULTS: Overall prostate-specific antigen decreased ≥50% in 75 of 161 patients (46.6%) in response to alternative non-steroidal antiandrogen therapy. Using five independent risk factors (initial serum level of prostate-specific antigen, hemoglobin, C-reactive protein, prostate-specific antigen nadir to second hormone therapy and Gleason sum), a nomogram was developed for the prediction of prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy. The receiver operating characteristic curve showed that the accuracy of the predicted probability was 72.5% for the model. CONCLUSIONS: This predictive nomogram could predict the prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy and might be of benefit to determine the sequential treatment strategy in patients with relapse after first combined androgen blockade.

Approach via a small retroperitoneal anterior subcostal incision in the supine position for gasless laparoendoscopic single-port radical nephrectomy: initial experience of 42 patients.

BACKGROUND: Gasless laparoendoscopic single-port surgery (GasLESS) for radical nephrectomy (GasLESSRN) in the flank position is a minimally invasive treatment option for patients with T1-3 renal cell carcinoma (RCC). However, RCC patients considered suitable for supine positioning rather than flank positioning for radical nephrectomy are occasionally encountered. This study evaluated the safety and feasibility of approach via a small retroperitoneal anterior subcostal incision (RASI) in the supine position for GasLESSRN (RASI-GasLESSRN) on the basis of our initial experience. METHODS: RASI-GasLESSRN was performed on 42 patients with RCC or suspected RCC from 2011-2013. The RASI, which was 6 cm long in principle, was made parallel to the tip of the rib from the lateral border of rectus abdominis muscle toward the flank in the supine position. The specimen was extracted via the RASI using a retrieval device. All procedures were performed retroperitoneally under flexible endoscopy with reusable instruments and without carbon dioxide insufflation or insertion of hands into the operative field. RESULTS: RASI-GasLESSRN was successfully performed in all patients without complications. The mean incision length was 6.3 cm, mean operative time was 198 minutes, and mean blood loss was 284 mL. All 42 patients were classified as Clavien grade I. The mean times to oral feeding and walking were 1.1 and 2 days, respectively. The mean number of postoperative days required for patients to be dischargeable was 3.7 days. CONCLUSIONS: The approach via a small RASI in the supine position for GasLESSRN is a safe and feasible technique. RASI-GasLESSRN in the supine position is an alternative minimally invasive treatment option, especially for RCC patients considered suitable for supine positioning.

External validation of risk classification in patients with docetaxel-treated castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) patients have poor prognoses, and docetaxel (DTX) is among the few treatment options. An accurate risk classification to identify CRPC patient groups for which DTX would be effective is urgently warranted. The Armstrong risk classification (ARC), which classifies CRPC patients into 3 groups, is superior; however, its usefulness remains unclear, and further external validation is required before clinical use. This study aimed to examine the clinical significance of the ARC through external validation in DTX-treated Japanese CRPC patients. METHODS: CRPC patients who received 2 or more DTX cycles were selected for this study. Patients were classified into good-, intermediate-, and poor-risk groups according to the ARC. Prostate-specific antigen (PSA) responses and overall survival (OS) were calculated and compared between the risk groups. A multivariate analysis was performed to clarify the relationship between the ARC and major patient characteristics. RESULTS: Seventy-eight CRPC patients met the inclusion criteria. Median PSA levels at DTX initiation was 20 ng/mL. Good-, intermediate-, and poor-risk groups comprised 51 (65%), 17 (22%), and 10 (13%) patients, respectively. PSA response rates ≥ 30% and ≥ 50% were 33%, 41%, and 30%, and 18%, 41%, and 20% in the good-, intermediate-, and poor-risk groups, respectivcixely, with no significant differences (p = 0.133 and 0.797, respectively). The median OS in the good-, intermediate-, and poor-risk groups were statistically significant (p < 0.001) at 30.1, 14.2, and 5.7 months, respectively. A multivariate analysis revealed that the ARC and PSA doubling time were independent prognostic factors. CONCLUSIONS: Most of CRPC patients were classified into good-risk group according to the ARC and the ARC could predict prognosis in DTX-treated CRPC patients. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number, UMIN000011969.

Nocturia Quality-of-Life questionnaire is a useful tool to predict nocturia and a risk of falling in Japanese outpatients: a cross-sectional survey.

OBJECTIVES: To evaluate the Japanese version of the Nocturia Quality-of-Life questionnaire for prediction of night-time voiding and risk of falling. METHODS: A survey was carried out from October 2008 to June 2009 in outpatients at 15 general hospitals and 80 general clinics in Tochigi, Japan, using the Nocturia Quality-of-Life questionnaire, overactive bladder symptom score and self-administered questionnaires on night-time symptoms (awakening, number of voids, incontinence and falling). RESULTS: The survey was completed by 2494 participants (1154 men, 1208 women; mean age 63.2 ± 15.1 years). Overactive bladder was diagnosed in 625 participants (25.1%) according to the Japanese overactive bladder guideline using overactive bladder symptom score. Awakening during sleep was reported by 80.1% of the participants, and 70.4% awakened to go to the toilet. The mean Nocturia Quality-of-Life score was 86.8 ± 16.9. The Nocturia Quality-of-Life score was lower in patients with overactive bladder, benign prostatic hyperplasia, diabetes, hypertension and cardiovascular diseases. The Nocturia Quality-of-Life score was significantly decreased in patients with night-time symptoms (P < 0.001). Nocturia Quality-of-Life scores and those for subdomains were correlated with overactive bladder symptom score. Nocturia Quality-of-Life ≤90 had 63.1% sensitivity and 78.6% specificity in indicating night-time voiding more than twice, and Nocturia Quality-of-Life questionnaire ≤80 had 70.2% sensitivity and 79.5% specificity in indicating the probability of falling at least once. Logistic analysis showed that 10-year increase in age and overactive bladder in all participants were significant risk factors for Nocturia Quality-of-Life ≤90. CONCLUSIONS: The Nocturia Quality-of-Life questionnaire represents a useful tool to predict nocturia and risk of falling in Japanese patients.

Factors affecting the use of a three-dimensional model during robot-assisted partial nephrectomy.

INTRODUCTION: This study aimed to identify cases that require a three-dimensional-printed kidney model in robot-assisted partial nephrectomy. METHODS: We enrolled 93 patients undergoing robot-assisted partial nephrectomy for renal tumors at a single institution between November 2018 and May 2021. The endpoints were how often and how long the surgeon consulted the three-dimensional-printed model, determined using intraoperative video. Multivariate analyses of the endpoints were adjusted by preoperative patient and kidney characteristics, including renal vascular complexity that was defined as the number of vascular branches penetrating the surface tangential to the ventral side of the kidney. RESULTS: Of the 93 cases, the median frequency and duration of intraoperative three-dimensional-printed model consultation were four times and 39 s, respectively. The multivariate linear regression analyses showed that the frequency of intraoperative three-dimensional-printed model consultation by the surgeon was significantly related to the complexity of the arterial structure (≥4 branches), presence of hilar tumor, and high Mayo Adhesive Probability score; the regression coefficients were 1.81, 2.79, and 1.34, respectively. All p-values were ≤.03. The duration of the three-dimensional-printed model consultation was significantly related to the complexity of the arterial structure (≥4 branches) and the presence of hilar tumor; the regression coefficients were 21.6, and 29.0 s, respectively. All p-values were <.01. CONCLUSION: During robot-assisted partial nephrectomy, a three-dimensional-printed model would be helpful in cases with a complex arterial structure or hilar tumor.

Hand-foot skin reaction is associated with the clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib.

BACKGROUND: To elucidate whether Hand-Foot skin reaction could become a biomarker of clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib, we retrospectively examined the association between the Hand-Foot skin reaction and the clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib. METHODS: Thirty-six Japanese metastatic renal cell carcinoma patients treated with sorafenib were enrolled and divided into the groups with or without Hand-Foot skin reaction. Patient characteristics, best tumor response, progression-free survival and adverse events were investigated and compared between these two groups. RESULTS: A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients was observed at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification, and with Eastern Cooperative Oncology Group Performance Status of one or less, prior nephrectomy, higher hemoglobin, lower lactate dehydrogenase and lower C-reactive protein. The mean best tumor response was significantly better in the group with Hand-Foot skin reaction (-16.7%) than that in the group without it (17.9%; P < 0.001). The median progression-free survival was significantly longer in the group with Hand-Foot skin reaction (4.6 months) than that in the group without it (1.5 months; P = 0.002). In multivariate analysis, only Hand-Foot skin reaction was shown to be a predictive factor of progression-free survival (hazard ratio 0.312, P = 0.010). CONCLUSIONS: A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients emerged at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification and was significantly associated with best tumor response and progression-free survival, suggesting that Hand-Foot skin reaction might be an independent predictive factor for clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib.

RhoC and guanine nucleotide exchange factor Net1 in androgen-unresponsive mouse mammary carcinoma SC-4 cells and human prostate cancer after short-term endocrine therapy.

BACKGROUND: Endocrine resistance is a critical issue in managing patients with prostate cancer. This study is undertaken to search for a potential molecular target connected with this process using a model system of androgen-dependent and androgen-unresponsive SC-3 and SC-4 cells. METHODS: Expression profiles, actin stress fiber organization, and the levels of activated Rho GTPases were compared between SC-4 and SC-3 cells using an oligonucleotide microarray, phalloidin staining, and a Rho activation assay. The cell viability was analyzed with a Rho inhibitor or by stable transfection with either a dominant-negative (DN) form of RhoC or a mutant form of NET1 (mutNET1). The expressions of RhoC, NET1, and epithelial-mesenchymal transition (EMT) markers were immunohistochemically analyzed in human prostate cancer specimens after short-term endocrine therapy and in an untreated condition. RESULTS: SC-4 cells exhibited mesenchymal phenotypes with activation of Rho signals. Treatment with a Rho inhibitor suppressed the cell viability in SC-4 cells, but not in SC-3 cells. The cell viability of SC-4 cells stably expressing DN-RhoC and mutNET1 was also attenuated. In the immunohistochemical analysis, NET1 and the EMT marker of N-cadherin were expressed at higher levels in prostate cancers after short-term endocrine therapy than in untreated tumors, and RhoC expression was maintained after short-term endocrine therapy. CONCLUSIONS: Rho signaling is involved in the cell survival of SC-4 cells. The higher expressions of RhoC and NET1 in human prostate cancers after short-term endocrine therapy suggest that RhoC and NET1 may become therapeutic targets during endocrine therapy.

Effect of host immunity on metastatic potential in renal cell carcinoma: the assessment of optimal in vivo models to study metastatic behavior of renal cancer cells.

There has been little information about metastatic behavior of renal cell carcinoma (RCC) cells because human cancers metastasize only rarely in immunodeficient mice. Moreover, it is difficult to know the effect of host immunity on RCC metastasis due to lack of such RCC cells as transplantable in not only xenograft models but also counterparts with intact immunity. Therefore, we scrutinized in vivo metastasis of RCC cells to seek for the optimal preclinical model to study metastatic behavior. The luciferase-expressing three representative human RCC cell lines (Caki-1, A498, and 786-O) and rat ACI-RCC cell which were established in our laboratory were transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice or immunocompetent ACI rats by intracardiac injection as well as orthotopic inoculation. Metastasis was monitored using a bioluminescent imaging technique. Metastasis was rare in the three human RCC cells even when they were directly disseminated into systemic circulation under the condition least susceptible to host immune attack in NOD/SCID mice. In contrast, ACI-RCC cells spontaneously metastasized to pulmonary tissue from orthotopic tumor sites and systemically spread via intracardiac route. Metastases were more extensive when the cells were inoculated into an immunodeficient host, implying suppressive effect of host immunity on colonization of RCC cells. These results suggest that the representative human RCC cells are not adequate resource to study metastasis but that the luciferase-labeled ACI-RCC cell characterized by its luminescent stability, enhanced tumorigenicity, and widespread metastatic potential provides a useful in vivo model for preclinical assessment of cancer progression and potential therapies against RCC.

Investigation of ejaculatory disorder by silodosin in the treatment of prostatic hyperplasia.

BACKGROUND: To assess the ejaculatory disorder caused by silodosin in the prostatic hyperplasia patients who carry out sexual actions (sexual intercourse, masturbation). METHOD: The subjects of this study were 91 patients who had been clinically diagnosed to have LUTS/BPH at this hospital, who were administered silodosin at 4 mg twice a day, and who gave response to a questionnaire survey related to ejaculatory disorder. Sexual intercourse and masturbation were regarded as sexual actions in this study. RESULTS: Ejaculatory disorder occurred in 38 (42%) of the 91 silodosin administration cases. Forty (44%) of the 91 patients answered that they carried out sexual actions after oral intake of silodosin. When the investigation was conducted only in those who exercised sexual actions, ejaculatory disorder was observed in 38 (95%) of these 40 patients, indicating a high incidence. When asked if disturbed by the ejaculatory disorder, 29 (76%) of the 38 patients who had ejaculatory disorder answered yes. Oral silodosin was discontinued due to the ejaculatory disorder in 2 (5%) of these patients. On the whole, the discontinuation rate of oral silodosin was 2% (2/91 patients). CONCLUSION: It was demonstrated that the administration of silodosin induced ejaculatory disorder at a high incidence. Since it is possible that the high frequency of ejaculatory disorder by silodosin may reduce QOL, it is considered necessary to provide sufficient information related to ejaculatory disorder at the time of treatment with silodosin.

Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience.

BACKGROUND: The significance of combination of docetaxel (DTX) with estramustine phosphate (EMP) in castration-resistant prostate cancer (CRPC) patients remains unclear. In this study, we aimed to retrospectively evaluate the efficacy and toxicity of DTX with or without EMP and to elucidate the significance of DTX and EMP combination therapy in Japanese EMP-refractory CRPC patients. METHODS: To compare the efficacy and toxicity of DTX and EMP, we divided CRPC patients, who were confirmed to be resistant to EMP, into the following two groups: group D (n = 28), which included patients treated with DTX (60 mg/m2, once in every four weeks) alone, and group DE (n = 33), which included patients treated with a combination of DTX (60 mg/m2, once in every four weeks) and EMP (twice daily oral administration at 280 mg). RESULTS: Prostate specific antigen (PSA) response (> 50% decline in PSA) was observed in six patients (21%) in group D and eight patients (24%) in group DE. The median time to progression (TTP) was 12.0 months and 6.2 months and the median overall survival (OS) was 26.4 months and 24.3 months in group D and DE, respectively. There was no statistical difference between the two groups in terms of PSA response, TTP, and OS. The incidence of adverse events of grade 3/4 was low in both the groups, and there was no statistical difference between the two groups. CONCLUSIONS: Although treatment with DTX at 60 mg/m2 was effective and highly tolerated in EMP-refractory Japanese CRPC patients, the DTX and EMP combination therapy might not exhibit any survival benefit for CRPC patients.

Life-threatening anaphylaxis to leuprorelin acetate depot: case report and review of the literature.

Gonadotropin-releasing hormone analog depots have been widely used for a variety of diseases including prostate cancer, breast cancer, endometriosis, uterine leiomyomas, and central precocious puberty. Most of the side/adverse effects of gonadotropin-releasing hormone analog depots, such as leuprorelin acetate depot, are related to hypotestosteronism in males. Anaphylaxis to gonadotropin-releasing hormone analog depot is extremely rare. We present the first case report of a Japanese man who developed anaphylaxis to leuprorelin acetate depot during the treatment of metastatic prostate cancer and recovered successfully by conservative treatment. A drug-lymphocyte stimulation test showed that not only leuprorelin acetate itself, but also its vehicle polylactic and glycolic acids, might be responsible for the anaphylaxis to leuprorelin acetate depot. Because anaphylaxis can be lethal, the present case suggests that one should bear in mind the possibility of anaphylaxis in all patients who receive gonadotropin-releasing hormone analog depot and monitor such patients carefully.

Clinical efficacy of primary combined androgen blockade for Japanese men with clinically localized prostate cancer unsuitable for local definitive treatment: a single institution experience.

BACKGROUND: Primary hormonal therapy has been mostly used for patients with advanced prostate cancer, as international guidelines do not recommend its use for patients at earlier disease stages. However, there seems to be a discrepancy between the guideline recommendations and clinical practice on the use of primary androgen deprivation therapy for localized prostate cancer in Japan. Therefore, we retrospectively analyzed a single-institution experience in primary combined androgen blockade (CAB) for localized prostate cancer. PATIENTS AND METHODS: The study included 187 patients with T1c-T3a prostate cancer unsuitable for local definitive treatment and treated with primary CAB. Clinical outcomes, predictive factors of PSA relapse and adverse events were investigated. RESULTS: The progression-free, disease-specific, and overall survival rates of all patients at 5 years were 63.0, 99.4 and 95.9%, respectively. Of the several parameters isolated as predictors of prostate-specific antigen (PSA) progression, nadir PSA level and the percentage of positive biopsy cores (%PBC) remained as independent prognostic factors on multivariate analysis. Toxicities were mild to moderate and well tolerated. CONCLUSIONS: Primary CAB treatment brought initial disease control without relapse in the majority of our selected cases. The %PBC may help predict time to relapse in the pretreatment setting. The results implicate that CAB can be an option as a primary treatment for clinically localized prostate cancer unsuitable for local definitive treatment. To confirm the exact efficacy of primary CAB, these findings should be reviewed in a large cohort of patients with long-term follow-up from various viewpoints, including disease control, toxicities, quality-of-life and medical cost.

[Effect of local cooling at injection site of goserelin acetate for pain relief].

OBJECTIVE: The objective of this study was to assess the usefulness of ice cubes and vapocoolant spray for relieving pain induced by goserelin acetate injections. MATERIAL AND METHOD: Fourty-seven patients with prostate cancer receiving hormonal manipulation by goserelin acetate were enrolled in this study. They received goserelin acetate injections after analgesic pretreatments with ice cubes until March 2009, and with vapocoolant spray and ethyl chroride after April 2009. We had them fill out a questionnaire asking whether they preferred to continue cooling pretreatments. We assessed the pricking pain using the face scale(FS)and the numerical rating scale(NRS). RESULT: The median FS and NRS scores at the first pretreatment(ice cube or vapocoolant spray)were lower than those at no pretreatment(p<0. 01 in both scores). Thirty-nine patients(83. 0%)preferred cooling pretreatment. Only 5 patients preferred no pretreatment. The differences in the median FS score and NRS score between ice cubes and vapocoolant spray were not significant(p=0. 353 in FS, p=0. 120 in NRS). No adverse events associated with the cooling pretreatment occurred except for late-onset subcutaneous hemorrhages in 2 cases. CONCLUSION: The local cooling at the injection site of goserelin acetate was effective irrespective of the method(ice cube or vapocoolant spray)for the relief of pricking pain without causing serious complications.