Oral 5-aminolevulinic acid-mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A multicenter phase III study.

OBJECTIVE: To confirm the reproducibility of the effectiveness and safety in photodynamic diagnosis of non-muscle-invasive bladder cancer using 5-aminolevulinic acid in a prospective multicenter non-randomized phase III trial. METHODS: A total of 61 patients with primary or recurrent non-muscle-invasive bladder cancer were prospectively enrolled from five hospitals between May 2015 and March 2016. 5-Aminolevulinic acid (20 mg/kg) was orally administered 3 h before transurethral resection of bladder tumors using white light or fluorescent light. Of 60 evaluable patients, 511 specimens were obtained from tumor-suspicious lesions and normal-looking mucosa. The primary end-point was sensitivity. The secondary end-points were specificity, positive and negative predictive values, and safety. RESULTS: The sensitivity of the fluorescent light source (79.6%) was significantly higher (P < 0.001) than that of the white light source (54.1%). In total, 25.4% (46/181) of tumor specimens were diagnosed as positive with only the fluorescent light source. In nine (15%) of 60 patients, the risk classification and recommended treatment after transurethral resection of bladder tumors were changed depending on the additional types of tumor diagnosed by the fluorescent light source. The specificity of the fluorescent light versus white light source was 80.6% versus 95.5%. No grade 4-5 adverse event was noted. Hypotension and urticaria were severe adverse events whose relationship to oral 5-aminolevulinic acid could not be excluded. CONCLUSIONS: These findings confirm the diagnostic efficacy and safety of photodynamic diagnosis with 20 mg/kg of oral 5-aminolevulinic acid, and show that transurethral resection of bladder tumors with a fluorescent light source using oral 5-aminolevulinic acid is well tolerated.

Reduced expression of the DNA glycosylase gene MUTYH is associated with an increased number of somatic mutations via a reduction in the DNA repair capacity in prostate adenocarcinoma.

8-Hydroxyguanine (8OHG), a major oxidative DNA lesion, is known to accumulate in prostate cancer; however, the status of one of its repair enzymes, MUTYH, in prostate cancer remains to be elucidated. In this study, we showed that the expression levels of MUTYH mRNA and protein were significantly lower in prostate cancer than in non-cancerous prostatic tissue by examining two independent, publicly available databases and by performing an immunohistochemical analysis of prostate cancer specimens obtained at our hospital, respectively. About two-thirds of the prostate cancers exhibited a reduced MUTYH expression. When the effect of reduced MUTYH expression in prostate adenocarcinoma on the somatic mutation load was examined using data from the Cancer Genome Atlas (TCGA) database, the numbers of total somatic mutations and somatic G:C to T:A mutations were significantly higher in the reduced MUTYH expression group than in the other group (P < 0.0001 and P = 0.0013, respectively). To determine the reason why reduced MUTYH expression leads to somatic mutation loads in prostate adenocarcinoma, we compared the DNA repair capacities between PC-3 prostatic cell line derived clones with different MUTYH expression levels. Both the capacities to cleave DNA containing adenine:8OHG mispairs and to suppress mutations caused by 8OHG were significantly lower in prostatic cell lines with lower MUTYH expression than in prostatic cell lines with higher MUTYH expression. These results suggested that reduced MUTYH expression is associated with somatic mutation loads via a reduction in DNA repair capacity in prostate adenocarcinoma. © 2016 Wiley Periodicals, Inc.

Systematic regional lymph node dissection for upper tract urothelial carcinoma improves patient survival.

OBJECTIVE: Unlike for bladder cancer, the impact of regional lymph node dissection for upper tract urothelial carcinoma is unclear. We explored whether patient survival was influenced by systematic regional lymph node dissection, using resection templates according to the main tumor location, during radical nephroureterectomy for upper tract urothelial carcinoma. METHODS: The systematic regional lymph node dissection group was defined as cases in which the dissection of nodes and surrounding tissues followed the established template, and the non-systematic regional lymph node dissection group as cases undergoing limited or no lymph node dissection. We performed radical nephroureterectomy on 98 consecutive patients with various stages of upper tract urothelial carcinoma from May 1994 to September 2014 at our institution. Of these, 77 patients with cTanyN0M0 of upper tract urothelial carcinoma undergoing radical nephroureterectomy were grouped into systematic regional lymph node dissection or non-systematic regional lymph node dissection cohorts according to the extent of dissection, and their outcomes compared. RESULTS: Forty-four patients were categorized as systematic regional lymph node dissection and 33 as non-systematic regional lymph node dissection, including 17 with more limited nodal dissection and 16 with no nodal dissection. Five-year recurrence-free survival and cancer-specific survival were significantly higher in the systematic regional lymph node dissection (93% and 94%, respectively) than in the non-systematic regional lymph node dissection group (75% and 77% recurrence-free survival and cancer-specific survival, respectively). Further, 5-year recurrence-free survival and cancer-specific survival of muscle-invasive upper tract urothelial carcinoma (pT2-4) were significantly higher in the systematic regional lymph node dissection (87% and 91%, respectively) than in the non-systematic regional lymph node dissection group (59% and 62%, respectively) (P = 0.0237 and P = 0.0224). Neither recurrence-free survival nor cancer-specific survival was significantly prolonged by systematic dissection in patients with pTis-1 histology. CONCLUSIONS: Systematic regional lymph node dissection during radical nephroureterectomy for cTanyN0M0 upper tract urothelial carcinoma patients has a significantly beneficial impact on survival compared with patients undergoing more limited dissection, especially in the cases involving muscle invasion.

[Evaluation of CT-Guided Percutaneous Needle Biopsy for Diagnosis of Renal Tumor].

We performed computed tomographic (CT)-guided percutaneous needle biopsy for renal tumors that were difficult to diagnose or were inoperable malignant renal tumors. Nineteen patients who underwent CT-guided percutaneous needle biopsy between November 2007 and March 2015 at Hamamatsu University Hospital were included in this study. The median tumor diameter was 78 mm (40-140 mm). Seventeen patients were diagnosed pathologically by biopsy, but 2 patients could not be diagnosed despite the existence of adequate sample volume. One patient had an adverse complication ; fever (CTCAE ver 4.0 grade 1). The median duration of follow-up was 21 months (0-111 months), no one had tumor seeding along a needle tract. CT-guided percutaneous needle biopsy of renal tumors is helpful for pathological diagnosis and further treatment planning. However, there are still some limitations to obtain an accurate diagnosis.

The expression of ß3-adrenoceptors and their function in the human prostate.

BACKGROUND: Little is known about ß3-adrenoceptor (AR) expression and function in human prostate. We examined the expression and distribution of ß-AR subtypes in normal prostate and benign prostatic hyperplasia (BPH) tissues, and investigated which selective ß-AR subtype agonist was most involved in the relaxation of isolated human prostate strips. METHODS: Messenger RNA (mRNA) expression for ß1-, ß2-, and ß3 -ARs was investigated using reverse transcriptase-polymerase chain reactions (RT-PCR). Quantitative analysis of mRNA expression of ß-AR subtypes between normal prostate and BPH tissues was performed using quantitative RT-PCR (qPCR). Distributions were examined by immunohistochemistry (IHC). Strips of human normal prostate or BPH were suspended in organ baths and exposed to isoproterenol, dobutamine, procaterol, and TRK-380 to investigate their relaxant effects on KCl-induced contractions, and their inhibitory effects on electrical field stimulation (EFS)-induced contractions. RESULTS: We confirmed the presence of mRNA for ß1-, ß2-, and ß3-ARs both in normal prostate and in BPH tissues. For ß3-AR, mRNA expression in BPH tissues was significantly higher than in normal prostate tissues, but there was no significant difference in ß1- and ß2-AR expression between normal and BPH tissues. IHC revealed differences in staining intensity between smooth muscle cells and glandular cells, with different proportions for different ß-AR subtypes. Staining of ß3-AR was particularly intense in smooth muscle cells as opposed to glandular cells. Isoproterenol and TRK-380 significantly decreased the tone of KCl-induced contractions of the normal prostate strips. The rank order of relaxant effects was isoproterenol > TRK-380 > procaterol > dobutamine. All selective ß-AR agonists significantly decreased the amplitude of EFS-induced contractions of the normal prostate strips. The rank order of inhibitory effects was isoproterenol > dobutamine >TRK-380 > procaterol. In BPH strips, all selective ß-AR agonists showed no significant relaxant or inhibitory effects on KCl- or EFS-induced contractions. CONCLUSIONS: ß3 -AR is abundant in human prostate smooth muscle, whose relaxation is mediated by ß1- and ß3-AR stimulation. ß3-AR agonists may have clinical use in the treatment of male non-BPH patients or neurogenic bladder patients with voiding dysfunction.

Comparison of mirabegron and imidafenacin for efficacy and safety in Japanese female patients with overactive bladder: A randomized controlled trial (COMFORT study).

OBJECTIVES: To evaluate the efficacy and safety of mirabegron compared with imidafenacin for the treatment of female patients with overactive bladder. METHODS: Patients (n = 89) were randomized to receive 0.1 mg imidafenacin twice daily (n = 47) or 50 mg mirabegron once daily (n = 42) for 12 weeks. The primary efficacy end-point was change in total Overactive Bladder Symptom Score. Secondary efficacy end-points included change in Overactive Bladder Symptom Score, 3-day micturition diary, International Prostate Symptom Score and Overactive Bladder Questionnaire. Safety assessments included adverse events, vital signs, post-void residual volume and patient-reported incidence, and severity of distinctive symptoms related to adverse events. RESULTS: The mirabegron group showed a significantly reduced mean total Overactive Bladder Symptom Score from baseline, but no significant differences were noted in change of total Overactive Bladder Symptom Score compared with the imidafenacin group. Significant improvements in secondary efficacy end-points were observed regarding the mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, total International Prostate Symptom Score and quality of life in both groups, with no significant differences between the groups. The overall incidence of adverse events and the incidence of dry mouth were significantly higher in the imidafenacin group than in the mirabegron group. Patient-reported incidence and the severity of dry mouth were significantly exacerbated in the imidafenacin group. CONCLUSIONS: Treatment with 50 mg mirabegron once daily effectively relieves overactive bladder symptoms in women with fewer adverse events than treatment with antimuscarinics.

[Strangulation of the Penis by Four Metallic Washers].

We report here a case of strangulation of the penis. A 69-year-old male visited our hospital suffering from a swollen penis and dysuria after installation of four metallic washers to the penis. He had mischievously put them on his penis four days before and subsequently was unable to remove them. We found erosion on the surface of the penis, reduction in blood flow by ultrasonography, and high C-reactive protein levels. Because we could not remove washers by blood removal from glans penis or ring cutter, we performed percutaneous cystostomy and then cut the washers with an electric grinder under general anesthesia. The operation took 2 hours and 25 minutes. The postoperative course was uneventful. Neither disturbance of blood flow nor urethral stricture was found. He completely recovered without erectile dysfunction or difficult urination 7 months after the operation. Management of this rare condition is discussed.

Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer.

BACKGROUND: We previously reported the pharmacokinetic profile and preliminary tolerability of cabazitaxel in a phase I study in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Here we report the final safety profile and anti-tumor activity of cabazitaxel in a larger population, including all patients enrolled in the expansion cohort of the study. METHODS: Japanese patients with mCRPC previously treated with docetaxel received cabazitaxel intravenously every 3 weeks plus daily prednisolone. In patients treated with the maximum tolerated dose of 25 mg/m(2) we evaluated adverse events including treatment-related neutropenia, prostate-specific antigen (PSA) response and objective response. RESULTS: In total, 44 patients were treated with the maximum tolerated dose. The most frequent adverse events (any grade) were neutropenia (100 %), febrile neutropenia (54.5 %), fatigue (54.5 %), nausea (52.3 %) and diarrhea (50.0 %). There were no deaths due to treatment-related adverse events. Neutropenia with prior docetaxel did not appear to influence the probability of febrile neutropenia with cabazitaxel. Most patients received therapeutic granulocyte colony-stimulating factor (G-CSF; cycle 1: 86.4 %; cycle 2 or later: 81.8 %). In the efficacy population, two of 12 patients with measurable disease had partial response (objective response rate: 16.7 %), while 10 had stable disease. PSA response rate was 29.3 % (12/41 patients). Median time to PSA progression was 3.68 months (95 % confidence interval 1.35-4.63). CONCLUSIONS: In this heavily pretreated Japanese population, the occurrence of neutropenia and febrile neutropenia was high, suggesting G-CSF prophylaxis may be required as part of toxicity management. However, the efficacy of cabazitaxel was consistent with global studies. ClinicalTrials.gov identifier: NCT01324583.

Laparoscopic simultaneous bilateral adrenalectomy for testosterone-secreting bilateral adrenal tumors.

Laparoscopic adrenalectomy is widely accepted as a safe and minimally-invasive procedure. Although it is a standard procedure for the surgical treatment of adrenal tumors, its simultaneous use with bilateral adrenalectomy is relatively rare. A 21-year-old woman was referred to Hamamatsu University School of Medicine University Hospital complaining of a deepening voice, hirsutism and secondary amenorrhea. Abdominal computed tomography showed bilateral adrenal tumors, and hormonal examinations showed that the tumors secreted excessive testosterone, resulting in virilizing symptoms. Laparoscopic simultaneous bilateral adrenalectomy was carried out. Postoperatively, serum testosterone levels immediately recovered to within the normal range. Menstruation began the month after the operation, and the hirsutism gradually regressed. This is the third reported case of bilateral virilizing adrenal tumors, and the first to be successfully treated with laparoscopic simultaneous bilateral adrenalectomy.

[Suicide attempt by an interstitial cystitis patient : a case report].

We report a suicide attempt by an interstitial cystitis patient. A 68-year-old woman consulted several clinics with complaints of urinary frequency and bladder pain, but her symptoms did not improve. She was admitted to our hospital and diagnosed with interstitial cystitis. Hydrodistention was performed, and the urethral catheter removed one day after surgery. The next day, the patient was afraid that her symptoms had not improved and, due to this physical and mental distress, cut her wrist with a razor. Vascular anastomosis and neuroanastomosis were performed accordingly. Eighteen months after hydrodistention, the patient's symptoms of interstitial cystitis have much improved.

[Chemotherapy for CRPC].

Cabazitaxel, new chemotherapeutic agent for castration resistant prostate cancer (CRPC) treated after docetaxel, was developed. In addition, new hormonal drugs for CRPC, such as enzalutamide and abiraterone were also approved in Japan recently. Treatment strategy for CRPC using these drugs is still controversial, therefore we need much more clinical data of Japanese patients with CRPC. Management of this severe condition and future of prostate cancer were discussed.

Relationship Between Adverse Events and Progression-free Survival in Patients Receiving Cabozantinib for Previously Treated Metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: Although the adverse events (AEs) of drugs, such as sunitinib and axitinib, have been shown to predict treatment responses, evidence to support cabozantinib-induced AEs as predictors of responses to treatment for metastatic renal cell carcinoma (mRCC) is limited. Therefore, we herein investigated the relationship between AE profiles and progression-free survival (PFS) in patients receiving cabozantinib for previously treated mRCC. PATIENTS AND METHODS: The present study retrospectively analyzed 40 patients receiving cabozantinib for previously treated mRCC between July 2020 and August 2022. PFS was estimated using the Kaplan-Meier method and the impact of several parameters, including cabozantinib-induced AEs, on PFS was investigated by a Cox proportional regression analysis. RESULTS: The median observation period was 15 (2-29) months, during which time 31 patients (77.5%) progressed, with median PFS of 11 months. Thirty-nine patients (97.5%) developed at least one AE. Liver toxicity occurred in 16 patients (40.0%) and hand-foot syndrome, hypertension, and diarrhea in 14 each (17.5%). Only hypertension correlated with longer PFS. A multivariate analysis identified hypertension as an independent prognostic factor for PFS (p=0.049). CONCLUSION: These results suggest the potential of treatment-induced hypertension as a significant predictor of prolonged PFS in patients receiving cabozantinib for mRCC.

Interindividual variations in aprepitant plasma pharmacokinetics in cancer patients receiving cisplatin-based chemotherapy for the first time.

The pharmacokinetics of aprepitant, a neurokinin-1 receptor antagonist, have not been fully evaluated in clinical settings. The aim of this study was to characterize the plasma pharmacokinetics of aprepitant and reveal their influence of laboratory tests and cytochrome P450 (CYP) 3A5 gene polymorphisms in cancer patients. Forty-four Japanese cancer patients receiving cisplatin-based chemotherapy for the first time following oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) were enrolled. The patients did not have gastrointestinal disease and the clinical laboratory values were within their normal reference levels. The plasma concentrations of aprepitant 24 (day 2 predose), 72, and 120 h after the first aprepitant administration were determined using LC-MS/MS. The relationships between plasma exposure to aprepitant and body weight, clinical laboratory values, age, gender, or CYP3A5*3 were investigated. The median and interquartile ranges of the 120-h area under the plasma concentration time curve (AUC)(0-120) of aprepitant were 73215 and 55518-91121 ng h/mL. The coefficient of variation value for aprepitant AUC(0-120) was 53%. The AUC(0-120) of aprepitant was correlated with the levels of total bilirubin and serum albumin, respectively (r=0.454, p<0.01 and r=0.287, p=0.06), but not with other non-genetic factors and CYP3A5 genetic variants in a univariate analysis. The AUC(0-120) of aprepitant was significantly correlated with the level of total bilirubin (adjusted R(2)=0.187, p<0.01) in a multivariate analysis. In conclusion, the plasma pharmacokinetics of aprepitant varied markedly in cancer patients receiving cisplatin-based chemotherapy for the first time and were correlated with the level of total bilirubin.

[Long-term survival of metastatic clear cell adenocarcinoma of the female urethra by multidisciplinary treatment: a case report].

We report a case of clear cell adenocarcinoma of the female urethra. A 57-year-old woman presented with complaint of gross hematuria. Abdominal ultrasonography, cystourethroscopy, computed tomography (CT) and magnetic resonance imaging (MRI) revealed the urethral tumor was invasive to bladder neck. Clinical stage was determined as cT3N1M0, then anterior pelvic exenteration and ileal conduit formation were performed. The pathological diagnosis was clear cell adenocarcinoma of urethra and the stage was pT3N1. The patient received TS-1 and cisplatin for postoperative recurrence, but she died from multiple lung metastasis 54 months after the operation. Clear cell adenocarcinoma of the female urethra is rare case in the Japanese literatures. Pathogenesis and management of this rare condition are discussed.

[Bilateral adrenal hemorrhage due to adrenal metastasis of lung cancer].

A 58-year-old man presented with nausea and left flank pain. The patient was referred to our hospital based on clear detection of anemia and computed tomography findings of bilateral adrenal tumors with hemorrhage and a mass in the apex of the left lung. Right adrenal artery embolization had no effect on enlargement of the right adrenal hematoma or advanced anemia. Right adrenalectomy was then performed in an attempt to control hemorrhaging and make a definitive diagnosis, and the patient's anemia improved following the operation. Histopathological diagnosis suggested adrenal metastasis of lung adenocarcinoma, which was subsequently diagnosed given similarities in transbronchial biopsy findings to those in the right adrenal gland. Adrenal hemorrhage due to metastasis of lung cancer is an extremely rare condition; indeed, to our knowledge, the present case is only the 26th reported worldwide. However, prognosis for this mortal condition may be improved should patients receive adrenalectomy followed by an appropriate treatment regimen.

[Salvage therapy for castration-refractory prostate cancer resistant to docetaxel].

OBJECTIVES: To evaluate the treatment for castration-refractory prostate cancer (CRPC) resistant to docetaxel MATERIALS AND METHODS: Among 45 patients with CRPC treated with docetaxel (70-75 mg/m2) every 3 to 4 weeks at Hamamatsu University Hospital from January 2004 to July 2012, 19 patients underwent salvage treatments. We retrospectively analyzed the medical records of 14 patients except for 5 patients who were enrolled in clinical trials. RESULTS: The median age and serum prostate-specific antigen (PSA) level at starting salvage treatments was 71 years (range 45 to 79) and 241.1 ng/mL (range 3.06 to 1,643.0), respectively. All patients maintained castration status. Salvage treatments include DTX (30 mg/m2) + cisplatin (CDDP) (70 mg/m2)/carboplatin (Area under the curve = 4), etoposide + CDDP, paclitaxel + CDDP, cyclophosphamide, S-l, tegaful-uracil. The reasons why 14 patients moved to salvage treatments after DTX were progressive disease in 12 patients and adverse events in 2. Eight patients had a PSA response, 3 patients>50% and 5 patients<50%. Six patients had a PSA progression. The median overall survival was 10.4 months (range 4.1 to 27.3). All patients died of cancer, 13 patients with prostate cancer and one patient with lung adenocarcinoma. Most adverse events were mild. Transitory grade 3 leukopenia was observed in 2 patients, and grade 3 anemia in 2. No grade 4 toxicities were noted. CONCLUSIONS: All salvage treatments without grade 4 toxicities described in this study may be acceptable in the patients with CRPC progressing after docetaxel although the effect would be limited.

The cost of antiemetic therapy for chemotherapy-induced nausea and vomiting in patients receiving platinum-containing regimens in daily practice in Japan: a retrospective study.

PURPOSE: The objective of this study was to estimate the cost of antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in daily practice in Japan. METHODS: This was a retrospective observational study using medical records. Eligible patients were those with bladder or testicular cancer receiving platinum-containing highly emetogenic chemotherapy. The incidence of CINV on days 1-5 in single-day chemotherapy and on days 1-9 in multiple-day chemotherapy, and the costs of antiemetic therapy directly associated with the administration of antiemetics were estimated. The analysis of costs was performed from a hospital perspective. RESULTS: A total of 54 patients or 169 chemotherapy courses were included. In all chemotherapy courses 5-HT(3) receptor antagonists were used on the day(s) that platinum-containing agents were administered and frequently used on subsequent days. In contrast, the use of corticosteroids was infrequent. Acute CINV in single-day chemotherapy was well controlled, but the incidences of delayed CINV in single-day chemotherapy and CINV in multiple-day chemotherapy were relatively high. The costs for antiemetic therapy were $484.65 in courses with CINV and $318.56 in courses without CINV, and the difference was approximately $170 per chemotherapy course, which was considered to be mainly imputable to the prevalence of CINV. CONCLUSIONS: The cost of antiemetic therapy for CINV is substantial in Japan as well as in other countries, and it is suggested that the onset of CINV is a possible cost driver. The improvements in antiemetic therapy may contribute not only to improved patient well-being but also to a reduction of economic burden.

[A clinical study of laparoscopic adrenalectomy for pheochromocytoma--analysis of clinical parameters influencing operative time and intraoperative systolic blood pressure].

PURPOSE: We retrospectively analyzed the preoperative clinical parameters which influence operative time and intraoperative maximum systolic blood pressure in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. MATERIALS AND METHODS: Between January 1992 and September 2010, we performed 28 laparoscopic adrenalectomies for pheochromocytoma at Hamamatsu University School of Medicine. These 28 cases were characterized based on the following parameters: body mass index (BMI), tumor size, history of hypertension, preoperative blood pressure, serum concentration of catecholamine, and 24-h urinary excretion of catecholamine metabolite. We retrospectively analyzed whether or not these parameters influenced operative time or intraoperative maximum systolic blood pressure. RESULTS: All 28 cases of laparoscopic adrenalectomy were performed safely and without intraoperative complications and needed neither blood transfusion nor conversion to laparotomy. The median operative time was 203 minutes, and intraoperative hypertension (systolic blood pressure > 200 mmHg) occurred in 46% (13/28) of cases. Median day of discharge in all patients was post-operative day 5. Significant positive correlation was shown between tumor size and operative time and between intraoperative maximum systolic blood pressure and serum concentration of catecholamine or 24-h urinary excretion of catecholamine metabolite (p < 0.05). CONCLUSION: The lengthened operative time for large tumors and elevated intraoperative blood pressure for tumors with high preoperative catecholamine activity necessitate careful perioperative management in patients receiving laparoscopic adrenalectomy for pheochromocytoma.

Should ipsilateral solitary adrenal involvement in renal cell carcinoma be staged as M1?

OBJECTIVE: In 2009, the TNM classification of malignant tumors was revised, and the renewal of the T2-4 stage in renal cell carcinoma was adopted. To date, however, the staging of ipsilateral solitary adrenal involvement in renal cell carcinoma has not been sufficiently evaluated. METHODS: We retrospectively reviewed the adrenal involvement in renal cell carcinoma among 1033 patients admitted to the Department of Urology at Hamamatsu University Hospital, Japan, and affiliated hospitals between 1978 and 2007. RESULTS: We identified 23 of the 1033 patients (2.2%) with adrenal involvement in renal cell carcinoma. In renal cell carcinoma patients with adrenal involvement, a tendency for a high histological grade of tumor and lower overall survival (P< 0.0001) was observed. Ipsilateral solitary adrenal involvement was detected in 4 of the 23 patients (15%), whereas 2 of the 23 (9%) had direct invasion of the adrenal gland. All tumors in the 14 patients without ipsilateral solitary adrenal involvement and recurrent adrenal tumors were classified as Stage IV. The TNM classification of the four renal cell carcinoma patients with ipsilateral solitary adrenal involvement was determined to be either pT3N0M0 or pT1-3N0M1. Among the four patients with ipsilateral solitary adrenal involvement, three patients had recurrent tumors, despite complete surgical resection. Two of these patients died of metastatic renal cell carcinoma after 2 and 10 years of radical nephrectomy, respectively, whereas one was still alive with cancer 3 years after the initial radical nephrectomy. The fourth had no recurrence of renal cell carcinoma, but did develop synchronous gall bladder cancer (pT2N0M0) and bile duct cancer (pT2N0M0). CONCLUSIONS: Adrenal involvement in primary renal cell carcinoma was observed more frequently in patients with advanced tumor stages. In the TNM classification system, we propose that ipsilateral solitary adrenal involvement in renal cell carcinoma should be staged as M1.