Transperitoneal laparoscopic umbilical resection of urachal remnants: a feasible surgical method.

BACKGROUND: To date, there is no standard established laparoscopic surgical method for managing urachal remnants because of their rarity, and several questions remain unanswered. Are there any problems for considering the operative indications about patients' factors for example, body mass index and so on? This study aimed to determine the feasible surgical method for managing urachal remnants and presents the operative outcomes of our cases in relation to the findings from the existing literature. METHODS: We analyzed the data of 16 patients (7 women and 9 men; age range, 19-48 years) who underwent surgery for urachal remnants between January 2013 and March 2019 at our institution. RESULTS: In our cases, all urachal remnants were urachal sinuses, and the primary complaints were umbilical pain and pus discharge. Most of these symptoms were controlled using umbilical drainage and oral antibiotic intake; however, incisional drainage was required in two cases. In all cases, we performed a laparoscopic resection of the urachal remnants; one patient underwent an open conversion due to a very thick abdominal wall. Therefore, "peri-umbilical distanse" was proposed as an index to verify the periumbilical abdominal wall thickness. This index may clear the difficulties of the laparoscopic resection of the urachal remnunts. A postoperative complication-local infection that was treated using re-suturing-was observed in one patient. No adverse events occurred in the other cases. Our method was appropriate because it allowed for complete urachal resection with good cosmetic results, i.e., a small and natural scar appearance. Additionally, if bladder injury occurred, bladder re-suturing was easily possible because of the laparoscopic port's position. CONCLUSIONS: We present an feasible method for laparoscopic urachal resection. This method may be recommended for young patients with an peri-umbilical distanse of < 2 cm.

Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival.

BACKGROUND: Adenosine and its adenosine 2A receptors (A2AR) mediate the immunosuppressive mechanism by which tumors escape immunosurveillance and impede anti-tumor immunity within the tumor microenvironment. However, we do not know whether the adenosine pathway (CD39/CD73/A2AR) plays a role in renal cell carcinoma (RCC). Therefore, we studied the role of immunosuppression in RCC by assessing the adenosine pathway in patients with RCC treated with anti-vascular endothelial growth factor (anti-VEGF) agents or immune checkpoints inhibitors (ICIs) or both. METHODS: In 60 patients with metastatic RCC, we examined the expression of CD39, CD73, A2AR, and programmed cell death 1 ligand 1 (PD-L1) immunohistochemically in surgically resected tumor tissues and studied the clinicopathological characteristics of these patients. Patients were treated by cytoreductive nephrectomy with systemic therapy with anti-VEGF agent or a combination of the ICIs anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody and programmed cell death 1 (PD-1) antibody. RESULTS: Increased expression of A2AR in the primary tumors was associated with metastatic profiles. Patients treated with anti-PD-1 antibody in monotherapy, a combination of anti-PD-1 and anti-CTLA4 antibodies, or anti-VEGF agents showed better response and longer overall survival if the primary tumor had higher PD-L1 expression and lower A2AR expression. In Cox multivariate regression analysis, higher expression of A2AR was associated with shorter overall survival. CONCLUSIONS: Our findings suggest that the expression of A2AR and PD-L1 in the primary tumors in RCC might predict the outcomes of treatment with anti-VEGF agents and ICIs and that the A2AR pathway might be a molecular target for immunotherapy.

Association of cancer progression with elevated expression of programmed cell death protein 1 ligand 1 by upper tract urothelial carcinoma and increased tumor-infiltrating lymphocyte density.

BACKGROUND: Increased expression of programmed cell death 1 ligand 1 (PD-L1) by tumor cells is thought to be a mechanism through which solid cancers promote immune tolerance. However, the association between PD-L1 expression and the prognosis of upper urinary tract urothelial carcinoma (UTUC) remains unknown. METHODS: We examined immunohistochemical PD-L1 expression and the tumor-infiltrating lymphocyte density (TILD) in 79 patients with UTUC who underwent nephroureterectomy. We classified the tumors into four types based on the combination of PD-L1 expression and TILD, and studied the clinicopathological characteristics of these four tumor types. RESULTS: Elevated expression of PD-L1 by tumor cells and a higher TILD were associated with a worse histological grade, higher pT stage, and higher peripheral blood neutrophil-to-lymphocyte ratio. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer differentiation and local invasion. These three variables were associated with shorter progression-free survival and overall survival in univariate analysis, but only the latter was an independent determinant according to multivariate analysis. The patients who had type II tumors with lower PD-L1 expression and a lower TILD showed more favorable survival than the other three groups. CONCLUSIONS: These findings suggest that PD-L1 expression and TILs in the tumor microenvironment influence the progression of UTUC. Accordingly, it is important to understand the immunologic characteristics of the tumor microenvironment to develop more effective treatment strategies for this cancer.

Association between serum prostate-specific antigen level and diabetes, obesity, hypertension, and the laboratory parameters related to glucose tolerance, hepatic function, and lipid profile: implications for modification of prostate-specific antigen threshold.

BACKGROUND: Previous studies indicated inverse relationships between body mass index (BMI), diabetes and prostate-specific antigen (PSA) concentration besides an established positive relationship between age and PSA. Other causal relationships between clinical parameters including hypertension, hepatic function, tests, lipid profile and PSA were also suggested. Thus, we incorporated these parameters all together into the analysis to identify possible determinants of PSA concentration to improve the accuracy of PSA tests. METHODS: Associations between PSA and the above-mentioned clinical parameters were examined among 14,486 men who visited our hospital for a routine health checkup, using linear regression analyses. RESULTS: Total of 1403 (9.7%) and 784 (5.4%) men were classified as diabetes and obesity, respectively. After adjusting age, significant PSA reductions were found in diabetic men, especially for men taking antidiabetics. Such association was seen when the diabetic status was represented by hemoglobin A1c (HbA1c) and fasting blood sugar (FBS) levels. That is, PSA levels were significantly reduced in men with higher HbA1c and FBS levels. Obesity was also associated with a reduction in PSA levels. Moreover, PSA levels were significantly decreased with increased ALT levels. CONCLUSIONS: PSA test results should be carefully interpreted especially for men with diabetes and obesity, in whom a substantial reduction in PSA concentration is likely to occur.

Immunohistochemical expressionof sodium-dependent glucose transporter - 2 (SGLT-2) in clear cell renal carcinoma: possible prognostic implications.

PURPOSE: Glucose is a major energy resource for tumor cell survival and growth, and its influx into cells is mainly carried out by facilitative glucose transporters (GLUTs). Sodium - dependent glucose transporters (SGLTs) have been highlighted as playing important roles in diabetic treatment. However, their potential roles in cancer remain unclear. We examined expression patterns of SGLTs in tumor tissues together with conventional pathological variables to determine prognostic significance in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Nephrectomy specimens were obtained from 68 patients. GLUT - 1, - 2 and SGLT - 1, - 2 expression in tumor and adjacent normal tissues were analyzed by immunohistochemical staining, and intensity was quantified using an image analyzer. RESULTS: The four glucose transporters evaluated were broadly distributed in tumor tissues as well as throughout the normal parenchyma. There was no significant correlation between transporter expression and conventional pathological variables. However, increased SGLT - 2 expression was significantly associated with shorter overall survival (p < 0.01), regardless of metastatic status. CONCLUSIONS: We propose possible prognostic significance of SGLT - 2 expression in human RCC. Given that glucose is a major energy resource for tumor cells and that glucose transport is largely mediated by SGLT, SGLT - 2 may serve as a possible therapeutic target in RCC.

Clinically significant association of elevated expression of nuclear factor E2-related factor 2 expression with higher glucose uptake and progression of upper urinary tract cancer.

BACKGROUND: There is growing evidence that the transcription factor nuclear factor E2-related factor 2 (Nrf2) is the major participant in regulating antioxidants and pathways for detoxifying reactive oxygen species (ROS), as well as having a vital role in tumor proliferation, invasion, and chemoresistance. It was also recently reported that Nrf2 supports cell proliferation by promoting metabolic activity. Thus, Nrf2 is involved in progression of cancer. Upper urinary tract urothelial carcinoma (UTUC) is a biologically aggressive tumor with high rates of recurrence and progression, resulting in a poor prognosis. However, the role of Nrf2 in UTUC is largely unknown. METHODS: In order to study the role of Nrf2 in UTUC from the metabolic perspective, we retrospectively assessed Nrf2 expression in the surgical specimen and the preoperative maximum standard glucose uptake (SUVmax) on [18F]fluorodeoxy-glucose positron emission tomography (18F-FDG-PET) of 107 patients with UTUC who underwent radical nephroureterectomy. RESULTS: Increased expression of Nrf2 in the primary lesion was correlated with less differentiated histology, local invasion, and lymph node metastasis, and was also an independent indicator of shorter overall survival according to multivariate analysis. Furthermore, increased expression of Nrf2 was associated with higher preoperative SUVmax by the primary tumor on 18F-FDG-PET, while Nrf2 expression and SUVmax were also significantly correlated in the metastatic lymph nodes. Among the 18 patients with lymph node metastasis at nephroureterectomy who underwent retroperitoneal lymph node dissection and received adjuvant chemotherapy, the patients with higher Nrf2 expression in the primary tumor had worse recurrence-free survival. CONCLUSIONS: These results suggest that constitutive activation of Nrf2 might be linked with tumor aerobic glycolysis and progression of UTUC, indicating that Nrf2 signaling in the tumor microenvironment promotes progression of UTUC.

Significance of sarcopenia as a prognostic factor for metastatic urothelial carcinoma patients treated with systemic chemotherapy.

BACKGROUND: Recently, numerous studies have reported an association between sarcopenia and poor outcomes in various kinds of malignancies. We investigated whether sarcopenia predicts the survival of patients with metastatic urothelial carcinoma who underwent systemic chemotherapy. METHODS: We reviewed 87 metastatic urothelial carcinoma patients who underwent chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin for cisplatin-unfit patients) between 2007 and 2015. A computed tomography scan prior to chemotherapy was used for evaluating sarcopenia, and we measured three cross-sectional areas of skeletal muscle at the third lumbar vertebra and calculated the skeletal muscle index (SMI), the paraspinal muscle index (PSMI), and the total psoas area (TPA) of each patient. Predictive values of survival were assessed using Cox regression analysis. RESULTS: The median overall survival (OS) was 16 months (95% CI 13.5-18). Although SMI alone was not a significant predictor of shorter OS (P = 0.117) in univariate analysis, SMI stratified by the value of the body mass index (BMI) was a significant predictor of shorter OS in univariate analysis (P = 0.037) and was also an independent predictor of shorter OS in multivariate analysis (P = 0.026). PSMI and TPA were not significant prognostic factors even when stratified by BMI (P = 0.294 and 0.448), respectively. CONCLUSION: Neither PSMI nor TPA could substitute SMI as a predictor for poor outcomes in metastatic urothelial carcinoma patients treated with systemic chemotherapy in our study. SMI stratified by BMI is a useful predictor of prognosis in these patients.

Increased serum level of soluble interleukin-2 receptor is associated with a worse response of metastatic clear cell renal cell carcinoma to interferon alpha and sequential VEGF-targeting therapy.

BACKGROUND: Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy. METHODS: We monitored the serum level of sIL-2R over time and examined phosphorylated Akt expression by the primary tumor in 47 patients with metastatic clear cell RCC (ccRCC) undergoing cytoreductive nephrectomy followed by first-line adjuvant therapy with IFN-alpha plus sequential VEGF-targeting therapy as second- or third-line adjuvant therapy. RESULTS: A preoperative increase of the serum level of sIL-2R was correlated with a higher preoperative serum level of programmed cell death 1 (PD-1)-ligand 1 (PD-L1), increased expression of phosphorylated Akt by the primary tumor, and a worse response to IFN-alpha/sequential VEGF-targeting therapy, as well as being an independent prognostic factor for a shorter overall survival time by multivariate analysis. Over time, the serum sIL-2R level largely reflected the tumor response to therapy. CONCLUSIONS: Monitoring the serum level of sIL-2R may help to predict the biological behavior of ccRCC, its response to IFN-alpha/sequential VEGF-targeting therapy, and the prognosis.

Performance characteristics of prostate-specific antigen density and biopsy core details to predict oncological outcome in patients with intermediate to high-risk prostate cancer underwent robot-assisted radical prostatectomy.

BACKGROUND: Many urologic surgeons refer to biopsy core details for decision making in cases of localized prostate cancer (PCa) to determine whether an extended resection and/or lymph node dissection should be performed. Furthermore, recent reports emphasize the predictive value of prostate-specific antigen density (PSAD) for further risk stratification, not only for low-risk PCa, but also for intermediate- and high-risk PCa. This study focused on these parameters and compared respective predictive impact on oncologic outcomes in Japanese PCa patients. METHODS: Two-hundred and fifty patients with intermediate- and high-risk PCa according to the National Comprehensive Cancer Network (NCCN) classification, that underwent robot-assisted radical prostatectomy at a single institution, and with observation periods of longer than 6 months were enrolled. None of the patients received hormonal treatments including antiandrogens, luteinizing hormone-releasing hormone analogues, or 5-alpha reductase inhibitors preoperatively. PSAD and biopsy core details, including the percentage of positive cores and the maximum percentage of cancer extent in each positive core, were analyzed in association with unfavorable pathologic results of prostatectomy specimens, and further with biochemical recurrence. The cut-off values of potential predictive factors were set through receiver-operating characteristic curve analyses. RESULTS: In the entire cohort, a higher PSAD, the percentage of positive cores, and maximum percentage of cancer extent in each positive core were independently associated with advanced tumor stage ≥ pT3 and an increased index tumor volume > 0.718 ml. NCCN classification showed an association with a tumor stage ≥ pT3 and a Gleason score ≥8, and the attribution of biochemical recurrence was also sustained. In each NCCN risk group, these preoperative factors showed various associations with unfavorable pathological results. In the intermediate-risk group, the percentage of positive cores showed an independent predictive value for biochemical recurrence. In the high-risk group, PSAD showed an independent predictive value. CONCLUSIONS: PSAD and biopsy core details have different performance characteristics for the prediction of oncologic outcomes in each NCCN risk group. Despite the need for further confirmation of the results with a larger cohort and longer observation, these factors are important as preoperative predictors in addition to the NCCN classification for a urologic surgeon to choose a surgical strategy.

Psychological impact of serial prostate-specific antigen tests in Japanese men waiting for prostate biopsy.

BACKGROUND: It is common to repeat prostate-specific antigen (PSA) measurements for men with intermediate PSA elevation before prostate biopsy. In this scenario, men with persistently elevated PSA values may have considerable psychological distress. We attempted to determine whether elevated PSA values have psychological effects on these men in association with the timing of measurement, PSA kinetics, and biopsy results. METHODS: In order to investigate the initial and late effects of PSA tests on psychological distress during serial measurements, two groups of men with screen-positive results (PSA ≥3 ng/ml) were studied-205 men whose first questionnaires regarding anxiety and depression were taken at initial screening (group A), and 103 men whose questionnaires were taken at repeated measurement for prior PSA elevation (group B). RESULTS: The level of distress was generally low. There were no significant differences in distress between the two groups, suggesting a constant psychological effect by elevated PSA values over a long period of time. The distress of men in group A increased significantly as PSA levels rose and decreased when they fell to normal range. On the other hand, the distress of men in group B did not change regardless of PSA kinetics, indicating that their psychological condition seemed susceptible to subtle PSA change only in the initial phase of measurements. Unexpectedly, men with benign results showed insignificant but higher distress after prostate biopsy. CONCLUSIONS: Although a small fraction of men have psychological distress caused by changes in PSA levels, the benefits, risks (psychological and physical), and limitations of PSA tests must be adequately explained to the patients before entering the screening program.

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.

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.

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.

Successful management of ureteral injury after gender-affirming laparoscopic hysterectomy: A case report.

INTRODUCTION AND IMPORTANCE: A two-step process involving ureteral stenting and surgical repair is generally recommended to manage a delayed diagnosis of postoperative ureteral injury; however, retrograde stenting is often difficult. CASE PRESENTATION: A 35-year-old female-to-male transgender person who underwent laparoscopic gender-affirming total hysterectomy with bilateral salpingo-oophorectomy developed right ureteral injury at 2 months postoperatively. Initially, the stenting guidewire could not pass through the stenotic tract and was diverted into the abdominal cavity. Using a 0.014-in. microguidewire and a 2-Fr microcatheter, both of which are designed for angiography, the ureteral stent was ultimately placed. The patient underwent surgical repair using the Boari flap technique. The double J catheter was removed at 1 month postoperatively, and postoperative retrograde pyelography revealed no urinary leakage or ureteral stricture. CLINICAL DISCUSSION: Immediate primary repair is desirable for intraoperative ureteral injuries. However, up to 70 % of ureteral injuries are diagnosed during the postoperative period. For a delayed diagnosis of ureteral injury, urinary diversion with ureteral stent, nephrostomy, or both, followed by delayed repair, is recommended to avoid the inflammatory phase. In this patient, ureteral stenting was difficult on the first attempt. Thin microguidewires designed for angiography could be useful in such difficult situation. CONCLUSION: A ureteral injury at the mid-ureter diagnosed at 2 months postoperatively was successfully managed using a two-step process involving ureteral stenting and surgical repair. A microguidewire and a microcatheter are useful for successful stenting in patients with late-diagnosed, severe ureteral strictures.

Cancer immunohistogram representing cancer-immunity cycle by immunohistochemistry predicts the efficacy of immune checkpoint inhibitors in urological cancer patients.

We developed an immunohistogram representing an individual cancer-immunity cycle based on immunohistochemical analyses. We evaluated its ability to predict the efficacy of immune checkpoint inhibitors (ICI) in 11 patients with urothelial carcinoma and 7 patients with renal cell carcinoma who underwent surgery and received ICIs for disease recurrence. Immunohistochemical analyses for CD8, TIA-1, HLA class I, HLA-DR, and PD-L1 were performed and scored 0-3. T-cell infiltration pattern was classified into desert, excluded, partially inflamed, and inflamed. Tumors with an inflamed or partially inflamed pattern and positive scores (score ≥ 1) for all five immune markers were classified as "immune-hot" and others as "immune-cold." Association between the immunohistogram and ICI treatment efficacy was evaluated with objective response rate, disease control rate (DCR), progression-free survival (PFS), and cancer-specific survival (CSS). Eight (44%) and 10 (56%) patients had immune-hot and immune-cold tumors, respectively. Immune-hot tumors showed a higher DCR (100% vs. 40%, p < 0.01), longer PFS (median unreached for hot, 1.3 months for cold, p < 0.01), and longer CSS (median unreached for hot, 3.3 months for cold, p < 0.01) than immune-cold tumors. The immunohistogram could be clinically useful as an accessible biomarker for precision cancer immunotherapy in urological cancer.

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.

Clinical Significance of 18F-fluorodeoxyglucose and Glucose Transporter 1 mRNA in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: 18F-fluorodeoxyglucose (FDG) uptake measurement on positron emission tomography/computed tomography (PET/CT) is difficult in renal tumors because of the nearby renal parenchyma and urinary tract, which excrete FDG. We carefully examined the maximum standardized uptake value (SUVmax) on FDG-PET/CT and investigated the relationship between major glucose transporters in the kidney and clear cell renal cell carcinoma (ccRCC) progression. PATIENTS AND METHODS: Forty-five patients with ccRCC underwent FDG-PET/CT for staging and nephrectomy. Glucose transporter mRNA expression was examined in the removed kidney. RESULTS: SUVmax was increased in high-stage and high-grade tumors. Glucose transporter 1 (GLUT1) mRNA expression was higher in tumor tissues, in contrast to other glucose transporters. SUVmax was not correlated with GLUT1 mRNA expression. Kaplan-Meier analysis showed reduced overall and recurrence-free survival in the high SUVmax group. CONCLUSION: Primary ccRCC lesions show a high SUVmax and GLUT1 mRNA over-expression. SUVmax increases with tumor upstaging and upgrading.

Immune-related myositis resulting from combination therapy of ipilimumab and nivolumab in patient with metastatic renal cell carcinoma.

Immune-related myositis is one of the rare immune-related adverse events whose underlying precise mechanisms are not fully understood. Here, we describe a case of immune-related myositis that developed after four cycles of combination therapy with nivolumab plus ipilimumab for the treatment of metastatic renal cell carcinoma. Negative results of autoimmune antibodies, including anti-acetylcholine receptor and anti-muscle-specific kinase antibodies suggested a T-cell-mediated mechanism. After recovery with steroid therapy, the patient resumed nivolumab monotherapy and survived without any evidence of disease progression or refractory of myositis. Differential diagnosis between T-cell-mediated and B-cell-mediated immune-related myositis and its impact on optimal management are discussed.

[Retroperitoneal solitary fibrous tumor: a case report].

A 63-year-old man with a retroperitoneal tumor found incidentally was referred to our hospital. Computed tomography showed a tumor ventrally adjacent to urinary bladder and prostate. Pathological examination of retroperitoneal tumor specimens obtained by percutaneous needle biopsy revealed hypercellularity of spindle cells positive for CD 34. Under the suspicion of solitary fibrous tumor (SFT) or stromal tumors of uncertain malignant potential (STUMP), we performed en bloc resection of tumor, urinary bladder and prostate because tumor was firmly fixed to urinary bladder and prostate. The final diagnosis of retroperitoneal tumor was SFT because pathological findings of the surgical specimen were the same as those of the biopsy specimens.