Primary amelanotic malignant melanoma of the male urethra with inguinal lymph node metastasis successfully controlled by nivolumab: A case report.

We report a rare case of primary amelanotic malignant melanoma of the male urethra. A 65-year-old man with a urethral mass was referred to our hospital. A pathological diagnosis of a biopsy specimen revealed malignant melanoma. Thereafter, the patient underwent partial penectomy. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received DAV-Feron in an adjuvant setting; however, PET-CT revealed multiple metastasis. After receiving more than 10 cycles of nivolumab, the accumulation of FDG was no longer observed on PET-CT. The patient is currently free from recurrence at 20 months after nivolumab treatment.

The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy.

BACKGROUND: Tyrosine-kinase inhibitor (TKI) targeting angiogenesis improves the prognosis of patients with metastatic renal cell carcinoma (RCC), but its effect is temporary. In order to understand the mechanism by which RCC acquires resistance to TKI, we investigated the change of glucose accumulation in RCC by FDG PET/CT when they demonstrated progression disease (PD) against TKI. METHODS: We monitored the FDG accumulation in RCC of 38 patients treated with TKI by 162 PET/CT sequentially until they were judged to demonstrate PD. Standardized uptake value (SUV), a simplified index of tissue FDG accumulation rate, was measured, and the sequential changes of max SUVmax (the highest SUV in an individual patient) was analyzed. Additionally, the expression of glucose transporter 1 (GLUT-1) and associated proteins in 786-O cells cultured under hypoxia were analyzed. RESULTS: The 10 patients with RCC which FDG accumulation was accelerated after beginning of TKI treatment demonstrated PD soon. The other 28 patients with RCC which FDG accumulation was suppressed by TKI showed longer progression-free survival (3.6 months vs 6.5 months, P = 0.0026), but this suppression in most cases (96%) was temporary and FDG accumulation was accelerated when tumor demonstrated PD. Interestingly, the FDG accumulation at PD was higher than that before TKI treatment in the half cases. The acceleration of FDG accumulation was suppressed by following treatment by mammalian target of rapamycin (mTOR) inhibitor. Additionally, in vitro assay demonstrated that the expression of GLUT-1 was increased in the RCC cells surviving under hypoxia condition via mTOR pathway. CONCLUSIONS: The acceleration of glucose accumulation dependent on mTOR in RCC assessed by FDG PET/CT demonstrated acquisition of resistance to TKI. FDG PET/CT had potential as an assessment method monitoring not only the initial response but also following status of RCC during TKI treatment. TRIAL REGISTRATION: UMIN0000008141 , 11 Jun 2012. This trial was retrospectively registered.

Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas.

High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs.

C-reactive protein in patients with advanced metastatic renal cell carcinoma: usefulness in identifying patients most likely to benefit from initial nephrectomy.

OBJECTIVE: C-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied. PATIENTS AND METHODS: We retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests. RESULTS: ROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (≥67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (≤18.0 mg/L, >18.0 and <67.0 mg/L, and ≥67.0 mg/L), ECOG PS (0, 1, and ≥2), and number of metastatic organ sites (0-1 and ≥2). The retrospective design is a limitation of this study. CONCLUSION: Our study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC.

A three-gene expression signature model to predict clinical outcome of clear cell renal carcinoma.

Renal cell carcinomas (RCCs) are morphologically and genetically heterogeneous tumors and present diverse clinical courses. We developed a scoring system using levels of gene expression to predict the outcome for clear cell RCC patients. We selected differentially expressed genes from the DNA microarray data of 27 clear cell RCCs; 16 were metastasis phenotypes and 11 were not. We compared the selected gene set with previously published data and identified 33 overlapping genes closely associated with patient outcome. We selected the 12 top-ranked genes and confirmed the level of expression using quantitative reverse transcriptase PCR. Multivariate Cox analysis revealed that 3 genes-vascular cell adhesion molecule 1 (VCAM1), endothelin receptor type B (EDNRB), and regulator of G-protein signaling 5 (RGS5)-were the most tightly associated with cancer-specific survival and that higher expression of the 3 genes correlated with better outcome. A formula for an outcome predictor was generated from integration of the measurements of the expression levels of the 3 genes. Multivariate Cox models combined with a split-sample cross-validation method in a cohort of 386 clear cell RCC patients demonstrated that the derived score for outcome prediction was an independent predictor in cancer-specific survival tests. The accuracy of the prediction of cancer death after nephrectomy was improved by the inclusion of this score in receiver operating characteristic analysis from multivariate logistic regression models, suggesting that a scoring system based on the expression levels of these 3 genes is useful in the prediction of survival for patients with clear cell RCC.

[Multi-center trial on the early effects of silodosin on lower urinary tract symptoms associated with benign prostatic hyperplasia].

Silodosin (URIEF), a new so-called 3rd generation alpha-1 blocker, is widely expected to be effective and useful for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), due to its high specificity to alpha-1A receptor. We evaluated the efficacy of Silodosin, on 187 males 50 years old or over with the diagnosis of BPH. Silodosin significantly improved the International Prostate Symptom Score (IPSS) and quality of life (QOL) score from the day after administration was started. Among 166 patients whose data were available for the analysis of efficacy of Silodosin, 77.5% showed apparent subjective improvement. Eighty three patients, who had been taking another alpha-1 blocker but without satisfactory effects, showed almost the same improvements in IPSS and QOL score after switching to Silodosin as the remaining 83 patients who had no preceding treatment with an alpha-1 blocker. The improvements were not only in voiding symptoms but also in storage symptoms. The patients, who had serious storage symptoms, responded rather well to Silodosin and showed significant improvement. Taken together, Silodosin showed a quick effect for improving subjective symptoms and QOL, and was found to be useful for the management of LUTS with BPH.

Expression of adipose differentiation-related protein: a predictor of cancer-specific survival in clear cell renal carcinoma.

PURPOSE: We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). To further evaluate the correlation between ADFP expression levels and clinicopathologic characteristics and patient outcome, we retrospectively examined patients with clear cell RCC. EXPERIMENTAL DESIGN: A series of 432 consecutive patients with sporadic clear cell RCC who underwent nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP expression levels in the primary tumors and in 18 metastases were measured by real-time quantitative PCR. The clinicopathologic and prognostic data were collected, as well as the von Hippel-Lindau disease (VHL) gene alteration status in selected cases. RESULTS: ADFP expression was apparently high in cases without a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL alteration-positive clear cell RCC, whereas it was down-regulated in undifferentiated tumors with a spindle/pleomorphic component or metastatic lesions. Univariate analyses showed that high ADFP expression was associated with better cancer-specific survival and cancer-free survival. Further Cox multivariate analyses combined with the split-sample validation method showed that ADFP expression still remains an independent predictor for cancer-specific survival in all tumor stages and in advanced metastatic cases, whereas the predictive value of ADFP expression for cancer recurrence is rather weak. CONCLUSIONS: The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC.

Vascular cell adhesion molecule 1 predicts cancer-free survival in clear cell renal carcinoma patients.

PURPOSE: Vascular cell adhesion molecule 1 (VCAM1) is a cell surface glycoprotein implicated in various pathophysiologic conditions. We measured VCAM1 expression levels in tumor tissues and evaluated its significance and prognostic use in renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: We used real-time quantitative PCR to examine the VCAM1 expression levels of a total of 485 sporadic renal tumors, including 429 clear cell, 21 papillary, 17 chromophobe, 11 oncocytomas, and 7 collecting duct carcinomas. We retrospectively examined the relationship of this expression to various clinicopathologic variables and the von Hippel-Lindau alteration status. We evaluated its significance with respect to patient survival rates using the Cox regression model combined with the split-sample method. RESULTS: Compared with normal kidney samples (n = 43), VCAM1 was significantly up-regulated in clear cell RCC and papillary RCC, whereas it was down-regulated in chromophobe RCC and oncocytoma. In clear cell RCC, VCAM1 expression levels were apparently high in patients asymptomatic at presentation and in patients with small tumor size, low-stage, low-grade, microvascular invasion-negative, and von Hippel-Lindau alteration-positive tumors. Univariate analyses showed that VCAM1 high expression is strongly associated with better outcomes in clear cell and papillary RCCs. Further, Cox multivariate analysis models combined with the split-sample method revealed that this association is significant only in cancer-free survival for patients with clear cell RCC after curative surgical resection. CONCLUSIONS: VCAM1 expression levels were found to be histologically subtype specific in renal tumors. Determination of the VCAM1 expression level as a biomarker can provide useful prognostic information for patients with clear cell RCC.

[Clinical significance of pelvic lymph-node dissection for the patients with locally invasive bladder cancer--correlation between the number of retrieved lymph nodes and prognosis].

The objective of this study was to know the effects of pelvic lymph node dissection on the survival of the patients who received radical cystectomy without neoadjuvant chemotherapy or radiotherapy. Between 1984 and 2000, 104 patients underwent operation at our institution for tumors clinically diagnosed as locally invasive bladder cancer (T2-4NxM0). Survival rates and 8 prognostic factors (age, sex, size, multiplicity, type, pT, N, pv) were analyzed by uni- and multivariate analysis. The significant factors were size, type, pT, N, pv by univariate analysis. Of these 5 factors, N factor was the most significant by multivariate analysis. Patients (N-) who had more than 20 lymph nodes retrieved showed better survival than the others.

Rapid progression of carcinoma of the penis after laser treatment.

We report a case of rapid progression of carcinoma of the penis, in a 90-year-old man, one year after yttrium-aluminum-garnet (YAG) laser therapy. This patient had received YAG laser ablation for well-differentiated, verrucous, squamous cell carcinoma of the penis at the age of 89, and was found on physical examination to have local recurrence. The recurrent tumors were surgically resected, and the histological examination revealed infiltrating, poorly-differentiated squamous cell carcinoma. The patient developed metastases of bilateral inguinal lymph nodes and liver and died of penile carcinoma. We should be aware of the possibility of an unfavorable outcome following the use of laser therapy against carcinoma of the penis.

[Bilateral adrenal masses from renal cell carcinoma: a case report].

We report a case of bilateral adrenal metastasis from renal cell carcinoma. A 65-year-old man was referred to our hospital for a right renal mass. A computed tomography revealed a 9 cm right renal tumor and bilateral adrenal masses (3.5 cm on the right side and 4.5 cm on the left). A right radical nephrectomy and bilateral adrenalectomy demonstrated renal cell carcinoma with metastasis to bilateral adrenal glands. The pathological findings of the right renal tumor showed clear cell carcinoma, G3 > G2 and both adrenal tumors showed the same pathology as the right renal tumor. The patient is alive with lung metastasis after 15 months postoperatively treated with interferon-alpha.

Successful recovery from interstitial pneumonitis, induced by bicalutamide and leuprorelin acetate given as treatment for prostate cancer.

We report a case of interstitial pneumonitis induced by bicalutamide and/or leuprorelin acetate given as therapy for prostate cancer, in which the pneumonitis was successfully managed by steroid treatment. Steroids were given promptly on the day following onset of pneumonitis, and the patient (72 years old) recovered almost completely within one and a half months. Interstitial pneumonitis, induced by hormone treatment given for prostate cancer, is a reversible condition and a quick diagnosis followed by prompt, proper treatment is important to ensure a successful recovery. The patient had been free of interstitial pneumonitis for 14 months, but died of pneumothorax.

Interstitial pneumonitis induced by bicalutamide and leuprorelin acetate for prostate cancer.

Maximal androgen blockade therapy is the standard endocrine treatment for advanced prostate cancer. We report here an unusual case of interstitial pneumonitis induced by bicalutamide and/or leuprorelin acetate treatment for metastatic prostate cancer.