TFE3-immunopositive papillary renal cell carcinoma: A clinicopathological, immunohistochemical, and genetic study.

It is possible that PRCCs may still contain a variety of unknown histologic subtypes. Some PRCCs express high expression of TFE3 protein without TFE3 gene rearrangement, but no reports have investigated the significance of this. Here we attempted to examine clinicopathological and molecular significance of the TFE3-immunopositive PRCC. We reviewed the histology and immunohistochemistry in 58 PRCCs. TFE3 immunoexpression was recognized in 7 cases. Because TFE3 immunostaining shows false-positive, to ensure the integrity of TFE3 immunostaining, the immunostaining was performed under strict control of internal controls and western blotting was performed on 2 positive cases and 5 negative cases, and differences in protein expression between two groups were confirmed. Significant immunohistochemical expressions of autophagy/lysosome proteins were observed in TFE3-positive group. No TFE3 gene arrangement was detected in all positive cases by fluorescence in situ hybridization. Whole-exome sequencing was performed on 6 TFE3-positive and 2 TFE3-negative cases. Gain of chromosome 7 was found in five of 6 TFE3-positive cases (83%). TFE3-positive group was correlated significantly with higher pTstage, cNstage, WHO/ISUP nuclear grade, and decreased OS. TFE3-immunopositive PRCC group had a poorer prognosis than TFE3-negative PRCC group and showed correlation with expressions of autophagy/lysosome proteins, suggesting that enhancement of autophagy/lysosome function drives an environment of energy metabolism that is favorable for cancer. It is necessary to recognize that there is TFE3-immunopositive group without TFE3 gene rearrangement within PRCC. Because of its aggressive biological behaviour, TFE3 can act as a biomarker in PRCC; moreover, autophagy-inhibiting drugs may have therapeutic effects on TFE3-immunopositive PRCC.

Prognostic Value of Lower Tract Urinary Symptoms in Clinically Regional Lymph Node-positive Prostate Cancer.

BACKGROUND/AIM: To explore the prognostic value of lower urinary tract symptoms (LUTS) in patients with newly diagnosed regional lymph node-positive prostate cancer. PATIENTS AND METHODS: The prognostic value of LUTS for progression-free (PFS) and overall (OS) survival, as well as the differential prognostic impact of radiotherapy by LUTS was investigated. RESULTS: Univariate Cox-model analysis showed a statistically significantly increased hazard risk for PFS and OS for men with International Prostate Symptom Score (IPSS)≥19 and Overactive Bladder Symptom Score (OABSS) ≥8 at diagnosis. Patients with lower IPSS had a better PFS at 5 years (70.0% vs. 51.9%, p=0.027) and OS at 5 year (89.3% vs. 73.6%, p=0.016). Similarly, a lower OABSS was associated with greater PFS at 5 years (67.4% vs. 23.4%, p<0.001) and OS at 5 years (85.3% vs. 57.1%, p=0.012). CONCLUSION: IPSS and OABSS were prognostic for PFS and OS in patients with regional lymph node-metastatic prostate cancer.

Lactate Dehydrogenase Is a Serum Prognostic Factor in Clinically Regional Lymph Node-positive Prostate Cancer.

BACKGROUND/AIM: Currently, there is no established prognostic serum parameter except PSA in clinically regional lymph node-positive prostate cancer. The aim of this study was to identify serum prognostic factors in clinically regional lymph node-positive prostate cancer. PATIENTS AND METHODS: Patients diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017 were included. The prognostic value of serum parameters for progression-free survival (PFS) and overall survival (OS) was investigated. RESULTS: Univariate and multivariate analyses showed a statistically significant increased hazard risk for PFS and OS for men with lactate dehydrogenase (LDH) ≥230 IU/l at diagnosis. PFS at 5 years for patients with high and low LDH levels were 69.9% (95% CI=56.8-79.8%) and 18.9% (95% CI=1.23-53.2%), respectively (p=0.003). OS at 5 years for low and high LDH levels were 89.2% (95% CI=78.6-94.7%) and 46.3 (95% CI=11.2-76.2%), respectively (p=0.006). CONCLUSION: This study shows that LDH is an independent predictor of PFS and OS in patients with regional lymph node metastatic prostate cancer.

The prognosis and the impact of radiotherapy in clinically regional lymph node-positive prostate cancer: Which patients are candidates for local therapy with radiation?

BACKGROUND: This study aimed to identify the prognostic and predictive factors of local radiotherapy in clinically regional lymph node-positive prostate cancer. PATIENTS AND METHODS: This study includes patients who were newly diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017. We investigated the prognostic value of clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) as well as the differential prognostic impact of radiotherapy by subgroup analysis. RESULTS: Among the 93 men enrolled as patients, 48 (51.6 %) were treated with radiotherapy. The biopsy positive core rate and biopsy Gleason score were associated with PFS, and the number of lymph node metastases was associated with both PFS and OS. Patients who underwent radiotherapy showed better PFS and OS. High-risk features (at least 2 criteria among ≥75% biopsy positive core rate, Gleason score ≥9, and ≥2 positive lymph nodes) were especially associated with improved outcomes after undergoing radiotherapy. CONCLUSION: We identified prognostic factors for clinically regional lymph node-positive prostate cancer and showed the benefits of local radiation therapy. Patients with high-risk features may be especially suitable candidates for radiotherapy.

Timing of changing therapy from gemcitabine and cisplatin chemotherapy based on real-world data of advanced urothelial carcinoma.

Cisplatin-based systemic chemotherapy is the gold-standard approach for the first-line treatment of patients with advanced or metastatic urothelial carcinoma (UC). However, the optimal number of cycles is still unclear. The current study retrospectively assessed the clinical outcome in patients who received gemcitabine and cisplatin (GC) chemotherapy as first-line treatment for metastatic urothelial cancer to clarify the timing of switching from GC therapy. A total of 61 patients with locally advanced or metastatic UC who received first-line chemotherapy with GC were retrospectively reviewed at National Hospital Organization Kyushu Cancer Center between June 2009 and August 2017. The progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The significance of associations between the clinical parameters and OS was assessed using the Cox proportional hazards regression model. The median cycle number for GC chemotherapy was 4. The median PFS and OS of all cases was 5.2 and 14.1 months, respectively. The multivariate analyses revealed that a neutrophil-to-lymphocyte ratio ≥3.0 (hazard ratio [HR], 2.521, 95% confidence interval [CI]=1.179-5.624; P=0.017) and best response to GC therapy of CR+PR (HR 0.110; 95% CI=0.028-0.411; P<0.001) were independent prognostic factors. However, the number of GC cycles (≤4 vs. >4) was not an independent prognostic factor (P=0.387). The current retrospective study indicated that changes to therapy should be considered at an early stage for cases with a therapeutic effect of SD or less, regardless of the number of GC therapy cycles.

Relapse of aseptic meningitis induced by ipilimumab and nivolumab therapy for metastatic renal cell carcinoma: A case report.

The combined immunotherapy of nivolumab and ipilimumab causes a variety of autoimmune-related adverse events (irAEs). The current report details a 70-year-old woman with clear cell renal cell carcinoma metastasis in the lung. Two weeks after two courses of treatment, the patient complained of headache, dizziness and nausea. Cerebrospinal fluid (CSF) analysis revealed an elevated protein level of 195 mg/dl and a significantly elevated white blood cell (WBC) count of 830/mm3 (lymphocytes, 825/mm3; neutrophils, 5/mm3). The results excluded malignancy and infection. The patient was diagnosed with aseptic meningitis and was administered intravenous prednisolone (1 mg/kg/day). On the 49th day of the 2nd course of treatment, no recurrence of clinical symptoms was exhibited during maintenance oral steroid treatment (prednisolone 10 mg/day) and CSF analysis revealed that the WBC count had dropped to 44/mm3 (lymphocytes only). Therefore, the 3rd course of treatment was readministered the next day. After two weeks, the patients again complained of nausea, anorexia and fatigue. CSF analysis demonstrated that the WBC count was not increased from the result obtained previously. However, brain MRI scans revealed the mild diffuse enlargement of the pituitary and endocrine system tests revealed reduced adrenocorticotropic hormone (ACTH; 2.0 pg/ml) and cortisol (1.12 µg/dl) levels. The patient was diagnosed with isolated ACTH deficiency and oral hydrocortisone was administered after prednisolone cessation. On the 25th day of the 3rd course of treatment, the patient complained of headache and anorexia. CSF examination revealed that the WBC count had increased a second time (53/mm3; lymphocytes only) and laboratory data revealed hepatic dysfunction. The patient was then diagnosed with relapse of aseptic meningitis and liver dysfunction. While continuing oral hydrocortisone treatment, the administration of intravenous prednisolone was started. The observed liver dysfunction and aseptic meningitis gradually improved. The current report may be useful for avoiding delays in the diagnosis and treatment of this life-threatening and uncommon irAE, in which CSF examinations are useful for diagnosis and management.