Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.     

Therapeutic effects of the combined androgen blockade therapy versus luteinizing hormone-releasing hormone analog monotherapy in patients with hormone naïve metastatic prostate cancer: a multi-institutional comparative analysis

BackgroundThe clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naïve metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC.MethodsWe retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients’ data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes.ResultsThe median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups.ConclusionsNo significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC.     

Dynamics of prostate-specific antigen as prognostic factors in endocrine treatment for prostate cancer

Prostate-specific antigen values provide important and unique information about prostate cancer to clinicians. However, there is conflicting information about the prognostic significance of the dynamics of PSA decline and elevation after treatment. To provide further insight into the dynamics of PSA as prognostic factors, we herein studied various PSA values as possible prognostic factors in 93 patients with prostate cancer treated with endocrine therapy. Thirteen (14.0%) had stage B tumors, 20 (21.5%) had stage C tumors, and 60 (64.5%) had stage D tumors. The overall 5-year survival rate was 41.2%. Relapse was observed in 32 (34.4%) patients. The influence of pre- and post-treatment PSA (both absolute and percentage values) on survival was analyzed. Normalization of PSA value was associated with prolonged survival regardless of interval to reach the lowest PSA level. The absolute value of PSA at 3 or 6 months following treatment was a significant discriminator, while the pre-treatment PSA level and percentage values of post-treatment PSA were not. These data show that the PSA nadir and PSA value at 3 or 6 months following treatment provide important prognostic information.     

Quantitative measurement of prefrontal lobe volume on three dimensional magnetic resonance imaging scan

This article describes the measurement of the frontal and prefrontal lobe volumes on three dimensional (3-D) MRI in 13 children aged 5 months to 14 years and in 3 adults aged 27 to 39 years. The 3-D MRI data were acquired by the fast spoiled gradient recalled (SPGR) sequence using a 1.5 T MR imager. The frontal and prefrontal lobe volumes were measured by the volume measurement function of the Workstation. We confirmed that this technique to analyze segmental brain volumes achieved acceptable levels of reliability and accuracy. There was an increase in the frontal and prefrontal lobe volumes with advancing age, being rapid between 8 and 15 years of age. The prefrontal to frontal lobe volume ratio also increased gradually, with spurts between 8 and 15 years of age. This approach may be particularly useful for studies on patients with frontal and prefrontal lobe dysfunctions.     

Eye-head coordination abnormalities and regional cerebral blood flow in Alzheimer's disease

1. Three patients with Alzheimer's disease (AD) and three healthy controls (HC) were examined for eye-head coordination. Regional cerebral blood flow (rCBF) was measured in AD patients. 2. Eye-head coordination was analyzed using a Vision analyzer, and magnetic sensors. The authors measured the rCBF with 123I-IMP, and 99mTc-ECD SPECT. 3. AD reduced gaze accuracy and head movements, and prolonged the latency of saccade as compared to HC. AD patients had a tendency to focus on the target by using eye movements only. 4. AD reduced the rCBF in the inferior parietal part and the visual area, relative to the motor area. Damage of these areas may have caused the eye-head coordination disorders in the AD patients.     

Pseudo-Meigs' syndrome caused by secondary ovarian tumors from gastrointestinal cancer. A case report and review of the literature

BACKGROUND: Pseudo-Meigs' syndrome is a condition characterized by nonmalignant ascites and/or pleural effusion caused by pelvic tumors other than solid benign ovarian tumors. This syndrome has only rarely occurred in association with gastrointestinal cancers. METHOD: We treated a 53-year-old woman who developed this syndrome due to ovarian metastasis from colon cancer. Diagnostic work-up for abdominal distension disclosed a sigmoid colon cancer and bilateral ovarian masses. Ultrasonography demonstrated massive ascites and a right pleural effusion. Repeated cytologic examinations of both effusions revealed no malignant cells. Laparotomy disclosed no peritoneal dissemination. A radical sigmoidectomy and hysterectomy with bilateral salpingo-oophorectomy were performed. RESULTS: Histologic examination confirmed ovarian metastases from the colonic primary tumor. After resection, both effusions disappeared promptly, confirming a diagnosis of pseudo-Meigs' syndrome caused by sigmoid colon cancer. The patient remains alive with disease after 52 months. CONCLUSION: Among 6 reported occurrences with gastrointestinal tumors including our case, the primary site was the colon or rectum in 5 and the stomach in 1. Two cases were due to Krukenberg tumors. Three patients with documented outcomes were alive 108, 52, and 12 months after resection. Clinicians should note that gastrointestinal cancers, especially colorectal tumors, rarely may cause pseudo-Meigs' syndrome and resection may provide long-term palliation.     

Difference of visual attention between smokers and never-smokers]

Nicotine is known to improve cognitive performance such as attention, concentration and working memory in humans and animals. Previous research suggests that nicotine enhances visuospatial attention. But it could be hypothesized that nicotine intake alleviate a withdrawal-induced deficit in smokers. To evaluate the cognitive performance in smokers and never-smokers, we investigate eye movement while 4-points saccade task is performed. 5 smokers and 6 never-smokers are matched for age and education. Eye movement was investigated by using TKK2920 (Takei Co.) which determines the direction of gaze over a two-dimensional visual field without attachments to the eye. We found that a tendency which Mean Gazing Time is prolonged in smokers. These data suggest that impairment of visual attention in smokers is not significant.     

Alteration of p53 Clonality Accompanying Colorectal Cancer Progression

The aim of this study was to clarify whether or not the status of gene alteration is heterogeneous in intramucosal carcinoma and homogeneous within invasive carcinoma. We selected 10 colorectal carcinoma cases (1 mucosal, 5 submucosal and 4 advanced carcinomas including 2 cases with lymph node metastasis) and analyzed the p53 gene sequence. Six colorectal cancers in this study showed heterogeneity in p53 mutations in cells from the intramucosal part. In the invasive part of a carcinoma, p53 mutation status was homogeneous intratumorally in all cases. These data indicate that, in regard to p53 gene alterations, colorectal cancers can be composed of various subclones when limited to the mucosa, but clonal selection occurs when one of these subclones commences invasion to the submucosa, generating a monoclonal invasive carcinoma.