Impact of self-decision to stop cancer treatment on advanced genitourinary cancer patients.

ABSTRACT: Decision-making to stop cancer treatment in patients with advanced cancer is stressful, and it significantly influences subsequent end-of-life palliative treatment. However, little is known about the extent to which the patient's self-decisions influenced the prognostic period. This study focused on the patient's self-decision and investigated the impact of the self-decision to stop cancer treatment on their post-cancer treatment survival period and place of death.We retrospectively analyzed 167 cases of advanced genitourinary cancer patients (kidney cancer: 42; bladder cancer: 68; prostate cancer: 57) treated at the University of Fukui Hospital (UFH), who later died because of cancer. Of these, 100 patients decided to stop cancer treatment by themselves (self-decision group), while the families of the remaining 67 patients (family's decision group) decided to stop treatment on their behalf because the patient's decision-making ability was already impaired. Differences in the post-cancer-treatment survival period and place of death between the 2 groups were examined. The association between place of death and survival period was also analyzed.The median survival period after terminating cancer treatment was approximately 6 times longer in the self-decision group (145.5 days in self-decision group vs 23.0 days in family's decision group, P < .001). Proportions for places of death were as follows: among the self-decision group, 42.0% of patients died at UFH, 45.0% at other medical institutions, and 13.0% at home; among the family's decision group, 62.7% died at UFH, 32.8% at other medical institutions, and 4.5% at home. The proportion of patients who died at UFH was significantly higher among the family's decision group (P = .011). The median survival period was significantly shorter for patients who died at UFH (UFH: 30.0 days; other institutions/home: 161.0 days; P < .001).Significantly longer post-cancer-treatment survival period and higher home death rate were observed among patients whose cancer treatment was terminated based on their self-decision. Our results provide clinical evidence, especially in terms of prognostic period and place of death that support the importance of discussing bad news, such as stopping cancer treatment with patients.

Low-dose Docetaxel Enhanced the Anticancer Effect of Temsirolimus by Overcoming Autophagy in Prostate Cancer Cells.

BACKGROUND/AIM: Chemotherapy with docetaxel (DTX) is used for castration-resistant prostate cancer (CRPC), but it is inadequate. MATERIALS AND METHODS: We evaluated the effect of the combination treatment DTX and the mTOR inhibitor temsirolimus (TEM) in the PC3 prostate cancer cell line, by focusing on the induction of autophagy and apoptosis. RESULTS: TEM induced autophagy but not apoptosis even at a high dose, whereas DTX induced apoptosis. The combination of low-dose DTX and TEM caused a 34% suppression in cell proliferation compared to monotherapy with a higher dose of DTX. The induction of apoptosis was increased by their combination. The combination with DTX overcame the induction of autophagy by TEM. The combination treatment suppressed tumor growth 72% less than the control group after 14 days of treatment in vivo. CONCLUSION: The combination of TEM and DTX induced apoptosis by overcoming autophagy and enhanced the anticancer effect compared to monotherapy.

Neurogenic bladder associated with xeroderma pigmentosum type A: A case report and literature review.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by a defect in deoxyribonucleic acid repair. Along with cutaneous symptoms, neurological symptoms are important clinical features of XP. However, information on neurogenic bladder occurrence among XP cases is rare. Herein, we describe a case of neurogenic bladder in a patient with XP type A (XPA). In this case, low bladder compliance, impaired bladder emptying, and urethral sphincter discoordination were significant cystometric findings, and frequent febrile urinary tract infection was a clinical problem. XPA patients often cannot express their symptoms because of cognitive dysfunction. Close follow-up and assessments are necessary.

Low and high body mass index values are associated with female nocturia.

AIMS: We evaluated the relationship between body mass index (BMI), including low BMI, and nocturia in Japanese women. METHODS: We collected data on 18 952 women who participated in a multiphasic health screening in Fukui, Japan, in 2006. The participants were asked to report any current or previous disease. Self-reported current body weight and height were used to calculate the BMI. We analyzed the relationship between nocturia, as assessed by a questionnaire, and other variables including age, BMI, and comorbidities. RESULTS: The participants' mean age was 60.6 years. Overall, the prevalence of nocturia (two or more voids/night) was 4.3% and increased in an age-dependent manner. BMI did not affect nocturia in the young participants. The prevalence of nocturia was higher in the high-BMI women (>25.0 kg/m 2 ) in their fifth and sixth decades, but the prevalence was higher in the low-BMI (<18.5 kg/m 2 ) in the women more than 80-years old. A multivariate analysis revealed a significant association between nocturia and the following: age, BMI, sleep disturbance, arteriosclerosis, cerebrovascular disease, chronic pulmonary disease, diabetes mellitus, and hypertension. Not only high BMI (which is already reported as a risk of nocturia) but also low BMI was a factor related to nocturia. CONCLUSION: Our findings indicate that in addition to obesity, low BMI is a factor of nocturia in women.

Advanced bladder cancer with malignant psoas syndrome: A case report with a focus on physical findings and complications.

Malignant psoas syndrome (MPS) is a rare clinical condition caused by cancer invasion of the iliopsoas muscle and has very poor prognosis. We report a case involving a 58-year-old woman with bilateral MPS caused by advanced bladder cancer. Rapid progress of a severe crouching posture with multiple deep venous thromboses was an important symptom of this case. Although 4 cycles of chemotherapy were administered, the patient died 8 months following disease onset. Since, these noteworthy symptoms have never been previously reported, in this report, we present the characteristic physical findings using photographs and cancer-related events that occur in MPS.

Serum C-reactive protein level is not associated with prostatic inflammation but with overactive detrusor in patients with benign prostatic hyperplasia.

AIM: Chronic prostatic inflammation is a critical factor that exacerbates lower urinary tract symptoms (LUTS). The serum C-reactive protein (CRP) level is one of the most common markers with which to assess the degree of inflammation, and it has been reported to be related to the severity of LUTS. However, it is not clear whether the CRP level is linked to the magnitude of prostatic inflammation. We evaluated the relationship between the serum CRP level and the magnitude of prostatic inflammation and assessed the influence of CRP on the severity of LUTS. METHODS: We evaluated the tissue specimens of 121 benign prostatic hyperplasia (BPH) patients who underwent surgery for BPH and preoperative measurement of the serum CRP level. We quantified the magnitude of prostatic inflammation histologically by determining the number of high endothelial venule (HEV)-like vessels and assessed the relationship between the serum CRP level and the HEV-like vessels. We divided the patients into two groups based on the median serum CRP level and compared the clinical parameters of the two groups. RESULTS: The serum CRP level was correlated with the overactive bladder symptom score, whereas it was not correlated with the number of HEV-like vessels. In filling cystometry and pressure-flow study, the proportion of patients with detrusor overactivity in the higher-CRP group was higher than that in the lower-CRP group. CONCLUSIONS: Our present study showed that the serum CRP level was significantly associated with storage dysfunction; in contrast, it was not a surrogate marker of prostatic inflammation.

Arterial Transit Time-corrected Renal Blood Flow Measurement with Pulsed Continuous Arterial Spin Labeling MR Imaging.

PURPOSE: The importance of arterial transit time (ATT) correction for arterial spin labeling MRI has been well debated in neuroimaging, but it has not been well evaluated in renal imaging. The purpose of this study was to evaluate the feasibility of pulsed continuous arterial spin labeling (pcASL) MRI with multiple post-labeling delay (PLD) acquisition for measuring ATT-corrected renal blood flow (ATC-RBF). MATERIALS AND METHODS: A total of 14 volunteers were categorized into younger (n = 8; mean age, 27.0 years) and older groups (n = 6; 64.8 years). Images of pcASL were obtained at three different PLDs (0.5, 1.0, and 1.5 s), and ATC-RBF and ATT were calculated using a single-compartment model. To validate ATC-RBF, a comparative study of effective renal plasma flow (ERPF) measured by 99mTc-MAG3 scintigraphy was performed. ATC-RBF was corrected by kidney volume (ATC-cRBF) for comparison with ERPF. RESULTS: The younger group showed significantly higher ATC-RBF (157.68 ± 38.37 mL/min/100 g) and shorter ATT (961.33 ± 260.87 ms) than the older group (117.42 ± 24.03 mL/min/100 g and 1227.94 ± 226.51 ms, respectively; P < 0.05). A significant correlation was evident between ATC-cRBF and ERPF (P < 0.05, r = 0.47). With suboptimal single PLD (1.5 s) settings, there was no significant correlation between ERPF and kidney volume-corrected RBF calculated from single PLD data. CONCLUSION: Calculation of ATT and ATC-RBF by pcASL with multiple PLD was feasible in healthy volunteers, and differences in ATT and ATC-RBF were seen between the younger and older groups. Although ATT correction by multiple PLD acquisitions may not always be necessary for RBF quantification in the healthy subjects, the effect of ATT should be taken into account in renal ASL-MRI as debated in brain imaging.

[A CASE OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE COMPLICATED WITH HENOCH-SCHÖNLEIN PURPURA NEPHRITIS].

Purpura nephritis and autosomal dominant polycystic kidney disease are relatively rare kidney disorders. We present a case complicated by these two diseases. A 68 year-old man with polycystic kidney disease was referred to our hospital with a high fever lasting 3 days and pyuria. Pyelonephritis was suspected based on computed tomography findings of bilateral swelling of the kidney. Inflammation subsided gradually after the initiation of antimicrobial therapy. However, approximately 3 weeks later, the patient developed a fever and skin purpura on the extremities, stomach colic pain, gross hematuria, and increased proteinuria was evident. Therefore, we diagnosed Henoch-Schönlein purpura complicated with nephritis based on biopsies of the skin and the kidney. Immunosuppressant therapy was administered; every symptom was relieved and proteinuria decreased for approximately 20 months.

[A case on hemodialysis with castration-resistant prostate cancer which responded to combination chemotherapy with docetaxel and prednisolone].

A 71-year-old man on hemodialysis was admitted for castration-resistant prostate cancer. He received chemotherapy with docetaxel(60mg/m2 every 3 weeks)and prednisolone(10mg/day). As severe adverse reactions due to chemotherapy were not encountered, he could receive chemotherapy in our outpatient clinic. A total of four courses of chemotherapy resulted in a 56% reduction in PSA, which was judged as PR. Chemotherapy with docetaxel and prednisolone can be safely carried out for a patient with castration-resistant prostate cancer, even while on hemodialysis with the usual dose of docetaxel.

[A case of testicular abscess with low-grade inflammation].

We report a case of testicular abscess with low-grade inflammation. A 55-year-old man was referred to our hospital because of right scrotal pain and swelling for approximately 3 weeks. Physical examination revealed mild tenderness and a hen's egg-sized mass in the right scrotum ; however, fever and scrotal erythema were absent. Magnetic resonance imaging (MRI) showed an enlarged right testis and spermatic cord, and an ultrasonography scan indicated loss of blood flow to these regions. Right testicular necrosis due to spermatic cord torsion or testicular cancer was suspected, and high orchiectomy was performed. However, abscess formation was detected in the testis, and testicular abscess caused by Escherichia coli was diagnosed. The clinical course of this case was unusual because of the small extent of inflammation observed. Typically, testicular abscess is characterized by severe systemic and local inflammation.

IPSS is lower in hypertensive patients treated with angiotensin-II receptor blocker: posthoc analyses of a lower urinary tract symptoms population.

AIMS: The existence of Angiotensin-II (Ang-II) receptors in the bladder wall and the pronounced contractile effect of Ang-II on the human detrusor muscle have been well established. Studies have presented the role of Ang-II as a mediator in smooth muscle growth and collagen production in the bladder with outlet obstruction. We investigated the associations between male lower urinary tract symptoms (LUTS) and hypertension (HT), and examined whether the medications used for HT treatment, particularly Ang-II receptor blockers (ARBs) influence LUTS. METHODS: Among 4,298 men with LUTS who were nominated to participate in a Japanese study using the International Prostate Symptom Score (IPSS) to gain information on the effects and the safety of silodosin, a total of 3,790 men for whom a baseline IPSS was available were sub-analyzed. We analyzed the influence of HT treatment on IPSSs. RESULTS: HT was the most common comorbidity (1,122 men, 29.6%), and 769 men (20.3%) were receiving some kinds of medication for the treatment. We found that the IPSS was lower in patients being treated for HT with ARB than in hypertensive patients who were not receiving any medication (16.8 ± 6.8 vs. 18.3 ± 6.6, P < 0.01). The baseline I-PSS in patients treated for HT with angiotensin converting enzyme inhibitor (ACE-I), calcium channel blocker (CCB), and normotensive patients were 18.3, 19.6, and 18.1, respectively. CONCLUSION: The IPSS is lower in patients with HT treated with ARB. Other drugs for HT, including ACE-I and CCB, did not improve the IPSS.

Expression of microRNAs associated with Gleason grading system in prostate cancer: miR-182-5p is a useful marker for high grade prostate cancer.

BACKGROUND: Expression profiles of some microRNAs (miRNAs) were associated with clinicopathological findings in human prostate cancer (PC), but the relative expression of miRNAs among Gleason patterns (GPs) remains unclear. In this study, we investigated the expression of several known microRNAs in each GP of PC. METHODS: Formalin-fixed, paraffin embedded (FFPE) tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n = 43, including (GP 3) n = 22, (GP 4) n = 35, and (GP 5) n = 12) and needle biopsy (patient set 2, n = 10, (GP 4) n = 10). Cancer tissues from each GP and adjacent normal counterparts were separately collected using laser-captured microdissection (LCM). Real-time RT-PCR was performed to determine the relative expression of miRNAs, including miR-31-5p, -34c-5p, -96-5p, -182-5p, -183-5p, -205-5p, -221-3p, and -222-3p, which were currently reported to be involved in PC progression. RESULTS: In radical prostatectomy samples, relative expression of miR-31-5p, miR-34c-5p, and miR-205-5p in any GP was significantly decreased compared to normal counterpart. However, no significant difference was detected among GP 3, GP 4, and GP 5. Meanwhile, in the same GP4, expression of miR-31-5p miR-182-5p, and miR-205-5p in cancer tissues obtained from high grade cancer was significantly higher than those obtained from intermediate grade cancer. Validation study using biopsy samples revealed that the relative expression of miR-182-5p was statistically higher in high grade cancer even in same GP4. CONCLUSIONS: We confirmed the expression of miR-182-5p depended on the cancer grade even in same GP 4. Expression of miRNA associated with Gleason grading system may contribute to more accurate preoperative cancer risk evaluation.

[Advanced sarcomatoid renal cell carcinoma effectively treated with sunitinib: report of a case].

We report a case of advanced sarcomatoid renal cell carcinoma (RCC) effectively treated with sunitinib. A 77-year-old female who had gross hematuria and left lower abdominal pain was found to have a left renal tumor by computed tomography (CT) and was referred to our hospital. CT revealed a poorly enhanced mass in the left kidney and an enlarged paraaortic lymph node. The patient underwent laparoscopic left nephrectomy, and the tumor was histologically diagnosed as a sarcomatoid RCC. Sunitinib was administered to treat lymph node metastasis, postoperatively, and a partial response was observed after 4 courses. Sunitinib administration has been continued without tumor re-growth.

Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma.

Hepatocyte growth factor (HGF) is a multifunctional molecule that acts as mitogen, motogen, and/or morphogen in a variety of cells. MET, a specific receptor tyrosine kinase for HGF, is upregulated in various tumors including squamous cell carcinoma of the human head and neck (HNSCC), but how HGF affects the expression of downstream functional genes has not yet been elucidated in detail. In the present study, we examined the expression of microRNA (miRNA), non-coding small RNA that regulate cell proliferation and functions by interfering with the translation of target mRNA, with or without HGF stimulation in HNSCC cell line HSC3. Among several miRNAs, in which the expression was altered after HGF stimulation, we focused on miR-200c and miR-27b, both of which were drastically downregulated after HGF stimulation. Expression of ZEB1, a target mRNA for miR-200c, was upregulated 3 and 6 h after HGF stimulation, and that of E-cadherin, a downstream molecule of ZEB1, was downregulated 12 h after HGF stimulation. Expression of ST14/matriptase, an enzyme for extracellular matrix (ECM) degradation and HGF activation and a target mRNA for miR-27b, was drastically upregulated in the protein level after HGF stimulation, although it was not statistically altered in the mRNA level. These results suggest that miR-200c and miR-27b downregulated by HGF might play an important role in epithelial-mesenchymal transition mediated by ZEB1/E-cadherin and ECM degradation and HGF autoactivation mediated by ST14/matriptase, respectively. Altered expression of miRNA directly regulated by HGF might contribute enhanced progressive and invasive characteristics of HNSCC by regulating the translation of HGF-induced functional molecules.

Urethral Sensations are Related to the Development of Detrusor Overactivity.

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C-fiber afferent nerves. α1A -adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A -adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.

[Investigation of urinary management after removal of indwelling urethral catheters in a general hospital: associations between bedridden state and impaired bladder emptying].

In this study we investigated the influences of decreased levels of activities of daily living (ADL), especially in bedridden patients,on lower urinary tract dysfunction and urinary management during hospital care. All 1,106 non-urological inpatients (896 non-bedridden patients and 210 bedridden patients) with an indwelling urethral catheter treated at Noto General Hospital between April 2006 and October 2009 were retrospectively evaluated. Maximum bladder capacity and post-void residual urine volume (PVR) were evaluated with uroflowmetry or voiding cystourethrography at the time the catheter was removed. Clean intermittent catheterization (CIC) and drug administration were performed for patients who had a PVR of 100 ml or more. Bedridden patients required urinary interventions at a higher rate than did non-bedridden patients (bedridden : 29.0%,non-bedridden : 17.6%). Although indwelling urethral catheters were reinserted in 13 patients in the bedridden group and 16 patients in the non-bedridden group,many patients in both groups could be free from the catheter. Our results indicate that patients with low ADL are vulnerable to impaired bladder emptying,and early diagnosis of impaired bladder emptying and active urinary management are required to solve their urinary problems.

[Mixed epithelial and stromal tumor of the kidney: a case report].

We report a case of a mixed epithelial and stromal tumor of the kidney. A 64-year-old female who had no complaint was found to have a left renal tumor by computed tomography (CT) for an examination of a right breast tumor and was referred to our department. CT revealed a gradually enhancing 5 cm mass in the left kidney. The patient underwent left radical nephrectomy, and the tumor was histologically diagnosed as a mixed epithelial and stromal tumor. The patient has been followed up for 6 months with no evidence of local recurrence or metastasis.