Hematobium schistosomiasis control for health management of labor force generation at Nkhotakota and Lilongwe in the Republic of Malawi-assumed to be related to occupational risk.

BACKGROUND: In Malawi, hematobium schistosomiasis is highly endemic. According to previous studies, countermeasures have been conducted mainly in school-aged children. In this study, we focused on the age groups, which are assumed to be major labor force generation. Hematobium schistosomiasis is supposed to be related to occupational activities in schistosome-endemic countries because of its infectious route. We chronologically followed the transition of schistosome egg-positive prevalence before and after mass drug administration of praziquantel (MDA) by using a urine filtering examination. We also analyzed the effectiveness of urine reagent strips from the cost perspective. RESULTS: The egg-positive prevalence was 34.3% (95% CI 28.5-40.5) just before MDA in June 2010 and the highest prevalence was in the age of twenties. The egg-positive prevalence reduced to 12.7% (95% CI 9.2-17.3, p < 0.01) 8 weeks after the first MDA and the prevalence reduced to 6.9% (95% CI 4.6-10.0, p < 0.01) after the second MDA in August 2011. The egg-positive prevalence after MDA in 2013 was reduced from 3.8% (95% CI 2.1-6.9) to 0.9% (95% CI 0.3-3.4) and p value was 0.050. Using urine reagent strips after MDA, the positive predictive value decreased, but the negative predictive value remained high. The cost of one urine reagent strip and one tablet of praziquantel were US$0.06 and US$0.125 in 2013 in Malawi. If the egg-positive prevalence is 40%, screening subjects for MDA using urine reagent strips, the cost reduction can be estimated to be about 24%, showing an overall cost reduction. CONCLUSIONS: MDA of praziquantel can assuredly reduce schistosome egg-positive prevalence. The combination of MDA and urine reagent strips could be both a practical and cost-effective countermeasure for hematobium schistosomiasis. It is key to recognize that hematobium schistosomiasis could be considered a disease that is assumed to have some concern with occupational risk at Nkhotakota and Lilongwe in Malawi. From this point of view, it is very important to manage workers' health; the sound labor force generation is vital for economic growth and development in these areas and countries.

The narrow vesicourethral angle measured on postoperative cystography can predict urinary incontinence after robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: Radical prostatectomy is associated with complications including urinary incontinence. A significant association between specific features of the vesicourethral anastomosis and urinary incontinence after radical prostatectomy has been demonstrated. The aim of this study was to identify the most useful predictor of postoperative urinary incontinence after robot-assisted laparoscopic radical prostatectomy (RALP) according to the features of the vesicourethral anastomosis as determined by postoperative cystography. MATERIALS AND METHODS: The final study cohort consisted of 150 patients. Postoperative cystography was performed within 1 week after RALP. The ratio between the longitudinal and horizontal lengths (L/H) of the bladder, the position of the urethrovesical junction (UVJ) and the bladder neck angle as seen on the cystogram were evaluated. Postoperative continence status was evaluated by a 1 h pad test 1 day after catheter removal and by the use of safety pads, retrieved retrospectively from patient records. The association between these variables and urinary incontinence was then analyzed. All patients were followed for at least 1 year postoperatively. RESULTS: The continence rates on the 1 h pad test and 1 month and 1 year after RALP were 31.3%, 56% and 93.3%, respectively. In multivariate analyses, urinary incontinence was significantly associated with nerve sparing, L/H and the vesical angle as determined on the 1 h pad test, but only with the vesical angle at 1 month and 1 year postoperatively. CONCLUSION: A narrow vesical angle measured on cystography is a useful predictor of postoperative urinary incontinence after RALP.

Laparoendoscopic single-site surgery for treatment of urachal remnants.

INTRODUCTION: To evaluate safety and excellent cosmetic outcome with laparoendoscopic single-site surgery (LESS). In this study, we compared the usefulness and efficacy of LESS versus conventional laparoscopic surgery for the treatment of urachal remnants. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 20 consecutive patients who underwent either conventional laparoscopic surgery or LESS from January 2007 to February 2015 at Kansai Medical University Hospital. Ten patients underwent surgery using the standard laparoscopic 3-port technique, and 10 patients underwent LESS. The patients included 12 males and 8 females (mean age, 24.5 years; range, 10-68 years). The patients' characteristics, surgical data, and postoperative pain assessment results were retrospectively collected and analyzed. RESULTS: The median operative time, pneumoperitoneal surgery time, and estimated blood loss did not differ between the LESS and conventional laparoscopic groups. However, the total incision length was longer in the conventional laparoscopic group than in the LESS group. The degree of pain at 2 to 5 days postoperatively according to the Wong-Baker FACES Pain Rating Scale was lower in the LESS group than in the conventional laparoscopic group (p < 0.05). CONCLUSIONS: Less is a possible option in the surgical treatment for urachal remnants. In this very small cohort, there is no conversion to traditional laparoscopic surgery or open surgery. This technique is possibly feasible and may achieve less pain. Accumulation of surgical outcomes especially in safety and cosmesis is required to be an established method.

Intestinal stem cells contribute to the maturation of the neonatal small intestine and colon independently of digestive activity.

The murine intestine, like that of other mammalians, continues to develop after birth until weaning; however, whether this occurs in response to an intrinsic developmental program or food intake remains unclear. Here, we report a novel system for the allotransplantation of small intestine and colon harvested from Lgr5 EGFP-IRES-CreERT2/+; Rosa26 rbw/+ mice immediately after birth into the subrenal capsule of wild-type mice. By histological and immunohistochemical analysis, the developmental process of transplanted small intestine and colon was shown to be comparable with that of the native tissues: mature intestines equipped with all cell types were formed, indicating that these organs do not require food intake for development. The intestinal stem cells in transplanted tissues were shown to self-renew and produce progeny, resulting in the descendants of the stem cells occupying the crypt-villus unit of the small intestine or the whole crypt of the colon. Collectively, these findings indicate that neonatal intestine development follows an intrinsic program even in the absence of food stimuli.

[Devices to Perform Laparo-Endoscopic Single Site Surgery for Urachal Remnants without Additional Ports].

The laparoscopic management of urachal remnants has gradually become a common practice. Recently, laparoscopic single-site surgery (LESS), a minimally invasive approach that provides excellent cosmetic results, has been adopted in several surgical procedures for treating urachal remnants. However, when suturing the bladder wall or peritoneal defect during LESS it may be difficult to conduct the procedure manually, and such cases require an additional port for suturing. Our strategy, however, employs a knot pusher to perform the suturing without the need for an additional port. We compared and examined the perioperative parameters of the patients with the additional port and one without it (knot-pusher group). For the additional-port and knot-pusher groups, the average operative time, was 146.8 and 161.7 minutes respectively, pneumoperitoneal surgery time was 90.8 and 88.0 minutes, respectively, suturing time for the bladder wall was 577 and 502 seconds, respectively suturing time for peritoneal defect was 758 vs 779 seconds, respectively, and estimated blood loss was 19 and 9.6 ml, respectively ; there being no significant difference between the two groups. We report our knot-pusher method because it can achieve comparable results without compromising the surgical outcome.

Preoperative sexual status of Japanese localized prostate cancer patients: comparison of sexual activity and EPIC scores.

OBJECTIVE: This study aimed to evaluate the relationship between sexual activity and sexual function using questionnaires distributed to middle-aged Japanese patients with localized prostate cancer. METHODS: A total of 145 patients who underwent radical prostatectomy were enrolled in the survey reported on herein. Sexual activity and sexual function were investigated via the Expanded Prostate Cancer Index Composite (EPIC) and an original self-reported questionnaire. RESULTS: Of participants, 24.1% and 20.7% had sexual activity within a month period as investigated via the EPIC and original questionnaire, respectively. However, 29.7% of all those who reported sexual activity rate reported "about once every 2 months to a year," as shown in the original questionnaire. Regarding sexual function as addressed through EPIC, no results within that questionnaire's measure of sexual function showed significant differences among patients with a rate of actual sexual activity. CONCLUSIONS: The present survey showed that more than quarter of preoperative middle-aged Japanese prostate cancer patients surveyed had actual sexual activity, though not within the preceding 4 weeks. To precisely evaluate sexual function of middle-aged Japanese patients, it is necessary to consider actual sexual activity.

Introduction of an Enhanced Recovery after Surgery Protocol for Robot-Assisted Laparoscopic Radical Prostatectomy.

INTRODUCTION: No studies have shown whether the enhanced recovery after surgery (ERAS) protocol is superior to the conventional protocol after robot-assisted laparoscopic radical prostatectomy (RALP). We compared intestinal function and perioperative parameters of patients with prostate cancer after the ERAS and conventional protocols to determine the superior protocol for recovery of intestinal function. MATERIAL AND METHODS: A retrospective analysis of 198 consecutive patients who underwent RALP between August 2013 and June 2015 was conducted. Our study design included 2 cohorts. Patients underwent conventional care in one group (n = 123) and the ERAS protocol in the other group (n = 75). The primary outcome was the time to first defecation. Secondary outcomes were perioperative parameters and the complication rate. RESULTS: The ERAS group showed a significantly shorter time to first defecation than did the conventional group (p = 0.006). Multivariate analysis showed that selection of the ERAS protocol was significantly associated with the number of days for first time to defecation. CONCLUSIONS: Successful application of an ERAS protocol was applied to our patients who underwent RALP and did not have major complications. The ERAS protocol included enhanced intestinal recovery. The ERAS group showed a significantly shorter time to first defecation than did the conventional group.

Intestinal cancer stem cells marked by Bmi1 or Lgr5 expression contribute to tumor propagation via clonal expansion.

Although the existence of cancer stem cells in intestine tumors has been suggested, direct evidence has not been yet provided. Here, we showed, using the multicolor lineage-tracing method and mouse models of intestinal adenocarcinoma and adenoma that Bmi1- or Lgr5- positive tumorigenic cells clonally expanded in proliferating tumors. At tumor initiation and during tumor propagation in the colon, the descendants of Lgr5-positive cells clonally proliferated to form clusters. Clonal analysis using ubiquitous multicolor lineage tracing revealed that colon tumors derived from Lgr5-positive cells were monoclonal in origin but eventually merged with neighboring tumors, producing polyclonal tumors at the later stage. In contrast, the origin of small intestine tumors was likely polyclonal, and during cancer progression some clones were eliminated, resulting in the formation of monoclonal tumors, which could merge similar to colon tumors. These results suggest that in proliferating intestinal neoplasms, Bmi1- or Lgr5-positive cells represent a population of cancer stem cells, whereas Lgr5-positive cells also function as cells-of-origin for intestinal tumors.

Prognostic Impact of Renin-Angiotensin Inhibitors in Patients with Bladder Cancer Undergoing Radical Cystectomy.

BACKGROUND: Renin-angiotensin system blockade has been effective for the treatment of patients with several types of malignancy. This study evaluated the prognostic impact of renin-angiotensin system inhibitors, including angiotensin-2 converting enzyme inhibitors and angiotensin 2 receptor blockers, in patients with bladder cancer undergoing radical cystectomy. METHODS: This retrospective study included 269 patients who had undergone radical cystectomy. The oncologic outcomes of patients treated or not treated with renin-angiotensin system inhibitors after surgery were evaluated. Overall survival and cancer-specific survival were assessed by the Kaplan-Meier method and by Cox regression analysis. RESULTS: The median follow-up duration after radical cystectomy in survivors was 44.5 months. The 5-year, cancer-specific survival rates in patients who did and did not receive renin-angiotensin system inhibitors were 79.0 and 66.4 %, respectively (P = 0.011). Similarly, the 5-year overall survival rates were 76.1 and 61.4 %, respectively (P = 0.0097). Multivariable analyses showed that use of renin-angiotensin system inhibitors was an independent prognostic factor for cancer-specific survival (hazard ratio 0.47, P = 0.036) and for overall survival (hazard ratio 0.36, P = 0.022). CONCLUSIONS: Renin-angiotensin system inhibitors significantly reduced the risks of cancer-specific and overall mortality after radical cystectomy in patients with bladder cancer. Renin-angiotensin system inhibitors may improve oncologic outcomes in high-risk patients with bladder cancer.

Influence of scars on body image consciousness with respect to gender following laparoendoscopic single-site versus conventional laparoscopic surgery.

OBJECTIVE: The aim of this study was to evaluate and compare the cosmetic outcomes of laparoscopic single-site surgery (LESS) and conventional laparoscopy (CL) in the treatment of ureteropelvic junction obstruction (UPJO) and urachal remnant removal. LESS is thought to produce better cosmetic results than CL; however, patients' perception of their scars has not been assessed. This study compared the subjective body image and cosmesis ratings of patients who had undergone LESS or CL for UPJO and urachal remnant removal. MATERIALS AND METHODS: Fifty patients who underwent LESS or CL for UPJO or urachal remnant removal between June 2008 and June 2015 were included. Cosmetic outcomes were evaluated using the Body Image Questionnaire (BIQ) and Photo-Series Questionnaire (PSQ). RESULTS: The body image and cosmetic scores were significantly higher for patients who underwent LESS than for those who underwent CL, for both pyeloplasty and urachal remnant removal (p < .05 each). When performed for either a pyeloplasty or urachal remnant removal, significantly greater BIQ and PSQ scores were observed in females after LESS compared to CL, but not in males. CONCLUSION: LESS for UPJO and urachal remnant removal has better self-reported body image and cosmesis ratings than CL. This trend is particularly strong in female patients.

Urinary l-type fatty acid-binding protein is a predictor of early renal function after partial nephrectomy.

PURPOSE: Urinary biomarkers of renal injury urinary may identify loss of renal function following nephron-sparing surgery (NSS). This study was designed to evaluate whether urinary l-type fatty acid-binding protein (l-FABP) is an early biomarker of loss of renal function after NSS. Specifically, the kinetics of urinary l-FABP level after NSS and its correlation with factors related to ischemic renal injury were analyzed. METHODS: This study prospectively evaluated 18 patients who underwent NSS between July and December 2014, including 12 who underwent laparoscopic and six who underwent robot-assisted partial nephrectomy. Urinary l-FABP concentrations were measured preoperatively and 1, 2, 3, 6, 12, 24, 48, and 72 h after renal artery declamping. Loss of renal function loss was calculated by comparing the effective renal plasma flow, as determined by 99mTc-mercaptoacetyltriglycine (MAG3) clearance, on the operated and normal sides. The decrease in estimated glomerular filtration rate from before surgery to six months after surgery was also measured. RESULTS: Urinary l-FABP concentration peaked within 2 h of declamping, which may quantify nephron damage caused by ischemia. The decrease in MAG3 reduction ratio correlated with both the ischemia time and peak urinary l-FABP concentration. Peak urinary l-FABP concentration showed a significant correlation with MAG3 reduction ratio. CONCLUSIONS: l-FABP is a suitable urinary biomarker for predicting the extent of ischemic renal injury.

Bmi1-positive cells in the lingual epithelium could serve as cancer stem cells in tongue cancer.

We recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells (LESCs), which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. However, the precise role of LESCs in generating tongue tumors and Bmi1-positive cell lineage dynamics in tongue cancers are unclear. Here, using a mouse model of chemically (4-nitroquinoline-1-oxide: 4-NQO) induced tongue cancer and the multicolor lineage tracing method, we found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor. Although many Bmi1-positive cells within the tongue cancer specimens failed to proliferate, some proliferated continuously and supplied tumor cells to the surrounding area. This process eventually led to the formation of areas derived from single cells after 1-3 months, as determined using the multicolor lineage tracing method, indicating that such cells could serve as cancer stem cells. These results indicate that LESCs could serve as the origin for tongue cancer and that cancer stem cells are present in tongue tumors.

Perioperative change in neutrophil-lymphocyte ratio predicts the overall survival of patients with bladder cancer undergoing radical cystectomy.

OBJECTIVE: To assess the prognostic value of perioperative changes in the neutrophil-lymphocyte ratio in patients with bladder cancer undergoing radical cystectomy. METHODS: We performed a retrospective analysis of 323 patients who had undergone radical cystectomy at our institutions. Overall survival was assessed with the Kaplan-Meier method and Cox regression analysis. RESULTS: Preoperative and postoperative neutrophil-lymphocyte ratios were significantly correlated with overall survival (both P = 0.0001). Changes in perioperative neutrophil-lymphocyte ratio stratified the patients into two groups, designated favorable- and poor-risk groups, with significantly different 5-year overall survival rates (75.1% and 41.4%, respectively; P < 0.0001). Multivariate Cox regression analyses showed that the perioperative change in neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival (hazard ratio 2.56, 95% confidence interval 1.75-3.73; P < 0.001). Moreover, a decrease in neutrophil-lymphocyte ratio after adjuvant chemotherapy was associated with favorable overall survival in patients with high postoperative neutrophil-lymphocyte ratio (P < 0.001), indicating that neutrophil-lymphocyte ratio may be a predictive factor for the efficacy of adjuvant chemotherapy. CONCLUSIONS: Perioperative changes in neutrophil-lymphocyte ratio are significantly associated with overall survival in patients with bladder cancer undergoing radical cystectomy. Follow-up of the neutrophil-lymphocyte ratio change may be useful for the clinical management of patients after surgery.

Intravesical Prostatic Protrusion as a Predicting Factor for the Adverse Clinical Outcome in Patients With Symptomatic Benign Prostatic Enlargement Treated With Dutasteride.

OBJECTIVE: To evaluate the role of intravesical prostatic protrusion (IPP) as a predictive factor for adverse clinical outcomes in patients treated with dutasteride for lower urinary tract symptoms secondary to benign prostatic enlargement (BPE). METHODS: In total, 111 patients treated with dutasteride for symptomatic BPE were analyzed. Stepwise multivariate logistic regression was applied to evaluate predictors for acute urinary retention (AUR) or benign prostatic hyperplasia (BPH)-related surgery. We applied an IPP cutoff value of 10 mm. The clinical variables were assessed using univariate analysis. RESULTS: Of 111 patients, 27 (24.3%) developed AUR or required surgical intervention. On multivariate analysis, IPP remained as the independent predictor for AUR and need for BPH-related surgery (odds ratio, 1.27; P < .001). Both international prostate symptom score and maximum urinary flow rate significantly improved in patients with low IPP (P = .03 and P < .001, respectively), but not in those with high IPP. No significant reduction was found in the degree of IPP despite the significant reduction in prostate volume after dutasteride treatment (P = .84 and P < .001, respectively). The 3-year cumulative incidence of AUR or BPH-related surgery in the low IPP group vs the high IPP group was 9.9% vs 71.5%, respectively (P < .001). CONCLUSION: High IPP is associated with a higher risk of treatment resistance, AUR, or the need for prostatic surgery in patients receiving dutasteride treatment for symptomatic BPE. Dutasteride might not be effective for IPP reduction.

Prognostic impact of perioperative lymphocyte-monocyte ratio in patients with bladder cancer undergoing radical cystectomy.

Various systemic inflammatory response biomarkers are associated with oncological outcome. We evaluated the superiority of prognostic predictive accuracy between neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR), and the prognostic significance of their perioperative change in patients with bladder cancer undergoing radical cystectomy (RC). We retrospectively analyzed 302 patients who had undergone RC in four institutions. Comparison of predictive accuracy between NLR and LMR was performed using receiver operating characteristic curve analysis. Overall survival (OS) and cancer-specific survival (CSS) were assessed with the Kaplan-Meier method and Cox regression analysis. Preoperative and postoperative LMR showed higher predictive accuracy for OS than NLR did (p = 0.034). Applying a cutoff of 3.41, change in perioperative LMR stratified patients into three groups (low, intermediate, and high risk), showing a significant difference in OS and CSS (p < 0.001, each), and pathological outcomes. Multivariable analyses for OS and CSS showed that poor changes in LMR (high risk) were an independent prognostic factor (hazard ratio 5.70, 95 % confidence interval 3.49-9.32, p < 0.001; hazard ratio 4.53, 95 % confidence interval 2.63-7.82, p < 0.001; respectively). Perioperative LMR is significantly associated with survival in patients with bladder cancer after RC, and it is possibly superior to NLR as a prognostic factor.

Comparison of diameter-axial-polar nephrometry score and RENAL nephrometry score for surgical outcomes following laparoscopic partial nephrectomy.

OBJECTIVES: To compare diameter-axial-polar nephrometry score with RENAL nephrometry score for surgical outcomes after laparoscopic partial nephrectomy. METHODS: We retrospectively reviewed data from 134 patients who underwent laparoscopic partial nephrectomy, using diameter-axial-polar and RENAL scores. We analyzed data for warm ischemic time and estimated blood loss intraoperatively, and percentage change in estimated glomerular filtration rate 6 months and 1 year postoperatively. Both scores were classified as low-, middle- and high-risk, and were used to compare the three analyzed parameters. RESULTS: The median tumor size was 2.3 cm (range 1.0-5.4 cm); warm ischemic time was 25.4 min (range 6.5-57 min); and at 6 months and 1 year, percentage change in estimated glomerular filtration rate was 93% (range 51.7-133.3%) and 91% (range 49.4-137.6%), respectively. There were no significant differences in warm ischemic time and estimated blood loss for RENAL between risk groups (P = 0.38 and 0.09, respectively), but significant differences between groups for diameter-axial-polar score (P = 0.02 and 0.01, respectively). There were no significant differences in either score between groups for percentage change in estimated glomerular filtration rate at 6 months and 1 year. A total of 27 high-risk cases with a diameter-axial-polar score of seven points underwent laparoscopic partial nephrectomy safely; all three cases with a diameter-axial-polar score of eight points were converted to open partial nephrectomy. CONCLUSIONS: Diameter-axial-polar score seems to estimate the complexity of tumor characteristics in patients undergoing laparoscopic partial nephrectomy better than RENAL score. It has a better correlation with warm ischemic time and estimated blood loss.

Short-term outcome and quality of life in kidney transplant recipient with monoclonal gammopathy.

Monoclonal gammopathy of undetermined significance (MGUS) is the common pre-malignant B cell disorders with a general prevalence of 3-5 % at age over 50. Because of the potential malignant transformation and immune insufficiency, pre-transplant MGUS recipient should be carefully followed after allograft transplantation. The post-transplant prognosis and quality of life (QOL) in patient with MGUS have not yet been fully determined. The aim of this study is to evaluate function and pathology of the renal allograft and self-assessment QOL changes during 2 years after transplantation in our case of MGUS-bearing recipient. We here studied the clinical course and QOL improvement before and 20 months after transplant in a 56-year-old woman, who had pre-existing MGUS and underwent living donor kidney transplantation. After the renal allograft transplant, the patients maintained normal GFR and had neither acute rejections nor histologic evidence of renal injuries related to the monoclonal gammopathy on the protocol biopsy of 1 year post-transplant. During further 20 months follow-up, the pre-transplant MGUS remained uneventful without any hematologic abnormalities and other medical complications, i.e., infection. Evaluation of QOL using a self-assessment questionnaire showed significant improvement for physical and mental items on both 6 and 18 months post-transplant. The renal transplant thus successfully provided a greater satisfaction for the recipient on both physical and mental health aspects. Our observations suggest that renal transplantation is beneficial even in those who had pre-existing MGUS if managed and followed carefully, which ultimately could significantly improve the patient QOL.

A novel risk stratification model, involving preoperative lymphocyte-monocyte ratio and standard pathological factors, for overall survival in patients with bladder cancer undergoing radical cystectomy.

OBJECTIVE: To evaluate the ability of preoperative lymphocyte-monocyte ratio to predict prognosis and determine post-operative risk stratification in patients with bladder cancer undergoing radical cystectomy. METHODS: A retrospective review of the 210 patients who had undergone radical cystectomy for bladder cancer from 2006 to 2013 identified 181 patients with sufficient data to evaluate the prognostic significance of the lymphocyte-monocyte ratio. Overall survival was assessed by the Kaplan-Meier method. The association of clinicopathological findings with overall survival was evaluated by a multivariate Cox proportional model, and a novel risk stratification model to predict prognosis was established. RESULTS: Median follow-up after radical cystectomy was 6.0 years. The 5-year overall survival rate was significantly lower for patients with low than high lymphocyte-monocyte ratio (27.6 vs 80.7%, P < 0.001). Multivariable analyses showed that pT ≥2, pN ≥1, positive margins and low lymphocyte-monocyte ratio were independent predictors of overall survival. A post-operative risk stratification model using these factors showed significant differences among the three subgroups (low, intermediate and high risk) with a concordance index of 0.84. The 5-year overall survival rates in patients at low, intermediate and high risk were 85.4, 45.5 and 0%, respectively (P < 0.001). CONCLUSIONS: Preoperative lymphocyte-monocyte ratio, pathological tumor and lymph node stage and positive margins are significantly associated with overall survival in patients who have undergone radical cystectomy for bladder cancer.

Maintenance of sweat glands by stem cells located in the acral epithelium.

The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes.

Bmi1 expression in long-term germ stem cells.

Asingle cells in undifferentiated spermatogonia are considered to be the most primitive forms of germ stem cells (GSCs). Although GFRα1 is thought to be a marker of Asingle cells, we found that Bmi1(High) is more specific than GFRα1 for Asingle cells. Bmi1(High) expression in Asingle cells is correlated with seminiferous stages, and its expression was followed by the proliferative stage of Asingle GSCs. In contrast, GFRα1 expression was seminiferous stage-independent. Fate analyses of EdU-positive Bmi1(High)-positive cell-derived Asingle cells revealed that these cells self-renewed or generated transient amplifying Apaired cells. Bmi1(High)-positive cells were resistant to irradiation-induced injury, after which they regenerated. Elimination of Bmi1(High)-positive cells from seminiferous tubules resulted in the appearance of tubules with seminiferous stage mismatches. Thus, in this study, we found that Bmi1(High) is a seminiferous stage-dependent marker for long-term GSCs and that Bmi1(High)-positive cells play important roles in maintaining GSCs and in regenerating spermatogenic progenitors after injury.