Butyrylcholinesterase level as an independent prognostic factor for overall survival in patients on maintenance hemodialysis: a single-center retrospective study.

BACKGROUND: We investigated whether butyrylcholinesterase (BChE) was independently related to the overall survival (OS) of patients on maintenance hemodialysis (MHD). METHODS: Baseline information, serum BChE level, and other laboratory data were collected from 295 patients on MHD in a single HD hospital in 2018. We retrospectively investigated the mortality of these patients after 38 months. We assessed the prognostic markers such as the Geriatric Nutritional Risk Index (GNRI), Erythropoiesis Resistance Index (ERI), and Simplified Creatinine Index (SCI) of each patient. The primary objective was to examine the impact of BChE on OS. The secondary objective included the designation of a risk score in predicting the OS. RESULTS: We evaluated 284 patients. The median value of the serum BChE level was 206 IU/L. Of 284 patients evaluated, eighty-six patients died; all had a higher ERI and a lower serum BChE level, SCI, and GNRI than the surviving patients. The optimal cutoff values of the BChE level, GNRI, ERI, and SCI for OS were 166 IU/L, 90.0, 8.00, and 20.6, respectively. The multivariate Cox regression analysis showed that the age, HD vintage, dialysis dose, GNRI of < 90.0, and serum BChE level of < 166 IU/L (hazard ratio, 2.03; P = 0.003) were the independent prognostic factors. We designed a risk score consisting of the GNRI and serum BChE level. The predictive value of our risk score was superior to that of GNRI alone. CONCLUSION: The serum BChE level could be an independent prognostic factor for patients on MHD.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

OBJECTIVE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes in patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy. METHODS: A total of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017 were retrospectively examined. Oncological outcomes, including intravesical recurrence-free, visceral recurrence-free, cancer-specific, and overall survival rates (intravesical RFS, visceral RFS, CSS, and OS, respectively) stratified by preoperative CKD status (CKD vs. non-CKD) were investigated. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and a prognostic factor-based risk stratification nomogram was developed. RESULTS: Of the 426 patients, 250 (59%) were diagnosed with CKD before radical nephroureterectomy. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS after radical nephroureterectomy were significantly shorter in the CKD group than in the non-CKD group. Background-adjusted IPTW analysis demonstrated that preoperative CKD was significantly associated with poor visceral RFS, CSS, and OS after radical nephroureterectomy. Intravesical RFS was not significantly associated with preoperative CKD. The nomogram for predicting 5-year visceral RFS and CSS probability demonstrated a significant correlation with actual visceral RFS and CSS (c-index = 0.85 and 0.83, respectively). CONCLUSIONS: Upper tract urothelial carcinoma patients with preoperative CKD had a significantly lower survival probability than those without CKD.

Risk-stratified surveillance and cost effectiveness of follow-up after radical cystectomy in patients with muscle-invasive bladder cancer.

BACKGROUND: The recurrence risk stratification and the cost effectiveness of oncological surveillance after radical cystectomy are not clear. We aimed to develop a risk stratification and a surveillance protocol with improved cost effectiveness after radical cystectomy. RESULTS: Of 581 enrolled patients, 175 experienced disease recurrences. The pathology-based protocol presented significant differences in recurrence-free survival between normal- and high-risk patients, but the medical expense was high, especially in normal-risk (≤pT2pN0) patients. Cox regression analysis identified six factors associated with recurrence-free survival. Risk score-based 5-year follow-up was significantly more cost effective than the pathology-based protocol. MATERIALS AND METHODS: We retrospectively evaluated 581 patients with radical cystectomy for muscle-invasive bladder cancer at 4 hospitals. Patients with routine oncological follow-up were stratified into normal- and high-risk groups by a pathology-based protocol utilizing pT, pN, lymphovascular invasion, and histology. Cost effectiveness of the pathology-based protocol was evaluated and a risk-score-based protocol was developed to optimize cost effectiveness. Risk-scores were calculated by summing risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate-, and high-risk score. Estimated cost per one recurrence detection by the pathology and by risk-scores were compared. CONCLUSIONS: Risk-score-stratified surveillance protocol has potential to reduce over-evaluation after radical cystectomy without adverse effects on medical cost.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy. METHODS: A total of 581 patients who underwent radical cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (pre-CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram. RESULTS: Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the pre-CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS (c-index = 0.73 and 0.77, respectively). CONCLUSIONS: Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.

Detecting asymptomatic recurrence after radical cystectomy contributes to better prognosis in patients with muscle-invasive bladder cancer.

The prognostic benefit of oncological follow-up to detect asymptomatic recurrence after radical cystectomy (RC) remains unclear. We aimed to assess whether routine follow-up to detect asymptomatic recurrence after RC improves patient survival. We retrospectively analyzed 581 RC cases for muscle-invasive bladder cancer at four hospitals between May 1996 and February 2017. All patients had regular follow-up examinations with urine cytology, blood biochemical tests, and computed tomography after RC. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of recurrence (asymptomatic group vs. symptomatic group) was estimated using the Kaplan-Meier method with the log-rank test. Cox proportional hazards regression analysis via inverse probability of treatment weighting (IPTW) was used to evaluate the impact of the mode of diagnosing recurrence on survival. Of the 581 patients, 175 experienced relapse. Among those, 12 without adequate data were excluded. Of the remaining 163 patients, 76 (47%) were asymptomatic and 87 (53%) were symptomatic at the time of diagnosis. The most common recurrence site and symptom were lymph nodes (47%) and pain (53%), respectively. Time of overall survival after RC and from recurrence to death was significantly longer in the asymptomatic group than in the symptomatic group. A multivariate Cox regression analysis using IPTW showed that in the patients with symptomatic recurrence was an independent risk factor for overall survival after RC and survival from recurrence to death. Routine oncological follow-up for detection of asymptomatic recurrence contributes to a better prognosis after RC.

Difference in toxicity reporting between patients and clinicians during systemic chemotherapy in patients with urothelial carcinoma.

OBJECTIVES: To compare toxicity reporting between patients and clinicians in the case of systemic chemotherapy for urothelial carcinoma. METHODS: Between June 2013 and March 2016, 100 urothelial carcinoma patients received two courses of chemotherapy of gemcitabine plus cisplatin or gemcitabine plus carboplatin, and they were prospectively enrolled in the present study. During chemotherapy, patients answered European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire C30 quality-of-life questionnaires, including four toxicity-related symptoms (appetite loss, nausea, constipation and diarrhea). Clinicians evaluated adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Differences of toxicity reporting were compared between patients and clinicians. Logistic regression analyses were carried out to investigate potential factors for underreporting by clinicians. RESULTS: Toxicity underreporting was most frequently for diarrhea (44%), followed by appetite loss (39%), constipation (33%) and nausea (22%). In total, toxicity underreporting was observed in 72% of patients. Background-adjusted logistic regression analyses showed pretreatment quality-of-life items of global, symptomatic scores to be predictors for toxicity underreporting by clinicians. The limitations of the present study included its retrospective nature and small sample size. CONCLUSIONS: Toxicity underreporting by clinicians is frequent in urothelial carcinoma patients receiving systemic chemotherapy. Pretreatment quality-of-life evaluation is essential not only for quality-of-life evaluation, but also to identify potential individuals at risk for toxicity underreporting.

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.

BACKGROUND: Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. METHODS: Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 or <60 mL/min/1.73 m2, respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. RESULTS: The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m2, and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. CONCLUSIONS: Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy. TRIAL REGISTRATION: This study was registered as a clinical trial: UMIN000023577.

Quality-of-life evaluation during platinum-based neoadjuvant chemotherapies for urothelial carcinoma.

BACKGROUND: Although quality of life (QOL) is one of the most important considerations in patients treated with anticancer therapies, desirable regimens for neoadjuvant chemotherapy including QOL in locally advanced urothelial carcinoma remain unclear. The present study evaluated the influence of neoadjuvant platinum-based chemotherapy on QOL in patients with locally advanced urothelial carcinoma. METHODS: Between June 2013 and March 2016, 83 urothelial carcinoma patients who received two courses of neoadjuvant chemotherapy were enrolled in this prospective observational study. Neoadjuvant regimens included gemcitabine + cisplatin (GCis) or gemcitabine + carboplatin (GCb) therapies. As a primary endpoint, we assessed QOL changes in each group before and after chemotherapy using the Quality of Life questionnaire on days 1, 3, and 15 of each cycle. Secondary endpoints included toxicity, safety, weight loss, renal function decline, and tumor responses. RESULTS: QOL analyses were performed in 39 patients receiving GCis and in 44 patients receiving GCb. Appetite loss, role functioning, nausea/vomiting, physical, and fatigue deteriorated >10% from baseline in the GCis group but not in the GCb group. Constipation worsened, whereas scores for pain and emotional items improved in both groups. Objective response rates were 38.5 and 43.2% in the GCis and GCb groups, respectively. CONCLUSIONS: Both GCis and GCb regimens were feasible in terms of QOL. The GCb regimen may be associated with a better QOL status especially in regard to gastrointestinal symptoms.

Preoperative butyrylcholinesterase level as an independent predictor of overall survival in clear cell renal cell carcinoma patients treated with nephrectomy.

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168-470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P = 0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients.

Switching hemodialysis patients from sevelamer hydrochloride to bixalomer: a single-center, non-randomized analysis of efficacy and effects on gastrointestinal symptoms and metabolic acidosis.

BACKGROUND: Bixalomer (BXL) was developed to improve gastrointestinal symptoms and reduce constipation, relative to sevelamer hydrochloride, in hemodialysis patients. We prospectively evaluated the safety and effectiveness of switching maintenance dialysis patients from sevelamer hydrochloride to BXL. METHODS: Twenty-eight patients were switched from sevelamer hydrochloride to BXL (1:1 dose) from July to October 2012, whereas 84 randomly selected patients not treated with sevelamer hydrochloride were enrolled as a control group. The primary endpoint was improvement of gastrointestinal symptoms; secondary endpoints included improvement in metabolic acidosis, changes in blood biochemistry, and safety 12 weeks after the switch. We also surveyed patient satisfaction with switching to BXL 12 weeks after the switch. RESULTS: Before switching, symptoms of epigastric fullness were significantly worse in the switch than in the control group. Twelve weeks after the switch, reflux, epigastric fullness, and constipation had improved significantly in the switch group. Other factors, including stomach ache, diarrhea, and form of stool, did not change significantly. Blood gas analysis showed that metabolic acidosis was significantly improved by switching. Four patients (14%) experienced grade 1 adverse events, all of which improved immediately after stopping BXL. Major adverse events were diarrhea and abdominal discomfort. Mean satisfaction score was 3.1 ± 0.7, with 64% of patients reporting they were "neither satisfied nor dissatisfied" after switching. CONCLUSIONS: A switch from sevelamer hydrochloride to BXL improved symptoms of reflux, epigastric fullness, constipation, and metabolic acidosis in hemodialysis patients. TRIAL REGISTRATION: The study was registered as Clinical trial: (UMIN000011150).

[Paget's disease mimicking metastatic prostate cancer on bone scan image : a case report].

A 61-year-old man was referred to our hospital complaining of elevated serum prostate-specific antigen (PSA) (5.1 ng/ml). Histopathologic diagnosis with trans-rectal prostate biopsy specimen was adenocarcinoma, Gleason score 4+5 = 9. Bone scintigraphy revealed an abnormal uptake on left coxal bone. The patient was diagnosed with prostate cancer with bone metastasis. He received androgen deprivation therapy for two years. Serum PSA decreased to an undetected level. However, the abnormal activity of left coxal bone lesion was not changed on bone scintigraphy. Coxal bone biopsy was performed. The bone lesion was histopathologically diagnosed as Paget's disease of bone.

[Testicular tumor arising in intra-abdominal testis which was not detected at prior orchidopexy : a case report].

A 35-year-old man with an intra-abdominal testicular tumor arising from the right unresolved intraabdominal testis is reported. At 10 years old, left orchidopexy was successfully performed for bilateral undescended testes. However, the right testis was not detected during the operation, and it was diagnosed as vanishing testis. Twenty-five years later, he was referred to our hospital with the complaint of right lower abdominal pain. Computed tomography revealed huge pelvic tumors and bulky para-aortic lymph node swellings. Histopathologic examination of the needle biopsy specimen obtained from the pelvic tumor revealed seminomatous germ cell tumor. Taking the results with a tumor marker study into consideration, the patient was tentatively diagnosed with non-seminomatous germ cell tumor NSGCT (stage IIB) arising from the unresolved intra-abdominal testis or extragonadal germ cell tumor. He received 3 courses of bleomycin, etoposide, cisplatin (BEP), and 4 courses of VP-16, ifosfamide, cisplatin (VIP). After chemotherapy, we performed tumorectomy and retroperitoneal lymphadenectomy because tumor markers were normalized and 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)-CT revealed normalization. We identified the pelvic tumor as an intra-abdominal testicular tumor arising from right unresolved intra-abdominal testis. Pathological examination revealed no residual tumor cells. There has been no recurrence 17 months after surgery.

Macroscale and microscale analyses of nitrification and denitrification in biofilms attached on membrane aerated biofilm reactors.

A membrane aerated biofilm reactor (MABR), in which O(2) was supplied from the bottom of the biofilm and NH(4)(+) and organic carbon were supplied from the biofilm surface, was operated at different organic carbon loading rates and intra-membrane air pressures to investigate the occurrence of simultaneous chemical oxygen demand (COD) removal, nitrification and denitrification. The spatial distribution of nitrification and denitrification zones in the biofilms was measured with microelectrodes for O(2), NH(4)(+), NO(2)(-), NO(3)(-) and pH. When the MABR was operated at approximately 1.0 g-COD/m(2)/day of COD loading rate, simultaneous COD removal, nitrification and denitrification could be achieved. The COD loading rates and the intra-membrane air pressures applied in this study had no effect on the start-up and the maximum rates of NH(4)(+) oxidation in the MABRs. Microelectrode measurements showed that O(2) was supplied from the bottom of the MABR biofilm and penetrated the whole biofilm. Because the biofilm thickness increased during the operations, an anoxic layer developed in the upper parts of the mature biofilms while an oxic layer was restricted to the deeper parts of the biofilms. The development of the anoxic zones in the biofilms coincided with increase in the denitrification rates. Nitrification occurred in the zones from membrane surface to a point of ca. 60microm. Denitrification mainly occurred just above the nitrification zones. The COD loading rates and the intra-membrane air pressures applied in this study had no effect on location of the nitrification and denitrification zones.