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.

Pre-dialysis serum creatinine as an independent predictor of responsiveness to zinc supplementation among patients on hemodialysis.

BACKGROUND: To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD). METHODS: We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of < 80 µg/dL three months after the study began. Patients were divided into two groups: late response (serum zinc level < 80 µg/dL) and early response (serum zinc level ≥ 80 µg/dL). Factors independently associated with a late response to zinc supplementation were determined using inverse probability of treatment weighting (IPTW) multivariate logistic analysis. RESULTS: Of 91 patients, 86 continued to receive zinc supplementation after three months. The mean pre-dialysis SCre level was 10.0 mg/dL. The number of patients with a late response and response to zinc supplementation was 32 and 54, respectively. There was a significant negative correlation between the pre-dialysis SCre and the Δserum zinc change for 3 months. (r = - 0.284, P = 0.008). IPTW multivariate analysis showed that a pre-dialysis SCre level ≥ 10.0 mg/dL (odds ratio, 3.71; 95% confidence interval; 1.24-11.1, P = 0.022) was an independent factor associated with a late response to zinc supplementation. CONCLUSIONS: Pre-dialysis SCre level was independently associated with responsiveness to zinc supplementation after three months in patients on MHD.

Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single-center, open-label, prospective randomized study.

The efficacy and safety of zinc acetate hydrate (ZAH) for zinc supplementation in patients on maintenance hemodialysis (MHD) remains unknown. In this prospective, single-center, open-label, parallel-group trial for MHD patients with serum zinc level <70 µg/dL, we compared ZAH (zinc; 50 mg/day) and polaprezinc (PPZ; zinc; 34 mg/day) beyond 6-month administration in a 1:1 randomization manner. The ZAH and PPZ groups had 44 and 47 patients, respectively. At 3 months, the change rate of serum zinc levels in the ZAH group was significantly higher than that in the PPZ group. Three months after the study, serum copper levels significantly decreased in the ZAH group, but not in the PPZ group. No significant differences were noted in anemia management in either group. ZAH was superior to PPZ in increasing serum zinc levels. Clinicians should note the stronger decline in serum copper levels when using ZAH for MHD patients.

Low serum butyrylcholinesterase is independently related to low fetuin-A in patients on hemodialysis: a cross-sectional study.

PURPOSE: Fetuin-A, which plays a protective role against the atherosclerosis and progression of vascular calcification, is decreased in patients on hemodialysis (HD). Fetuin-A and serum butyrylcholinesterase (BChE) levels decrease during malnutrition. We explored whether BChE was independently related to fetuin-A in patients on HD. METHODS: Laboratory data including BChE and serum fetuin-A were acquired from 230 patients on HD between August 2017 and April 2018. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). Abdominal aortic calcification index (ACI) was measured using computed tomography. Patients were stratified into two groups: low fetuin-A (< lowest quartile) and non-low fetuin-A (≥ lowest quartile) groups. Patient background, medication, and laboratory data were compared. The receiver operating characteristic analysis was conducted to determine the optimal cutoff values of BChE and GNRI for lower fetuin-A level. Factors independently related with lower fetuin-A levels were determined using multivariate logistic regression analysis. RESULTS: The lowest quartile value of fetuin-A and optimal cutoff values of BChE and GNRI were 0.213 g/L, 200 IU/L, and 92.6, respectively. The study included 57 and 173 patients in the low fetuin-A and non-low fetuin-A groups, respectively. Significant between-group differences were observed for age, C-reactive protein (CRP), history of cardiovascular disease, serum albumin, GNRI, and BChE. Multivariate analysis showed that BChE of < 200 IU/L [odds ratio (OR) 3.05], CRP (OR 2.49), and GNRI of < 92.6 (OR 2.34) were independent factors for lower fetuin-A level after adjusting for confounders. CONCLUSIONS: BChE was a significant independent marker for fetuin-A levels in patients on HD, in addition to GNRI.

Proton pump inhibitor as an independent factor of progression of abdominal aortic calcification in patients on maintenance hemodialysis.

BACKGROUNDS: Proton pump inhibitors (PPIs) can be associated with vascular calcification in patients undergoing dialysis through hypomagnesemia. However, only few studies have demonstrated the influence of PPIs on vascular calcification in patients on maintenance hemodialysis (HD). This study aimed to investigate whether the use of PPIs accelerates vascular calcification in patients on HD. MATERIALS AND METHODS: We retrospectively evaluated 200 HD patients who underwent regular blood tests and computed tomography (CT) between 2016 and 2017. The abdominal aortic calcification index (ACI) was measured using abdominal CT. The difference in the ACI values between 2016 and 2017 was evaluated as ΔACI. Patients were divided into PPI and non-PPI groups, and variables, such as patient background, medication, laboratory data, and ΔACI were compared. Factors independently associated with higher ΔACI progression (≥ third tertile value of ΔACI in this study) were determined using multivariate logistic regression analysis. RESULTS: The PPI and non-PPI groups had 112 (56%) and 88 (44%) patients, respectively. Median and third tertile value of ΔACIs were 4.2% and 5.8%, respectively. Serum magnesium was significantly lower in the PPI (2.1 mg/dL) than in the non-PPI (2.3 mg/dL) group (P <0.001). Median ΔACI was significantly higher in the PPI (5.0%) than in the non-PPI (3.8%) group (P = 0.009). A total of 77 (39%) patients had a higher ΔACI. Multivariate analysis revealed that PPIs (odds ratio = 2.23; 95% confidence interval = 1.11-4.49), annual mean calcium phosphorus product, ACI in 2016, baseline serum magnesium levels, and HD vintage were independent factors associated with higher ΔACI progression after adjusting for confounders. CONCLUSION: PPI use may accelerate vascular calcification in patients on HD. Further studies are necessary to elucidate their influence on vascular calcification.

Butyrylcholinesterase level as an independent factor of erythropoiesis-stimulating agent resistance in patients on maintenance hemodialysis: a single-center cross-sectional study.

BACKGROUND: Erythropoiesis-stimulating agent (ESA) responsiveness is related to the nutritional status of patients on hemodialysis (HD). Serum butyrylcholinesterase (BChE), an alpha-glycoprotein, may decrease in case of malnutrition. We investigated whether BChE was independently related to ESA resistance in patients on HD. METHODS: The laboratory data and ESA resistance index (ERI), defined as ESA dosage per week divided by dry weight and hemoglobin, were investigated in 215 patients on HD between July and September 2017. Malnutrition was defined as Geriatric Nutritional Risk Index (GNRI) of < 91.2. The patients were stratified into two groups: ERI-high (ERI ≥ 9.44) and ERI-low (ERI < 9.44) groups. Variables such as patient's background, medication, and laboratory data were compared between the two groups. The optimal cutoff value of BChE for higher ERI was determined using receiver operating characteristic analysis. Factors independently associated with higher ERI were determined using multivariate logistic regression analysis. RESULTS: The median and optimal cutoff values of ERI and BChE were 6.51 and 200 IU/L, respectively. The study included 71 (33%) and 144 (67%) patients in the ERI-high and ERI-low groups, respectively. Significant between-group differences were observed concerning age, hemoglobin, ESA dose, lipid profiles, serum albumin, body mass index, GNRI, iron metabolism markers, ferric medicines, and BChE. Multivariate analysis showed that BChE < 200 IU/L (odds ratio 3.67; 95% confidence interval 1.73-7.77) continued to be an independent factor associated with higher ERI after adjusting for potential confounders, which was a similar odds ratio as GNRI < 91.2. CONCLUSION: BChE may be an independent indicator of ESA resistance.

Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas.

The aim of this study to determine whether the aberrant N-glycosylated serum immunoglobulins (Igs) can be applied as a diagnostic marker of urothelial carcinoma (UC). Between 2009 and 2016, we randomly obtained serum available from 237 UC and also 96 prostate cancer as other cancer controls from our serum bank and also obtained-from 339 healthy volunteers (HV)-controls obtained from community-dwelling volunteers in Iwaki Health Promotion Project. A total of 32 types of N-glycan levels on Igs were determined by high-throughput N-glycomics and analyzed by multivariable discriminant analysis. We found five UC-associated aberrant N-glycans changes on Igs and also found that asialo-bisecting GlcNAc type N-glycan on Igs were significantly accumulated in UC patients. The diagnostic N-glycan Score (dNGScore) established by combination of five N-glycans on Igs discriminated UC patients from HV and prostate cancer (PC) patients with 92.8% sensitivity and 97.2% specificity. The area under the curve (AUC) for of the dNGScore was 0.969 for UC detection that was much superior to that of urine cytology (AUC, 0.707) and hematuria (AUC, 0.892). Furthermore, dNGScore can detect hematuria and urine cytology negative patients. The dNGscore based on aberrant N-glycosylation signatures of Igs were found to be promising diagnostic biomarkers of UCs.

Surgery without Blood Transfusion for Giant Paraganglioma in a Jehovah's Witness Patient.

A retroperitoneal tumor was identified in a 57-year-old female belonging to Jehovah's Witnesses during a health check. Subsequent examination led to the suspicion of a right pheochromocytoma. The patient wished to be treated by bloodless surgery and consulted our hospital after being refused surgery by several hospitals. She signed a liability waiver for blood transfusion refusal. After obtaining consent for diluted autotransfusion and preoperative administration of erythropoietin, the surgery was scheduled. The tumor was attached to the inferior vena cava and left renal vein and engulfed the right renal artery and vein. The tumor and right kidney were removed en bloc. Operative time was 8 h and 18 min, with 1,770 ml of blood loss. The histopathological diagnosis was paraganglioma with the normal adrenal gland within the border of the tumor. The patient was discharged from the hospital with no postoperative complications.

Invadopodia are essential in transurothelial invasion during the muscle invasion of bladder cancer cells.

Muscle invasive bladder cancer is an aggressive type of epithelial tumor with a high rate of metastasis. For bladder cancer cells to reach the muscle layer, cells must invade through an urothelial cell monolayer (transurothelial invasion) and basement membrane. However, the process by which transurothelial invasion occurs has not been fully characterized. In this study we developed a novel method to evaluate the transurothelial invasion capacity and investigated its cellular and molecular processes using primary culture cells from bladder cancer patients. The analysis revealed that compared with the prognosis for patients with non­muscle invasive bladder cancer that of patients with muscle invasive bladder cancer was particularly poor due to metastatic recurrence. Cancer cells from patients with muscle invasive bladder cancer exhibited a higher invasive capacity through the urothelial cell monolayer compared with those from non­invasive bladder cancer patients. Furthermore, muscle invasive bladder cancer cells demonstrated a greater ability to form invadopodia, the filamentous actin­based membrane protrusions required for matrix degradation and invasion compared with non­invasive cells. Bladder cancer cell lines were established with reduced invadopodia formation by silencing the expression of cortactin, an essential component of invadopodia. The cortactin knockdown bladder cancer cells with reduced invadopodia formation demonstrated a markedly reduced ability to invade through the urothelial cell monolayer, indicating that invadopodia are essential for transurothelial invasion. The results indicate that invadopodia formation is required for muscle invasion of aggressive bladder cancer cells.

A Case of Malignant Pheochromocytoma Detected during Fertility Treatment.

We report a case of malignant pheochromocytoma in a 35-year-old Japanese woman during fertility treatment, successfully treated with surgical excision. The patient recovered without any postoperative problems, and plasma catecholamine levels normalized. At present, 18 months after the operation, there are no signs of relapse.

[Adult mature teratoma of the testis: a case report].

A 33-year-old man visited our hospital complaining of painless left scrotal swelling. Serum alphafetoprotein (AFP) and human chorionic gonadotropin-beta (HCG-ß) were within normal range. Computed tomography revealed a heterogeneous tumor in the left scrotum and para-aortic lymph node swelling. We diagnosed the tumor as stage IIA testicular cancer and performed left high inguinal orchiectomy. Histopathological diagnosis was mature teratoma with no associated malignant germ cell tumor. The patient was followed-up without adjuvant chemotherapy because the size of para-aortic lymph nodes was remarkably reduced one month after the orchiectomy. The patient must be followed up carefully for possible metastasis.

Blood group antigen-targeting peptide suppresses anti-blood group antibody binding to antigen in renal glomerular capillaries after ABO-incompatible blood reperfusion.

BACKGROUND: Antibody-mediated rejection after ABO-incompatible kidney transplantation (ABO-I KTx) is a major barrier to transplantation success. The advent of immunosuppressive therapy has markedly improved graft survival in ABO-I KTx. However, compared with normal KTx, clinical conditions during ABO-I KTx are difficult to control because of overimmunosuppression. To reduce the need for immunosuppression, we aimed to develop a novel blood group antigen-neutralizing therapy. METHODS: We screened for an ABO blood group antigen-targeting peptide (BATP) by screening of T7 phage-displayed peptide library. After screening, hemagglutination inhibition assays, enzyme-linked immunosorbent assay, and cytotoxicity assay were used to analyze the blood group antigen-blocking effect and toxicity of BATP. We also tested the inhibitory effects on anti-blood group antibody binding in normal human kidney tissues blocked with BATP and excised kidneys perfused ex vivo with BATP. RESULTS: We identified six peptide sequences that efficiently suppressed hemagglutination of red blood cells by anti-ABO blood group antibodies and binding of these antibodies to ABO histo-blood group antigens in kidney tissues. Surprisingly, ex vivo perfusion of BATP in kidneys excised from renal cell carcinoma patients caused significant suppression of anti-blood group antibody binding to antigen and IgG and IgM deposition in renal glomerular capillaries after ABO-I blood reperfusion. CONCLUSIONS: These data indicate that A/B blood group antigens on red blood cells and in kidney tissues may be neutralized by BATP. This approach may enable the development of a novel blood group antigen-neutralizing therapy to overcome the challenges of ABO-I KTx.

Carboplatin-gemcitabine combination chemotherapy upregulates AKR1B10 expression in bladder cancer.

BACKGROUND: AKR1B10 is considered to contribute to cell proliferation and chemoresistance. In the present study, we examined whether AKR1B10 expression is associated with disease-free survival in bladder cancer patients. METHODS: We obtained bladder cancer specimens from 10 patients before and after chemotherapy and measured AKR1B10 mRNA levels using real-time PCR. In addition, we conducted an immunohistochemical examination of AKR1B10 expression in 57 patients with bladder cancer before and after chemotherapy. RESULTS: AKR1B10 mRNA expression was significantly higher in the post-chemotherapy group than in the pre-chemotherapy group (p < 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared with the significantly higher score of 2.03 ± 1.03 in the post-chemotherapy group (p < 0.001). The disease-free survival rate of post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(-) patients (100%) (log-rank test, p = 0.039). CONCLUSIONS: Although the present study is small and preliminary, our data suggest that post-chemotherapy AKR1B10 expression may be associated with a poor prognosis in patients who received carboplatin-gemcitabine combination chemotherapy and underwent cystectomy. Further study is warranted to elucidate its clinical significance.

Skin perfusion pressure is a prognostic factor in hemodialysis patients.

Peripheral arterial disease (PAD) is common in hemodialysis patients and predicts a poor prognosis. We conducted a prospective cohort study to identify risk factors for PAD including skin perfusion pressure (SPP) in hemodialysis patients. The cohort included 373 hemodialysis patients among 548 patients who received hemodialysis at Oyokyo Kidney Research Institute, Hirosaki, Japan from August 2008 to December 2010. The endpoints were lower limb survival (peripheral angioplasty or amputation events) and overall survival of 2 years. Our results showed that <70 mmHg SPP was a poor prognosis for the lower limb survival and overall survival. We also identified age, history of cardiovascular disease, presence of diabetes mellitus, smoking history, and SPP < 70 mmHg as independent risk factors for lower limb survival and overall survival. Then, we constructed risk criteria using the significantly independent risk factors. We can clearly stratify lower limb survival and overall survival of the hemodialysis patients into 3 groups. Although the observation period is short, we conclude that SPP value has the potential to be a risk factor that predicts both lower limb survival and the prognosis of hemodialysis patients.

[Adrenal pheochromocytoma with multiple neurofibromatosis on the trunk].

We report a case of adrenal pheochromocytoma in a patient with neurofibromatosis type 1 (NF1). A 65-year-old female patient was admitted to our hospital for examination of a right adrenal mass. The adrenal tumor was incidentally discovered by abdominal computed tomography during examination for hypertension in another hospital. She had large multiple neurofibromatous lesions and café-au-lait spots on the trunk. We thought that it was difficult to make a skin incision on normal skin. Serum and urinary catecholamines were markedly increased. Magnetic resonance imaging revealed a solid round tumor 3 cm in diameter, located in the right adrenal gland. Laparoscopic right adrenalectomy was performed. Serum and urinary catecholamines returned to the normal range on post-operative day 10. Laparoscopic surgery may be a good option for NF1 patients with pheochromocytoma, especially those who had multiple neurofibromatosis on the trunk.

Effect of an Oral Adsorbent, AST-120, on Dialysis Initiation and Survival in Patients with Chronic Kidney Disease.

The oral adsorbent AST-120 has the potential to delay dialysis initiation and improve survival of patients on dialysis. We evaluated the effect of AST-120 on dialysis initiation and its potential to improve survival in patients with chronic kidney disease. The present retrospective pair-matched study included 560 patients, grouped according to whether or not they received AST-120 before dialysis (AST-120 and non-AST-120 groups). The cumulative dialysis initiation free rate and survival rate were compared by the Kaplan-Meier method. Multivariate analysis was used to determine the impact of AST-120 on dialysis initiation. Our results showed significant differences in the 12- and 24-month dialysis initiation free rate (P < 0.001), although no significant difference was observed in the survival rate between the two groups. In conclusion, AST-120 delays dialysis initiation in chronic kidney disease (CKD) patients but has no effect on survival. AST-120 is an effective therapy for delaying the progression of CKD.

Efficacy of SMART Stent Placement for Salvage Angioplasty in Hemodialysis Patients with Recurrent Vascular Access Stenosis.

Vascular access stenosis is a major complication in hemodialysis patients. We prospectively observed 50 patients in whom 50 nitinol shape-memory alloy-recoverable technology (SMART) stents were used as salvage therapy for recurrent peripheral venous stenosis. Twenty-five stents each were deployed in native arteriovenous fistula (AVF) and synthetic arteriovenous polyurethane graft (AVG) cases. Vascular access patency rates were calculated by Kaplan-Meier analysis. The primary patency rates in AVF versus AVG at 3, 6, and 12 months were 80.3% versus 75.6%, 64.9% versus 28.3%, and 32.3% versus 18.9%, respectively. The secondary patency rates in AVF versus AVG at 3, 6, and 12 months were 88.5% versus 75.5%, 82.6% versus 61.8%, and 74.4% versus 61.8%, respectively. Although there were no statistically significant difference in patency between AVF and AVG, AVG showed poor tendency in primary and secondary patency. The usefulness of SMART stents was limited in a short period of time in hemodialysis patients with recurrent vascular access stenosis.

An aggressive signet ring cell carcinoma of the prostate in a Japanese man.

Signet ring cell carcinoma (SRCC) of the prostate is rare, with approximately 100 case reports to date. Here we report a very aggressive case of SRCC of the prostate in a Japanese man. The patient received estramustine, docetaxel, and carboplatin combination chemotherapy, followed by TS-1 and CPT-11 combination therapy. Unfortunately, the disease progressed, and he died of general metastatic disease treated over 16 month with systemic chemotherapy.