Factors associated with thrombocytopenia in patients treated with pegfilgrastim.

OBJECTIVES: Pegfilgrastim is a long-acting, granulocyte colony-stimulating factor approved in Japan for the prevention of neutropenia caused by antineoplastic agents. Severe thrombocytopenia was reported with pegfilgrastim, however, the factors associated with thrombocytopenia are unclear. This study aimed to explore the factors associated with thrombocytopenia in patients with metastatic castration-resistant prostate cancer treated with pegfilgrastim for primary prophylaxis of febrile neutropenia (FN) with cabazitaxel. MATERIALS AND METHODS: This study included metastatic castration-resistant prostate cancer patients who received pegfilgrastim for primary prophylaxis of FN with cabazitaxel. The timing and severity of thrombocytopenia and factors associated with the reduction rate of platelets were examined in patients who received pegfilgrastim for the primary prevention of FN during the first course of cabazitaxel and by multiple regression analysis. RESULTS: Thrombocytopenia was most common within 7 days of pegfilgrastim administration, with 32 cases of grade 1 and 6 cases of grade 2 as per the Common Terminology Criteria for Adverse Events version 5.0. Multiple regression analysis revealed that the reduction rate of platelets after pegfilgrastim administration was significantly positively correlated with monocytes. In contrast, the presence of liver metastases and neutrophils was significantly negatively correlated with the reduction rate of platelets. CONCLUSION: Thrombocytopenia due to pegfilgrastim administered as primary prophylaxis for FN with cabazitaxel was most likely to occur within one week after pegfilgrastim administration, suggesting that monocytes, neutrophils, and liver metastases were associated with a reduction in platelets.

Comparison between the Effects of Loxoprofen and Acetaminophen on Postoperative Pain Following Radical Prostatectomy: A Propensity Score Matching Analysis.

Non-steroidal anti-inflammatory medications are associated with renal impairment. However, there is little information on whether these medications affect postoperative renal function compared with acetaminophen. The objective of this study was to compare the effects of acetaminophen and loxoprofen, used as postoperative analgesic, effect on postoperative analgesia using propensity score matching analysis. We retrospectively enrolled 328 patients treated with loxoprofen or acetaminophen after open radical prostatectomy between October 2017 and February 2020. We analyzed postoperative pain intensity, the incidence rate of acute kidney injury, drug-induced liver injury, and rate of elevation in serum creatinine after open radical prostatectomy. Eighty-one matched pairs of patients treated with loxoprofen or acetaminophen were selected using propensity score matching analysis. The postoperative numerical rating scale was significantly higher in the acetaminophen group than in the loxoprofen group on postoperative day 5. The use of patient-controlled anesthesia and rescue analgesics was significantly higher in the acetaminophen group than in the loxoprofen group. The loxoprofen group had a significantly higher postoperative increase in serum creatinine than the acetaminophen group on postoperative days 5 and 8. The incidence of acute kidney injury was 4.9% in the loxoprofen group and 0% in the acetaminophen group, while the incidence of drug-induced liver injury was 0% in both groups. Acetaminophen appears to be safer than loxoprofen in terms of effects on renal function. Nevertheless, the number of acetaminophen doses and the dose per dose may need to be increased for patients with significant postoperative pain.

Evaluation of renal function using cystatin C-based estimated glomerular filtration rate in patients with urothelial carcinoma treated with gemcitabine and cisplatin chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Cisplatin-based chemotherapy is a first-line treatment for advanced or metastatic urinary tract urothelial carcinoma (UC). Accurate assessment of renal function is indispensable for determining cisplatin dosing to enhance the safety and effectiveness of cisplatin. The objective of this study was to assess serum cystatin C (sCys C) levels in patients with urothelial carcinoma and to explore its clinical value as a serum marker of glomerular filtration rate (GFR). METHODS: This study retrospectively enrolled 18 UC patients treated with a combination of gemcitabine and cisplatin between April 2018 and November 2020. We calculated the estimated GFR (eGFR) based on serum creatinine (sCr) or sCys C and estimated Cr clearance (eCCr) based on sCr. The correlation, bias, accuracy and creatinine height index between eGFR or eCCr and measured GFR (mGFR) based on Cr clearance were calculated from urinary Cr and sCr. RESULTS AND DISCUSSION: Estimated GFR based on sCys C correlated most strongly with mGFR. Moreover, the bias, mean error, mean absolute error and root mean square error were significantly lower in eGFRs based on sCyc C than in eGFRs based on sCr and eCCr. The correlation between eGFR based on sCys C/mGFR and creatinine height index was weaker than that between eGFR based on sCr/mGFR and creatinine height index, suggesting that sCys C was less affected by muscle mass. WHAT IS NEW AND CONCLUSION: In UC patients, eGFR based on sCys C reflected renal function more accurately than eGFR based on sCr, suggesting that sCys C may be useful for assessing renal function in clinical practice.

[CLINICAL STUDY OF SEQUENTIAL THERAPY WITH ABIRATERONE AND ENZALUTAMIDE FOLLOWING DOCETAXEL THERAPY FOR CASTRATION-RESISTANT PROSTATE CANCER].

(Purpose) This study is to evaluate the efficacy and safety of sequential therapy with two novel drugs, abiraterone and enzalutamide after docetaxel (DOC) therapy for castration-resistant prostate cancer (CRPC). (Material and methods) Twenty-one patients were identified received sequential therapy with abiraterone and enzalutamide after DOC therapy at our institution. We investigated PSA response (decrease of 50% or more) to prior administered drug as primary endpoint, and overall survival rate and occurrence of adverse events as secondary endpoint. (Results) There were 12 patients in the group preliminarily administered enzalutamide (Group E) and 9 patients in the group preliminarily administered abiraterone (Group A). The novel drugs were administered immediately following DOC therapy in nearly all cases. Of the 9 patients in Group A, only one patient (11%) and of the 12 patients in Group E, only one patient (9%) achieved PSA decrease of 50% or more, thus resulting in a poor response rate. There was not significantly difference in both groups. The overall survival rates of Group A and E were not significantly difference. There were three adverse events which required change drug. Those were two cases (appetite loss and general fatigue) on enzalutamide and one case (edema) on abiraterone. (Conclusion) This study suggested that sequential therapy with abiraterone and enzalutamide after DOC therapy had poor clinical benefit regardless of the order of administration of both drugs.

[A CASE OF METASTATIC BLADDER UROTHELIAL CARCINOMA WHOSE DISEASE WAS CONTROLLED FOR A RELATIVE LONG PERIOD BY MULTIDISCIPLINARY TREATMENT INCLUDING RADIATION TO A LUNG METASTASIS AND MULTIPLE COURSES OF CHEMOTHERAPY].

A 67-year-old woman complained of urinary frequency and gross hematuria. She was referred to our hospital with the diagnosis of bladder tumor. Transurethral resection of the bladder tumor (TURBT) was performed and pathological diagnosis was urothelial carcinoma (G2>G3) with muscular invasion. Because she hoped bladder preservation therapy, she received two courses of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy, one course of arterial infusion chemotherapy, and chemoradiotherapy with cisplatin. After those therapies she underwent 4 times of TURBT and two courses intravesical BCG therapy. However, solitary lung metastasis appeared 19 months after the initial TURBT. Multidisciplinary treatments including 25 courses of various multiagent chemotherapies, radiation therapy to the lung metastasis and surgical resection of a urethral recurrence were performed. Although a localized radiation pneumonitis was developed, the lung metastasis appeared to be controlled for 26 months after the radiation therapy to the lung. Bilateral ureteral and renal pelvic tumors appeared after the radiation therapy. Severe bleeding was occurred from renal pelvic tumors several times and she needed the hospital stay 2 times. Active bleeding stopped after the administration of chemotherapy each time. Although she died of occlusive jaundice due to the liver metastasis, she had been alive due to the multidisciplinary treatment for 67 months after lung metastasis appearance with relatively good performance status.

Sialylated IgG-Fc: a novel biomarker of chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: Sialylation in Fc portion of IgG plays a crucial role in the pathogenesis of autoimmune diseases and the working mechanism of intravenous immunoglobulin (IVIG). We aim to test whether IgG-Fc sialylation is a biomarker of disease activity for chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: By using specific lectins for sialylation, galactosylation and agalactosylation, lectin-enzyme assay and lectin blotting with pretreatment of IgG degradating enzyme of Streptococcus pyogenes were performed to compare the glycosylation levels of serum IgG-Fc (1) between patients of untreated CIDP (n=107) and normal control subjects (n=27), (2) among patients with untreated CIDP of different clinical severities and (3) before and after IVIG treatment of patients with CIDP (n=12). RESULTS: Sialylation and galactosylation of IgG-Fc were significantly reduced in patients with CIDP than normal control subjects (p=0.003 and 0.033, respectively), whereas agalactosylation was increased in CIDP (p=0.21). Ratios of sialylated/agalactosylated IgG-Fc levels were significantly reduced in CIDP (p<0.001) and inversely related to disease severity (p=0.044). After IVIG treatment, levels of sialylated IgG-Fc significantly increased (p=0.003). CONCLUSIONS: Sialylation of IgG-Fc is reduced in CIDP. Its level correlated with clinical severity and increased after IVIG treatment. Sialylated as well as ratio of sialylated/agalactosylated IgG-Fc could be new measures to monitor the disease severity and treatment status in CIDP.

A case of pure autotopagnosia following Creutzfeldt-Jakob disease.

A 69-year-old male (N.A.) with Creutzfeldt-Jakob disease showed pure autotopagnosia. We administered tests evaluating his ability to name his own body parts, to point to body parts (his own and examiner's), and to recognize positional relationships between his body parts by verbal questions and responses. We found impaired localization of the patient's own body parts by pointing and impaired recognition of positional relationships between his body parts. However, there was no impairment in naming his own body parts or in localizing the examiner's body parts. The results suggest a pure autotopagnosia in N.A. leading to an impairment of recognition of the spatial position of his body parts in a three-dimensional body representation within the egocentric reference frame. We were able to rule out the possibility that his pattern of performance could have been due to a disability in programming reaching movements of the arm.

Erratum: Increased fatty acid synthase expression in prostate biopsy cores predicts higher Gleason score in radical prostatectomy specimen.

[This corrects the article DOI: 10.1186/1472-6890-14-3.].

[Vesicoappendiceal Fistula: A Case Report].

A 65-year-old man had been aware of pieces of food occasionally in the urine since February 2008. In November 2010, he came to an outpatient clinic with high fever and cloudy urine and was diagnosed with urinary tract infection. Because he had fecaluria, interconnection between urinary bladder and digestive tract was suspected. Although excretory urography showed no remarkable findings, an outflow of contrast media into the appendix was demonstrated in the cystography. By cystoscopy, the fistula hole was confirmed on the posterior wall of the bladder and inflow of feces from the hole was noticed. Operation was performed under the diagnosis of vesicoappendiceal fistula. The appendix was adhesive to the ileum, the right side of the bladder and the upper side of the rectum, and an en bloc resection was performed. Because the fecalith existed near the fistula, appendicitis appeared to induce inflammatory change and abscess formation around the appendix, and the abscess might have perforate into the bladder.

Elevated fatty acid synthase expression in prostate needle biopsy cores predicts upgraded Gleason score in radical prostatectomy specimens.

BACKGROUND: We examined whether fatty acid synthase (FAS) expression in prostate biopsy cores had valuable information and could predict a Gleason score (GS) upgraded from biopsy to radical prostatectomy (RP) specimens. METHODS: Immunostaining with a FAS antibody was performed on paraffin-embedded prostate biopsy cores with GS 5-6 obtained from 80 patients who subsequently underwent RP. The correlations between FAS expression and clinicopathological parameters, upgrading group, and clinicopathological parameters including FAS expression were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for upgrading GS. RESULTS: A total of 46 patients (57.5%) with biopsy GS 5-6 were upgraded to GS ≥7 at RP. FAS expression was significantly associated with clinical T stage (P = 0.0232) and positive core rate (P = 0.0245). Upgrading from biopsy GS 5-6 to GS ≥7 at RP was significantly associated with clinical T stage (P = 0.0337), positive core rate (P = 0.0262), and FAS expression (P < 0.0001). FAS expression was a significant predictor for upgrading from biopsy GS 5-6 to GS ≥7 at RP in multivariate analysis (P < 0.0001; odds ratio, 12.35). FAS scores showed the largest area under the receiver-operating characteristic curve (AUC) in preoperative parameters (AUC = 0.753). CONCLUSIONS: Increased FAS expression in prostate biopsy cores could be a novel parameter for upgrading from biopsy GS 5-6 to GS ≥7 at RP. If a biopsy GS is low, the treatment strategy for patients with high FAS expression in prostate biopsy cores should be carefully determined.

Preoperative risk factors for extraurothelial recurrence in patients with ureteral cancer treated with radical nephroureterectomy.

PURPOSE: Recent studies have suggested that lymph node dissection may improve the prognosis in patients with upper tract urothelial carcinoma. Therefore, patients who will benefit from lymph node dissection need to be selected before surgery. Because patients who have extraurothelial recurrence theoretically include those whose prognoses are improved by lymph node dissection, we conducted this study to determine the preoperative predictors of extraurothelial recurrence in patients with ureteral cancer. MATERIALS AND METHODS: Because it is not appropriate to categorize the preoperative radiologic findings of ureteral cancer and those of renal pelvic cancer using the same classification criteria, we focused on ureteral cancer. We reviewed preoperative factors in 70 patients with ureteral cancer treated with radical nephroureterectomy. Laboratory tests including inflammatory indices, tumor markers and estimated glomerular filtration rate, along with radiologic findings, were evaluated. Multivariate analyses were performed to determine independent factors predicting extraurothelial recurrence in patients with ureteral cancer. RESULTS: Positive cytology, cT stage 3 or greater, length of ureteral cancer 3 cm or greater and estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 were independent predictors of extraurothelial recurrence on multivariate analysis. When patients were stratified into 3 groups according to the number of risk factors, the 3-year extraurothelial recurrence-free survival rates were 95.2% in the low risk group, 75.8% in the intermediate risk group and 25.1% in the high risk group. CONCLUSIONS: Positive cytology, cT stage 3 or greater, length of ureteral cancer 3 cm or greater and estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 were preoperative predictive factors of extraurothelial recurrence in patients with ureteral cancer and lymph node dissection may be omitted for low risk patients.

Prognostic impact of fatty acid synthase expression in upper urinary tract urothelial carcinoma.

OBJECTIVE: Fatty acid synthase has been shown to be highly expressed in various types of cancers with increased tumour aggressiveness. In this study we examined the level of fatty acid synthase expression in surgically resected upper urinary tract urothelial carcinoma specimens and evaluated the relations between fatty acid synthase expression and the patients' pathological features and clinical outcomes. METHODS: Sections of paraffin-embedded tumour specimens from 113 patients who underwent surgical treatment for upper urinary tract urothelial carcinoma were immunostained with a polyclonal fatty acid synthase antibody, and a tumour was considered to have high fatty acid synthase expression if >50% of the cancer cells stained with moderate-to-strong intensity. Associations between fatty acid synthase expression and the patients' pathological parameters and survival were analyzed statistically. RESULTS: During the follow-up time (median: 46.8 months), 61 patients (54.0%) had recurrence and 17 (15.0%) died of upper urinary tract urothelial carcinoma. High fatty acid synthase expression was significantly associated with high tumour grade (P = 0.0273). Patients with high fatty acid synthase expression had significantly worse recurrence-free survival and extravesical-recurrence-free survival than those with low fatty acid synthase expression (P = 0.0171, P = 0.0228, respectively). In multivariate analysis, high fatty acid synthase expression was an independent predictor of shortened recurrence-free survival (P = 0.0220, hazard ratio (HR) = 1.970). CONCLUSIONS: Fatty acid synthase expression in upper urinary tract urothelial carcinoma is an independent predictor for tumour recurrence. Patients with high fatty acid synthase expression in upper urinary tract urothelial carcinoma should be followed carefully and adjuvant therapy for them should be considered.

Increased fatty acid synthase expression in prostate biopsy cores predicts higher Gleason score in radical prostatectomy specimen.

BACKGROUND: Fatty acid synthase (FAS) is highly expressed in various types of cancer, and elevated expression of FAS has been suggested to be a predictor of tumor aggressiveness and poor prognosis. We examined whether FAS expression in prostate biopsy cores could predict the pathological characteristics of radical prostatectomy (RP) specimens. METHODS: Paraffin-embedded prostate biopsy cores, obtained from 102 patients who subsequently underwent RP, were immunostained with polyclonal anti-FAS antibody. The staining intensity was categorized into non-staining, weak, moderate, and strong. Tumors with moderate or strong immunostaining were considered to show high FAS expression, and other tumors were considered to show low FAS expression. The relation between the FAS expression status in biopsy cores and pathological parameters in RP specimens was analyzed. RESULTS: The FAS expression in the biopsy cores of 64 of the 102 tumors (63%) was high, whereas it was low in the biopsy cores of the other 38 tumors (37%). High FAS expression was significantly associated with Gleason Score (GS) ≥ 7 in RP specimens (p< 0.0001). In multivariable logistic regression analyses, GS ≥7 in biopsy cores (p <0.0001), higher preoperative PSA (p = 0.0194), and high FAS expression (p = 0.0004) were independent predictors of GS ≥ 7 in the RP specimen. CONCLUSIONS: Increased FAS expression in prostate biopsy cores could be a novel parameter for predicting higher GS in RP specimens. The treatment strategy for patients with high FAS expression in prostate biopsy cores should be carefully determined.

Association Between Telecommuting Preference-frequency mismatch and Insomnia among Japanese Workers in the COVID-19 Pandemic: A Prospective Cohort study.

OBJECTIVE: We hypothesized that telecommuting's impact on sleep varied based on preference-frequency mismatch. Here, we evaluated this relationship in a large cohort of Japanese workers. METHODS: We collected data from 33,302 Japanese workers through an online survey, and analyzed participant preferences and frequency of telecommuting in 9,425 individuals who responded to a follow-up survey. We evaluated sleep using the Athens Insomnia Scale, and estimated odds ratios of insomnia using multilevel logistic regression. RESULTS: Workers preferring telecommuting had a higher risk of insomnia as telecommuting frequency decreased. OR for insomnia was 1.87 (p < 0.001) in those who telecommuted less than once per week. CONCLUSION: Telecommuting's impact on workers' sleep depends on preference mismatch, with a higher risk of insomnia among those who prefer telecommuting but are unable to utilize it.

Differentiation of speech in Parkinson's disease and spinocerebellar degeneration using deep neural networks.

INTRODUCTION: Assessing dysarthria features in patients with neurodegenerative diseases helps diagnose underlying pathologies. Although deep neural network (DNN) techniques have been widely adopted in various audio processing tasks, few studies have tested whether DNNs can help differentiate neurodegenerative diseases using patients' speech data. This study evaluated whether a DNN model using a transformer architecture could differentiate patients with Parkinson's disease (PD) from patients with spinocerebellar degeneration (SCD) using speech data. METHODS: Speech data were obtained from 251 and 101 patients with PD and SCD, respectively, while they read a passage. We fine-tuned a pre-trained DNN model using log-mel spectrograms generated from speech data. The DNN model was trained to predict whether the input spectrogram was generated from patients with PD or SCD. We used fivefold cross-validation to evaluate the predictive performance using the area under the receiver operating characteristic curve (AUC) and accuracy, sensitivity, and specificity. RESULTS: Average ± standard deviation of the AUC, accuracy, sensitivity, and specificity of the trained model for the fivefold cross-validation were 0.93 ± 0.04, 0.87 ± 0.03, 0.83 ± 0.05, and 0.89 ± 0.05, respectively. CONCLUSION: The DNN model can differentiate speech data of patients with PD from that of patients with SCD with relatively high accuracy and AUC. The proposed method can be used as a non-invasive, easy-to-perform screening method to differentiate PD from SCD using patient speech and is expected to be applied to telemedicine.

[Evaluation of clinical results in patients undergoing laparoscopic nephroureterectomy].

We evaluated the efficacy of laparoscopic radical nephroureterectomy (LNUx) by comparing the clinical results in 55 patients undergoing LNUx at the National Defense Medical College since 2001 with those in patients undergoing open radical nephroureterectomy (ONUx) there over the same period. LNUx was performed successfully in 54 of the patients, but one patient required conversion to ONUx. The mean operating time for LNUx was not significantly different from that for ONUx, and the mean estimated blood loss during LNUx was significantly lower than that during ONUx. Major complications occurring early in our laparoscopic series of cases were injury of the duodenum and bleeding from the inferior vena cava. Oncological outcomes were compared between LNUx (n＝50) and ONUx (n＝50) in patients with pathologically-confirmed urothelial carcinoma. The pT stage, histological grade, percentage of lymph node dissection and percentage of high grade hydronephrosis did not differ significantly between the two groups. Because the intravesical recurrence-free survival rates, extravesical recurrence-free survival rates, and disease specific survival rates were also similar in the two groups, we concluded that LNUx is an appropriate treatment for upper urinary tract urothelial carcinoma.

[Causes and salvage of failed urethroplasties for traumatic urethral injury].

OBJECTIVES: Salvage urethroplasty after failed repair of traumatic urethral injury is a urological challenge, and we herein describe our experience with it. METHODS: From October 2010 to January 2012, five patients underwent salvage repair of failed urethroplasties for traumatic urethral injuries: three bulbar straddle injuries and two pelvic fracture urethral injuries. One of the three failed urethroplasties for bulbar straddle injuries was a stricture excision and primary anastomosis, and its failure was due to periurethral abscess formation. Another was an augmented anastomotic urethroplasty using buccal mucosa, and its failure was due to periurethral abscess formation. The third was a tube graft urethroplasty using buccal mucosa, and its failure was due to a stricture at the anastomotic site. Two failed urethroplasties for pelvic fracture urethral injuries were perineal anastomotic repairs combined with corporal separation and inferior pubectomy, and the failures of both were due to ischemic bulbar necrosis. The urethral gap lengths estimated from urethrograms ranged from 12 to 45 mm (mean = 26 mm). RESULTS: Urethroplasties in all patients with bulbar straddle injuries were salvaged by stricture excision and primary anastomosis with corporal separation, and urethroplasties in both patients with pelvic fracture urethral injuries were salvaged by abdominal transpubic perineal urethroplasty. Although the patients who underwent transpubic urethroplasty had transient pelvic girdle pain, no severe complications were observed. All patients were for 10 to 25 months postoperatively (mean = 16 months) able to void satisfactorily without additional treatment. CONCLUSIONS: Failed urethroplasties for traumatic urethral injuries can be salvaged with a second reconstruction surgery. The procedure of choice for this salvage is anastomotic urethroplasty with techniques for tension-free anastomosis.