Identifying Crude Drugs in Kampo Medicines Associated with Drug-Induced Liver Injury Using the Japanese Adverse Drug Event Report Database: A Comprehensive Survey.

The current study aimed to identify the crude drugs associated with drug-induced liver injury (DILI) in 148 Kampo medicines prescribed throughout Japan using the Japanese Adverse Drug Event Report (JADER) database, a large-scale spontaneous reporting system in Japan. First, we tabulated the number of DILI reports from the report-based dataset and the background information from the patient-based dataset. Thereafter, we combined the 126 crude drugs into 104 crude drug groups to examine multicollinearity. Finally, the reporting odds ratios (RORs), 95% confidence intervals, p values for Fisher's exact test, and number of reports were calculated for each crude group to identify those associated with DILI. Notably, the number of adverse event reports for DILI (63,955) exceeded that for interstitial lung disease (51,347), the most common adverse event. In total, 78 crude drug groups (90 crude drugs) were reported to have an ROR > 1, a p < 0.05, and ≥10 reported cases. Our results highlight DILI as an essential issue, given that it was among the most frequently reported adverse drug reactions. We were able to clearly identify the crude drugs associated with DILI, which could help manage adverse drug reactions attributed to Kampo medicines and crude drugs.

Prognostic parameter for high risk prostate cancer patients at initial presentation.

BACKGROUND: High-risk prostate cancer can be defined by a patient's Gleason score (GS), prostate-specific antigen (PSA) level, and clinical T (cT) stage, but a novel marker is needed due to heterogeneity of the disease. In this study, we evaluated whether intraductal carcinoma of the prostate (IDC-P) confirmed by needle biopsy is an adverse prognostic parameter for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with high-risk prostate cancer. METHODS: We retrospectively evaluated 204 patients with high-risk prostate cancer treated by radical prostatectomy from 1991 to 2005 at Nagoya University and its affiliated hospitals. Data on each patient's PSA level, biopsy GS, cT stage, presence of Gleason pattern 5, presence of IDC-P, percentage of the core involved with cancer, and maximum percentage of the core involved with cancer were analyzed. RESULTS: The median follow-up period was 108 months (range, 11-257 months). Forty-eight patients (24%) showed disease progression. Thirty-four patients (17%) died of the disease during follow-up. The IDC-P component was detected in 74 (36%) needle biopsy samples. The 5-, 10-, and 15-year CSS rates of the IDC-P-negative cases were 3.2%, 9.0%, and 23.7%; the corresponding rates of the IDC-P-positive cases were 23.9%, 33.7%, and 52.7%, respectively (P = 0.0001). In the Fine and Gray's model for PFS, IDC-P, maximum percentage of the core involved with cancer, and cT stage were significantly associated (P = 0.013, P = 0.003, P = 0.007). In the Fine and Gray's model for CSS, only IDC-P was significant (P = 0.027). In a multivariate Cox regression analysis, IDC-P (P = 0.04; hazard ratio [HR], 1.95) and maximum percentage of the core involved with cancer (P = 0.021; HR, 0.43) were significant factors in predicting overall survival (OS). CONCLUSIONS: The presence of IDC-P in a needle biopsy was a prognostic factor for PFS, CSS, and OS in patients with high-risk prostate cancer who underwent radical prostatectomy. Multimodal pre-and/or post- surgical therapy may be needed when IDC-P is found in a needle biopsy specimen.

The presence of intraductal carcinoma of the prostate in needle biopsy is a significant prognostic factor for prostate cancer patients with distant metastasis at initial presentation.

Intraductal carcinoma of the prostate is an adverse prognostic factor in localized prostate cancer patients. However, whether it influences outcome of those patients with distant metastases discovered at initial diagnosis is unclear. Here, we evaluated whether the presence of intraductal carcinoma of the prostate in prostate needle biopsies is an adverse prognostic factor for cancer-specific survival and overall survival in such prostate cancer patients. We retrospectively enrolled 150 eligible patients. All patients received androgen-deprivation therapy and/or chemotherapy. Their age, performance status, pain, metastatic sites, clinical T stage, serum prostate-specific antigen, alkaline phosphatase, hemoglobin, Gleason score, and the presence of Gleason pattern 5 were analyzed. Primary end point was cancer-specific survival; secondary end points included prostate-specific antigen progression-free survival and overall survival. Fine and Gray's model and the Cox proportional hazards model were used as statistical tests. Intraductal carcinoma of the prostate was detected in 100 (67%) patients. At a median follow-up of 38 months, 79 patients (53%) had died of the disease and nine (6%) had died of other causes. The average time interval to cancer-related death was 28 months. On multivariate analysis, only intraductal carcinoma of the prostate was significantly associated with cancer-specific survival (P=0.018) and overall survival (P=0.001), and only the presence of Gleason pattern 5 was significantly associated with prostate-specific antigen progression-free survival (P=0.026). The presence of intraductal carcinoma of the prostate was the only significant prognostic parameter for cancer-specific survival and overall survival in prostate cancer patients with distant metastasis at presentation. These results may prove useful in planning future treatments.

Core lower urinary tract symptom score questionnaire: a psychometric analysis.

OBJECTIVES: To analyze the reliability and validity of the Japanese version of the core lower urinary symptom score questionnaire with psychometric methods. METHOD: The present study included 140 women and 125 men who filled in a core lower urinary symptom score questionnaire while attending two lectures on lower urinary tract symptoms. Missing response rates to individual questions were 1.5-5.3%. After the descriptive analyses including box plot, Cronbach's α coefficients and Spearman's ρ were calculated for reliability and validity assessment, respectively. Factor analysis was also carried out to explore the underlying structure. RESULTS: Of the scores for 10 core symptoms, the interquartile range for pain in the bladder and urethra was 0 in both sexes, and that for stress incontinence was 0 in men. Cronbach's α of the core lower urinary symptom score was 0.733 in women and 0.721 in men. Questions regarding daytime frequency, nocturia, urgency and urgency urinary incontinence, and those on slow stream, straining and feeling of incomplete emptying were significantly correlated with each other in both sexes. Pain in the urethra and bladder showed more extensive associations in women than in men. Factor analysis showed four components in both sexes: the first was storage symptoms, second was voiding symptoms, third was pain and the fourth was urinary incontinence. CONCLUSIONS: The core lower urinary symptom score questionnaire shows good reliability and validity for both sexes, and it could be used as screening tool for lower urinary tract symptoms in any clinical setting or epidemiological investigation.

A new treatment for retroperitoneal fibrosis: initial experiences of using Seprafilm® to wrap the ureter.

OBJECTIVE: To confirm the efficacy of using Seprafilm® (Genzyme Corp., Cambridge, MA, USA) for wrapping the ureter to treat the ureteric stenosis caused by retroperitoneal fibrosis (RPF). PATIENTS AND METHODS: Between August 2010 and September 2012, 11 ureters in eight patients with RPF (seven males and one female, mean age 65 years) were treated. The mean (range) length of the narrow segment of the ureter was 30 (10-90) mm. During surgery, after having been released from adhesive tissue, the stenotic segment of the ureter was wrapped with Seprafilm to isolate it from the surrounding tissue. A radiographic follow-up was performed every 6 months using computed tomography, i.v. pyelography and/or (99m) Tc-mercapto-acetylglycyl-glycyl-glycine ((99m) Tc-MAG3) renal scintigraphy. RESULTS: For the unilateral operations, the mean estimated blood loss was 39 mL, and the mean operating time was 154 min. All ureters were isolated from the fibrotic tissue and wrapped with Seprafilm successfully without major complications. During the mean follow-up period of 17 months, no ureteric restenoses were observed in the affected sides, but new stenosis occurred in the contralateral side of the ureter in one patient. CONCLUSIONS: Although the follow-up period is still limited, we believe that the use of Seprafilm has the potential to become an effective option in the treatment of ureteric stenosis caused by RPF, when the omentum cannot be used. To establish the relative advantages of using Seprafilm over performing a standard omental wrap, further experimentation will be required to compare the two techniques.

Prognostic value of intraductal carcinoma of the prostate in radical prostatectomy specimens.

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is an adverse prognostic factor for radical prostatectomy (RP). The endpoint in most IDC-P studies is increased prostate-specific antigen (PSA) levels. The aim of this study was to evaluate whether IDC-P in RP specimens is an adverse prognostic factor for progression-free survival (PFS) and cancer-specific survival (CSS). METHODS: We retrospectively evaluated 206 high-risk prostate cancer patients treated with RP and analyzed data on age, serum PSA level at diagnosis, biopsy Gleason score (bGS), surgical margin (SM), clinical T stage (cT), extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node metastasis (LN), and neoadjuvant therapy. RESULTS: An IDC-P component was found in 104 cases. Forty-four patients experienced clinical failure, and 20 patients died of the disease. Patients with IDC-P showed a higher bGS and stage (including cT, EPE, SVI, and LN) than those without IDC-P. In univariate analysis, IDC-P, PSA level, bGS, SM, cT, SVI, LN, and EPE (P < 0.0001) were significantly associated with PFS. IDC-P (P = 0.0004), PSA level (P < 0.0001), SM (P = 0.0013), cT (P = 0.0019), SVI (P = 0.0012), and LN (P = 0.0002) were significantly associated with CSS. In multivariate analysis, IDC-P (P = 0.0038), and cT (P = 0.0001) were significantly associated with PFS. IDC-P (P = 0.0238) and PSA level (P = 0.0112) were significantly associated with CSS. CONCLUSIONS: IDC-P in RP specimens was an independent risk factor for PFS and CSS and could predict clinical outcomes.

[Renal cell carcinoma presenting high serum level of CA19-9 due to hydronephrosis: a case report].

A 58-year old female was referred to our hospital due to left renal cyst that was pointed out at her health check-up. Abdominal CT scan showed left hydronephrosis with a 20 x 12 x 11cm tumor. The serum CA19-9 level elevated to 4,400 U/ml. Urinary cytology in the left renal pelvis was negative, therefore we could not diagnose whether the mass was renal cell carcinoma or renal pelvic tumor before surgery. She underwent left radical nephrectomy, and frozen section revealed renal cell carcinoma. Immunohistological stain clarified CA19-9 was limited to epithelium lining the renal pelvis and was not contained in carcinoma cells. After the surgery, the serum CA19-9 decreased to the normal range. Serum CA19-9 is known to be sometimes elevated in patients with urothelial carcinoma, but rarely elevated in those with renal cell carcinoma. We thought that hydronephrosis by tumor occlusion caused CA19-9 elevation in our case.

[Triple cancer in the urinary system: a case report].

A 74-year-old male was referred to our hospital due to microhematuria that was pointed out at his health check-up. Cystoscopy showed many papillary bladder tumors under 5 mm in size. Intravenous pyelography also showed deformity of the right kidney and shadow defects in the left renal pelvis. Abdominal computed tomography revealed an 8 cm tumor invading the renal vein in the right kidney, and a 3 cm tumor in the left renal pelvis. Prostate biopsy was performed with PSA 3.4 ng/ml, and he was also diagnosed with prostate carcinoma. First, he received right radical nephrectomy, and secondly left nephroureterectomy and cystectomy. Our case should be called triple cancer because bladder cancer was thought to be daughter tumor of renal pelvic tumor. This is, to our knowledge, the 11th case report that occurred in the urinary tact, and the first case that needed total resection of urinary tract.

[A case in which severely irritable bladder following intravesical instillation of Bacillus Calmette Guerin was successfully treated by steroid therapy].

We report a patient whose irritable bladder symptoms following Bacillus Calmette Guerin (BCG) instillation were satisfactorily treated by steroid administration. A 59-year-old male had undergone transurethral resection for the bladder carcinoma recurred three times. The histopathological examination revealed the tumor as transitional cell carcinoma, G1 to G2, and pTa. Subsequently an instillation of 80 mg BCG into the bladder was planned 8 times every 7 days. After the 5th instillation he presented with gross hematuria, painful micturition, pollakisuria, urgency and reduced bladder capacity of 15 ml. The dose was reduced to 40 mg and another 3 instillations were accomplished. Since conventional treatments of anti-cholinergics, analgesics and epidural anesthesia were of little help for the subjective symptoms, he was put on the steroid pulse therapy 2 weeks after completion of the BCG regimen. The treatment gradually improved the subjective symptoms and increased the bladder capacity up to 160 ml. In conclusion, we believe that the steroid pulse therapy deserves considering in the early stage of irritable bladder symptoms following BCG instillation.