Thrombotic events and rebleeding after hemorrhage in patients taking direct oral anticoagulants for non-valvular atrial fibrillation.

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.

Preoperative positive urine cytology is a risk factor for subsequent development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

PURPOSE: To determine the independent risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (UUT-UC). METHODS: A total of 364 patients underwent nephroureterectomy (NUx) for UUT-UC between January 2005 and April 2009 in Okayama University and 17 affiliated hospitals. Patients with concomitant bladder cancer were excluded from the analysis. The clinicopathologic data for the remaining 288 patients with UUT-UC were retrospectively reviewed. Median follow-up after NUx was 20.2 months. The following variables were evaluated for any association with bladder recurrence: sex, age, tumor stage, tumor grade, venous invasion, lymphatic invasion, tumor location, multifocality, surgical modalities, time of ligation of the ureter, and preoperative urine cytology. The significance of each variable was tested univariately using the log-rank test. The simultaneous effects of multiple risk factors were estimated by multiple regression analysis using the Cox proportional hazards model. RESULTS: Bladder recurrence occurred in 103 patients (35.8%). Median time to first bladder recurrence was 6.9 months. Significant risk factors for bladder recurrences on univariate analysis were tumor location (P = 0.046) and preoperative positive urine cytology (P < 0.001). Multivariate analysis revealed that preoperative urine cytology positive was significant for bladder recurrence (HR: 1.977; 95% CI: 1.310-2.983, P = 0.001). CONCLUSION: Risk factor for subsequent development of bladder cancer after NUx was preoperative positive urine cytology.

Renal cell carcinoma with a tumor thrombus in the ureter: a case report.

BACKGROUND: Renal cell carcinoma (RCCs) is the most common malignancy of the kidney. When RCC progresses, it is known to form tumor thrombus in the renal vein and/or inferior vena cava. However, RCC does not normally form tumor thrombus in the ureter or renal pelvis. CASE PRESENTATION: A 43-year-old man presented to our department for the treatment of a renal tumor with asymptomatic gross hematuria. In a dynamic CT study, contrast enhancement revealed a tumor suspected to be RCC, but atypical finding as a tumor thrombus that filled the renal pelvis and the whole ureter was also observed. Nephroureterectomy was performed, and the tumor was diagnosed histopathologically as RCC. CONCLUSION: We report here a very rare case of RCC with a tumor thrombus in the whole ureter.

Prognostic factors influencing survival after nephroureterectomy for transitional cell carcinoma of the upper urinary tract.

We analyzed the prognostic factors influencing survival after surgeries for upper urinary tract urothelial carcinoma (UUT-UC) with longer follow-up periods than in previous studies. Between January 2000 and December 2004, 386 patients underwent nephroureterectomy for UUT-UC. The data for the 221 patients with UUT-UC were retrospectively reviewed. Nine variables were evaluated for association with the survival outcomes of disease-specific survival. The prognostic significance was tested univariately with the log-rank test. The simultaneous effects of multiple prognostic factors were estimated by multiple regression analysis using the Cox proportional hazards model. The median follow-up was 38.4 months. The 5-year over all survival was 62.3%. Significant prognostic factors for disease-specific survival rate on univariate analysis were pathological stage (p＜0.0001), tumor grade (p＝0.0324), and venous invasion (p＜0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p＝0.0205). Venous invasion was the only independent prognostic factor in pathologically localized UUT-UC.

Prognostic factors influencing survival after nephroureterectomy for transitional cell carcinoma of the upper urinary tract.

We analyzed the prognostic factors influencing survival after surgeries for upper urinary tract urothelial carcinoma (UUT-UC) with longer follow-up periods than in previous studies. Between January 2000 and December 2004, 386 patients underwent nephroureterectomy for UUT-UC. The data for the 221 patients with UUT-UC were retrospectively reviewed. Nine variables were evaluated for association with the survival outcomes of cause-specific survival. The prognostic significance was tested univariately with the log-rank test. The simultaneous effects of multiple prognostic factors were estimated by multiple regression analysis using the Cox proportional hazards model. The median follow-up was 38.4 months. The 5-year over all survival was 62.3%. Significant prognostic factors for disease-specific survival rate on univariate analysis were pathological stage (p < 0.0001), tumor grade (p = 0.0324), and venous invasion (p < 0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p = 0.0205). Venous invasion was the only independent prognostic factor in pathologically localized UUT-UC.

Prospective longitudinal comparative study of health-related quality of life in patients treated with radical prostatectomy or permanent brachytherapy for prostate cancer.

To determine health-related quality of life (HRQOL) after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (BT), third party-conducted QOL surveys were prospectively compared. Between 2004 and 2005, 37 patients underwent RRP and 36 were treated with BT. A QOL survey consisting of the Medical Outcomes Study 36-Item Short Form (SF-36), the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and the International Prostate Symptoms Score (IPSS) was completed prospectively by a research coordinator at baseline, and at 1, 3, 6 and 12 months after treatment. The RRP patients scored well in general QOL except at 1 month after surgery, with their mental health better than at baseline by 6 months after surgery. Disease-specific QOL in RRP patients received a low score at 1 month for both urinary and sexual function, though urinary function rapidly recovered to baseline levels. BT patient QOL was not affected by the therapy except in the IPSS score. However, general and mental health scores in BT patients were inferior to those in RRP patients. This prospective study revealed differences in QOL after RRP and BT. These results will be helpful in making treatment decisions.

The benefits of clamping the renal artery in laparoscopic partial nephrectomy.

The purpose of this study is to compare the performance of laparoscopic partial nephrectomy (LPN) with and without clamping of the renal artery and to evaluate the impact of clamping on postoperative renal function. A total of 20 patients underwent LPN, 13 without and 7 with clamping of the renal artery. The 2 groups were compared with respect to complications, blood loss, operative time, mean tumor size, and incidence of positive margins. Renal function was evaluated by pre- and postoperative renal scintigraphy using 99m Technetium-mercaptoacetyltriglycine (99mTc-MAG3). Intraoperative blood loss was significantly higher in the group without clamping than in the group with clamping (p0.04). In the group with clamping, the median warm ischemic time was 35 min (range 25-40 min). The serum creatinine values and the renal scintigraphy showed no influence on postoperative renal function with or without clamping. In the group without clamping, 2 cases were showed positive surgical margins. The procedure performed with clamping of the renal artery is superior to the procedure performed without clamping as it provides the advantages of controlling hemorrhaging without injury to renal function and prolonging the surgical time and allowing for more accurate resection of renal tumors.

Iodine-125 seed implantation (permanent brachytherapy) for clinically localized prostate cancer.

From January 2004 to March 2007, 308 patients with clinically localized prostate cancer were treated using iodine-125 (125I) seed implantation (permanent brachytherapy) at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. We evaluated the treatments efficacy and morbidity in 300 prostate cancer patients who were followed up for more than 1 month after brachytherapy. Based on the National Comprehensive Cancer Network (NCCN) guidelines, patients with a prostate volume of less than 40 ml in transrectal ultrasound imaging were classified as low or intermediate risk. The median patient age was 67 years (range 50 to 79 years), the median prostate-specific antigen (PSA) value before biopsy was 6.95 ng/ml (range 1.13 to 24.7 ng/ml), and the median prostate volume was 24.33 ml (range 9.3 to 41.76 ml). The median follow-up was 18 months (range 1 to 36 months) and the PSA levels decreased in almost all patients after brachytherapy. Although 194 of 300 patients (64.7%) complained of difficulty in urination, pollakisuria/urgency, miction pain, and/or urinary incontinence, all of which might be associated with radiation prostatitis during the first month after brachytherapy, these symptoms gradually improved. 125I seed implantation brachytherapy is safe and effective for localized prostate cancer within short-term follow up.

Initial report of hybrid radical prostatectomy for prostate cancer: reduced bleeding, clear vision, and secure surgical margins.

To evaluate morbidity in Hybrid Radical Prostatectomy (HRP, hybridized laparoscopic and open retropubic radical prostatectomy). The operative and pathological outcomes obtained in 25 consecutive patients who underwent HRP were reviewed. The median operating time was 220 min, median blood loss was 550 ml, and no patient required an allogenic blood transfusion. No severe postoperative complications were observed. The surgical margin was positive in 12% of all patients, and in 1 patient with pT2 or less (4.5%). These results indicate that HRP is safe and may be able to combine the benefits of both laparoscopic and open procedures.

Health-related quality of life after radical cystectomy for bladder cancer in elderly patients with an ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir: a comparative questionnaire survey.

To compare the health-related quality of life of elderly patients after radical cystectomy for bladder cancer in urinary diversion groups: ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir. The 109 participating elderly patients aged 75 or older completed self-reporting questionnaires: the QLQ-C30, and on satisfaction with urinary diversion methods. Fifty-six patients had undergone constructions for ileal conduit diversion, 31 for ureterocutaneostomy, and 22 for orthotopic urinary reservoir (OUR). The median follow-up period for each group was 4.0 years (range 0.3-11.2), 4.5 years (range 0.3-18.0), and 3.3 years (range 0.3-6.7), respectively. Regardless of the type of urinary diversion, the majority of patients reported having good overall quality of life, although with some problem of pain. No significant differences among urinary diversion subgroups were found in any quality of life area in the QLQ-C30 questionnaire. More patients in the OUR sub-group felt disappointment than those in the ileal conduit or cutaneostomy sub-groups. However, a questionnaire which asked which diversion method would be preferable showed a trend that more patients in the OUR subgroup would have chosen the same one. Health-related quality of life appeared relatively good in these 3 groups. Patient demands and expectations may be so different from the results that the details of each urinary diversion method should be explained thoroughly. OUR construction could be a candidate even for elderly patients.

Suicide gene therapy with adenoviral delivery of HSV-tK gene for patients with local recurrence of prostate cancer after hormonal therapy.

We conducted a Phase I study of in situ herpes simplex virus thymidine kinase (HSV-tk) plus ganciclovir (GCV) gene therapy, which was approved by the Japanese government as the first prostate cancer gene therapy trial. Major inclusion criteria were local recurrence of prostate cancer after hormonal therapy and no metastasis. Adv.HSV-tk was injected directly into the prostate in escalating doses from 10(9) to 10(10) infection units, followed by intravenous administration of GCV for 14 days. Eight patients received nine courses of this gene therapy. The detection of vector DNA in blood/urine was only transient and no remarkable adverse events were observed in any patient. With regard to clinical response, significant prolongation of the median serum prostate-specific antigen (PSA) doubling time from 2.9 to 6.2 months (P = 0.041) was detected. In five patients (six injections), a clear decrease of PSA values was observed. One patient showed repeated clinical response after repeated injections. Serum cytokine analysis showed no notable changes after treatment. Fluorescence-activated cell sorting analysis also showed no influence on phenotypic distribution in peripheral blood samples, except for an increasing trend of CD8(+)/HLA-DR(+) after therapy. This study confirmed the safety profile and possibility of clinical response at the surrogate marker level in a clinical trial of HSV-tk gene therapy for hormone-refractory prostate cancer.

Comparative study of oncologic outcome of laparoscopic nephroureterectomy and standard nephroureterectomy for upper urinary tract transitional cell carcinoma.

OBJECTIVES: To determine the oncologic safety of laparoscopic nephroureterectomy (LNU), we compared the long-term oncologic outcome of LNU versus open nephroureterectomy (ONU) in patients with upper tract transitional cell carcinoma. METHODS: A total of 367 nephroureterectomy procedures were performed at our institutes for upper tract transitional cell carcinoma without distant metastases. Of 224 patients without concomitant or previous bladder cancer, 58 underwent LNU with open intact specimen retrieval plus open distal ureter and bladder cuff removal and 166 underwent ONU. Their data were reviewed and analyzed retrospectively. The mean follow-up was 13.6 months (range 14 to 34) for the LNU group and 28.0 months (range 14 to 36) for the ONU group. RESULTS: Bladder recurrence was recognized in 19 patients (32.8%) after LNU at a median follow-up of 5.6 months compared with 63 patients (38.0%) after ONU. Local recurrence only developed in 2 patients (1.1%) after ONU. One port site metastasis occurred in a patient who had undergone LNU. Distant metastases developed in 10 patients (17.2 %) after LNU and 33 patients (19.9%) after ONU. The frequency of bladder recurrence, local recurrence, and distant metastases did not differ significantly between the two groups. The actual disease-free 2-year survival rates were similar (75.6% versus 81.7%). In all patients, the risk of metastases and death increased with advanced tumor stage and grade, but not by surgical procedure. CONCLUSIONS: In the surgical management of upper tract transitional cell carcinoma, LNU does not negatively affect long-term oncologic control and can be considered an alternative modality. Tumor stage and grade are, however, important prognostic factors in the incidence of metastases and cancer-specific mortality.

The efficacy of neoadjuvant androgen deprivation therapy as a prostate volume reduction before brachytherapy for clinically localized prostate cancer.

From September 2003 to December 2005, 188 patients who visited our hospital and allied institutions for the purpose of prostate brachytherapy were administrated hormonal therapy for volume reductions before brachytherapy. The pretreatment and posttreatment of prostate volume using a transrectal ultrasound volumetric study and the types and duration of hormonal therapy were analyzed. We administered 91 patients with Luteinizing hormone-releasing hormone (LH-RH) agonist, 49 patients with anti-androgen (bicaltamide/flutamide), and 48 patients with maximum androgen blockade (MAB). The duration of the hormonal therapy was 1-3 months for 49 patients, 4-6 months for 59 patients, 7-9 months for 40 patients, 10-12 months for 32 patients, and over 13 months for 8 patients. Before the initiation of hormonal therapy, the mean prostate volume was 35.12 ml (11.04-78.71 ml), and the average of prostate volume before and after hormonal therapy was 36.79 ml and 24.79 ml, respectively (a 32.4% reduction). The prostate volume reduction rate was 32.0% for the LH-RH agonist only, 18.1% for the anti-androgen only and 41.2% for the MAB. No statistically significant difference was observed for the duration of hormonal therapy between 3 groups. A three-month course of the neoadjuvant LH-RH agonist indicated a sufficient volume reduction effectiveness for a large prostate volume.

Routine transurethral biopsy of the bladder is not necessary to evaluate the response to bacillus calmette-guerin therapy.

We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy results. Fifty-three of 54 patients (98.1%) with no visible recurrent tumor and negative urinary cytology demonstrated negative pathological results on bladder biopsy. When not found in conjunction with positive urinary cytology, erythematous mucosa on cystoscopy was not an indicator of tumor recurrence or residual cancer. In conclusion, routine transurethral biopsy of the bladder for evaluating the response to BCG intravesical therapy is not necessary in patients who have no visible tumor on cystoscopy and negative urinary cytology.

Combination chemotherapy with estramustine phosphate, ifosfamide and cisplatin for hormone-refractory prostate cancer.

We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.

Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute.

This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease.

The female partner's satisfaction with sildenafil citrate treatment of erectile dysfunction.

BACKGROUND: Data on female partners' satisfaction are scarce, although there have been many articles on patient satisfaction after sildenafil citrate treatment. The aim of this study was to evaluate the satisfaction of female partners of patients receiving sildenafil citrate for their erectile dysfunction (ED) and to assess the female partners' sexual function. METHODS: Ninety-eight patients with ED were treated. Their female partners were asked to answer a questionnaire we have prepared to evaluate the efficacy of treatment, sexual satisfaction and changes in quality of life. It also included a question about female sexual function. From the results, the relationship between their female partner's satisfaction and efficacy of treatment, as well as female sexual function, were assessed. RESULTS: Thirty (31%) questionnaires were returned to us for analysis. Effectiveness of the treatment was acknowledged by 90% of the partners. An improvement in their partner's quality of life was noticed by 60% of the women. The majority (66.7%) of the female partners were satisfied with sildenafil citrate treatment and 20% were disappointed. Moreover, 20% of the female partners were concerned about adverse events. Regarding female sexual function, some form of sexual dysfunction affected 46.7% of the women. Furthermore, a significant number (P = 0.0230) of the female partners disappointed with the treatment had some kind of sexual dysfunction. CONCLUSIONS: The results indicated that female partners reported relatively high levels of treatment satisfaction. Female partners' sexual function and anxiety regarding adverse events should be evaluated when their satisfaction with sildenafil citrate treatment is poor despite an improvement of erectile function.

[The analysis of thymidine phosphorylase examined by ELISA in bladder cancer].

PURPOSE: Some reports suggest that the high level expression of thymidine phosphorylase (TP), which is known as one of angiogenic factors, is related to high malignancy and also poor prognosis in the field of gastrointestinal cancer. So the authors investigated the expression of TP in bladder cancer. MATERIALS AND METHODS: The expression of TP in cancer tissues and normal tissues, which were obtained during transurethral resection of the tumor of 66 patients with initial primary bladder cancer, was examined by enzyme-linked immunosorbent assay (ELISA). And relationship of the TP expression and clinicopathologic factors was investigated. RESULTS: The level of TP expression was significantly high in cancer tissues compared with normal tissues (P < 0.0001). About the level of TP expression of cancer tissues, there was a significant difference between G1 and G3 in grade (P = 0.0099), Ta and T2 or greater (P = 0.0059), Ta, T1 and T2 or greater (P = 0.0157) in T stage, papillary and non-papillary in surface form (P = 0.0056), pedunculated and sessile in tumor shape (P = 0.0458), and 1 cm or under and 3 cm or greater in size (P = 0.0267). The level was higher in latter, respectively. About the level of TP expression of normal tissues, the level was significantly higher in the cases with sessile tumor than the cases with pedunculated tumor (P = 0.0078). CONCLUSION: There is correlation between the level of TP expression of cancer tissues and their grade of malignancy, so we can expect that the level of TP expression of cancer tissues will be a prognostic factor. And what does it mean in the fact that the level of TP expression of normal tissues in patients with sessile tumor is higher? It should be clear after accumulation of the cases and collecting the episodes in the follow-up period.