Tomotaka Hattori

Clinical evaluation of soluble cytokeratin 19 fragments (cyfra 21-1) in serum and urine of patients with bladder cancer

OBJECTIVES CYFRA 21-1 is a new tumor marker that measures cytokeratin 19 (CK-19) fragments by a sandwich enzyme-linked immunosorbent assay (ELISA). In this study, we evaluated the usefulness of serum and urine CYFRA 21-1 as a tumor marker for bladder cancers. METHODS We measured serum and urine CYFRA 21-1 levels in a group of patients with bladder cancer (n = 58) and a group without bladder cancer (n = 220). The latter group was divided into five subgroups of patients (those with cystitis, benign prostatic hyperplasia (BPH), urolithiasis, or renal dysfunction, and a group of healthy, controls). In the bladder cancer group, we measured CYFRA 21-1 levels after transurethral resection of bladder tumor (TUR-Bt), and we also analyzed the relationship between serum and urine CYFRA 21-1 levels and tumor-related factors. RESULTS Serum and urine CYFRA 21-1 levels were significantly higher in the bladder cancer group than in each of the non-bladder cancer subgroups. However, urine CYFRA 21-1 levels did not differ significantly between the bladder cancer group and the cystitis subgroup. In the bladder cancer group, serum CYFRA 21-1 levels were significantly higher in patients with local advanced-stage tumors and in those who had metastases. Urine CYFRA 21-1 levels decreased as a function of time after TUR-Bt. These levels were strongly correlated with tumor volume and were significantly better than urine cytology for the detection of bladder cancers of grades 1 and 2. CONCLUSIONS These results suggest that urine CYFRA 21-1 is a useful tumor marker in screening for bladder cancer, and that serum CYFRA 21-1 may be a tumor marker for advanced bladder cancers.

Tumor progression and expression of matrix metalloproteinase-2 (MMP-2) mRNA by human urinary bladder cancer cells

Abstract Tumor cells at the stage of tumor progression build up a high tolerance to intrinsic and extrinsic defence systems and/or therapeutic procedures, and the cells deeply infiltrate the adjacent tissue, which is followed by tumor metastasis to remote organs and tissues. This study was designed to investigate the relationship between expression of matrix metalloproteinase-2 (MMP-2) and invasiveness of human bladder cancer cells, using cell lines derived from a parental human urinary bladder tumor cell line, T24. Two subpopulations of the human bladder cancer cell line T24, Hi-T24 and Lo-T24, were selected using an invasion assay and then expression of MMP-2 mRNA and protein was analyzed by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme immunoassay (EIA). The gross morphology, cell growth rate, and adhesion activity to a basement membrane extract (matrigel) of the high-invasive Hi-T24 cells were similar to those of the low-invasive Lo-T24 cells, but the Hi-T24 cells were 3.8-fold more haptotactic through matrigel than the Lo-T24 cells. The haptotactic activity of the Hi-T24 cells was suppressed by the addition of an anti-MMP-2 antibody, and the amounts of MMP-2 protein secreted into the spent medium by the Hi-T24 and Lo-T24 cells were 7.8 ± 0.2 and 3.8 ± 0.3 ng/ml (P < 0.05), respectively. The quantities of tissue inhibitor of metalloproteinase-2 (TIMP-2) protein secreted by Hi-T24 and Lo-T24 cells were 133.2 ± 4.3 and 168.7 ± 5.6 ng/ml, respectively (P < 0.05). The levels of transcription of the genes encoding MMP-2 and the transmembrane MMP, MT-MMP, evaluated by RT-PCR, were higher in the Hi-T24 cells than in the Lo-T24 cells. Expression of the TIMP-2 gene was slightly lower in the Hi-T24 cells than in the Lo-T24 cells. These results indicate that expression of the metalloproteinases are imbalanced at the gene level in human urinary bladder cancer cells at the stage of tumor progression.

Study of macrophages in prostatic fluid from nonbacterial prostatitis patients. V. Relation between activation of macrophages and stage of prostatitis.

Relationship between activation of macrophages in prostatic fluid and stage of nonbacterial prostatitis was studied by observing the rate of adherence of leukocytes, percentage of macrophages among adherent leukocytes and presence of spreading of macrophages. As a result, it was found that macrophages in the early stage of NBP were more activated than macrophages in the chronic stage.

Recombinant Interleukin-2-Expanded Tumor Infiltrating Lymphocytes from Human Renal Cell Cancer Do Not Exhibit Autologous Tumor Cell-Specific Cytotoxicity

We studied subsets and cytotoxicity of recombinant interleukin-2 (rIL-2)-expanded tumor-infiltrating lymphocytes (TIL) from renal cell cancer (RCC) patients. TIL were successfully expanded in 13 of 14 RCC cases using anti-CD3 during the initial 48 h of culture. Percentages of CD8-positive cells among rIL-2-expanded TIL at 1-4 week(s) of culture were 56.2 +/- 15.1% (range 26.2-79.8%, n = 13) and not necessarily predominant over CD4-positive cells. Natural killer and lymphokine-activated killer (LAK) activities of TIL at 3-6 weeks of culture were 31.6 +/- 15.8% (range 1.4-57.4%, n = 9) and 16.6 +/- 11.6% (range 3.8-35.6%, n = 6), respectively. Autologous and allogeneic RCC cytotoxicity of TIL at 3-4 weeks of culture were 17.9 +/- 19.7% (range 0-47.6%, n = 4) and 18.9 +/- 14.8% (range 0-47.3%, n = 12), respectively. Since there was no statistical difference between them, autologous specific cytotoxicity was not demonstrated. From these result of the present study, it is unlikely that most of effector cells of rIL-2-expanded TIL in autologous RCC lysis are major histocompatibility complex-restricted cytotoxic T cells. We concluded that it is doubtful whether TIL is significantly superior over LAK cells in immunotherapy of human RCC.

[Combined immunotherapy using interferon-alpha, interleukin-2 and lymphokine-activated killer cells--improvement of quality of life in patients with advanced renal cell carcinoma].

The goal of any treatment strategy for cancer is to improve not only patient survival but also quality of that survival. Between March 1990 and February 1993, we treated 10 patients with advanced RCC (9 men and 1 woman) by combined immunotherapy using natural interferon-alpha (IFN-alpha), recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells, and resulting the quality of life (QOL) issues examined. The ages of the patients ranged from 36 to 78 years (mean: 60.2) and the performance status (PS) ranged from 30 to 100% (mean: 77%). There were 8 lung, 3 bone, 2 brain and 1 neck and para-aortic lymph node metastases. We could evaluate 8 patients, 2 patients dropped out because of bone fracture and acute pneumonia. The protocol was as follows; 1 x 10(6) IU of rIL-2 as an intravenous infusion and 6 x 10(6) IU of IFN-alpha intramuscularly on days 1-7 and 15-21. In additions LAK cells obtained from the patients were given on days 14, 21, 28, and 35 intravenously. This protocol was repeated for more than three cycles (mean: 4.13 cycles) in each patient. The maintenance therapy on outpatient basis were performed in 4 patients after confirmation of the safety of the combined immunotherapy. This outpatient regimen was composed of 1 x 10(6) IU of rIL-2 intravenously, 6 x 10(6) IU of IFN-alpha intramuscularly on days, 1, 8, 15, 22, and 29, plus LAK cells on days 15 and 29. We repeated this protocol for 3-5 cycles (mean: 4.25 cycles).(ABSTRACT TRUNCATED AT 250 WORDS)

Is it safe to continue antithrombotic agents before prostate biopsy

Background Whether antithrombotic agents should be stopped before prostate biopsy is unsettled. We investigated the impact of antithrombotic agents on bleeding complications after prostate biopsy. Materials and methods Among the patients who underwent transrectal ultrasound-guided prostate biopsy from June 2006 to December 2013 at Ebina General Hospital, Kanagawa, Japan, 1817 cases were retrospectively assessed. Patients were divided into two groups: those not taking antithrombotic agents (control group) and those taking them (experimental group). The frequency and severity of bleeding complications after the procedure were compared. The severity of bleeding events was graded using the Common Terminology Criteria for Advanced Events vol. 4.0. Results Hemorrhagic complications were classified into grades 1 to 3. Patients with complications of Grade 2 and above needed treatment. As for the Grade 1 event, there were no differences between two groups. The frequency of more than Grade 2 bleeding events was 1.7% and 3.5% in the control and experimental group, respectively; the odds ratio was 2.18 (P = 0.039). Grade 3 events occurred in seven patients of the control group (0.5%) and four patients of the experimental group (1.2%). Conclusions The present study showed that continuation of antithrombotic agents increased the frequency of hemorrhagic complications requiring intervention. It suggests that attention should be paid to the patients taking antithrombotic agents before prostate biopsy.

MP77-02 THE ANTITHROMBOTIC AGENTS DO NOT NEED TO DISCONTINUE PRIOR TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BIOPSY: A SINGLE CENTER EXPERIENCE.

INTRODUCTION AND OBJECTIVES: The natural history of prostatic lesions identified on multiparametric MRI (mpMRI) is unknown. We aimed to describe changes observed over time on serial mpMRI, and to determine especially how these influenced management of men on active surveillance (AS). METHODS: Between January 2008 and October 2014, 754 men underwent mpMRI, of whom 65 had 2 studies. Imaging findings and corresponding clinico-pathologic parameters were compared and related to the discontinuation of AS. RESULTS: Serial mpMRIs were performed for AS monitoring in 42 men and for suspicion of prostate cancer in 23 men. Collectively, there were 93 lesions on 1st mpMRI and 143 on 2nd mpMRI for analysis. The median time between scans was 19.7 months (IQR 13.529.5). New lesions were seen in 34 of 65 (52.3%) patients. The Median (IQR) number of lesions seen per patient increased from 1 (1-2) to 2 (13). Lesion size increased in 29.4% (mean 3.0 mm/yr) and decreased in 18.5% (mean -2.1mm/yr ). The ADC value decreased in 47.9 % of lesions (>300 unit decrease in 15%) between scans and increased in a further 25 %. Three of 47 (6%) lesions moved from ADC>600 to ADC <600. Forty-nine (53%) lesions were scored PIRADS 3 on first MRI, of which 5 (10%) converted to PIRADS 4. There were 21 de novo PIRADS 4/5 lesions identified in 15 patients (23%). Overall, 10 (24.3%) men on AS chose to undergo definitive therapy following an increase in suspicion of cancer on their MRI. Eight of the 10 men were confirmed to have pathological progression on biopsy. Four of these developed a new PIRADS 4 lesion, and 2 had conversion of PIRADS 3 to PIRADS 4. Two additional patients had an increase in lesion size between scans. CONCLUSIONS: In general, serial mpMRI demonstrates small changes in lesion appearance over time. However, new lesions are common, and changes in lesion characteristics between MRIs significantly influenced the management of men on AS.

Urothelial mucosal concentration of levofloxacin administered before transurethral resection: Is the mucosal concentration predictable?

Background: Although it is an established surgical technique, transurethral resection (TUR) is associated with a certain incidence of postoperative bacteriuria. Assessment was made whether the urothelial mucosal concentration of an antibiotic administered before TUR was high enough to decrease the incidence of urinary tract infection (UTI). Also investigated were factors predicting the organ concentration.

The efficacy of Bacillus Calmette-Guerin instillation therapy of the upper urinary tract for carcinoma in situ

AbstractBackground. Treatment of carcinoma in situ (CIS) of the upper urinary tract is still difficult. In this study, we assessed the efficacy and safety results of Bacillus Calmette-Guerin (BCG) instillation therapy for CIS of the upper urinary tract. Methods. Thirteen renal units with CIS in eight patients 60–77 years old (median, 68 years) were treated with BCG. BCG (Tokyo 172 strain) was instilled at a dose of 160 mg into each renal unit once a week for 6 consecutive weeks via nephrostomy. The follow-up period ranged from 7 to 63 months (median, 26 months). Results. Of 13 renal units in eight patients, 12 units (92.3%) in eight patients became negative by cytology. Only 1 renal unit showed recurrence. The duration of the response ranged from 7 to 63 months (median, 25 months). Few side effects were observed after BCG instillation. Fever was most frequent (6/8, 75%), followed by symptoms of irritation such as frequency (5/8, 62.5%). Conclusion. BCG instillation therapy is safe and effective for CIS of the upper urinary tract. It can be used as a first-line therapy instead of any surgical option.