A simple flow cytometric scoring system is useful for distinguishing myelodysplastic syndromes from non-clonal anemic disorders

Myelodysplastic syndromes (MDS) are a myeloid neoplasm characterized by abnormal differentiation, ineffective hematopoiesis, and genetic instability with enhanced risk of transforming to acute myeloid leukemia (AML). The diagnosis of MDS is principally made based on the percentage of blasts in the bone marrow and peripheral blood, type and degree of dysplasia and the presence of ring sideroblasts. Recently, for making an accurate diagnosis of MDS, the aberrant antigen expression detection of hematopoietic cells by flow cytometry has been reported to be a useful. However, the diagnostic systems utilized in those studies are rather complicated. We modified an existing flow cytometric scoring system (FCMSS) based on aberrancies in the myeloid lineage and evaluated its usefulness in diagnosing various anemic disorders, including myelodysplastic syndromes (MDS). The flow cytometric score was significantly higher in MDS patients than in those with other anemic disorders, the exception being megaloblastic anemia (i.e., Vitamin B12 deficiency, folate deficiency). The data suggest that our FCMSS may provide useful information for making the diagnosis of MDS and other anemic disorders

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.</p

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.</p

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

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./</p

The Effect of Changing the Contraction Mode During Resistance Training on mTORC1 Signaling and Muscle Protein Synthesis

Acute resistance exercise (RE) increases muscle protein synthesis (MPS) via activation of mechanistic target of rapamycin complex (mTORC), and chronic resistance exercise training (RT) results in skeletal muscle hypertrophy. Although MPS in response to RE is blunted over time during RT, no effective restorative strategy has been identified. Since eccentric muscle contraction (EC) has the potential to strongly stimulate mTORC1 activation and MPS, changing the muscle contraction mode to EC might maintain the MPS response to RE during chronic RT. Male rats were randomly divided into RE (1 bout of RE) and RT (13 bouts of RE) groups. Additionally, each group was subdivided into isometric contraction (IC) and EC subgroups. The RE groups performed acute, unilateral RE using IC or EC. The RT groups performed 12 bouts of unilateral RE using IC. For bout 13, the RT-IC subgroup performed a further IC bout, while the RT-EC subgroup changed to EC. All muscle contractions were induced by percutaneous electrical stimulation. Muscle samples were obtained at 6 h post exercise in all groups. After the 1st RE bout, the EC group showed significantly higher p70S6K Thr389 phosphorylation than the IC group. However, the phosphorylation of other mTORC1-associated proteins (4E-BP1 and ribosomal protein S6) and the MPS response did not differ between the contraction modes. After the 13th bout of RE, mTORC1 activation and the MPS response were significantly blunted as compared with the 1st bout of RE. Changing from IC to EC did not improve these responses. In conclusion, changing the contraction mode to EC does not reinvigorate the blunted mTORC1 activation and MPS in response to RE during chronic RT

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.</p

Multiple myeloma with t(11;14)-associated immature phenotype has lower CD38 expression and higher BCL2 dependence

CD38 expression on myeloma cells is a critical factor affecting the early response to the anti-CD38 antibody daratumumab. However, factors affecting CD38 expression in untreated multiple myeloma are not fully elucidated. In this study, we found that CD38 expression was significantly lower in myeloma patients with the translocation t(11;14)-associated immature plasma cell phenotype, and particularly in those expressing B-cell-associated genes such as PAX5 and CD79A. CD138, a representative marker of plasmacytic differentiation, was also significantly lower in these patients, suggesting that CD38 expression may be associated with the differentiation and maturation stages of myeloma cells. Furthermore, the BCL2/BCL2L1 ratio, a response marker of the BCL2 inhibitor venetoclax, was significantly higher in patients with the immature phenotype expressing B-cell-associated genes. The BCL2/BCL2L1 ratio and CD38 expression were significantly negatively correlated. We also confirmed that patients with translocation t(11;14) expressing B-cell-associated genes were indeed less sensitive to daratumumab-mediated direct cytotoxicity but highly sensitive to venetoclax treatment in ex vivo assays. Moreover, all-trans-retinoic acid, which enhances CD38 expression and induces cell differentiation in myeloma cells, reduced B-cell marker expression and the BCL2/BCL2L1 ratio in myeloma cell lines, leading to reduced efficacy of venetoclax. Venetoclax specifically induces cell death in myeloma with t(11;14), although why patients with translocation t(11;14) show BCL2 dependence is unclear. These results suggest that BCL2 dependence, as well as CD38 expression, are deeply associated with the differentiation and maturation stages of myeloma cells. This study highlights the importance of examining t(11;14) and considering cell maturity in myeloma treatment strategies

VLBI Astrometry of AGB Variables with VERA -- A Semiregular Variable S Crateris --

We present a distance measurement for the semiregular variable S Crateris (S Crt) based on its annual parallax. With the unique dual beam system of the VLBI Exploration for Radio Astrometry (VERA) telescopes, we measured the absolute proper motion of a water maser spot associated with S Crt, referred to the quasar J1147-0724 located at an angular separation of 1.23$^{\circ}$. In observations spanning nearly two years, we have detected the maser spot at the LSR velocity of 34.7 km s$^{-1}$, for which we measured the annual parallax of 2.33$\pm$0.13 mas corresponding to a distance of 430$^{+25}_{-23}$ pc. This measurement has an accuracy one order of magnitude better than the parallax measurements of HIPPARCOS. The angular distribution and three-dimensional velocity field of maser spots indicate a bipolar outflow with the flow axis along northeast-southwest direction. Using the distance and photospheric temperature, we estimate the stellar radius of S Crt and compare it with those of Mira variables.Comment: 9 pages, 4 figures, accepted for publication in PASJ (Vol.60, No.5, October 25, VERA special issue

Feasibility of cord blood transplantation in chemosensitive adult T-cell leukemia/lymphoma: a retrospective analysis of the Nagasaki Transplantation Network

It has been reported that cord blood transplantation (CBT) for patients with aggressive adult T-cell leukemia/ lymphoma (ATL) results in poorer outcomes than transplantation using other stem cell sources. To identify a subset of ATL in which CBT is feasible, we retrospectively analyzed 27 patients treated with CBT at three institutions in Nagasaki Prefecture, Japan. The estimated overall survival (OS) rate at 3 years was 27.4 %. Of 16 patients who received CBT during remission (complete, CR, or partial, PR), the OS rate at 3 years was 50 %, while during refractory periods (non-CR or non-PR), the OS rate was 9.1 %. Reduced intensity conditioning (RIC) was given to 18 patients, and myeloablative conditioning (MAC) was used in nine, with 3-year OS of 50.0 and 0 %, respectively. Of the 19 deaths, nine were due to progressive disease, eight (five MAC and three RIC) to infection, and two to multiple organ failure. These results suggest that CBT provides similar results with those in other transplantation procedures for selected ATL patients, such as those in CR or PR. Further studies are needed to evaluate the use of CBT in aggressive ATL