Sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: Incidence, risk factors and outcomes.

This retrospective study was conducted in Japan to determine the incidence, risk factors and outcomes of sinusoidal obstruction syndrome (SOS) after allogeneic hematopoietic stem cell transplantation (HSCT). Among 4290 patients undergoing allogeneic HSCT between 1999 and 2010, 462 were diagnosed with SOS according to the Seattle criteria (cumulative incidence, 10.8%). The cumulative incidence of SOS diagnosed by the modified Seattle criteria was 9.3%. Of 462 patients, 107 met the Baltimore criteria and 168 had severe SOS with renal and/or respiratory failure. The median onset for SOS was 12 days after HSCT (range, -2-30). Overall survival at day 100 was 32% for SOS and 15% for severe SOS. Multivariate analyses showed that significant independent risk factors for SOS were the number of HSCTs, age, performance status, hepatitis C virus-seropositivity, advanced disease status and myeloablative regimen. SOS was highly associated with overall mortality (hazard ratio, 2.09; P<0.001). Our retrospective survey showed that the cumulative incidence of SOS in Japan was 10.8%, similar to that previously reported in Western countries, and that the overall survival of patients who developed SOS was low. Furthermore, several risk factors were identified. Preventive and therapeutic strategies for high-risk SOS patients must be established to improve overall survival.

Postoperative changes of sperm chromatin heterogeneity, using acridine orange staining, in varicocele patients.

The aim of this study was to evaluate postoperative changes in sperm chromatin heterogeneity in varicocele patients. In 15 infertile patients with varicocele, sperm parameters including concentration, motility, and morphology were evaluated before and after surgical correction of varicocele. Sperm motion analysis using computer-assisted semen analyzer (CASA) was also performed. To analyze the sperm nuclear proteins, the acridine orange staining method was used. On semen analysis, sperm concentration and motility significantly increased after surgery (p = 0.002, p = 0.003, respectively), although sperm morphology was unaltered postoperatively. CASA parameters, including velocity, linearity, amplitude of lateral head displacement and beat cross frequency were unaltered postoperatively. On the other hand, acridine orange staining significantly increased postoperatively (p = 0.002). Varicocele influences the sperm chromatin condition, as well as sperm concentration and motility.

Treatment with prednisolone of hormone-refractory prostate cancer.

Fifteen patients 60 to 80 years old (a mean of 72 years) with hormone-refractory prostate cancer were treated with low dose prednisolone. All patients had previously undergone hormone therapy. Prostate specific antigen (PSA) values decreased in 11 cases (73%), of which 4 had PSA decreases of 50% or greater. Serum levels of DHEAS significantly decreased at 4 and 8 weeks after treatment (both intervals were p < 0.05 vs pretreatment). Of 8 patients with bone metastasis evaluation, 2 (25%) showed improvement of the lesion. In 5 patients (33%), relief of pain was observed one month after starting prednisolone. The one-year survival rate was 58%. The side effects were mild and manageable in an outpatient clinic.

Usefulness of sperm quality analyzer-V (SQA-V) for the assessment of sperm quality in infertile men.

The aim of this study was to evaluate the correlation of new of Sperm Quality Analyzer (SQA-V) with the computer-assisted sperm analysis (CASA) and manual semen analysis estimates. One hundred five fresh semen samples were analyzed using SQA-V and CASA and manual semen analysis. Significant correlations of sperm concentration (p < 0.0001), sperm motility (p < 0.0001), and normal morphology (p < 0.0001) were observed between SQA-V variables and manual semen analysis estimates. There also were significant correlations of sperm concentration (p < 0.0001), sperm motility (p < 0.0001), and sperm velocity (p = 0.0235) between SQA-V variables and CASA estimates. Meanwhile, it did not correlate with amplitude of lateral head displacement, beat cross frequency, lineality assessed by CASA. The value of the sperm concentration and the sperm motility measured by SQA-V showed high correlations with the value of those measured by CASA and manual semen analysis. In addition, velocity and sperm morphology may also be evaluated to some extent using SQA-V.

Assessment of sperm quality analyzer II B: comparison with manual semen analysis and CASA.

Two hundred and seven patients with male infertility were investigated. Total sperm concentration and percent progressive motility by SQA IIB showed high correlations with those of conventional manual method. Percent of normal morphology showed a significant correlation among these techniques. The sperm motility index (SMI) and total functional sperm concentration (TFSC) demonstrated high correlations with any variables of manual analysis. Only velocity and amplitude of lateral head displacement showed significant correlations with the variables obtained by SQA IIB, especially with SMI and TFSC. It was suggested that SQA IIB could be a useful instrument in the clinical practice of infertility as a screening test for semen quality.

Transurethral treatment of ejaculatory duct obstruction in infertile men.

Ten cases of ejaculatory duct obstruction with midline cyst, complaining of male infertility, were treated with transurethral incision. They had azoospermia or oligozoospermia, and physical examination did not show any abnormal findings. Serum levels of testosterone, LH, and FSH were within normal limits. The diagnosis of ejaculatory duct obstruction with midline cyst was made by transurethral ultrasonography and vasography. Thereafter, patients underwent transurethral incision of the verumontanum with a cold knife. Semen volume increased in all patients, and sperm concentration and/or motility improved in 7 patients (70%). Pregnancy was achieved by 3 couples (30%). Incision of the ejaculatory duct via an endoscopic technique could improve seminal findings and subsequent fertility.

Evaluation of acrosome reactivity using the Acrobeads test in varicocele patients: findings before and after treatment.

The Acrobeads test was performed on semen samples from 43 patients with varicocele before and after varicocelectomy. Sperm motility significantly increased after surgery (p <.05), while sperm concentration and motile sperm concentration did not alter postoperatively. Sperm motion analysis using CellSoft 3000 did not demonstrate a significant change after treatment. Acrobeads score significantly increased after the procedure (p<.005). Pregnancy was achieved in 10 patients (28%). Acrobeads score in cases that achieved pregnancy was increased postoperatively (p<.005). The percentage of patients with a postoperative increase in Acrobeads score in the group that achieved pregnancy was significantly higher than that observed in the unsuccessful group (p <.05). Sperm parameters other than the Acrobeads score did not show a significant difference between the successful and unsuccessful patients. The Acrobeads test assessed postoperatively can be useful in precisely evaluating fertility potential after varicocele repair.

Tubularized incised plate urethroplasty for distal hypospadia, using overlapping dorsal subcutaneous flaps.

This paper presents a newly developed simple procedure using overlapping vascularized dorsal dartos subcutaneous flaps to cover the neourethra after hypospadias correction. A 3-year old boy with distal hypospadias underwent the tubularized incised plate urethroplasty using this method. Postoperative complications, which include urethrocutaneous fistula, were not observed, but the glans did exhibit a vertical, slit-like meatus. Covering the neourethra with overlapping dorsal dartos flaps is expected to prevent the development of urethrocutaneous fistula in patients with distal hypospadias.

Upregulation of the klotho gene expression by thyroid hormone and during adipose differentiation in 3T3-L1 adipocytes.

A defect in the klotho gene expression in mice leads to a syndrome resembling human aging. The klotho gene encodes a single membrane protein whose extracellular domain carries homology to beta-glucosidases. However, either its function or regulatory mechanism of the gene expression still remains unknown. In the present study, we investigated the klotho gene expression in 3T3-L1 adipocytes using quantitative reverse transcription-polymerase chain reaction. Both membrane and secreted forms of the klotho gene were expressed in 3T3-L1 preadipocytes. Accompanied with adipose differentiation, not the secreted form but the membrane form was gradually increased. In 3T3-L1 adipocytes, triiodothyronine significantly increased the expression levels of membrane form of the klotho gene. These results suggest that the expression of membrane and secreted forms of klotho transcripts are regulated by different mechanisms and that the klotho gene product may play a role in adipose differentiation.

Kinetic analysis of cytokine gene expression in patients with GVHD after donor lymphocyte infusion.

Patients who receive a donor lymphocyte infusion (DLI) for the treatment of relapsed leukemia after allogeneic BMT (alloBMT) often developed GVHD. To determine whether cytokines might have a role in GVHD, an intensive kinetic analysis of in vivo cytokine gene expression was performed on PBMC from three such patients. Expression of IL-1beta, IL-2, IFN-gamma, IL-4, IL-5, IL-8, IL-10, IL-12, TNF-alpha, and IL-2Ralpha was examined using a sensitive semi-quantitative reverse transcription (RT)-PCR assay system. Six normal controls were also analyzed for comparison. Expression of type 1 T helper (Th1) cytokines, IL-2 and IFN-gamma was greatly increased in all three patients. In particular, the changes in IL-2 gene expression correlated well with disease progression, suggesting that IL-2 has a critical role in the development of GVHD. Although the pattern of type 2 T helper (Th2) cytokine gene expression differed in each patient, the expression of IL-4 was inversely related to expression of Th1 cytokines. These results suggest that Th1 dominates in the development of human clinical GVHD.

An experience of percutaneous embolization to post-traumatic arterial priapism in a child.

We report an experience of percutaneous transcatheter embolization to posttraumatic arterial priapism in a child. Priapism was successfully treated with this method. Angiography with subsequent selective embolization should be considered to be the treatment of choice for arterial priapism in children as well as in adults when less invasive treatments fail.

T-cell receptor gammadelta T-cell leukemia with the morphology of T-cell prolymphocytic leukemia and a postthymic immunophenotype.

T-cell prolymphocytic leukemia (T-PLL) is a postthymic T-cell neoplasm with a characteristic morphology and heterogeneous immunophenotype. Most cases of T-PLL express membrane T-cell receptors (TCRs) of the alphabeta phenotype. We experienced a 30-year-old man suffering from TCRgammadelta T-cell leukemia with morphology compatible to T-PLL with a postthymic phenotype. He was admitted with skin eruption and pancytopenia. Peripheral blood and bone marrow were occupied with medium-sized lymphocytes, which had moderately condensed chromatin with a single nucleolus and sparse, nongranular basophilic cytoplasm. The immunophenotype was CD1a-, CD2-, CD3+, CD4-, CD5+, CD7+, CD8-, and terminal deoxynucleotidyl transferase negative. Hepatosplenomegaly was absent. He was diagnosed as having T-PLL and was treated with combination chemotherapy. Six months later the leukemic cell became chemoresistant. Although the patient showed transient improvement in response to pentostatin, he died 13 months after the diagnosis. To our knowledge, this is the first case of T-PLL with a TCRgammadelta phenotype.

Successful Cytoreduction with CAG (cytarabine, Aclarubicin and G-CSF) Therapy in Refractory Acute Myelogenous Leukemia before Allogeneic Stem Cell Transplantation.

Refractory acute myelogenous leukemia (AML) has a poor prognosis, and a long-term survival cannot be expected in most patients even if allogeneic bone marrow transplantation (allo-BMT) or allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is performed. An abundance of residual leukemic cells and poor performance status of patients before allo-BMT are often associated with a high relapse rate and high transplant-related mortality. Thus, to improve the prognosis of patients with refractory AML undergoing allo-BMT, it is necessary to reduce the leukemic cell volume as low as possible without severe complications. In this report, we used CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor (G-CSF)) therapy for cytoreduction before allo-BMT or allo-PBSCT in five patients with refractory AML. One of them achieved complete remission (CR) by CAG therapy alone and others achieved major tumor reduction prior to BMT and PBSCT. All patients achieved CR after allo-BMT and allo-PBSCT without severe complications. Three of them have remained CR for 9, 21 and 30 months, respectively. Although the results of this feasibility study are preliminary, the pre-transplant CAG therapy for refractory AML deserves further evaluation.

Epstein-Barr virus-negative high grade B cell lymphoma of donor origin developing 19 months after unrelated allogeneic bone marrow transplantation.

A 22-year-old man, in first complete remission of acute myelogenous leukemia, developed a high grade B cell lymphoma 19 months after an allogeneic bone marrow transplant (allo-BMT) from an HLA-identical unrelated donor. Biopsy of a cervical lymph node revealed a lymphoma that was negative for Epstein-Barr virus-encoded small nuclear RNAs (EBERs) in situ hybridization. Genotypic analyses identified the lymphoma to be of donor origin, and there was no evidence of the Epstein-Barr virus (EBV) DNA in the lymphoma by Southern blot analysis. The lymphoma went into complete remission, following four courses of combination chemotherapy, but relapsed after a month and the patient died of congestive heart failure. The patient was thought to be persistently immunosuppressed 11 months after cessation of immunosuppressants, and the lymphoma was thought to be induced by one or more factors other than EBV.

[Progression of refractory thrombocytopenia to chronic myelomonocytic leukemia accompanied by various inflammatory reactions].

A 51-year-old man was admitted for treatment of severe thrombocytopenia in May 1997. A diagnosis of MDS RA (refractory thrombocytopenia; RTC) was made by bone marrow examination, which revealed mild marrow hypoplasia and a reduced number of megakaryocytes accompanied by micromegakaryocytes and hypolobular megakaryocytes. Chromosome analysis demonstrated 46, XY, t(5;7) (q31;q22) in all 20 cells examined. The patient received only supportive therapy including platelet transfusion, until leukocytosis and monocytosis gradually developed in November 1998. In view of a marked increase in the number of monocytes (more than 3,000/microliter), a diagnosis of CMML was made in December 1998. As the leukocytosis progressed, various inflammatory symptoms such as facial erythema and endophthalmitis developed. Administration of interferon alpha (IFN alpha) unexpectedly worsened the leukocytosis and monocytosis, suggesting abnormal responses of these cells to IFN alpha. Detailed molecular analysis of these cells might reveal a novel mechanism of leukemogenesis associated with 5q31.

Long-term molecular remission induced by donor lymphocyte infusions for recurrent acute myeloblastic leukemia after allogeneic bone marrow transplantation.

A case of acute myelogenous leukemia with a t(8;21) translocation relapsed 5 months after allogeneic bone marrow transplantation (allo-BMT). After chemotherapy-induced hematologic remission, the patient received donor lymphocyte infusions (DLI); 4.9 x 108/kg T cells were infused. After DLI, she achieved molecular CR for the first time after allo-BMT, which lasted for 40 months. However, she suffered from grade III acute GVHD of the skin and the liver. Hepatic GVHD was sustained and resulted in fatal outcome. The case demonstrates that DLI is a double-edged sword. Further study is necessary before DLI can be considered to be a beneficial therapy for acute leukemia. Bone Marrow Transplantation (2000) 26, 809-810.

Multifocal fibrosclerosis as a possible cause of panhypopituitarism with central diabetes insipidus.

Multifocal fibrosclerosis denotes a combination of similar fibrous disorders occurring at different anatomical sites. We encountered a 53-year-old male patient with orbital pseudotumor, chronic paranasal sinusitis, fibrous nodules of the lungs, intracranial pachymeningitis, and panhypopituitarism with central diabetes insipidus (DI) as a possible manifestation of multifocal fibrosclerosis. It has been reported that intracranial pachymeningitis or orbital pseudotumor associated with multifocal fibrosclerosis could invade the sella turcica causing a variety of anterior and/or posterior pituitary dysfunctions. In our case, intracranial pachymeningitis apparently involved the pituitary stalk and gland. Isolated gonadotropin deficiency, in addition to central DI, preceded panhypopituitarism. Although panhypopituitarism with central DI due to multifocal fibrosclerosis is quite rare and only one case has ever been reported, this systemic fibrotic disorder can be a possible cause of panhypopituitarism with central DI.

A phase III randomized study comparing doxifluridine and 5-fluorouracil as supportive chemotherapy in advanced and recurrent gastric cancer.

We conducted a phase III randomized study to investigate effects of supportive chemotherapy with oral doxifluridine (group A, 75 patients) or 5-fluorouracil (group B, 75 patients) in advanced gastric cancer when intensive chemotherapy was not an option. Although there were no significant differences between the groups with regard to survival, hospital-free survival and time to progression, median values of 3 endpoints were superior in group A. Secondary analysis showed that group A patients with prior chemotherapy tended to have longer survival and hospital-free survival and significantly longer time to progression.