WT1-guided pre-emptive therapy after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia.

Measurable residual disease (MRD)-guided pre-emptive therapies are now widely used to prevent post-transplant hematological relapse in patients with acute myeloid leukemia (AML). This single-center retrospective study aimed to clarify the significance of pre-emptive treatment based on Wilms' tumor gene-1 mRNA (WT1) monitoring for MRD in patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with AML who received chemotherapy for hematological relapse or WT1 increase after allo-HSCT were eligible for inclusion. From January 2017 to June 2022, 30 patients with a median age of 57 (16-70) years were included and stratified into two groups: 10 with WT1 increase and 20 with hematological relapse. The median times from HCT to WT1 increase or hematological relapse were 309 days (range: 48-985) or 242 days (range: 67-1116), respectively. Less intensive chemotherapy using azacitidine or cytarabine was selected for all patients with WT1 increase and 12 (60%) with hematological relapse. The 1-year overall survival and event-free survival rates for WT1 increase and hematological relapse were 70% vs. 44% (P = 0.024) and 70% vs. 29% (P = 0.029), respectively. These real-world data suggest that WT1-guided pre-emptive therapy may be superior to therapy after hematological relapse in patients with AML who have undergone allo-HSCT.

Robot-assisted radical prostatectomy using the novel hinotoriTM surgical robot system: initial experience and operation learning curve at a single institution.

Background: The hinotoriTM surgical robot system (HSRS) is the first made-in-Japan robotic system used for radical prostatectomy. Here, we report initial results and describe our learning curve (skill development) implementing robot-assisted radical prostatectomy using HSRS (h-RARP). Methods: Between November 2021 and December 2022, 97 patients who underwent h-RARP at our institution were enrolled in this study. We retrospectively evaluated the surgical outcomes of the initial cases using h-RARP, comparing those of RARP using da Vinci surgical robot system (d-RARP) in our institution. Furthermore, the learning curves of two surgeons with the highest number of h-RARP were analyzed. Patients treated by each surgeon were categorized into two groups: 1-15 cases (earlier group) and >15 cases (later group). Preoperative patient characteristics, operation parameters, and complication rates were compared between the two groups. Results: In terms of surgical outcome, h-RARP was comparable to d-RARP. The procedures performed by the HSRS were successfully completed in all cases. There was no complication of grade 3 or higher. Comparing the two surgeons, surgeon 1, who had performed 40 d-RARP procedures, had time using robot system of the later group that was significantly shorter than that of the earlier group. However, for surgeon 2 with more than 100 d-RARP procedures, there was no statistically significant difference in time using robot system between groups. Other parameters showed no difference between earlier and later groups for the two surgeons. Conclusions: Our results show that surgical outcomes of h-RARP are comparable to those of d-RARP during the initial experience of clinical application. In addition, the surgeons' learning curves for the total RARP experience suggest that the experience of d-RARP can carry over to performance using the novel HSRS.

Pretransplantation Inflammatory and Nutritional Status in Elderly Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Value of C-Reactive Protein-to-Albumin Ratio.

There are no clear criteria for selecting elderly patients with hematologic malignancies eligible for allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to evaluate inflammatory and nutritional status biomarkers as prognostic indicators of allogeneic HSCT in elderly patients. We compared the prognostic effects of 4 representative pretransplantation biomarkers: C-reactive protein-to-albumin ratio (CAR), Glasgow Prognostic Score (GPS), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR). A total of 143 patients age ≥60 years who underwent their first allogeneic HSCT for a hematologic malignancy were enrolled between 2010 and 2020 in our single-center cohort. The median patient age was 65 years (range, 60 to 72 years). Pretransplantation high CAR, high GPS, and low PNI scores were associated with poor overall survival (OS), but the AGR was not associated with OS. Among the 4 biomarkers, CAR stratified OS most significantly (P < .001). Multivariate analyses identified only high CAR as an independent prognostic factor associated with OS (hazard ratio [HR], 1.98; P = .031) and showed that a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≥3 also was associated with OS (HR, 2.04; P = .012). High CAR was correlated with poor performance status, male sex, and high Disease Risk Index, but not with high HCT-CI score. When the patients were stratified into 3 groups according to a composite risk assessment using CAR and HCT-CI, the 3-year OS decreased significantly with increasing scores (82.8%, 50.3%, and 27.0%, respectively; P < .0001). In conclusion, CAR is the most useful prognostic indicator among the inflammatory and nutritional status biomarkers for allogeneic HSCT in elderly patients. Inflammatory and nutritional status in the elderly may be important prognostic factors for allogeneic HSCT independent of HCT-CI score.

A Case Report of Successful Kidney Transplantation in a Patient With Chronic Myelogenous Leukemia (CML) Who Has Been in Remission for 15 Years on Imatinib.

For chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal disease into a manageable chronic disease with a close-to-normal life expectancy. Active malignancy is an absolute contraindication to kidney transplantation. However, it is controversial whether kidney transplantation can be safely performed in patients with a history of CML who are in remission. We describe the clinical course of a 64-year-old male patient with chronic kidney disease from diabetic nephropathy (DMN) who underwent living donor kidney transplantation. The patient was diagnosed with CML 15 years ago and promptly achieved cytogenetic and molecular biological remission after starting imatinib. After that, he continued imatinib treatment for 15 years and was in remission, but his chronic kidney disease from DMN gradually worsened. A preemptive living donor kidney transplant was performed in July 2020. Imatinib for CML was discontinued because the patient maintained deep molecular remission (DMR) of major molecular response for more than 15 years before kidney transplantation. After kidney transplantation, the transplanted kidney function remained good at approximate serum creatinine levels of 1.1 mg/dL without histopathologic rejection, and the 3 monthly BCR-ABL1 measurement results were negative and are in progress. Thus, he continues to maintain treatment-free remission status without imatinib for 26 months after renal transplantation. In conclusion, this result suggests that CML with long-lasting DMR on imatinib therapy can be considered an inactive malignancy and therefore a relative indication for kidney transplantation.

A regressed germ cell tumor discovered secondary to azoospermia.

Introduction: Regressed germ cell tumors are a rare disease commonly diagnosed with metastatic symptoms without local symptoms in the testis. Case presentation: A 33-year-old man with azoospermia was referred to our hospital. His right testis was slightly swollen, and ultrasonography revealed hypoechogenicity of the right testis with decreased blood flow. Right high orchiectomy was performed. Pathologically, the seminiferous tubules were absent or highly atrophied with vitrification degeneration; however, no neoplastic lesion was confirmed. One-month post-surgery, the patient noticed a mass in the left supraclavicular fossa, of which a biopsy revealed seminoma. The patient was diagnosed with a regressed germ cell tumor and underwent systemic chemotherapy. Conclusion: We reported the first case of a regressed germ cell tumor discovered due to complaints of azoospermia.

[Haploidentical stem cell transplantation for acute myeloid leukemia associated with adult-onset Shwachman-Diamond syndrome].

A 21-year-old man presented with bone marrow failure, short stature, fatty degeneration of the pancreas on CT images, and Shwachman-Bodian-Diamond syndrome (SBDS) gene abnormalities (exon 2: c.258+2T>C and deletion of exon 3). Thus, the patient was diagnosed with Shwachman-Diamond syndrome (SDS). In the clinical course, the patient developed acute myeloid leukemia (AML). Hematopoietic stem cell transplantation from the human-leukocytic-antigen-haploidentical father of the patient was performed. The patient was conditioned with 150 mg/m2 fludarabine, 6.4 mg/kg busulfan, and 4 Gy total body irradiation. Graft-versus-host disease prophylaxis included tacrolimus, micophenolate mofetil, and posttransplant cyclophosphamide. Although the patient achieved a complete remission on day 21, AML relapsed on day 434 after the transplantation. He died of sepsis. The prognosis of patients with SDS and AML is poor. Adult-onset cases must be recognized, and transplantation should be performed during bone marrow failure.

Seminal oxidation-reduction potential and sperm DNA fragmentation index increase among infertile men with varicocele.

Varicocele is a common cause of male infertility. It is reported that low sperm concentration, motility and morphology are indicative of increased sperm DNA fragmentation index (DFI) in men with varicocele. Although research has been conducted into the relationship between varicocele and DFI, little is known about seminal oxidation-reduction potential (ORP) in varicocele patients. We assessed the relationship between varicocele with seminal ORP and sperm DFI in both fertile and infertile men. This prospective case-control study compared the findings from infertile men with varicocele to those of men with normal spermatogenesis without varicocele. Semen samples were collected and assessed using the WHO (2010) guidelines. ORP was measured (mV) and normalized to sperm concentration (mV/106 sperm/mL). DFI was measured using the sperm chromatin structure assay (SCSA) method. For group comparisons, only samples with a concentration >1 × 106 sperm/mL were included. Infertile men with varicocele had significantly lower mean sperm concentration, motility and total sperm count. Conversely, infertile men with varicocele had a significantly higher mean serum FSH level, and higher ORP and DFI values than fertile controls. ORP was higher in patients with varicocele and positively correlated with DFI (p < 0.01). ORP and DFI showed significant negative correlations with semen parameters (sperm concentration, motility and total sperm count) in infertile men with a varicocele.

The Diagnostic Accuracy of Testicular Torsion by Doctors on Duty Using Sonographic Evaluation with Color Doppler.

As testicular torsion is a medical emergency, it requires quick diagnosis and treatment. Color Doppler ultrasound (CDUS) is useful for the diagnosis of testicular torsion. An accurate diagnosis can be difficult when CDUS indicates the preservation of blood flow in the testis. We examined the accuracy of testicular torsion diagnosis in patients with acute scrotum made by doctors on duty using CDUS. The subjects included 26 patients who visited our department between January 2016 and June 2018 presenting with acute scrotal pain. Patients were placed into one of three groups based on testicular blood flow evaluated by CDUS. The first group had no testicular blood flow, the second had diminished blood flow, and the last group had normal or increased blood flow. Patients were also diagnosed through scrotal exploration. Finally, patients were further divided into two groups identified by CDUS frequency utilized during diagnosis (12 MHz groups and ≤8 MHz groups), and the diagnostic accuracy of the two groups was compared. Characterizing torsion by either the absence of or diminished, testicular blood flow in the CDUS evaluation, the sensitivity and specificity of the CDUS performed by doctors on duty accounted for 69.2% and 53.8%, respectively. No improvement in diagnostic accuracy was evident despite the usage of a 12-MHz ultrasonic transducer. In this study, the sensitivity of CDUS performed by doctors on duty was about 70%, suggesting that scrotal exploration should be performed promptly even if testicular blood flow is observed and testicular torsion is suspected from medical history and body findings.

Impact of Pretreatment Total Cholesterol Level Is Associated With Metastasis of Prostate Cancer.

Metabolic syndrome is reported to play a role in the genesis and development not only of angina, arteriosclerosis, diabetes, and osteoporosis but also of prostate cancer. Hypercholesterolemia is a strong risk factor in prostate cancer development. The current study was conducted to analyze whether pretreatment serum levels of cholesterol correlate with prostate cancer metastasis. Three hundred fifty-one subjects who received a histopathological diagnosis of prostate cancer were evaluated by clinical factors such as age, body mass index (BMI), disease stage, Gleason score, prostate-specific antigen (PSA), total cholesterol, Luteinizing hormone (LH), testosterone, and free testosterone. A multivariate analysis was performed on these factors, and a statistically significant difference was identified in total cholesterol level (p =.01) and PSA (p < .001). The total cholesterol level was higher in cases of metastatic prostate cancer compared to nonmetastatic prostate cancer in this study and therefore may be a predictive factor for poor prognosis.

Comparison between semen parameters in specimens collected early in the morning and in the evening.

The majority of facilities in Japan that offer artificial insemination as part of assisted reproduction programs currently perform semen collection in the early morning. The total motile sperm count of the semen used in intrauterine insemination is an important factor in achieving successful fertilization and subsequent childbirth. The present study was initiated to determine whether semen parameters varied with the time of day at which the semen sample was collected. The study subjects were 20 fertile males and 20 infertile males with abnormal seminograms who attended our Reproduction Center. Semen was collected early in the morning (morning collection group) and in the evening (evening collection group) from the same subjects, and total motile sperm count was assessed as the primary outcome measure. As secondary outcome measures, semen volume, sperm concentration, sperm motility and total sperm count were assessed. A sexual abstinence period of 3 days was set for all participants. The semen samples were analyzed using CASA CEROS, a sperm motility analysis system, and the data from the morning and evening collection groups were compared using a Wilcoxon signed rank test. We found that the fertile males had a significantly higher total motile sperm count and total sperm count in the evening collection group than in the morning collection group. In contrast, the male infertility patients showed no significant difference in total sperm count between the two collection times; however, the total motile sperm count was significantly higher in the evening collection group than the morning collection group. Our analyses indicate that total motile sperm count in ejaculated semen is significantly higher after evening collection than after morning collection. From a male side perspective, we suggest that successful intrauterine insemination might be easier to achieve using semen collected in the evening than in the early morning.Abbreviations: IUI: intrauterine insemination; OAT: oligoasthenoteratozoospermia; TSC: total sperm count; TMSC: total motile sperm count.

Chemopreventive effects of nanoparticle curcumin in a mouse model of Pten-deficient prostate cancer.

The present study investigated the antitumor activity and chemopreventive effects of a nanoparticle formulation of curcumin in preclinical models of mouse Pten-deficient prostate cancer. The antitumor activity of the nanoparticle curcumin was evaluated in mouse castration-naïve (7113-D3) and castration-resistant prostate cancer (2945-E10) derived cell lines in vitro. Cell viability was reduced in both cell lines in a dose and time-dependent manner. The effects of long-term dietary supplementation with the nanoparticle curcumin formulation were evaluated in a conditional Pten-deficient mouse model. Prostate tissues from Pten-deficient prostate cancers were obtained after sixteen weeks of dietary supplementation of 76 mg/kg/day or 380 mg/kg/day nanoparticle curcumin. Daily supplementation of nanoparticle curcumin did not affect mouse bodyweights or spleen size but did result in enlargement of the liver. Dietary supplementation did not influence tumor burden, however, mice fed high-dose curcumin had lower cancer cell proliferation rates at 12 and 16 weeks of age. Together, these results show that daily supplementation of a nanoparticle formulation of curcumin is tolerable and suggest that curcumin could have chemopreventive activity in early-stage prostate cancer.

Efficacy of Recombinant Human Soluble Thrombomodulin in Treating Disseminated Intravascular Coagulation Complicating Allogeneic Hematopoietic Stem Cell Transplantation.

The prognosis for patients who experience hemostatic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. However, no report has investigated disseminated intravascular coagulation (DIC) caused by the complications of allo-HSCT without infection. Recombinant human soluble thrombomodulin (rhTM) was used to treat 12 episodes of DIC (n = 10; group 1) caused by allo-HSCT complications such as acute graft-versus-host disease (aGVHD) or thrombotic microangiopathy (TMA), and the clinical outcomes were compared with those of historical controls (n = 9; group 2) treated for DIC without rhTM. In group 1, the mean DIC score was significantly improved after using rhTM. Fibrinogen degeneration product (FDP), C-reactive protein (CRP), and the inflammatory cytokine high-mobility group box 1 (HMGB1) were also significantly decreased. Serial changes from the baseline values of platelet counts and levels of FDP were significantly better in group 1 than in group 2. The recovery rate from DIC was significantly higher in group 1 than in group 2. These findings suggest that rhTM is effective against both DIC and systemic inflammatory complications after allo-HSCT.

Correction to: Cell dynamics during differentiation therapy with all-trans retinoic acid in acute promyelocytic leukemia.

In the original publication of the article, Table 2 was published incorrectly. The column names were swapped under the column heading "Prom (%)". The correct column names are PB and BM.

Cell dynamics during differentiation therapy with all-trans retinoic acid in acute promyelocytic leukemia.

The introduction of all-trans retinoic acid (ATRA) has made acute promyelocytic leukemia (APL) a curable disease; however, early death prior to the completion of treatment remains a problem. In quantitative evaluation of response to ATRA treatment, lymphocytes must be excluded as they do not originally have t(15;17). We categorized peripheral blood leukocytes by nuclear morphology into polymorphonuclear cells (PMNs) comprising segmented granulocytes, and non-polymorphonuclear cells (NPMs) which includes lymphocytes, monocytes, band cells, and immature myeloid cells. We consecutively evaluated the ratio of t(15;17)-positive cells using fluorescence in situ hybridization in eight newly diagnosed patients with APL. We confirmed the differentiation of APL cells until cytogenetic complete remission; the association of a decrease of t(15;17)-positive NPMs and an increase of t(15;17)-positive PMNs was followed by a decrease of t(15;17)-positive PMNs. The kinetic pattern of t(15;17)-positive NPMs and PMNs was consistent in most patients, irrespective of leukocyte counts at diagnosis, additional chromosomal changes, and ATRA with or without chemotherapies. Kinetic analysis enables us to evaluate treatment response and the recovery of normal hematopoiesis in individuals.

Efficacy of Testosterone Treatment in Hemodialysis Patients as Assessed by Aging Males' Symptoms Scores: A Pilot Study.

Numerous reports point to the beneficial effects of testosterone replacement therapy for patients with late-onset hypogonadism (LOH) syndrome. The aim of this study was to evaluate the effect of intramuscular injection of testosterone enantholactam acid ester on Aging Males' Symptoms (AMS) scores in hemodialysis patients with LOH. A total of 24 male patients with LOH (total AMS scores ≥27) were randomized into groups receiving intramuscular injections of either placebo or testosterone enantholactam acid ester at the dose of 250 mg for 6 months. In all, 13 and 11 participants from the active treatment and placebo groups, respectively, completed this study. An intramuscular injection of either placebo or testosterone enantholactam acid ester was given every 2 weeks. Self-administered AMS questionnaires were completed at the start, at Week 12 and at Week 24. The total AMS score was significantly more improved in the treatment group than in the placebo group ( p = .049) during the 24-week period. The change in the mean of total AMS score was +1% in the placebo group and -13.2% in the treatment group. The mean somato-vegetative domain scores decreased significantly only in the treatment group, and not in the placebo group (-1.21 vs. -2.43, p = .028). Although a large-scale study is needed, testosterone treatment may be effective in male patients with hemodialysis who have poor health-related quality of life resulting from LOH.

[MALT lymphoma with t (X;14) (p11.2;q32) developing during the course of cutaneous leukocytoclastic angitis].

A 73-year-old man with left parotid gland swelling over 2 months was referred to our hospital in March 201X. Purpura on the lower legs had been recurrent for >20 years. Biopsy of the parotid gland demonstrated diffuse infiltration of abnormal lymphocytes that were negative for CD10 and positive for CD19, CD20, and κ-chain. The Ki-67 positivity was <10%; lymphoepithelial lesions were observed. The patient was diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Chromosome analysis revealed t (X;14) (p11.2;q32), and fluorescence in situ hybridization (FISH) of metaphase spreads showed three signals of the immunoglobulin heavy chain (IGH) gene on the derivative chromosomes X and 14, besides the normal chromosome 14. CT findings of parotid glands were suggestive of Sjogren syndrome, and biopsy of the purpura on the leg demonstrated leukocytoclastic vasculitis. In the literature, only seven patients with lymphoma and t (X;14) translocation have been reported. Of these, five patients had MALT lymphoma, one had nodal marginal zone lymphoma, and one had diffuse large B-cell lymphoma. In all patients, lymphoma evolved from previous autoimmune diseases. It is suggested that MALT lymphoma with the t (X;14) translocation forms a new entity of lymphoma.