根治的前立腺全摘標本における神経線維周囲浸潤の生化学的再発予知因子としての意義

著者らは, 臨床的限局性前立腺癌に対して術前内分泌療法を施行せずに根治的前立腺全摘除術を施行した202症例を対象に, 全摘標本における神経線維周囲浸潤の臨床病理学的意義を検討した.その結果, 1)神経線維周囲浸潤は131例(64.9%)に陽性であった.また, 神経線維周囲浸潤の存在は, 臨床病期, 病理学的病期, Gleasonスコア, 精嚢浸潤, リンパ節転移および腫瘍体積と有意に相関したが, 術前PSA値との相関は認めなかった. 2)経過観察期間(中央値34ヵ月)中, 20例に生化学的再発を認めたが神経線維周囲浸潤はこの内17例に陽性であった. 3)神経線維周囲浸潤陽性131例および陰性71例の5年生化学的非再発率は, それぞれ84.4%および94.3%であり統計学的有意差を認めた.神経線維周囲浸潤の他, 病理学的病期, 精嚢浸潤, リンパ節転移および腫瘍体積が生化学的非再発率と有意な相関を示した.しかし, 多変量解析の結果, これら5因子の内, 精嚢浸潤のみが生化学的再発の独立した予知因子であった.以上, これらのことからも, 根治的前立腺全摘標本における神経線維周囲浸潤の存在は, 種々の予後規定因子と有意な相関を示すが, 生化学的再発の独立した予知因子とは成りえない可能性が示唆されたThe objective of this study was to determine whether the presence of perineural invasion (PNI) in radical prostatectomy specimens could be a useful prognostic parameter in Japanese men with prostate cancer. Between January 1995 and September 2003, 202 Japanese men underwent radical retropubic prostatectomy for prostate cancer without any neoadjuvant therapies prior to surgery. We retrospectively analyzed the relationship between PNI in radical prostatectomy specimens and other prognostic factors, and also assessed the significance of PNI in biochemical recurrence after radical prostatectomy. The presence of PNI was significantly related to clinical stage, pathological stage, Gleason score, seminal vesicle invasion, lymph node metastasis and tumor volume, but not pretreatment serum prostate specific antigen value. During the observation period, biochemical recurrence occurred in 20 patients (3 in patients without PNI and 17 in those with PNI), and the biochemical recurrence-free survival rate in patients with PNI was significantly lower than that in patients without PNI. In addition to-PNI, pathological stage, seminal vesicle invasion, lymph node metastasis and tumor volume were significantly associated with the biochemical recurrence-free survival rate; however, among these five factors, only seminal vesicle invasion was an independent predictor of biochemical recurrence on multivariate analysis. Despite a significant association between several prognostic parameters, PNI was not an independent predictor of biochemical recurrence; therefore, it may not provide an additive effect to consider the presence of PNI in predicting the prognosis of Japanese men who underwent radical prostatectomy if there are other conventional parameters available

Use of Balloon Enteroscopy in Preoperative Diagnosis of Neurofibromatosis-Associated Gastrointestinal Stromal Tumours of the Small Bowel: A Case Report

Neurofibromatosis type I (NF1) is one of the most common inheritable disorders and is associated with an increased risk of gastrointestinal stromal tumours (GISTs). However, the predominant location of these lesions in the small bowel makes them difficult to diagnose. We report the successful use of balloon enteroscopy in conjunction with conventional methods for clinical diagnosis of jejunal GISTs in a 70-year-old man with NF1 who presented with melaena. The importance of screening NF1 patients for GISTs and the complementary role of balloon enteroscopy with capsule endoscopy in such diagnoses is discussed

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients with Central Nervous System Involvement

AbstractCentral nervous system (CNS) involvement in adult acute myeloid leukemia (AML) is rare and associated with poor outcomes. Therefore, CNS involvement in AML is an indicator for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of CNS involvement in AML on the outcome of allo-HSCT remains unclear. We performed a large-scale nationwide retrospective analysis to elucidate the outcomes of allo-HSCT on AML with CNS involvement (CNS+AML). Clinical data were collected from a registry database of the Japan Society for Hematopoietic Cell Transplantation. CNS involvement was defined as the infiltration of leukemia cells into the CNS or myeloid sarcoma in the CNS identified at any time from diagnosis to transplantation. One hundred fifty-seven patients with CNS+AML underwent allo-HSCT between 2006 and 2011. The estimated overall survival, cumulative incidence of relapse and nonrelapse mortality at 2 years for CNS+AML (51.2%, 30.2%, and 14.5%, respectively) were comparable with those for AML without CNS involvement (48.6%, 27.4%, and 22.0%, respectively). Univariate and multivariate analyses indicated that the development of chronic graft-versus-host disease, disease status, and cytogenetic risk category were independent prognostic factors for overall survival for CNS+AML. These results suggest that allo-HSCT may improve outcomes in patients with CNS+AML

Personalized prediction of overall survival in patients with AML in non‐complete remission undergoing allo‐HCT

Allogenic hematopoietic stem cell transplantation (allo-HCT) is the standard treatment for acute myeloid leukemia (AML) in non-complete remission (non-CR); however, the prognosis is inconsistent. This study aimed to develop and validate nomograms and a web application to predict the overall survival (OS) of patients with non-CR AML undergoing allo-HCT (cord blood transplantation [CBT], bone marrow transplantation [BMT], and peripheral blood stem cell transplantation [PBSCT]). Data from 3052 patients were analyzed to construct and validate the prognostic models. The common significant prognostic factors among patients undergoing allo-HCT were age, performance status, percentage of peripheral blasts, cytogenetic risk, chemotherapy response, and number of transplantations. The conditioning regimen was a significant prognostic factor only in patients undergoing CBT. Compared with cyclophosphamide/total body irradiation, a conditioning regimen of ≥3 drugs, including fludarabine, with CBT exhibited the lowest hazard ratio for mortality (0.384; 95% CI, 0.266-0.554; p < 0.0001). A conditioning regimen of ≥3 drugs with CBT also showed the best leukemia-free survival among all conditioning regimens. Based on the results of the multivariable analysis, we developed prognostic models showing adequate calibration and discrimination (the c-indices for CBT, BMT, and PBSCT were 0.648, 0.600, and 0.658, respectively). Our prognostic models can help in assessing individual risks and designing future clinical studies. Furthermore, our study indicates the effectiveness of multi-drug conditioning regimens in patients undergoing CBT

Determination of paroxetine in serum treated with simple pretreatment by pre-column high-performance liquid chromatography using 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride as a fluorescent labeling reagent.

The therapeutic drug monitoring of paroxetine could be used to optimize the pharmacological treatment of depressed patients. A simple and sensitive high-performance liquid chromatography procedure was developed for the determination of paroxetine in serum. After simple pretreatment of serum (50 μL) with acetonitrile and o-phthalaldehyde, paroxetine was derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70°C for 20 min in borate buffer (0.1 mol/L, pH 8.0) to produce a fluorescent product. The derivative was separated on a reversed-phase column at 40°C for stepwise elution with (A) acetic acid (10 mmol/L) and (B) acetonitrile. The flow rate was 1.0 mL/min. The fluorescence intensity was monitored at excitation and emission wavelengths of 320 and 400 nm, respectively. The within-day and day-to-day relative standard deviations were 3.0-3.4 and 2.7-8.3%, respectively. The detection limit of paroxetine was 8.3 fmol at a signal-to-noise ratio of 3. As the proposed method that only requires a small quantity of serum (50 μL) is simple, sensitive and reproducible, it would be useful for clinical and biochemical research as well as drug monitoring.The therapeutic drug monitoring of paroxetine could be used to optimize the pharmacological treatment of depressed patients. A simple and sensitive high-performance liquid chromatography procedure was developed for the determination of paroxetine in serum. After simple pretreatment of serum (50 μL) with acetonitrile and o-phthalaldehyde, paroxetine was derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70°C for 20 min in borate buffer (0.1 mol/L, pH 8.0) to produce a fluorescent product. The derivative was separated on a reversed-phase column at 40°C for stepwise elution with (A) acetic acid (10 mmol/L) and (B) acetonitrile. The flow rate was 1.0 mL/min. The fluorescence intensity was monitored at excitation and emission wavelengths of 320 and 400 nm, respectively. The within-day and day-to-day relative standard deviations were 3.0-3.4 and 2.7-8.3%, respectively. The detection limit of paroxetine was 8.3 fmol at a signal-to-noise ratio of 3. As the proposed method that only requires a small quantity of serum (50 μL) is simple, sensitive and reproducible, it would be useful for clinical and biochemical research as well as drug monitoring

Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells

A specific kinetic pattern of c-MYC expression is essential for optimal generation of functional platelets from human induced pluripotent stem cells

Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT

Acute erythroid leukemia (FAB-M6) and acute megakaryoblastic leukemia (FAB-M7) exhibit closely related properties in cells regarding morphology and the gene expression profile. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the mainstay of the treatment for both subtypes of leukemia due to their refractoriness to chemotherapy and high rates of relapse, it remains unclear whether allo-HSCT is curative in such cases due to their scarcity. We retrospectively examined the impact of allo-HSCT in 382 patients with M6 and 108 patients with M7 using nationwide HSCT data and found the overall survival (OS) and relapse rates of the M6 patients to be significantly better than those of the M7 patients after adjusting for confounding factors and statistically comparable with those of the patients with M0/M1/M2/M4/M5 disease. Consequently, the factors of age, gender, performance status, karyotype, disease status at HSCT and development of graft-vs.-host disease predicted the OS for the M6 patients, while the performance status and disease status at HSCT were predictive of the OS for the M7 patients. These findings substantiate the importance of distinguishing between M6 and M7 in the HSCT setting and suggest that unknown mechanisms influence the HSCT outcomes of these closely related subtypes of leukemia. © 2016 Elsevier Ltd.Embargo Period 12 month