[Show abstract][Hide abstract] ABSTRACT: Toxoplasmic encephalitis represents a rare, but often fatal infection after allogeneic hematopoietic stem cell transplantation. Polymerase chain reaction (PCR)-based preemptive therapy is considered promising for this disease, but is not routinely applied, especially in low seroprevalence countries including Japan. We encountered 2 cases of toxoplasmic encephalitis after transplantation that were successfully treated. The diagnosis of toxoplasmic encephalitis in these cases was confirmed by PCR testing when neurological symptoms were observed. Both patients received pyrimethamine and sulfadiazine treatments within 2 weeks of the development of neurological symptoms, and remained free of recurrence for 32 and 12 months. These results emphasized the importance of the PCR test and immediate treatment after diagnosis for the management of toxoplasmic encephalitis. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (P<0.001). Furthermore, relapse with a new lesion only in the absence of the primary lesion was more frequent in allo-SCT (P=0.014). Lesions were more frequently observed in the central nervous systems of patients who relapsed with new lesions only (P=0.005). Thus, the clinical manifestation of relapsed ATL was slightly complex, especially in post-transplant patients. Our results emphasized the need to develop adoptive modalities for early and accurate diagnoses of relapsed ATL.Bone Marrow Transplantation advance online publication, 26 January 2015; doi:10.1038/bmt.2014.308.
Bone Marrow Transplantation 01/2015; 50(4). DOI:10.1038/bmt.2014.308 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:Circulating tumour DNA (ctDNA) is an emerging candidate biomarker for malignancies and may be useful for monitoring the disease status of gastric cancer.Methods:We performed targeted deep sequencing of plasma cell-free DNA (cfDNA) by massively parallel sequencing in patients with tumours harbouring TP53 mutations. The quantitative values of TP53-ctDNA during the clinical course were compared with the tumour status.Results:Three out of ten patients with TP53 mutations in primary tumours showed detectable TP53 mutation levels in preoperative cfDNA. Although the cfDNA concentrations were not always reflective of the disease course, the ctDNA fraction correlated with the disease status.Conclusions:ctDNA may serve as a useful biomarker to monitor gastric cancer progression and residual disease.British Journal of Cancer advance online publication 9 December 2014; doi:10.1038/bjc.2014.609 www.bjcancer.com.
British Journal of Cancer 12/2014; 112(2). DOI:10.1038/bjc.2014.609 · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR-ABL-negative ALL. Patients aged 15-24 years (n=139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58-75%) and 73% (95% CI 64-80%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, P<0.001). These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR-ABL-negative ALL.Blood Cancer Journal (2014) 4, e252; doi:10.1038/bcj.2014.72; published online 17 October 2014.
Blood Cancer Journal 10/2014; 4(10):e252. DOI:10.1038/bcj.2014.72 · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A potential link between arsenic (ATO)-based therapy and delayed hematopoietic recovery after autologous hematopoietic SCT (HSCT) for acute promyelocytic leukemia (APL) has previously been reported. We retrospectively reviewed the clinical histories of 58 patients undergoing autologous HSCT for APL at 21 institutions in the United States and Japan. Thirty-three (56%) of the patients received ATO-based therapy prior to stem cell collection. Delayed neutrophil engraftment occurred in 10 patients (17%): 9 of the 10 patients (90%) received prior ATO (representing 27% of all ATO-treated patients), compared with 1 of the 10 patients (10%) not previously treated with ATO (representing 4% of all ATO-naïve patients; P<0.001). Compared with ATO-naïve patients, ATO-treated patients experienced significantly longer times to ANC recovery (median 12 days vs 9 days, P<0.001). In multivariate analysis, the only significant independent predictor of delayed neutrophil engraftment was prior treatment with ATO (hazard ratio 4.87; P<0.001). Of the available stem cell aliquots from APL patients, the median viable post-thaw CD34+ cell recovery was significantly lower than that of cryopreserved autologous stem cell products from patients with non-APL AML. Our findings suggest that ATO exposure prior to CD34+ cell harvest has deleterious effects on hematopoietic recovery after autologous HSCT.Bone Marrow Transplantation advance online publication, 22 Septmber 2014; doi:10.1038/bmt.2014.201.
Bone Marrow Transplantation 09/2014; 50(1). DOI:10.1038/bmt.2014.201 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and study aims: Steady pressure automatically controlled endoscopy (SPACE) is a new insufflation system that provides constant carbon dioxide (CO2) insufflation pressure during prolonged procedures. The system consists of an overtube, a surgical insufflator, and a newly developed leak-proof valve. The aims of this study were to validate the feasibility and safety of SPACE for esophageal endoscopic submucosal dissection (ESD). Patients and methods: This was a clinical phase I trial, involving 10 patients who underwent esophageal ESD. The primary end point was the rate of adverse events within 30 days (grade 0 to 4). Secondary end points were changes in partial pressure of carbon dioxide (PaCO2) and vital signs during ESD, completion rate of ESD, and degree of abdominal distension by patient assessment and radiographic grading. Results: All adverse events were Grade 2 or less. Mild PaCO2 elevation after ESD was noted; however, no associated symptoms were reported. The procedure was completed under SPACE alone in 8 of 10 patients. Minimal post-procedural bowel distension was observed. Conclusions: In this small pilot study, SPACE was feasible and appeared to be safe. Further study with larger case numbers is required to demonstrate efficacy and safety. Clinical trial registration: UMIN000005434.
[Show abstract][Hide abstract] ABSTRACT: The efficacy and feasibility of laparoscopic surgery (LAP) for gastric GISTs >5 cm has not been adequately assessed. Here we investigated the clinical outcomes of these patients.
Twenty-seven consecutive patients who underwent resection for gastric GISTs >5 cm were enrolled in this retrospective study. We assessed the tumor characteristics, surgical outcomes, tumor recurrence, and patient survival in the open surgery (OPEN) group and in the LAP group.
The tumor size in the OPEN group was larger than that in the LAP group, but there were no differences in the mitotic count. There were no differences in operative complications. Finally, there were no differences in the disease-free and no patients in the LAP group died.
In patients with gastric GISTs >5 cm, LAP can be performed with outcomes equivalent to those of OPEN if patient selection and intraoperative judgment are appropriate.
[Show abstract][Hide abstract] ABSTRACT: To clarify the cooperative roles of recurrently identified mutations and to establish a more precise risk classification system in acute myeloid leukemia (AML), we comprehensively analyzed mutations in 51 genes, as well as cytogenetics and 11 chimeric transcripts, in 197 adult patients with de novo AML who were registered in the Japan Adult Leukemia Study Group (JALSG) AML201 study. We identified a total of 505 mutations in 44 genes, while only five genes, FLT3, NPM1, CEBPA, DNMT3A and KIT, were mutated in more than 10% of the patients. Although several cooperative and exclusive mutation patterns were observed, the accumulated mutation number was higher in cytogenetically normal AML, and lower in AML with RUNX1-RUNX1T1 and CBFB-MYH11, indicating a strong potential of these translocations for the initiation of AML. Furthermore, we evaluated the prognostic impacts of each sole mutation and the combinations of mutations and/or cytogenetics, and demonstrated that AML patients could be clearly stratified into five risk groups for overall survival by including the mutation status of DNMT3A, MLL-PTD and TP53 genes in the risk classification system of the European LeukemiaNet. These results indicate that the prognosis of AML could be stratified by the major mutation status in combination with cytogenetics.Leukemia accepted article preview online, 3 February 2014. doi:10.1038/leu.2014.55.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2014; 28(8). DOI:10.1038/leu.2014.55 · 9.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Myeloperoxidase (MPO) has been associated with both a myeloid lineage commitment and favorable prognosis in patients with acute myeloid leukemia (AML). DNA methyltransferase inhibitors (decitabine and zeburaline) induced MPO gene promoter demethylation and MPO gene transcription in AML cells with low MPO activity. Therefore, MPO gene transcription was directly and indirectly regulated by DNA methylation. A DNA methylation microarray subsequently revealed a distinct methylation pattern in 33 genes, including DNA methyltransferase 3 beta (DNMT3B), in CD34-positive cells obtained from AML patients with a high percentage of MPO-positive blasts. Based on the inverse relationship between the methylation status of DNMT3B and MPO, we found an inverse relationship between DNMT3B and MPO transcription levels in CD34-positive AML cells (P=0.0283). In addition, a distinct methylation pattern was observed in five genes related to myeloid differentiation or therapeutic sensitivity in CD34-positive cells from AML patients with a high percentage of MPO-positive blasts. Taken together, the results of the present study indicate that MPO may serve as an informative marker for identifying a distinct and crucial DNA methylation profile in CD34-positive AML cells.Leukemia advance online publication, 24 January 2014; doi:10.1038/leu.2014.15.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 01/2014; 28(7). DOI:10.1038/leu.2014.15 · 9.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Although its theoretical usefulness has been reported, the true value of automatic smoke evacuation system in laparoscopic surgery remains unknown. This is mainly due to the lack of objective evaluation. The purpose of this study was to determine the efficacy of the automatic smoke evacuator in laparoscopic surgery, by real-time objective evaluation system using an industrial smoke-detection device. METHODS: Six pigs were used in this study. Three surgical ports were placed and electrosurgical smoke was generated in a standard fashion, using either a high-frequency electrosurgical unit (HF-ESU) or laparosonic coagulating shears (LCS). The smoke was evacuated immediately in the evacuation group but not in the control nonevacuation group. The laparoscopic field-of-view was subjectively evaluated by ten independent surgeons. The composition of the surgical smoke was analyzed by mass spectrometry. The residual smoke in the abdominal cavity was aspirated manually into a smoke tester, and stains on a filter paper were image captured, digitized, and semiquantified. RESULTS: Subjective evaluation indicated superior field-of-view in the evacuation group, compared with the control, at 15 s after activation of the HF-ESU (P < 0.05). The smoke comprised various chemical compounds, including known carcinogens. The estimated volume of intra-abdominal residual smoke after activation of HF-ESU was significantly lower in the evacuation group (47.4 ± 16.6) than the control (76.7 ± 2.4, P = 0.0018). Only marginal amount of surgical smoke was detected in both groups after LCS when the tissue pad was free from burnt tissue deposits. However, the amount was significantly lower in the evacuation group (21.3 ± 10.7) than the control (75 ± 39.9, P = 0.044) when the tissue pad contained tissue sludge. CONCLUSIONS: Automatic smoke evacuation provides better field-of-view and reduces the risk of exposure to harmful compounds.
[Show abstract][Hide abstract] ABSTRACT: The efficacy of unrelated transplantation for patients with ALL who lack an HLA-matched sibling remains unclear. We performed a decision analysis to determine the efficacy of myeloablative transplantation from a genetically HLA-A, -B, -DRB1 allele-matched unrelated donor for patients with Ph chromosome-negative ALL aged 21-54 years. The transition probabilities were estimated from the Japan Adult Leukemia Study Group studies (ALL93; n=80, ALL97; n=82), and the Japan Marrow Donor Program database (transplantation in first CR (CR1): n=177). The primary outcome measure was the 10-year survival probability with or without quality of life (QOL) adjustment. Subgroup analyses were performed according to risk stratification based on the WBC count and cytogenetics, and according to age stratification. In all patients, unrelated transplantation in CR1 was shown to be superior in analyses both with and without QOL adjustment (40.8 vs 28.4% and 43.9 vs 29.0%, respectively). A similar tendency was observed in all subgroups. The decision model was sensitive to the probability of leukemia-free survival following chemotherapy and the probability of survival after transplantation in standard-risk and higher-aged patients. Unrelated transplantation in CR1 improves the long-term survival probability in patients who lack an HLA-matched sibling. However, recent improvements in treatment strategies may change this result.Bone Marrow Transplantation advance online publication, 4 February 2013; doi:10.1038/bmt.2013.4.
Bone marrow transplantation 02/2013; 48(8). DOI:10.1038/bmt.2013.4 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Use of rigid instruments via transvaginal (TV) route has been proposed as a practical alternative to natural orifice translumenal endoscopic surgery (NOTES) using flexible devices. However, its safety has not been fully evaluated for each abdominal organ with different positional relationship to the vagina. The aim of this study is to obtain baseline anatomical data necessary for safer use of rigid TV instruments, by three-dimensional (3-D) radiologic measurements. PATIENTS AND METHODS: A retrospective study was conducted on 51 consecutive female Japanese patients with aortic aneurysm who underwent whole-body multidetector computed tomography as preoperative evaluation. The gallbladder (GB), esophagogastric junction (EGJ), and spleen were located on 3-D images, and the following were obtained: (1) the distance from the vagina, (2) the transverse deviation from the midline, and (3) the sagittal deviation from the "vagina-promontory (V-P)" line. RESULTS: The median distance from the vagina was 26.1 cm for GB, 30.6 cm for EGJ, and 31.1 cm for spleen. The transverse deviation from the midline was 17.7° for GB, 7.0° for EGJ, and 12.9° for spleen. The sagittal deviation from the V-P line was 7.6 degrees for GB, -7.0° for EGJ, and -10.3° for spleen. The percentage of "negative angle" cases, which means that the target is located "below" the V-P line, was only 9.8 % for GB versus 88 % for EGJ and spleen. CONCLUSIONS: The intra-abdominal length of TV instruments should be more than 35 cm in Japanese population. GB is widely deviated from the midline and therefore can be safely approached even with rigid/straight instruments. Access to more midline and distant targets may suffer from interference by the sacral promontory, and be potentially dangerous in terms of risk of compression injury by rigid and straight instruments.