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Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia. ITP is generally characterized by an increased percentage of RP, and a normal or slightly increased plasma TPO level. We now report three cases of thrombocytopenia after allo-HSCT. RP% was elevated in these patients, as it is in primary ITP. However, in contrast to primary ITP, plasma TPO levels were high in two of three patients. Anti-αIIbβ3 and anti-GPIb/IX-specific direct IgG antibodies were detected as well, suggesting occurrence of immune-mediated platelet destruction in addition to bone marrow suppression in two patients. All three patients were successfully treated with corticosteroids and/or thrombopoietin receptor agonists (TPO-RAs). These results suggest that increased RP% and detection of glycoprotein-specific platelet autoantibodies are useful for the diagnosis of ITP after HSCT.

The relapse of acute lymphoblastic leukemia (ALL) usually involves the bone marrow, with the central nervous system being the most frequent extramedullary site. The relapse of ALL in the female genital organs, particularly the uterus, is markedly rare. We report such a patient who developed relapse in the bone marrow and uterus. The uterine lesion, which presented as abnormal uterine bleeding, consisted of a mass on MRI and proliferation of ALL cells on histology. MRI revealed a heterogeneous high-intensity mass (T2-WI/D-WI) with a diameter of 6.8 cm, a notable decrease in the apparent diffusion coefficient (ADC), and mild enhancement by contrast enhancement study. Histological findings of the uterine cervix demonstrated the infiltration of ALL. The patient achieved remission by allogeneic haplo-identical hematopoietic stem-cell transplantation, but died of complications of the transplantation. This case suggested that attention should be paid to the uterus as a site of extramedullary relapse. In addition, abnormal uterine bleeding, which is a common sign of hormonal imbalance and hormone replacement therapy after chemotherapy, may be an initial sign of extramedullary recurrence. To confirm uterine relapse as an intractable disease, the accumulation of more cases is required.

A 23-year-old woman was admitted to our hospital because of rapidly developing lower abdominal pain. Computed tomography revealed ascites, splenomegaly, and a huge mass that occupied the pouch of Douglas and surrounded her uterus. A markedly elevated white blood cell count of 495×10

Background It remains unclear whether men have more favorable survival outcomes after out-of-hospital cardiac arrest (OHCA) than women. Methods We reviewed a total of 386,535 patients aged ≥ 18 years with OHCA who were included in the Japanese registry from 2013 to 2016. The study endpoints were the rates of 1-month survival and neurologically intact survival (Cerebral Performance Category Scale score = 1 or 2). Based on age, the reviewed patients were categorized into the following eight groups: 0.02). Moreover, after hierarchical propensity score matching, the survival outcomes did not significantly differ between both sexes (all P > 0.05). Conclusions No significant sex-specific differences were found in the rates of 1-month survival and neurologically intact survival after OHCA. Electronic supplementary material The online version of this article (10.1186/s13054-019-2547-x) contains supplementary material, which is available to authorized users.

Background Guidelines for cardiopulmonary resuscitation (CPR) recommend using the universal termination-of-resuscitation (TOR) rule to identify out-of-hospital cardiac arrest (OHCA) patients eligible for field termination of resuscitation, thus avoiding medically futile transportation to the hospital. However, in Japan, emergency medical services (EMS) personnel are forbidden from terminating CPR in the field and transport almost all patients with OHCA to hospitals. We aimed to develop and validate a novel TOR rule to identify patients eligible for field termination of CPR. Methods We analyzed 540,478 patients with OHCA from 2011 to 2015 using a Japanese registry. Main outcome measures were specificity and positive predictive value (PPV) of the newly developed TOR rule in predicting 1-month mortality after OHCA. Results Recursive partitioning analysis in the development group (n = 434,208) showed that EMS personnel could consider TOR if patients with OHCA met all of the following five criteria: (1) initial asystole, (2) arrest unwitnessed by a bystander, (3) age ≥81 years, (4) no bystander-administered CPR or automated external defibrillator use before EMS arrival, and (5) no return of spontaneous circulation after EMS-initiated CPR for 14 min. For patients meeting these criteria, specificity and PPV for predicting 1-month mortality were 99.2% [95% confidence interval (CI), 99.0–99.3%] and 99.7% (95% CI, 99.6–99.7%), respectively, for the development group and were 99.5% (95% CI, 99.3–99.7%) and 99.8% (95% CI, 99.7–99.9%), respectively, for the validation group. Implementation of this novel rule would reduce patient transports to hospitals by 10.6% in the development group and 10.4% in the validation group. Conclusions Having both high specificity and PPV of >99% for predicting 1-month mortality, our developed TOR rule may be applied in the field for Japanese patients with OHCA who meet all five criteria. Prospective validation studies and establishment of prehospital EMS protocol are required before implementing this rule.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation. In addition to reactivation of Epstein–Barr virus in immunocompromised patients, impaired tumor immunity is suggested to be a risk factor for PTLD. However, it remains unclear whether immune suppressive tumor-infiltrating lymphocytes (TILs) correlate with the occurrence or prognosis of PTLD. We analyzed TILs in 26 patients with PTLD to elucidate the clinicopathological significance of the expression of PD-1 and FoxP3, which are associated with exhausted T-cells and regulatory T-cells (Tregs), respectively. Numbers of PD-1+ TILs in the PTLD specimens were significantly higher in patients who developed PTLD early after transplantation (P = 0.0040), while numbers of FoxP3+ TILs were not (P = 0.184). There was no difference in overall response rate regardless of the expression of PD-1 or FoxP3. FoxP3high patients tended to have a shorter time to progression compared with FoxP3low patients, especially in the case of FoxP3high patients with diffuse large B-cell lymphoma-subtype PTLD (P = 0.011), while PD-1high patients did not. These results suggest that T-cell exhaustion may be mainly associated with PTLD development, while immune suppression by Tregs may be dominant in enhanced progression of PTLD following disease occurrence.

It remains unclear how specific innovations in allogeneic hematopoietic cell transplantation (HCT) attained over the past decades have contributed to improvement in transplantation outcomes. To address this question, we conducted a registry-based study of adults with acute myeloid leukemia in first or second complete remission who underwent allogeneic HCT between 1994 and 2013 from a sibling (N = 1600) or unrelated (N = 2113) donor matched at the antigen level for HLA-A, -B, and -DR. Preliminary analysis led us to focus on comparisons between the 1994–2006 and 2007–2013 periods. Significant improvement in survival was observed in the later cohort compared to the earlier cohort for unrelated HCT (P = 0.004), but not for related HCT (P = 0.767). The improvement in unrelated HCT was solely due to diminished non-relapse mortality (P = 0.001), while incidence of relapse did not change over time (P = 0.934). The percentage of patients receiving transplants from 8/8-matched unrelated donors was significantly higher in the later cohort (P

The quality of acute aortic syndrome (AAS) assessment by emergency medical service (EMS) and the incidence and prehospital factors associated with 1-month survival remain unclear.We retrospectively analyzed the data collected for 94,468 patients with non-traumatic medical emergency excluding out-of-hospital cardiac arrest during the period of 2011-2014.Of these transported by EMS, 22,075 had any of the AAS-related symptoms, and 330 had an EMS-assessed risk for AAS; of these, 195 received an in-hospital AAS diagnosis. Of the remaining 21,745 patients without EMS-assessed risk, 166 were diagnosed with AAS. Therefore, the sensitivity and specificity of our EMS-risk assessment for AAS was 54.0% (195/361) and 99.4% (21,579/21,714), respectively. EMS assessed the risk less frequently when patients were elderly and presented with dyspnea and syncope/faintness. Sign of upper extremity ischemia was rarely detected (6.9%) and absence of this sign was associated with lack of EMS-assessed risk. The calculation of modified aortic dissection detection risk score revealed that rigorous assessment based on this score may increase the EMS sensitivity for AAS. The 1-month survival rate was significantly higher in patients admitted to core hospitals with surgical teams for AAS than in those admitted to all other hospitals [87.5% (210/240) vs 69.4% (84/121); P0.01]. Multiple logistic regression analysis demonstrated that Stanford type A, Glasgow coma scale ≤14, and admission to core hospitals providing emergency cardiovascular surgery were associated with 1-month survival.Improvement of AAS survival is likely to be affected by rapid admission to appropriate hospitals providing cardiovascular surgery.

Introduction: Placenta previa (PP) is one of the most significant risk factors for adherent placenta (AP). The aim of this study was to evaluate the diagnostic efficacy of a novel scoring system for predicting AP in pregnant women with PP. Methods: This prospective cohort study enrolled 175 women with PP. The placenta previa with adherent placenta score (PPAP score) is composed of 2 categories: (1) past history of cesarean section (CS), surgical abortion, and/or uterine surgery; and (2) ultrasonography and magnetic resonance imaging findings. Each category is graded as 0, 1, 2, or 4 points, yielding a total score between 0 and 24. When women with PP had PPAP score ≥8, they were considered to be at a high risk for AP and received placement of preoperative internal iliac artery occlusion balloon catheters. If they were found to have AP during CS, they underwent hysterectomy or placenta removal using advanced bipolar with balloon catheter occlusion. The predictive accuracy of PPAP score was evaluated. Results: In total, 23 of the 175 women with PP were diagnosed as having AP, histopathologically or clinically. Twenty-one of 24 women with PPAP score ≥8 had AP, whereas two of 151 women with PPAP score

The purpose of this study was to clarify whether a gait analysis using an accelerometer could estimate gait independence. Eighty-six stroke patients and 21 healthy control subjects participated in this study. Stroke patients were identified as dependent or independent based on their gait ability. The acceleration of the trunk and bilateral thigh was measured using three wireless sensors during walking. The root mean square, gait regularity, and symmetry were calculated from the acceleration to estimate gait quality. ANCOVA showed that gait regularity of the trunk and bilateral thigh were significantly lowest in the dependent group, regardless of gait velocity. A logistic regression analysis showed that the regularity and root mean square of the anteroposterior acceleration of the unaffected thigh were the key factors for estimating gait independence. This study suggests that an acceleration-based gait analysis facilities gait independence estimation, and is a useful tool during the rehabilitation of stroke patients.

Objectives: This study aimed to investigate the validity of gastric cancer surgery in elderly patients. Methods: A total of 544 patients who underwent elective gastrectomy for gastric cancer were divided into an elderly group (age ≥75 years, n = 171) and a control group (age n = 373). The clinicopathological data of the patients were reviewed. Results: The overall morbidity rate (26.3 vs. 16.1%, p = 0.005) and the incidence rate of anastomotic leakage (6.4 vs. 1.6%, p = 0.003) were significantly higher in the elderly group. The proportion of patients who had severe complications (≥grade IIIa) was relatively higher in the elderly group (10.5 vs. 5.7%); however, the difference was not significant (p = 0.074). A stage-matched survival analysis revealed no significant differences between the groups (stage I: p = 0.978; stage II: p = 0.964; stage III: p = 0.199). For the pathological stages II and III, the overall survival of the patients in the elderly group who received adjuvant chemotherapy for >3 months was significantly better than that of the patients who received it for ≤3 months or did not receive it (p = 0.023). Conclusions: An aggressive treatment strategy should be adopted in selected elderly patients with gastric cancer.

Purpose To investigate the impacts of emergency calls made using mobile phones on the quality of dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) and survival from out-of-hospital cardiac arrests (OHCAs) that were not witnessed by emergency medical service (EMS). Methods In this prospective study, we collected data for 2530 DA-CPR-attempted medical emergency cases (517 using mobile phones and 2013 using landline phones) and 2980 non-EMS-witnessed OHCAs (600 using mobile phones and 2380 using landline phones). Time factors and quality of DA-CPR, backgrounds of callers and outcomes of OHCAs were compared between mobile and landline phone groups. Results Emergency calls are much more frequently placed beside the arrest victim in mobile phone group (52.7% vs. 17.2%). The positive predictive value and acceptance rate of DA-CPR in mobile phone group (84.7% and 80.6%, respectively) were significantly higher than those in landline group (79.2% and 70.9%). The proportion of good-quality bystander CPR in mobile phone group was significantly higher than that in landline group (53.5% vs. 45.0%). When analysed for all non-EMS-witnessed OHCAs, rates of 1-month survival and 1-year neurologically favourable survival in mobile phone group (7.8% and 3.5%, respectively) were higher than those in landline phone group (4.6% and 1.9%; p, Embargo Period 12 months

Various central nervous system (CNS) complications may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can result in severe clinical problems. Diagnosis is often difficult, as distinctive clinical symptoms may be absent and different neurological disorders may exhibit similar symptoms. Despite the fact that antibodies responding to brain cell surface antigens have become well recognized in several CNS disorders, cases of autoimmune CNS disorders after allo-HSCT have rarely been reported. Here, we report on a patient who developed encephalitis associated with antibodies against N-methyl-D-aspartate (NMDA)-type glutamate receptor (GluR) after allo-HSCT. To the best of our knowledge, this is the first report of the involvement of antibodies against NMDA-type GluR in post-transplantation encephalitis. Autoimmunity to NMDA-type GluR may have contributed to neurological complications after transplantation in unresolved cases.

A 68-year-old female was diagnosed with follicular lymphoma (FL) grade 2, based on the excisional biopsy of her enlarged left cervical lymph node. Positron-emission tomography/computed tomography (PET/CT) revealed the

The human gut harbours diverse microorganisms, and gut dysbiosis has recently attracted attention because of its possible involvement in various diseases. In particular, the lack of diversity in the gut microbiota has been associated with complications of haematopoietic stem cell transplantation (HSCT), such as infections, acute graft-versus-host disease and relapse of primary disease, which lead to a poor prognosis. However, few studies have serially examined the composition of the intestinal microbiota after HSCT. In this study, we demonstrated, using next-generation sequencing of the bacterial 16S ribosomal RNA gene, combined with uniFrac distance analysis, that the intestinal microbiota of patients undergoing allogeneic HSCT substantially differed from that of healthy controls and recipients of autologous transplants. Faecal samples were obtained daily throughout the clinical course, before and after transplantation. Notably, the proportions of Bifidobacterium and genera categorized as butyrate-producing bacteria were significantly lower in patients with allogeneic HSCT than in healthy controls. Furthermore, among allogeneic transplant recipients, a subgroup with a preserved microbiota composition showed a benign course, whereas patients with a skewed microbiota showed a high frequency of complications and mortality after transplantation. Thus, we conclude that the stability of intestinal microbiota is critically involved in outcomes of HSCT.

Aggregation of monoclonal immunoglobulin can lead to organ damage. However, the necessity of invasive examination such as biopsy has hampered better understanding of the pathophysiology. Corneal crystalline deposition is a rarely reported but known ocular manifestation of multiple myeloma. It is unclear whether the cornea is a common target of monoclonal immunoglobulin deposition. We conducted a prospective clinical case-control study to objectively quantify monoclonal gammopathy-associated corneal changes as well as any therapeutic response. Using an ophthalmic Scheimpflug camera imaging for noninvasive corneal assessments, we quantified densitometry values in 30 patients. Although none had crystalline keratopathy, corneal transparency in monoclonal gammopathy patients was significantly impaired compared to that in age-matched controls, based on noninvasive Scheimpflug camera imaging. Furthermore, treatment for multiple myeloma seemed to eradicate the diffuse aggregation of monoclonal proteins. Our results indicate that exposure to monoclonal immunoglobulin may induce the accumulation of monoclonal immunoglobulin in the cornea, and ophthalmic examinations such as corneal densitometry measurements with a Scheimpflug camera may be useful for noninvasive evaluation of monoclonal immunoglobulin deposition diseases.

We analyzed data from 64,539 consecutive patients in the Japanese national transplant registry, including 40,195 after allogeneic hematopoietic stem cell transplantation (HSCT), 24,215 after autologous HSCT and 129 after syngeneic HSCT, of whom 299 developed Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (PTLD). The probability of developing PTLD at 2 years post-HSCT was .79% after allogeneic transplantation, .78% after syngeneic transplantation, and .11% after autologous transplantation. The following variables were identified as risk factors after allogeneic HSCT in multivariate analysis: antithymocyte globulin (ATG) use in a conditioning regimen, ATG use for acute graft-versus-host disease (GVHD) treatment, donor other than an HLA-matched related donor, aplastic anemia, second or subsequent allogeneic HSCT, the most recent year of transplantation, and acute GVHD. The probability at 2 years increased particularly after 2009 (1.24%) than before 2009 (.45%). To stratify the risk of PTLD before allogeneic HSCT, we developed a novel 5-point scoring system based on 3 pretransplant risk factors: ATG use in a conditioning regimen (high dose, 2 points; low dose, 1 point), donor type (HLA-mismatched related donor, 1 point; unrelated donor, 1 point; cord blood, 2 points), and aplastic anemia (1 point). Patients were classified into 4 risk groups according to the summed points: low risk (0 or 1 point), intermediate risk (2 points), high risk (3 points), and very high risk (4 or 5 points) groups, with probabilities at 2 years of .3%, 1.3%, 4.6%, and 11.5%, respectively. Our scoring system is useful for predicting patients at high risk for PTLD. Careful observation and close monitoring of Epstein-Barr virus reactivation are warranted for these high-risk patients.

To compare the factors associated with survival after out-of-hospital cardiac arrests (OHCAs) among three time-distance areas (defined as interquartile range of time for emergency medical services response to patient's side).From a nationwide, prospectively collected data on 716,608 OHCAs between 2007 and 2012, this study analyzed 193,914 bystander-witnessed OHCAs without pre-hospital physician involvement.Overall neurologically favourable 1-month survival rates were 7.4%, 4.1% and 1.7% for close, intermediate and remote areas, respectively. We classified BCPR by type (compression-only vs. conventional) and by dispatcher-assisted CPR (DA-CPR) (with vs. without); the effects on time-distance area survival were analyzed by BCPR classification. Association of each BCPR classification with survival was affected by time-distance area and arrest aetiology (p0.05). The survival rates in the remote area were much higher with conventional BCPR than with compression-only BCPR (odds ratio; 95% confidence interval, 1.26; 1.05-1.51) and with BCPR without DA-CPR than with BCPR with DA-CPR (1.54; 1.29-1.82). Accordingly, we classified BCPR into five groups (no BCPR, compression-only with DA-CPR, conventional with DA-CPR, compression-only without DA-CPR, and conventional without DA-CPR) and analyzed for associations with survival, both cardiac and non-cardiac related, in each time-distance area by multivariate logistic regression analysis. In the remote area, conventional BCPR without DA-CPR significantly improved survival after OHCAs of cardiac aetiology, compared with all the other BCPR groups. Other correctable factors associated with survival were short collapse-to-call and call-to-first CPR intervals.Every effort to recruit trained citizens initiating conventional BCPR should be made in remote time-distance areas.

A conditioning regimen with fludarabine and myeloablative dose of busulfan (FLU/BU4) has been commonly used in allogeneic hematopoietic cell transplantation (allo-HCT). However, there are two major problems with this regimen: insufficient anti-leukemic effect, especially in advanced cases, and slow time to complete donor-type chimerism, especially T-cell chimerism. To overcome these issues, we designed a combination regimen with FLU (150 mg/m2), intravenous BU (12.8 mg/kg), and melphalan (100 mg/m2) (FLU/BU4/MEL) and conducted retrospective analyses of treatment outcomes at our institute. Forty-two patients with myeloid malignancies received allogeneic bone-marrow transplantation or peripheral blood stem-cell transplantation (allo-BMT/PBSCT) with FLU/BU4/MEL regimen. The median age of patients was 46.5 years (20–63 years). Thirteen patients (31%) did not achieve complete hematological remission at transplantation. All patients examined achieved complete whole and T-cell chimerism within 1 month after allo-HCT. The 4-year overall survival and disease-free survival rates were 66.0% [95% confidence interval (CI) 49.4–78.3%] and 59.5% (95% CI 43.2–72.6%) in all patients, and 49.4% (95% CI 19.7–73.6%) and 38.5% (95% CI 14.1–62.8%) in patients who were not in remission. In conclusion, FLU/BU4/MEL showed curative potential, even in patients with advanced myeloid malignancies, accompanied by achievement of rapid complete chimerism after allo-BMT/PBSCT.

Objectives: This study aimed to investigate the validity of laparoscopic gastric cancer surgery in elderly patients. Methods: A total of 202 patients who underwent laparoscopic gastrectomy for gastric cancer between January 2007 and December 2016 were divided into an elderly group (age ≥75 years, n = 36) and a control group (age < 75 years, n = 166). The patients’ clinicopathological data were reviewed. Results: The overall morbidity rate was relatively higher in the elderly group (16.7 vs. 11.4%, p = 0.389), whereas the incidence of serious complications ≥grade III according to the Clavien-Dindo classification did not increase significantly in the elderly group (8.3 vs. 7.8%, p = 0.920). Univariate and multivariate analyses revealed that age ≥75 years was not a significant predictive factor of postoperative morbidity (p = 0.568). There was no significant difference in the 5-year overall survival rate of patients with pathological stage I gastric cancer between the groups (97.1 vs. 96.1%, p = 0.704; hazard ratio, 0.669; 95% confidence interval, 0.036–3.692). Conclusions: Laparoscopic gastrectomy has an acceptable morbidity rate in elderly patients, and the long-term outcome of patients with stage I gastric cancer was similar to that of the control group.

Staphylococcus aureus as a pathogen in human gestational membranes, a rather rare phenomenon, has recently been the focus of several researches. S. aureus forms biofilms on these membranes and potentially causes chorioamnionitis in pregnant women. We report a case of persistent methicillin-resistant S. aureus (MRSA) bacteremia owing to placental infection, causing chorioamnionitis and preterm birth. A 29-year-old Japanese woman at the 27th gestational week was diagnosed with acute promyelocytic leukemia and underwent all-trans retinoic acid therapy. Soon after hospitalization, the patient presented with persistent MRSA bacteremia of unknown origin. Despite various antimicrobial therapies, she experienced 12 MRSA bacteremia episodes over 6 weeks. However, after child birth, MRSA bacteremia disappeared without any complications. A pathologic examination of her placenta revealed placenta abscess, resulting in a diagnosis of MRSA-associated chorioamnionitis. Molecular analysis proved that a single MRSA strain (SCCmec Type IVa), which tested negative for Panton-Valentine leukocidin and toxic shock syndrome toxin-1, caused the obstinate infection. We should be aware that persistent MRSA bacteremia in pregnant women can originate from placental abscess.

The present study involved 6 patients who had urgent surgery for acute cholecystitis(AC)complicated with gallbladder cancer(GBC)in our hospital from January 2014 to December 2016. We analyzed the clinical outcome of early surgery for AC complicated with GBC. According to Tokyo Guidelines 2013, the AC severity was classified as Mild 1 case, Moderate 5 cases. Only one patient was diagnosed with GBC before the operation for AC. The others were during or after the laparoscopic cholecystectomy. Histopathologically, all patients had Stage II disease or greater. Two patients had adjunctive radical operation with the wedge resection of the gallbladder bed, lymphadenectomy and bile duct resection, and they survived without recurrence for 28 months and 12 months, respectively. Of the 3 patients without any additional surgery, 2 patients died in several months after the operation. In consideration of the concurrence of GBC, early surgery for AC must be decided carefully.

Compared with 4-times-daily infusion of intravenous busulfan (ivBU4), the safety and efficacy of once-daily infusion of ivBU (ivBU1) has not been fully clarified. We have been routinely using ivBU1 in a conditioning regimen in adult patients with myeloid malignancy who undergo allogeneic hematopoietic stem cell transplantation. In this study, a total of 91 patients who received ivBU1 for 2 days (n = 18) or 4 days (n = 73) in our institutions were compared with 273 control patients who received ivBU4, who were matched for age, sex, performance status, disease risk, conditioning regimen, and donor type, selected from the database of the Japanese Society for Hematopoietic Cell Transplantation using optimal matching algorithms. One-year overall survival (56.8% versus 57.1%, P = .94), disease-free survival (51.6% versus 50.8%, P = .73), relapse rate (28.5% versus 26.2%, P = .94), nonrelapse mortality (19.9% versus 23.0%, P = .71), and the incidence of graft-versus-host disease were not significantly different between the ivBU1 and ivBU4 groups. In patients who received ivBU1, neutrophil recovery was slower (median days: 22 versus 17, P = .001), and the incidence of veno-occlusive disease was lower (2.6% versus 17.4%, P = .04). In conclusion, ivBU1 can be safely administered with clinical outcomes similar to those with ivBU4.

Purpose To investigate temporal variations in dispatcher-assisted and bystander-initiated resuscitation efforts and their association with survival after bystander-witnessed out-of-hospital cardiac arrests (OHCAs). Methods We retrospectively analyzed the neurologically favorable 1-month survival and the parameters related to dispatcher assisted cardiopulmonary resuscitation (DA-CPR) and bystander CPR (BCPR) for 227,524 OHCA patients between 2007 and 2013 in Japan. DA-CPR sensitivity for OHCAs, bystander's compliance to DA-CPR assessed by the proportion of bystanders who follow DA-CPR, and performance of BCPR measured by the rate of bystander-initiated CPR in patients without DA-CPR were calculated as indices of resuscitation efforts. Results Performance of BCPR was only similar to temporal variations in the survival (correlation between hourly paired values, R2 = 0.263, P = 0.01): a lower survival rate (3.4% vs 4.2%) and performance of BCPR (23.1% vs 30.8%) during night-time (22:00–5:59) than during non-night-time. In subgroup analyses based on interaction tests, all three indices deteriorated during night-time when OHCAs were witnessed by non-family (adjusted odds ratio, 0.73–0.82), particularly in non-elderly patients. The rate of public access defibrillation for these OHCAs markedly decreased during night-time (adjusted odds ratio, 0.49) with delayed emergency calls and BCPR initiation. Multivariable logistic regression analyses revealed that the survival rate of non-family-witnessed OHCAs was 1.83-fold lower during night-time than during non-night-time. Conclusions Dispatcher-assisted and bystander-initiated resuscitation efforts are low during night-time in OHCAs witnessed by non-family. A divisional alert system to recruit well-trained individuals is needed in order to improve the outcomes of night-time OHCAs witnessed by non-family bystanders.

Aim To determine the effectiveness of ventilations in bystander cardiopulmonary resuscitation (BCPR) and to identify the factors associated with ventilation-only BCPR. Methods From out-of-hospital cardiac arrest (OHCA) data prospectively collected from 2005 to 2011 in Japan, we extracted data for 210,134 bystander-witnessed OHCAs with complete datasets but no prehospital involvement of physician [no BCPR, 115,733; ventilation-only, 2093; compression-only, 61,075; and conventional (compressions+ventilations) BCPR, 31,233] and determined the factors associated with 1-month neurologically favourable survival using simple and multivariable logistic regression analyses. In 91,885 patients with known BCPR durations, we determined the factors associated with ventilation-only BCPR. Results The rate of survival in the no BCPR, ventilation-only, compression-only and conventional group was 2.8%, 3.9%, 4.5% and 5.0%, respectively. After adjustment for other factors associated with outcomes, the survival rate in the ventilation-only group was higher than that in the no BCPR group (adjusted OR; 95% CI, 1.29; 1.01–1.63), but lower than that in the compression-only (0.76; 0.59–0.96) or conventional groups (0.70; 0.55–0.89). Conventional CPR had the highest OR for survival in almost all OHCA subgroups. The adjusted OR (95% CI) for survival after dividing BCPR into ventilation and compression components was 1.19 (1.11–1.27) and 1.60 (1.51–1.69), respectively. Older guidelines, female sex, younger patient age, bystander-initiated CPR without instruction, early BCPR and short BCPR duration were associated with ventilation-only BCPR. Conclusions Ventilation is a significant component of BCPR, but alone is less effective than compression in improving neurologically favourable survival after OHCAs.

To investigate differences in chronological variations in characteristics and outcomes of out-of-hospital cardiac arrests (OHCAs) between elderly and non-elderly patients.We retrospectively analyzed bystander-witnessed OHCAs without prehospital involvement of physicians between January 2007 and December 2014 in Japan. We considered the following time periods: night-time (23:00-5:59) and non-night-time; we further divided non-night-time into dinnertime (18:00-20:29) and other non-night-time. Subsequently, we analyzed chronological variations in factors associated with OHCA survival using univariate and multivariable logistic regression analyses for unmatched and propensity-matched pairs, respectively.For elderly (≥65 years old, N = 201,073) and non-elderly (≥10,65 years old, N = 57,124) OHCA patients, survival rates were lower during night-time than during non-night-time (elderly, 2.8% vs 1.6%; non-elderly, 9.8% vs 7.7%). The trend for incidences of bystander-witnessed OHCA in the elderly showed three peaks associated with breakfast-time, lunchtime, and dinnertime. However, a transient but considerable decrease in survival rates was observed at dinnertime (1.9% at dinnertime and 3.0% during other non-night-time). OHCAs in the elderly at dinnertime were characterized by low proportions of presumed cardiac etiologies and shockable initial rhythm. However,even after adjusting for these and other factors associated with survival,survival rates were significantly lower at dinnertime than during other non-night-time for elderly OHCA patients (adjusted odds ratio, 1.29; 95% confidence interval, 1.18-1.41, with dinnertime as reference). This difference was significant even after propensity matching with significant augmentation in winter.Dinnertime, particularly in winter, is associated with lower survival in elderly OHCA patients.

Purpose To investigate the fusion of pelvic magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (PET) for assessment of locoregional extension and nodal staging of cervical cancer. Methods PET/computed tomography (CT), MRI, and non-fused and fusion of PET and MRI for assessing the extent of the primary tumor and metastasis to nodes were evaluated. Results Accuracy for T-status was 83.3% for fused and non-fused PET/MRI and MRI proved significantly more accurate than PET/CT (53.3%) ( P =.0077). Sensitivity, specificity, and accuracy for nodal metastasis were 92.3%, 88.2%, and 90.0% for fused PET/MRI and PET/contrast-enhanced CT; 84.6%, 94.1%, and 90.0% for non-fused PET/MRI; and 69.2%, 100%, and 86.7% for MRI. Conclusion Fused PET/MRI combines the individual advantages of MRI and PET.

Background To evaluate the diagnostic value of retrospective image fusion from pelvic magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (PET) in detecting intra-pelvic recurrence of gynecological tumor. Methods Thirty patients with a suspicion of recurrence of gynecological malignancy underwent inline contrast-enhanced PET/computed tomography (CT) and pelvic contrast-enhanced MRI for restaging. Diagnostic performance about the local recurrence, pelvic lymph node and bone metastasis and peritoneal lesion of PET/low-dose non-enhanced CT (PET/ldCT), PET/full-dose contrast-enhanced CT (PET/ceCT), contrast-enhanced MRI, and retrospective image fusion from PET and MRI (fused PET/MRI) were evaluated by two experienced readers. Final diagnoses were obtained by histopathological examinations, radiological imaging and clinical follow-up for at least 6 months. McNemar test was employed for statistical analysis. Results Documented positive locally recurrent disease, pelvic lymph node and bone metastases, and peritoneal dissemination were present in 53.3, 26.7, 10.0, and 16.7 %, respectively. Patient-based sensitivity for detecting local recurrence, pelvic lymph node and bone metastasis and peritoneal lesion were 87.5, 87.5, 100 and 80.0 %, respectively, for fused PET/MRI, 87.5, 62.5, 66.7 and 60.0 %, respectively, for contrast-enhanced MRI, 62.5, 87.5, 66.7 and 80.0 %, respectively, for PET/ceCT, and 50.0, 87.5, 66.7 and 60.0 %, respectively, for PET/ldCT. The sensitivity of diagnosing local recurrence by fused PET/MRI was significantly better than that of PET/ldCT (p = 0.041). The patient-based sensitivity, specificity and accuracy for the detection of intra-pelvic recurrence/metastasis were 91.3, 100 and 93.3 % for fused PET/MRI, 82.6, 100 and 86.7 % for contrast-enhanced MRI, 82.6, 100 and 86.7 % for PET/ceCT and 78.3, 85.7 and 80.0 % for PET/ldCT. Conclusion Fused PET/MRI combines the individual advantages of MRI and PET, and is a valuable technique for assessment of intra-pelvic recurrence of gynecological cancers.

We report the case of a 44-year-old woman with Masaoka stage IV, World Health Organization type B1 thymoma associated with pure red cell aplasia, thrombocytopenia, and myasthenia gravis, which occurred during preoperative chemotherapy with high-dose methylprednisolone. Noninvasive positive-pressure ventilation, intravenous immunoglobulin infusion, and methylprednisolone pulse therapy were performed for the myasthenic crisis. Disseminated thymoma was markedly reduced after these treatments, and macroscopic complete resection was performed after achieving control of pure red cell aplasia, myasthenia gravis, and thrombocytopenia using cyclosporine A. Chemotherapy, including high-dose methylprednisolone, may carry a risk of myasthenic crisis, although the regimen is effective against lymphocyte-rich thymoma.

Review: An increased number of rescuers may improve the survival rate from out-of-hospital cardiac arrests (OHCAs). The majority of OHCAs occur at home and are handled by family members. Materials and methods: Data from 5078 OHCAs that were witnessed by citizens and unwitnessed by citizens or emergency medical technicians from January 2004 to March 2010 were prospectively collected. The number of rescuers was identified in 4338 OHCAs and was classified into two (single rescuer (N = 2468) and multiple rescuers (N = 1870)) or three (single rescuer, two rescuers (N = 887) and three or more rescuers (N = 983)) groups. The backgrounds, characteristics and outcomes of OHCAs were compared between the two groups and among the three groups. Results: When all OHCAs were collectively analysed, an increased number of rescuers was associated with better outcomes (one-year survival and one-year survival with favourable neurological outcomes were 3.1% and 1.9% for single rescuers, 4.1% and 2.0% for two rescuers, and 6.0% and 4.6% for three or more rescuers, respectively (p = 0.0006 and p < 0.0001)). A multiple logistic regression analysis showed that the presence of multiple rescuers is an independent factor that is associated with one-year survival (odds ratio (95% confidence interval): 1.539 (1.088-2.183)). When only OHCAs that occurred at home were analysed (N = 2902), the OHCAs that were handled by multiple rescuers were associated with higher incidences of bystander CPR but were not associated with better outcomes. Conclusions: In summary, an increased number of rescuers improves the outcomes of OHCAs. However, this beneficial effect is absent in OHCAs that occur at home. © 2012 Elsevier Ireland Ltd. All rights reserved.

This study evaluated the effect of foot progression angle on the reduction in knee adduction moment caused by a lateral wedged insole during walking. Twenty healthy, young volunteers walked 10 m at their comfortable velocity wearing a lateral wedged insole or control flat insole in 3 foot progression angle conditions: natural, toe-out, and toe-in. A 3-dimensional rigid link model was used to calculate the external knee adduction moment, the moment arm of ground reaction force to knee joint center, and the reduction ratio of knee adduction moment and moment arm. The result indicated that the toe-out condition and lateral wedged insole decreased the knee adduction moment in the whole stance phase. The reduction ratio of the knee adduction moment and the moment arm exhibited a close relationship. Lateral wedged insoles decreased the knee adduction moment in various foot progression angle conditions due to decrease of the moment arm of the ground reaction force. Moreover, the knee adduction moment during the toe-out gait with lateral wedged insole was the smallest due to the synergistic effect of the lateral wedged insole and foot progression angle. Lateral wedged insoles may be a valid intervention for patients with knee osteoarthritis regardless of the foot progression angle.

Background Population aging has rapidly progressed in Japan. However, few data exist regarding the characteristics of extremely elderly patients with out-of-hospital cardiac arrest (OHCA). We aimed to determine the prehospital predictors of one-month survival with favorable neurological outcomes (Cerebral Performance Category scale, category 1 or 2; CPC 1–2) in this population. Methods We investigated 23,520 OHCA patients aged ≥95 years from a prospectively recorded, nationwide, Utstein-style Japanese database between 2008 and 2012. The primary study endpoint was one-month CPC 1–2 after OHCA. Results The one-month CPC 1–2 rate was 0.27% (63/23,520). Only two variables were significantly associated with one-month CPC 1–2 in a multivariate logistic regression model: prehospital return of spontaneous circulation (ROSC) [adjusted odds ratio (aOR), 94.4; 95% confidential interval (CI), 50.1–191.7] and emergency medical service (EMS)-witnessed arrest (aOR, 5.1; 95% CI, 2.6–10.2). When stratified by these two predictors, the one-month CPC 1–2 rates were 20.2% (18/89) for patients who had both prehospital ROSC and EMS-witnessed arrest, 4.2% (33/783) for those who had prehospital ROSC without EMS-witnessed arrest, 0.28% (3/1065) for those who had EMS-witnessed arrest without prehospital ROSC, and 0.04% (9/21,583) for those who had neither predictor, respectively. Conclusions The crucial prehospital predictors for one-month CPC 1–2 in elderly OHCA patients aged ≥95 years in Japan were prehospital ROSC and EMS-witnessed arrest and the former was the predominant predictor.

For patients chronically infected with hepatitis C virus (HCV), mutations in the non-structural 5A (NS5A) gene are important predictive factors for the response to interferon (IFN) therapy. In the present study, factor analysis of the therapeutic response of patients following pegylated IFN and ribavirin combination therapy was assessed in a multicenter study. Chronic HCV-infected patients with genotype 1b and high viral load (n=96, mean age 56.5 years; 59 males, 68 females) treated with pegylated IFN-α-2b and ribavirin combination therapy were enrolled. This study was conducted at Kobe University Hospital and 25 affiliated hospitals in Hyogo prefecture. Sixty-five patients (68%) completed treatment with both pegylated IFN and ribavirin at >80% of the weight-based scheduled dosages. Patients who reduced or terminated therapy were frequently aged women (mean age 60.8 years; 11 males, 17 females). Overall, a sustained viral response (SVR) was achieved in 42 (44%) patients out of 96. Based on per-protocol-based (PPB) analysis, the SVR rate in patients with ≥6 amino acid (aa) mutations in the IFN resistance-determining region (IRRDR) (75%) or ≥1 aa mutation in the IFN sensitivity-determining region (ISDR) (61%) was significantly higher than that in patients with

We have recently reported that the outcome of acute myeloid leukemia (AML) patients with t(6;9)(p23;q34) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) was comparable to that of patients with a normal karyotype. We performed a further analysis regarding the prognostic factors for t(6;9)(p23;q34) AML patients who underwent a HSCT. Seven pediatric patients and 57 adult patients, transplanted between 1996 and 2007, were assessed in this study. The overall survival (OS) of the pediatric patients tended to be better than the OS of the adults, although there were no statistically significant differences. The present study focused on the adult patients revealed that the disease status at HSCT was the sole prognostic factor affecting the OS identified in the univariate analysis. A multivariate analysis showed that the disease status at HSCT and M2 in the FAB classification were extracted as the significant variables affecting the OS. The patients who were not in remission at HSCT and had non-FAB-M2 showed a poorer outcome; 6 deaths in the 9 patients were due to a relapse of the AML. These findings suggest that novel therapeutic approaches might be needed for patients with these poor prognostic factors., 発行後6か月より全文公開

Acute myeloid leukemia (AML) with t(6;9)(p23;q34) is well known to have a poor prognosis treated with chemotherapy and autotransplantation. The presence of this karyotype is an indicator for allogeneic hematopoietic stem cell transplantation (HSCT); however, the impact of t(6;9)(p23;q34) on the HSCT outcome remains unclear. We conducted a matched-pair analysis of de novo AML patients with and without t(6;9)(p23;q34) using data obtained from the Japanese HSCT data registry. A total of 57 patients with t(6;9)(p23;q34) received transplants between 1996 and 2007, and 171 of 2056 normal karyotype patients matched for age, disease status at HSCT and graft source were selected. The overall survival, disease-free survival, cumulative incidence of relapse and the non-relapse mortality in t(6;9)(p23;q34) patients were comparable to those for normal karyotype patients. A univariate analysis showed that t(6;9)(p23;q34) had no significant impact on the overall survival. These findings suggest that allogeneic HSCT may overcome the unfavorable impact of t(6;9)(p23;q34) as an independent prognostic factor. © 2012 Macmillan Publishers Limited All rights reserved.

To evaluate the interobserver variability and diagnostic performance of a developed magnetic resonance imaging (MRI)-based scoring system for invasive placenta previa.Prenatal MR images of 70 women were retrospectively evaluated, 18 of whom were diagnosed with invasive placenta. The six MR features (dark band on T2 -weighted images, intraplacental abnormal vascularity, placental bulge, heterogeneous placenta, myometrial thinning, and placental protrusion sign) were scored on 5-point Likert scale separately, and the cumulative radiological score (CRS) was defined as the sum of each score. Two more experienced radiologists (readers A and B) and two less experienced residents (readers C and D) calculated the CRS. Interobserver variability was assessed by measuring the intraclass correlation coefficient. Diagnostic performance was evaluated by means of receiver operating characteristic (ROC) analysis.Interobserver variability for CRS was excellent for the more experienced radiologists (0.85), and good for all readers (0.72) and the less experienced residents (0.66). The area under the ROC curve (Az) and accuracy (Acc) for CRS were significantly higher or equivalent to those of other MR features for all readers (Az and Acc for reader A; CRS, 0.92, 91.4%; intraplacental T2 dark band, 0.83, P = 0.009, 81.4%, P = 0.03; intraplacental abnormal vascularity, 0.9, P = 0.3, 90.0%, P = 1.00; placental bulge, 0.81, P = 0.0008, 80.0%, P = 0.02; heterogeneous placenta, 0.85, P = 0.11, 74.3%, P = 0.002; myometrial thinning, 0.84, P = 0.06, 60.0%, P0.0001; placental protrusion sign, 0.81, P = 0.01, 81.4%, P = 0.26).This developed MRI-based scoring system demonstrated excellent or good interobserver variability, and good diagnostic performance for invasive placenta previa. J. Magn. Reson. Imaging 2016;44:573-583.

The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

The purpose of this article is to review fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) findings in a variety of benign, malignant, and borderline malignant ovarian tumors. It is advantageous to become familiar with the wide variety of FDG-PET/CT findings of this entity. Benign ovarian tumors generally have faint uptake, whereas endometriomas, fibromas, and teratomas show mild to moderate uptake. Malignant ovarian tumors generally have intense uptake, whereas tumors with a small solid component often show minimal uptake.

To evaluate the diagnostic value of integrated 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) to discriminate malignant from benign ovarian tumors.One hundred and eight women suspected of having ovarian cancer underwent preoperative FDG-PET/CT scans. FDG uptake was quantified by calculating the maximum standardized uptake value (SUV max) of each tumor. The receiver operating characteristic curve was drawn to determine the optimal cut-off values of SUV max that would best discriminate between benign and malignant tumors. Histopathologic results served as the reference standard. We assessed the association between SUV max and with International Federation of Gynecology and Obstetrics stage in borderline and malignant tumors, using one-factor analysis of variance and an unpaired t test with Bonferoni correction.The SUV max of benign (n=26), borderline (n=12) and malignant (n=73) lesions was 2.00 ± 1.02, 2.72 ± 1.04, and 7.55 ± 4.29, respectively. Although there were significant differences between benign and malignant, and borderline and malignant lesions (P0.0001), there was no significant difference between benign and borderline lesions. Using an SUV max cutoff of 2.55, the sensitivity, specificity and accuracy of FDG-PET/CT scanning to detect malignant or borderline tumors were 82.4, 76.9, and 81.1%, respectively. The SUV max of stage I (n=35), stage II (n=8), stage III (n=34) and stage IV (n=8) was 3.59 ± 2.32, 5.18 ± 1.34, 8.72 ± 2.69, and 15.05 ± 3.77, respectively, and significant differences were observed between SUV max values and the various International Federation of Gynecology and Obstetrics stage (P0.0001).FDG-PET/CT scanning has a high diagnostic value in differentiating between malignant and benign tumors, and a low diagnostic value in differentiating between borderline and benign tumors.

The aim of this study was to examine the dexterity of both lower extremities in patients with stroke. Twenty patients with stroke and 20 age-matched control subjects participated in this study. To determine the dexterity of the lower extremities, we examined the ability to control muscle force during submaximal contractions in the knee extensor muscles using a force tracking task. The root mean square errors were calculated from the difference between the target and response force. The root mean square error was significantly greater in the affected limb of patients with stroke compared with those of the unaffected limb and the control subjects, and in the unaffected limb compared with that of the control subjects. Furthermore, the root mean square error of the affected limb was related significantly to motor function as determined by Fugl-Myer assessment. These results demonstrate impairment of the dexterity of both the affected and the unaffected lower extremities in patients with stroke.

BACKGROUND Although one clinical sign of aging and/or photoaging is a yellowish discoloration of the facial skin, little is known about the cause of this change. In addition to the increase in the epidermal melanin content, it has been suggested that advanced glycation end products (AGEs), which are known to accumulate in photoaged skin, may affect this discoloration. AIM The objective of this pilot study was to non-invasively investigate the roles of melanin and AGEs in this yellowish discoloration of the facial skin. METHODS We examined the spectral reflectance at the cheek in 40 healthy Japanese women of various ages (mean age, 38.1 years) using a reflectance spectrophotometer and a spectrofluorimeter. The degree of yellowish tint was evaluated in terms of b(*). The amount of melanin in the skin was evaluated by calculating the melanin index (MI) A(640)-A(670) [A(lambda): log(10) (1/reflectance) at a wavelength of lambda]. The amount of AGEs was roughly evaluated using the AGEs index, which is thought to linearly correlate with the amount of intrinsic fluorescence markers irrespective of the concentration of melanin and is defined as follows: AGEs index=I(5)/SQR (I(1)xI(2)). In this equation, the intensities of reflectance are I(1) at an excitation wavelength of 335 nm, I(2) at an emission wavelength of 390 nm and I(5) at 390 nm under an excitation wavelength of 335 nm. RESULTS Both b(*) and the AGEs index were significantly correlated with subject age (r=0.34, P

We have evaluated the antifungal activity of micafungin in serum by using the disk diffusion method with serum-free and serum-added micafungin standard curves. Serum samples from micafungin-treated patients have been shown to exhibit adequate antifungal activity, which was in proportion to both the applied dose and the actual concentration of micafungin measured by high-performance liquid chromatography. The antifungal activity of micafungin in serum was also confirmed with the broth microdilution method.

The present study was conducted to clarify the role of carbon-11 choline ((11)C-choline) positron emission tomography (PET)/computed tomography (CT) in the management of uterine carcinoma.Twenty-two patients who underwent (11)C-choline PET/CT and pelvic MRI were evaluated retrospectively. The images were reviewed by a board-certified radiologist and a nuclear medicine specialist who were unaware of any clinical information, and a consensus was reached. Diagnostic accuracy of PET/CT was evaluated for staging. The reference standard consisted of histological examination (n = 17) and follow-up conventional CT (n = 5). In five patients with cervical carcinoma, (11)C-choline PET/CT was performed before and after treatment that consisted of cisplatin infusion and subsequent radiotherapy. Standardized uptake value (SUV) was compared with uni-dimensional and volumetric measurements that were made on magnetic resonance images (MRI) before and after treatment.Based on PET/CT interpretations, the reviewers correctly classified T stage in 8 patients (47%), N stage in 21 patients (96%), M stage in 20 patients (91%), and TNM stage in 15 patients (88%). Tumor size, volume, and SUV decreased after treatment in five patients with cervical carcinoma. Using the Pearson correlation test, a significant correlation was found between the reduction rate of SUV and reduction rate of tumor volume.(11)C-choline PET/CT is an accurate means for the management of patients with uterine carcinoma. The combination of (11)C-choline PET/CT and MRI increases the accuracy of staging in patients with uterine carcinoma.

Objectives: FOLFIRI is one of the current standard first-line regimens for advanced colorectal cancer, but its administration is onerous. Because the replacement of 2-day-infusional 5-fluorouracil (5-FU) of FOLFIRI with oral tegafur-uracil/leucovorin (UFT/LV) would be highly beneficial for clinical management, we performed a phase I trial using oral UFT/LV and a pharmacokinetic evaluation. Methods: Treatment consisted of infusional irinotecan (100 mg/m 2 )/l-LV (15 mg/m 2 ) and a bolus injection of 5-FU (500 mg/m 2 ) on day 1, and oral UFT (300 mg as tegafur/m 2 /d)/LV (75 mg/d) on days 1-5 (level 1), days 1-7 (level 2), or days 1-10 (level 3). Cycles were repeated every 14 days. After determination of the recommended UFT/LV administration period, irinotecan was dose-escalated (level 4: 125 mg/m 2 ; level 5: 150 mg/m 2 ). Results: Nineteen patients were enrolled. One dose-limiting toxicity (DLT), grade 4 neutropenia lasting for ≥4 days was observed at level 2. At level 3, one DLT of treatment delay of ≥8 days occurred due to prolonged neutropenia, and 2 patients refused to continue the treatment because of prolonged grade 2 anorexia. Therefore, a 7-day administration of UFT/LV was recommended. No DLT was observed at levels 4 and 5. Pharmacokinetic evaluation suggested continuous exposure to 5-FU by means of oral UFT/LV administration in this combination. Conclusions: The recommended administration period was 7 days for oral UFT/LV, and the recommended dose of irinotecan was 150 mg/m 2 . A phase II study is ongoing to validate the clinical outcome.

To report the efficacy of intravitreal chemotherapy for primary intraocular lymphoma (PIOL).Retrospective, noncomparative interventional case reports are presented for six patients (ten eyes; mean age, 58.8 years) with pathologically confirmed PIOL who participated in this study and were treated at our hospital with intravitreal injections of methotrexate (MTX) between January 2004 and February 2007. Intravitreal injections of MTX (400 microg MTX/50 microl Opeguard-MA) were administered once or twice weekly for 1 month followed by ten monthly injections. Interleukin-10 (IL-10) and IL-6 were measured in the vitreous before and after injections to determine tumor activity.All eyes were clinically cleared of malignant cells. One eye lost vision. After intravitreal chemotherapy, the vitreous IL-10 concentration reached barely detectable levels.Intravitreal chemotherapy achieves clinical remission and preserves vision in patients with PIOL.

The purpose of the present study was to determine the diagnostic accuracy of non-enhanced CT and contrast-enhanced CT in integrated PET/CT studies for preoperative nodal staging of rectal cancer.Retrospective analysis was performed in 53 patients with pathologically proven rectal cancer who had been referred for preoperative staging. All patients underwent integrated PET/CT consisting of non-enhanced and contrast-enhanced CT followed by whole-body fluorine-18-fluorodeoxyglucose ([(18)F]FDG) PET. Both non-enhanced and contrast-enhanced PET/CT images were evaluated separately by two observers in consensus. The reference standard was histopathologic results. For nodal staging of rectal cancer, we compared diagnostic accuracy on a per-patient basis between the two modalities.Nodal staging was correctly determined with non-enhanced studies in 37 patients (70%) and with contrast-enhanced studies in 42 patients (79%). On a per-patient basis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of regional lymph node staging were 85%, 68%, 83%, 72%, and 79%, respectively, with contrast-enhanced studies, and 85%, 42%, 73%, 62%, and 70%, respectively, with non-enhanced studies. The difference in the accuracy of nodal staging between the two modalities was not significant (p = 0.063). Compared with non-enhanced studies, contrast-enhanced studies determined more correctly the status of pararectal lymph nodes (p = 0.002), internal iliac lymph nodes (p = 0.004), and obturator lymph nodes (p0.0001).Contrast-enhanced PET/CT is superior to non-enhanced PET/CT for precise definition of regional nodal status in rectal cancer.

[F-18]-fluorodeoxy-D-glucose (18FDG) positron emission tomography (PET) is a sensitive modality for detecting malignant lesions. The purpose of the present study was to describe unknown bone and soft tissue lesions in adults identified at cancer screening using PET.A total of 4283 individuals of more than or equal to 40 years of age were enrolled. All individuals underwent scans from the base of the skull to proximal thigh. The images were reviewed and a consensus was reached by two board-certified radiologists and a nuclear medicine specialist for the diagnoses. Diagnoses of the lesions were confirmed by histological examination, typical radiologic findings, obvious progression in number and/or size of the lesion on follow-up examinations, and medical examination of interview.Unsuspected focal abnormality in the bone and soft tissue were found in 62 individuals (1.4%). The mean size of the lesion was 26 mm (range, 6-155 mm). There were 29 bone lesions (47%) and 33 soft tissue lesions (53%). A malignant lesion was found in one case (1.6%) and histologic diagnosis was primary non-Hodgkin lymphoma of the vertebra. Other major diagnoses were healing bone (n = 11, 18%) and benign cystic lesions of bone and soft tissue (n = 9, 15%), and brown fat of soft tissue (n = 4, 6%).Unsuspected bone and soft tissue lesions of a wide variation of pathologic and clinical diagnoses were encountered at cancer screening using PET. Correlation with clinical history and other imaging findings is essential in the differential diagnosis.

Recent studies have revealed the crucial role of the niche which supports B-lymphocyte differentiation from hematopoietic stem cells. In this study, we aimed to identify a novel regulator of B lymphopoiesis secreted in the specific niche using the signal sequence trap method. Among the identified proteins from MS5 stromal cells, expression of pleiotrophin, placental proliferin 2, and osteoblast stimulating factor 5 (OSF-5) was dominantly high in several stromal cell lines. We found that OSF-5 suppressed early B lymphopoiesis in transgenic mice producing the target protein. The number of pre-B and immature B cells was reduced by more than half compared with control in the transgenic mice. In vitro studies showed that a secreted variant of OSF-5 inhibited the proliferation and colony formation of pre-B cells, whereas cell-intrinsic form had no influence on B lymphopoiesis. The main components of the B-lymphopoietic niche, osteoblasts in mice and mesenchymal cells in humans, are primary producers of OSF-5. These results define a novel mechanism of B lymphopoiesis in bone marrow. In the specific niche, B-lymphocyte differentiation is fine-tuned by negative regulators as well as supportive factors.

Bronchial granular cell tumor is an uncommon benign tumor that causes pulmonary complications due to obstruction of the airways. We report a case presenting bronchial obstruction on high resolution (HR) computed tomography (CT).

To evaluate the usefulness of metabolic parameters obtained by 18F-FDG PET/CT for preoperative stratification of high-risk and low-risk endometrial carcinomas. Preoperative 18F-FDG PET/CT was performed in 56 women with endometrial cancer. Maximum standardized uptake values (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumours were compared with clinicopathological features of surgical specimens. Diagnostic performance in terms of differentiation of low-risk disease (endometrioid histology, histological grade 1 or 2, invasion of less than half of the myometrium, and FIGO stage I) from high-risk disease was assessed. MTV and TLG were significantly higher in patients with higher histological grade (p = 0.0026 and p = 0.034), larger tumour size (p = 0.002 and p = 0.0017), lymphovascular space involvement (LVSI; p = 0.012 and p = 0.0051), myometrial invasion (p = 0.027 and p = 0.031), cervical stromal invasion (p = 0.023 and p = 0.014), ovarian metastasis (p = 0.00022 and p = 0.00034), lymph node metastasis (p