Search

Objective Resection is usually recommended for locally recurrent rectal cancer (LRRC) for which R0 resection is possible, but its suitability varies by individual patient risk. Here, we report outcomes of resected LRRC in our hospital. Methods We retrospectively evaluated short- and long-term results of 33 patients who underwent resections for LRRC from January 2003 to December 2019. Results At the initial surgeries for these 33 patients, their disease stages at that time were Stage I: n=2, Stage II: n=12, Stage III: n=11, Stage IV: n=6, and unknown: n=2. Patients with Stage IV disease at their initial surgeries underwent radical one-step or two-step procedures. Metastasis to other organs was observed in 5 patients at the their initial LRRC diagnoses. At the LRRC surgeries, 7 patients received palliative surgeries; 26 received intent-to-treat resections, of which 17 were R0 resections. All-grade postoperative complications were observed in 11 patients, including 1 surgery-related death. Five-year overall survival rates were all cases: 38.4%; R0 group: 52.3%, R1 or R2 group: 19.4%, and palliative surgery group: 0%. The R0 group thus had significantly better prognosis than other patients (P = 0.0012). Eleven patients in the R0 group (64.7%) suffered re-recurrences but some patients achieved long-term survival through chemotherapy, radiation therapy, and surgery for metastasis to other organs, even after re-recurrence. Conclusion Long-term prognosis after surgery for LRRC was significantly better for patients with R0 margins. Multimodal treatments may greatly improve survival for patients who suffer re-recurrences after local recurrence resections.

To evaluate the frequency, characteristics, and clinical significance of transient hyperintensity foci on T1-weighted images (T1WI) in acute disseminated encephalomyelitis (ADEM). Patients diagnosed with ADEM underwent MR studies at the time of disease onset and every 3 months or more often thereafter. The frequency and appearance timing of abnormal signals including T1WI and their morphological characteristics were evaluated. Relations between patient symptoms and abnormal signals on MRI were also evaluated. Five ADEM patients were included in this study. Linear (n = 2) or nodular (n = 1) T1-hyperintensity foci appeared in 3 patients (60%, 3/5). Locations of T1-hyperintensity foci were both cortical/subcortical region and basal ganglia (n = 1), subcortical region alone (n = 1), and internal capsule (n = 1). Those T1-hyperintensity foci were located within the T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) hyperintensity foci on initial MRI. Some T1-hyperintensity foci also showed hyperintensity on diffusion-weighted image (DWI) and contrast enhancement. T1-hyperintensity appeared at 14–43 days (median, 28 days), and disappeared in 2 patients at 91 days and 627 days after disease onset. There were no neurological sequelae remained in any patients. T1-hyperintensity foci is not a rare finding (60%) and it can be observed after improvement in symptoms in ADEM.

Background/objective With increased life expectancy, the incidence of colorectal cancer in oldest-old patients has been rising. Advanced age is a risk factor for adverse outcomes after surgery. This study aimed to evaluate the short- and long-term outcomes of curative resection for colorectal cancer in nonagenarians. Methods Patients who had undergone curative resection for colorectal cancer (CRC) at Stage I to III from January 2010 to December 2019 were included. Cases of emergent surgery were excluded. The clinical characteristics were documented retrospectively, and factors affecting the long-term outcome were analyzed using multivariate analysis. Results Fifty patients met the selection criteria. Most of them were women (58.0%), and the median age was 92 years. Among these patients, 29 (58.0%) had a poor performance status (ASA-PS≥3). Laparoscopic surgery was performed in 42.0% of the patients, and 50% of the patients had postoperative complications classified as Clavien–Dindo grade 2 or severer, including 3 patients (6.0%) with grade 3 disease. No postoperative mortality occurred. The 30-day, 180-day, 1-year, 3-year and 5-year survival rates were 100%, 80.4%, 71.0%, 46.3%, and 33.8%, respectively. Multivariate analysis showed that a preoperative poor performance status (ASA-PS≥3) (HR: 3.067; 95% CI: 1.220–7.709; p = 0.017) was an independent prognostic factor for OS. Conclusion Curative elective resections for CRC in nonagenarians were performed safely without postoperative mortality. The preoperative performance status was significantly associated with OS after curative elective resection of colorectal cancer in nonagenarians. Our results suggest that excellent long-term outcomes can be achieved in a selected group with a good performance status.

We experienced a case of right sided accessory breast cancer complicated by contralateral breast cancer. A 50-year-old woman came to us for an examination because a tumor in her left breast was pointed out at breast cancer screening. A breast MRI confirmed a tumor in her left breast and a tumor continuing from the skin to the subcutis of the right axilla. A skin biopsy for the tumor in the right axilla and a core needle biopsy(CNB)for the tumor in the left breast were performed. The pathological result of the CNB for the left breast indicated an invasive ductal carcinoma of the tubular formative scirrhous type. Although the tumor of the right axilla was poorly differentiated adenocarcinoma demonstrating cord-like arrays, it was examined by skin biopsy and therefore no deep part of the tissue was included. We conducted immunostaining, in consideration of the possibility of metastasis from the left sided breast cancer. ER, PgR, mammaglobin, GATA 3 were positive, strongly suggesting that the tumor in the right axilla was also derived from a mammary gland. We also performed a wide local excision of the right axilla plus axillary dissection(level Ⅰ)in addition to conducting a left mastectomy plus sentinel lymph node biopsy, in consideration of the possibility of primary right sided accessory breast cancer. The pathological result following surgery confirmed a difference in the histologic features between both sides, residual normal accessory mammary glands around the tumor on the right side, and the presence of rich DCIS and a lobular replacement image, leading to a definitive diagnosis of primary invasive ductal carcinoma of the accessory breast on the right side.

Imaging findings of pilocytic astrocytoma (PA) vary widely, sometimes resembling those of high-grade glioma (HGG). This study aimed to identify the imaging parameters that can be used to differentiate PA from HGG. Altogether, 60 patients with PAs and 138 patients with HGGs were included in the study. Tumor properties and the presence of hydrocephalus, peritumoral edema, and dissemination were evaluated. We also measured the maximum relative cerebral blood flow (rCBFmax) and volume (rCBVmax) and determined the minimum apparent diffusion coefficient (ADCmin) in the tumor’s solid components. The relative T1 (rT1), T2 (rT2), and contrast-enhanced T1 (rCE-T1) intensity values were evaluated. Parameters were compared between PAs and HGGs using the Mann–Whitney U test. Receiver operating characteristic (ROC) curve analysis was also used to evaluate these imaging parameters. A value of P

Osteoporosis has become a worldwide public health problem, in part due to the fact that it increases the risk of fragility hip fractures (FHFs). The epidemiological assessment of FHFs is critical for their prevention; however, datasets for FHFs in Japan remain scarce. This was a multicenter, prospective, observational study in the northern district of Kyushu Island. Inclusion criteria were age > 60 years with a diagnosis of FHF and acquisition of clinical data by an electronic data capture system. Of 1294 registered patients, 1146 enrolled in the study. Nearly one third of patients (31.8%) had a history of previous fragility fractures. The percentage of patients receiving osteoporosis treatment on admission was 21.5%. Almost all patients underwent surgical treatment (99.1%), though fewer than 30% had surgery within 48 h after hospitalization. Bone mineral density (BMD) was evaluated during hospitalization in only 50.4% of patients. The rate of osteoporosis treatment increased from 21.5% on admission to 39.3% during hospitalization. The main reasons that prescribers did not administer osteoporosis treatment during hospitalization were forgetfulness (28.4%) and clinical judgment (13.6%). Age and female ratio were significantly higher in patients with previous FHFs than in those without. There was a significant difference in the rate of osteoporosis treatment or L-spine BMD values in patients with or without previous FHFs on admission. In conclusion, this study confirmed that the evaluation and treatment of osteoporosis and FHFs is still suboptimal in Japan, even in urban districts.

Background/aim Identifying useful biomarkers is central to selecting optimal therapeutic strategies for esophageal squamous cell carcinoma (ESCC). Serum p53 antibody (S-p53Ab), squamous cell carcinoma antigen (SCC-Ag), and carcinoembryonic antigen (CEA) were investigated to evaluate the significance of single and combined tumor markers in determining the diagnosis and prognosis of ESCC. Materials and methods Serum samples were obtained preoperatively from 133 patients with histologically-confirmed ESCC, including 32 patients with stage I (24.1%). Levels of S-p53Ab were assessed by enzyme-linked immunosorbent assay, using a new version of a highly specific, quantitative kit. The cut-off value for S-p53Ab was 1.3 U/ml. Results S-p53Ab was detected in 39.1% (52 out of 133) of patients with ESCC, including 40.0% (20 out of 50) of patients with early-stage ESCC. Positive rates for S-p53Ab, CEA, and SCC-Ag among patients with stage I ESCC (n=32) were 40.6%, 12.5%, and 31.3%, respectively. Positivity for S-p53Ab was not associated with positivity for CEA or SCC-Ag (p=0.249 and 0.747, respectively). The positive rate for diagnosis of ESCC increased from 39.1% to 65.4% when S-p53Ab was combined with SCC-Ag in this study. We found no significant correlation between the presence of S-p53Ab in ESCC and overall survival. Conversely, Cox regression analysis revealed that the International Union Against Cancer/TNM classification and systemic inflammation score were independent prognostic factors for ESCC in this series (hazard ratio(HR)=3.811, 95% confidence interval(CI)=1.548-9.378, p=0.004; and HR=2.218; 95% CI=1.087-4.523, p=0.029, respectively). Kaplan-Meier analysis revealed significant differences between patients with elevated S-p53Ab and SCC-Ag and patients with elevated levels of only one or neither of these factors (p=0.009). Conclusion The diagnostic rate with S-p53Ab was better than that with SCC-Ag and CEA in patients with early-stage ESCC. Combined detection of S-p53Ab and SCC-Ag can markedly improve diagnostic sensitivity and may permit more accurate stratification of patients with ESCC.

Background/aim Elderly patients usually have various comorbidities. Laparoscopic gastrectomy as a minimally-invasive treatment might be feasible for these patients. The aim of this study was to evaluate the safety and efficacy of laparoscopy-assisted distal gastrectomy (LADG) in elderly patients with gastric cancer by comparing the surgical outcomes and prognosis. Patients and methods We analyzed 136 patients who had undergone LADG between January 2013 and December 2014. We compared elderly patients (75 years old or more) with non-elderly patients. Results The incidence of all postoperative complications did not differ between groups, and there were no significant differences in the time to first oral intake or the duration of postoperative hospital stay. The 3-year overall and recurrence-free survival rates were not significantly different between the groups. Conclusion LADG is a safe and less invasive treatment for gastric cancer in elderly patients, who have a greater incidence of comorbidity.

A 77-year-old female case who underwent laparoscopic distal gastrectomy with D2 dissection, Billroth I reconstruction for gastric cancer. Since the stage was III A, she received an adjuvant chemotherapy with S-1 after surgery. However, about 2 years after surgery, she was referred to our hospital for anorexia and vomiting. As a result of the examination, we diagnosed stenosis due to peritoneal recurrence near the anastomotic site. We performed laparoscopic remnant gastrojejunal bypass (Billroth II method, with Braun anastomosis). A camera port was inserted into a median umbilical incision. Following this, 4 additional ports(1 ports of 12mm in diameter and 3 ports of 5mm in diameter)were inserted under laparoscopic imaging into the right lower, right upper, left upper, and left lower quadrants. We first detached the adhesion considered as the influence of the previous surgery, and the anastomosis of remnant stomach and jejunum and the Braun anastomosis were performed by the linear stapler. The postoperative course was good. She started oral intake from the day after surgery, was discharged on the 6 days after operation, and received chemotherapy promptly. This procedure was effective for recurrent gastric cancer with stenosis which is difficult to resect and it was considered to be a minimally invasive method with a view to initiating chemotherapy early after operation.

In recent years, the development of chemotherapy has been remarkable. Some cases of conversion surgery for unresectable gastric cancer have been reported.The clinical outcome of 11 patients with far advanced gastric cancer who underwent conversion surgery in our hospital from January 2013 to May 2017 were analyzed retrospectively.The median survival time was 592 days(355-1,460). Four patients died of recurrent gastric cancer. Patients with undifferentiated carcinoma dominant had significantly poor survival rather than with differentiated carcinoma dominant(p= 0.039). Meanwhile, the pathological responders for chemotherapy did not have significantly better survival rather than nonresponders.Although the short term outcome of conversion surgery was acceptable, recurrent rate was still high. To improve the prognosis, clarifying the optimal timing of operation and more effective adjuvant chemotherapy are mandatory.

Background: To investigate the hematological features of infants with bronchopulmonary dysplasia (BPD) and their relationships with clinical severity. Methods: This prospective observational study enrolled 73 BPD patients from a total of 331 infants with a birth weight of

Background We examined the association between pre-admission risk scores and severity on admission and functional outcome in acute ischemic stroke with atrial fibrillation (AF). Methods Between September 2011 and April 2014, we retrospectively extracted consecutive ischemic stroke patients with AF whose pre-admission modified Rankin Scale (mRS) score was 2 or less from our prospective database. Pre-admission CHADS 2 , CHA 2 DS 2 -VASc, and R 2 CHADS 2 scores were calculated in each patient, and their association with the National Institutes of Health Stroke Scale (NIHSS) score on admission or unfavorable outcome (mRS ≥3 at 3 months from the onset) was assessed. Results A total of 344 patients (189 were men; age, 77.7 ± 10.0 years) were included in the analysis. The median pre-admission CHADS 2 , CHA 2 DS 2 -VASc, and R 2 CHADS 2 scores were 2, 4, and 4, respectively. NIHSS score on admission was positively correlated with pre-admission CHADS 2 (ρ = .116, P = .031), CHA 2 DS 2 -VASc (ρ = .166, P = .020), and R 2 CHADS 2 scores (ρ = .106, P = .049). Receiver operating characteristic (ROC) curve analysis revealed that pre-admission CHADS 2 score of 2 or more (sensitivity, 80%; specificity, 45%; area under the ROC curve [AUC], .654), CHA 2 DS 2 -VASc score of 3 or more (sensitivity, 86%; specificity, 44%; AUC, .683), and R 2 CHADS 2 score of 4 or more (sensitivity, 61%; specificity, 62%; AUC, .657) were associated with unfavorable outcome. The pre-admission CHA 2 DS 2 -VASc score was better than the pre-admission CHADS 2 score in estimating unfavorable outcome ( P = .017). In multivariate analysis, cutoffs of these scores, female sex, higher NIHSS score, and internal carotid artery occlusion were associated with unfavorable outcome. Conclusions Pre-admission CHADS 2 , CHA 2 DS 2 -VASc, and R 2 CHADS 2 scores were associated with onset severity and functional outcome in acute ischemic stroke with AF.

Serum tumor markers in patients with cancer assist with establishing diagnosis, estimating prognosis, monitoring treatment, and detecting tumor recurrence. Changes in the p53 tumor suppressor gene are the most common genetic abnormalities in many different human malignancies. Several studies have demonstrated that serum p53 antibodies (S-p53Ab) comprise an early marker of malignant disease, a marker for treatment effects and a prognostic factor for patients with several types of tumors. We recently reported that S-p53Ab is useful for patients with gastric cancer. We describe a rare situation in which unusually high serum p53 antibodies helped to detect recurrent gastric cancer in the small intestine after gastrectomy. Further studies are required to gain a more precise understanding of the clinical impact of S-p53Ab titer monitoring in gastric cancer.

Background The aim of this retrospective study was to evaluate the clinical relevance of serum p53 antibody (S-p53Ab) as a biomarker and to investigate whether its diagnostic value could be improved when combined with other biomarkers of gastric cancer (GC). Patients and methods Serum samples were obtained preoperatively from 208 patients with histologically-confirmed GC, including 126 stage I patients (60.6%). Levels of S-p53Ab were assessed by a commercial laboratory using an anti-p53 detection kit. The cut-off value for S-p53Ab was 1.3 U/ml. Results S-p53Ab was detected in 16.3% (34 of 208) of patients with GC, including 13.6% (22 of 162) of patients with early-stage GC. The positive rates for S-p53Ab, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) of patients with stage I GC were 10.3% (13/126), 2.4% (3/126), and 8.7% (11/126), respectively. Positivity for S-p53Ab was not associated with CA19-9 or CEA positivity (p=0.098 and 0.053, respectively). The positive rate for a diagnosis of GC increased from 16.3% to 29.3% when S-p53-Ab was combined with CEA in this study. We found no significant correlation between the presence of S-p53Ab in GC and overall survival. Conversely, Cox regression analysis revealed that a high level of CA19-9 was an independent prognostic factor for GC in this series (hazard ratio(HR)=3.864; 95% confidence interval(CI)= 1.248-11.959; p=0.019). Kaplan-Meier analyses demonstrated significant differences in survival between patients with elevated levels of both S-p53Ab and CEA and those with elevated levels of only one or neither. Conclusion The diagnostic rate of S-p53Ab was better than that of CA19-9 and CEA in patients with stage I GC. Combined detection of S-p53Ab and CEA may improve the diagnostic sensitivity and may permit more accurate stratification of GC patients.

Purpose: Fragility hip fractures (FHFs) are associated with a high risk of mortality, but the relative contribution of various factors remains controversial. This study aimed to evaluate predictive factors of mortality at 1 year after discharge in Japan. Methods: A total of 497 patients aged 60 years or older who sustained FHFs during follow-up were included in this study. Expected variables were finally assessed using multivariable Cox proportional hazards models. Results: The 1-year mortality rate was 9.1% (95% confidence interval: 6.8–12.0%, n = 45). Log-rank test revealed that previous fractures ( p = 0.003), Barthel index (BI) at discharge ( p = 0.011), and place-to-discharge ( p = 0.004) were significantly associated with mortality for male patients. Meanwhile, body mass index (BMI; p = 0.023), total Charlson comorbidity index (TCCI; p = 0.005), smoking ( p = 0.007), length of hospital stay (LOS; p = 0.009), and BI ( p = 0.004) were the counterparts for females. By multivariate analyses, previous vertebral fractures (hazard ratio (HR) 3.33; p = 0.044), and BI 2 (HR 2.70, p = 0.023), TCCI ≥5 (HR 2.61, p = 0.032), smoking history (HR 3.59, p = 0.018), LOS Conclusions: Previous vertebral fractures and BI 2, TCCI ≥5, smoking history, LOS

Oxidative stress is defined as an imbalance between the pro-oxidant and antioxidant potential of cells leading to intracellular DNA damage. To clarify the oxidative stress response as a tumor marker, we investigated measurement of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in hepatobiliary diseases.Relationships between urinary 8-OHdG levels and clinicopathological factors were analyzed in 101 patients, including 84 with hepatobiliary malignancies, and 18 healthy volunteers. Co-existing biliary inflammation was detected in 8 patients.Urinary 8-OHdG levels did not correlate with any clinical or liver functional parameters. The existence of inflammation and any tumor-related factor did not correlate with urinary 8-OHdG levels either. Urinary 8-OHdG levels were significantly higher in patients with benign and malignant diseases than in healthy volunteers (p0.05), but not significantly different between benign and malignant diseases. Among patients with intrahepatic cholangiocarcinoma and gallbladder carcinoma, urinary 8-OHdG levels tended to be higher in patients with lymph node metastasis-positive than in those with lymph node-negative disease (p=0.057).The clinical significance of oxidative DNA damage and increases in its urinary metabolites in patients with hepatobiliary malignancies or inflammatory diseases remain unknown. Further studies are necessary to clarify the relationship between node metastasis and oxidative stress as a prognostic marker.

Background: The substantial risk of iron overload is not routinely monitored in most of the neonatal intensive care units (NICUs) in Japan; however, blood transfusion is an essential strategy for successfully treating preterm low-birth-weight infants. Objective: The aim of this study was to investigate the iron status and clinical features of infants with a birth weight of Methods: This prospective observational study enrolled 176 (82.6%) patients from a total of 213 VLBWIs admitted to our NICU from 2009 to 2014. Clinical information was collected including maternal records and infant morbidity and treatment. Management strategies including enteral iron supplementation, erythropoietin administration and blood transfusion were allowed according to the consensus in Japan. The hematological status was surveyed from birth to 12 postnatal weeks of age. The iron status was determined according to serum iron, unbound iron-binding capacity and serum ferritin. The definition of hyperferritinemia was set as a value of ≥500 ng/ml. Results: Twenty-four (13.6%) infants displayed hyperferritinemia. A multiple logistic analysis selected 3 associated factors of hyperferritinemia: surgical ligation for patent ductus arteriosus, sepsis and moderate or severe states of bronchopulmonary dysplasia. We also verified that the value of ferritin was significantly correlated with those of aspartate transaminase, creatine kinase and C-reactive protein according to a multilinear regression analysis. After excluding the ferritin data of these outliers, we did not observe any factors associated with hyperferritinemia. Conclusions: Hyperferritinemia might be associated with oxygen radical diseases and susceptibility to infection.

Background: We aimed to determine the predictive factors for excellent or extremely poor functional outcome in patients with first-ever atrial fibrillation (AF)-related cardioembolic stroke. Methods: Retrospective observational study from a database. Patients with AF-related cardioembolic stroke with a premorbid modified Rankin Scale (mRS) score of 0 or 1 and without a previous history of stroke were included. Results: Factors associated with excellent functional outcome (mRS scores of 0 or 1; n = 77; 30.4% of patients) included age >78 years (OR 0.31, 95% CI 0.15-0.61), male sex (OR 2.16, 95% CI 1.04-4.60), absence of hypertension (OR 0.46, 95% CI 0.22-0.94) and initial National Institutes of Health Stroke Scale (NIHSS) score of >9 (OR 0.08, 95% CI 0.03-0.16). Factors associated with extremely poor functional outcome (mRS scores of 5 or 6; n = 63; 24.9%) included age >78 years (OR 3.30, 95% CI 1.54-7.39), initial NIHSS score of >9 (OR 12.38, 95% CI 5.40-32.56), congestive heart failure (OR 4.82, 95% CI 2.00-12.19) and ischemic heart disease (OR 4.02, 95% CI 1.18-14.69). Conclusions: Predictive factors exist to delineate excellent and extremely poor functional outcomes after a first-time stroke associated with AF.

Atrial fibrillation (AF)-related cardioembolic stroke is a serious problem in the aging society. The present study examined the clinical characteristics and outcomes of AF-related cardioembolic stroke in patients aged ≥80 years.Between September 2011 and April 2014, consecutive patients with ischemic stroke and AF were retrospectively extracted from the multicenter database. Clinical characteristics were compared between patients aged ≥80 years and80 years. Multivariate cox proportional hazard models were used to estimate hazard ratios and 95% confidential intervals on 90-day mortality for age of ≥80 years.A total of 253 patients aged ≥80 years (87 men, 86.4 ± 5.0 years) and 196 patients aged80 years (134 men, 70.4 ± 7.1 years) were included. Patients aged ≥80 years were more frequently female, and more likely to have higher premorbid modified Rankin Scale score (mRS), lower body mass index, previous history of stroke, prior antiplatelet therapy, congestive heart failure, and persistent AF. Patients aged ≥80 years had higher initial National Institutes of Health Stroke Scale score and were more likely to have occlusion of the cervicocephalic arteries, but less likely to receive thrombolysis. Patients aged ≥80 years had a higher mRS and mortality after 3 months. Age of ≥80 years was a significant predictor of 90-day mortality after adjustment for sex (hazard ratio 2.20, 95% confidential interval 1.25-4.09), but was no longer significant after further adjustment for other clinical characteristics and stroke severity.In AF-related cardioembolic stroke, patients aged ≥80 years had different clinical characteristics and poorer outcome compared with patients aged80 years. Geriatr Gerontol Int 2017; 17: 708-713.

Posture control during a dual-task involves changing the distribution of attention resources between the cognitive and motor tasks and involves the frontal cortex working memory (WM). The present study aimed to better understand the impact of frontal lobe activity and WM capacity in postural control during a dual-task. High and low WM-span groups were compared using their reading span test scores. High and low WM capacity were compared based on cognitive and balance performance and hemoglobin oxygenation (oxyHb) levels during standing during single (S-S), standing during dual (S-D), one leg standing during single (O-S), and one leg standing during dual (O-D) tasks. For sway pass length, significant difference in only the O-D task was observed between both groups. oxyHb levels were markedly increased in the right dorsolateral prefrontal cortex and supplementary motor area in the high-span group during a dual-task. Therefore, WM capacity influenced the allocation of attentional resources and motor performance.

Magnetic resonance imaging (MRI) is often used to detect and treat neonatal cerebral disorders. However, neonatal MR image interpretation is limited by intra- and inter-observer variability. To reduce such variability, a template-based computer-aided diagnosis system is being developed, and several methods for creating templates were evaluated.Spatial normalization for each individual's MR images is used to accommodate the individual variation in brain shape. Because the conventional normalization uses as adult brain template, it can be difficult to analyze the neonatal brain, as there are large difference between the adult brain and the neonatal brain. This article investigates three approaches for defining a neonatal template for 1-week-old newborns for diagnosing neonatal cerebral disorders. The first approach uses an individual neonatal head as the template. The second approach applies skull stripping to the first approach, and the third approach produces a template by averaging brain MR images of 7 neonates. To validate the approaches, the normalization accuracy was evaluated using mutual information and anatomical landmarks.The experimental results of 7 neonates (revised age 5.6 ± 17.6 days) showed that normalization accuracy was significantly higher with the third approach than with the conventional adult template and the other two approaches (P 0.01).Three approaches to neonatal brain template matching for spinal normalization of MRI scans were applied, demonstrating that a population average gave the best results.

To evaluate the efficacy of the current clinical pathway for pulmonary resections.This study examined variances from expected clinical pathway outcomes for pulmonary resections performed between 2005 and 2009. Data on a total of 383 patients were retrospectively analyzed.The median length of hospital stay (LOS) using the clinical pathway was 12 days (range: 1-188 days); the mean LOS was 15.5 days. The cost per day with use of the clinical pathway was 102 726 yen. Poor control of pain from intercostal neuralgia was the most frequently observed variance from expected outcomes. It affected 119 of 168 electronic clinical pathway patients (70.8%). The clinical pathway was terminated in 3.9% of patients (15/383) due to serious or life-threatening complications.This study showed the single institutional experience of the clinical pathway for pulmonary resections. These findings indicate a need to revise certain aspects of the pathway, based on data from our analysis of variances.

The calcineurin inhibitors, tacrolimus and ciclosporin, are two useful immunosuppressive drugs for the treatment of myasthenia gravis (MG), for patients who have low responses to glucocorticoids. We have studied the suppressive potencies of tacrolimus and ciclosporin on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) obtained from 38 MG patients and 26 healthy volunteers. Differences in the IC50 values of the two calcineurin inhibitors between the patients and the healthy subjects were evaluated. The median (range) IC50 values for tacrolimus and ciclosporin on the blastogenesis of PBMCs of MG patients were 0.06 (0.001–100) and 0.41 (0.09–83.0) ng mL−1, respectively. In contrast, the median (range) IC50 values of tacrolimus and ciclosporin on healthy PBMCs were 0.16 (0.001–0.33) and 5.59 (1.4–31.3), respectively, and thus ciclosporin potencies against PBMCs of MG patients were significantly higher than those against PBMCs of healthy subjects (P < 0.0001). The differences in tacrolimus IC50 values between the patients and healthy subjects were not significant. There was a correlation between ciclosporin IC50 values against the blastogenesis of PBMCs of MG patients and the duration of the disease (r = 0.35, P = 0.049). A significant correlation between the IC50 values of ciclosporin and those of prednisolone against the blastogenesis of PBMCs of MG patients was also observed (r = 0.56, P = 0.003). Furthermore, the ciclosporin IC50 values significantly correlated with the periods of glucocorticoid administration for MG treatment (r = 0.42, P = 0.038). Such correlations were not observed with the tacrolimus IC50 values. These results suggested that glucocorticoid administration had an influence on PBMC response to the suppressive efficacy of ciclosporin in MG.

Background Pure dysarthria (PD) and dysarthria-facial paresis syndrome (DFP) mainly result from lenticulostriate artery territory infarction. PD and DFP are rare clinical entities, often grouped without distinction. The purpose of this study was to examine clinical and radiographic differences between PD and DFP due to unilateral internal capsule and/or corona radiata infarction. Methods Using a database that included consecutive patients with ischemic stroke admitted to the neurological stroke units of three hospitals within 7 days from onset between September 2011 and April 2014, we retrospectively extracted first-ever stroke patient data, who presented with PD or DFP with a single ischemic lesion localized in the internal capsule and/or corona radiata. Patients with weakness, ataxia, sensory deficit, or cortical symptoms were excluded. Ischemic lesion volume was calculated by the ABC/2 method on diffusion-weighted imaging (DWI). DWI images were normalized and superimposed to the template for PD and DFP. We compared patients' characteristics between PD and DFP. Results A total of 2126 patients, including 65 patients (3.1 %) with PD or DFP, were registered. Of these, 13 PD patients and 18 patients with DFP due to unilateral internal capsule and/or corona radiata infarction were included for analysis. Compared with DFP patients, PD patients had longer onset-to-door time (median 37.5 vs. 10.8 h, p = 0.031), shorter vertical length (C component) of ischemic lesions (median 12.0 vs. 18.8 mm, p = 0.007), and smaller ischemic lesion volume (median 285 vs. 828 mm3, p = 0.023). Ischemic lesions causing PD were located more frequently in the left hemisphere than DFP (92 % vs. 56 %, p = 0.045). The superimposed lesion pattern indicated that DFP had lesions more medial and involving posterior portions of the putamen and the caudate body, as well as more of the genu and posterior limb of the internal capsule, than PD. Ninety days after onset, symptoms disappeared in 21 (72 %) out of 29 patients. Conclusions In cerebral infarction limited to the internal capsule and/or corona radiata, PD is derived from smaller and left-sided lesions with delay in diagnosis compared with DFP. The clinical course of those with PD and DFP might be benign.

Self-agency is the recognition of one's own movement and plays a vital role in purposeful, voluntary movement. A sense of self-agency can be elicited in individuals who view their own simple finger movements as they are projected onto a screen and aligned with their actual hand position. Here, we examined whether individuals perceived self-agency when they viewed a video of a hand grasping a wooden cylinder and whether the perception of self-agency correlated with simultaneous changes in oxy-hemoglobin in the parietal or the prefrontal cortical areas. All participants reported the perception of self-agency, which was correlated with oxy-hemoglobin increases in the right prefrontal area. We conclude that self-agency also relates to hand-held objects displayed on video.

In 56 pediatric and adolescent patients (median age 7 years, range 1-21) with various solid tumors, peripheral blood stem cells (PBSC) were mobilized with granulocyte colony-stimulating factor (G-CSF) alone, and the yields of PBSC and engraftment kinetics following autologous peripheral blood stem cell transplantation (PBSCT) were evaluated retrospectively. Granulocyte colony-stimulating factor (10 microg/kg) was injected subcutaneously for mobilization when patients showed no influence of previous chemotherapy, and administration was continued for 5 days. The peaks of CD34+ cells and colony-forming units-granulocyte/macrophage in the blood were observed on days 4 through 6 of G-CSF administration in all patients. Peripheral blood stem cell harvest was commenced on day 5 of G-CSF treatment. Compared to the results in patients mobilized by chemotherapy plus G-CSF (N=18), the progenitor cell yields were lower in patients mobilized with G-CSF alone. However, there were no significant differences in WBC and ANC engraftment compared to the chemotherapy plus G-CSF mobilization group. Platelet recovery following autologous PBSCT was delayed in patients mobilized with G-CSF alone. The median time taken for ANC and platelet counts to reach 0.5 x 10(9) and 20 x 10(9)/l was 12 days (range: 9-28) and 15 days (8-55), respectively, in all patients who received PBSC mobilized by G-CSF alone. In summary, mobilization with G-CSF alone can mobilize sufficient CD34+ cells for successful autografting and sustained hematological reconstitution in pediatric and adolescent patients with solid tumors, and even in heavily pre-treated patients.

Autosomal dominant leukodystrophy is an extremely rare disease. Here we report on a dominantly inherited disease in a Japanese family with slowly progressive clinical course. Their symptoms and signs started in early childhood and very slowly progressed. In most patients spastic gait was the initial symptom. Neurological manifestations were characterized by pyramidal signs, ataxia, and mental deterioration. In addition to these neurological signs, the skeletal anomalies such as scoliosis and congenital hip dislocation were also present. MR images showed no abnormality in the early stage, but T2-weighted images revealed high intensity areas in the cerebral and cerebellar white matter, and the dentate nucleus in the advanced stage. Proton MR spectroscopy showed decrease of N-acetylaspartate/creatine ratio and increase of choline/creatine ratio in the advanced stage. Proton MR spectroscopy revealed normal N-acetylaspartate/creatine ratio and increase of choline/creatine ratio in the early stage. We suggested that these patients had abnormality in the white matter when MRI was still normal. We considered that intracranial demyelination was gradually progressed as the symptoms got aggravated.

Background Several rare neurologic complications of ulcerative colitis have been reported. Review summary We report a 69-year-old Japanese woman who developed bilateral sensorineural deafness, 2 attacks of bilateral ophthalmoplegia, and bilateral facial nerve palsy in association with ulcerative colitis. Laboratory data showed elevated cerebrospinal fluid (CSF) protein without pleocytosis, abnormal auditory brainstem evoked potentials, and multiple high signal lesions on magnetic resonance imaging of the brainstem and cerebral deep white matter. Her symptoms improved with corticosteroid therapy except for sensorineural deafness and an exacerbation of cerebral deep white matter lesions without any new clinical signs. Conclusion Immunologic mechanisms may have led to her central and peripheral nervous system findings in addition to her colon disorder.

The principles of echo-shifting with a train of observations (PRESTO) magnetic resonance (MR) imaging technique employs an MR sequence that sensitively detects susceptibility changes in the brain. The effectiveness of PRESTO MR imaging was examined for distinguishing between cerebellopontine angle (CPA) schwannomas and meningiomas in 24 patients with CPA tumors, 12 with vestibular schwannomas, and 12 with meningiomas. Histopathological study of surgical specimens showed that 11 of the 12 schwannomas contained hemosiderin deposits and all had microhemorrhages. One meningioma contained hemosiderin deposits and two involved microhemorrhages. Abnormal vessel proliferation, and dilated and thrombosed vessels were observed in all schwannomas and in 4 meningiomas. In addition to MR imaging with all basic sequences, PRESTO MR imaging and computed tomography were performed. PRESTO imaging showed significantly more schwannomas (n = 12) than meningiomas (n = 2) exhibited intratumoral spotty signal voids which were isointense to air in the mastoid air cells (p < 0.001). These spotty signal voids were significantly associated with histopathologically demonstrated hemosiderin deposits (p < 0.001), microhemorrhages (p < 0.01), and abnormal vessels (p < 0.04). The visualization of spotty signal voids on PRESTO images is useful to distinguish schwannomas from meningiomas.

Despite recent advances in surgical techniques, blood loss is an important factor associated with postoperative outcomes in pancreatectomy. It is useful to identify risk factors of increased blood loss.The clinical records of 161 patients who underwent an elective pancreatectomy for peripancreatic diseases between 1994 and March 2011 were retrospectively examined. Univariate and multivariate analysis of clinicopathological and surgical parameters influencing intraoperative blood loss were performed. We determined the cut-off value of the amount of blood loss based on the analyzed results.The mean and median blood loss was 1346±901 and 1070 mL, respectively. Red cell blood transfusion was performed in 72 patients (45%). Based on ROC analysis, the predictive value of blood loss in patients who received red cell blood transfusion was 880 mL (p0.001); however, blood loss was not significantly associated with postoperative complications (p = 0.40). The cut-off level of estimated amount of blood loss in the present study was set at 880 mL. Male patients, fatty pancreas, higher serum alkaline phosphatase level, longer operating time, performance of pancreaticoduodenectomy (PD) and combined resections of adjacent major vessels were associated with significantly more increased blood loss (p0.05). Based on multivariate analysis, longer operation time over 480 minutes and performance of PD were significantly associated with increased blood loss (p0.05).Attempting to reduce operating time in cases of PD is necessary to reduce intraoperative blood loss.

Extended thymectomy and high-dose alternate-day prednisolone administration may increase the chance of remission in myasthenia gravis (MG) patients. In cases of remission, ocular symptoms sometimes reappear after a gradual decrease or discontinuation of prednisolone administration. We compared relapsed patients with those who experienced complete remission. We found that the period from onset of MG to thymectomy and initiation of prednisolone administration was longer in the relapsed cases, which suggests that early thymectomy and administration of prednisolone can lead to a superior outcome in MG patients.

In a cohort of more than 500,000 individuals who experienced out-of-hospital cardiac arrest in Japan, Akihito Hagihara and colleagues studied whether administration of lactated Ringer's solution was associated with survival and functional outcomes., Background No studies have evaluated whether administering intravenous lactated Ringer's (LR) solution to patients with out-of-hospital cardiac arrest (OHCA) improves their outcomes, to our knowledge. Therefore, we examined the association between prehospital use of LR solution and patients' return of spontaneous circulation (ROSC), 1-month survival, and neurological or physical outcomes at 1 month after the event. Methods and Findings We conducted a prospective, non-randomized, observational study using national data of all patients with OHCA from 2005 through 2009 in Japan. We performed a propensity analysis and examined the association between prehospital use of LR solution and short- and long-term survival. The study patients were ≥18 years of age, had an OHCA before arrival of EMS personnel, were treated by EMS personnel, and were then transported to hospitals. A total of 531,854 patients with OHCA met the inclusion criteria. Among propensity-matched patients, compared with those who did not receive pre-hospital intravenous fluids, prehospital use of LR solution was associated with an increased likelihood of ROSC before hospital arrival (odds ratio [OR] adjusted for all covariates [95% CI] = 1.239 [1.146–1.339] [p, Editors' Summary Background Cardiac arrest, a condition in which the heart suddenly stops pumping, is caused by problems with the heart's internal electrical system, which controls the rate and rhythm of the heart contractions that pump blood around the body. If this electrical system malfunctions, an abnormal heartbeat or “arrhythmia” develops that, in some cases, causes cardiac arrest. Because blood is no longer being pumped around the body, the organs and tissues of the body do not receive the oxygen they need to function. Consciousness is lost immediately and, if medical attention is not provided quickly, death follows within a few minutes—about 95% of people who have a cardiac arrest die before they reach hospital or emergency medical help. Moreover, survivors of cardiac arrest are often left with permanent damage to the brain and other organs. Early cardiopulmonary resuscitation (CPR; chest compression to pump the heart and mouth-to-mouth resuscitation to inflate the lungs) and early defibrillation (delivery of an electric shock to the heart to restore its normal rhythm) reduce the risk of death and permanent organ damage after cardiac arrest. Why Was This Study Done? Another procedure that is sometimes used during pre-hospital resuscitation of cardiac arrest cases is intravenous fluid administration—delivering liquid into a vein through an intravenous needle. A solution that is often used for this purpose is lactated Ringer's (LR) solution, a mixture of inorganic salts and sodium lactate. However, the effects of intravenous LR solution on the outcomes of patients who have an out-of-hospital cardiac arrest have not been studied. In this prospective cohort analysis, the researchers examine the association between the pre-hospital use of LR solution and the return of spontaneous circulation, one-month survival, and neurological and physical outcomes at one month after cardiac arrest among patients in Japan who have had an out-of-hospital cardiac arrest. A prospective cohort analysis identifies a group of patients with a specific condition and examines how they subsequently fare. What Did the Researchers Do and Find? In Japan, the Fire and Disaster Management Agency records all out-of-hospital cardiac arrest cases in a nationwide database. The researchers used this database to identify more than half a million out-of-hospital cardiac arrest cases that occurred in Japan between 2005 and 2009. To examine the association between pre-hospital use of LR solution and short- and long-term survival, the researchers used a statistical technique called propensity analysis. This technique is used in observational studies to control for confounding—unknown differences between people who receive an intervention and those who do not receive an intervention that might affect outcomes and thus make it hard to draw conclusions about the intervention's true effects. By examining a large number of variables (for example, age, sex, and time taken for help to arrive), the researchers gave every patient a propensity score that indicated their probability of receiving pre-hospital LR solution, and then used this score to match each patient who received LR solution with a similar patient who did not receive LR solution. Among propensity-matched patients, pre-hospital use of LR solution was associated with a slightly increased chance of return of spontaneous circulation before arrival at a hospital and with a decreased chance of 1-month survival with minimal neurological or physical impairment. Among the whole cohort, pre-hospital use of LR solution was not associated with overall one-month survival. What Do These Findings Mean? These findings suggest that, among Japanese patients with out-of-hospital cardiac arrest, pre-hospital use of LR solution was associated with less chance of good functional outcomes at one month. However, the present study has several limitations. For example, data on in-hospital treatment following out-of-hospital cardiac arrest were not available, so the outcome differences between patients receiving and not receiving LR solution potentially could reflect differences in their in-hospital treatment. Moreover, although the researchers undertook a propensity analysis, this study, like all observational studies, can only partly control for selection bias and confounding factors. Thus, the observed associations between LR solution use and short- and long-term outcomes may actually reflect the effects of some unknown characteristic shared by the patients who received LR solution. Because of these and other limitations, it is essential that the findings of this study are verified before recommendations about the pre-hospital use of LR solution in patients with out-of-hospital cardiac arrest are made. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001394. The US National Heart Lung and Blood Institute provides information on sudden cardiac arrest and on heart arrhythmias The American Heart Association also information in several languages on sudden cardiac death and on arrhythmias; a selection of personal stories about arrhythmia and cardiac arrest is also available The not-for-profit Sudden Cardiac Arrest Foundation provides information on all aspects of cardiac arrest, including survivor stories MedlinePlus provides links to other resources about cardiac arrest (in English and Spanish)

Epinephrine is widely used in cardiopulmonary resuscitation for out-of-hospital cardiac arrest (OHCA). However, the effectiveness of epinephrine use before hospital arrival has not been established.To evaluate the association between epinephrine use before hospital arrival and short- and long-term mortality in patients with cardiac arrest.Prospective, nonrandomized, observational propensity analysis of data from 417 188 OHCAs occurring in 2005-2008 in Japan in which patients aged 18 years or older had an OHCA before arrival of emergency medical service (EMS) personnel, were treated by EMS personnel, and were transported to the hospital.Return of spontaneous circulation before hospital arrival, survival at 1 month after cardiac arrest, survival with good or moderate cerebral performance (Cerebral Performance Category [CPC] 1 or 2), and survival with no, mild, or moderate neurological disability (Overall Performance Category [OPC] 1 or 2).Return of spontaneous circulation before hospital arrival was observed in 2786 of 15,030 patients (18.5%) in the epinephrine group and 23,042 of 402,158 patients (5.7%) in the no-epinephrine group (P.001); it was observed in 2446 (18.3%) and 1400 (10.5%) of 13,401 propensity-matched patients, respectively (P.001). In the total sample, the numbers of patients with 1-month survival and survival with CPC 1 or 2 and OPC 1 or 2, respectively, were 805 (5.4%), 205 (1.4%), and 211 (1.4%) with epinephrine and 18,906 (4.7%), 8903 (2.2%), and 8831 (2.2%) without epinephrine (all P.001). Corresponding numbers in propensity-matched patients were 687 (5.1%), 173 (1.3%), and 178 (1.3%) with epinephrine and 944 (7.0%), 413 (3.1%), and 410 (3.1%) without epinephrine (all P.001). In all patients, a positive association was observed between prehospital epinephrine and return of spontaneous circulation before hospital arrival (adjusted odds ratio [OR], 2.36; 95% CI, 2.22-2.50; P.001). In propensity-matched patients, a positive association was also observed (adjusted OR, 2.51; 95% CI, 2.24-2.80; P.001). In contrast, among all patients, negative associations were observed between prehospital epinephrine and long-term outcome measures (adjusted ORs: 1-month survival, 0.46 [95% CI, 0.42-0.51]; CPC 1-2, 0.31 [95% CI, 0.26-0.36]; and OPC 1-2, 0.32 [95% CI, 0.27-0.38]; all P.001). Similar negative associations were observed among propensity-matched patients (adjusted ORs: 1-month survival, 0.54 [95% CI, 0.43-0.68]; CPC 1-2, 0.21 [95% CI, 0.10-0.44]; and OPC 1-2, 0.23 [95% CI, 0.11-0.45]; all P.001).Among patients with OHCA in Japan, use of prehospital epinephrine was significantly associated with increased chance of return of spontaneous circulation before hospital arrival but decreased chance of survival and good functional outcomes 1 month after the event.

To clarify perioperative factors associated with poor survival following hepatectomy.Clinical parameters and stress score, including surgical stress score (SSS) and comprehensive risk score (CRS) were examined from 183 hepatocellular carcinoma patients who underwent hepatectomy.Factors associated with tumor relapse were increased blood loss/weight, uncontrolled ascites and grade B liver damage (p0.05). Ascites was identified as an independent risk factor by multivariate logistic regression analysis. Increased blood loss/weight, transfusion, high SSS, high CRS, ascites, and grade B liver damage were associated with poor disease-free survival (p0.05). Increased blood loss/weight, transfusion, ascites, and grade B liver damage were associated with poor overall survival (p0.05), and ascites, transfusion, male sex and grade B liver damage were identified as independent risk factors.Reducing blood loss and avoiding transfusion appear important for improving prognosis. Maintenance of liver function is necessary in cases showing poor liver function and uncontrolled ascites.

A 2.5-year-old girl died suddenly during the course of rotavirus gastroenteritis. The autopsy showed encephalopathy with rotavirus systemic infection. Here, we provide evidence of rotavirus replication in multiple organs. Our findings clarify that rotavirus infection in children can extend beyond the intestinal tract through viremia.

Despite recent advances in surgical techniques, blood loss can still determine the postoperative outcome of hepatectomy. Thus, the preoperative identification of risk factors predicting increased blood loss is important.We studied retrospectively the clinical records of 482 patients who underwent elective hepatectomy for liver disease, and analyzed the clinicopathological and surgical parameters influencing intraoperative blood loss.Red cell transfusion was required for 165 patients (35 %). Based on blood transfusion requirement and hepatic failure, we estimated predictive cut-off values at 850 and 1500 ml. The factors found to be significantly associated with increased blood loss were as follows: male gender, obstructive jaundice, non-metastatic liver carcinoma, Child-Pugh B disease, decreased uptake ratio on liver scintigraphy, platelet count, or prothrombin activity, longer hepatic transection time, operating time, the surgeon's technique, J-shape or median incision, major hepatectomy, and not using hemostatic devices (p0.05). Multivariate analysis identified male gender, low prothrombin activity, longer transection time, longer operation time, and not using hemostatic devices as factors independently associated with increased blood loss (p0.05).Male gender and low prothrombin activity represent risk factors for increased blood loss during hepatectomy. Moreover, every effort should be made to reduce the transection and operating times using the latest hemostatic devices.

Deceased donor liver transplantation has been an established surgical procedure since the 1960s. More recently, the technique of living donor liver transplantation (LDLT) was introduced, and it is being performed with increasing frequency. However, there is a paucity of information on the clinical outcomes of donor patients. In this study, which was conducted at a single university hospital, the relationship between potentially relevant factors (eg, patient characteristics, preoperative status, and operation characteristics) and postoperative developments in donor patients was examined. We used electronic critical pathways, which are charts of medical process that include favorable states (defined as outcomes) to be achieved during the hospital stay of a patient; predefined outcomes that are not achieved are recorded as variances. With the electronic critical pathway system, objective data about the conditions of patients and relevant clinical processes could be collected readily. Using data from the electronic critical pathways for LDLT donor patients and applying multiple logistic regression analysis, we examined factors that were related to the variance of each outcome measure for postoperative developments. Among the various donor characteristics, the duration of the operation was related to variance in 5 types of health outcomes, age and blood loss volume were related to variance in 2 types of health outcomes, and other characteristics (ie, sex, body surface area, operation urgency, and volume ratio of the remnant liver) were related to variance in 1 type of health outcome. In conclusion, the findings in this study may facilitate improvements in the postoperative status of LDLT donor patients. Further studies that incorporate analogous data from other medical facilities are necessary to verify these findings.

To evaluate the effectiveness of radiofrequency ablation (RFA) for liver metastases of colorectal cancer.RFA was used to treat 31 tumors (median diameter 1.5 cm, range 0.5-3.9 cm) in 13 patients of liver metastases of colorectal cancer. The median number of tumors treated per patient was 2. 9 (range, 1-10).Two patients had complications; bleeding and liver dysfunction. Four (12.9%) of 31 lesions developed a local recurrence after the treatment. We achieved a local control in 2 (92.6%) of 27 lesions3.0 cm in diameter. In 4 (30.8%) of 13 patients, new metastases were observed at follow-up. One year survival rate from the initial ablation was 92.3% and 2-year was 46.2%. One year total local recurrence rate from the initial ablation was 55.6%.In the case of tumor greater than 3 cm, RF ablation is an effective method to treat hepatic metastases from colorectal carcinoma.

We report 4 cases of myasthenia gravis in which myasthenic symptoms developed after a thymoma was known to be present. They include 3 invasive thymomas and one thymoma. In 3 of them, myasthenic symptoms developed 2-7 months after removal of the thymoma; in 1 case, myasthenic symptoms developed 11 years after the thymoma was known to be present. We also discuss here the possible pathogenetic mechanism of post-thymomectomic myasthenia gravis, and propose that it is due to the natural course of the disease.

We describe a rare case of autoimmune polyglandular syndrome type 2 initially presenting as Addison disease and autoimmune thyroid disease, with subsequent development of autoimmune hepatitis and myasthenia gravis (MG) crisis in a Japanese woman. MG improved with oral prednisolone followed by plasmapheresis for immunoadsorption; thymectomy was not performed. Conventional treatment for MG was effective and safe in this case, in which there was positivity for human leukocyte antigen A23, B52, B62, DR11, and DR15.

We report on the case of a 32-year-old woman with tuberculous meningitis (TBM) with electroencephalogram (EEG) output displaying triphasic waves (TWs). The EEG on day 8 revealed generalized slowing, frontal bilateral TWs, a background of 2 Hz delta waves, and no epileptiform activity. The patient's condition improved slowly with antituberculosis chemotherapy treatment. A follow-up EEG on day 34 showed marked improvement, with no TWs, background activity improved to a 12 Hz symmetric alpha wave pattern, and no epileptiform activity, as before. To our knowledge, this is the first report of TWs observed in a TBM case.

The clinical features of familial Creutzfeldt-Jakob disease with a codon 200 point mutation [fCJD (E200K)] are similar to those of sporadic CJD (sCJD). MRI diffusion-weighted imaging (MRI-DWI) has been reported to be useful for the early diagnosis of CJD. We describe a Japanese fCJD (E200K) case in which thalamic symptoms were the initial manifestations. On admission, electroencephalography (ECG) showed no periodic synchronous discharge (PSD), and MRI showed no abnormalities. However, single photon emission computed tomography (SPECT) using (99m)Tc-ethyl cysteinate dimer ((99m)Tc-ECD) revealed hypoperfusion in the right thalamus. We conclude that the thalamic form of CJD tends to show no high-intensity area (HIA) by MRI-DWI, and that SPECT may be more useful for visualizing the affected area responsible for the thalamic symptoms at an early stage.

Recent reports have discussed the many causes of dropped head syndrome and bent spine syndrome. We described a case of myasthenia gravis with concomitant severe degeneration of spinal muscle, mitochondrial DNA4977 deletion and sensorineural deafness. These associations were thought to be independent, however this is an important case to consider the etiology of bent spine syndrome.

Background: The most common treatment of myasthenia gravis is high-dose prednisolone administration and thymectomy. A well-known adverse effect of prednisolone is hyperglycemia, however, to date there is no such detailed report. Patients and Methods: We treated 325 myasthenia gravis patients in a recent 35 years period, and found 11 patients with diabetes mellitus. We compared these 11 diabetic patients with previously-reported cases. Results: These 11 patients did not have any antibody against β-cells in the pancreas such as anti-glutamic acid decarboxylase antibody. In 10 of 11 patients diabetes mellitus was controlled with oral medications. Conclusion: Myasthenic patients with diabetes mellitus could be classified into 2 groups, one group with positive organ-specific autoantibodies to many organs (with type 1 diabetes mellitus), and the other group with diabetes mellitus onset during prednisolone administration (with type 2 diabetes mellitus).

Tacrolimus hydrate (FK506) reduces the symptoms of myasthenia gravis (MG) due to its immunosuppressive properties. A drug efflux pump P-glycoprotein (P-gp) actively transports FK506 out of target cells, thereby reducing their efficacy. We investigated the influence of FK506 therapy on the P-gp function of peripheral-blood mononuclear cells (PBMCs) in MG patients. Six MG patients treated with FK506 (MG(FK+)), four MG patients treated without FK506 administration (MG(FK-)), and 18 healthy subjects were included in this study. P-gp function was estimated by transporter activity that was inferred from a decrease in fluorescent P-gp substrate Rhodamine 123 (Rh123) and its inhibition by cyclosporine A (CsA). The P-gp efflux function in MG (FK+) patients assessed by the Kolmogorov-Smirnov (KS) statistic D was lower than in the healthy subjects (p=0.0084). However, PBMC sensitivity to FK506 in MG (FK+) patients was significantly higher compared to that of the healthy subjects (p=0.02). There was a significant correlation between the Rh123 efflux activity and PBMC sensitivity to FK506 in vitro (p=0.011). The data raise the possibility that FK506 treatment attenuated P-gp function in the PBMCs of the MG patients.

Objectives: To determine the use of the mucin proteins MUC5B and MUC5AC as prognosis markers for non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) mutations. Setting: Patients who underwent surgical resection at Nagasaki University Hospital and related facilities in Japan between June 1996 and March 2013. Participant: 159 Japanese patients (male: n=103; female: n=56) with NSCLC, who underwent surgical resection (EGFR-mutant type: n=78, EGFR wild type: n=81). Results: Patients whose tumours expressed MUC5B had significantly longer overall survival and relapse-free survival compared to the MUC5B-negative patients with EGFR mutant NSCLC (p=0.0098 and p=0.0187, respectively). In patients with EGFR wild-type NSCLC, there was no association with MUC5B expression. MUC5AC expression was not different between EGFR mutant and wild-type NSCLC. Conclusions: Present findings indicate that MUC5B, but not MUC5AC, is a novel prognostic biomarker for patients with NSCLC carrying EGFR mutations but not for patients with NSCLC carrying wild-type EGFR., BMJ Open, 5(7), e008366; 2015

We have evaluated a flow cytometric method that allows assessment of micronucleated reticulocytes (MN-RETs) in microliter quantities of peripheral blood and compared results using this assay with those of established microscopic methods of scoring bone marrow and peripheral blood from rats treated with well-characterized genotoxic agents. Young reticulocytes (RETs) are labeled with FITC-anti-CD71 (transferrin receptor) and micronuclei with propidium iodide (with RNase treatment). Red blood cells parasitized with Plasmodia serve as a calibration standard for DNA content. Microscopic scoring used acridine orange (AO) staining of methanol-fixed slides or supravital AO staining. The effect of the rat spleen on the parameters evaluated was determined by comparing age- and sex-matched normal and splenectomized rats treated with cyclophosphamide, cis-platin, or vinblastine under treatment conditions that established a steady-state frequency of MN-RETs in the bone marrow and peripheral blood compartments. The data demonstrate the sensitivity and reproducibility of the flow cytometric assay in the Sprague-Dawley rat, and comparative studies using identical blinded samples at multiple laboratories show that inter- and intra-laboratory reproducibility is much higher with the flow method than with the microscopic methods currently employed for regulatory studies. A significant effect of splenic selection against genotoxicant-induced MN-RETs was observed with each of the three scoring methodologies, despite the fact that the flow and supravital AO techniques restrict analysis to the youngest fraction of RETs. The high precision of flow-based measurements also demonstrated a slight but statistically significant level of selection against spontaneously arising MN-RET. Despite these spleen effects, assay sensitivity for blood-based analyses was maintained by the flow method as it was shown to have superior counting statistics, lower variability, and higher sensitivity than manual scoring. The data suggest that flow cytometric assessment of micronucleus induction can be integrated into routine toxicity testing, eliminating the need for a separate bioassay.

Autoimmune diseases are frequently associated with malignant tumor. In addition, prolonged immunosuppression may favor the development of malignancy. While the coincidence of myasthenia gravis and extrathymic tumor has been reported, the risk and features of these tumors are not well understood.We treated 305 patients with myasthenia gravis from 1968-2003, including 48 thymoma cases. Two hundred twenty-nine patients had undergone thymectomy and 76 had not. We examined cancer risk, tumor characteristics, and associations to medications. We encountered 9 cases of extrathymic tumor. Cancer risk in the thymoma cases was 6.3% and 2.3% in the nonthymoma cases, a statistically insignificant difference. Azathioprine was administered to only 14 in this series of patients; however, 2 patients developed cancer.Cancer risk in patients with myasthenia gravis is 2.6%, similar to that of the general population in Japan. We neurologists need to be aware that prolonged immunosuppression may favor the development of malignancy.