Atrial electrical remodeling and function after transcatheter aortic valve replacement in patients with aortic stenosis.

To examine reverse atrial electrical remodeling in patients with aortic stenosis (AS) after trans-catheter aortic valve replacement (TAVR). In 65 consecutive patients with severe AS (83 ± 4 years, 47 (72.3%) females), we analyzed ECG records for the P wave duration (PWD) in lead II and P-terminal force (PTFV1) in V1, and measured cardiac dimensions and function by echocardiography (ECHO) following TAVR. Biomarkers were measured to assess myocardial injury by TAVR. TAVR was successfully performed without major complications: the aortic valve area increased from 0.62 ± 0.14 cm2 to 1.52 ± 0.24cm2, and the trans-aortic pressure gradient decreased from 58.4 ± 15.9 mmHg to 15.0 ± 19.6 mmHg. PWD and PTFV increased immediately after TAVR and returned to the pre-TAVR levels on the next day. Then, the PWD declined toward 6 months after TAVR non-significantly in all patients, but significantly in 25 patients with baseline PWD ≥ 130 ms (P = 0.039). PTFV1 showed no long-term change. Improvement was observed in the ejection fraction, all thickness of the left ventricle and in the left atrial dimensions on ECHO. After recovery from transient aggravation by TAVR procedure, PWD reversed slowly, and the change was significant in those with baseline PWD ≥ 130 ms while change in PTFV1 was not significant at 6 months of follow-up. ECHO showed a reversal of remodeling in the left ventricle and in the left atrial dimension after TAVR.

Long-Term Outcomes of Breast Cancer Patients with Local Recurrence After Mastectomy Undergoing Immediate Breast Reconstruction: A Retrospective Multi-institutional Study of 4153 Cases.

BACKGROUND: The number of breast cancer patients in Japan undergoing immediate breast reconstruction (IBR) has increased and the postoperative follow-up period has been extended. This study was conducted to clarify the clinical aspects of, and factors associated with, local recurrence (LR) after IBR. METHODS: This was a multicenter study which included 4153 early breast cancer patients who underwent IBR. Clinicopathological characteristics were examined and factors potentially contributing to LR were analyzed. Risk factors for LR were examined separately for non-invasive and invasive breast cancers. RESULTS: The median follow-up period was 75 months. The 7-year LR rates were 2.1% and 4.3% for non-invasive and invasive cancers, respectively (p < 0.001). The proportions of LR detected by palpation, subjective symptoms, and ultrasonography were 40.0%, 27.3%, and 25.9%, respectively. Overall, 75.7% of LR were solitary, and 92.7% of these cases had no further recurrences during the observational period. Multivariate analysis of LR for invasive cancer showed that skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), the presence of lymphovascular invasion, cancer at the surgical margin, and not receiving radiation therapy were factors related to LR. The 7-year overall survival rates of the patients with LR and non-LR of invasive cancers were 92.5% and 97.3%, respectively, (p = 0.002). CONCLUSIONS: The rate of LR after IBR was acceptably low and IBR can thus be performed safely for early breast cancer patients. Invasive cancer, SSM/NSM, lymphovascular invasion, and/or cancer at the surgical margin should prompt awareness of the possibility of LR.

Brain TDP-43 pathology in corticobasal degeneration: Topographical correlation with neuronal loss.

AIMS: Neuronal and glial inclusions comprising transactive response DNA-binding protein of 43 kDa (TDP-43) have been identified in the brains of patients with corticobasal degeneration (CBD), and a possible correlation between the presence of these inclusions and clinical phenotypes has been speculated. However, the significance of TDP-43 pathology in the pathomechanism of CBD has remained unclear. Here, we investigated the topographical relationship between TDP-43 inclusions and neuronal loss in CBD. METHODS: We estimated semi-quantitatively neuronal loss and TDP-43 pathology in the form of neuronal cytoplasmic inclusions (NCIs), astrocytic inclusions (AIs), oligodendroglial cytoplasmic inclusions (GCIs), and dystrophic neurites in 22 CNS regions in 10 patients with CBD. Then, the degree of correlation between the severity of neuronal loss and the quantity of each type of TDP-43 inclusion was assessed. We also investigated tau pathology in a similar manner. RESULTS: TDP-43 pathology was evident in nine patients. The putamen and globus pallidus were the regions most frequently affected (80%). NCIs were the most prominent form, and their quantity was significantly correlated with the severity of neuronal loss in more than half of the regions examined. The quantities of TDP-43 NCIs and tau NCIs were correlated in only a few regions. The number of regions where the quantities of TDP-43 AIs and GCIs were correlated with the severity of neuronal loss was apparently small in comparison with that of NCIs. CONCLUSIONS: TDP-43 alterations in neurons, not closely associated with tau pathology, may be involved in the pathomechanism underlying neuronal loss in CBD. There was a significant topographical correlation between neuronal cytoplasmic aggregation of TDP-43 and neuronal loss in CBD, suggesting that TDP-43 protein aberration might be associated with neuronal degeneration in CBD. There was no close correlation between the burden of TDP-43 and that of tau in neurons.

A retrospective 5-year survival analysis of surgically resected gastric cancer cases from the Japanese Gastric Cancer Association nationwide registry (2001-2013).

BACKGROUND: The nationwide registry of the Japanese Gastric Cancer Association collected data of surgically resected cases of gastric cancer between 2001 and 2013. These retrospective analyses aimed to delineate tumor characteristics, surgical history, and survival distribution. METHODS: Data from 254,706 patients with primary gastric cancer were included. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The number of patients over 70 years old increased from 2001 to 2013. The frequency with which laparoscopic gastrectomy was opted for increased dramatically (from 3.5 to 40.8%) in 13 years. We focused on the patients registered between 2010 and 2013, for whom data collection was based on the 3rd edition of the Japanese classification and guidelines. Five-year overall survival (OS) rate among 92,305 patients with resected tumors was 70.6%. The 5-year OS rates of patients with pathological stage IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV disease were 89.6%, 83.2%, 77.6%, 68.1%, 59.3%, 45.6%, 29.9%, and 14.0%, respectively. CONCLUSION: Our detailed analysis highlights the historical changes in outcomes of surgically treated gastric malignancies in Japan, and provides robust dataset for future analysis.

γ-Secretase Activity Is Associated with Braak Senile Plaque Stages.

Amyloid ß-proteins (Aßs) Aß1-42 and Aß1-43 are converted via two product lines of γ-secretase to Aß1-38 and Aß1-40. This parallel stepwise processing model of γ-secretase predicts that Aß1-42 and Aß1-43, and Aß1-38 and Aß1-40 are proportional to each other, respectively. To obtain further insight into the mechanisms of parenchymal Aß deposition, these four Aß species were quantified in insoluble fractions of human brains (Brodmann areas 9 to 11) at various Braak senile plaque (SP) stages, using specific enzyme-linked immunosorbent assays. With advancing SP stages, the amounts of deposited Aß1-43 in the brain increased proportionally to those of Aß1-42. Similarly, the amounts of deposited Aß1-38 correlated with those of Aß1-40. Surprisingly, the ratios of deposited Aß1-38/Aß1-42 and Aß1-40/Aß1-43 were proportional and discriminated the Braak SP stages accurately. This result indicates that the generation of Aß1-38 and Aß1-40 decreased and the generation of Aß1-42 and Aß1-43 increased with advancing SP stages. Thus, Aßs deposition might depend on γ-secretase activity, as it does in the cerebrospinal fluid. Here, the extracted γ-secretase from Alzheimer disease brains generates an amount of Aß1-42 and Aß1-43 compared with cognitively normal brains. This refractory γ-secretase localized in detergent-solubilized fractions from brain cortices. But activity modulated γ-secretase, which decreases Aß1-42 and Aß1-43 in the cerebrospinal fluid, localized in detergent-insoluble fractions. These drastic alterations reflect Aß situation in Alzheimer disease brains.

Amyotrophic Lateral Sclerosis with Pallidonigroluysian Degeneration: A Clinicopathological Study.

OBJECTIVE: The pallidonigroluysian (PNL) system, the primary component of corticosubcortical circuits, is generally spared in amyotrophic lateral sclerosis (ALS). We evaluated the clinicopathological features of an unusual form of ALS with PNL degeneration (PNLD) and assessed whether ALS with PNLD represents a distinct ALS subtype. METHODS: From a cohort of 97 autopsied cases of sporadic ALS with phosphorylated 43kDa TAR DNA-binding protein (TDP-43) inclusions, we selected those with PNLD and analyzed their clinicopathological features. RESULTS: Eleven cases (11%) that showed PNLD were divided into 2 subtypes depending on the lesion distribution: (1) extensive type (n = 6), showing widespread TDP-43 pathology and multisystem degeneration, both involving the PNL system; and (2) limited type (n = 5), showing selective PNL and motor system involvement, thus being unclassifiable in terms of Brettschneider's staging or Nishihira's typing of ALS. The limited type showed a younger age at onset and predominant PNLD that accounted for the early development of extrapyramidal signs. The limited type exhibited the heaviest pathology in the subthalamus and external globus pallidus, suggesting that TDP-43 inclusions propagated via indirect or hyperdirect pathways, unlike ALS without PNLD, where the direct pathway is considered to convey TDP-43 aggregates from the cerebral cortex to the substantia nigra. INTERPRETATION: The PNL system can be involved in the disease process of ALS, either nonselectively as part of multisystem degeneration, or selectively. ALS with selective involvement of the PNL and motor systems exhibits unique clinicopathological features and TDP-43 propagation routes, thus representing a distinct subtype of ALS. ANN NEUROL 2020;87:302-312.

Novel electrocardiographic criteria for short QT syndrome in children and adolescents.

AIMS: Although shortening of the corrected QT interval (QTc) is a key finding in the diagnosis of short QT syndrome (SQTS), there may be overlap of the QTc between SQTS patients and normal subjects in childhood and adolescence. We aimed to investigate electrocardiographic findings for differentiation of SQTS patients. METHODS AND RESULTS: The SQTS group comprised 34 SQTS patients <20 years old, including 9 from our institutions and 25 from previous reports. The control group comprised 61 apparently healthy subjects with an QTc of <360 ms who were selected from 13 314 participants in a school-based screening programme. We compared electrocardiographic findings, including QT and Jpoint-Tpeak intervals (QT and J-Tpeak, respectively), those corrected by using the Bazett's and Fridericia's formulae (cB and cF, respectively) and early repolarization (ER) between the groups. QT, QTc by using Bazett's formula (QTcB), QTc by using Fridericia's formula (QTcF), J-Tpeak, J-Tpeak cB, and J-Tpeak cF were significantly shorter in the SQTS group than in the control group. On receiver operating characteristic curve analysis, the area under the curve (AUC) was largest for QTcB (0.888) among QT, QTcB, and QTcF, with a cut-off value of 316 ms (sensitivity: 79.4% and specificity: 96.7%). The AUC was largest for J-Tpeak cB (0.848) among J-Tpeak, J-Tpeak cB, and J-Tpeak cF, with a cut-off value of 181 ms (sensitivity: 80.8% and specificity: 91.8%). Early repolarization was found more frequently in the SQTS group than in the control group (67% vs. 23%, P = 0.001). CONCLUSION: A QTcB <316 ms, J-Tpeak cB < 181 ms, and the presence of ER may indicate SQTS patients in childhood and adolescence.

Surgically treated gastric cancer in Japan: 2011 annual report of the national clinical database gastric cancer registry.

BACKGROUND: The National Clinical Database (NCD) nationwide registry program of gastric cancer started in 2018. The purpose of this study was to report the treatment results of the NCD registry in the form of treatment results of the real world in Japan. METHODS: Patients' characteristics, tumor features, treatments, and outcomes were collected using a web-based data entry system. We analyzed the initial NCD database for data on surgically treated gastric cancer patients in 2011. RESULTS: A total of 30,257 patients with malignant gastric tumors were enrolled by the NCD registry program from 501 hospitals in all 47 prefectures. Of these, the status of data entry was not approved in 8.8% of the registered data, and follow-up information was missing in 1.2% of the approved cases. Excluding 1777 cases, which were not resected for primary gastric cancer, 25,306 resected cases included 44.4% of stomach surgeries recorded in the NCD. The 5 year survival rate of the resected cases was 71.3% and the operative mortality rate was 0.41%. The stage-specific 5 year survival rates were as follows: 89.6% for stage IA, 83.8% for stage IB, 77.3% for stage IIA, 69.1% for stage IIB, 58.7% for stage IIIA, 44.1% for stage IIIB, 30.1% for stage IIIC, and 13.4% for stage IV. CONCLUSIONS: The NCD gastric cancer registry program demonstrated validity for database construction. The gastric cancer registry is expected to become a nationwide registry with the dissemination of data entry system and method in the NCD.

Accuracy of Japanese claims data in identifying diabetes-related complications.

PURPOSE: To evaluate the accuracy of various claims-based definitions of diabetes-related complications (coronary artery disease [CAD], heart failure, cerebrovascular disease and dialysis). METHODS: We evaluated data on 1379 inpatients who received care at the Niigata University Medical & Dental Hospital in September 2018. Manual electronic medical chart reviews were conducted for all patients with regard to diabetes-related complications and were used as the gold standard. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each claims-based definition associated with diabetes-related complications based on Diagnosis Procedure Combination (DPC), International Classification of Diseases, Tenth Revision (ICD-10) codes, procedure codes and medication codes were calculated. RESULTS: DPC-based definitions had higher sensitivity, specificity, and PPV than ICD-10 code definitions for CAD and cerebrovascular disease, with sensitivity of 0.963-1.000 and 0.905-0.952, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. Sensitivity, specificity, and PPV were high using procedure codes for CAD and dialysis, with sensitivity of 0.963 and 1.000, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. DPC and/or ICD-10 codes + medication were better for heart failure than the ICD-10 code definition, with sensitivity of 0.933, specificity of 1.000, and PPV of 1.000. The PPVs were lower than 60% for all diabetes-related complications using ICD-10 codes only. CONCLUSION: The DPC-based definitions for CAD and cerebrovascular disease, procedure codes for CAD and dialysis, and DPC or ICD-10 codes with medication codes for heart failure could accurately identify these diabetes-related complications from claims databases.

Determinant Factors on Differences in Survival for Gastric Cancer Between the United States and Japan Using Nationwide Databases.

BACKGROUND: Although the incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. An international study reported higher survival in Korea and Japan than other countries, including the United States. We examined the determinant factors of the high survival in Japan compared with the United States. METHODS: We analysed data on 78,648 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007 and compared them with 16,722 cases from the Surveillance, Epidemiology, and End Results Program (SEER), a United States population-based cancer registry data from 2004-2010. We estimated 5-year relative survival and applied a multivariate excess hazard model to compare the two countries, considering the effect of number of lymph nodes (LNs) examined. RESULTS: Five-year relative survival in Japan was 81.0%, compared with 45.0% in the United States. After controlling for confounding factors, we still observed significantly higher survival in Japan. Among N2 patients, a higher number of LNs examined showed better survival in both countries. Among N3 patients, the relationship between number of LNs examined and differences in survival between the two countries disappeared. CONCLUSION: Although the wide differences in GC survival between Japan and United States can be largely explained by differences in the stage at diagnosis, the number of LNs examined may also help to explain the gaps between two countries, which is related to stage migration.

P-wave indices in Japanese patients with ischemic stroke: Implication of atrial myopathy in subtype of ischemic stroke.

BACKGROUND: P-wave indices have been not fully studied in subtypes of ischemic stroke. We compared P-wave indices among embolic stroke, lacunar stroke and the control. METHODS: P-wave duration, advanced interatrial block (aIAB) defined as P-wave duration ≥120 ms and biphasic (positive negative) morphology in inferior leads, and P-terminal force in lead V1 (PTFV1) were measured at the time of the first episode of cardioembolic stroke in 81 patients with paroxysmal atrial fibrillation (PAF), and in 64 patients with lacunar stroke, and compared with 100 control subjects. The latter two groups had no episode of PAF. RESULTS: The age of participants was 76 ± 11 years. Age, sex distribution, body mass index and CHADS2 score were comparable among three groups. Maximum P-wave duration, the longest across 12 leads, was significantly prolonged in cardioembolic and lacuna stroke compared to the control; 118 ± 12 ms and 118 ± 11 ms vs. 110 ± 11 ms, respectively (P < 0.0001). P-wave duration ≥120 ms and aIAB were more prevalent in ischemic stroke groups than the control, and associated with a higher Odds ratio for stroke, more so in cardioembolic stroke. However, PTFV1 value and the prevalence of PTFV1 ≥ 4.0 ms·mV were significantly not different among the three groups. Abnormal P-wave duration and aIAB indicating the presence of atrial myopathy were present in cardioembolic and lacuna stroke. CONCLUSION: Atrial myopathy was present in cardioembolic and lacunar stroke, but it can't be the direct cause of small vessel occlusion in lacunar stroke. Roles of atrial myopathy in each subtype of ischemic stroke should be studied.

Optimal extent of lymph node dissection for remnant advanced gastric carcinoma after distal gastrectomy: a retrospective analysis of more than 3000 patients from the nationwide registry of the Japanese Gastric Cancer Association.

BACKGROUND: No guidelines are available for defining the extent of lymph node (LN) dissection in patients with remnant gastric carcinoma (RGC). Hence, this retrospective study aimed to determine the optimal extent of LN dissection in patients with RGC. METHODS: We retrospectively evaluated the therapeutic outcomes of node dissection for RGC from a nationwide registry. When the metastatic rate or 5-year survival rate exceeded 10%, dissection was recommended. We calculated the dissection index by multiplying the incidence of metastasis at that nodal station by the 5-year survival rate of patients with metastasis at the station. A dissection index of > 1.0 was considered significant. RESULTS: We included 1133 patients with RGC (T2-T4 tumor) who had undergone distal gastrectomy as the primary surgery for the evaluation of the survival benefit of nodal dissection. Any regional node station was considered significant. When the primary surgery was for malignant disease, the index was high for Nos. 3 (10.2), 7 (9.5), 1 (7.1), and 9 (8.0) nodes. For nodes at the splenic hilum, the index value was 4.4, which was higher than that for the perigastric nodes (Nos. 4sa and 4sb). The index for No. 10 nodes was the highest (10.5) when tumors involved a greater curvature. CONCLUSIONS: The therapeutic strategy for RGC remains the same, regardless of the histology of the primary disease during the initial surgery. Total gastrectomy and dissection of the perigastric LNs (Nos. 1-4), suprapancreatic LNs (Nos. 7-9 and 11), and LNs at the splenic hilum (No. 10) are justified.

Surgical outcomes of elderly patients with Stage I gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association.

BACKGROUND: The proportion of elderly patients undergoing surgery for gastric cancer is increasing. However, limited number of therapeutic outcomes in the elderly has been reported. Here we examined the surgical results based on a nationwide survey of elderly patients who underwent surgery for Stage I gastric cancer. METHODS: Data from 68,353 Stage I patients who underwent gastrectomy between 2001 and 2007 were retrospectively collected. The accumulated data were reviewed and analyzed by the Japanese Gastric Cancer Association registration committee. We first classified the patients as those aged ≤ 74 years and ≥ 75 years. We further classified those patients aged ≥ 75 years into groups by 5-year increments to examine their short- and long-term postoperative outcomes. RESULTS: Patients aged ≥ 75 years accounted for 46.5%. The 30-day mortality rate was < 0.7% for any age group, but for those aged ≥ 75 years, the 60-day and 90-day mortality rates were 0.9-2.3% and 1.2-5.1%, respectively. An examination of long-term survival indicated that, as the class of age increased, the 5-year overall survival (OS) was 47.0-93.1% and disease-specific survival (DSS) was 91.4-98.2%, respectively. Although high DSS rates of ≥ 90% were found for all age groups, OS only accounted for ≤ 82% of patients aged ≥ 75 years. CONCLUSION: Among elderly patients with Stage I gastric cancer, deaths due to other diseases were frequently observed in the long term. Thus, for elderly patients, it may be appropriate to reconsider the treatment strategy with respect to the balance between the invasiveness of the treatment and the prognosis.

Professional Oral Care Reduces Carcinogenic Acetaldehyde Levels in Mouth Air of Perioperative Esophageal Cancer Patients: A Prospective Comparative Study.

Acetaldehyde is a potential carcinogen for esophageal cancer, and some oral microorganisms produce acetaldehyde from ethanol or glucose. In this prospective study, we examined the influence of professional oral care on acetaldehyde levels in mouth air of esophageal cancer patients. Acetaldehyde concentrations in mouth air and breath were measured by a portable gas chromatograph, and acetaldehyde production from oral microbiota was also evaluated. Samples were taken from 21 esophageal cancer patients (median age 68 years) and 20 age-matched healthy volunteers (control group) before and after oral care. Post-operative samples were also taken from 17 patients who had undergone surgery. All samples (mouth air, breath, and saliva) were collected 2 to 3 hours after lunch. Oral microbial samples were prepared from saliva. Genotype analysis of alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes revealed no significant differences in the genotypes between the two groups. In the control group, acetaldehyde levels in mouth air showed no significant changes after oral care, while the amount of microbial acetaldehyde production from ethanol was significantly decreased. By contrast, among the patients, acetaldehyde levels in mouth air were significantly decreased after oral care and after operation, while the amount of microbial acetaldehyde production from ethanol showed no significant changes. Moreover, microbial acetaldehyde production from glucose was significantly decreased after operation. Overall, oral health was poorer in the patient group. In conclusion, professional oral care for esophageal cancer patients is effective for reducing acetaldehyde levels in mouth air due to the reduction of microbial count.

Targeting complete response with upfront bortezomib consolidation versus observation after the achievement of complete response following autologous transplantation for multiple myeloma (TUBA study).

Complete response (CR) after treatment for multiple myeloma is associated with superior progression-free survival (PFS). Multiple myeloma patients were prospectively recruited for induction treatment with bortezomib and dexamethasone (BD) followed by autologous hematopoietic cell transplantation (auto-HCT) between 2010 and 2012. If patients did not achieve CR after auto-HCT, BD consolidation therapy was added to target CR. After the BD induction phase (n = 46), greater than or equal to CR was achieved in 4 patients (8%). After auto-HCT (n = 34), greater than or equal to CR was achieved in 9 patients (20%) and very good partial response (VGPR) was achieved in 11 (24%). Of the 24 patients who received auto-HCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses. Finally, the maximum response with or without BD consolidation was greater than or equal to CR in 19 (41%), VGPR in 7 (15%), and PR in 6 (13%). Through BD consolidation, CR was achieved in 8 of 11 patients with post-HCT VGPR and in 2 of 12 patients with post-HCT PR. In total, 4 year PFS and overall survival were 43 and 80%, respectively. After adjusting for clinical factors, there was no difference in PFS between CR patients after auto-HCT and BD consolidation, while patients with less than or equal to VGPR after consolidation had a significantly lower PFS. Patients with post-HCT CR showed good PFS, and targeting CR through BD consolidation could improve the CR rate. It would be worthwhile to prospectively compare the efficacy of consolidation only for patients who failed to achieve CR to a universal consolidation strategy.

Prediction of pathological response to neoadjuvant chemotherapy in breast cancer patients by imaging.

BACKGROUND: Diagnostic imaging is important for predicting the pathological response to chemotherapy during neoadjuvant chemotherapy (NAC) and for considering the surgical management with appropriate resection after NAC. This study was performed to examine the accuracy of the present radiological imaging for predicting the pathological complete response (pCR). METHODS: From 188 patients in our previous JONIE1 Study, a randomized controlled trial comparing chemotherapy with and without zoledronic acid for patients with human epidermal growth factor receptor 2-negative breast cancer, we evaluated 122 patients whose tumor size was examined by magnetic resonance imaging or ultrasound at three points: before NAC; after administering fluorouracil, epirubicin, and cyclophosphamide; and after NAC. The maximum tumor diameter was evaluated by magnetic resonance imaging or ultrasound. Tumor reduction ratios were calculated at the same three points. The association between the radiological clinical response and the pCR was examined. RESULTS: Among the 122 patients evaluated, there were 98 and 24 patients with luminal (Lum) and triple-negative (TN) subtypes, respectively. There were no patients who showed tumor progression after treatment. The radiological size of the tumors was finally reduced by an average of 58.4%. Clinical complete response and pCR were achieved in 22 (18.0%) and 15 (12.3%) patients, respectively. In the overall population (n = 122), the accuracy, sensitivity, and specificity for predicting pCR were 86.1%, 88.8%, and 66.7%, respectively. The negative predictive value and false-negative rate were 45.5% and 11.2%, respectively. According to subtypes, the accuracies were 83.7% and 95.8% in Lum and TN, respectively. Negative predictive value and false-negative rate were markedly different between the Lum (29.4% and 13.5%) and TN subtypes (100% and 0%), respectively. CONCLUSIONS: This randomized clinical trial demonstrated that NAC was safe for operable breast cancer patients with appropriate radiological monitoring. Radiological evaluation after NAC may be a reliable method for predicting pathological response in the TN subtype, but not in the Lum subtype.

Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001-2007).

BACKGROUND: The aim of this retrospective study was to investigate the tumor characteristics, surgical details, and survival distribution of surgically resected cases of gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association. METHODS: Data from 118,367 patients with primary gastric carcinoma who underwent resection between 2001 and 2007 were included in the survival analyses. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The median age of the patients was 67 years. The proportions of patients with pathological stage (Japanese Gastric Cancer Association) IA, IB, II, IIIA, IIIB, and IV disease were 44.0%, 14.7%, 11.7%, 9.5%, 5.0%, and 12.4% respectively. The death rate within 30 days of operation was 0.5%. The 5-year overall survival rate in the 118,367 patients who were treated by resection was 71.1%. The 5-year overall survival rates of patients with pathological stage IA, IB, II, IIIA, IIIB, and IV disease were 91.5%, 83.6%, 70.6%, 53.6%, 34.8%, and 16.4% respectively. The 5-year disease-specific survival rates in the patients with pT1 (mucosa) disease after D1+ dissection of lymph node station no. 7 (D1 + α), D1+ dissection of lymph node station nos. 7, 8, and 9 (D1+ ß), and D2 lymphadenectomy were 99.4%, 99.6%, and 99.1% respectively. The 5-year disease-specific survival rates in the patients with pT1 (submucosa) disease after D1 + α, D1 + ß, and D2 lymphadenectomy were 97.3%, 98.1%, and 96.9% respectively. CONCLUSION: Detailed analyses of the data from more than 100,000 patients show the recent trends of the outcomes of gastric cancer treatment in Japan and provide baseline information for use by medical communities around world.

Clinicopathological features in anterior visual pathway in neuromyelitis optica.

OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia-neuron interaction in NMOsd. METHODS: Thirty Japanese patients with serologically verified NMOsd were assessed with a neuro-ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP. RESULTS: The AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Müller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4(+) astrocytes, indicating secondary retrograde degeneration after ON. INTERPRETATION: Severe and widespread neuroaxonal damage and unique dynamics of astrocytes/Müller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd.