Transthyretin amyloid cardiomyopathy: Literature review and red-flag symptom clusters for each cardiology specialty.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is a progressive and infiltrative cardiac disorder that may cause fatal consequences if left untreated. The estimated survival time from diagnosis is approximately 3-6 years. Because of the non-specificity of initial symptom manifestation and insufficient awareness among treating physicians, approximately one-third of patients with ATTRwt-CM are initially misdiagnosed with other cardiac diseases. Although heart failure (HF) is the most common initial manifestation of ATTRwt-CM, observed in nearly 70% of affected patients, patients may also present with other cardiologic symptoms, such as atrial fibrillation (AF) and aortic stenosis (AS). This non-specific and diverse nature of the initial ATTRwt-CM presentation indicates that various cardiology subspecialties are involved in patient diagnosis and management. Standard guideline-directed pharmacological treatment for HF is not recommended for patients with ATTRwt-CM because of its limited effectiveness. However, no established algorithms are available regarding HF management in this patient population. This literature review provides an overview of the red flags for ATTRwt-CM and research findings regarding HF management in this patient population. In addition to commonly recognized red flags for ATTRwt-CM (e.g., HF, AF and severe AS), published literature identified potential red flags such as coronary microvascular dysfunction. For HF management in patients with ATTRwt-CM, the use of mineralocorticoid receptor antagonists (MRAs) was reported as a well-tolerated option associated with a low discontinuation rate and reduced mortality. Although there is no concrete evidence for recommendations against sodium-glucose cotransporter 2 inhibitor (SGLT2i) administration, research supporting its use is limited to small-scale studies. Robust evidence is lacking for AF ablation, implantable cardioverter-defibrillators and cardiac resynchronization therapy. Based on the published findings and our clinical experience as Japanese ATTRwt-CM experts, red-flag symptom clusters for each cardiology specialty (HF, arrhythmia and ischaemia/structural heart disease) and a treatment scheme for HF management are presented. As this research area remains at an exploratory stage, our observations would require further discussion among experts worldwide.

Combined effect of interstitial-substitutional elements on dislocation dynamics in nitrogen-added austenitic stainless steels.

Combined addition of interstitial-substitutional elements has been acknowledged to contribute to the increase in the strengths of steels. For further improvements in mechanical properties, their atomic-scale interaction mechanisms with dislocations are required to be examined. In this study, both high-resolution transmission electron microscopy and atom-probe tomography were used to correlate interstitial-substitutional elements with dislocation characteristics in austenitic stainless steels. Three types of dislocation core structures are identified and associated with their strain fields as well as N and Cr atoms in the N-added steels. It is revealed that N atoms interact elastically with the dislocations, followed by the segregation of Cr atoms via the chemical interaction between N and Cr atoms. This insight significantly improves the understanding of the multiple alloying mechanism in metallic materials such as interstitial alloys and high-entropy alloys.

Transversal Survey of Emergency Medicine Policy and Quality Metrics in Japan's Regional Health Care Plans.

Introduction: It is essential to establish appropriate medical quality metrics and make improvements to safely and efficiently deliver optimum emergency medical services. The Ministry of Health, Labor and Welfare (MHLW) recommends prefectures to establish numerical quality metrics in their regional healthcare plans (RHCP). The 7th RHCP was issued by the MHLW in 2017 along with a notice of planning in covering the six-year period from 2018 to 2023. In this descriptive study, the emergency medicine policies in the 7th RHCP of each prefecture were analyzed from a quality improvement perspective. Method: The authors examined the chapters on emergency medicine in the RHCPs of 47 prefectural governments for the overall structure, cost-benefits, and connection to community-based integrated care systems. The type and number of clinical measures listed as numerical metrics and their classification methods were emphasized. Result: Regarding the overall plan structure, 40 prefectural governments began their description with an analysis of current surroundings. In total, 24 prefectural governments mentioned community-based integrated care systems but none mentioned cost-benefit analysis. Altogether, only 43 of 47 prefectural governments (91%) indicated numerical metrics. The maximum number of numerical targets for quality measures by prefecture was 19, the minimum was 0, and the median was 4 (IQR: 3-6.5); there were 220 metrics in total, with 82 structural, 96 process, and 42 outcome measures. Additionally, 13 prefectures (28%) classified quality measures according to the MHLW's guidance, 6 (13%) used their own classification manner, while the others did not classify their measures. Conclusions: There were significant differences in emergency medicine policies and quality metrics among the prefectural governments. Further research is needed to develop and establish more comprehensive and appropriate metrics based on a common methodology to improve the quality of emergency medicine.

Down-regulating Effect of a Standardized Extract of Cultured Lentinula edodes mycelia on Cortactin in Prostate Cancer Cells Is Dependent on Malignant Potential.

BACKGROUND/AIM: The incidence and mortality rates of prostate cancer have been increasing worldwide. Although prostate cancer cells grow slowly in the local original site, once the cancer cells spread to distant organs they grow rapidly and show very aggressive features. Cortactin is a protein that regulates the actin cytoskeleton and plays crucial roles in cancer metastasis. Up-regulated cortactin is correlated with the metastatic capacity of prostate cancer cells. AHCC®, a standardized extract of cultured Lentinula edodes mycelia, has been previously reported to have cortactin-down-regulating effects on human pancreatic cancer cells. In the present study, the effects of AHCC® treatment on cortactin levels in prostate cancer cells was evaluated. MATERIALS AND METHODS: LNCaP.FGC, DU145, and PC-3 are human prostate cancer cell lines. LNCaP.FGC is well differentiated, androgen-dependent, and poorly metastatic. DU145 is less differentiated, androgen-independent, and moderate metastatic. PC-3 is less differentiated, androgen-independent, and highly metastatic. The effects of AHCC® treatment on cortactin levels in prostate cancer cells was evaluated by western blot. RESULTS: In vitro AHCC® treatment decreased cortactin levels in LNCaP.FGC and DU145 cells but did not change those in PC-3 cells. CONCLUSION: AHCC® treatment down-regulated cortactin expression in poor and moderate metastatic LNCaP.FGC and DU145 cells but showed no effect on cortactin expression in the highly metastatic PC-3 cells. Further studies are required to elucidate the mechanism of the resistance to AHCC® treatment in highly metastatic PC-3 cells.

Reevaluation of Gastric Cancer Screening by Levin's Equation.

INTRODUCTION: This study aimed to reevaluate the effectiveness of fluoroscopy and endoscopy in reducing gastric cancer mortality at the population level. METHODS: Crude and age-adjusted mortality rates of gastric cancer and the introduction rates of gastric cancer screening were extracted from the Cancer Registry and Statistics database. The population-attributable risk (PAR) percent of no screening for gastric cancer mortality was calculated using Levin's equation. The PAR of each mortality rate in the no-screening group was estimated as follows: mortality × PAR%. The Jonckheere-Terpstra test for trends and linear regression were performed to compare the PAR of gastric cancer mortality rates among the decades. RESULTS: The PAR of crude and age-adjusted mortality rates in the no-screening group significantly decreased in the total population ( P for trend <0.001), as well as individually in the male ( P for trend <0.001) and female ( P for trend <0.001) populations. The PAR of the crude mortality rate in the female population significantly decreased in 2000-2009 and 2010-2019, compared with that in 1980-1989. There was no significant difference in the PAR of crude mortality rate in the male population among the decades. The PAR of the age-adjusted mortality rate significantly decreased in 2000-2009 and 2010-2019, compared with that in 1980-1989, in the male and female populations. DISCUSSION: PAR% and PAR of no screening for gastric cancer mortality could be estimated using Levin's equation, and the effectiveness of the present gastric cancer screenings with fluoroscopy and endoscopy has been decreasing, especially in the female population.

Alcohol Consumption and Age-related Macular Degeneration: A Systematic Review and Dose-response Meta-analysis.

Purpose: To perform a systematic review on the association between alcohol consumption and risk of age-related macular degeneration (AMD) using a meta-analytical approach.Method: Systematic literature research was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Both categorical and dose-response meta-analysis was performed separately for early and late AMD. A fixed-effect model was used to calculate pooled effect estimates with 95% confidence interval (CI).Result: Seven studies were included in the analysis with 4,566 and 440 cases of early and late AMD, respectively. Compared to the nondrinkers or occasional drinkers, the pooled effect estimates for early AMD with moderate (1.19, 95% CI [1.03-1.37]) and heavy (1.24, [1.10-1.39]) alcohol consumption, but not light (0.95, [0.90-1.06]) alcohol consumption, were statistically significant. However, the pooled effect estimates for late AMD with light (1.03, [0.79-1.33]), moderate (1.13, [0.83-1.55]), and heavy (0.98, [0.63-1.53]) alcohol consumption were found to be insignificant. A linear dose-response relationship was established (P < .05) between alcohol consumption and risk of early AMD, and the pooled effect estimate for an increase in alcohol consumption of 10 g/day was 1.14 (1.08-1.21).Conclusion: Moderate and heavy alcohol consumption could increase the risk of early AMD, but not late AMD, with a linear dose-response relationship.

Plan-view characterization of intergranular precipitates on grain boundaries by combination of FIB lift out method and TEM analyses: A case study in austenitic stainless steel.

A new characterization method is proposed to study intergranular precipitates of polycrystalline material in the planar manner. A dual beam focused ion beam (FIB) - scanning electron microscopy (SEM) was applied to fabricate thin FIB lamella with a grain boundary parallel to the lamella to investigate for transmission electron microscopy (TEM). Distributions, microstructures and compositions of intergranular precipitates of austenitic stainless steel were then examined by TEM, scanning transmission electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDS). This plan-view microstructural characterization methods would play important roles in the case of materials where the intergranular precipitates play key roles for their physical and chemical properties.

NONO Is a Negative Regulator of SOX2 Promoter.

BACKGROUND/AIM: Sex determining region Y (SRY)-box 2 (SOX2) is a transcription factor essential for the maintenance of proliferation and self-renewal of cancer stem cells and is associated with breast cancer initiation. Regulation of cancer stem cell plasticity by SOX2 requires both positive and negative SOX2 transcription factors, but the negative regulator is still largely unknown. MATERIALS AND METHODS: SOX2 promoter-binding proteins were identified by liquid chromatography-mass spectrometry/mass spectrometry, luciferase assay, and chromatin immunoprecipitation. The effects of one such transcription factor on SOX2 expression was investigated by knockdown and overexpression experiments. RESULTS: Non-POU domain-containing octamer-binding protein (NONO) (also known as 54-kDa nuclear RNA-binding protein, P54NRB) was identified as a SOX2 promoter-binding protein and a negative regulator of SOX2 expression. Its activity was controlled by its coiled-coil domain and the C-terminal domain. CONCLUSION: These results suggest that NONO acts as a key regulator of SOX2 transcription through the repression of SOX2 promoter activity in breast cancer cells.

ADAR2 Regulates Malignant Behaviour of Mesothelioma Cells Independent of RNA-editing Activity.

BACKGROUND/AIM: Malignant pleural mesothelioma (MPM) is an intractable cancer, and causes of its malignant transformation are not well known. Adenosine deaminase acting on RNA (ADAR) is an RNA-editing enzyme that converts adenosine into inosine in double-stranded RNAs potentially involved in malignant development. MATERIALS AND METHODS: To examine the role of ADAR1 and ADAR2 in MPM, small interfering RNAs (siRNAs) against ADAR1 or ADAR2 were used. RESULTS: Transfection of siRNA against ADAR2 suppressed proliferation, motility, and invasiveness of MPM cells expressing both ADAR1 and ADAR2; however, siRNA against ADAR1 did not affect these cellular activities. Overexpression of ADAR2, that was incapable of binding to RNA, suppressed growth, motility, and invasion of MPM cells. However, overexpression of ADAR2 that had no enzyme activity did not alter the malignant properties of MPM cells. CONCLUSION: Enhancement of the malignant characteristics of cultured MPM cells via ADAR2 was independent of RNA-editing activity.

Receptor Tyrosine Kinases: Principles and Functions in Glioma Invasion.

Protein tyrosine kinases are enzymes that are capable of adding a phosphate group to specific tyrosines on target proteins. A receptor tyrosine kinase (RTK) is a tyrosine kinase located at the cellular membrane and is activated by binding of a ligand via its extracellular domain. Protein phosphorylation by kinases is an important mechanism for communicating signals within a cell and regulating cellular activity; furthermore, this mechanism functions as an "on" or "off" switch in many cellular functions. Ninety unique tyrosine kinase genes, including 58 RTKs, were identified in the human genome; the products of these genes regulate cellular proliferation, survival, differentiation, function, and motility. Tyrosine kinases play a critical role in the development and progression of many types of cancer, in addition to their roles as key regulators of normal cellular processes. Recent studies have revealed that RTKs such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), c-Met, Tie, Axl, discoidin domain receptor 1 (DDR1), and erythropoietin-producing human hepatocellular carcinoma (Eph) play a major role in glioma invasion. Herein, we summarize recent advances in understanding the role of RTKs in glioma pathobiology, especially the invasive phenotype, and present the perspective that RTKs are a potential target of glioma therapy.

Combined effects of body mass index and unhealthy behaviors on disability in older Japanese adults: the Okayama study.

BACKGROUND: Body mass index (BMI) is a significant predictor of functional disability in older adults. However, when evaluated, the association between BMI and incident functional disability, considering behaviors only as covariates or not, may not be appropriate. The primary purpose of the study was to investigate the combined effects of BMI and unhealthy behaviors on the risk of incident functional disability. METHODS: This was a retrospective cohort study that took place in Okayama City, Japan. Data on BMI and unhealthy behaviors were obtained using the health check-up questionnaire. The certification of Long-Term Care Insurance was used to measure functional disability. Cox proportional hazard models were used; adjusted hazard ratios (HRs) with 95% confidence interval (CI) were calculated for incidence of functional disability across categories of BMI and number of unhealthy behaviors. RESULTS: The relationship between BMI and incident functional disability was U-shaped (HR = 1.18, 95% CI [1.11-1.25], among the underweight range; and 1.26 [1.19-1.34] among the obesity range), and its risk was significantly higher within the normal-to-overweight range of BMI values with co-occurring unhealthy behaviors (with normal weight range and one, 1.17 [1.01-1.21]; two, 1.29 [1.18-1.41]; and three or four unhealthy behaviors 1.38 [1.24-1.54]; as well as among overweight range and one, 1.16 [1.05-1.27]; two, 1.26 [1.15-1.38]; and three or four unhealthy behaviors, 1.47 [1.31-1.64]). In each BMI category, the risk of incident functional disability increased with increasing number of unhealthy behaviors (p < 0.05 for linear tread), with the highest risk (1.87 [1.58-2.20]) occurring in combination with at least three unhealthy behaviors with BMI ≥ 27.5, for both sexes (2.20 [1.64-2.92] in men and 1.66 [1.35-2.04] in women). CONCLUSION: It is necessary to consider the combined effects of BMI and behaviors on incident functional disability. Furthermore, interventions targeting multiple behaviors should be considered as such interventions may offer greater benefits than simple interventions.

Alcohol consumption and incident dementia in older Japanese adults: The Okayama Study.

AIM: To evaluate the association between the amount and frequency of alcohol consumption and incident dementia in older Japanese adults using large sample size data over a long follow-up period. METHODS: This was a retrospective cohort study carried out in Japan. A total of 53 311 older adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess the amount and frequency of alcohol consumption. The Dementia Scale of long-term care insurance was used as a measure of incident dementia. Cox proportional hazards models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of alcohol consumption by sex. RESULTS: During a 7-year follow-up period, 14 479 participants were regarded as having incident dementia. Compared with non-drinkers, the multivariate adjusted hazard ratios for participants with alcohol consumption ≤2 units per day, occasionally (0.88, 95% CI 0.81-0.96 in men and 0.84, 95% 0.79-0.90 in women) and daily (0.79, 95% 0.73-0.85 in men and 0.87, 95% 0.78-0.97 in women) were statistically significant, and the difference between occasional and daily consumption was only statistically significant in men; however, for participants with alcohol consumption >2 units per day, occasionally (0.91, 95% 0.71-1.16 in men and 1.09, 95% 0.72-1.67 in women) and daily (0.89, 95% 0.81-1.00 in men and 1.16, 95% 0.84-1.81 in women) were not significant. CONCLUSIONS: Alcohol consumption of ≤2 units per day, occasionally or daily, could reduce the risk of incident dementia, with greater benefit for men with such daily consumption. Geriatr Gerontol Int 2019; 19: 740-746.

Physical activity and incident dementia in older Japanese adults: The Okayama study.

OBJECTIVE: To evaluate the association between regular physical activity and the risk of incident dementia in older Japanese adults. METHODS: This was a retrospective cohort study performed in Okayama City, Japan. Overall, 51 477 older Japanese adults were followed from 2008 to 2014. A health checkup questionnaire was used to assess regular physical activity. The Dementia Scale of long-term care insurance was used as a measure of incident dementia. Cox proportional hazard models were used to calculate adjusted hazard ratios, with their 95% confidence intervals, for the incidence of dementia across the categories of physical activity. RESULTS: During a 7-year follow-up, 13 816 subjects were considered as having incident dementia. Compared with participants who performed physical activity less than or equal to one time per week, the multivariate adjusted hazard ratio values (95% confidence intervals) for participants who performed physical activity greater than or equal to two times per week but not every day and those who performed physical activity every day were 0.79 (0.75-0.84) and 0.94 (0.89-0.98), respectively. The interaction of physical activity and sex was statistically significant (P < .01). In subgroup analysis, the multivariate-adjusted hazard ratio values (95% confidence intervals) remained low, at 0.76 (0.70-0.84) in males and 0.81 (0.76-0.87) in females who performed physical activity greater than or equal to two times per week but not every day; they were 0.82 (0.76-0.89) in males and 1.01 (0.95-1.07) in females who performed physical activity every day. CONCLUSIONS: Regular physical activity could reduce the risk of incident dementia in older Japanese adults, except females who performed physical activity every day.

Dominant-negative p53 mutant R248Q increases the motile and invasive activities of oral squamous cell carcinoma cells.

The tumor suppressor gene TP53 (gene) codes for a transcription factor which transactivates its target genes responsible for cell cycle arrest, DNA repair, apoptosis, and senescence. TP53 is well known to be the most frequent target of genetic mutations in nearly half of human cancers including oral squamous cell carcinoma (OSCC). Many p53 mutants including R248Q and R248W not only lose its tumor-suppressor activities, but also interfere with the functions of wild-type p53; this is so-called dominant-negative (DN) mutation. The DN p53 mutation is a predictor of poor outcome in patients with various cancers, and also a risk factor for metastatic recurrence in patients with OSCC. Recently it has been reported that DN p53 mutants acquire new oncogenic activities, which is named gain-of-function (GOF). This study aimed at determining whether R248Q and R248W were involved in OSCC cells' acquiring aggressive phenotypes, using SAS, HSC4 and Ca9-22 cell lines. First, two mutants p53, R248Q and R248W, were respectively transfected into SAS cells harboring recessive-type p53 (E336X). As a result, SAS cells expressing R248Q showed highly spreading, motile and invasive activities compared to parent or mock-transfected cells whereas those expressing R248W did not increase those activities. Secondly, in HSC4 cells harboring R248Q and Ca9-22 cells harboring R248W, expressions of the mutants p53 were inhibited by the transfection with siRNAs targeting p53. The inhibition of the mutants p53 decreased spreading, motile and invasive activities of HSC4 cells whereas it did not affect those activities of Ca9-22 cells. These findings suggest that R248Q p53 mutation, but not R248W p53 mutation, induces more motile and invasive potentials in human OSCC cells.

CUB Domain-containing Protein 1 (CDCP1) Is Down-regulated by Active Hexose-correlated Compound in Human Pancreatic Cancer Cells.

BACKGROUND/AIM: We have previously reported that treatment of pancreatic cancer cells with active hexose-correlated compound (AHCC), an extract of a basidiomycete mushroom, decreases the levels of tumor-associated proteins including heat-shock protein 27 (HSP27), heat shock factor 1 (HSF1) and sex-determining region Y-box 2 (SOX2). The transmembrane glycoprotein, CUB domain-containing protein 1 (CDCP1) has been reported to be up-regulated in various cancers, and be associated with invasion and metastasis. The aim of this study was to examine the effect of AHCC on the expression of CDCP1 in KLM1-R cells. MATERIALS AND METHODS: Gemcitabine-resistant pancreatic cancer cells (KLM1-R) were treated with AHCC (10 mg/ml) for 48 h. Western blot analysis of cell extracts with anti-CDCP1 or anti-actin antibodies was performed to assess the expression of CDCP1. RESULTS: Expression of CDCP1 was reduced by AHCC treatment of KLM1-R cells, whereas expression of actin was not affected. The ratio of intensities of CDCP1/actin in AHCC-treated KLM1-R cells was significantly suppressed (p<0.05) compared to untreated cells. CONCLUSION: AHCC down-regulated CDCP1 expression and inhibited the malignant progression of pancreatic cancer cells.

Characterization of Anti-Ice Nucleation Activity of the Extract from Coffee Refuse.

　The supercooling-facilitating (SCF) activities, that is, the anti-ice nucleation activity of the hot water extracts from five types of processed food refuse was examined. The extract with the highest activity among five hot water extracts was coffee refuse, showing 1.50℃ of SCF activity at a final concentration of 0.1 mg/ml. From the hot water extract of coffee refuse, the coffee refuse extract containing various polyphenols was prepared by the ultrafiltration (less than MWCO 10,000), a solvent fractionation of ethyl acetate. The yield of coffee refuse extract was 0.9% (w/w) from dried coffee refuse. The SCF activity of the coffee refuse extract at a final concentration of 1.0 mg/ml was 4.2℃. HPLC analysis of the coffee refuse extract showed that caffeine and chlorogenic acid, which are major components of coffee, could be found at 173 and 62.3 µg/ml, respectively. However, the SCF activities of both compounds (0.70 and 1.06℃) at a final concentration of 0.1 mg/ml were lower than those of ferulic acid and coumaric acid, respectively at 3.40 and 2.35℃. This is the first report to our knowledge on the SCF activity of caffeine. The SCF activity of caffeine at a final concentration of 1.0 mg/ml was 2.3℃. The specificity of caffeine against various ice nuclei containing calcium oxalate, 9-fluorenon, and ice nucleating bacteria was examined. Caffeine at a final concentration of 1.0 mg/ml could inhibit the ice nucleation activity of calcium oxalate, and Pseudomonas fluorescens KUIN-1 at the same level that of as silver iodide. From these results, it was suggested that the extract could be able to be applied to the field to control the frost damage of the vegetables and that the harvested vegetables might be stored unfrozen even at 0℃ or less.

Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan.

Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal-regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis.

Massive Hemorrhage from the Posterior Ethmoidal Artery during Transsphenoidal Surgery: Report of 2 Cases.

Nasal bleeding is a major complication that can occur during and after transsphenoidal surgery (TSS) for intra- and suprasellar tumors. In most cases, the cause of this bleeding can be attributed to a branch of the maxillary artery called the sphenopalatine artery, injury to which can lead to life-threatening situations. Upon exposure of the suprasellar region and planum sphenoidale during surgery, it is also important to avoid damaging the posterior ethmoidal artery (PEA), a branch of the ophthalmic artery. While recent advancement in endoscopic techniques enables the performance of extended TSS, the chances of PEA injury seem to be increasing. In the current report, we present two cases that showed massive PEA bleeding during regular (not extended) TSS. The total blood loss was 2280 ml and 2150 ml, and endoscopic views disturbed by the massive hemorrhages remarkably delayed accurate stanching of the responsive artery. Therefore, anatomical recognition of the PEA is required to avoid fatal hemorrhaging during even regular TSS, especially for the beginners of this surgery.

Pure Lymphocytic Infundibuloneurohypophysitis Caused by the Rupture of Rathke's Cleft Cyst: Report of 2 Cases and Review of the Literature.

The major symptoms that are caused by Rathke's cleft cysts (RCCs) are visual disturbances, headaches, and endocrine insufficiencies. Among these symptoms, the endocrine insufficiencies are thought to result from the spreading of inflammation that is induced by the cyst contents onto the pituitary gland or the compression of the gland and the pituitary stalk by RCCs. Here, we present 2 rare cases with lymphocytic infundibulohypophysitis with the sudden onset of headaches and subsequent diabetes insipidus (DI). Magnetic resonance imaging revealed remarkable swelling of the pituitary gland with a small mass that was located between the anterior and the posterior lobe of the pituitary gland. Transsphenoidal surgery was performed to remove the mass, and pathological examinations of the cyst wall demonstrated that the epithelial tissue of the RCC and the posterior lobe were affected by massive lymphocytic infiltration. The clinical courses and pathological results of these patients strongly suggested that the rupture of the RCC onto the posterior lobe caused the lymphocytic hypophysitis. Postoperatively, the DI could be controlled with a smaller amount of anti-diuretic hormone replacement compared to that required preoperatively.