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BACKGROUND Adrenal incidentaloma (AI) has been frequently encountered in the clinical setting. It has been shown that primary aldosteronism (PA) or subclinical Cushing’s syndrome (SCS) are the representative causative diseases of AI. However, the coexistence of PA and SCS has been reportedly observed. Recently, we encountered a case of AI, in which PA and SCS coexisted, confirmed by histopathological examinations after a laparoscopic adrenalectomy. We believe that there were some clinical implications in the diagnosis of the present case. CASE SUMMARY A 58-year-old man presented with lower right abdominal pain with a blood pressure of 170/100 mmHg. A subsequent computed tomography scan revealed right ureterolithiasis, which was the cause of right abdominal pain, and right AI measuring 22 mm × 25 mm. After the disappearance of right abdominal pain, subsequent endocrinological examinations were performed. Aldosterone-related evaluations, including adrenal venous sampling, revealed the presence of bilateral PA. In addition, several cortisol-related evaluations showed the presence of SCS on the right adrenal adenoma. A laparoscopic right adrenalectomy was then performed. The histopathological examination of the resected right adrenal revealed the presence of a cortisol-producing adenoma, while CYP11B2 immunoreactivity was absent in this adenoma. However, in the adjacent non-neoplastic adrenal, multiple CYP11B2-positive adrenocortical micronodules were detected, showing the presence of aldosterone-producing adrenocortical micronodules. CONCLUSION Careful clinical and pathological examination should be performed when a patient harboring AI presents with concomitant SCS and PA.

Approximately 30% of patients experience nausea after initiation of opioid therapy, which can lead to poor quality of life. We aimed to identify risk factors for opioid-induced nausea at the initiation of opioid therapy by conducting a retrospective review of medical records of patients diagnosed by palliative care specialists with solid cancer and pain at the lesion site at Showa University Hospital between June 2005 and June 2011. The primary endpoint was the development of nausea grade ≥1 according to the Common Terminology Criteria for Adverse Events version 4.0 within 48 hours of initiation of opioid therapy. The median age of the 134 enrolled patients was 67.7 (range 28-95) years. Fifty-three percent were male and 44% had gastrointestinal cancer. Furthermore, 22.4% had opioid-induced nausea. Age (odds ratio (OR) 1.74; 95% confidence interval (CI), 1.13-2.69), edema (OR 5.83; 95% CI, 1.22-28.19), and gastrointestinal cancer (OR 2.61, 95% CI 1.07-6.36) were significantly associated with opioid-induced nausea. Prophylactic antiemetics were found to be ineffective.

Treatment with a combination of norepinephrine and doxazosin was effective in a patient with pheochromocytoma who had blood pressure fluctuation, hypotension, and recurrent syncope. After adrenalectomy, his blood pressure, heart rate, and plasma levels of catecholamines remained normal and stable without any medication. (Level of Difficulty: Beginner.), Graphical abstract, Treatment with a combination of norepinephrine and doxazosin was effective in a patient with pheochromocytoma who had blood pressure fluctuation…

BackgroundSchool urinary screening has been performed in Japan.MethodsIkeda City and Toyono Town introduced, in 2012 and 2013, urinary protein/creatinine (Cr) ratio measurement into the urine-screening protocols designed for students aged between 4 and 15 years. For each student whose urinary protein/Cr ratio was ≥ 0.15 g/gCr (positive case), an appointment was made with a specialist at Ikeda City Hospital. The results of these screening urinalyses conducted through 2018 are summarized.Results14,606 junior high and elementary school students aged between 6 and 15 years were included. On average, they underwent 4.16 screening tests. 77 positive cases were detected, and seven students were diagnosed with high-risk chronic kidney disease (CKD). Of these, four underwent renal biopsy, and two, one, and one were diagnosed with IgA nephropathy, MPGN, and FSGS, respectively. In three students, detection of CKD would have been difficult without urinary screening. Incident rates of high-risk CKD and IgA nephropathy are estimated as 11.5 and 3.3 cases/100,000 students/year. 78.0% of positive cases without high-risk CKD showed no urinary abnormality after one year. 2301 kindergarten students aged between 4 and 6 years received an average of 1.74 screening urinalyses; none was positive or high-risk CKD. The estimated cost of detecting one high-risk CKD student whose detection would have been difficult without this screening was 3,156,711 Japanese yen.ConclusionSchool urinary screening using the urinary protein/Cr ratio can efficiently refer to a specialist. It detects a few children with high-risk CKD early with spending high cost.

The COL2A1 gene encodes the alpha-1 chain of procollagen type 2. Pathogenic variants in the COL2A1 gene are associated with several different types of skeletal dysplasia collectively known as type 2 collagenopathies. Type 2 collagenopathies have an autosomal dominant inheritance. Some germline or somatogonadal mosaicism cases have been reported. We investigated whether somatogonadal mosaicism occurred in a family with two children suspected of type 2 collagenopathies or related diseases. First, we detected a pathogenic variant in the COL2A1 gene in the two affected children by whole exome sequencing (WES). Next, we performed targeted deep sequencing to their parents without the variant by WES. A low level of COL2A1 mosaicism was revealed in the mother's tissues. We concluded that the mother had somatogonadal mosaicism with the COL2A1 mutation arose in the epiblast, and that the intrafamilial recurrence rate of the disease by the somatogonadal mosaicism was higher than by the germline mosaicism. This report suggests that parental low-level mosaicism should be evaluated in those parents with children carrying de novo germline mutations and the targeted deep sequencing is useful to detect them.

Aims/Introduction Insomnia is associated with type 2 diabetes mellitus, and results in a low quality of life. There are several known relationships between insomnia and personality. Thus, we clarified the association between some personality traits and insomnia among Japanese type 2 diabetes mellitus patients. Materials and Methods The participants were 504 type 2 diabetes mellitus patients (mean age 63.9 ± 12.5 years). Sleep disturbance and personality traits were evaluated using the Pittsburgh Sleep Quality Index‐Japanese version and the Ten‐Item Personality Inventory Japanese version, respectively. Lifestyle factors, glycated hemoglobin levels and depressive status of the patients were also included in the analyses. Results Among the 504 participants with type 2 diabetes mellitus, 154 (30.6%) showed probable insomnia. After adjustment for confounders, being female, living alone, high body mass index and “high neuroticism” were found to be significantly correlated with current insomnia. No other relationships between insomnia and glycated hemoglobin or lifestyle factors, such as smoking, drinking alcohol or exercise frequency, were found. Conclusions The prevalence of insomnia in individuals with type 2 diabetes mellitus was high, and the risk factors included some personality factors. Future prospective studies are required to confirm the therapeutic effects of behavioral interventions for insomnia in patients with type 2 diabetes mellitus.

Congenital generalized lipodystrophy type 4 (CGL4) is a rare disease caused by mutations in the gene polymerase I and transcript release factor (PTRF), the main symptoms of which are systemic reductions in adipose tissue and muscular dystrophy. The strategy of treating CGL4 is to improve the insulin resistance and hypertriglyceridemia that result from systemic reductions in adipose tissue. Metreleptin, a synthetic analog of human leptin, is effective against generalized lipodystrophies; however, there are no reports of the use of metreleptin in the treatment of CGL4. Herein, we discuss the treatment of a six-year-old boy diagnosed with CGL4 due to a homozygous mutation in PTRF with metreleptin. His serum triglyceride level and homeostasis model assessment of insulin resistance (HOMA-IR) value decreased after two months of metreleptin treatment. However, the efficacy of metreleptin gradually decreased, and the treatment was suspended because anaphylaxis occurred after the dosage administered was increased. Subsequently, his serum triglyceride level and HOMA-IR value significantly increased. Anti-metreleptin-neutralizing antibodies were detected in his serum, which suggested that these antibodies reduced the efficacy of metreleptin and caused increased hypersensitivity. Thus, metreleptin appeared to be efficacious in the treatment of CGL4 in the short term, although an adverse immune response resulted in treatment suspension. Further studies are needed to evaluate metreleptin treatments for CGL4.

Cole-Carpenter syndrome is a rare skeletal dysplasia associated with low-bone mass or an osteogenesis imperfecta (OI)-like syndrome. Only 3 and 6 variants in SEC24D have been reported in patients with Cole-Carpenter syndrome type 2 and autosomal recessive OI, respectively. We describe a 15-year-old Japanese boy with short stature of the short-trunk type and craniofacial abnormalities including ocular proptosis, marked frontal bossing, midface hypoplasia, and micrognathia. These features were consistent with a diagnosis of Cole-Carpenter syndrome. He had low-bone mineral density and basilar impression. Whole exome sequencing analysis identified biallelic variants in SEC24D (p.Arg484* and p.Arg313His) in the patient. We will report a patient with compound heterozygous variants of SEC24D causing Cole-Carpenter syndrome type 2.

Endosalpingiosis is a benign condition characterized by the presence of tubal epithelium outside the fallopian tube and the absence of endometrial stroma. Florid cystic endosalpingiosis is a very rare form of endosalpingiosis that presents as a tumor-like lesion. We report the case of a 67-year-old woman who presented with a cystic lesion of the uterus. Macroscopically, a cut section revealed a multicystic, whitish mass in the myometrium of the fundus. Histologically, the lesion consisted of numerous variably sized glands that were lined with a single or stratified layer of ciliated columnar cells similar to tubal epithelium.

Kazutaka Yoshida,1 Hideyuki Otaka,2 Hiroshi Murakami,2 Hirofumi Nakayama,1 Masaya Murabayashi,2 Satoru Mizushiri,2 Koki Matsumura,2 Jutaro Tanabe,2 Yuki Matsuhashi,2 Miyuki Yanagimachi,2 Norio Sugawara,3 Kazuhiko Nakamura,1 Makoto Daimon,2 Norio Yasui-Furukori1 1Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 2Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 3Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan Purpose: Insomnia, which is associated with type 2 diabetes mellitus (DM), results in a low quality of life, and several relationships exist between insomnia and coping style. Thus, we clarified the association between some coping styles and insomnia among Japanese type 2 DM patients. Subjects and methods: The subjects included 503 type 2 DM patients (mean age 63.9±12.5years). Sleep disturbance and personality traits were evaluated using the Japanese version of the Pittsburgh Sleep Quality Index and the Brief Scale for Coping Profile, respectively. Lifestyle factors, glycated hemoglobin A1c (HbA1c) levels, and the depression statuses of the patients were also included in the analyses. Results: Among the 503 subjects with type 2 DM, 141 (28.0%) subjects exhibited probable insomnia. After adjusting for confounders, being female, living alone, and using “avoidance and suppression” were significantly correlated with current insomnia. No other relationships were found between insomnia and HbA1c or lifestyle factors, such as smoking, drinking alcohol, and exercise frequency. Conclusion: The prevalence of insomnia in individuals with type 2 DM was high, and the protective factors included some emotion-focused coping styles. Future prospective studies are required to confirm the therapeutic effects of behavioral interventions on insomnia in patients with type 2 DM. Keywords: cross-sectional studies, coping style, Japanese, insomnia, type 2 DM

Heart failure pandemic is rapidly approaching in Japan, requiring nationwide actions. In particular, the Japanese Circulation Society and related societies launched the Stroke and Cardiovascular Disease Control Act, which was passed by the National Diet, as the first ever legislative policy measure against stroke and cardiovascular disease. In association with this, actions against heart failure pandemic from the scientific field are also important. Because heart failure pandemic is a critical problem not only in Japan but also in many developed countries, we believe the nationwide approach, as summarized here, will greatly contribute to the development of cardiovascular medicine, particularly the management and treatment of heart failure worldwide.

There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan. In this survey, we found that 250 children were diagnosed with symptomatic vitamin D deficiency. The estimated number of patients with symptomatic vitamin D deficiency per year was 183 (95% confidence interval (CI): 145-222). The overall annual incidence rate among children under 15 years of age was 1.1 per 100,000 population (95% CI: 0.9-1.4). The second survey has provided detailed information on 89 patients with symptomatic vitamin D deficiency under 5 years of age in hospitals in the current research group. The nationwide and second surveys estimated the overall annual incidence rate of symptomatic vitamin D deficiency in children under 5 years of age to be 3.5 (2.7-4.2) per 100,000 population. The second survey revealed 83% had bowed legs, 88% had exclusive breastfeeding, 49% had a restricted and/or unbalanced diet and 31% had insufficient sun exposure among the 89 patients. This is the first nationwide survey on definitive clinical vitamin D deficiency in children in Japan. Elucidating the frequency and characteristics of symptomatic vitamin D deficiency among children is useful to develop preventative public health strategies.

Background Lymphovascular invasion (LVI) in high-grade clinical T1 bladder cancer is usually considered a poor prognostic factor, but it is often difficult to achieve correct staging of T1 bladder cancer and diagnose the presence of LVI because of the inadequacy of conventional transurethral resection specimens. The aims of this study were to evaluate the prognostic value of LVI in patients with correctly staged high-grade pathological T1 (pT1) bladder cancer who initially underwent transurethral resection in one piece (TURBO). Methods Eighty-six high-grade pT1 bladder cancer patients who underwent TURBO were enrolled. Risk of tumor understaging was avoided by examining the vertical resection margin of the TURBO specimen. Immunohistochemical staining using D2-40 and CD31 was performed to confirm LVI. We examined the association of LVI with other clinicopathological factors and the impact of LVI on progression-free survival and cancer-specific survival. Results The median follow-up period was 49 months (range, 6-142). In all patients, the tumors were accurately staged as pT1 at initial TURBO. LVI was detected in 15 patients (17%) and was significantly associated with tumor growth pattern (P = 0.001). Multivariate analysis identified LVI as the only independent predictor for reduced progression-free survival (HR, 4.48; 95% CI, 1.45-13.90; P = 0.009) and cancer-specific survival (HR, 4.35; 95% CI, 1.17-16.24; P = 0.029). Conclusions The presence of LVI in TURBO specimens independently predicts poor clinical outcomes in patients with high-grade pT1 bladder cancer. This information may help urologists to counsel their patients when deciding whether to choose a bladder-preserving strategy or radical cystectomy.

Aims/Objectives Glycemic control varies according to stress level and the efficacy of control measures, affecting the outcomes of diabetes. Although detailed coping styles have not been well studied in patients with type 2 diabetes mellitus, problem‐focused coping strategies are believed to be related to better control of blood glucose. Associations between coping profiles/dimensions and blood glucose control were examined in individuals with type 2 diabetes. Materials and Methods The participants included 503 Japanese patients (mean age 63.9 ± 12.6 years) with type 2 diabetes. The average glycated hemoglobin A1c (HbA1c) levels were calculated from HbA1c levels measured more than four times within the 12 months before the assessment. Coping profiles were assessed using the Brief Scale for Coping Profile. Lifestyle factors were also included in the analyses. Results Factors other than age were not associated with HbA1c levels in patients who used insulin. Conversely, habitual alcohol consumption, single status, the adaptive emotion‐focused coping dimension, and changing mood and changing one’s point of view profiles were associated with HbA1c levels. Conclusions These findings suggest that adaptive emotion‐focused coping supports glycemic control in type 2 diabetes patients who do not use insulin. Additional studies using a longitudinal design are required to further examine the relationships between psychological factors and glycemic control., This study investigated coping styles associated with glucose control in people with type 2 diabetes. An adaptive emotion‐focused coping dimension supports glycemic control in people with type 2 diabetes who do not use insulin.

The combination chemotherapy regimen of eribulin (ERI) and trastuzumab (TRA)—the ERI-TRA regimen—has been shown to be highly tolerable for patients with recurrent or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, no sufficient clinical evidence is available for the long-term safety profile of the regimen. We report on three patients in the Phase I combination study of the regimen, for whom the regimen could be conducted over the long term. Patient #1 was a 68-year-old woman and underwent the regimen until cycle 23. Patient #2 was a 61-year-old woman and underwent the regimen until cycle 27. Patient #3 was a 59-year-old woman and underwent the regimen until cycle 22. All these patients had undergone TRA-based combination therapy before the onset of the regimen. Any new categories of adverse events did not occur in association with the long-term combination chemotherapy. Neutropenia experienced by these patients was reversible and easily manageable by dose adjustment (interruption/delay and reduction). Neither increase in the risk of cardiomyopathy nor the worsening of peripheral neuropathy greater than grade 1 was found. The present regimen was suggested to be a novel chemotherapeutic option for patients with HER2-positive recurrent or metastatic breast cancer. The fact that the long-term ERI-TRA regimen was successfully conducted for these patients can be supplementary clinical information that is beneficial for clinical oncologists.

OBJECTIVE Serum amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) levels have been proposed as a biomarker of linear growth in healthy children. The usefulness of NT-proCNP in patients with achondroplasia (ACH)/hypochondroplasia (HCH) remains to be elucidated. The objective was to study whether serum NT-proCNP level is a good biomarker for growth in ACH/HCH and other patients of short stature. DESIGN This was a longitudinal cohort study. PATIENTS Sixteen children with ACH (aged 0·4-4·3 years), six children with HCH (2·7-6·3 years), 23 children with idiopathic short stature (ISS) (2·2-9·0 years), eight short children with GH deficiency (GHD) (2·9-6·8 years) and five short children born small for gestational age (SGA) (2·0-6·6 years). Patients with ACH/HCH received GH treatment for 1 year. MEASUREMENTS Serum NT-proCNP levels and height were measured. RESULTS NT-proCNP levels positively correlated with height velocity in these short children (P < 0·05, r = 0·27). NT-proCNP levels inversely correlated with age in children with ISS alone (P < 0·01, r = -0·55). Serum NT-proCNP levels in patients with ACH/HCH were increased 3 months following the initiation of GH treatment (P < 0·05). Height SDS gain during GH treatment for 1 year was positively correlated with the changes in NT-proCNP levels after the initiation of GH (P < 0·01, r = 0·72). CONCLUSION Serum NT-proCNP levels may be a good biomarker to indicate the effect of GH treatment on growth in patients with ACH/HCH at least in the first year and height velocity in short stature patients.

The onset of type 2 diabetes mellitus(T2DM) is based on the insulin resistance and decreasing of insulin secretion. Residual β-cell function is a key factor in achieving optimal glycemic control in patients with type 2 diabetes. Glucagon induces insulin secretion by direcdtly stimulating β-cells, therefore glucagon stimulaton test(GST) is a reliable marker for β-cell function. Fasting C-peptide(CPR)-index(CPR[ng/ml] to glucose[mg/dl] ratio x100; F-CPRI) is used as a marker of insulin secretion. We evaluated the efficacy of postprandial CPR to glucose ratio(P-CPRI) as a tool for evaluating β-cell function. Japanese T2DM patients with inadequte glycemic control(HbA1c>7.0%) were enrolled in the study(n=333, insulin therapy =217). HbA1c, fasting CPR and glucose were measured, and F-CPRI was calculated. Postprandial(120 min after breakfast) CPR and glucose were measured, and P-CPRI was calculated. For the GST, CPR was determinated before and 6 min after 1mg of glucagon injection. GSTδCPR(CPR[6 min] - CPR[0 min]) was calculated. Factors correlated with GSTδCPR were analyzed using simple and multiple stepwise regression analysis. P value Disclosure Y. Matsuhashi: None. S. Chikazawa: None. H. Nakayama: None. M. Murabayashi: None. S. Mizushiri: None. S. Osonoi: None. K. Takahashi: None. H. Otaka: None. M. Yanagimachi: None. H. Murakami: None. M. Daimon: None.

The Stroke and Cardiovascular Disease Control Act was enacted in Japan in December 2018. This law has become the first ever legislative countermeasure against stroke and cardiovascular disease in Japan. The government shall make a “Basic Plan to Promote Stroke and Cardiovascular Disease Control Programs” with input from a council consisted of stakeholders. In accordance with the government plan, each prefecture shall make a prefectural plan. Both government and prefectural plans will be reviewed at least every six years. A nationwide approach is expected to contribute to reducing the burden of disease and to prolong healthy life expectancy.

Background: An immediate ambulance call offers the greatest opportunity for acute stroke therapy. Effectively using ambulance services requires strengthening the association between knowledge of early stroke symptoms and intention to call an ambulance at stroke onset, and encouraging the public to use ambulance services. Methods: The present study utilized data from the Acquisition of Stroke Knowledge (ASK) study, which administered multiple-choice, mail-in surveys regarding awareness of early stroke symptoms and response to a stroke attack before and after a 2-year stroke education campaign in two areas subject to intensive and moderate intervention, as well as in a control area, in Japan. In these three areas, 3833 individuals (1680, 1088 and 1065 participants in intensive intervention, moderate intervention, and control areas, respectively), aged 40 to 74 years, who responded appropriately to each survey were included in the present study. Results: After the intervention, the number of correctly identified symptoms significantly associated with intention to call an ambulance (P < 0.05) increased (eg, from 4 to 5 correctly identified symptoms), without increasing choice of decoy symptoms in the intensive intervention area. Meanwhile, in other areas, rate of identification of not only correct symptoms but also decoy symptoms associated with intention to call an ambulance increased. Furthermore, the association between improvement in the knowledge of stroke symptoms and intention to call an ambulance was observed only in the intensive intervention area (P = 0.009). Conclusions: Our results indicate that intensive interventions are useful for strengthening the association between correct knowledge of early stroke symptoms and intention to call an ambulance, without strengthening the association between incorrect knowledge and intention to call an ambulance.

Background Renal cell carcinoma is well-known for its propensity to metastasize to unusual sites. However, metastasis to the gallbladder has been rarely reported in the literature. Case presentation A 75-year-old Japanese (Asian) woman presented for further evaluation of a gallbladder polyp, 15 years after right radical nephrectomy for renal cell carcinoma. Computed tomography revealed a 12 mm enhancing pedunculated tumor in the gallbladder fundus. Open simple cholecystectomy was performed and the tumor was histologically confirmed as a metastasis of renal cell carcinoma to the gallbladder. Our patient is alive and has been disease-free for 3 years after cholecystectomy. Conclusions Although metastasis of renal cell carcinoma is a rare differential diagnosis of gallbladder tumors, simple cholecystectomy is likely to offer a chance of long-term survival for patients with gallbladder metastases of renal cell carcinoma.

Cystic lymphangiomas of the mesocolon are very rare in adults. They are usually asymptomatic, but can present with an acute abdomen. We report an adult patient with cystic lymphangioma of the mesocolon that manifested with peritonitis. A 33-year-old man presented with fever and severe pain with muscle guarding in the left abdomen. Laboratory data indicated high-grade inflammation. Enhanced computed tomography (CT) showed multiple low-density masses with peripherally enhancing rims, strongly suspicious for cysts, in the left abdomen. Based on a diagnosis of peritonitis, emergency surgery was performed and revealed many cysts in the descending mesocolon. Histopathological examination findings indicated a cystic lymphangioma. The post-operative course was uneventful, and 1-year follow-up CT showed no recurrence. This case demonstrates that cystic lymphangiomas of the mesocolon in adults can present with acute peritonitis, although this is extremely rare. Complete resection is required for accurate diagnosis and for preventing recurrence.

A 66-year-old woman presented with a 2-year history of asthma has progression of dyspnea within a week, and a computed tomography (CT) revealed an endotracheal tumor at level of aortic arch. The resected tumor, measured by 18 × 12 × 10 mm, has histologically malignant features including frank invasion with desmoplastic stroma and foci of necrosis. Presence of glycogen and mucin was confirmed by periodic acid-Schiff (PAS) and diastase PAS staining. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin (CK) 7 and AE1/3, focally positive for CK5/6 and CK14, but negative for CK20. Thyroid transcription factor-1 (TTF-1), Napsin A, and SP-A, indicating lung parenchymal origin were all negative. Other muscular markers, neuroendocrine markers, renal cell carcinoma markers, and markers related to perivascular epithelioid cell tumors were all negative. Postoperative systemic examination suggests no primary tumor outside the lung. The follow up was excellent being recurrence free for 14 months in spite of the positive surgical margin by the tumor cells. This is a first report of rare neoplasm, clear cell carcinoma of salivary gland type, presenting as an endotracheal mass.

Background: It is important that the general population be aware of the early symptoms, since it has been shown that early arrival to hospitals leads better prognosis of stroke patients. However, the general population is not well informed about the early symptoms of stroke. This study was conducted to clarify which stroke symptoms are less well known and which information sources are related to awareness of stroke symptoms. Methods: A multiple-choice, mail-in survey involving 5,540 randomly selected residents, aged 40-74 years, of 3 cities in Japan was conducted. Their knowledge about stroke symptoms and their information sources were surveyed; information sources were classified as mass media (television/newspaper/radio) and personal communication sources (posters/leaflets/internet/health professionals/family and/or friends). ‘Awareness' was defined as selecting all 5 of the correct stroke symptoms from among 10 listed symptoms with decoy choices. The estimated fraction of the possible impact due to each source on the whole population was also calculated by odds ratios (ORs) and the proportion of respondents who selected each source (Pe). The combined effects of mass media and personal communication sources on awareness were also assessed. Results: Of the 5,540 residents, only 23% selected all 5 correct symptoms. Visual disturbance was the least known of the 5 symptoms (35%). All sources were positively related to awareness, with ORs (Pe) of: television, 1.58 (72.5%); newspaper, 1.79 (48.0%); radio, 1.74 (13.3%); posters, 1.73 (7.6%); leaflets, 1.50 (24.7%); Internet, 1.66 (5.6%); health professionals, 1.33 (34.8%), and family/friends, 1.21 (44.6%). The estimated fraction of the possible impact due to each source was higher for mass media (television, 0.31 and newspaper, 0.28) than personal communication sources (Internet, 0.04 and leaflets, 0.12). Mass media only and mass media/personal communication sources were significantly associated (ORs: 1.66, 2.75, respectively). Conclusions: As a single method of public education, television could be the most effective strategy. Moreover, the combined approach involving mass media and personal communication sources might have a synergistic effect. Less well-known symptoms, such as visual disturbances, should be noted in public education campaigns.

S-1 plus cisplatin is the standard chemotherapy for recurrent gastric cancer. While depression and delirium are frequent in cancer patients, hypomania during chemotherapy is rare. We describe a rare case of hypomania during S-1 plus cisplatin treatment for recurrent gastric cancer. A 66-year-old woman, with no previous psychiatric disorder, received S-1 plus cisplatin for recurrent gastric cancer. She showed peculiar behavior. Physical examination, urine, blood and imaging findings were normal. There was no gastric cancer progression. During psychiatric consultation, she behaved inappropriately. However, she behaved normally while performing daily activities. She manifested a persistently elevated, expansive or irritable mood, clearly different from her usual non-depressed state, meeting hypomania diagnostic criteria. Her condition did not require chemotherapy discontinuation or additional medication. During the second and subsequent S-1 plus cisplatin cycles, symptoms were stable. Cancer patients often have adjustment disorders, depression and delirium, but rarely hypomania. Our patient showed no significant changes in blood biochemistry and brain and whole body imaging. While S-1 plus cisplatin-induced hypomania cannot be excluded, hypomanic symptoms did not improve during the chemotherapy rest period, nor was there deterioration during subsequent cycles, suggesting drug-induced mania to be unlikely. Possible onset mechanisms include manic defense phenomena, common with stressful life events. There are no reports of recurrent gastric cancer patients experiencing hypomania during S-1 or S-1 plus cisplatin therapy, i.e. our patient represents a rare course. Clinicians should recognize psychosis or mood disorders during gastric cancer treatment. Further accumulation of such rare cases might elucidate pathological mechanisms underlying hypomania in cancer patients.

Hayashi T, Sentani K, Oue N, Anami K, Sakamoto N, Ohara S, Teishima J, Noguchi T, Nakayama H, Taniyama K, Matsubara A & Yasui W (2011) Histopathology59, 710–721 Desmocollin 2 is a new immunohistochemical marker indicative of squamous differentiation in urothelial carcinoma Aims: Urothelial carcinoma (UC) with squamous differentiation tends to present at higher stages than pure UC. To distinguish UC with squamous differentiation from pure UC, a sensitive and specific marker is needed. Desmocollin 2 (DSC2) is a protein localized in desmosomal junctions of stratified epithelium, but little is known about its biological significance in bladder cancer. We examined the utility of DSC2 as a diagnostic marker. Methods and results: We analysed the immunohistochemical characteristics of DSC2, and studied the relationship of DSC2 expression with the expression of the known markers uroplakin III (UPIII), cytokeratin (CK)7, CK20, epidermal growth factor receptor (EGFR), and p53. DSC2 staining was detected in 24 of 25 (96%) cases of UC with squamous differentiation, but in none of 85 (0%) cases of pure UC. DSC2 staining was detected only in areas of squamous differentiation. DSC2 expression was mutually exclusive of UPIII expression, and was correlated with EGFR expression. Furthermore, DSC2 expression was correlated with higher stage (P = 0.0314) and poor prognosis (P = 0.0477). Conclusions: DSC2 staining offers high sensitivity (96%) and high specificity (100%) for the detection of squamous differentiation in UC. DSC2 is a useful immunohistochemical marker for separation of UC with squamous differentiation from pure UC.

Objectives: To demonstrate the usefulness of transurethral resection in one piece (TURBO) as an accurate pathological staging tool for bladder tumor. Methods: Ninety-seven patients with newly diagnosed bladder cancer underwent TURBO that was performed either in an en bloc or in a divisional manner. The histological quality of the resection specimens was evaluated and the pathological stage was assigned on the basis of the depth of invasion, which was histologically determined. Results: Specimens obtained by TURBO were well oriented and their 3-D architecture was maintained. This allowed a histological assessment of the entire specimen. Portions of muscularis propria were identified beneath the tumor base in the specimens of 80 (82%) patients. In only seven (7%) patients, the tumors had a deep resection margin positive for carcinoma and were ambiguously staged as “pT1 or higher” or “pT2 or higher”. Thus, definite pathological staging of TURBO specimens was possible in 90 (93%) patients (pTa, 30; pT1, 58; pT2, 2). Conclusions: An accurate pathological stage can be assigned to the TURBO specimen in most bladder cancer patients.

We report a case of sylvian hematoma enlarging 3 days after neck clipping for a ruptured anterior communicating artery aneurysm, in the contralateral sylvian fissure to the operative approach. This 65-year-old man was admitted with sudden loss of consciousness by ambulance. Angiography revealed a saccular aneurysm at the anterior communicating artery complex, measuring 2.3×2.4 mm and pointing inferiorly. The aneurysmal neck was successfully clipped by using the right pterional approach. To minimize predictable vasospasm, the hematoma in the left sylvian stem was removed. Postoperative CT scan showed a considerable decrease in hematoma in the basal cistern, but a slight decrease in the vertical portion of the left sylvian fissure. The patient’s consciousness gradually recovered, but deteriorated again 3 days after the operation. CT scan showed a large high-density area in the sylvian fissure suggesting unexpected enlargement of sylvian hematoma. A left fronto-temporal craniotomy was performed. When the subpial hematoma around the sylvial fissure was removed, a large amount of bloody cerebrospinal fluid (CSF) flowed out. The cavity containing bloody fluid was located in the temporal lobe. Postoperative course was uneventful. He recovered well, but moderate sensory aphasia remained. Sylvian hematoma is rarely associated with ruptured anterior communicating artery aneurysms. Furthermore, there has been no report describing delayed onset sylvian hematoma as far as we are aware. The following mechanism was considered to explain this very rare condition. Removal of subarachnoid hematoma in the left sylvian fissure made a recovery of CSF flow up to the limen insulae, but CSF appeared to be blocked from entering the distal sylvian fissure by the thick subpial sylvian hematoma. Instead of normal CSF flow route, CSF may enter into the weakened subpial space to allow accumulation of bloody CSF in the temporal lobe. Subpial hematoma may act as a one-way valve.

A 61-year-old woman was referred to our hospital with epigastralgia and appetite loss. Barium examination and upper gastrointestinal endoscopy revealed uneven erythematous mucosa with multiple elevated lesions from the gastric fornix to the upper corpus. Abdominal computed tomography showed thickening of the wall of the fornix and swelling of perigastric lymph nodes, but whole-body gallium scintigraphy and bone marrow examination did not indicate further involvement. Biopsy specimens showed diffuse infiltration of large atypical lymphoid cells in which Epstein-Barr virus (EBV) was detected by in situ hybridization. Diffuse large B-cell lymphoma (DLBCL), stage II1, was diagnosed. Combination chemotherapy [cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP)], was given, and this was followed by radiotherapy. Partial remission was achieved by chemotherapy, but the disease progressed rapidly during radiotherapy. Because the reported prognosis of EBV-positive DLBCL is unfavorable, the therapeutic strategy for EBV-positive gastric DLBCL should be considered carefully.

To examine whether dexamethasone suppression can reduce fluorine 18 fluorodeoxyglucose (FDG) uptake in false-positive (FP) findings in pulmonary and mediastinal lymph nodes in non-small cell lung cancer (NSCLC).Institutional ethics review board approved this prospective study with written informed consent. The study population was composed of 17 patients with NSCLC who underwent both baseline and dexamethasone suppression (24 hours after oral administration of 8 mg dexamethasone) FDG positron emission tomography/computed tomography and surgery. FDG uptake was evaluated by using a five-point visual scoring system (negative findings, score of 0-1; positive findings, score of 2-4) and maximum standardized uptake value (SUVmax). The Mann-Whitney U, Wilcoxon signed-rank, Kruskal-Wallis, or Spearman rank correlation tests were used as necessary for statistical evaluations.In 17 primary lesions, no significant difference was noted in visual score between baseline (mean, 3.4 ± 1.2) and dexamethasone suppression scans (mean, 3.3 ± 1.2; P = .16), although SUVmax was significantly lower on dexamethasone suppression scans (mean, 7.1 ± 5.2) than on baseline scans (mean, 8.6 ± 6.6; P = .005). In eight nodes with true-positive (TP) findings, there were no significant differences in visual score (mean for both, 3.8 ± 0.5) and SUVmax (mean, 5.3 ± 2.3 vs 5.5 ± 2.5, respectively; P = .81) between baseline and dexamethasone suppression scans. In 19 nodes with FP findings at baseline, dexamethasone suppression resulted in significantly lowered visual score (mean, 3.4 ± 0.6 vs 2.4 ± 0.8, respectively; P.001) and SUVmax (mean, 3.5 ± 0.8 vs 2.7 ± 0.7, respectively; P.001), and four nodes with FP findings were rated as true-negative findings on dexamethasone suppression scans, which resulted in a significant difference in SUVmax between nodal lesions with TP and FP findings (P = .014).Oral dexamethasone has the potential to reduce FDG uptake in pulmonary and mediastinal nodes with FP findings in NSCLC.

Cadherin-17 (CDH17), also called liver-intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis.

Regenerating islet-derived family, member 4 (Reg IV) is a candidate marker for cancer and inflammatory bowel disease. In the present study, immunohistochemical analysis of Reg IV was performed in various human neoplastic (n = 289) and non-neoplastic tissues. In the stomach, foveolar epithelium was negative for Reg IV, whereas goblet cells of intestinal metaplasia and neuroendocrine cells at the base of intestinal metaplasia expressed Reg IV. Neuroendocrine cells of the small intestine and colon showed strong expression of Reg IV, whereas goblet cells of the small intestine and colon showed weak or no expression of Reg IV. Insulin-producing beta cells of the endocrine pancreas were positive for Reg IV. Among 143 gastric adenocarcinomas, Reg IV expression was detected in 42 (29.4%) and was associated with both the intestinal mucin phenotype and neuroendocrine differentiation. No association was found between Reg IV expression and clinical characteristics such as tumour stage and patient prognosis. Of 36 colorectal adenocarcinomas, 13 (36.1%) were positive for Reg IV, which was associated with tumour stage (p = 0.0379, Fisher's exact test). Expression of Reg IV was detected in 14 (93.3%) of 15 colorectal carcinoid tumours. Reg IV expression was also detected in 5 (21.7%) of 23 ductal adenocarcinomas of the pancreas. In contrast, lung cancers (n = 30) and breast cancers (n = 30) did not express Reg IV. This is the first immunohistochemical analysis of the expression and distribution of Reg IV protein in human tumours. These data suggest that Reg IV is expressed by gastrointestinal and pancreatic tumours, including adenocarcinomas and carcinoid tumours, and that Reg IV is associated with intestinal and neuroendocrine differentiation of the stomach and gastric carcinoma.

Gastric cancer (GC) is still a serious health problem and remains the second most common type of fatal cancer worldwide. Comprehensive gene expression analyses may be useful to identify genes associated with invasion/metastasis in GC. Among them, array-based hybridization and serial analysis of gene expression (SAGE) are currently the most common approaches. Over the past 3 years, several large-scale gene expression studies with array-based hybridization and SAGE have been performed and several genes have been identified. This review describes genes associated with invasion/metastasis in GC which have been identified by array-based hybridization and SAGE. We compared the expression levels of the genes identified by array-based hybridization with our SAGE data. In addition, expression of the candidate genes obtained by SAGE was further investigated by quantitative RT-PCR of 40 GC samples. MIA and GW112 were overexpressed in 10 (25%) and 22 (55%) of 40 GC samples, and the overexpression of these two genes was associated with tumor stage, respectively. We also discuss the significance of HMGB1/amphoterin in invasion and metastasis of GC.

Gastric carcinoma (GC) is one of the most common malignancies worldwide. To better understand the genetic basis of this disease, we performed serial analysis of gene expression (SAGE) on four primary GC samples and one associated lymph node metastasis. We obtained a total of 137,706 expressed tags (Gene Expression Omnibus accession number GSE 545, SAGE Hiroshima gastric cancer tissue), including 38,903 that were unique. Comparing tags from our GC libraries containing different stages and different histologies, we found several genes and tags that are potentially involved in invasion, metastasis, and carcinogenesis. Among these, we selected 27 genes and measured mRNA expression levels in an additional 46 GC samples by quantitative reverse transcription-PCR. Frequently overexpressed genes (tumor/normal ratio > 2) were COL1A1 (percentage of cases with overexpression, 78.3%), CDH17 (73.9%), APOC1 (67.4%), COL1A2 (58.7%), YF13H12 (52.2%), CEACAM6 (50.0%), APOE (50.0%), REGIV (47.8%), S100A11 (41.3%), and FUS (41.3%). Among these genes, mRNA expression levels of CDH17 and APOE were associated with depth of tumor invasion (P = 0.0060 and P = 0.0139, respectively), and those of FUS and APOE were associated with degree of lymph node metastasis (P = 0.0416 and P = 0.0006, respectively). In addition, mRNA expression levels of FUS, COL1A1, COL1A2, and APOE were associated with stage (P = 0.0414, P = 0.0156, P = 0.0395, and P = 0.0125, respectively). Quantitative reverse transcription-PCR analysis also showed a high level of REGIV expression (>100 arbitrary units) in 14 of 46 GC samples (30.4%) but not in noncancerous tissues. We detected V5-tagged RegIV protein in the culture media of cells transfected with pcDNA-RegIV-V5 by Western blot. Our results provide a list of candidate genes that are potentially involved in invasion, metastasis, and carcinogenesis of GC. REGIV may serve as a specific biomarker for GC.

BACKGROUND AND PURPOSE The very old are expected to become a growing part of the stroke population in the industrialised part of the world. The aims of this study were to evaluate clinical characteristics of patients aged 85 years or more at stroke onset and to investigate very old age as an independent predictor of short- and long-term outcome. METHODS In the community-based Copenhagen Stroke Study we recorded admission clinical characteristics in 1197 consecutive stroke patients. Patients were stratified according to age groups on admission. Follow-up was performed at a mean of 7 years after stroke onset. By way of multiple logistic regression and survival analyses very old age was independently related to short- and long-term mortality and nursing home placement independent of other clinical characteristics. RESULTS 16% of patients were 85 years or older at the time of stroke onset. More of the very old were women (75% versus 50%, P

Pot1, a telomere end-binding protein in fission yeast and human, is proposed not only to cap telomeres but also to recruit telomerase to the ends of chromosomes. No study has been performed regarding Pot1 expression status in human cancers. Thus, we examined POT1 mRNA expression in 51 gastric cancer (GC) tissues and evaluated telomere length and 3′ telomeric overhang signals in 20 of the 51 GC tissues. Quantitative reverse transcription-PCR analysis showed that POT1 expression levels in the tumor relative to those in nonneoplastic mucosa (T/N ratio) were significantly higher in stage III/IV tumors than in stage I/II tumors (P = 0.005). Down-regulation of POT1 (T/n < 0.5) was observed more frequently in stage I/II GC (52.4%, 11 of 21) than in stage III/IV GC (23.3%, 7 of 30; P = 0.033), whereas up-regulation of POT1 (T/n > 2.0) was observed more frequently in stage III/IV GC (33.3%, 10 of 30) than in stage I/II GC (9.5%, 2 of 21; P = 0.048). POT1 expression levels showed decreased in accordance with telomere shortening (r = 0.713, P = 0.002). In-gel hybridization analysis showed that 3′ telomeric overhang signals decreased in accordance with decreases in POT1 expression levels (r = 0.696, P = 0.002) and telomere shortening (r = 0.570, P = 0.013). Reduced POT1 expression was observed in GC cell lines with telomeres shortened by treatment with azidothymidine. In addition, inhibition of Pot1 by antisense oligonucleotides led to telomere shortening as well as inhibition of telomerase activity in GC cells. Moreover, inhibition of Pot1 decreased 3′ overhang signals and increased the frequency of anaphase bridge (P = 0.0005). These data suggest that Pot1 may play an important role in regulation of telomere length and that inhibition of Pot1 may induce telomere dysfunction. Moreover, changes in POT1 expression levels may be associated with stomach carcinogenesis and GC progression.

症例は56歳の男性で, 主訴は右下腹部痛, 嘔吐. 精査したところイレウス管からの造影で回腸末端に閉塞部位を認め, 小腸腫瘍による腸閉塞の診断で, イレウス解除術を施行した. 術中, 虫垂が腫大し回腸に癒着, 内腔を閉塞しており, 虫垂癌の診断で回盲部切除術を施行した. 組織学的には低分化腺癌を合併した虫垂杯細胞カルチノイドの診断であった. 術後の補助化学療法は行わず術後半年が経過している. 杯細胞性カルチノイドはカルチノイド腫瘍の一亜型とされているが, 悪性度が高く予後不良であり腺癌の一種とも考えられている. 我々の集計では杯細胞カルチノイドの本邦報告は71例と少なく, 治療法, 予後に対する一定の見解は定まっていない. さらに, 本症例のように腺癌を合併した例は少なく, 今後, 腫瘍の発生機序, 治療法を確立していく上で興味深いと考え, 若干の文献的考察を加えて報告する.

Objectives:RhoC, a member of the ras-related small GTPase protein family, regulates cytoskeletal structures and has the potential to transform cultured cells. It has recently been reported that RhoC contributes to the metastatic phenotype of melanoma cells. The purpose of this study was to clarify its biological relevance to gastric carcinogenesis and metastasis. Methods: We examined the expression of RhoC by quantitative RT-PCR in 51 cases of gastric carcinoma tissues from prior surgical cases (intestinal type: 24 cases, diffuse type: 27 cases) and in 8 gastric carcinoma cell lines. Results:RhoC expression levels in primary tumors were significantly higher in cases with metastasis than in those without metastasis (p = 0.0202; Mann-Whitney U test). RhoC expression levels in primary tumor and their metastatic tumors were significantly higher than their corresponding nonneoplastic mucosa (p = 0.0357, and 0.0173, respectively; Wilcoxon signed rank test). RhoC mRNA expression was confirmed in the gastric carcinoma cell lines. Conclusion: Our findings suggest that elevated expression of the RhoC gene may be involved in the metastasis of gastric carcinomas and may be a good genetic marker for the prediction of a metastatic potential.

Thrombospondin-1 (TSP-1) has been shown to play a role in angiogenesis in a variety of cancers, but some studies indicated a difference in the mechanism of TSP-1 on neovascularization according to organ or histological type. Wild-type p53 protein has been shown to induce TSP-1 expression. We examined the expression of TSP-1 protein in 80 gastric carcinomas using immunohistochemistry and studied the relationship with microvessel counts, p53 expression and clinicopathological factors. We also performed reverse-transcriptase polymerase chain reaction analysis for the TSP-1 mRNA expression in gastric carcinoma cell lines and gastric cancer tissue after laser capture microdissection. Strong expression of TSP-1 protein was detected in 30 (38%) of the 80 cases. Positive staining for TSP-1 was seen in the cytoplasm of the cancer cells. TSP-1 mRNA expression was confirmed in a majority of gastric carcinoma cell lines and carcinoma tissues. Microvessel counts were significantly higher in tumors with strong TSP-1 protein expression than in those without expression or weak expression of TSP-1 ( P=0.011). No significant correlation was found between TSP-1 expression and p53 staining and clinicopathological factors. Our results support an idea that increased TSP-1 expression may be associated with an angiogenic phenotype in gastric carcinoma and suggest that TSP-1 may play diverse roles in each organ.

Aims: To investigate the smooth muscle nature of the spindle stromal cells in the capsule of thyroid tumours and tumour-like lesions. Methods: Immunostaining for high molecular weight caldesmon (HCD), a highly specific marker for smooth muscle differentiation, was performed in 70 primary thyroid tumours and tumour-like lesions (21 hyperplastic nodules, 29 follicular adenomas, five minimally invasive follicular carcinomas, six widely invasive follicular carcinomas, and nine encapsulated papillary carcinomas). Results: HCD positive stromal cells (HCD+ cells) were detected in the capsule of 20 of the 21 hyperplastic nodules, and all of the 29 follicular adenomas and five minimally invasive follicular carcinomas, whereas HCD+ cells were seen in the capsule of only four of the six widely invasive follicular carcinomas and no HCD+ cells were seen in the capsule of the nine encapsulated papillary carcinomas examined. Conclusions: The presence of HCD+ cells in the capsule is characteristic of thyroid follicular tumours and tumour-like lesions. The stromal cells in the capsule of thyroid follicular tumours and tumour-like lesions are different from those of encapsulated papillary carcinoma.

Aims: To investigate the distribution and roles of α smooth muscle actin (ASMA) positive stromal cells (ASMA+ cells), which belong to the myofibroblast group, within gastric carcinomas, with reference to three histological types (diffuse type, intestinal type, and solid type). Methods: In total, 74 surgically resected gastric carcinomas (24 diffuse type, 43 intestinal type, and seven solid type) were examined. ASMA positive and high molecular weight caldesmon (HCD) negative stromal cells were regarded as ASMA+ cells. The distribution of CD34 positive stromal cells (CD34+ cells) was also analysed immunohistochemically. Results: In the 24 diffuse-type gastric carcinomas, six of the 13 carcinomas invading the subserosa had ASMA+ cells in the tumour stroma, whereas all six diffuse-type gastric carcinomas confined to the submucosa and all five invading the muscularis propria had no ASMA+ cells in the tumour stroma. In the 43 intestinal-type gastric carcinomas, only five of the 21 carcinomas confined to the submucosa had ASMA+ cells in the tumour stroma, whereas 21 of the 22 intestinal-type gastric carcinomas invading the muscularis propria and the subserosa had ASMA+ cell bundles in the tumour stroma. The distribution of CD34+ cells in diffuse-type and intestinal-type gastric carcinomas was similar to that seen in a previously published series. All seven solid-type gastric carcinomas examined had ASMA+ cells but not CD34+ cells in the tumour stroma. No stromal cells double positive for ASMA and CD34 were detected within the diffuse-type tumours examined. Conclusions: These results suggest that ASMA expression in stromal cells is associated with tumour stroma formation of diffuse-type gastric carcinomas invading the subserosa, intestinal-type gastric carcinomas invading the muscularis propria and subserosa, and solid-type gastric carcinomas.

Background and Purpose — Body temperature is considered crucial in the management of acute stroke patients. Recently hypothermia applied as a therapy for stroke has been demonstrated to be feasible and safe in acute stroke patients. In the present study, we investigated the predictive role of admission body temperature to the long-term mortality in stroke patients. Methods — We studied 390 patients with acute stroke admitted within 6 hours from stroke onset. Admission clinical characteristics (age, sex, admission stroke severity, admission blood glucose, cardiovascular risk factor profile, and stroke subtype) were recorded for patients with hypothermia (body temperature ≤37°C) versus patients with hyperthermia (body temperature >37°C). Univariately the mortality rates for all patients were studied by Kaplan-Meier statistics. To find independent predictors of long-term mortality for all patients, Cox proportional-hazards models were built. We included all clinical characteristics and body temperature as a continuous variable. Results — Patients with hyperthermia had more severe strokes and more frequently diabetes, whereas no difference was found for the other clinical characteristics. For all patients mortality rate at 60 months after stroke was higher for patients with hyperthermia (73 per 100 cases versus 59 per 10 cases, P =0.001). When body temperature was studied in a multivariate Cox proportional-hazards model, a 1°C increase of admission body temperature independently predicted a 30% relative increase (95% CI, 4% to 57%) in long-term mortality risk. For 3-month survivors we found no association between body temperature and long-term survival when studied in a multivariate Cox proportional hazard model (hazards ratio, 1.11 per 1°C; 95% CI, 0.82 to 1.52). Conclusion — Low body temperature on admission is considered to be an independent predictor of good short-term outcome. The present study suggests that admission body temperature seems to be a major determinant even for long-term mortality after stroke. Hypothermic therapy in the early stage in which body temperature is kept low for a longer period after ictus could be a long-lasting neuroprotective measure.

Objectives- To estimate the need for and the costs of carotid Doppler and carotid endarterectomy after stroke or TIA in non-selected hospitalized patients. Material and methods - During 25 months hospitalized patients with stroke or TIA, in whom carotid endarterectomy could be relevant, were examined with carotid Doppler. If a significant stenosis was found, they were further evaluated for surgery. Based on our results, the requirement for future carotid endarterectomy and Doppler screening was estimated, and the costs of the procedures calculated. Results - Among 1351 patients 703 were screened with carotid Doppler. Forty-five had severe (70 99%) stenosis of the relevant carotid artery. Only 3 were operated on. The future costs of screening were estimated under different assumptions. Conclusion Carotid endarterectomy is expensive due to the large number of patients screened with carotid Doppler per operated patient. A careful clinical selection of patients for screening is necessary.

This study examines blood pressure (BP) and independent factors related to BP in the acute phase of stroke. The study is part of the community-based Copenhagen Stroke Study. In a multivariate regression model we analyzed the impact of clinical and medical factors on admission BP. BP declined with increasing time from stroke onset with a total of 8/4 mm Hg. Independent factors related to diastolic BP were ischemic heart disease (–3.9 mm Hg), male gender (2.2 mm Hg), known hypertension prior to stroke (8.6 mm Hg), and primary hemorrhage (9.7 mm Hg). Independent factors related to systolic BP were age (3.6 mm Hg/10-year increase), atrial fibrillation (–7.2 mm Hg), ischemic heart disease (–6.0 mm Hg), intracerebral hemorrhage (13.3 mm Hg), and known hypertension prior to stroke (16.3 mm Hg). No independent relations were seen between BP and diabetes, claudication, previous stroke, smoking, daily alcohol consumption, initial stroke severity and lesion size. The increase in BP in the acute phase of stroke is a uniform response to the ischemic event per se. BP is not related to stroke severity. Several factors are independently related to the BP level in acute stroke. The clinical significance of this is yet to be tested, but these factors may contribute to the seemingly complex relation between BP and outcome.

Background and purpose— Educating the youth about stroke is a promising approach for spreading stroke knowledge. The aim of this study was to verify communication of stroke knowledge to parents by educating junior high school students about stroke. Methods— We enrolled 1127 junior high school students (age, 13–15 years) and their parents in the Tochigi prefecture, Japan. All students received a stroke lesson, watched an animated cartoon, and read the related Manga comic as educational aids. The students took back home the Manga and discussed what they learned with their parents. Questionnaires on stroke knowledge were given to all at baseline and immediately after the lesson. Results— A total of 1125 students and 915 parents answered the questionnaires. In the students, the frequency of correct answers increased significantly for all questions on stroke symptoms except for headache, and for all questions on risk factors after the lesson. In the parents, the correct answer rates increased for stroke symptoms except for headache and numbness in one side of the body, and for all questions on risk factors except for hypertension. Ninety-one percent of students and 92.7% of parents correctly understood the Face, Arm, Speech, and Time (FAST) mnemonic after the lesson. Conclusions— Improvement of stroke knowledge immediately after the stroke lesson was observed in parents as well as their children, which indicated that our teaching materials using the Manga was effective in delivering the stroke knowledge to parents through their children.

To investigate the difference of surrounding stromal structure between the polypoid and flat adenomas in the colorectum, we performed microscopic study including immunohistochemistry in a total of 32 colorectal adenomas (typical 24 polypoid and eight flat adenomas), especially focusing on vessels around muscularis mucosa. All 24 polypoid adenomas accompanied vasculo-smooth muscle hamartomatous structure in association with muscularis mucosa and submucosal vessels, whereas none of eight flat adenomas had vasculo-smooth muscle hamartomatous structure; surrounding muscularis mucosa and submucosa of the flat adenomas are identical to those of normal colorectal tissue. Vasculo-smooth muscle hamartomatous structure is linked to the morphogenesis of colorectal polypoid adenomas.