A Nationwide Epidemiological Survey of Adolescent Patients With Diverse Symptoms Similar to Those Following Human Papillomavirus Vaccination: Background Prevalence and Incidence for Considering Vaccine Safety in Japan.

BACKGROUND: Since June 2013, Japan has suspended proactive recommendation of human papillomavirus (HPV) vaccination due to self-reported diverse symptoms, including pain and motor dysfunction, as possible serious adverse events following immunization. Although these symptoms may be seen in adolescents without HPV vaccination, their frequency, taking into account disease severity, has not been examined. METHODS: A two-stage, descriptive, nationwide epidemiological survey was conducted in 2016, with a 6-month target period from July 1 to December 31, 2015, to estimate the prevalence and incidence of diverse symptoms among Japanese adolescents without HPV vaccination. Participants were 11,037 medical departments in hospitals selected nationwide by stratified random sampling. Eligible patients had to satisfy four criteria: (1) aged 12-18 years upon visiting hospital; (2) having at least one of four symptoms/disorders (pain or sensory dysfunction, motor dysfunction, autonomic dysfunction, or cognitive impairment); (3) symptoms/disorders persisting for at least 3 months; and (4) both criteria (2) and (3) influence attendance at school or work. We then extracted data of patients with diverse symptoms similar to those after HPV vaccination while considering opinions of doctors in charge. RESULTS: Estimated 6-month period prevalence of diverse symptoms among girls aged 12-18 years without HPV vaccination was 20.2 per 100,000. Annual incidence was estimated to be 7.3 per 100,000. CONCLUSION: Adolescent Japanese girls without HPV vaccination also visited hospitals with diverse symptoms similar to those following HPV vaccination. Our findings predict the medical demands for coincident diverse symptoms, which are temporally associated with but not caused by HPV vaccination of Japanese adolescents.

[Usefulness of CT in the Lateral Decubitus Position for Preoperative Evaluation of Cranioplasty].

Patients with massive brain swelling undergo external decompressive craniectomy to manage intracranial pressure. Following supratentorial craniectomy, and after the brain swelling is relieved, cranioplasty is performed. Although feasibility of the surgery is usually assessed by CT scanning in a supine position, it is sometimes difficult to determine whether the surgery can be performed safely. Although nine patients underwent a decompressive craniectomy during the study period, only six patients could undergo brain CT-first in a supine position and next in a lateral decubitus position with the surgical side upward-before cranioplasty. On CT images, the distance from the midline to the brain surface was measured on the image where brain bulging was maximal, and the bulging was calculated by comparing the image with the distance measured on the contralateral side. In all cases, brain bulging decreased with this change in position. The decrease ranged from 5.5-9.2mm(mean 7.1mm). Patients with brain bulging of 2.8-3.6mm in the lateral decubitus position needed no additional procedure, or only required drainage of a very small amount of cerebrospinal fluid(CSF)from the brain surface. Those with brain bulging of 5.1-12mm showed ventricular dilatation on CT images, and required ventricular puncture or spinal CSF drainage to decrease brain bulging for cranioplasty. We believe that the lateral decubitus position, with the surgical side upward, ameliorates the local brain shift induced by gravity. A lateral position during CT simulates the surgical head position for cranioplasty and can help to assess whether cranioplasty is feasible.

Multiple Cerebral Hemorrhagic Lesions Depicted by Susceptibility-Weighted Imaging in a Patient with Down Syndrome: Case Report.

Our objective is to study a 53-year-old woman with Down syndrome presented with massive lobar hematoma in the left fronto-parietal lobe, and who underwent craniotomy and hematoma evacuation. Histopathological diagnosis of surgical specimen was amyloid angiopathy. Postoperative magnetic resonance studies were performed. The lesion this time showed mixed intensity on susceptibility-weighted imaging. In addition, multiple hypointense lesions were evident. An old previously unidentified hemorrhage in the right temporo-parietal lobe was accompanied by superficial cortical siderosis. Old bleeds were apparent in subcortical areas. These various kinds of hemorrhagic lesion were consistent with findings of amyloid angiopathy reported in the elderly. Most reported cases of Down syndrome associated with intracerebral hemorrhage have involved middle-aged patients. Magnetic resonance studies for Down syndrome patients before old age may disclose the degree to which amyloid angiopathy progresses in the brain of these patients.

Subarachnoid hemorrhage secondary to a ruptured middle cerebral aneurysm in a patient with osteogenesis imperfecta: a case report.

BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders that occur owing to the abnormalities in type 1 collagen, and is characterized by increased bone fragility and other extraskeletal manifestations. We report the case of a patient who was diagnosed with OI following subarachnoid hemorrhage (SAH) secondary to a ruptured saccular intracranial aneurysm (IA). CASE PRESENTATION: A 37-year-old woman was referred to our hospital because of sudden headache and vomiting. She was diagnosed with SAH (World Federation of Neurosurgical Society grade 2) owing to an aneurysm of the middle cerebral artery. She then underwent surgical clipping of the aneurysm successfully. She had blue sclerae, a history of several fractures of the extremities, and a family history of bone fragility and blue sclerae in her son. According to these findings, she was diagnosed with OI type 1. We performed genetic analysis for a single nucleotide G/C polymorphism (SNP) of exon 28 of the gene encoding for alpha-2 polypeptide of collagen 1, which is a potential risk factor for IA. However, this SNP was not detected in this patient or in five normal control subjects. Other genetic analyses did not reveal any mutations of the COL1A1 or COL1A2 gene. The cerebrovascular system is less frequently involved in OI. OI is associated with increased vascular weakness owing to collagen deficiency in and around the blood vessels. SAH secondary to a ruptured IA with OI has been reported in only six cases. CONCLUSION: The patient followed a good clinical course after surgery. It remains controversial whether IAs are caused by OI or IAs are coincidentally complicated with OI.

Sellar Masses that Present with Severe Hyponatremia.

OBJECTIVE: Hyponatremia is a known but underrecognized presentation of sellar lesions. Herein, we present a series of patients who presented with single or multiple episodes of hyponatremia. METHODS: Over 5 years, patients undergoing endonasal surgery for a de novo sellar mass with hyponatremia as an initial presentation were included. Pathology, sodium levels, pituitary hormonal status, and treatment course were documented. RESULTS: Of 282 patients, 16 (5.7%) (9 males, 7 females, age 32 to 84 years) presented with severe hyponatremia, with a mean serum sodium level of 115 ± 6 mmol/L (range, 101 to 125 mmol/L), and 3 patients had 2 or more episodes. Severe hyponatremia was a presenting sign in 0, 4.1, 14.3, and 37.5% of patients with craniopharyngiomas (n = 10), pituitary adenomas (n = 243), Rathke's cleft cysts (RCCs) (n = 21), and sellar arachnoid cysts (n = 8), respectively (P<.01). Half of the patients presenting with hyponatremia, including 6 of 10 patients with adenomas and 2 of 3 patients with RCCs, had pituitary apoplexy or cyst rupture. All patients had anterior pituitary gland dysfunction, including 81% with hypoadrenalism and 69% with hypothyroidism. Following surgery, hormonal status was unchanged or improved in 15 patients (median follow-up, 14 months). No patient had tumor/cyst recurrence or recurrent hyponatremia. CONCLUSION: Severe hyponatremia was a presenting sign in 5.7% of patients with sellar pathology, most frequently in patients with arachnoid cysts, RCCs, and pituitary apoplexy. Patients with new-onset severe hyponatremia and no obvious pharmacologic or systemic cause should undergo pituitary hormonal evaluation and brain imaging. Surgical resection and correction of hormonal deficiencies are associated with resolution of recurrent hyponatremic episodes.

Molecular status of pituitary carcinoma and atypical adenoma that contributes the effectiveness of temozolomide.

There have been several reports of temozolomide (TMZ) treatment of pituitary carcinomas and atypical adenomas. O(6)-methyl-guanine-DNA methyltransferase is not the sole molecule determining the sensitivity to TMZ in pituitary carcinomas and atypical adenomas. The Japan Society of Hypothalamic and Pituitary Tumors study suggests that MSH6, one of mismatch repair pathway enzyme, fulfills a contributory role to the efficacy of TMZ treatment for pituitary carcinomas and atypical adenomas. The preserved MSH6 function might be essential for the responsiveness to TMZ treatment in pituitary carcinomas and atypical adenomas.

Reversible and multiphasic parenchymal changes in MRI after coil embolization for a ruptured cerebral aneurysm.

Background: Reversible and multiphasic parenchymal changes in magnetic resonance imaging (MRI) are exceedingly rare. The authors experienced a case of reversible and multiphasic parenchymal changes in MRI after coil embolization for a ruptured cerebral aneurysm. Case Description: A 48-year-old woman had a sudden onset of severe headaches and was referred to us for coil embolization. She was alert-oriented and had no neurologic deficits. Her medical history was atopic dermatitis and metal allergy. A head computed tomography (CT) scan demonstrated subarachnoid hemorrhage, and three-dimensional-CT angiography revealed a left internal carotid artery-posterior communicating artery aneurysm. Coil embolization was performed on the next day and seven coils made by three different manufacturers were used for the embolization. Despite no neurologic deficits after the surgery and no abnormal findings in MRI 7 days after the coil embolization, an MRI 2 weeks after embolization demonstrated delayed multiple white matter high intense lesions on T2-weighted image and fluid-attenuated inversion recovery in the left hemisphere. Repeat MRI scans showed multiple high intense lesions at various locations and at different timings. The blood test revealed the elevation of the proportion of EOS up to 9.7%, strongly indicating some allergic response. The MRI scan obtained 3 months after the onset confirmed the complete disappearance of the lesions. Conclusion: Given her history of metal allergy, and the reversible and multiphasic lesions in the non-vascular territories of the treated aneurysm, metal allergic encephalitis was most likely despite no clear evidence.

Aneurysmal subarachnoid hemorrhage in a patient with human immunodeficiency virus type 1 infection. Case report.

A 54-year-old human immunodeficiency virus type 1 (HIV-1)-infected homosexual Japanese male was found to have collapsed in his bathroom and was brought to our facility with diminished level of consciousness. Computed tomography showed subarachnoid hemorrhage (SAH). He was severely dehydrated with unstable general status that deterred us from performing emergent surgery. Cerebral angiography performed on the 18th hospital day revealed bilateral distal anterior cerebral artery aneurysms. Clipping of these aneurysms was performed on the 30th hospital day and no postoperative complications were experienced. The scalp wound showed no delayed healing, whereas the tracheostomy wound showed repeated wound dehiscence and delayed healing. Postoperative highly active antiretroviral therapy with antibiotic treatment gradually improved his general and immunological conditions. The patient was finally discharged as independent with mild muscle weakness in the bilateral lower extremities. HIV-1 infection should not be the guiding factor in the decision to aggressively treat concomitant aneurysmal disease. Clipping of cerebral aneurysms with full craniotomy or endovascular obliteration should be considered even in HIV-1-infected patients with SAH.

Lemierre Syndrome Associated with Ipsilateral Recurrent Laryngeal Nerve Palsy: A Case Report and Review.

Lemierre syndrome (LS) is a rare life-threatening disease that is often caused by an acute oropharyngeal infection with a secondary thrombophlebitis of the internal jugular vein. LS rarely manifests as cranial nerve palsy. To the best of our knowledge, this is the second case report of LS associated with recurrent laryngeal nerve palsy. A 66-year-old female presented to a dental clinic with gingivitis and sore throat. Due to moderate periodontitis, her left first upper molar was extracted. A few days later, she subsequently developed a coarse voice and occipital headaches, and was referred to an otolaryngologist. She was diagnosed with left recurrent laryngeal nerve palsy and subsequent left-sided otitis media, and was referred to us for persistent headaches. She intermittently presented with high-grade fever and complained of salty taste disturbance. Her head magnetic resonance imaging (MRI) revealed left mastoiditis, thrombosis in the left transverse and sigmoid sinus, and left internal jugular vein. Her laboratory tests revealed an elevated white blood cell count, levels of C-reactive protein, and D-dimer. No endogenous coagulopathy was confirmed. Although, blood and cerebrospinal fluid culture grew no microorganisms, respectively, the empirically determined antibiotic therapy was initiated. In a week, the patient defervesced and had no headaches despite persistent thrombosis. Early diagnosis and an immediate antibiotic treatment are crucial for LS patients. Anticoagulation therapy was not needed for our patient and is still controversial for LS.

[Multiple extracranial metastases from a meningeal hemangiopericytoma and severe hypoglycemia: a case report].

Extracranial multiple metastases from meningeal hemangiopericytoma have been reported only rarely. The authors describe the case of a 61-year-old woman, who was previously diagnosed as having primary meningeal hemangiopericytoma with its multiple metastases to the liver, lumbar spine, etc. and who suffered from a sudden attack of hypoglycemia. Considering the history of her present illness, this hypoglycemic shock was most likely brought on by the remarkable metastatic tumors to the liver. Recent literature pertinent to hypoglycemia suggests that insulin-like growth factor-II (IGF-II) produced by tumor is strongly suspected to be involved in the development of hypoglycemia.

Cancer stem cells: progress and challenges in lung cancer.

The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called "cancer stem cells" (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs.

Scedosporium aurantiacum brain abscess after near-drowning in a survivor of a tsunami in Japan.

Many victims of the tsunami that occurred following the Great East Japan Earthquake on March 11, 2011 developed systemic disorders owing to aspiration pneumonia. Herein, we report a case of tsunami lung wherein Scedosporium aurantiacum was detected in the respiratory tract. A magnetic resonance image of the patient's head confirmed multiple brain abscesses and lateral right ventricle enlargement. In this case report, we describe a potential refractory multidrug-resistant infection following a tsunami disaster.

Clinicopathological and molecular histochemical review of skull base metastasis from differentiated thyroid carcinoma.

Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma.

Single stage multiple stenting in Takayasu's arteritis. Case report.

A 32-year-old Filipino female presented with Takayasu's arteritis manifesting as an abrupt onset of syncope. Physical examination revealed diminished consciousness, right hemiparesis, and a large discrepancy in blood pressure between the upper and lower extremities. Magnetic resonance imaging revealed cerebral infarcts in the left basal ganglia and the left temporal lobe. Angiography revealed complete occlusion of the left common carotid artery and severe stenosis of the brachiocephalic artery, the right common carotid artery, and the left subclavian artery. Based on the clinical examination and studies, the diagnosis was Takayasu's arteritis, type I. The patient's condition stabilized after 2 months of prednisone and anti-platelet therapy. Single stage multiple stenting in the brachiocephalic artery, the right common carotid artery, and the left subclavian artery was then performed using high pressure inflation to dilate the arteries due to the remarkably rigid lesions that resulted from extensive and diffuse fibrosis throughout the vessel walls. Although a small intimal flap occurred during inflation of the left subclavian artery, re-dilation was possible with the stent. Even with evidence of notable recovery in blood pressure and cerebral blood flow, no further neurological improvement was observed. In view of the favorable short- and intermediate-term results, single stage multiple stenting may be the optimum treatment option for first-line stent-supported angioplasty in patients with Takayasu's arteritis.

Factors associated with the empowerment of Japanese families raising a child with developmental disorders.

We identified factors associated with the empowerment of Japanese families using the Family Empowerment Scale (FES) to contribute to the improvement of empowerment in Japanese families raising a child with developmental disorders (DDs). The study was conducted in 350 caregivers who raised children aged 4-18 years with DDs in urban and suburban districts in Japan. Multiple regression analysis of data collected from 275 respondents revealed that a decrease in family empowerment level correlated with a higher number of siblings reared together, a shorter period since the diagnosis was made, and lower awareness of social support and self-efficacy in caregivers. Medications, possession of an intellectual disability certificate, infrequent hospital visits of the child, disuse of local services by caregivers, and young caregivers also correlated with a lower level of empowerment in the Japanese family.

Tumor suppressor gene-based nanotherapy: from test tube to the clinic.

Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.

Multiple Scedosporium apiospermum abscesses in a woman survivor of a tsunami in northeastern Japan: a case report.

INTRODUCTION: Scedosporium apiospermum is increasingly recognized as a cause of localized and disseminated mycotic infections in near-drowning victims. CASE PRESENTATION: We report the case of a 59-year-old Japanese woman who was a survivor of a tsunami in northeastern Japan and who had lung and brain abscesses caused by S. apiospermum. Initially, an aspergillus infection was suspected, so she was treated with micafungin. However, computed tomography scans of her chest revealed lung abscesses, and magnetic resonance images demonstrated multiple abscesses in her brain. S. apiospermum was cultured from her bronchoalveolar lavage fluid, and antimycotic therapy with voriconazole was initiated. Since she developed an increase in the frequency of premature ventricular contractions, an adverse drug reaction to the voriconazole was suspected. She was started on a treatment of a combination of low-dose voriconazole and liposomal amphotericin B. After combination therapy, further computed tomography scans of the chest and magnetic resonance images of her brain showed a demarcation of abscesses. CONCLUSIONS: Voriconazole appeared to have a successful record in treating scedosporiosis after a near drowning but, owing to several adverse effects, may possibly not be recommended. Thus, a combination treatment of low-dose voriconazole and liposomal amphotericin B may be a safe and effective treatment for an S. apiospermum infection. Even though a diagnosis of scedosporiosis may be difficult, a fast and correct etiological diagnosis could improve the patient's chance of recovery in any case.