Successful perioperative management for a breast cancer patient with Bernard–Soulier syndrome

We herein report the first case of a Bernard–Soulier syndrome (BSS) patient undergoing a surgical procedure for breast cancer. BSS is a rare hereditary thrombocytopathy associated with defects of the platelet glycoprotein complex glycoprotein Ib/V/IX and characterized by large platelets, thrombocytopenia, and severe bleeding symptoms. Because of the rarity of BSS, there are as yet no defined protocols for the perioperative management, which can be very complex and challenging in patients with coagulopathies, in particular BSS. In this case we successfully performed both an interventional examination as well as mastectomy with axillary lymph node dissection, under the preventive and intermittent transfusion of platelets. No intra- or postoperative bleeding complications occurred. Unfortunately, the patient was diagnosed as having metastatic disease involving liver, lungs, and bones 10 months after the surgery. She had received 1st, 2nd, and 3rd line chemotherapy without severe adverse events. However, gastrointestinal bleeding appeared after she was treated with 4th line chemotherapy. Finally, she succumbed 22 months after the breast surgery.     

Invasive ductal carcinoma of the pancreas showing exophytic growth

BACKGROUND:Invasive pancreatic carcinoma generally appears as poorly defined mass reflecting the infiltrative growth.We aimed to identify the histological and immunohistochemical features in a rare case of pancreatic carcinoma showing exophytic growth. METHODS:A 67-year-old woman presented with a mass of 5.0 cm in diameter in the pancreatic head.Preoperative computed tomography revealed a well-demarcated, primarily solid mass with a central low-density area. Magnetic resonance cholangiopancreatography revea...     

Sleep modulates cortical connectivity and excitability in humans: Direct evidence from neural activity induced by single‐pulse electrical stimulation

Sleep‐induced changes in human brain connectivity/excitability and their physiologic basis remain unclear, especially in the frontal lobe. We investigated sleep‐induced connectivity and excitability changes in 11 patients who underwent chronic implantation of subdural electrodes for epilepsy surgery. Single‐pulse electrical stimuli were directly injected to a part of the cortices, and cortico‐cortical evoked potentials (CCEPs) and CCEP‐related high‐gamma activities (HGA: 100–200 Hz) were recorded from adjacent and remote cortices as proxies of effective connectivity and induced neuronal activity, respectively. HGA power during the initial CCEP component (N1) correlated with the N1 size itself across all states investigated. The degree of cortical connectivity and excitability changed during sleep depending on sleep stage, approximately showing dichotomy of awake vs. non‐rapid eye movement (REM) [NREM] sleep. On the other hand, REM sleep partly had properties of both awake and NREM sleep, placing itself in the intermediate state between them. Compared with the awake state, single‐pulse stimulation especially during NREM sleep induced increased connectivity (N1 size) and neuronal excitability (HGA increase at N1), which was immediately followed by intense inhibition (HGA decrease). The HGA decrease was temporally followed by the N2 peak (the second CCEP component), and then by HGA re‐increase during sleep across all lobes. This HGA rebound or re‐increase of neuronal synchrony was largest in the frontal lobe compared with the other lobes. These properties of sleep‐induced changes of the cortex may be related to unconsciousness during sleep and frequent nocturnal seizures in frontal lobe epilepsy. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc .     

Non-palpable ductal carcinomain situ (DCIS) with microinvasion arising in a radial scar presenting with spiculation alone on mammograms: A case report

A case of ductal carcinoma in situ (DCIS) with microinvasion arising in a radial scar of the breast is presented. A 57-year-old woman visited our hospital with bloody discharge from her left nipple. There were no abnormal findings on cytology, carcinoembryonic antigen (CEA) level of nipple discharge was <500 ng/ml, and mammograms were normal. After 2 years of careful periodic follow-up, spiculation without a central core appeared on mammograms. The CEA level of the nipple discharge increased to 1,000 ng/ml. Ductgraphy showed a connection between the duct with the discharge and the center of the spiculation. Since these findings suggested malignancy, she underwent segmentectomy of the breast, and pathological examination showed a radial scar and DCIS with microinvasion in the ducts within the radiating bands of fibrous tissues. We discuss the characteristics of a radial scar and its relationship to breast cancer based on our experience and a review of the literature.     

Immunotherapy-responsive Non-paraneoplastic Encephalitis with Antibodies against GAD,LGI1, and GABAA Receptor

A 62-year-old man showed abnormal behavior. Brain magnetic resonance imaging revealed multifocal lesions on T2-weighted images. Initial screening revealed that he was seropositive for antibodies against glutamate decarboxylase, which usually indicates treatment resistance to autoimmune encephalitis (AE). Intensive immunosuppressive therapies, however, improved the neurological symptoms. In line with this, we also detected seropositivity for antibodies against leucine-rich glioma-inactivated 1 and gamma-aminobutyric acid A receptor (GABA_AR). Brain imaging and treatment responsiveness suggested that antibodies against GABA_AR were the main cause of symptoms. Furthermore, the patient showed the presence of triple anti-neural antibodies in the absence of malignancy and had a favorable clinical course.     

Hepatoma-targeted gene delivery using a tumor cell–specific gene regulation system combined with a human liver cell–specific bionanocapsule

Hepatoma (hepatocellular carcinoma) is the most common type of malignant tumor originating in the liver and has a relatively low 5-year survival rate. The development of hepatoma-targeted therapy is needed to increase treatment efficiency and to reduce the incidence of undesirable side effects. In this study we developed a novel hepatoma-targeted gene delivery system. The gene delivery system was prepared by combining a human liver cell–specific bionanocapsule (BNC) and a tumor cell–specific gene regulation polymer, which responds to hyperactivated protein kinase Cα in hepatoma cells. The complex of the polymer-DNA with BNCs was delivered into cells and tissues. The developed system showed increased transfection efficiency and resulted in cell-specific gene expression in hepatoma cells and tissues (HuH-7), but no gene expression in normal human hepatocytes or human epidermoid tumor cells (A431). The combination of a tumor cell-specific gene regulation system responding to protein kinase Cα and BNCs showed excellent potential for the selective treatment of hepatomas. The system could be a useful method with applications in hepatoma-specific gene therapy and molecular imaging.From the Clinical EditorHepatocellular carcinoma is the most common type of malignant tumor in the liver with a low 5-year survival rate. In this study, a novel hepatoma-targeted gene delivery system was prepared by combining a human liver cell-specific bionanocapsule and a tumor cell-specific gene regulation polymer, which responds to hyperactivated protein kinase C (PKC)a in hepatoma cells. The system could be a useful in hepatoma-specific gene therapy and molecular imaging.     

Mitoxantrone for the treatment of Japanese patients with multiple sclerosis]

We retrospectively evaluated the benefits of mitoxantrone (MITX) treatment in Japanese patients with multiple sclerosis (MS) with more than 3 relapses per year or a deterioration of more than one Expanded Disability Status Scale (EDSS) of Kurtzke score per year despite having IFN beta 1b therapy. Monthly intravenous injections of MITX, 10-12 mg/m2, for 3 months were followed by an additional treatment every 3 months. Nine patients (6 women, 3 men) with a mean age of 39 years, a mean disease duration of 3.9 years, and a mean EDSS score of 6.7 were studied. Seven patients had long spinal cord lesions (LCL-MS). Most patients tolerated the treatment, although 2 patients stopped MITX therapy after 3 injections because of severe appetite loss. The 7 patients who continued MITX therapy for more than 3 times significantly decreased their relapse rate and EDSS deterioration. The average relapse count in the year preceding initiation of MITX therapy was 4.3 (range: 3-6)/year, EDSS score increased by 2.7 (range: 1-7)/year. The average relapse count was 2.3 (range: 0-4)/year from 0 to 6 months after MITX therapy (p = 0.114), and 1.1 (range: 0-4)/year from 7 to 12 months (p = 0.285). The average EDSS deterioration was -0.4 (range -2-1) from 0 to 6 months after MITX therapy (p = 0.018), and there was no deterioration from 7 to 12 months. Most patients received granulocyte colony stimulating factor because of leukocytopenia caused by MITX. No patients showed any decrease in cardiac ejection fraction during this observation period. For Japanese MS patients, MITX therapy was very effective to suppress relapses without incurring severe adverse events.     

Short History of EUFOS

The aim of this study was to analyze the causes for revision procedures, surgical findings and audiological outcome in reoperated cochlear implant patients. The medical records of 45 patients were reviewed retrospectively for age at the time of implantation, the implant was used for initial and revision surgeries, the duration of implant use before revision, surgical findings, and postoperative audiological results. Generally, children were reoperated more often than adults (12.5 vs. 6.9%) and, with one exception of improper electrode insertion, there were no major post-revision complications. Device failure (DF) was the main cause for revision surgery (23/45) followed by wound/flap problems, magnet/receiver-stimulator displacement, foreign body/allergic reaction, subperiosteal abscess, misplaced electrode, intractable vertigo, cholesteatoma and extrusion of the positioner. No significant difference was found in the rate of DF between children and adults for each implant separately (P = 0.289 for Nucleus 22, P = 0.355 for Nucleus 24, P = 0.683 for Clarion and P = 1.0 for Med-El). The failure rates of different implants did not differed significantly among adults. DF in the Clarion group was significantly higher compared to the Nucleus and Med-El combined for pediatric patients (P = 0.0218) and all CI recipients (adults + children; P = 0.0055). The post-revision audiological benefit was unchanged or improved compared to the initial implantation values in all reimplanted patients and was not influenced by minor surgical procedures (wound revision, drainage of any collection, magnet replacement, or relocation of receiver-stimulator). Since DF was found to be the most common cause for reoperation, improving device technology could prevent the vast majority of revision procedures.     

Diverse fibrillar peptides directly bind the Alzheimer's amyloid precursor protein and amyloid precursor-like protein 2 resulting in cellular accumulation

The Alzheimer's disease Abeta peptide can increase the levels of cell-associated amyloid precursor protein (APP) in vitro. To determine the specificity of this response for Abeta and whether it is related to cytotoxicity, we tested a diverse range of fibrillar peptides including amyloid-beta (Abeta), the fibrillar prion peptides PrP106-126 and PrP178-193 and human islet-cell amylin. All these peptides increased the levels of APP and amyloid precursor-like protein 2 (APLP2) in primary cultures of astrocytes and neurons. Specificity was shown by a lack of change to amyloid precursor-like protein 1, tau-1 and cellular prion protein (PrP(c)) levels. APP and APLP2 levels were elevated only in cultures exposed to fibrillar peptides as assessed by electron microscopy and not in cultures treated with non-fibrillogenic peptide variants or aggregated lipoprotein. We found that PrP106-126 and the non-toxic but fibril-forming PrP178-193 increased APP levels in cultures derived from both wild-type and PrP(c)-deficient mice indicating that fibrillar peptides up-regulate APP through a non-cytotoxic mechanism and irrespective of parental protein expression. Fibrillar PrP106-126 and Abeta peptides bound recombinant APP and APLP2 suggesting the accumulation of these proteins was mediated by direct binding to the fibrillated peptide. This was supported by decreased APP accumulation following extensive washing of the cultures to remove fibrillar aggregates. Pre-incubation of fibrillar peptide with recombinant APP18-146, the putative fibril binding site, also abrogated the accumulation of APP. These findings show that diverse fibrillogenic peptides can induce accumulation of APP and APLP2 and this mechanism could contribute to pathogenesis in neurodegenerative disorders.     

PINEAL CHANGE IN REESE'S SYNDROME

Two autopsy cases of Reese's syndrome showing conspicuous retinal dysplasia are reported. Stress Is laid on pineal changes seen in both, one of which was severe devastation assumed to be hypoplasia and the other was inability of its identification at autopsy being explained as aplasia or severe hypoplasia of this particular organ.
Anomalous changes of various degrees have been reported to exist not rarely in various organs including the central nervous system in this syndrome, but the most constant and important one is believed to be retinal dysplasia frequently associated with microphthalmia. On the other hand, the pineal gland is said to be closely related to the eye, which fact seems to have been already accepted with lower animals but only postulated, although with considerable reasonability, in higher animals. Our hypothesis is that the pineal hypoplasia of our cases may not have occurred simultaneously by chance, but, may have resulted from close relation to their ocular hypoplasia.
The moot phenomenon, pineal change in Reese's syndrome, should be confirmed in other cases before being established, and should this be accepted, it would be adequate to add pineal hypoplasia as another Important finding of Reese's syndrome.