Correlation of Aβ deposition in the nasal cavity with the formation of senile plaques in the brain of a transgenic mouse model of Alzheimer's disease

The deposition of β-amyloid peptides (Aβ) is commonly reported in the nasal cavity of Alzheimer's disease (AD) patients, although the pathological significance of this finding is unknown. This study compared Aβ concentrations in the nasal area with those in the brain, blood, and cerebrospinal fluid, respectively. Immunohistochemical analysis identified Aβ deposits in the nasal epithelium of Tg2576 mice. Enzyme-linked immunosorbent assay measurements revealed a correlation between the content of Aβ42 in the nasal area and that in the brain, but not with that in the blood. These results suggest that the highly accessible nasal cavity could be a useful site for diagnostic analysis of AD based on Aβ content.     

Surgical removal of infected pacemaker leads without cardiopulmonary bypass after failed extraction using the Excimer Laser Sheath Extraction System

With the growing number of cardiac pacemakers and internal cardioverter defibrillator implantations, problems with endocardial lead infection have been increasing. The newly developed Excimer Laser Sheath Lead Extraction System has been recognized as being highly useful for removing chronic infected leads. However, serious bleeding complications are a concern when this system is used. Here we report our experience with a 67-year-old man who was diagnosed with pacemaker endocarditis. Initially, lead removal was attempted using the Excimer Laser Sheath Extraction System, though this was abandoned because of severe adhesion of the leads and the junction of the supra vena cava (SVC) with the right atrium. Surgical removal of the leads was performed without using cardiopulmonary bypass and the leads were removed without any complications. During surgery, we found there was a silent perforation of the innominate vein brought about by the Excimer Laser Sheath System. Also, the junction of the SVC with the right atrium was thought to be an area potentially at high risk of perforation, because of a lack of surrounding tissue. It is our opinion that those who carry out procedures with the Excimer Laser Sheath System should understand the potential risk of perforation based on cardiac anatomy and should be prepared for lethal bleeding complications. Also, for emergent situations, we believe that close backup by a cardiovascular surgical team should be considered essential for performing the Excimer Laser Sheath Lead Extraction safely.     

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex.

OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.     

Investigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma

Purpose

Recently a combination of paclitaxel and carboplatin (TC) (without an anthracycline) has begun to be used as an adjuvant or remission induction therapy, without any critical supportive evidence of its efficacy relative to a combination chemotherapy of taxane, platinum and anthracycline such as TEC (paclitaxel, epirubicin and carboplatin). The aim of our present study was to conduct the required clinical evaluations of the relative effectiveness of TC compared to TEC.

Methods

A retrospective comparison between the efficacy of TEC and TC regimens used for endometrial carcinoma at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, respectively, from 1999 to 2009 was performed. The clinical characteristics of the patients who received either TEC or TC were not significantly different, and TEC and TC therapies were initiated based on similar indications for chemotherapy. TEC regimen was paclitaxel (150?mg/m²), epirubicin (50?mg/m²) and carboplatin (AUC 4). TC regimen consisted of paclitaxel (175?mg/m²) and carboplatin (AUC 5).

Results

TEC was demonstrated to provide significantly better survival than TC as an adjuvant therapy for resected Stage III/IV diseases (p?=?0.017 for progression-free survival and p?=?0.014 for overall survival, by the log-rank test). However, in recurrent or more advanced cases, TC and TEC demonstrated similar effects on survival (p?=?0.55 for progression-free survival and p?=?0.63 for overall survival).

Conclusions

TEC should be offered as an adjuvant therapy to Stage III/IV patients. TC may be considered for recurrent or unresectable cases as a remission induction therapy.     

Second-line chemotherapy for advanced or recurrent endometrial carcinoma previously treated with paclitaxel and carboplatin, with or without epirubicin

Purpose

A combined chemotherapy of taxane and platinum, with or without anthracycline, has been used as a standard first-line regimen. The purpose of this study was to investigate the effectiveness of second-line chemotherapy for treatment of advanced or recurrent endometrial carcinoma previously treated with a combined chemotherapy of taxane and platinum, with or without anthracycline.

Methods

During the 2000?C2008 study period, 723 patients were diagnosed with endometrial cancer at the Departments of Obstetrics and Gynecology of the Osaka University and the Osaka Rosai Hospitals, Osaka, Japan. The subset of these cases that eventually required treatment by second-line chemotherapy was retrospectively analyzed.

Results

Response rate to second-line chemotherapy was 25%. Treatment-free interval (TFI) of ???or?<6?months was demonstrated to be significantly associated with the response to second-line chemotherapy (P?=?0.0026), progression-free survival (P?=?0.0003) and overall survival (P?=?0.025). The second-line chemotherapy similar to the first-line regimen was ineffective in all the 7 cases (100%) whose TFI was shorter than 6?months. Multivariate analysis showed that TFI was the most significantly important factor predicting the effectiveness of second-line chemotherapy (the adjusted hazard ratio of TFI on PFS and OS: 3.482, 95% CI, 1.641?C7.388, P?=?0.0012, and 2.341, 95% CI, 1.034?C5.301, P?=?0.042, respectively).

Conclusions

Our present study provides, for the first time, evidence that the majority of refractory or recurrent diseases, if they occur within 6?months of a first-line chemotherapy using taxane and platinum with or without anthracycline, are non-responsive to the current regimens of second-line chemotherapy.     

A rare case of huge triple-negative of accessory breast cancer enlarged during the course of chemotherapy

A 38-year-old premenopausal woman with a right axillary mass was told that she had an atheroma. The mass enlarged. An infectious atheroma was suspected, and incision and drainage were performed. A mass 4 cm in diameter was palpated in the right axillary region. Ultrasonography showed a mass 6 cm in diameter, and magnetic resonance imaging revealed a hypervascular mass at the same site. Stage IIIB triple-negative of accessory breast cancer (T4bN1M0) was diagnosed. The patient received four courses of FEC 100 (5-fluorouracil, epirubicin, and cyclophosphamide) as preoperative chemotherapy, but progressive disease was diagnosed, and the regimen was switched to weekly paclitaxel. The tumor became ulcerated and friable, and the hemoglobin level fell to 6 g/dL. Emergency surgery was thus performed. Postoperatively, the patient received six courses of chemotherapy with paclitaxel plus gemcitabine. Accessory breast cancer is extremely rare, but should be borne in mind when an axillary mass is encountered. In our patient, progressive disease had developed during the preoperative chemotherapy for accessory breast cancer. Although treatment was switched to a different regimen, bleeding was detected, and the patient underwent a semi-emergency surgery.     

The prognosis of skin recurrence in breast carcinoma patients

In this study, we evaluated the clinical presentation of patients with skin recurrence in breast cancer patients. We treated 1, 228 cases of breast cancer patients during 2004 to 2010. The skin recurrences were recognized in 11 patients. The duration of showing skin recurrence was 1 .8 years. The muscle preserving radical mastectomy was performed in all cases. And surgical margins of all cases were negative. All cases were not performed radiation therapy. Nine cases were received chemotherapy as adjuvant therapy. Seven cases received endocrine therapy. After recurrence, they were treated by multi- disciplinary therapy. The surgical resection was useful to judge the effect of other therapies. The observation period was 2. 2 years. Two patients died, but 8 other patients are still alive.     

A case of six metachronous primary malignancies

Recently, the early detection and the advances in therapy for malignant diseases have contributed to prolonged survival of patients, resulting in an increment of multiple primary malignancies. We describe a 55-year-old man, at the first presentation, with six malignancies over 14 years(malignant lymphoma, gastric cancer, ureteral cancer, small cell lung cancer, bladder cancer, and squamous cell lung cancer). A case of six primary malignancies is extremely rare and, as far as we know, this is the 16th case of its kind reported in Japan. The overlapping of many malignant diseases resulted in some difficulties with treatment. Whereas the ureteral cancer and small cell lung cancer were synchronous, considering the therapeutic duration of lung cancer, we proceeded with the operation for ureteral cancer and had to delay the start of chemotherapy for small cell lung cancer for more than one month. Moreover, dose intensity of the chemotherapy for the small cell lung cancer was limited by expectancy of augmented myelosuppression, due to the effect of prior chemotherapy for malignant lymphoma. However, a strong neutropenia-induced postoperative abdominal infection necessitated discontinuation of chemotherapy and treatment with radiotherapy alone. In addition, the therapies for the newly developed squamous cell lung cancer, the sixth malignancy, were also limited because of reduced lung function and myelopoiesis. In treatment or follow-up of patients with multiple primary malignancies, as opposed to those with a single malignant disease, the characteristics of other malignancies and the morbidities by preceding therapies must be considered.     

A case of breast adenomyoepithelioma that was diagnosed by local excision

A case is a 72-year-old woman with right breast lump detected by palpation. In the end of November 2009, we palpated a mass with clear boundaries in the right D area. Breast echography showed a nearly 3 cm tumor in the cyst. MRI showed an augmented effect of marginal irregular 3 cm in size. A diagnosis was adenomyoepithelioma by needle biopsy. We performed lumpectomy because a breast cancer was suspected. Histopathology findings were adenomyoepithelioma ER(+), PgR(-), HER2(0), α SMA(+). A diagnosis of adenomyoepithelioma is rather hard by means of imaging or biopsy. When this disorder was in doubt, a tissue analysis is indispensable for a determination of diagnosis because we were able to make a diagnosis by local excision without an excessive invasion. So we herein report our experience of adenomyoepithelioma with reference.     

Cytoplasmic accumulation of connexin32 expands cancer stem cell population in human HuH7 hepatoma cells by enhancing its self‐renewal

Although the connexin32 (Cx32)‐mediated gap junction is abolished in hepatocellular carcinoma (HCC), the expression of cytoplasmic Cx32 tends to increase in correspondence with the grade of malignancy. Establishing a Tet‐off expression system in human nonmetastatic HuH7 HCC cells where cytoplasmic Cx32 was overexpressed by doxycycline (Dox) withdrawal, we previously demonstrated that overexpression of cytoplasmic Cx32 made HuH7 cells metastatic in mice. In our study, hypothesizing that the cytoplasmic Cx32‐induced metastasis may involve expansion of the cancer stem cell (CSC) population, we examined whether cytoplasmic Cx32 controlled the size of the side population (SP) in HuH7 Tet‐off Cx32 cells. Fluorescence‐activated cell sorting revealed that SP was expanded in a Dox‐free medium compared with a Dox‐supplemented one. Although cytoplasmic Cx32 did not block maturation from SP to non‐SP, purified SP reconstituted a larger SP fraction in the Dox‐free medium than in the Dox‐supplemented one. Furthermore, although SP from HuH7 Tet‐off mock cells formed a similar number of CSC spheres of a similar size whether with or without Dox, SP from HuH7 Tet‐off Cx32 cells developed a greater number of larger CSC spheres in the Dox‐free medium than in the Dox‐supplemented one. Taken together, these results suggest that accumulation of cytoplasmic Cx32 should enhance self‐renewal of CSC to expand the CSC population in HCC.