Ipsilateral breast tumor control following hypofractionated and conventional fractionated whole-breast irradiation for early breast cancer: a long-term follow-up.

PURPOSE: Long-term follow-up of Japanese women with breast cancer who underwent hypofractionated whole-breast irradiation (HF-WBI) has not been well documented. Therefore, we compared the treatment results of HF-WBI and conventional fractionated (CF)-WBI. METHODS: Patients with stage 0-II breast cancer receiving partial mastectomy were eligible for this prospective observational study. The HF-WBI consisted of 43.2 Gy in 16 fractions to the whole breast, with an additional tumor-bed boost of 8.1 Gy in three fractions for patients with positive or less than 5 mm surgical margins. A total of 615 patients (400: HF-WBI and 215: CF-WBI) who were treated between 2006 and 2008 were investigated. Propensity score matching was conducted based on age, tumor grade, and margin status, and 372 matched cases were investigated for examining factors relating to intrabreast tumor recurrence (IBTR). RESULTS: With a median follow-up period of 9.4 years, age and margin status were independent factors associated with IBTR occurrence (P = 0.006 and 0.016, respectively). The 10-year ipsilateral breast tumor control (IBTC) rates after HF-WBI and CF-WBI were 96.5% and 95.3%, respectively (P = 0.606). The 10-year IBTC rates according to margin status were 88.0% with positive margins, 94.9% with 5 mm margins, and 98.0% with negative margins (P = 0.014). CONCLUSIONS: There was no difference in IBTC between CF-WBI and HF-WBI in our patients. Positive surgical margin was a risk factor independently associated with IBTC rates after CF-WBI and HF-WBI. Further investigation is required to establish adequate treatment strategies for patients with positive surgical margins.

Development of MRI Projection Mapping System for Breast-Conserving Surgery in the Operating Room: Preliminary Clinical Results in Invasive Breast Cancer.

AIM: To evaluate the feasibility of a newly developed prototype MRI projection mapping (PM) system for localization of invasive breast cancer before breast-conserving surgery. METHODS: This prospective study enrolled 10 women with invasive breast cancer. MRI was performed in both prone and supine positions. The tumor location was drawn on the breast skin using palpation and sonography while referring to the prone MRI (i.e., a conventional method). A maximum intensity projection image generated from the supine MRI was projected using our PM system, and the tumor location was drawn. The PM system consisted of a projector and a camera and was used to measure the shape of the breast surface using the structured light method. Breast-conserving surgery was performed based on the conventional method. We compared the tumor size and location between the PM and conventional methods or pathology. RESULTS: There were no significant differences in the maximum diameters of invasive cancers between the PM system and the conventional method or pathology. The maximum discrepancy in tumor location between the PM and conventional method was 3-8 mm. CONCLUSIONS: This PM system may support breast-conserving surgery by showing the tumor size and location on the breast surface.

Comparison of success rates in eye drop instillation between sitting position and supine position.

PURPOSE: To compare the success rates of eye drop instillation in the sitting position and supine position among Japanese patients with ocular diseases (cataract, glaucoma, or retinal and vitreous diseases). METHODS: Patients who were hospitalized in Okayama University Hospital for eye surgery were studied. Instillation procedures of each patient in both the sitting and supine positions were recorded using a video camera at the time of instillation. We defined "success" when one drop fell accurately onto the ocular surface at the first attempt. Instillation of two or more drops, drops delivered to a site other than the eye surface, and touching the eyelashes, eyelids, or conjunctiva with the tip of the eye drop bottle were regarded as "failure". We excluded patients with vision below counting finger. RESULTS: One-hundred and two patients (54 males and 58 females, aged 70.2 ± 12.3 years) with ocular disease who were hospitalized for surgery (cataract: 61.8%, glaucoma: 15.7%, retinal and vitreous diseases: 22.5%) were included in this prospective observational study. The mean duration of eye drop use was 3.1 ± 5.2 years. The success rate of eye drop instillation was significantly higher in the supine position than in the sitting position (64.7% vs. 50%, P = 0.0039). The mean age was significantly higher in the failure group than in the success group (74.0 ± 11.5 vs. 67.7 ± 12.4 years, P = 0.0085) for the sitting position, but not significantly different for the supine position (72.3 ± 12.9 vs. 70.1 ± 12.0 years, P = 0.3849). No significant differences in mean duration of drop use, mean corrected VA, and mean spherical equivalent refraction were observed between success and failure groups, for both sitting and supine positions. CONCLUSIONS: In the present study, the success rate of eye drop instillation was significantly higher when applied in the supine position than in the sitting position.

Overcoming the Adverse Effects of Everolimus to Achieve Maximum Efficacy in the Treatment of Inoperable Breast Cancer: A Review of 11 Cases at Our Hospital.

Everolimus is an effective treatment for advanced and/or metastatic breast cancer, especially in hormone receptor-positive cases. However, adverse events have prevented considerable numbers of clinicians from using this drug. Herein, we reviewed our clinical experiences and endeavored to identify patients in whom the benefits of everolimus treatment would outweigh these adverse events. If measures were available to prevent or minimize adverse effects prior to treatment, everolimus would be a more widely applicable drug. This retrospective study involved 11 patients in whom nonresectable or recurrent breast cancers were treated with everolimus between April 2014 and January 2016. Two patients achieved a partial response (PR) and 4 showed stable disease (SD) (1 showed long SD, i.e., > 24 weeks). The response rate was 18%, and the clinical benefit rate (PR + long SD) was 27%. Regarding adverse events, interstitial pneumonia (grade 3) developed in 3 patients (18%), necessitating treatment discontinuation. When using everolimus, it may be important to select suitable patients for whom this treatment can be continued with sufficient control of adverse events. Herein, we provide information relevant to the clinical use of everolimus based on our daily practice experiences with this agent.

Predictive markers for efficacy of everolimus plus exemestane in patients with luminal HER2-negative metastatic breast cancer.

Metastatic breast cancer (MBC) is essentially incurable despite recent improvements in systemic therapies. We often encounter difficulties in choosing the most appropriate treatments, with optimal timing, for individual patients. Everolimus, one of the mTOR inhibitors, is usually used with endocrine therapy for MBC. Identification of predictive markers for everolimus-based treatment remains a major issue, but to date, no predictive markers have been established. We retrospectively investigated predictive markers for treatments with everolimus plus exemestane in patients with ER-positive and HER2-negative breast cancer. Clinicopathological features of 18 patients, with locally advanced disease or MBC given everolimus plus exemestane treatments, were examined in relation to treatment effects. Also, primary breast cancer specimens, all ER positive and HER2 negative, were immunohistochemically investigated for phospho-S6 (pS6) and PTEN, to evaluate the mTOR and PIK3CA/Akt pathways. Those showing a good clinical response had a significantly lower Ki67 labeling index than the poor responders. A similar trend was observed in pS6 level but without statistical significance. Interestingly, there was no correlation between the Ki67 labeling index and pS6, and when both indexes were low, the good clinical response rate was high. The median progression-free survival was longer in the group showing a low Ki67 labeling index (109 weeks) than in that with high Ki67 (19 weeks). There was no trend between PTEN expression and treatment effects. Our results suggest that the primary tumor in luminal HER2-negative breast cancer patients with a low Ki67 labeling index and pS6 level has the potential to respond well to everolimus plus exemestane.

[Potent primary leptomeningeal lymphoma masquerading as tuberculous meningitis - a case report].

A 45-year-old man presented with fever, progressive mutism and memory loss, was admitted to our hospital. MR imaging and angiography suggested multiple foci of infarctions and vasculitis without Gadrinium-enhancement. CSF examination revealed pleocytosis with mononuclear cell dominance and elevated protein content. Adenosine deaminase activity was accelerated, and no malignant cell was found. Whole body CT imaging and Garium-scintigraphy were normal. Under the clinical diagnosis of tuberculous meningitis, anti-tubercular drugs with steroid were administered, resulting in marked attenuation of his neurological impairments. Four months later, his symptoms aggravated and restudy of Garium-scintigraphy revealed enhanced accumulation in the submandibular and abdominal lymphnodes. A lymph node biopsy revealed diffuse large B-cell lymphoma cells. In such a case of this clinical statue, careful and repeated observations should be required to establish the correct diagnosis of occult lymphoma.

[Living situation of the in-home patients suffering from amyotrophic lateral sclerosis in Aichi prefecture, Japan].

It is essential that we know the real situation of at-home patients with amyotrophic lateral sclerosis (ALS) in order to improve their medical support system. We indirectly investigated the daily living status of ALS patients and their families at home by conducting on individual questionnaires survey for nurses working at public health centers in Aichi prefecture, Japan. Detailed information about 136 cases was obtained, and we could clarify the need for variety of communication methods, plasticity of medical interrelations and care between neurologists and home doctors, incomplete utilization of social resources including various official support, overwork among single caregivers, and underdeveloped immature individual medical care support programs for them. Thus it might be important that we should promote the sure utilization of social resources and programming the individual medical care support in their earlier stages. And moreover, we should also consider constructing a general support system for at-home patients with ALS, in which each professional would owe the dividing responsibility, without role duplications. These strategies would lead to overall the better quality of life among ALS patients, and their families.

Serum alkaline phosphatase isoenzymes in SD rats detected by polyacrylamide-gel disk electrophoresis.

Serum alkaline phosphatase (ALP) activity is frequently measured in toxicity studies. In the present study, we assessed the usefulness of a commercially available polyacrylamide-gel disk electrophoresis kit used in humans (AlkPhor System, Jokoh Co. Ltd., Tokyo, Japan) for identifying serum ALP isoenzymes in rats of the Sprague-Dawley strain (SD rats), which are commonly used in toxicity studies. We also examined age-related changes in serum ALP isoenzymes in SD rats. In order to identify the origin of each ALP isoenzyme, tissue ALP extracts from the liver, bone and small intestine (SI) and serum samples were treated with neuraminidase, antiintestinal ALP antibody, ALP inhibitor levamisole, and/or wheat germ agglutinin. It became clear that pretreatment of serum with neuraminidase is necessary for rat serum ALP isoenzyme analysis. The kit revealed that the main serum ALP isoenzymes in fasted 8-week-old intact rats were bone- and SI-derived and they tended to decrease with age. Serum liver-derived isoenzyme was slightly detected in both sexes of all ages examined, but it greatly increased in cholestasis model rats with bile-duct ligation, and rats of this model also had large molecular ALP detected in the stacking gel, suggesting hepatic damage. High-molecular intestinal ALP isoenzyme was slightly observed at the most cathodal side of the resolving gel. These results suggest that the present method is a useful tool for detecting serum ALP isoenzymes in SD rats and that concomitant levamisole inhibition with another gel is applicable for the evaluation of organ toxicity.

Testosterone-lowering activity of canola and hydrogenated soybean oil in the stroke-prone spontaneously hypertensive rat.

Canola and some other types of oil unusually shorten the survival of stroke-prone spontaneously hypertensive rats (SHRSP), compared with soybean oil, perilla oil and animal fats. Since differential effects of canola and soybean oil on steroid hormone metabolism were suggested by a preliminary DNA microarray analysis as a reason for this, the steroid hormone levels in the serum and tissues of SHRSP fed different oils were investigated. The testosterone levels in the serum and the testes were found to be significantly lower in the canola oil group than in the soybean oil group, while no significant differences were detected in the corticosterone and estradiol levels in tissues. In a second experiment, it was found that hydrogenated soybean oil, with a survival-shortening activity comparable to that of canola oil, also decreased the testosterone level in testes to a similar degree. The testosterone-lowering activity of canola and hydrogenated soybean oil observed in SHRSP was considered in relation to other factors possibly affecting the physiology of SHRSP.