Characterization of High-Fat, Diet-Induced, Non-alcoholic Steatohepatitis with Fibrosis in Rats

An ideal animal model is necessary for a clear understanding of the etiology, pathogenesis, and mechanisms of human non-alcoholic steatohepatitis (NASH) and for facilitating the design of effective therapy for this condition. We aimed to establish a rat model of NASH with fibrosis by using a high-fat diet (HFD). Male Sprague–Dawley (SD) rats were fed a HFD consisting of 88 g normal diet, 10 g lard oil, and 2 g cholesterol. Control rats were fed normal diet. Rats were killed at 4, 8, 12, 16, 24, 36, and 48 weeks after HFD exposure. Body weight, liver weight, and epididymal fat weight were measured. Serum levels of fasting glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), free fatty acids (FFA), insulin, and tumor necrosis factor-alpha (TNF-α) were determined. Hepatic histology was examined by H&E stain. Hepatic fibrosis was assessed by VG stain and immunohistochemical staining for transforming growth factor beta 1 (TGF-β1), and alpha-smooth-muscle actin (α-SMA). The liver weight and liver index increased from week 4, when hepatic steatosis was also observed. By week 8, the body weight and epididymal fat weight started increasing, which was associated with increased serum levels of FFA, cholesterol, and TNF-α, as well as development of simple fatty liver. The serum ALT level increased from week 12. Steatohepatitis occurred from weeks 12 through 48. Apparent hepatic perisinosodial fibrosis did not occur until week 24, and progressed from week 36 to 48 with insulin resistance. Therefore, this novel model may be potentially useful in NASH study

Intraoperative radiotherapy (IORT) is an option for patients with localized breast recurrences after previous external-beam radiotherapy

<p>Abstract</p> <p>Background</p> <p>For patients suffering of recurrent breast cancer within the irradiated breast, generally mastectomy is recommended. The normal tissue tolerance does not permit a second full-dose course of radiotherapy to the entire breast after a second breast-conserving surgery (BCS). A novel option is to treat these patients with partial breast irradiation (PBI). This approach is based on the hypothesis that re-irradiation of a limited volume will be effective and result in an acceptable frequency of side effects. The following report presents a single center experience with intraoperative radiotherapy (IORT) during excision of recurrent breast cancer in the previously irradiated breast.</p> <p>Methods</p> <p>Between 4/02 and 11/06, 15 patients were treated for in-breast recurrences at a median of 10 years (3–25) after previous EBRT (10 recurrences in the initial tumor bed, 3 elsewhere in-breast failures, 2 invasive recurrences after previous DCIS). Additional 2 patients were selected for IORT with new primary breast cancer after previous partial breast EBRT for treatment of Hodgkin's disease. IORT with a single dose of 14.7 – 20 Gy 50 kV X-rays at the applicator surface was delivered with the Intrabeam™-device (Carl Zeiss, Oberkochen, Germany).</p> <p>Results</p> <p>After a median follow-up of 26 months (1–60), no local recurrence occurred. 14 out of 17 patients are alive and free of disease progression. Two patients are alive with distant metastases. One patient died 26 months after BCS/IORT due to pulmonary metastases diagnosed 19 months after BCS/IORT. Acute toxicity after IORT was mild with no Grade 3/4 toxicities and cosmetic outcome showed excellent/good/fair results in 7/7/3 cases.</p> <p>Conclusion</p> <p>IORT for recurrent breast cancer using low energy X-rays is a valuable option for patients with recurrent breast cancer after previous radiotherapy.</p

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment