Interaction between CYP19A1 polymorphisms and body mass index in the risk of endometrial cancer in postmenopausal Japanese women

Extra-ovarian sex hormone production plays an important role in endometrial cancer in postmenopausal women. Aromatase, which is encoded by CYP19A1, is a key enzyme in estrogen biosynthesis after menopause. To examine the association between polymorphisms in CYP19A1 and endometrial cancer risk among postmenopausal Japanese women, we conducted a hospital-based case control study in 48 patients with histologically diagnosed incident endometrial cancer and 253 non-cancer control subjects. Information on lifestyle factors was obtained from a self-administered questionnaire. Twenty-five tag SNPs (single nucleotide polymorphisms) of CYP19A1 were examined by TaqMan methods and haplotype blocks were identified by LD analysis. Associations were assessed by an unconditional logistic regression model adjusted for potential confounders. We found no significant association between CYP19A1 genotypes and haplotypes and endometrial cancer risk. However, among women with a BMI (body mass index) >23, significantly positive associations were observed for rs2899473, rs1865803, rs16964220, rs2008691, rs17647707, rs17647719, rs1902586, rs936306, and rs1004982, while negative associations were seen for rs1902585, rs752760 and rs2445768. These showed significant interactions with BMI. Further, of the six haplotype blocks identified, the haplotype CTT of block 1, GATA of block 5 and CA of block 6 showed statistically significant interactions with BMI. These results suggest that CYP19A1 polymorphisms might play an important role in the etiology of endometrial cancer, and that the effect of these polymorphisms might be influenced by BMI.     

Apparent diffusion coefficient measurements with diffusion-weighted magnetic resonance imaging for evaluation of hepatic fibrosis

PURPOSE: To evaluate the use of apparent diffusion coefficient (ADC) measurements based on diffusion-weighted MRI (DWI) to assess stage of liver disease. MATERIALS AND METHODS: A total of 31 patients who underwent both a liver biopsy and DWI and 132 patients who only underwent DWI were enrolled. Biopsy specimens were scored for fibrosis and necroinflammation according to the Knodell histology activity index (HAI). The 31 patients consisted of 21 patients with chronic hepatitis and 10 with cirrhosis (Child-Pugh stage A in nine and stage B in one), and the 132 patients consisted of 56 patients with cirrhosis (Child-Pugh stage A in 41, stage B in 10, and stage C in five), 42 with chronic hepatitis, and 34 with normal liver function. The ADCs in the liver parenchyma were measured using DWI with relatively low b factors (b = 0.01 and 128.01 seconds/mm(2)) and were compared among the HAI scores and among patients with cirrhosis, chronic hepatitis, and normal liver function. RESULTS: The ADCs decreased as the fibrosis score in the HAI increased, and the correlation was statistically significant (P < 0.0001). No relationship between the ADCs and the necroinflammation scores in the HAI was found. The ADCs decreased as the stage of liver disease progressed or as the Child-Pugh stage progressed, and these relationships were statistically significant (P < 0.0001). CONCLUSION: ADC measurements are potentially useful for the evaluation of fibrosis staging in the liver.     

Ingrown nails and pachyonychia of the great toes impair lower limb functions: improvement of limb dysfunction by medical foot care

Background Painful feet and lower limb dysfunction are risk factors for falling. Toenail deformities are common disorders in elderly people, but the relationship between nail deformities and lower limb function remains unclear. The aims of the present study were to assess the impairment of lower limb function in patients with deformities of the great toe and to determine whether foot care treatment is beneficial in reducing the risk of falling. Methods Functional tests of the lower extremities were performed in 263 adults, including patients with any of hallux valgus, ingrown nail, or pachyonychia, and volunteers. Fifty‐five subjects with nail disorders of the great toe received medical foot care treatment. Results The presence of ingrown nail, pachyonychia, or tenderness of the great toe was significantly correlated with impaired postural performance and reduced muscular strength as assessed by functional tests. Medical foot care markedly reduced pain levels in the great toe and improved scores on functional tests of the lower extremities. Conclusions Toenail disorders of the great toe cause dysfunction of the lower extremities and are likely to increase the risk of falling in daily life. Foot care management of toenail disorders has the potential to improve functional abilities in daily life, particularly in elderly individuals.     

Uniportal video-assisted thoracic surgery and perioperative pirfenidone for lung cancer and idiopathic pulmonary fibrosis: a case report

Patients with idiopathic pulmonary fibrosis (IPF) occasionally experience acute exacerbations after surgery for lung cancer. Several recent studies have revealed a prophylactic effect of perioperative pirfenidone treatment on postoperative acute exacerbations of IPF in patients with lung cancer. A 75-year-old woman consulted with her pulmonologist because of an IPF shadow detected by follow-up chest computed tomography 2 months after surgical treatment of biliary cancer. Another 7 months later, chest computed tomography showed a 23- × 14-mm nodule located in the right lower lobe with high accumulation of fluorodeoxyglucose detected by positron emission tomography, resulting in a radiological diagnosis of primary lung cancer with IPF. We administered perioperative pirfenidone treatment followed by right lower lobectomy using uniportal video-assisted thoracoscopic surgery after attaining a pathological diagnosis of adenocarcinoma. The patient developed no acute exacerbations of IPF during the postoperative period, and she had no recurrence of lung cancer for 15 months after surgery. We successfully used a combination of perioperative antifibrotic medication and minimally invasive surgery after lung cancer surgery in a patient with IPF.     

Expression of cell polarity protein scribble differently affects prognosis in primary tumor and lymph node metastasis of breast cancer patients

Background

We evaluated the relationship between the immunohistochemically determined expression of the cell polarity protein scribble to prognosis in different environments of estrogen receptor (ER) expression and epithelial-to-mesenchymal transition (EMT).

Methods

We immunohistochemically evaluated the expression level of scribble in primary tumors and lymph node metastases of 225 node-positive breast cancer patients who had received chemotherapy. We then evaluated metastasis-free survival (MFS) in the absence or presence of ER and the EMT-related protein vimentin.

Results

Among patients with ER–positive tumors, patients with low scribble expression in the primary tumor had a significantly shorter MFS than patients with high scribble expression (p = 0.0225). Furthermore, among patients with vimentin-negative tumors, patients with low expression of scribble in the primary tumor had significantly shorter MFS than patients with high expression of scribble (p = 0.0463). In contrast, among patients with vimentin-positive tumors, patients with high expression of scribble in the primary tumor had significantly shorter MFS than patients with low expression of scribble (p = 0.0343). Moreover, among patients with ER–negative tumors, patients with high expression of scribble in lymph node metastases showed significantly higher expression of E-cadherin in metastases (p = 0.0407) and had significantly shorter MFS than patients with low expression of scribble (p = 0.0064).

Conclusions

The prognostic significance of cell polarity depended on the ER expression and EMT. Furthermore, the preservation of cell polarity in metastases was associated with mesenchymal-to-epithelial transition and worse prognosis. Cell polarity promotes the diversity of metastasis in combination with malignancy grade in breast cancer patients.

     

Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension

This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker. The primary end point was the mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks. An efficacy analysis was performed in 195 patients (98 in the eplerenone group and 97 in the thiazide group). Systolic and diastolic blood pressures at 48 weeks were similar in the two groups. The mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks was similar in the two groups (P=.804). In the safety analysis, the withdrawal rates for adverse events were similar in both groups. The antialbuminuric effects and safety of eplerenone therapy were similar to those of thiazide diuretics when combined with an angiotensin II receptor blocker in patients with hypertension and albuminuria.     

CD25 as an adverse prognostic factor in elderly patients with acute myeloid leukemia

Objectives: CD25 has been reported to be highly expressed in leukemia stem cells and correlated with adverse outcomes in young patients with acute myeloid leukemia (AML). However, the significance of CD25 expression in elderly patients with AML has not yet been investigated.

Methods: We retrospectively analyzed 154 newly diagnosed AML patients aged 60 years or over by flow cytometry.

Results: CD25-positive AML was characterized by high white blood cell counts, secondary AML, rare favorable karyotypes, and positivity for CD34 and CD7 antigens, compared with CD25-negative AML. CD25 positivity was significantly correlated with an inferior complete remission (CR), event-free survival (EFS), and overall survival. Multivariate analysis showed CD25 positivity to be a significant prognostic predictor of CR and EFS. A regimen of low-dose cytarabine and aclarubicin combined with granulocyte-colony-stimulating factor (CAG) led to higher CR rates in the CD25-positive AML patients than intensive chemotherapies. CD25 expression was increased at relapse and in the development of leukemic status from myelodysplastic syndrome or myeloproliferative neoplasm.

Discussion: An effective treatment strategy for elderly patients with CD25-positive AML has not been established. Further studies are needed to evaluate the effect of a CAG regimen and allogenic stem cell transplantation in patients.

Conclusion: CD25 is an independent prognostic factor in elderly AML patients. Alternative therapies for CD25-positive elderly AML patients are needed.