Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases

Purpose

To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in patients with unresectable liver metastases from neuroendocrine tumours (NETLMs).

Methods

This retrospective study included 40 patients with progressive NETLMs (22 women, 18 men, mean age 61.6 years) who underwent SIRT with ⁹⁰Y-labelled resin microspheres. Tumour response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) on CT or MR images. Medical records were reviewed.

Results

In the 40 patients, 54 evaluable SIRT procedures were performed, 33 to the right liver lobe (mean activity 1.31 GBq), 13 to the left lobe (mean activity 0.85 GBq), and 8 to both lobes (mean activity 1.61 GBq). Late follow-up imaging (mean 20 months) was performed after 44 of the treatments. Objective tumour response and disease control rates were 54 % (29 of 54 treatments) and 94 % (51 treatments), respectively, at the early follow-up examination (mean 3 months) and 34 % (15 treatments) and 57 % (25 treatments), respectively at the late follow-up examination. Mean overall survival from the first SIRT was 34,8 months and survival rates at 1, 2, 3 and 5 years were 76 %, 59 %, 52 % and 35 % respectively. Adverse effects were generally mild and easily manageable, except in one patient who died from radiation-induced liver failure. Of the 45 patients, 18 (45 %) had received peptide receptor radionuclide therapy (PRRT) prior to SIRT.

Conclusion

SIRT with ⁹⁰Y-labelled resin microspheres is a safe and effective treatment for patients with progressive NETLM, and also for those who have received prior PRRT.

     

人骨髓间充质干细胞分离培养及血管内皮生长因子对其产生的诱导分化作用

目的：目前有关骨髓间充质干细胞向内皮细胞诱导分化的研究较少。本实验分离和培养人骨髓间充质干细胞，用带有VEGF165的质粒转染人骨髓间充质干细胞，探讨血管内皮生长因子对其体外诱导分化的作用。 方法：实验于2005—04／2006—04在吉林大学人兽共患病教育部重点实验室完成。取成人的已排除血液系统肿瘤疾病的新鲜骨髓（自愿提供），采用Percoll梯度分离培养骨髓间充质干细胞，于倒置显微镜下观察细胞形态变化和生长情况。原代细胞培养至增殖接近融合状态时，单克隆培养法分离传代培养，扩增骨髓间充质干细胞。采用流式细胞术检测细胞免疫学表型。在原核细胞大肠杆菌DH5α中复制扩增和提取，纯化、克隆pcDNA3．0-VEGF165质粒。用脂质体转染法转染骨髓间充质干细胞：应用流式细胞术检测诱导后骨髓间充质干细胞免疫学表型变化j并采用免疫荧光染色鉴定转染情况，并设质粒空载和未转染的骨髓间充质干细胞为对照。 结果：人骨髓间充质干细胞原代培养1周后，造血细胞消失，贴壁细胞体积增大，呈现梭形外观，有粗大的细胞突起伸出。2周后细胞融合成单层，梭形突起变长，排列有明显的方向性，细胞排列成旋涡状、网状、辐射状。流式细胞术显示，人骨髓间充质干细胞免疫学表型CD44、CD29阳性，CD34、CD31、CD45阴性。VEGF165诱导骨髓间充质千细胞后CD44表达明显降低，CD31明显升高。免疫荧光染色显示，用FITC标记后的VEGF抗体使细胞显现绿色荧光，用cy3标记的CD31抗体使细胞显现了红色荧光。 结论：转染后的骨髓间充质干细胞细胞表型发生明显转变，CD31表达率明显增高，呈现典型的内皮细胞的表型特征，这说明骨髓间充质干细胞具有向内皮细胞分化的潜能。     

Subungual squamous cell carcinoma presenting with minimal nail changes: A factor in delayed diagnosis?

Squamous cell carcinoma of the nail bed is a relatively uncommon tumour that may be diagnosed only after considerable delay. The first case presented is a 79-year-old man with a history of discomfort and discoloration affecting the right thumbnail of 3 years duration. The second case is a 70-year-old man who presented with a recurrent, offensive discharge from beneath the left thumbnail of 40 years duration. Clinical examination of the affected digits revealed minor nail abnormalities. The presence of tumour was fully apparent only after removal of the nail plate and inspection and biopsy of the nail bed. The cases demonstrate that subungual squamous cell carcinoma may present with prolonged symptoms and a deceptively benign appearance. The importance of consideration of the possibility of malignancy, removal of the nail plate for inspection of the nail bed and appropriate biopsy is emphasized.     

Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study)

OBJECTIVE

To examine whether serum 25-hydroxyvitamin D (25OHD) and dietary calcium predict incident type 2 diabetes and insulin sensitivity.

RESEARCH DESIGN AND METHODS

A total of 6,537 of the 11,247 adults evaluated in 1999–2000 in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, returned for oral glucose tolerance test (OGTT) in 2004–2005. We studied those without diabetes who had complete data at baseline (n = 5,200; mean age 51 years; 55% were women; 92% were Europids). Serum 25OHD and energy-adjusted calcium intake (food frequency questionnaire) were assessed at baseline. Logistic regression was used to evaluate associations between serum 25OHD and dietary calcium on 5-year incidence of diabetes (diagnosed by OGTT) and insulin sensitivity (homeostasis model assessment of insulin sensitivity [HOMA-S]), adjusted for multiple potential confounders, including fasting plasma glucose (FPG).

RESULTS

During the 5-year follow-up, 199 incident cases of diabetes were diagnosed. Those who developed diabetes had lower serum 25OHD (mean 58 vs. 65 nmol/L; P < 0.001) and calcium intake (mean 881 vs. 923 mg/day; P = 0.03) compared with those who remained free of diabetes. Each 25 nmol/L increment in serum 25OHD was associated with a 24% reduced risk of diabetes (odds ratio 0.76 [95% CI 0.63–0.92]) after adjusting for age, waist circumference, ethnicity, season, latitude, smoking, physical activity, family history of diabetes, dietary magnesium, hypertension, serum triglycerides, and FPG. Dietary calcium intake was not associated with reduced diabetes risk. Only serum 25OHD was positively and independently associated with HOMA-S at 5 years.

CONCLUSIONS

Higher serum 25OHD levels, but not higher dietary calcium, were associated with a significantly reduced risk of diabetes in Australian adult men and women.Accumulating evidence suggests that vitamin D deficiency is associated with an increased risk of developing type 2 diabetes (1–3). Animal and human studies indicate that vitamin D can have a direct (via activation of the vitamin D receptor on pancreatic β-cells and insulin-sensitive organs) and indirect (via regulation of calcium homeostasis) positive effect on insulin secretion and sensitivity (3,4). Several prospective studies also support the hypothesis that low vitamin D status is a risk factor for the development of type 2 diabetes (1–3,5,6); however, these studies were limited by small study sample sizes (3), indirect measures of vitamin D status as a surrogate marker (6,7), and incomplete identification of incident diabetes cases (1,2,5). In addition, most did not include an assessment of dietary calcium, which may have an independent or synergistic effect with vitamin D on lowering type 2 diabetes risk (7). The aim of this study was to examine the relationship between serum 25-hydroxyvitamin D (25OHD), dietary calcium, and risk of developing type 2 diabetes as assessed by an oral glucose tolerance test (OGTT) in a large national, population-based prospective study: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study.     

Thalidomide in combination with dexamethasone for pretreated patients with multiple myeloma: serum level of soluble interleukin-2 receptor as a predictive factor for response rate and for survival

The aim of this study was to assess the side effects and the efficacy of thalidomide alone or in combination with dexamethasone in relapsed multiple myeloma (MM) and to evaluate possible predictive factors for response rate and survival. Twenty-nine pretreated patients were enrolled, including 13 patients with a relapse after high-dose chemotherapy. The median number of relapses was 3 (range: 1–7). Twenty-two patients received thalidomide in combination with dexamethasone and seven patients thalidomide alone. The dosage of thalidomide was 400 mg/day and the dosage of dexamethasone 20 mg/m² daily for 4 consecutive days every 3 weeks. Cycles of dexamethasone were given until maximal decline of myeloma protein was achieved, whereas therapy with thalidomide was maintained until disease progression. Responses occurred in 62% of patients, including 5 (17%) complete remissions and 13 (45%) partial remissions. The median event-free survival (EFS) was 7.2 months and the median overall survival (OS) 26.1 months. In multivariate analysis, pretreatment serum levels of soluble interleukin-2 receptor (sIL-2R) were a significant prognostic factor for EFS, and those of ₂-microglobulin (2M) and sIL-2R for OS. Serum levels of sIL-2R significantly increased after 3 weeks of treatment in 89% of patients, possibly representing lymphocyte activation induced by thalidomide. Two patients died of septic complications within 3 months after starting treatment with thalidomide and dexamethasone and one patient of herpes encephalitis after 26 months of treatment with thalidomide alone. Also, one case of pneumonia and one case of deep venous thrombosis of the lower limb occurred. Other side effects were somnolence, peripheral neuropathy, and bradycardia occurring in 35, 55, 38 and 55% of patients, respectively. The combination of thalidomide and dexamethasone is an effective therapy in heavily pretreated myeloma patients with a high response rate and acceptable toxicities. A powerful predictive factor both for EFS and OS was the pretreatment serum level of sIL-2R.