Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue

Purpose Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients and Methods Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Results Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Conclusion Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.     

Shoulder instability: impact of glenohumeral arthrotomography on treatment

We used arthrotomography to study the glenoid labrum in 114 patients. Sixty-nine of the patients had anatomic instability of the shoulder (including recurrent dislocation and subluxation of the shoulder), and 45 patients had functional instability of the shoulder (denoted by chronic pain, clicking of the joint, and the sensation that an unstable condition exists without the objective signs of it). Labral tears were revealed arthrotomographically in 86% of the patients with anatomic instability, while only 40% of the patients with functional instability had labral abnormalities, and these were primarily of minor severity. Fifty-six patients (44 of whom had anatomic instability; 12, functional instability) required surgery. The surgical findings were correlated with the arthrotomographic findings, and no false-positive results were revealed. However, arthrotomography demonstrated only part of the pathologic condition of two patients. These results confirm that there is a strong correlation between labral pathologic conditions and anatomic instability of the shoulder. Arthrotomographic studies have a great impact on the selection of therapy in cases of both anatomic and functional instability of the shoulder.     

Sickle cell anemia patients have low erythropoietin levels for their degree of anemia

We have studied serum immunoreactive erythropoietin (SIE) levels in 28 patients with sickle cell anemia (SCA) without renal insufficiency and in 17 patients with nonhemoglobinopathy anemias of comparable severity using a sensitive radioimmunoassay procedure. An exponential relationship between SIE level and degree of anemia was noted in all patients. However, in nonhemoglobinopathy anemia, a sharp rise in the SIE level occurred as hemoglobin (Hb) levels fell below about 12 g/dL, whereas in sickle cell patients the increase was not marked until hemoglobin fell to about 9 g/dL. The response was more blunted in older SCA patients than in younger ones. A linear regression model relating SIE level to Hb level, presence/absence of SCA, and age explained 63% of the variation in SIE. We conclude that the serum erythropoietin levels in SCA increased at a lower hemoglobin concentration and are of a lower magnitude than that of the other anemias.     

Management of oral Kaposi's sarcoma and a proposal for clinical staging

Kaposi's sarcoma (KS) is the most common neoplastic disease in patients with disease due to human immunodeficiency virus (HIV), and oral KS (OKS) is the commonest oral neoplasia. OKS has been managed by local excision, intralesional chemotherapy regional radiotherapy, and systemic chemotherapy. Comparison between studies is difficult as the severity of oral involvement is not well defined in most studies. This paper reviews the approach to the management of OKS and also presents a proposal for the clinical staging of OKS. Clinical staging of OKS will facilitate comparisons of outcomes of treatment of OKS and improve our understanding of the natural history of the neoplasia, which has varied presentation and rates of progression.     

Effect of shunt surgery on spleen size, portal pressure and oesophageal varices in patients with non-cirrhotic portal hypertension

Shunt surgery is considered to be the treatment of choice in patients with non-cirrhotic portal hypertension. There is little data on the effect of side-to-side lieno-renal (SSLR) shunt on oesophageal variceal size, splenic size and splenic pulp pressure (SPP) in patients with non-cirrhotic portal hypertension. We evaluated pre- and postoperatively endoscopic grading of varices, splenic size and SPP for predicting shunt patency in 86 patients with non-cirrhotic portal hypertension: 56 with extrahepatic portal venous obstruction (EHPVO) and 30 with non-cirrhotic portal fibrosis (NCPF). The EHPVO patients with patent shunts (n= 47) showed significant reduction in SPP (pre-operative 43.56±7.9 vs postoperative 29.96±7.7 cm of saline), splenic size (6.5±2.8 vs 4.00±2.6 cm below costal margin) and varices grades (2.96±0.5 vs 0.92±0.8). Patients with blocked shunt (n= 9) did not show significant reduction in SPP and varices grades. However, there was reduction in spleen size (8.6±3.0 vs 6.3±4.3). In the NCPF group, 28 had patent shunts and showed significant reduction in SPP (46.3±13.5 vs 33.8±7.6 cm of saline), splenic size (9.1±3.3 vs 6.8±4.6 cm below costal margin) and varices grades (2.8±0.7 vs 1.05±0.96). As only two patients with NCPF had blocked shunts, no statistical comparison between patients with patent and patients with blocked shunts could be done. In conclusion, following SSLR, there is a significant reduction in SPP and varices grades in patients with patent shunts. Endoscopic grading of varices can be used to predict shunt patency. However, spleen size is not a good criteria for predicting shunt patency.     

小叶买麻藤中买麻藤甲素的结构研究

从小叶买麻藤[Gnetum parvifolium(Warb.)C.Y.Cheng]茎的乙酸乙酯部分得到五个成分,经理化常数测定、光谱(UV,IR,MS,~1HNMR,~(13)CNMR和2D-NMR)分析和衍生物制备,确定买麻藤甲素为一个新的2-苯基苯并呋喃类化合物,结构为2-(3′,5′-二羟基-4′-甲氧基苯基)_-3-甲氧基5-羟基苯并呋喃。另外三个鉴定为异丹叶大黄素、白黎芦醇和β-谷甾醇.还有一个化合物正在鉴定中。