The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers – a study of the National Cancer Institute of Canada Clinical Trials Group

A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma, who had no more than one prior line of progestins and never had chemotherapy (except adjuvant). Archival paraffin-embedded tumor samples were retrieved to determine the expression level of estrogen (ER) and progesterone receptor (PgR), p53, HER-2, bcl-2 and PTEN protein, and phosphorylation status of protein kinase B (PKB/Akt). Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously, of whom 10 (31%) had prior progestins. Of the 28 patients evaluated for response, one complete and two partial responses were noted; overall response was 9.4% (95% confidence interval 2-25%). Eleven patients had stable disease for a median duration of 6.7 months (range 3.7-19.3 months). Amongst 22 patients who had tumor blocks available, the proportion showing positive expression of the following markers includes: PgR (86%), ER (86%), PTEN (82%), phosphorylated PKB/Akt (59%), bcl-2 (45%), p53 (32%), and HER-2 (0%). None of these markers correlated with response to letrozole or disease progression. In conclusion, letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer.     

Further studies on interactions between periaqueductal gray, nucleus accumbens and habenula in antinociception.

Previous findings from this laboratory with the intracerebral microinjection technique suggested that the periaqueductal gray (PAG), nucleus accumbens, and habenula might constitute a unidirectional loop to play their roles in pain modulation. In the present study we demonstrate that intra-habenular injection of naloxone antagonizes the analgesia elicited by morphine injected into the periaqueductal gray (PAG) and that intra-accumbens injection of naloxone is capable of attenuating the analgesic effects of morphine injected into the habenula. These results indicate that the relationships between these nuclei may be more complex than the putative unidirectional loop.     

Changes in malondialdehyde contents in serum and tissues after ischemia and reperfusion of the bowel in dogs]

The portal circulation was reduced to 50% for one hour by partially occluding the superior mesenteric artery, and the relationship between the changes in malondialdehyde (MDA) and multiple organ damage was studied. The results showed that there was a marked change in hepatic enzymology, with MDA values significantly elevated in serum and lung and liver tissues after the reperfusion when compared with controls. These results suggested that lipid peroxidation initiated by free oxygen radicals played an important role in the multiple organ damages, and the extent of organ damage was closely correlated with the contents of MDA in tissues.     

Expression of EGF receptors in cell lines derived from female genital cancers and enhancement of the therapeutic effect of anticancer drugs by EGF]

Manifestation of EGF receptors and enhancement of an anticancer agent by EGF were studied in cultured cells derived from female genital cancers. 1) The numbers of EGF-receptors of SKG-3a, RMUG-s, HUOA, A-431 and HEC-1 were 1.22 x 10(4), 6.94 x 10(4), 2.75 x 10(4), 5.25 x 10(5) and 0.92 x 10(4) sites per cell respectively. The values for the dissociation constant (Kd) of RMUG-s, SKG-3a, HUOA and HEC-1 were 340pM, 477pM, 989pM and 2,187pM, respectively. 2) All cell lines were stimulated by EGF at low concentrations and inhibited at higher concentrations. The growth stimulation rates for SKG-3a, HEC-1, HUOA and RMUG-s in the presence of 0.01 nM EGF at 48 hours were 8, 18, 21.1 and 3.7%, respectively. The growth inhibition rates for SKG-3a, A-431, HEC-1, HUOA and RMUG-s in the presence of 1.0 nM EGF at 48 hours were 32, 28, 25.8, 11.2 and 6.8%, respectively. 3) The antitumor effect of CDDP was enhanced by the presence of EGF at both a concentration of 0.01 nM (except for A-431) and a concentration of 1.0 nM, in all cell lines. 4) EGF receptors of RMUG-s and HUOA were decreased by CDDP. The values for RMUG-s and HUOA were 1.71 x 10(4), 0.52 x 10(4) (CDDP 0.4 microgram/ml) and 0.95 x 10(4), 0.29 x 10(4) sites per cell (CDDP 2.0 micrograms/ml), respectively. The effect of CDDP on EGF receptors was not recognized in SKG-3a and HEC-1. In brief, EGF receptors were significantly expressed in cell lines derived from female genital cancers.(ABSTRACT TRUNCATED AT 250 WORDS)     

卵巢恶性生殖细胞肿瘤患者保留生理功能的治疗

卵巢恶性生殖细胞肿瘤多发于青少年,在中国和亚洲其他地区,其发病率远高于西方国家,占全部卵巢恶性肿瘤的5%～20%.卵巢恶性生殖细胞肿瘤主要包括无性细胞瘤、未成熟畸胎瘤、内胚窦瘤、胚胎癌、原发性绒癌以及混合性生殖细胞肿瘤,前三者最常见.由于该疾病大多数生长迅速、恶性程度高、预后差且多发于年轻妇女甚至是幼女而受到临床医生的高度重视.在有效的化疗方法使用前,卵巢内胚窦瘤及未成熟畸胎瘤手术治疗后的存活率仅为7.1%和27%,而且过大的手术范围不仅使患者丧失了生育功能,更因为卵巢的切除而影响第二性征的发育,严重影响患者今后的生存质量.随着联合化疗的应用和不断改进,卵巢恶性生殖细胞肿瘤的存活率逐渐提高,达到87%～97.3%.与卵巢其他恶性肿瘤有所不同的是,该病的治疗方案需根据临床期别、病理组织学特征、患者年龄及生育要求等综合考虑.     

住院糖尿病病人病情分析

目的:通过对近年来我院住院糖尿病病人的资料分析,观察糖尿病转归、并发症的发生率及死亡原因.方法:查阅全院住院糖尿病病人病历,对患者的相关临床资料登记.结果:糖尿病患病率呈逐年增加的趋势,与1993年相比,1997年患病率增加0.5倍,1998年患病率增加1倍,2001年前半年增加2倍.2001年上半年住院糖尿病病人高血压、冠心病和心梗的患病率分别为39.1%,35.2%和6.7%,住院高血压病人糖尿病患病率由1998年的6%增至2001年的9%,住院冠心病病人糖尿病患病率增高约10%(P＜0.01).住院心梗病人糖尿病患病率增高约15%(P＜0.05).近3.5年,有2618例糖尿病病人住院(1.95%),与非糖尿病病人相比,病死率无显著性差异.糖尿病主要死亡原因为感染(41.2%),终末期肾病(39.2%)及癌症(31.4%).由于冠心病及脑血管意外死亡仅为15%及13%,而呼吸道感染(81%)及足感染(63%)为主要死因.结论:近8.5年中,在33 005病人中糖尿病病人逐年增多,特别是在近4年中,提高约2倍.高血压、冠心病及心梗病人糖尿病患病率逐年增高.近3.5年中住院糖尿病病人的死亡主要原因并非是心血管病变,而是感染.糖尿病病人癌症病死率有所增加.提倡早期诊断,早期预防,早期治疗糖尿病,采取健康的生活方式.     

应用避孕套保护喉镜

喉镜是气管插管的必备工具，为在不影响其使用功能的同时避免交叉感染，我科使用避孕套保护喉镜，取得了良好效果。现介绍如下。     

Robot-assisted thoracoscopic brachytherapy for lung cancer: comparison of the ZEUS robot, VATS, and manual seed implantation.

OBJECTIVE: Interstitial brachytherapy is becoming an accepted treatment option for lung cancer patients for whom surgery poses a high risk. Robotic surgery has the potential to deliver brachytherapy seeds into tumors while keeping surgeons at a safe distance from the radioactive source. Our aim was to compare the accuracy, number of attempts, and time needed to place seeds next to a target when using a manual technique, video-assisted thoracoscopic surgery (VATS), and the ZEUS robot for minimally invasive surgery (MIS). METHODS: A brachytherapy seed injector was developed and attached to one of the ZEUS robotic arms. Four subjects each inserted inactive dummy brachytherapy seeds into clear agar-gelatin cubes containing a 1.6-mm stainless steel ball target. Two orthogonal radiographs were taken of each agar cube, and the corresponding distances were measured in triplicate using ImageJ processing software. The mean distance between the center of each seed and the corresponding target was calculated using the Pythagorean theorem. Comparisons were made using analysis of variance, t-tests, and Kruskal-Wallis tests, as appropriate. RESULTS: A total of 384 tests (128 for each technique) were performed. The median accuracies for the manual technique, VATS, and ZEUS were 1.8 mm (range: 0.9-6.7 mm), 2.4 mm (range: 1.0-11.3 mm), and 3.6 mm (range: 1.3-16.7 mm), respectively (p < 0.01). The median numbers of attempts for the manual technique, VATS, and ZEUS were 1 (range: 1-5), 4 (range: 1-14), and 3 (range: 1-20), respectively (p < 0.01). The median times for the manual technique, VATS, and ZEUS were 3.0 s (range: 1-43 s), 86.5 s (range: 6-372 s), and 64.5 s (range: 5-356 s), respectively (p < 0.01). CONCLUSIONS: The manual technique is the most accurate, least traumatic, and fastest method of inserting seeds into tumors. The ZEUS robotic platform was able to place seeds beside a target within a clinically acceptable distance, with an acceptable amount of trauma and time required. It achieved results equal to or better than those obtained with VATS.     

Use of Cyclooxygenase Inhibitors and Risk of Melanoma in High-Risk Patients

Background Results from in vitro and animal studies suggest that cyclooxygenase (COX) inhibitors may reduce the risk of melanoma, but among humans, the evidence remains limited.
Objective In a pilot retrospective cohort, to determine the relationship between the use of COX inhibitors and the incidence, recurrence, and metastases of melanoma in high-risk patients.
Methods Reviewing computerized records at the Miami Veterans Affairs Medical Center, we retrospectively examined the association between COX inhibitor use and melanoma incidence, recurrence, and metastases in high-risk subjects: white subjects previously diagnosed with melanoma (1996–2003). We evaluated three potential outcomes: new melanoma diagnosis, recurrence of a previous melanoma, and melanoma metastasis.
Results Eighty-three subjects with melanoma were included. There was one metastasis among 28 subjects prescribed COX inhibitors, whereas four new melanomas (7.3%), two melanoma recurrences, and six metastases (10.9%) occurred among 55 patients not prescribed COX inhibitors. Although no individual outcomes measures reached statistical significance, combining the three measures, these were significantly lower in users of COX inhibitors compared with nonusers (1 vs 12;  p = .05  ). After adjustment for age and tumor depth of invasion, COX inhibitor users had significantly lower rates of melanoma outcome measures (odds ratio 0.08; 95% confidence interval 0.01–0.77;  p = .03  ).
Conclusion Potential exists for chemoprevention of melanoma among high-risk patients.