Second look laparotomy in the management of malignant epithelial ovarian neoplasias

In the present study we examined 15 patients with malignant epithelial ovarian neoplasms who underwent primary surgery and chemotherapy at the Institute of Obstetric and Gynecologic Clinic of the University of Pisa between 1983 and 1985. At the time of diagnosis and monthly during chemotherapy plasma levels of CEA, CA 19-9, CA 125 and TPA were detected. At the end of pharmacological treatment a second-look laparotomy was performed in each patient to assess the status of cancer. At this time the clinical response was complete in 13 patients and partial in 2. These results were confirmed at second-look laparotomy in 11 of 13 cases of complete clinical remission and in 1 of the 2 cases of partial clinical remission. Two patients in complete clinical remission showed persistent disease. The other one in partial clinical remission was surgically found to have unmodified tumor. Tumoral markers, and especially CA 125, have a good correlation with the clinical course of the disease. However these tumor associated antigens cannot replace second-look laparotomy for assessing the response to cytostatic drugs. In fact patients with normal serum levels of these markers at the end of chemotherapy, were surgically found to have both complete pathological remission and persistent disease. Therefore we have come to the conclusion that the second-look laparotomy and the evaluation of tumor markers have to be performed together in the management of malignant ovarian neoplasms.     

A comparison of the usefulness of serum measurements of CA 125, CA 50 and TATI in patients with malignant and benign gynecological pathology

CA 125, CA 50 and Tumor Associated Trypsin Inhibitor (TATI) levels were assayed in blood samples drawn at diagnosis from 149 patients with malignant or benign gynecological pathology. CA 125 serum levels greater than 35 U/ml and 65 U/ml were respectively found in 34/38 (89.5%) and in 33/38 (86.8%) patients with ovarian carcinoma, in 17/61 (27.9%) and in 6/61 (9.8%) with benign ovarian pathology, in 6/30 (20.0%) and in 1/30 (3.3%) with cervical carcinoma, in 6/20 (30.0%) and in 6/20 (30.0%) with endometrial carcinoma. TATI serum levels greater than 22 ng/ml were observed in 17/38 (44.7%) patients with ovarian carcinoma, in 3/61 (4.9%) with benign ovarian pathology, in 1/30 (3.3%) with cervical carcinoma and in 3/20 (15.0%) with endometrial carcinoma. CA 50 serum levels greater than 20 U/ml were found in 11/38 (28.9%) patients with ovarian carcinoma, in 19/61 (31.1%) with benign ovarian pathology, in 7/30 (23.3%) with cervical carcinoma and in 6/20 (30%) with endometrial carcinoma. This study confirmed that CA 125 is the most reliable marker for ovarian carcinoma; however TATI could have a role in the diagnostic evaluation of adnexal masses, because of its very good specificity, CA 125 and CA 50, but not TATI, could be of some benefit in the management of endometrial and cervical carcinoma.     

慢性移植肾失功356例危险因素分析

目的:慢性移植肾失功是导致后期移植肾丧失的重要原因之一,文章拟探讨慢性移植肾失功的相关因素及防治措施。方法:①选择1993-12/2006-12于解放军第三军医大学大坪医院行肾移植术后发生慢性移植肾失功患者356例,回顾性分析其临床资料。②调整免疫抑制剂方案,停服硫唑嘌呤、环孢素A或减少环孢素A30%￣50%剂量,改用他克莫司0.5￣1mg/(kg·d)、霉酚酸酯1￣2g/d、西罗莫司1￣2mL/d等药;控制血糖、血脂、血压,抗凝及补充鱼肝油丸;服用雷公藤、百令胶囊或尿毒清等中药,给予低蛋白、低磷及高维生素、氨基酸饮食;必要时手术切除移植肾。③分析肾移植术后发生慢性移植肾失功的危险因素并观察其治疗结果。结果:①慢性移植肾失功的危险因素:急性排斥反应254例(71.35%),巨细胞病毒感染65例(18.26%),移植肾肾小球肾炎21例(5.9%),药物中毒(环孢素A/他克莫司)9例(2.53%),高血压/高血脂/高血糖5例(1.41%),肾单位减少(高龄供肾/性别差异)2例(0.56%)。②治疗结果:切除移植肾194例(54.49%),带肾存活、恢复血液透析87例(24.44%),经治疗血肌酐维持在200￣300μmol/L63例(17.70%),死亡12例(3.37%)。结论:急性排斥反应是引起肾移植术后慢性移植肾失功的主要因素。提高供肾质量,严格组织配型,减少移植肾功能延迟恢复的发生,制定个体化免疫方案,定期监测药物浓度及肝肾功能,预防巨细胞病毒感染,可减少慢性移植肾失功的发生。     

Competitive engraftment of hematopoietic stem cells genetically modified with a truncated erythropoietin receptor

Transplantation of genetically modified hematopoietic stem cells (HSCs) has therapeutic potential for a variety of blood genetic disorders. Engraftment of HSCs, however, requires toxic myeloablative treatments, which render this approach questionable for non-life-threatening disorders. A potential alternative is the use of transgenes, which allows positive selection of HSCs in vivo. We used retroviral vectors to express a truncated derivative of the erythropoietin receptor (tEpoR) in murine and human hematopoietic cells. Murine HSCs expressing tEpoR at different levels (1500 to 13,000 receptors/cell) acquire a competitive repopulation capacity in vivo upon transplantation into fully or partially myeloablated co-isogenic mouse recipients. Long-term analysis of transplanted mice showed that expression of tEpoR at paraphysiological levels (approximately 1500 receptors/cell) has no effect on steady-state hematopoiesis and induces no further expansion of transduced cells after the engraftment period. Human cord blood-derived CD34+ stem/progenitor cells transduced with a lentiviral vector expressing tEpoR expand their clonogenic capacity in vitro, and significantly increase their marrow repopulation capacity upon xenotransplantation into sublethally irradiated NOD-SCID mice, with no alteration in their phenotype, survival, and differentiation properties. These data indicate that expression of tEpoR is an effective strategy to promote selective engraftment of genetically modified HSCs upon transplantation in both myeloablative and nonmyeloablative conditions, without the use of toxic drugs for selection.     

Specific inductive potential of a novel nanocomposite biomimetic biomaterial for osteochondral tissue regeneration

Osteochondral lesions require treatment to restore the biology and functionality of the joint. A novel nanostructured biomimetic gradient scaffold was developed to mimic the biochemical and biophysical properties of the different layers of native osteochondral structure. The present results show that the scaffold presents important physicochemical characteristics and can support the growth and differentiation of mesenchymal stromal cells (h‐MSCs), which adhere and penetrate into the cartilaginous and bony layers. H‐MSCs grown in chondrogenic or osteogenic medium decreased their proliferation during days 14–52 on both scaffold layers and in medium without inducing factors used as controls. Both chondrogenic and osteogenic differentiation of h‐MSCs occurred from day 28 and were increased on day 52, but not in the control medium. Safranin O staining and collagen type II and proteoglycans immunostaining confirmed that chondrogenic differentiation was specifically induced only in the cartilaginous layer. Conversely, von Kossa staining, osteocalcin and osteopontin immunostaining confirmed that osteogenic differentiation occurred on both layers. This study shows the specific potential of each layer of the biomimetic scaffold to induce chondrogenic or osteogenic differentiation of h‐MSCs. These processes depended mainly on the media used but not the biomaterial itself, suggesting that the local milieu is fundamental for guiding cell differentiation. Copyright © 2013 John Wiley & Sons, Ltd.     

Possible prognostic role of IL-17R in osteosarcoma

Purpose An intense vascularization of primary tumor mass is associated with a fatal outcome in various types of invasive solid tumors. Interleukin 17 (IL-17), a CD4+ T-cell-derived cytokine, stimulates some tumor cells to secrete angiogenic factors, among which venous endothelial growth factor (VEGF). We assessed whether the expression of IL-17 receptor (IL-17R) represents a marker for the metastasizing ability of osteosarcoma (OS), a very malignant bone tumor. Methods We immunoassayed the amount of VEGF secreted by three OS cell lines expressing IL-17R in differing amounts: HOS, MG63 and U-2 OS, and their sensitivity to IL-17 stimulation to secrete VEGF. Results U-2 OS, which best expresses IL-17R, secreted the highest amounts of VEGF and was the most sensitive to IL-17, whereas MG63 expressed the lowest level of IL-17R, secreted the lowest amount of VEGF and was not sensitive to IL-17. IL-17R expression correlated with VEGF secretion and IL-17 sensitivity. U-2 OS expressed the most dedifferentiated phenotype, which is associated with tumor malignancy. Conclusions These results suggest that IL-17R in OS might represent a marker of tumor metastasis potential.     

The role of tissue microarray in the era of target-based agents

Tissue microarray (TMA) technologies have been developed over the last years, mainly to identify biomarkers useful for the correct identification and characterization of tumors. Moreover, TMA has been implemented in retrospective studies in order to identify predictive biomarkers of response to a given therapy and/or to find potential new targets for biological therapy. We analyzed the fields of application of TMA technology and the design of TMA varying according to the objectives to be studied. In this article, the reader will learn how to design TMAs in order to cover the objectives of clinical trials based upon the use of target-based agents. The main limits and advantages of TMA and the results achieved in cancer diagnosis will be also described. Tissue microarray technology should be systematically applied to define critical markers, in retrospective studies and in the screening of most human tumors in order to find new possible molecular targets and to molecularly define the diagnosis of the neoplastic diseases. TMAs have substantially improved the field of translational studies, even in the design and follow-up of studies based upon the use of target-based agents in cancer therapy.     

Knee synovectomy in children with juvenile idiopathic arthritis

The purpose of the study was to assess the outcomes of knee synovectomies in children with juvenile idiopathic arthritis. Thirty-one arthroscopic synovectomies were performed in 19 children (six oligoarthritis, 20 polyarthritis, five psoriatic arthritis). The percentage of recurrence in the group with oligoarthritis was 67%, in the group with polyarthritis was 95%, whereas all psoriatic arthritis recurred. The overall mean survival (i.e. free from recurrence) was 1.05 years (95% confidence interval, 0.74-1.35). Mean survival time was 1.69, 0.80 and 1.30 years, respectively, for oligoarthritis, polyarthritis and psoriatic arthritis. After synovectomy we observed two complications: thrombophlebitis of the omolateral superior femoral vein and septic arthritis. In conclusion, the mainstay of therapy for juvenile idiopathic arthritis remains medical treatment and intensive physiotherapy. The aim of arthroscopic synovectomy is to allow to make the most of nonsurgical therapy. It revealed more accurate and less invasive results than open synovectomy, maintained the range of motion of the joint, allowed early mobilization and required shorter hospitalization. Best results were observed in the group of oligoarthritis.