Eradication of Metastatic Renal Cell Carcinoma after Adenovirus-Encoded TNF-Related Apoptosis-Inducing Ligand (TRAIL)/CpG Immunotherapy

Despite evidence that antitumor immunity can be protective against renal cell carcinoma (RCC), few patients respond objectively to immunotherapy and the disease is fatal once metastases develop. We asked to what extent combinatorial immunotherapy with Adenovirus-encoded murine TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus CpG oligonucleotide, given at the primary tumor site, would prove efficacious against metastatic murine RCC. To quantitate primary renal and metastatic tumor growth in mice, we developed a luciferase-expressing Renca cell line, and monitored tumor burdens via bioluminescent imaging. Orthotopic tumor challenge gave rise to aggressive primary tumors and lung metastases that were detectable by day 7. Intra-renal administration of Ad5mTRAIL+CpG on day 7 led to an influx of effector phenotype CD4 and CD8 T cells into the kidney by day 12 and regression of established primary renal tumors. Intra-renal immunotherapy also led to systemic immune responses characterized by splenomegaly, elevated serum IgG levels, increased CD4 and CD8 T cell infiltration into the lungs, and elimination of metastatic lung tumors. Tumor regression was primarily dependent upon CD8 T cells and resulted in prolonged survival of treated mice. Thus, local administration of Ad5mTRAIL+CpG at the primary tumor site can initiate CD8-dependent systemic immunity that is sufficient to cause regression of metastatic lung tumors. A similar approach may prove beneficial for patients with metastatic RCC

Clinical approach for the classification of congenital uterine malformations

A more objective, accurate and non-invasive estimation of uterine morphology is nowadays feasible based on the use of modern imaging techniques. The validity of the current classification systems in effective categorization of the female genital malformations has been already challenged. A new clinical approach for the classification of uterine anomalies is proposed. Deviation from normal uterine anatomy is the basic characteristic used in analogy to the American Fertility Society classification. The embryological origin of the anomalies is used as a secondary parameter. Uterine anomalies are classified into the following classes: 0, normal uterus; I, dysmorphic uterus; II, septate uterus (absorption defect); III, dysfused uterus (fusion defect); IV, unilateral formed uterus (formation defect); V, aplastic or dysplastic uterus (formation defect); VI, for still unclassified cases. A subdivision of these main classes to further anatomical varieties with clinical significance is also presented. The new proposal has been designed taking into account the experience gained from the use of the currently available classification systems and intending to be as simple as possible, clear enough and accurate as well as open for further development. This proposal could be used as a starting point for a working group of experts in the field

Comparative efficacy and complications of vena caval filters

AbstractPurpose: A variety of vena caval filters (VCFs) are available for usage. The choice of filter type depends on physician preference and certain patient variables. An evaluation of the different VCFs used in our institution was done to compare their efficacy and complication rates.Methods: The medical records of all patients who underwent insertion of a VCF from January 1987 to June 1993 at the University of Iowa Hospitals & Clinics and the affiliated Veterans Administration Medical Center were reviewed. One hundred ninety-nine VCFs were placed in 196 patients (123 males, 73 females), with a mean age of 61 years (range 13 to 87 years). Thirty-five (18%) VCFs (30 stainless steel Greenfield filters [SGFs] and five titanium Greenfield filters with modified hook [TGF-MHs]) were inserted in the operating room via an open technique. The remaining 164 VCFs (82%) were inserted in the radiology suite by a percutaneous technique (38 SGF, 23 TGF-MH, 51 Vena Tech filters [VTFs], 48 Bird's nest filters [BNFs] and 4 Simon Nitinol filters). Thromboembolic risk factors in these 196 patients included malignancy (99), trauma (21), recent surgery (27), cerebrovascular accident with paralysis (6), and miscellaneous conditions (43). Indications for VCF placement included a contraindication to anticoagulation (92), complication of anticoagulation (44), failure of anticoagulation (26), prophylaxis (31), adjunct to pulmonary embolectomy (1), noncompliance (1), hemodynamically unstable patient (1), and prior VCF complication (3). Mean follow-up of the patients was 12 months (range 0 to 87 months). Because there were only four Simon Nitinol filters inserted during the study period, they were excluded from further analysis.Results: A comparative analysis revealed that there was a significantly higher incidence of symptomatic IVC thrombosis with the use of the BNF (n = 7) (14.6%) versus the SGF (n = 0) (0%), TGF-MH (n = 1) (3.6%), or VTF (n = 2) (4%) (p < 0.05 by chi-squared testing). The VCF-related mortality rate was also higher with the BNF (n = 5) (10.9%) versus the SGF (n = 1) (1.5%), TGF-MH (n = 1) (3.6%), or VTF (n = 0) (0%) (p < 0.05 by chi-squared testing). However there was no significant difference in the occurrence of clinically apparent recurrent pulmonary embolism during follow-up between the four different filter types (2 [4.2%] BNF, 3 [4.4%] SGF, 1 [3.6%] TGF-MH, and 1 [2%] VTF).Conclusion: These data indicate that the use of the BNF was associated with increased morbidity and mortality rates compared with the use of the SGF, TGF-MH, and VTF filters. (J VASC SURG 1995;21:235-46.

Effect of clinical factors on length of stay after coronary artery bypass surgery: results of the cooperative cardiovascular project

BACKGROUND: Rising health care costs have prompted careful review of comparative hospital resource use. Length of stay after bypass surgery has received particular attention. However, many providers assert that these variations are caused by differences in the clinical mix of patients treated. Our goals were to identify the major clinical predictors of postoperative length of stay (PLOS) after coronary artery bypass graft surgery (CABG), document variations in PLOS among 28 hospitals, and assess the degree to which patient characteristics account for hospital variations in PLOS. METHODS: Detailed clinical data on 3605 Medicare patients undergoing CABG in 28 Alabama and Iowa hospitals were analyzed by stepwise linear regression to identify significant clinical predictors of PLOS. Analysis of variance was used to compare hospitals\u27 PLOS while controlling for significant patient risk factors. RESULTS: The mean age was 72.1 years, 34.7% were female, and the in-hospital mortality rate was 5.6%. The median and mean PLOS were 8 and 11.1 days, respectively. Significant predictors of longer PLOS included increasing age, female sex, history of chronic obstructive pulmonary disease, cerebrovascular disease, or mitral valve disease, elevated admission blood urea nitrogen, and preoperative placement of an intraaortic balloon pump. Hospitals varied significantly (P =.0001) in their unadjusted PLOS. These hospital-level variations persisted despite adjustment for both preoperative patient characteristics (P =.0001) and postoperative complications and death (P =.0001). CONCLUSIONS: This study found significant between-hospital variations in PLOS that were not explained by patient factors. This finding suggests the potential for increased efficiency in the care of patients undergoing CABG at many institutions. Further research is needed to determine the practice patterns contributing to variations in length of stay after bypass surgery