Improvements in immunosuppressive therapy have greatly reduced acute rejection (ARj) episodes, ensuring better short-term graft outcome, but have not modified long-term survival in renal transplantation. It is now well accepted that chronic rejection (CRj) can be determined by both immune and/or nonimmune mechanisms. The aim of this study was to evaluate the importance of the posttransplant humoral immune response towards mismatched HLA graft antigens in CRj occurrence and graft outcome. Serum samples from 120 nonpresensitized renal transplant recipients were prospectively screened for 1 year after surgery by means of flow cytometry cross-match (FCXM) and FlowPRA beads (microbeads coated with purified HLA class I and class II antigens) assays. All transplants were followed-up for 2 years or until graft removal. FCXM monitoring identified donor-specific antibodies (DS-Abs) in 29 (24.2%) of 120 transplanted patients. Correlation with clinical data highlighted a higher incidence of ARj in DS-Abs–positive patients compared to negative patients (62% vs. 13%, P <0.00001). Furthermore, graft failure occurred more frequently among FCXM-positive patients than among negative patients (34% vs. 1%, P <0.00001). The deleterious effect of DS-Abs on graft function was confirmed by serum creatinine levels 2 years after transplantation. These were in fact higher in subjects producing DS-Abs than in subjects with only ARj (mean creatinine: 2.5±1.3 mg/dL vs.1.7±0.5 mg/dL, P =0.04). FlowPRA analysis of DS-Ab HLA specificity highlighted the presence of anti-HLA class I antibodies in 85% of FCXM-positive patients, who also presented with a higher incidence of HLA-B mismatches than FCXM-negative patients (1.23±0.66 vs. 0.92±0.59, P =0.02). Flow cytometric techniques are precious tools for investigating the activation of the humoral response against HLA antigens of the graft in renal transplantation. DS-Abs production has a worse impact on organ function and survival than ARj episodes. These findings represent further proof of the threat posed by DS-Abs on long-term graft function and draw attention to the need for a specific immunosuppressive therapy aimed at counteracting the different kinds of immune activation toward graft.
The efficacy of continuous wound infiltration with local anesthetic has not been compared with that of thoracic paravertebral block (PVB) after breast surgery. In this study, we evaluated the analgesic efficacy and morphine consumption of the two techniques after mastectomy. Forty-eight patients undergoing modified radical mastectomy with axillary dissection were randomly assigned to either a preoperative PVB with 20 mL of ropivacaine 0.5% (group PVB) or a continuous ropivacaine 0.5% infusion (CRI) at a 2 mL/h rate for each of two multilumen catheters placed subcutaneously at the end of the procedure (group CRI). The catheters were left in place for 24 h postoperatively. A standardized general anesthetic was administered to all patients. Postoperative morphine consumption, pain scores and painful restricted movement of the shoulder for 24 h postoperatively as well as incidence of adverse events, including postoperative nausea and vomiting, were recorded. Morphine consumption was similar between groups (PVB: 42.6 +/- 11 vs CRI: 38.7 +/- 11 mg in 24 h, P = 0.225). Absolute pain scores were low in both groups. Four hours after surgery, group PVB showed a significant reduction in postoperative pain (PVB: 0 [0-10] vs CRI: 0 [0-30], P = 0.002) and reduced painful restricted movement (P = 0.004), whereas the CRI group had lower pain scores (PVB: 10 [0-30] vs CRI: 0 [0-20], P = 0.034) and painful restricted movement (P = 0.043) 16 and 24 h (PVB: 10 [0-30] vs CRI: 0 [0-30], P = 0.012) after surgery. Postoperative nausea and vomiting was significantly more frequent in the CRI group (P = 0.017). Continuous wound infiltration of local anesthetics is an effective alternative to paravertebral analgesia after mastectomy with axillary dissection.
The development of the sequencing technologies allowed the generation of huge amounts of molecular data from a single cancer specimen, allowing the clinical oncology to enter the era of the precision medicine. This massive amount of data is highlighting new details on cancer pathogenesis but still relies on tissue biopsies, which are unable to capture the dynamic nature of cancer through its evolution. This assumption led to the exploration of non-tissue sources of tumoral material opening the field of liquid biopsies. Blood, together with body fluids such as urines, or stool, from cancer patients, are analyzed applying the techniques used for the generation of omics data. With blood, this approach would allow to take into account tumor heterogeneity (since the circulating components such as CTCs, ctDNA, or ECVs derive from each cancer clone) in a time dependent manner, resulting in a somehow “real-time” understanding of cancer evolution. Liquid biopsies are beginning nowdays to be applied in many cancer contexts and are at the basis of many clinical trials in oncology.
To evaluate in vivo the efficacy of a newly developed breast radiofrequency (RF) ablation system in human small invasive breast carcinomas in terms of induction of complete tumor necrosis, reproducibility of ablation lesion size and shape, and cosmetic outcome. This study had institutional review board approval, and written informed consent was obtained. Thirty-four postmenopausal women (mean age, 53 years +/- 5 [standard deviation]; range, 49-62 years) with small (< or = 2 cm) biopsy-proved invasive ductal breast carcinomas were enrolled. RF energy was delivered through a 25-mm 15-gauge monopolar cool-tip needle electrode by using the temperature-controlled mode. Patients were divided into three groups according to their breast pattern as assessed at mammography. The volumetric size and geometry of the coagulation zone, together with ablation time, were determined. Histopathologic data were compared with postprocedural 3.0-T contrast material-enhanced magnetic resonance (MR) images. Cosmesis after RF ablation was assessed. Four weeks after RF ablation, patients underwent definitive surgery. All ablation procedures were performed successfully. For 97% of the procedures, nicotinamide adenine dinucleotide in its reduced form-diaphorase staining showed no evidence of viable cells. The mean induced ablation volume, as assessed with histologic analysis, was 12.50 cm(3) +/- 0.8. Tumor ablation volume on the postablation MR images showed good correlation with results of histopathologic analysis (r = 0.823, P < .005). No differences were observed in terms of duration of the procedure or ablation volume with respect to the glandular pattern of the breast (P > .05 for both). The general shape of the induced necrosis was close to a sphere in all cases. Cosmesis was excellent in 28 patients. A dedicated breast cool-tip RF ablation system can induce complete tumor necrosis and reproducible ablation volumes independently of breast glandular pattern, providing excellent cosmesis. Postablation MR images are a reliable tool in predicting histologic findings.