Bovine Acellular Dermal Matrix in Immediate Breast Reconstruction: A Retrospective, Observational Study with SurgiMend.

BACKGROUND: Acellular dermal matrices can be combined with implant-based breast reconstruction to help optimize outcomes. SurgiMend PRS is a fetal bovine dermis-derived acellular dermal matrix composed of type I collagen and approximately 30 percent type III collagen, sharing many of the properties of human cadaveric acellular dermal matrix. METHODS: This was a retrospective, single-center analysis of 111 adult patients (147 breasts) undergoing one-stage (83.7 percent) or two-stage (16.3 percent) immediate breast reconstruction after mastectomy. The aims were to characterize the safety profile of SurgiMend and investigate associations between risk factors and complications. RESULTS: The mean age of the patients was 47.9 years and the mean body mass index was 24.7 kg/m. After a median follow-up of 24.3 months, the overall rates of minor and major complications were 25.2 percent (n = 37 of 147) and 12.9 percent (n = 19 of 147), respectively. The most common major complications were seroma [n = 12 (8.2 percent)] and necrosis [n = 9 (6.1 percent)]. All occurred within 3 months after surgery. The rate of capsular contracture was 2.7 percent (n = 4). A total of 2.7 percent of implanted breasts (n = 4) required explantation. In a univariate analysis, smokers had a greater risk of major complications (p = 0.013), and postoperative radiation therapy and obesity were associated with an increased risk of capsular contracture (p = 0.006) and explantation (p = 0.006), respectively. In a multivariate analysis, several factors were associated with complications or explantation, including obesity (p < 0.05), preoperative chemotherapy (p < 0.001), and mastectomy weight (p < 0.05). These associations align with other studies of implant-based reconstruction and do not appear to be specific to this acellular dermal matrix. CONCLUSION: The results are consistent with previous analyses of SurgiMend, and support its value in implant-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes.

Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression. This strategy should lead to pioneering clinical trials with xenotransplantation for treatment of diabetes and, thereby, represents a previously unidentified approach to efficient cell replacement for a broad spectrum of endocrine disorders and other organ dysfunctions.

Replication timing aberrations and aneuploidy in peripheral blood lymphocytes of breast cancer patients.

BACKGROUND: Peripheral blood lymphocytes of patients with hematological malignancies or solid tumors, such as renal cell carcinoma or prostate cancer, display epigenetic aberrations (loss of synchronous replication of allelic counterparts) and genetic changes (aneuploidy) characteristic of the cancerous phenotype. This study sought to determine whether such alterations could differentiate breast cancer patients from cancer-free subjects. METHODS: The HER2 locus-an oncogene assigned to chromosome 17 whose amplification is associated with breast cancer (BCA)-and the pericentromeric satellite sequence of chromosome 17 (CEN17) were used for replication timing assessments. Aneuploidy was monitored by enumerating the copy numbers of chromosome 17. Replication timing and aneuploidy were detected cytogenetically using fluorescence in situ hybridization technology applied to phytohemagglutinin-stimulated lymphocytes of 20 women with BCA and 10 control subjects. RESULTS: We showed that both the HER2 and CEN17 loci in the stimulated BCA lymphocytes altered their characteristic pattern of synchronous replication and exhibited asynchronicity. In addition, there was an increase in chromosome 17 aneuploidy. The frequency of cells displaying asynchronous replication in the patients' samples was significantly higher (P < 10(-12) for HER2 and P < 10(-6) for CEN17) than the corresponding values in the control samples. Similarly, aneuploidy in patients' cells was significantly higher (P < 10(-9)) than that in the controls. CONCLUSIONS: The HER2 and CEN17 aberrant replication differentiated clearly between BCA patients and control subjects. Thus, monitoring the replication of these genes offers potential blood markers for the detection and monitoring of breast cancer.

The expression of three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain.

PURPOSE: Brain metastases affect 25% of patients with non-small cell lung cancer (NSCLC). We hypothesized that the expression of genes in primary NSCLC tumors could predict brain metastasis and be used for identification of high-risk patients, who may benefit from prophylactic therapy. EXPERIMENTAL DESIGN: The expression of 12 genes was measured by real-time quantitative reverse transcriptase PCR in 142 frozen NSCLC tissue samples. Univariate and multivariate Cox regression analysis was used to analyze the correlation between gene expression and the occurrence of brain metastasis. Immunohistochemistry on independent samples was used to verify the findings. RESULTS: A score based on the expression levels of three genes, CDH2 (N-cadherin), KIFC1, and FALZ, was highly predictive of brain metastasis in early and advanced lung cancer. The probability of remaining brain metastasis-free at 2 years after diagnosis was 90.0+/-9.5% for patients with stage I/stage II tumors and low score compared with 62.7+/-12% for patients with high score (P<0.01). In patients with more advanced lung cancer, the brain metastasis-free survival at 24 months was 89% for patients with low score compared with only 37% in patients with high score (P<0.02). These results were confirmed by immunohistochemical detection of N-cadherin in independent cohort of primary NSCLC. CONCLUSIONS: The expression levels of three genes in primary NSCLC tumors may be used to identify patients at high risk for brain metastasis who may benefit from prophylactic therapy to the central nervous system.