Vulvar cancer in Botswana in women with and without HIV infection: patterns of treatment and survival outcomes.

OBJECTIVES: Vulvar cancer is a rare gynecological malignancy. However, the incidence of human papillomavirus (HPV)-associated vulvar disease is increasing, particularly in low- and middle-income countries. HIV infection is associated with an increased risk of HPV-associated vulvar cancer. We evaluated treatment patterns and survival outcomes in a cohort of vulvar cancer patients in Botswana. The primary objective of this study was to determine overall survival and the impact of treatment modality, stage, and HIV status on overall survival. METHODS: Women with vulvar cancer who presented to oncology care in Botswana from January 2015 through August 2019 were prospectively enrolled in this observational cohort study. Demographics, clinical characteristics, treatment, and survival data were collected. Factors associated with survival including age, HIV status, stage, and treatment were evaluated. RESULTS: Our cohort included 120 women with vulvar cancer. Median age was 42 (IQR 38-47) years. The majority of patients were living with HIV (89%, n=107) that was well-controlled on antiretroviral treatment. Among women with HIV, 54.2% (n=58) were early stage (FIGO stage I/II). In those without HIV, 46.2% (n=6) were early stage (stage I/II). Of the 95 (79%) patients who received treatment, 20.8% (n=25) received surgery, 67.5% (n=81) received radiation therapy, and 24.2% (n=29) received chemotherapy, either alone or in combination. Median follow-up time of all patients was 24.7 (IQR 14.2-39.1) months and 2- year overall survival for all patients was 74%. Multivariate analysis demonstrated improved survival for those who received surgery (HR 0.26; 95% CI 0.08 to 0.86) and poor survival was associated with advanced stage (HR 2.56; 95% CI 1.30 to 5.02). Survival was not associated with HIV status. CONCLUSIONS: The majority of women with vulvar cancer in Botswana are young and living with HIV infection. Just under half of patients present with advanced stage, which was associated with worse survival. Improved survival was seen for those who received surgery.

Radical hysterectomy is not associated with a survival benefit for patients with stage II endometrial carcinoma.

OBJECTIVE: To evaluate the role of radical hysterectomy in the management of patients with stage II endometrial carcinoma. MATERIALS: Patients diagnosed between 2004 and 2015, with stage II (based on the revised FIGO staging) endometrial carcinoma who had hysterectomy and regional lymph node surgery were identified in the National Cancer Database. Those who had radical or modified radical (RH), or total hysterectomy (TH) were selected. Overall survival (OS) was assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to evaluate survival after controlling for confounders. RESULTS: A total of 7552 patients who met the inclusion criteria were identified. Rate of RH was 10.5%. Those who underwent RH had longer hospital stay (median 3 vs 2 days, p < 0.001) and a higher 90-day (1.6% vs 0.8%, p = 0.05) mortality. There was no difference in OS between patients who had RH (n = 712) and SH (n = 5955) (p = 0.62); 5-year survival rates were 77.4% and 76.9%, respectively. After controlling for patient age (<65, ≥65 years), race (white, black, other/unknown), insurance status, presence of comorbidities, tumor size (<5, ≥5 cm, unknown), histology (endometrioid, non-endometrioid), performance of adequate lymphadenectomy, and receipt of adjuvant chemotherapy and radiation therapy, performance of radical hysterectomy was not associated with better survival (HR: 1.01, 95% CI: 0.85, 1.21). CONCLUSIONS: Radical hysterectomy was not associated with a survival benefit in a cohort of patients with stage II endometrial carcinoma.

Preemptive ultrasound-guided paravertebral block and immediate postoperative lung function.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the effects of preemptive ultrasound-guided thoracic paravertebral block versus intercostal block on postoperative respiratory function and pain control in patients undergoing video-assisted thoracoscopic surgery. SUBJECTS: 50 consecutive patients undergoing video-assisted thoracoscopic surgery. METHOD: A prospective cohort of patients who received either ultrasound-guided thoracic paravertebral block immediately before the procedure or intercostal block placed by the surgeon at the end of the procedure were studied. Pulmonary function was assessed before surgery and 4 h postoperatively. Pain was assessed with the visual analog scale at 2 and 4 h after surgery both at rest and on coughing. RESULTS: 30 patients on the paravertebral block group and 20 on the intercostal block group were studied. Forced vital capacity (p < 0.001), forced expiratory volume at 1 s (p < 0.001) and forced expiratory flow 25-75% (p = 0.001) were significantly higher at 4 h with paravertebral block compared to the intercostal block group. The visual analog score for pain was significantly improved with paravertebral block at rest (p < 0.05) and with cough (p = 0.00). Perioperative narcotic use was significantly reduced with paravertebral block in comparison to intercostal block (p = 0.04). CONCLUSIONS: When compared to intercostal blocks, ultrasound-guided thoracic paravertebral block appears to preserve lung function and provide better pain control in the immediate postoperative period after video-assisted thoracoscopic surgery.

A breast cancer cell microarray (CMA) as a rapid method to characterize candidate biomarkers.

Tissue microarrays (TMAs) have become an invaluable tool in cancer research to evaluate expression and subcellular localization of proteins in cells and tissues. As the catalogs of candidate biomarkers and therapeutic targets become more extensive, there is a need to characterize and validate these targets and biomarkers in cell lines as a primary biological system in research laboratories. Thus, cell microarrays (CMAs) are useful as a high-throughput screening tool. Here, we constructed a CMA containing 32 publicly available immortalized breast cell lines with the goal of creating a method to rapidly screen for antigens of interest in breast cancer research in a relatively easy, rapid and cost-effective manner. As proof of concept, we performed immunocytochemical staining of the HER2 receptor, as the status of this protein is relevant to breast cancer and has previously been reported for these cell lines. We observed a complete concordance of our staining with the published status of HER2 in these cell lines. In addition, we examined the expression of CD44, epithelial markers EpCAM and E-cadherin and tyrosine phosphoproteins. The labeling of these proteins correlates with the known biology of the cell lines. Our results demonstrate the utility of our method to screen for potential biomarkers and therapeutic targets in breast cancer and we suggest that CMAs be used as a general approach in breast cancer research.

Oxidative stress and nerve function after cardiopulmonary bypass in patients with diabetes.

BACKGROUND: Chronic hyperglycemia has been associated with increased oxidative stress in skeletal muscle and sympathetic nerve dysfunction. We investigated the effect of chronic hyperglycemia on the myocardium of patients with uncontrolled diabetes (UD) compared with patients with well-controlled diabetes (CD) and patients without diabetes (ND) after cardioplegic cardiopulmonary bypass (CP/CPB) with acute intraoperative glycemic control. METHODS: Atrial tissue and serum were collected from 47 patients (ND=18 with glycated hemoglobin [HbA1c] of 5.8±0.2; CD=8 with HbA1c of 6.1±0.1; with UD=21 with HbA1c=9.6±0.5) before and after CP/CPB for immunoblotting, protein oxidation assays, immunohistochemical evaluation, and microarray analysis. RESULTS: The uncontrolled group had increased total protein oxidation (p<0.05) and decreased levels of antioxidative enzyme manganese superoxide dismutase (MnSOD) (p<0.05) after CP/CPB compared with the controlled group. Collagen staining revealed increased fibrosis in patients with UD (p<0.05) compared with patients with CD and patients without diabetes. The uncontrolled group also showed a decrease in the neurogenic and angiogenic markers nerve growth factor (NGF) (p<0.05), neurotrophin (NT)-3 (p<0.05), and platelet-derived growth factor (PDGF)-ß (p<0.05) compared with the other groups after CP/CPB. Atrial and serum microarray analysis showed increased oxidative stress and sympathetic nerve damage, increased fibrosis, and a decrease in angiogenesis in patients with UD (p<0.03) compared with patients without diabetes. CONCLUSIONS: CP/CPB led to higher oxidative stress in patients with UD before surgical intervention, even after normal glucose levels were maintained intraoperatively. Thus, controlled HbA1C in addition to acute intraoperative glucose control may be a more suitable end point for patients with diabetes undergoing cardiac operations.

Pancreatic Cancer Database: an integrative resource for pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death in the world. The etiology of pancreatic cancer is heterogeneous with a wide range of alterations that have already been reported at the level of the genome, transcriptome, and proteome. The past decade has witnessed a large number of experimental studies using high-throughput technology platforms to identify genes whose expression at the transcript or protein levels is altered in pancreatic cancer. Based on expression studies, a number of molecules have also been proposed as potential biomarkers for diagnosis and prognosis of this deadly cancer. Currently, there are no repositories which provide an integrative view of multiple Omics data sets from published research on pancreatic cancer. Here, we describe the development of a web-based resource, Pancreatic Cancer Database (http://www.pancreaticcancerdatabase.org), as a unified platform for pancreatic cancer research. PCD contains manually curated information pertaining to quantitative alterations in miRNA, mRNA, and proteins obtained from small-scale as well as high-throughput studies of pancreatic cancer tissues and cell lines. We believe that PCD will serve as an integrative platform for scientific community involved in pancreatic cancer research.

Rapid characterization of candidate biomarkers for pancreatic cancer using cell microarrays (CMAs).

Tissue microarrays have become a valuable tool for high-throughput analysis using immunohistochemical labeling. However, the large majority of biochemical studies are carried out in cell lines to further characterize candidate biomarkers or therapeutic targets with subsequent studies in animals or using primary tissues. Thus, cell line-based microarrays could be a useful screening tool in some situations. Here, we constructed a cell microarray (CMA) containing a panel of 40 pancreatic cancer cell lines available from American Type Culture Collection in addition to those locally available at Johns Hopkins. As proof of principle, we performed immunocytochemical labeling of an epithelial cell adhesion molecule (Ep-CAM), a molecule generally expressed in the epithelium, on this pancreatic cancer CMA. In addition, selected molecules that have been previously shown to be differentially expressed in pancreatic cancer in the literature were validated. For example, we observed strong labeling of CA19-9 antigen, a prognostic and predictive marker for pancreatic cancer. We also carried out a bioinformatics analysis of a literature curated catalog of pancreatic cancer biomarkers developed previously by our group and identified two candidate biomarkers, HLA class I and transmembrane protease, serine 4 (TMPRSS4), and examined their expression in the cell lines represented on the pancreatic cancer CMAs. Our results demonstrate the utility of CMAs as a useful resource for rapid screening of molecules of interest and suggest that CMAs can become a universal standard platform in cancer research.