Inflammation and Prostate Cancer.

Chronic inflammation resulting from infections, altered metabolism, inflammatory diseases or other environmental factors can be a major contributor to the development of several types of cancer. In fact around 20% of all cancers are linked to some form of inflammation. Evidence gathered from genetic, epidemiological and molecular pathological studies suggest that inflammation plays a crucial role at various stages of prostatic carcinogenesis and tumor progression. These include initiation, promotion, malignant conversion, invasion, and metastasis. Detailed basic and clinical research in these areas, focused towards understanding the etiology of prostatic inflammation, as well as the exact roles that various signaling pathways play in promoting tumor growth, is critical for understanding this complex process. The information gained would be useful in developing novel therapeutic strategies such as molecular targeting of inflammatory mediators and immunotherapy-based approaches.

Sedation for Bronchoscopy and Complications in Obese Patients.

BACKGROUND: Bronchoscopy is a safe and minimally invasive diagnostic tool, but no studies have reported prospectively on sedation and outcomes in patients with objectively defined obesity. OBJECTIVES: The purpose of the study is to determine if obese patients require more sedation or had more procedural complications during bronchoscopy under moderate sedation than non-obese patients. METHODS: We evaluated complications and sedation requirements in non-obese versus obese patients, defined by multiple criteria including body mass index (BMI), neck circumference, abdominal height, and Mallampati scores. RESULTS: Data were collected prospectively in 258 patients undergoing bronchoscopy under moderate sedation. By varying criteria, there were the following proportions of obese patients: 30% by BMI >30, 39% by neck circumference >40 cm, and 35% by abdominal height >22 cm in males and >20 cm in females. Sedative and analgesic dosing was not clinically significantly higher in obese patients than in non-obese patients. There was no difference in complications or procedural success based on obesity criteria. Hemoglobin oxygen desaturations occurred more often during bronchoscopy in patients with increasing Mallampati scores (p = 0.04), but this had no effect on bronchoscopy time or successful completion of the procedure. A subset of patients with previous polysomnogram-proven obstructive sleep apnea were more likely to have earlier termination of their procedure (15.8%) than patients with no diagnosed sleep apnea (2.3%; p = 0.002). CONCLUSION: In this prospective assessment of patients with obesity, we found neither clinically significant differences in sedation needs nor increases in complications in obese versus non-obese patients using a variety of indices of obesity.

Training in and experience with endobronchial ultrasound.

BACKGROUND: Diagnosing mediastinal and hilar lymphadenopathy and staging lung cancer with endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) are on the rise, but uncertainty surrounds the optimal number of cases needed to achieve acceptable yields. OBJECTIVES: To determine the threshold at which EBUS-TBNA reaches adequate yields among trainees and skilled bronchoscopists. METHODS: We reviewed all EBUS-TBNAs performed at our medical center since implementing the use of EBUS (n = 222). RESULTS: EBUS-TBNAs were performed in 222 patients (344 nodes). The percentage of adequate specimens sampled (diagnostic specimens or nodal tissue) rose from 66% in 2008 to 90% in 2012 (p < 0.01) and cancer yield improved from 34% in 2008 to 48% in 2012 (p < 0.01). Attending physicians who performed an average of more than 10 procedures per year had higher yields compared to those who performed fewer than 10 procedures per year (86 vs. 68%, p < 0.01). The yield of trainees also improved with every 10 procedures (79, 90 and 95%, p < 0.001) and that of attending physicians with experience (1-25 procedures: 78% yield, 26-50 procedures: 87% yield and 50+ procedures: 90% yield; p < 0.01). Among trainees, failure rates declined steadily. CONCLUSION: EBUS-TBNA yield (malignant and benign) increases with increasing experience amongst experienced bronchoscopists and trainees as early as the first 20-25 procedures. Pulmonary trainees had a rapid decline in failure rates. These findings suggest that in an academic environment a minimum of 20-25 procedures is needed to achieve acceptable yields.

Epidemiological survey of bovine gammaherpesvirus 4 (BoHV-4) infection in cattle and buffalo from Pakistan.

This study was conducted to evaluate the prevalence of bovine gammaherpesvirus 4 (BoHV-4) among healthy cattle and buffaloes as well as those associated with different diseases (respiratory tract infection, mastitis and reproductive tract infection) in District Chakwal, Pakistan. Blood, swab and milk samples of cattle and buffaloes were randomly collected from different areas of Chakwal. DNA was isolated from the samples and subjected to nested PCR using thymidine kinase gene primers. Out of 300 samples (200 blood, 50 swab and 50 milk samples) from both species (cattle and buffalo), an overall prevalence of BoHV-4 of 3.33% was obtained. Samples from cattle showed a higher species-specific prevalence (4.16%) than samples from buffalo (2.78%). One sample out of 50 swab samples and 1 out of 50 milk samples were also positive for BoHV-4. DNA sequencing of a positive PCR product from cattle confirmed that the sequence was from the thymidine kinase gene of BoHV-4. Phylogenetic analysis also revealed close similarities with other BOHV-4 thymidine kinase sequences. To detect BoHV-4 antibodies, an indirect ELISA was also performed. Two hundred blood samples were also collected from the same animals in nonanticoagulant-containing tubes for the isolation of serum and were subjected to indirect ELISA. Sixteen samples (8%) were positive for BoHV-4 antibodies. This study will be useful in further diagnoses of BoHV-4 in Pakistan and in devising measures to control the spread of BoHV-4.

Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences.

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

Epigenetic analysis identifies factors driving racial disparity in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is the second most leading cause of death in men worldwide. African-American men (AA) represent more aggressive form of the disease compared to Caucasian (CA) counterparts. Several lines of evidences suggest that biological factors are responsible for the observed racial disparity. AIM: This study was aimed at identifying the epigenetic variation among AA and CA PCa patients and whether DNA methylation differences have an association with clinical outcomes in the two races. METHODS AND RESULTS: The cancer genome atlas (TCGA) dataset (2015) was used to identify existing epigenetic variation in AA and CA PCa patients. Reduced Representation Bisulfite Sequencing (RRBS) was performed to identify global DNA methylation changes in a small cohort of AA and CA PCa patients. The RRBS data were then used to identify survival and recurrence outcomes in AA and CA PCa patients using publicly available datasets. The TCGA data analysis revealed epigenetic heterogeneity, which could be categorized into four classes. AA associated primarily to methylation cluster 1 (p = 0.048), and CA associated to methylation cluster 3 (p = 0.000146). Enrichment of the Wnt signaling pathway was identified in both the races; however, they were differentially activated in terms of canonical and non-canonical Wnt signaling. This was further validated using the Decipher Genomics Resource Information Database (GRID). The RRBS data also identified discrete methylation patterns in AA compared with CA and, in part, validated our TCGA findings. Survival analysis using the RRBS data suggested hypomethylated genes to be significantly associated with recurrence of PCa in CA (p = 6.07 × 10-6) as well as in AA (p = 0.0077). CONCLUSION: Overall, we observed epigenetic-based racial disparity in PCa which could affect survival and should be considered during prognosis and treatment.

Bronchoscopy Safety in Patients With Chronic Obstructive Lung Disease.

BACKGROUND: Flexible bronchoscopy is a safe and minimally invasive diagnostic tool used by pulmonologists, but few studies have prospectively compared outcomes in patients with objectively defined obstructive lung disease to those without obstruction. METHODS: We determined whether complications in patients undergoing moderate sedation bronchoscopy differ in those without obstruction compared with chronic obstructive pulmonary disease (COPD). We prospectively followed all patients undergoing moderate sedation bronchoscopy in an inpatient or outpatient setting. RESULTS: Over 12 months, data were collected prospectively in 258 patients. A total o 151 patients had pulmonary function testing with classification of COPD according to GOLD Criteria. Sixty-seven of those patients (44%) had COPD: 6 mild (9%), 29 moderate (42%), 27 severe (41%), and 5 very severe (8%). COPD patients were more likely to receive outpatient inhaled corticosteroids and long-acting bronchodilators and anticholinergics (P<0.001) as would be clinically appropriate. Among all patients with COPD, there were 13% minor complications and 5% major complications, with no deaths. Respiratory complications occurred more often in patients with severe to very severe COPD (22%) compared with patients without COPD (6%) (P=0.018). When adjusted for age, body mass index, and use of home oxygen, this difference was still significant (P=0.045). CONCLUSION: Bronchoscopy is generally safe with few complications in most patients with COPD. Patients with objectively confirmed severe to very severe COPD had more frequent respiratory complications than patients without COPD. The risks were not prohibitively high, but should be taken into consideration for COPD patients undergoing moderate sedation flexible bronchoscopy.

Differences in Renal Tumor Size Measurements for Computed Tomography Versus Magnetic Resonance Imaging: Implications for Patients on Active Surveillance.

PURPOSE: To evaluate and compare the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in predicting the final pathologic tumor size of partial nephrectomy specimens. MATERIALS AND METHODS: We analyzed a multi-institutional database of 807 patients who underwent robotic partial nephrectomy for a cT1a renal mass from 2006 to 2016. Patients who had a solitary tumor with complete data on the baseline imaging modality and the tumor size (baseline and pathologic) (n = 349) were included for analysis. Baseline tumor size evaluated by both imaging modalities, in addition to the difference between the measurements and final pathologic tumor size (cm) measurements, was compared between patients who received a baseline CT (n = 276, 79.1%) and those who received an MRI (n = 73, 20.9%). RESULTS: There were no statistically significant differences between any baseline characteristics and receipt of a CT versus MRI. In multivariable analysis adjusting for confounders, there was no significant difference in the baseline tumor size between patients receiving an MRI and those receiving a CT (2.3 versus 2.6 cm; ß = -0.13; 95% confidence interval [CI] = -0.33 to 0.07; P = .208). Tumor size on imaging was smaller from final pathology by 0.43 cm on average (P = .002). Measurement error for the measured baseline versus actual pathologic tumor size did not significantly differ for patients receiving an MRI versus those receiving a CT (0.38 versus 0.44 cm; ß = -0.06; 95% CI = -0.16 to 0.04; P = .232). CONCLUSION: Baseline renal tumor size measurements were not significantly different for CT scan and MRI. Choice of imaging modality can be based on doctor and patient preference, including cost and exposure to radiation.

A new pattern of pulmonary graft vs host disease in a hematopoietic stem cell transplant patient.

BACKGROUND: The primary pulmonary manifestation of chronic graft vs host disease (GvHD) is the development of bronchiolitis obliterans. Other pulmonary manifestations of chronic GvHD that have been reported include diffuse alveolar damage, lymphocytic interstitial pneumonia, bronchiolitis organising pneumonia and lymphocytic bronchiolitis/bronchitis. CASE PRESENTATION: We report an unusual case of a 34-year-old patient with acute myeloid leukaemia, status post-allogenic hematopoietic stem cell transplantation who subsequently developed GvHD with skin involvement. He presented to our hospital with new onset respiratory failure and on subsequent surgical lung biopsy was found to have non-specific interstitial pneumonia (NSIP). CONCLUSION: This is the third case of a patient with biopsy-proven GvHD who had NSIP pattern on surgical lung biopsy. We believe this may represent a rare manifestation of pulmonary GvHD.

Survey of academic pulmonologists, oncologists, and infectious disease physicians on the role of bronchoscopy in managing hematopoietic stem cell transplantation patients with pulmonary infiltrates.

BACKGROUND: In the absence of evidence-based guidelines, there is potential for variability in the management of hematopoietic stem cell transplantation (HSCT) patients with pulmonary infiltrates. We decided to perform a nationwide survey of pulmonologists, oncologists, and infectious disease physicians on the role of bronchoscopy in managing HSCT patients. METHODS: An 18-question survey was prepared, and after being internally reviewed it was sent through electronic mail to all hematology oncology, pulmonary and critical care, and infectious disease fellowship programs in the United States. Both faculty and fellows from all training programs were asked to electronically fill out the survey. RESULTS: A total of 167 responses, representing 76 different institutions were collected (62 pulmonary, 49 oncology, 53 infectious disease). Pulmonologists felt that bronchoscopy was less likely to yield a positive result or change pharmacological therapy (P-value=0.02 and 0.02). With regard to timing for bronchoscopy in HSCT recipients, there was consensus between all the 3 groups that patients who are non-neutropenic and do not have cavitating infiltrates on chest computed tomography scan should receive bronchoscopy only after failure of empiric antimicrobial therapy. However, there was no agreement between the 3 groups on when neutropenic patients or those with cavitating lesions should receive bronchoscopy. CONCLUSIONS: In the absence of randomized clinical trials and evidence-based guidelines, disparities exist in the use of bronchoscopy in the management of infiltrates. These differences were observed within and between both specialties. This study reflects the need for further research to better define the role of bronchoscopy in these patients.

Use of microdebrider bronchoscopy for the treatment of endobronchial leiomyoma.

AIMS: Pulmonary leiomyomas are rare benign tumors that may cause symptoms when they spread endobronchially. Traditionally they were managed surgically or through interventional bronchoscopy with the aid of thermal modalities to assist in debulking of tumor. We report the novel use of microdebrider bronchoscopy to debulk an endobronchial leiomyoma in a symptomatic patient. METHOD/RESULTS: The microdebrider successfully débrided the endobronchial leiomyoma. CONCLUSION: This modality can be successfully employed when oxygenation is an issue, preventing use of thermal modalities. In addition, use of microdebrider not only reduced procedure time but also decreased the risk of airway fire and damage to adjacent normal tissue in our patient.