Faculty Bibliography

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.

Background/UNASSIGNED:Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods/UNASSIGNED:The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls. We used conditional logistic regression to evaluate the association between circulating cotinine and lung cancer, and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration), using receiver-operating characteristic (ROC) curve analysis. Results/UNASSIGNED:We observed a strong positive association between cotinine and lung cancer risk for current smokers [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32-1.47]. Cotinine concentrations consistent with active smoking (≥115 nmol/L) were common in former smokers (cases: 14.6%; controls: 9.2%) and rare in never smokers (cases: 2.7%; controls: 0.8%). Former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L) also showed increased lung cancer risk. For current smokers, the risk-discriminative performance of cotinine combined with self-reported smoking (AUCintegrated: 0.69, 95% CI: 0.68-0.71) yielded a small improvement over self-reported smoking alone (AUCsmoke: 0.66, 95% CI: 0.64-0.68) (P = 1.5x10-9). Conclusions/UNASSIGNED:Circulating cotinine concentrations are consistently associated with lung cancer risk for current smokers and provide additional risk-discriminative information compared with self-report smoking alone.

Objective: To validate prior findings of retrospective studies that endometriosis presents with left-sided predominance. Design: Retrospective cohort study. Settings: A single university medical center. Patients: Patients undergoing robot-assisted gynecologic procedures from December 2013 to January 2018. Based on distribution of endometriotic specimens submitted to pathology, patients were divided into three groups: left-predominant, right-predominant, and bilateral/midline. [Figure presented] Interventions: Robot-assisted laparoscopic treatment of endometriosis. Measurements/Results: The three study groups did not differ in median in age, body mass index (BMI), gravidity, parity, and type of prior endometriosis treatment. Distribution of endometriosis was significantly more likely to exhibit left predominance than right-predominant or bilateral distribution (median number of total specimens: 6 vs. 3 vs. 3, p < .05). Endometriotic lesions were significantly located in the left periureteral and uterosacral regions compared to right-predominant and bilateral distribution (median number of total specimens: 1 vs. 0 vs. 0, p < .05 and 1 vs. 0 vs. 0, p = .05, respectively). There was no significant difference in distribution of endometriomas (median number of total endometriomas: 1 vs. 1 vs. 2, left vs. right vs. bilateral, respectively, p = .34). Operative times were not significantly different between groups (60 vs. 84 vs. 90 minutes, left-predominant vs. right-predominant vs. bilateral/midline distribution, respectively, p = .20). Overall complication rates were low with a total of 5 patients requiring intraoperative consults to other surgical teams including general surgery, gynecology oncology, and urology. Four total reoperations were performed in non-urgent fashion due to recurrence of endometriosis. Conclusions: This study reaffirms prior findings that endometriosis often demonstrates a left-predominant distribution. Surgical time, which may function as a surrogate for disease severity, was not significantly different between groups, though may be underpowered. Further investigation will focus on the clinical significance of endometriosis distribution, such as complication rates, intraoperative consults, and disease recurrence.

Objective: To investigate the effects of decreasing insufflation pressure during robotic-assisted gynecologic surgery on intraoperative and postoperative parameters. The primary outcomes were patient-reported postoperative pain scores and length of stay in the post-anesthesia care unit (PACU). Secondary outcomes included intraoperative respiratory parameters, duration of surgery, total anesthesia time, and postoperative pain medication use. Design: Retrospective cohort study. Settings: Single academic urban hospital. Patients: Female patients undergoing robot-assisted surgery for benign gynecologic conditions performed by a single surgeon from 2014 to 2018. Interventions: Exposure to surgery performed at four different insufflation pressures: 15 mmHg (n = 99), 12 mmHg (n = 100), 10 mmHg (n = 99), and 8 mmHg (n = 300). Measurements/Results: 598 patients were identified. P values for continuous variables were determined using analysis of variance. Two-sided chi² test was used for categorical variables. When comparing the four groups, each decrease in insufflation pressure correlated with a significant decrease in initial pain scores (5.9 vs 5.4 vs 4.4 vs 3.8, p = < 0.0001), anesthesia time (p = .007), and length of stay in the PACU (449 vs 467 vs 351 vs 317 minutes, p = < 0.0001). There was no difference in duration of surgery (p = .31) or estimated blood loss (p = .09). Throughout the surgery, lower operating pressure was correlated with significantly lower peak inspiratory pressures (p < .0001) and tidal volumes (p < .0001), but a higher end tidal CO2 (p < .0001). Conclusions: Robot-assisted gynecologic surgery is associated with improved intraoperative and postoperative clinical outcomes with each decrease in insufflation pressure. Significant improvements include faster postoperative recovery times, decreased immediate postoperative pain, and improved intraoperative respiratory parameters without increasing duration of surgery or blood loss. [Figure presented] [Figure presented] [Figure presented]

Diets with high inflammatory potential are suspected to increase risk for pancreatic cancer (PC). Using pooled analyses, we examined whether this association applies to populations from different geographic regions and population subgroups with varying risks for PC, including variation in ABO blood type. Data from six case-control studies (cases, n=2,414; controls, n=4,528) in the Pancreatic Cancer Case-Control Consortium (PanC4) were analyzed, followed by replication in five nested case-control studies (cases, n=1,268; controls, n=4,215) from the Pancreatic Cancer Cohort Consortium (PanScan). Two polymorphisms in the ABO locus (rs505922 and rs8176746) were used to infer participants' blood types. Dietary questionnaire-derived nutrient/food intake was used to compute energy-adjusted dietary inflammatory index (DII®) scores to assess inflammatory potential of diet. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression. Higher E-DII scores, reflecting greater inflammatory potential of diet, were associated with increased PC risk in PanC4 (ORQ5 vs. Q1=2.20, 95% CI=1.85-2.61, Ptrend<0.0001; ORcontinuous=1.20, 95% CI=1.17-1.24), and PanScan (ORQ5 vs. Q1=1.23, 95% CI=0.92-1.66, Ptrend=0.008; ORcontinuous=1.09, 95% CI=1.02-1.15). As expected, genotype-derived non-O blood type was associated with increased PC risk in both the PanC4 and PanScan studies. Stratified analyses of associations between E-DII quintiles and PC by genotype-derived ABO blood type did not show interaction by blood type (Pinteraction=0.10 in PanC4 and Pinteraction=0.13 in PanScan). The results show that consuming a pro-inflammatory diet and carrying non-O blood type are each individually, but not interactively, associated with increased PC risk.