Jocelyn Sendecki

Targeted cyst wall puncture and aspiration during EUS-FNA increases the diagnostic yield of premalignant and malignant pancreatic cysts

BACKGROUND Characterization of pancreatic cysts by using EUS-FNA includes chemical and cytologic analysis. OBJECTIVE To evaluate whether material obtained from FNA of the cyst wall increases diagnostic yield. DESIGN Prospective series. SETTING Tertiary referral center. PATIENTS Consecutive patients with pancreatic cysts referred for EUS-FNA between March 2010 and March 2011. INTERVENTION FNA was performed with aspiration of cyst fluid for carcinoembryonic antigen (CEA) and cytology, followed by cyst wall puncture (CWP). CWP is defined as puncturing the far wall of the cyst and moving the needle back and forth through the wall to sample the wall epithelium. MAIN OUTCOME MEASUREMENTS The diagnostic yield for mucinous cystic pancreatic neoplasms by CEA and cytology obtained from cyst fluid compared with cytology obtained from CWP. CEA ≥192 ng/mL was considered mucinous. RESULTS A total of 69 pancreatic cysts from 66 patients were included. Adequate amounts of fluid were aspirated for CEA, amylase, and cytology in 60 cysts (81%). Cellular material adequate for cytologic assessment from CWP was obtained in 56 cysts (81%). Ten (30%) of 33 cysts with CEA <192 ng/mL and negative results of cyst fluid cytology had a mucinous diagnosis from CWP; 6 of 9 (67%) cysts with an insufficient amount of fluid for CEA analysis and cyst fluid cytology had a mucinous diagnosis from CWP. Furthermore, 4 malignant cysts were independently diagnosed by CWP cytology. The incremental diagnostic yield of CWP for mucinous or malignant cysts was therefore 29% (20 of 69 cysts, P = .0001). An episode of pancreatitis (1.45%) occurred. LIMITATION Lack of surgical criterion standard. CONCLUSIONS CWP during EUS-FNA is a safe and effective technique for improving the diagnostic yield for premalignant and malignant pancreatic cysts.

Suture compared with staple skin closure after cesarean delivery: a randomized controlled trial.

OBJECTIVE: To compare the incidence of wound complications between suture and staple skin closure after cesarean delivery. METHODS: This prospective, randomized clinical trial conducted at three hospitals in the United States between 2010 and 2012 included women undergoing cesarean delivery at 23 weeks of gestation or greater through a low-transverse skin incision. Women were randomized to closure of the skin incision with suture or staples after stratifying by body mass index and primary compared with repeat cesarean delivery. The primary outcome was incidence of wound complications, predefined as a composite of infection, hematoma, seroma, separation of 1 cm or longer, or readmission for wound complications. Analysis was according to the intention-to-treat principle; results were stratified by randomization group and adjusted for hospital by including it as a covariate. RESULTS: A total of 746 women were randomized, 370 to suture and 376 to staple closure. The median gestational age was 39 weeks. Fifty-eight women (7.8%) had wound complications—4.9% in the suture group and 10.6% in the staple group (adjusted odds ratio [OR] 0.43, 95% confidence interval [CI] 0.23–0.78); this was largely the result of the decreased incidence of wound separation in the respective groups (1.6% compared with 7.4%; adjusted OR 0.20, 95% CI 0.07–0.51). CONCLUSIONS: Suture closure of the skin incision at cesarean delivery is associated with a 57% decrease in wound complications compared with staple closure. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT01211600. LEVEL OF EVIDENCE: I

Circadian Gene Expression and Clinicopathologic Correlates in Pancreatic Cancer

IntroductionThe circadian rhythm is responsible for physiologic homeostasis, behavior, and components of multiple metabolic processes. Disruption of the circadian rhythm is associated with cancer development, and several circadian clock genes have been implicated in loss of cell cycle control, impaired DNA damage repair, and subsequent tumor formation. Here, we investigated the expression profiles of several circadian clock genes in pancreatic ductal adenocarcinoma (PDA).MethodsQuantitative real-time polymerase chain reaction was used to examine the circadian clock genes (brain-muscle-like (Bmal)-ARNTL, circadian locomotor output cycles kaput (Clock), cryptochrome 1 (Cry1), cryptochrome 2 (Cry2), casein kinase 1ε (CK1ε), period 1 (Per1), period 2 (Per2), period 3 (Per3), timeless (Tim), and timeless-interacting protein (Tipin)) in PDA, as well as matching adjacent and benign tissue. Logistic regression models with robust variance were used to analyze the gene expression levels, and Kaplan–Meier survival curves were generated based on gene expression.ResultsIn the tumor tissue of PDA patients, compared to their matched adjacent tissue, expression levels of all circadian genes were lower, with statistical significance for Per1, Per2, Per3, Cry1, Cry2, Tipin, Tim, CK1ε, Bmal-ARNTL, and Clock (p < 0.025). PDA tumors also expressed significantly lower levels of the circadian genes when compared to benign lesions for Per1, Per2, Per3, Cry2, Tipin, and CK1ε. A significant association between low levels of expression in the tumors and reduced survival was found with Per1, Per2, Per3, Cry2, Tipin, CK1ε, Clock, and Bmal-ARNTL.ConclusionsOur results reveal for the first time a dysregulated transcription of several circadian genes in PDA. Elevation of the gene levels in the benign and matched adjacent tissues may be indicative of their role during the process of tumorigenesis. The potential of using circadian genes as predictive markers of the outcomes and survival and distinguishing PDA from benign pancreas must be studied in larger populations to validate and demonstrate their eventual clinical utility.

Minimally Invasive Esophagectomy Provides Significant Survival Advantage Compared with Open or Hybrid Esophagectomy for Patients with Cancers of the Esophagus and Gastroesophageal Junction

BACKGROUND Minimally invasive esophagectomy (MIE) is increasingly being used to treat patients with cancer of the esophagus and gastroesophageal junction. We previously reported that oncologic efficacy may be improved with MIE compared with open or hybrid esophagectomy (OHE). We compared survival of patients undergoing MIE and OHE. STUDY DESIGN Our contemporary series of patients who underwent MIE (2008 to 2013) was compared with a cohort undergoing OHE (3-hole [n = 39], Ivor Lewis [n = 16], hybrid [n = 13], 2000 to 2013). Summary statistics were calculated by operation type; Kaplan-Meier methods were used to compare survival. Cox regression was used to assess the impact of operation type (MIE vs OHE) on mortality, adjusting for age, sex, total lymph nodes, lymph node ratio (LNR), neoadjuvant chemoradiotherapy (CRT), and stage. RESULTS The MIE (n = 104) and OHE (n = 68) groups were similar with respect to age and sex. The MIE group tended to have higher BMI, earlier stage disease, and was less likely to receive CRT. The MIE group experienced lower operative mortality (3.9% vs 8.8%, p = 0.35) and significantly fewer major complications. Five-year survival between groups was significantly different (MIE, 64%, OHE, 35%, p < 0.001). Multivariate analysis demonstrated that patients undergoing OHE had a significantly worse survival compared with MIE independent of age, LNR, CRT, and pathologic stage (hazard ratio 2.00, p = 0.019). CONCLUSIONS This study supports MIE for EC as a superior procedure with respect to overall survival, perioperative mortality, and severity of postoperative complications. Several biases may have affected these results: earlier stage in the MIE group and disparity in timing of the procedures. These results will need to be confirmed in future prospective studies with longer follow-up.

Cost‐effectiveness of a standard intervention versus a navigated intervention on colorectal cancer screening use in primary care

Colorectal cancer (CRC) screening is cost‐effective but underused. The objective of this study was to determine the cost‐effectiveness of a mailed standard intervention (SI) and tailored navigation interventions (TNIs) to increase CRC screening use in the context of a randomized trial among primary care patients.

Clinical Significance of Serum COL6A3 in Pancreatic Ductal Adenocarcinoma

Type VI collagen (COL6) forms a microfibrillar network often associated with type I collagen and constitutes a major component of the desmoplastic reaction in pancreatic ductal adenocarcinoma (PDA). We have demonstrated recently that the α3 chain of COL6, COL6A3, is highly expressed in PDA tissue and undergoes tumor-specific alternative splicing. In this study, we investigated the diagnostic value and clinical significance of circulating COL6A3 protein and mRNA in PDA. COL6A3 levels in sera from patients with PDA (n = 44), benign lesions (n = 46) and age-matched healthy volunteers (n = 30) were analyzed by enzyme-linked immunosorbent assays (ELISA). Predictive abilities of COL6A3 were examined using receiver operating characteristic (ROC) curves from logistic regression models for PDA versus normal or benign serum levels. Expression levels were correlated with clinicopathological parameters. Real-time PCR was used to analyze the presence of COL6A3 mRNA containing alternative spliced exons E3, E4, and E6. Circulating COL6A3 protein levels were significantly elevated in PDA patients when compared to healthy sera (p = 0.0001) and benign lesions (p = 0.0035). The overall area under the ROC was 0.975. Log(COL6A3) alone provided good discrimination between PDA and benign lesions (area under the curve (AUC) = 0.817), but combined with CA19-9 provided excellent discrimination (AUC = 0.904). Interestingly, high COL6A3 serum levels were significantly associated with perineural invasion and cigarette smoking. Combined E3, E4, and E6 serum RNA values provided good sensitivity but low specificity. Our data demonstrate for the first time the potential clinical significance of circulating COL6A3 in the diagnosis of pancreatic malignancy.

Pain Characteristics and Age-Related Pain Trajectories in Infants and Young Children with Sickle Cell Disease

The epidemiology of painful episodes in infants and younger children with SCD has not been well studied, particularly for pain managed at home.

Musculoskeletal Effects of 2 Functional Electrical Stimulation Cycling Paradigms Conducted at Different Cadences for People With Spinal Cord Injury: A Pilot Study.

OBJECTIVE To compare the musculoskeletal effects of low cadence cycling with functional electrical stimulation (FES) with high cadence FES cycling for people with spinal cord injury (SCI). DESIGN Randomized pre-post design. SETTING Outpatient rehabilitation clinic. PARTICIPANTS Participants (N=17; 14 men, 3 women; age range, 22-67y) with C4-T6 motor complete chronic SCI were randomized to low cadence cycling (n=9) or high cadence cycling (n=8). INTERVENTIONS Low cadence cycling at 20 revolutions per minute (RPM) and high cadence cycling at 50 RPM 3 times per week for 6 months. Cycling torque (resistance per pedal rotation) increased if targeted cycling cadence was maintained. MAIN OUTCOME MEASURES Dual-energy x-ray absorptiometry was used to assess distal femur areal bone mineral density, magnetic resonance imaging was used to assess to assess trabecular bone microarchitecture and cortical bone macroarchitecture and thigh muscle volume, and biochemical markers were used to assess bone turnover. It was hypothesized that subjects using low cadence cycling would cycle with greater torque and therefore show greater musculoskeletal improvements than subjects using high cadence cycling. RESULTS A total of 15 participants completed the study. Low cadence cycling obtained a maximal average torque of 2.9±2.8Nm, and high cadence cycling obtained a maximal average torque of 0.8±0.2Nm. Low cadence cycling showed greater decreases in bone-specific alkaline phosphatase, indicating less bone formation (15.5% decrease for low cadence cycling, 10.7% increase for high cadence cycling). N-telopeptide decreased 34% following low cadence cycling, indicating decreased resorption. Both groups increased muscle volume (low cadence cycling by 19%, high cadence cycling by 10%). Low cadence cycling resulted in a nonsignificant 7% increase in apparent trabecular number (P=.08) and 6% decrease in apparent trabecular separation (P=.08) in the distal femur, whereas high cadence cycling resulted in a nonsignificant (P>.3) 2% decrease and 3% increase, respectively. CONCLUSIONS This study suggests that the greater torque achieved with low cadence cycling may result in improved bone health because of decreased bone turnover and improved trabecular bone microarchitecture. Longer-term outcome studies are warranted to identify the effect on fracture risk.

The Effects of Test Preference, Test Access, and Navigation on Colorectal Cancer Screening

Background: Little is known about how colorectal cancer screening test preferences operate together with test access and navigation to influence screening adherence in primary care. Methods: We analyzed data from a randomized trial of 945 primary care patients to assess the independent effects of screening test preference for fecal immunochemical test (FIT) or colonoscopy, mailed access to FIT and colonoscopy, and telephone navigation for FIT and colonoscopy, on screening. Results: Preference was not associated with overall screening, but individuals who preferred FIT were more likely to complete FIT screening (P = 0.005), whereas those who preferred colonoscopy were more likely to perform colonoscopy screening (P = 0.032). Mailed access to FIT and colonoscopy was associated with increased overall screening (OR = 2.6, P = 0.001), due to a 29-fold increase in FIT use. Telephone navigation was also associated with increased overall screening (OR = 2.1, P = 0.005), mainly due to a 3-fold increase in colonoscopy performance. We estimated that providing access and navigation for both screening tests may substantially increase screening compared with a preference-tailored approach, mainly due to increased performance of nonpreferred tests. Conclusions: Preference influences the type of screening tests completed. Test access increases FIT and navigation mainly increases colonoscopy. Screening strategies providing access and navigation to both tests may be more effective than preference-tailored approaches. Impact: Preference tailoring in colorectal cancer screening strategies should be avoided if the objective is to maximize screening rates, although other factors (e.g., costs, necessary follow-up) should also be considered. Cancer Epidemiol Biomarkers Prev; 23(8); 1521–8. ©2014 AACR.

Using routinely collected growth data to assess a school-based obesity prevention strategy

Background:Studies of school-based anti-obesity interventions have yielded inconsistent results. Using growth screening data from a school administrative database, we re-evaluated an obesity prevention strategy that was previously reported to have a beneficial effect on weight status of a sample of students in grades 5–7.Methods:Ten K-8 schools (five control and five intervention) participated in a 2-year cluster-randomized trial of a multi-component nutrition education intervention. We obtained student height and weight data for 6 consecutive school years and imputed missing baseline and follow-up measurements (53% and 55%, respectively) and defined the target population based on the intent-to-treat principle. We analyzed changes in body mass index (BMI) Z-scores via mixed-effects linear regression and in the prevalence of overweight/obesity via conditional logistic regression. We also assessed incidence and remission of overweight/obesity and long-term effects.Results:We analyzed data for 8186 (96%) K-8 students in the 10 schools (4511 in intervention; 3675 in control). From baseline to the end of the intervention period, mean increases in BMI Z-score were 0.10 and 0.09 in the control and intervention groups, respectively (P=0.671). The prevalence of overweight/obesity increased by 3% in both groups (P=0.926). There was no significant intervention effect on the incidence or remission of overweight/obesity. Among 5469 students who attended study schools during both years of the intervention, there was no significant intervention effect. Furthermore, there was no long-term effect among students with up to 2 years of data beyond the end of the intervention.Conclusion:Using routinely collected data for the entire target population, we failed to confirm earlier findings of an intervention effect observed in a subset of students in grades 5–7. Volunteer bias in the prior evaluation and/or measurement error in the routinely collected data are potential reasons for the discrepant findings.