Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials

BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers.METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test.RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501).CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.</p

Dorsal and Ventral Hippocampus Differentiate in Functional Pathways and Differentially Associate with Neurological Disease-Related Genes during Postnatal Development

The dorsal and ventral regions of the hippocampus are important in cognitive and emotional processing, respectively. Various approaches have revealed the differential molecular and structural characteristics, and functional roles of the hippocampus. Recent RNA sequencing (RNA-seq) technology has enriched our understanding of the hippocampus by elucidating more detailed information on gene expression patterns. However, no RNA-seq–based study on gene profiles in the developing hippocampus has been reported. Using RNA-seq–based bioinformatic analysis in conjunction with quantitative real-time polymerase chain reaction analysis and a comparison of in situ hybridization data obtained from the Allen Brain Atlas, we provide a thorough analysis of differentially expressed genes in the dorsal and ventral hippocampus at specific developmental ages representing the postnatally maturing hippocampus. Genes associated with particular functional pathways and marker genes for particular neurological diseases were found to be distinctively segregated within either the dorsal or ventral hippocampus at specific or at all developmental ages examined. We also report novel molecular markers enriched in the dorsal or ventral hippocampus. Taken together, this study provides insights into the molecular mechanisms underlying physiological functions linked to the dorsal or ventral hippocampus. The information provided in the study also contributes to a better understanding of brain functions and serves as a resource for future studies on the pathophysiology of dorsal and ventral hippocampal functions

Graphene-Based Gas Sensors with High Sensitivity and Minimal Sensor-to-Sensor Variation

Graphene as an atom-thick carbon material is promising for the detection of gaseous molecules owing to extremely high surface-to-volume ratio. However, the majority of graphene-based gas sensors, prepared by chemical vapor deposition (CVD), have suffered from non-uniformity in their responses. Such a high sensor-to-sensor variation in responses has not been systematically studied, limiting application of graphene gas sensors. Here we report processes that lead to a highly sensitive and uniform graphene gas sensor. We examined four types of graphene sensors by varying two conditions: (1) whether or not there is a carbon precursor while cooling down the reactor after graphene synthesis and (2) whether poly(methyl methacrylate) (PMMA), a polymer for transferring the graphene onto another substrate, is removed by annealing at high temperature or by rinsing with acetone. Using 5 ppm dimethyl methylphosphonate (DMMP), a nerve agent simulant, as a model analyte, we found that uniform responses are obtained by cooling down the reactor without carbon precursor and by removing PMMA by annealing. Additional heat treatment of the graphene in air greatly enhances the sensitivity, regardless of the synthesis conditions, by removing residual PMMA and impurities from the graphene surface. The uniform graphene sensors enabled us to find that the edge-to-surface ratio of graphene does not affect sensitivity, whereas noise increases at higher edge-to-surface ratio. Our study presents a design rule for fabricating sensitive and uniform graphene gas sensors, which may facilitate their applications in detecting a broad range of analytes

The Optimal Cutoff Value of Tumor Markers for Prognosis Prediction in Ampullary Cancer

Background: Carbohydrate antigen 19-9 (CA 19-9) is a representative tumor marker used for the diagnosis of pancreatic and biliary tract cancers. There are few published research results that can be applied to actual clinical practice for ampullary cancer (AC) alone. This study aimed to demonstrate the relationship between the prognosis of AC and the level of CA 19-9, and to determine the optimal thresholds. Methods: Patients who underwent curative resection (pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD)) for AC at the Seoul National University Hospital between January 2000 and December 2017 were enrolled. To determine the optimal cutoff values that could clearly stratify the survival outcome, the conditional inference tree (C-tree) method was used. After obtaining the optimal cutoff values, they were compared to the upper normal clinical limit of 36 U/mL for CA 19-9. Results In total, 385 patients were enrolled in this study. The median value of the tumor marker CA 19-9 was 18.6 U/mL. Using the C-tree method, 46 U/mL was determined to be the optimal cutoff value for CA 19-9. Histological differentiation, N stage, and adjuvant chemotherapy were significant predictors. CA 19-9 36 U/mL had marginal significance as a prognostic factor. In contrast, the new cutoff value, CA 19-9 46 U/mL, was found to be a statistically significant prognostic factor (HR: 1.37, p = 0.048). Conclusions: The new cutoff value of CA 19-9 46 U/mL may be used for evaluating the prognosis of AC. Therefore, it may be an effective indicator for determining treatment strategies such as surgical treatments and adjuvant chemotherapy

Aqueous Microlenses for Localized Collection and Enhanced Raman Spectroscopy of Gaseous Molecules

Raman spectroscopy of gaseous molecules has been challenging, requiring complicated experimental procedures and peripheral devices for concentrating the analytes. Here, Raman spectroscopy of gaseous molecules at parts-per-billion (ppb) levels is demonstrated using aqueous microlenses of LiCl solution that spontaneously absorb water-soluble gas molecules from the environment. The lenses are easily formed by filling the microwells of an elastomeric stamp with an aqueous solution of LiCl and stamping onto a substrate. Because LiCl is hygroscopic, the aqueous lenses maintain their liquid states under various ambient conditions. Gaseous molecules in the air dissolve in the aqueous microlens and can be identified based on their Raman fingerprints. Lowering the humidity causes the aqueous lens to transition into a salt crystal, while preserving the dissolved molecules within the crystal and facilitating the long-term storage and analysis of gaseous analytes. By forming the aqueous microlenses on a surface-enhanced Raman scattering (SERS) substrate, 800 ppb dimethyl methylphosphonate, a nerve agent simulant, is detected in a collection time of only 5 s. Aqueous microlenses that are responsive to the chemical environment are useful for analyzing various water-soluble gaseous molecules and therefore have broad implications for healthcare, food safety, and environmental-monitoring applications

Prediction of malignancy in main duct or mixed-type intraductal papillary mucinous neoplasms of the pancreas

© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.Background/Purpose: Surgical indications of main duct-involved intraductal papillary mucinous neoplasm (IPMN), especially for main pancreatic duct (MPD) of 5-9 mm, remain controversial. We aimed to predict malignancy risk of main duct-involved IPMN. Methods: Total 258 patients with main duct-involved IPMN between 2000 and 2017 in our institute were retrospectively analyzed. Main duct IPMN was classified into segmental and diffuse-type by dilated MPD pattern. Clinicopathologic features and predictive factors for malignancy were analyzed. Results: Among 258 patients, 47 and 211 had pure main duct (segmental: 27, diffuse type: 20) and mixed type, respectively. Malignant IPMN presented higher in main duct type (66.0%) compared to mixed type (46.9%). The diffuse type (72.2%) had more invasive carcinoma than the segmental type (40.7%). Invasive IPMN risk increased proportionally to the MPD diameter (5 ≤ MPD &lt;10 mm vs 10 ≤ MPD &lt; 15 mm vs MPD ≥ 15 mm; 23.4% vs 40.0% vs 48.6%). Symptoms, elevated serum carbohydrate antigen, MPD ≥10 mm, mural nodule, thickened wall, and distal atrophy were independent predictive factors for malignancy. Patients with MPD of 5-9 mm with at least one predictive factor had 35.0% of malignancy risk. Conclusions: The invasive IPMN risk was different according to the dilated main duct pattern. Patients with main duct type, diffuse type, MPD ≥10 mm, and MPD 5-9 mm with at least one predictive factor should be candidates for immediate surgery.N

Scheduled Naps Improve Drowsiness and Quality of Nursing Care among 12-Hour Shift Nurses

Scheduled naps in the workplace are an effective countermeasure to drowsiness in safety-sensitive industries. This quasi-experimental study with a one-group, pre- and post-test design aimed to examine the effects of scheduled naps on nurses working 12-h shifts. Nurses in two pediatric intensive care units at a tertiary hospital were provided 30-min scheduled nap opportunities during their shifts. A total of 38 nurses completed pre- and post-test work diaries for sleepiness, fatigue, work demands and pace, and quality of nursing care at the end of each shift. The drowsiness of 13 nurses was continuously assessed during their shifts using infrared reflectance oculography. Nurses who reached naps reported improved levels of fatigue on the first night shift and better quality of nursing care the second night and day shifts post-test, while nurses who did not reach naps showed no significant improvements. The oculography successfully assessed drowsiness during 73% and 61% of the pre- and post-test total work hours, respectively. The total cautionary and cautionary or higher levels of drowsiness decreased. Nurse managers should consider scheduled naps in clinical settings to improve nurses&rsquo; alertness during their shifts