Association between serum ferritin, incident primary liver cancer, and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: A nested case-control study.

BACKGROUND AND AIM: Previous studies suggest that serum ferritin may be associated with higher risk of liver cancer. However, additional studies of the association are needed. It is also not clear whether serum ferritin is associated with mortality from chronic liver disease (CLD). METHODS: We performed a nested case-control study in the Linxian Nutrition Intervention Trials. Baseline serum ferritin was measured for 226 incident primary liver cancer cases, 281 CLD mortalities diagnosed, and 1061 age-matched, gender-matched, and trial-matched controls. We used multivariable logistic regression models to calculate odds ratios and 95% confidence intervals. Subgroup analysis and interaction tests were performed by age, gender, alcohol drinking, hepatitis B virus seropositivity (HBV+)/hepatitis C virus seropositivity (HCV+), and trial. RESULTS: Participants with serum ferritin in the highest quartile, as compared with those in the lowest quartile, had an increased risk of CLD mortality (odds ratio = 1.72, 95% confidence interval = 1.12, 2.64, P-trend < 0.01). Moreover, the association with higher serum ferritin was stronger among alcohol drinkers and those who were HCV+ (P-interaction < 0.05). For incident liver cancer, risk estimates were above one but were not statistically significant. CONCLUSION: In this study, higher levels of serum ferritin at baseline were associated with subsequent mortality from CLD, particularly if combined with alcohol drinking or viral hepatitis. Further work is warranted to confirm our findings.

Self-rated health in relation to fruit and vegetable consumption and physical activity among older cancer survivors.

PURPOSE: We aimed to investigate associations of self-rated health with fruit and vegetable consumption (FVC) and physical activity (PA) among older cancer survivors. METHODS: We used the 2017 Behavioral Risk Factor Surveillance System to identify cancer survivors ≥ 65 years (N = 2663). Self-reported FVC and PA were categorized as ordinal variables to approximate quartiles. Low general health (LGH) was defined as fair or poor self-rated health. A multivariable logistic regression treating LGH as the outcome was used to calculate adjusted odd ratios (aORs) and 95% confidence intervals (CIs) for FVC and PA. Restricted cubic spline depicted non-linear dose-response curves for FVC and PA. In comparative analysis, we used the same logistic regression and dose-response model to calculate ORs of FVC and PA in 73,134 people ≥ 65 years without cancer history. RESULTS: Overall, 470 (17.7%) survivors had LGH. Survivors' mean age was 73.3 years (SD = 5.2), 55.1% of them were female, and 95.4% self-reported as white. In cancer survivors, FVC was not associated with LGH (≥ 28 vs. < 14 times/week: aOR = 1.02, 95% CI = 0.75-1.39, p-trend = 0.50), whereas PA was inversely associated with LGH (≥ 30 vs. < 7 MET-hours/week: aOR = 0.55, 95% CI = 0.41-0.75, p-trend < 0.01). Dose-response curves demonstrated consistent association patterns. In comparative analysis, ORs of PA did not change substantially but we observed inverse association for FVC. CONCLUSIONS: An inverse association between PA and LGH was observed among older cancer survivors, but no significant association was obtained for FVC among them. Regular PA may maintain or indicate a favorable health in older cancer survivors, whereas impacts of FVC deserve further investigations.

High-Speed Integrated Endoscopic Photoacoustic and Ultrasound Imaging System.

Endoscopic integrated photoacoustic and ultrasound imaging has the potential for early detection of the cancer in the gastrointestinal tract. Currently, slow imaging speed is one of the limitations for clinical translation. Here, we developed a high speed integrated endoscopic PA and US imaging system, which is able to perform PA and US imaging simultaneously up to 50 frames per second. Using this system, the architectural morphology and vasculature of the rectum wall were visualized from a Sprague Dawley rat in-vivo.

Two New Tools for Glycopeptide Analysis Researchers: A Glycopeptide Decoy Generator and a Large Data Set of Assigned CID Spectra of Glycopeptides.

The glycopeptide analysis field is tightly constrained by a lack of effective tools that translate mass spectrometry data into meaningful chemical information, and perhaps the most challenging aspect of building effective glycopeptide analysis software is designing an accurate scoring algorithm for MS/MS data. We provide the glycoproteomics community with two tools to address this challenge. The first tool, a curated set of 100 expert-assigned CID spectra of glycopeptides, contains a diverse set of spectra from a variety of glycan types; the second tool, Glycopeptide Decoy Generator, is a new software application that generates glycopeptide decoys de novo. We developed these tools so that emerging methods of assigning glycopeptides' CID spectra could be rigorously tested. Software developers or those interested in developing skills in expert (manual) analysis can use these tools to facilitate their work. We demonstrate the tools' utility in assessing the quality of one particular glycopeptide software package, GlycoPep Grader, which assigns glycopeptides to CID spectra. We first acquired the set of 100 expert assigned CID spectra; then, we used the Decoy Generator (described herein) to generate 20 decoys per target glycopeptide. The assigned spectra and decoys were used to test the accuracy of GlycoPep Grader's scoring algorithm; new strengths and weaknesses were identified in the algorithm using this approach. Both newly developed tools are freely available. The software can be downloaded at http://glycopro.chem.ku.edu/GPJ.jar.

GlycoPep MassList: software to generate massive inclusion lists for glycopeptide analyses.

Protein glycosylation drives many biological processes and serves as markers for disease; therefore, the development of tools to study glycosylation is an essential and growing area of research. Mass spectrometry can be used to identify both the glycans of interest and the glycosylation sites to which those glycans are attached, when proteins are proteolytically digested and their glycopeptides are analyzed by a combination of high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) methods. One major challenge in these experiments is collecting the requisite MS/MS data. The digested glycopeptides are often present in complex mixtures and in low abundance, and the most commonly used approach to collect MS/MS data on these species is data-dependent acquisition (DDA), where only the most intense precursor ions trigger MS/MS. DDA results in limited glycopeptide coverage. Semi-targeted data acquisition is an alternative experimental approach that can alleviate this difficulty. However, due to the massive heterogeneity of glycopeptides, it is not obvious how to expediently generate inclusion lists for these types of analyses. To solve this problem, we developed the software tool GlycoPep MassList, which can be used to generate inclusion lists for liquid chromatography tandem-mass spectrometry (LC-MS/MS) experiments. The utility of the software was tested by conducting comparisons between semi-targeted and untargeted data-dependent analysis experiments on a variety of proteins, including IgG, a protein whose glycosylation must be characterized during its production as a biotherapeutic. When the GlycoPep MassList software was used to generate inclusion lists for LC-MS/MS experiments, more unique glycopeptides were selected for fragmentation. Generally, ∼30 % more unique glycopeptides can be analyzed per protein, in the simplest cases, with low background. In cases where background ions from proteins or other interferents are high, usage of an inclusion list is even more advantageous. The software is freely publically accessible. Graphical abstract Software increases the number of glycopeptides that get selected for MS/MS analysis.

New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets.

Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. The software is provided at https://desairegroup.ku.edu/research.

Associations of Pap test utilisation with comorbidity and functional impairment among middle-aged non-Hispanic black women in the USA: a cross-sectional analysis of the 2018 BRFSS data.

OBJECTIVES: Limited evidence exists on the association of Pap test utilisation with comorbidity and functional impairment among middle-aged non-Hispanic black (NHB) women in the USA. We aimed to assess whether middle-aged NHB women with a higher burden of comorbidity and functional impairment have a lower rate of Pap test utilisation. DESIGN: Nationwide cross-sectional survey in the USA. SETTING: 2018 Behavioral Risk Factor Surveillance System. PARTICIPANTS: 6359 middle-aged NHB women. EXPOSURES AND OUTCOME: The primary exposures were comorbidity and functional impairment. The outcome of interest was whether a woman reported having a Pap test in the last 3 years. DATA ANALYSIS: We fit unadjusted and multivariable logistic regression models to calculate ORs and 95% CI for comorbidity and functional impairment. Sensitivity analysis was restricted to women without a history of hysterectomy or cancer. We added interaction terms between exposures and age, as well as lifestyle indicators. RESULTS: Of the 6359 women, 4141 (65.1%) had comorbidity and 2429 (38.2%) had functional impairment. Middle-aged NHB women with comorbidity (≥2 vs 0, aOR=0.72, 95% CI=0.61 to 0.85, p trend<0.01) or functional impairment (≥2 vs 0, aOR=0.69, 95% CI=0.57 to 0.83, p trend<0.01) had a lower rate of Pap test utilisation compared with healthier counterparts, regardless of histories of hysterectomy and prior cancer. The analyses for age and lifestyle indicators subgroup difference indicated no statistically significant effect (p interaction>0.05). However, the magnitude of these associations was stronger among women with adverse lifestyle factors (eg, comorbidity ≥2 v.s. 0, aOR=0.53, 95% CI=0.40, to 0.71; functional impairment ≥2 v.s. 0, aOR=0.35, 95% CI=0.16, to 0.72 among binge drinkers). CONCLUSION: Comorbidity or functional impairment could be a potential barrier to Pap test utilisation among middle-aged NHB women in the USA. Our study highlights the importance of implementing targeted intervention programmes and prioritised health resource allocation to promote Pap test utilisation. Cohort studies with clear temporality and indicators reflecting disease severity will be essential for further understanding this association.

Quantitative Optical Coherence Elastography of the Optic Nerve Head In Vivo.

OBJECTIVE: Optical coherence elastography (OCE) was used to demonstrate the relationship between the elasticity of the optic nerve head (ONH) and different intraocular pressure (IOP) levels in an in-vivo rabbit model for the first time. METHOD: Both ex-vivo and in-vivo rabbit ONH were imaged using OCE system. A mechanical shaker initiated the propagation of elastic waves, and the elasticity of the ONH was determined by tracking the wave propagation speed. The elasticity of the ONH under varying IOP levels was reconstructed based on the wave speed. Notably, the ONH exhibited increased stiffness with elevated IOP. RESULTS: In the in-vivo rabbit models, the Young's modulus of ONH increased from 14 kPa to 81 kPa with the IOP increased from 15 mmHg to 35 mmHg. This revealed a positive correlation between the Young's modulus of the ONH and intraocular pressure. CONCLUSION: The OCE system proved effective in measuring the mechanical properties of ONH at different IOP levels, with validation in an in-vivo rabbit model. SIGNIFICANCE: Considering ONH plays a critical role in vision and eye diseases, the capability to image and quantify in vivo ONH biomechanical properties has great potential to advance vision science research and improve the clinical management of glaucoma patients.

Preliminary analysis of stimulation parameters for sacral neuromodulation in different indications: a multicenter retrospective cohort study from China.

BACKGROUND: Sacral neuromodulation (SNM) is an effective approach for treating lower urinary tract dysfunction (LUTD), and stimulation programming is essential for successful treatment. However, research on SNM programming for various indications is limited. Thus, the authors aimed to determine whether there were differences in the stimulation parameters for different SNM indications and the appropriate programming recommendations. MATERIALS AND METHODS: Clinical data were retrospectively collected from patients with LUTD who underwent SNM and completed internal pulse generator implantation. The parameters with the highest patient satisfaction or the most symptom improvement during the test period were considered optimal and used to set the programming after internal pulse generator implantation. RESULTS: After screening, 282 patients were enrolled and categorized into four groups based on the following indications: refractory overactive bladder (OAB) ( n =61), neurogenic lower urinary tract dysfunction (nLUTD) ( n =162), interstitial cystitis/painful bladder syndrome (IC/BPS) ( n =24), and idiopathic nonobstructive urinary retention (NOUR) ( n =35). When analyzing the optimal stimulus parameters, disparities in the stimulation amplitude and pulse frequency were noted among the four groups. The stimulation amplitude in the nLUTD group was higher than that in the idiopathic NOUR group ( P =0.013). Differences in pulse frequency were observed between the refractory OAB and nLUTD groups ( P <0.001) and between the refractory OAB and idiopathic NOUR groups ( P =0.001). No differences in the electrode configuration or pulse width settings existed among the four groups. CONCLUSIONS: The stimulation parameters for SNM varied among the different indications. For the initial programming of stage I, most patients are recommended to start with stimulation amplitudes below 2 V, although patients with nLUTD may benefit from higher amplitudes. A standard pulse width of 210 µs is recommended for all patients. However, for individuals experiencing nLUTD or idiopathic NOUR, the pulse frequency can begin above the standard 14 Hz but not exceed 50 Hz.

GlycoPep Detector: a tool for assigning mass spectrometry data of N-linked glycopeptides on the basis of their electron transfer dissociation spectra.

Electron transfer dissociation (ETD) is commonly used in fragmenting N-linked glycopeptides in their mass spectral analyses to complement collision-induced dissociation (CID) experiments. The glycan remains intact through ETD, while the peptide backbone is cleaved, providing the sequence of amino acids for a glycopeptide. Nonetheless, data analysis is a major bottleneck to high-throughput glycopeptide identification based on ETD data, due to the complexity and diversity of ETD mass spectra compared to CID counterparts. GlycoPep Detector (GPD) is a web-based tool to address this challenge. It filters out noise peaks that interfere with glycopeptide sequencing, correlates input glycopeptide compositions with the ETD spectra, and assigns a score for each candidate. By considering multiple ion series (c-, z-, and y-ions) and scoring them separately, the software gives more weighting to the ion series that matches peaks of high intensity in the spectra. This feature enables the correct glycopeptide to receive a high score while keeping scores of incorrect compositions low. GPD has been utilized to interpret data collected on six model glycoproteins (RNase B, avidin, fetuin, asialofetuin, transferrin, and AGP) as well as a clade C HIV envelope glycoprotein, C.97ZA012 gp140ΔCFI. In every assignment made by GPD, the correct glycopeptide composition earns a score that is about 2-fold higher than other incorrect glycopeptide candidates (decoys). The software can be accessed at http://glycopro.chem.ku.edu/ZZKHome.php .

Characterizing O-linked glycopeptides by electron transfer dissociation: fragmentation rules and applications in data analysis.

Studying protein O-glycosylation remains an analytical challenge. Different from N-linked glycans, the O-glycosylation site is not within a known consensus sequence. Additionally, O-glycans are heterogeneous with numerous potential modification sites. Electron transfer dissociation (ETD) is the method of choice in analyzing these glycopeptides since the glycan side chain remains intact in ETD, and the glycosylation site can be localized on the basis of the c and z fragment ions. Nonetheless, new software is necessary for interpreting O-glycopeptide ETD spectra in order to expedite the analysis workflow. To address the urgent need, we studied the fragmentation of O-glycopeptides in ETD and found useful rules that facilitate their identification. By implementing the rules into an algorithm to score potential assignments against ETD-MS/MS data, we applied the method to glycopeptides generated from various O-glycosylated proteins including mucin, erythropoietin, fetuin, and an HIV envelope protein, 1086.C gp120. The site-specific O-glycopeptide composition was correctly assigned in every case, proving the merits of our method in analyzing glycopeptide ETD data. The algorithm described herein can be easily incorporated into other automated glycomics tools.

Effect of WC Content on Microstructure and Properties of CoCrFeNi HEA Composite Coating on 316L Surface via Laser Cladding.

Laser cladding technology is used to fabricate CoCrFeNi HEA/WC composite coatings with different mass fractions of WC on the surface of 316L stainless steel. The microstructures of HEA/WC composite coatings were analyzed by combining multiple characterization techniques. The results show that the HEA/WC composite coatings have good surface formation without pores and hot cracks, and the metallurgical bonding is well formed between the coating and the 316L SS substrate. Under the action of a laser beam and molten pool, WC particles partially or slightly melt and diffuse to the matrix, which hinders the orderly growth of grains and forms multiple strengthening. The phase structure of the HEA/WC composite coatings is composed of a main phase with FCC. The hardness and corrosion resistance of the HEA/WC composite coatings are clearly enhanced, and the HEA/WC composite coating with 5% WC has optimum properties.

Phase-resolved dynamic wavefront imaging of cilia metachronal waves.

Background: The coordination and the directional order of ciliary metachronal waves are the major factors that determine the effectiveness of mucociliary clearance (MCC). Even though metachronal waves play an essential part in immune response, clinical diagnostic tools and imaging techniques that can reliably and efficiently capture their spatial distribution and function are currently limited. Methods: We present label-free high-speed visualization of ciliary metachronal wave propagations in freshly-excised tracheal explants using a spectrally-encoded interferometric microscope over a two-dimensional (2D) plane of 0.5 mm × 0.5 mm at an acquisition rate of 50 frame-per-second. Furthermore, phase-resolved enhanced dynamic (PHRED) analysis of time-series doppler images was performed, where spatial-temporal characteristics of cilia metachronal wave motions are revealed through frequency component analysis and spatial filtering. Results: The PHRED analysis of phase-resolved Doppler (PRD) images offers a capability to distinguish the propagation direction of metachronal waves, and quantitatively assess amplitude and dominant frequency of cilia beating at each spatial location. Compared to the raw PRD images, the phase-resolved dynamic wavefront imaging (PRDWI) method showed the direction and coordination of collective cilia movement more distinctively. Conclusions: The PRDWI technique can have broad application prospects for the diagnosis of human respiratory diseases and evaluation of the curative effect of treatments and open new perspectives in biomedical sciences.

Enhance the delivery of light energy ultra-deep into turbid medium by controlling multiple scattering photons to travel in open channels.

Multiple light scattering is considered as the major limitation for deep imaging and focusing in turbid media. In this paper, we present an innovative method to overcome this limitation and enhance the delivery of light energy ultra-deep into turbid media with significant improvement in focusing. Our method is based on a wide-field reflection matrix optical coherence tomography (RM-OCT). The time-reversal decomposition of the RM is calibrated with the Tikhonov regularization parameter in order to get more accurate reversal results deep inside the scattering sample. We propose a concept named model energy matrix, which provides a direct mapping of light energy distribution inside the scattering sample. To the best of our knowledge, it is the first time that a method to measure and quantify the distribution of beam intensity inside a scattering sample is demonstrated. By employing the inversion of RM to find the matched wavefront and shaping with a phase-only spatial light modulator, we succeeded in both focusing a beam deep (~9.6 times of scattering mean free path, SMFP) inside the sample and increasing the delivery of light energy by an order of magnitude at an ultra-deep (~14.4 SMFP) position. This technique provides a powerful tool to understand the propagation of photon in a scattering medium and opens a new way to focus light inside biological tissues.

Microstructures and Mechanical Properties of an AlCoCrNiFe HEA/WC Reinforcing Particle Composite Coating Prepared by Laser Cladding.

In this study, an AlCoCrFeNi HEA coating with a 10% mass fraction of WC particles was fabricated on the surface of 316L stainless steel by laser cladding technology. WC powders were formed by the partial or total dissolution of the initial WC particles with different sizes in the AlCoCrFeNi HEA coating. Micron WC particles were dispersed in the coating homogeneously, and millimeter WC particles were deposited on the bottom of coating because of their high density. The addition of the WC powers prompted Columnar dendritic and cellular grains, observed in the bottom and top regions of the coating, respectively. Additionally, this led to a higher micro-hardness and better corrosion resistance than that of the pure HEA coating.

Prognostic Significance of Signet Ring Cells in Gastric Cancer: The Higher Proportion, The Better Survival.

BACKGROUND: Due to the fact that the definition of gastric signet ring cell cancer (GSRC) was still controversial in the past decades, the prognosis affected by the proportion of signet ring cells within gastric cancer is uncertain. This study compared the clinicopathological features and prognosis of GSRC with the various proportions of signet ring cells. METHODS: We collected GSRC cases without metastasis who underwent curative (R0) resection between 2011 and 2018. Individuals who were in the low-proportion signet ring cell group (LSRC, <50%) were matched to those who were in the high-proportion signet ring cell group (HSRC, >50%) through propensity score matching (1:1). We used Cox proportional hazard regression to calculate the adjusted hazard ratios (HR) and 95% confidence intervals (CI) and explored interactions with gender and stage. RESULTS: We had 1:1 matched individuals including 231 cases from the LSRC group and 231 cases from the HSRC group. Patients with HSRC had a significantly higher overall survival rate in the multivariable model (aHR = 0.56, 95%CI = 0.38, 0.84) compared with those with LSRC. The association of HSRC appeared to be more substantial among individuals at early stage and N0 stage (p-interaction < 0.01). CONCLUSIONS: This study confirms that GSRC with different proportions of signet ring cells could affect the survival of the patient. Further clinical studies should be developed in the future to provide an appropriate treatment strategy for GSRC.

Mammography use in relation to comorbidities and functional limitations among older breast cancer survivors.

PURPOSE: We sought to examine associations of mammography utilization with comorbidities and functional limitations in older breast cancer survivors. METHODS: Female breast cancer survivors (N = 1064) identified in the 2016 and 2018 Behavioral Risk Factor Surveillance System (BRFSS) who were aged ≥ 65 years were included for this study. Mammography use, major comorbidities (diabetes mellitus, myocardial infarction, coronary heart disease, stroke, chronic obstructive pulmonary disease, arthritis, chronic kidney disease, depression, and malignancy other than breast cancer), functional limitations (impairment of vision, audition, cognition, and mobility), and other covariates were measured by self-report. We used multivariable logistic regression models to calculate adjusted odds ratios (aOR) of comorbidities and functional limitations. Subgroup analyses were conducted by age (65-74 vs. ≥ 75 years) and survival time (< 10 vs. ≥ 10 years), and interactions were examined by Wald tests. RESULTS: Of the 1064 respondents, 841 (79.0%) had comorbidities, 418 (39.3%) had functional limitations, and 744 (69.9%) underwent mammography last year. Overall, the mean age was 73.8 years (SD = 5.1 years) and 91.4% were white. The multivariable model identified inverse associations with mammography use for functional limitations (≥ 2 vs. 0: aOR = 0.61, 95% CI = 0.39-0.95, p-trend = 0.09) but not comorbidities (≥ 2 vs. 0: aOR = 0.91, 95% CI = 0.61-1.35, p-trend = 0.62). The Wald test did not find any significant interaction. CONCLUSIONS: A higher burden of functional limitations, not comorbidities, is associated with a lower rate of mammography use among older breast cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Interventions are needed to individualize surveillance mammography among older breast cancer survivors based on their health status.

Serum Levels of Androgens, Estrogens, and Sex Hormone Binding Globulin and Risk of Primary Gastric Cancer in Chinese Men: A Nested Case-Control Study.

Gastric cancer shows a strong male predominance, and sex steroid hormones have been hypothesized to explain this sex disparity. Previous studies examining the associations between sex hormones and sex hormone binding globulin (SHBG) and risk of gastric cancer come primarily from western populations and additional studies in diverse populations will help us better understand the association. We performed a nested case-control study in Linxian Nutrition Intervention Trials cohorts to evaluate the associations among Chinese men, where we had sufficient cases to perform a well-powered study. Using radioimmunoassays and immunoassays, we quantitated androgens, estrogens, and SHBG in baseline serum from 328 men that developed noncardia gastric cancer and matched controls. We used multivariable unconditional logistic regression to calculate ORs and 95% confidence intervals (CI) and explored interactions with body mass index (BMI), age, alcohol drinking, smoking, and follow-up time. Subjects with SHBG in the highest quartile, as compared with those in the lowest quartile, had a significantly increased risk of gastric cancer (OR = 1.87; 95% CI, 1.01-3.44). We found some evidence for associations of sex steroid hormones in men with lower BMI. Our study found a novel association suggesting that higher serum concentrations of SHBG may be associated with risk of gastric cancer in men. We found no overall associations with sex hormones themselves, but future studies should expand the scope of these studies to include women and further explore whether BMI modifies a potential association. PREVENTION RELEVANCE: It was the first study to investigate the association of gastric cancer with prediagnostic sex steroid hormones and SHBG in an Asian male population. Although there were no overall associations for sex steroid hormone concentrations, higher concentrations of SHBG was associated with increased risk of noncardia gastric cancer.

Gastric Signet Ring Cell Carcinoma: Current Management and Future Challenges.

Recent advances in the epidemiology, pathology, molecular mechanisms, and combined modality therapy (CMT) fields have shown that gastric signet ring cell carcinoma (GSRC) should be considered a distinct cancerous entity. Clinical management of this cancer is challenging, with chemoradioresistance and poor outcomes in advanced stages. Pathological and molecular sets of GSRC demonstrate different features of poor cohesion and differentiation according to the WHO, Japanese Gastric Cancer Association, and Laurén classifications. These features also result in poor response to adjuvant and neoadjuvant chemoradiotherapy. Certain studies of GSRC showed the disputed effectiveness of hyperthermic intraperitoneal chemotherapy and immunotherapy. Our aim was to discuss how an improved understanding of these therapeutic benefits may provide better treatment selection for patients, and therefore improve survival. The challenges in the new understanding of GSRC in routine practice and pathology, and the current limitations of treatment will also be discussed.

Improving survival of stage II-III primary gastric signet ring cell carcinoma by adjuvant chemoradiotherapy.

BACKGROUND: There is no consistent evidence about the appropriate treatment strategies for gastric signet ring cell carcinoma (GSRC) to improve prognosis. We conducted a population-based study to examine the effects of combined modality therapies on survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) data. METHODS: Analyses included stage II-III primary GSRC patients who were diagnosed between 2006 and 2016. Therapies were categorized as gastrectomy group, adjuvant chemotherapy (CT) group, neoadjuvant radiotherapy (RT) group, and adjuvant chemoradiotherapy (CRT) group. Survival analyses were conducted by Kaplan-Meier method and Cox proportional hazards models and subgrouped by gender, tumor site, stage at diagnosis, and number of lymph nodes removed. RESULTS: Of the 1717 cases of stage II-III primary GSRC, the mean (SD) age was 59.6 (13.3) years, and over a half were male (52.8%). A total of 39.9% patients received adjuvant CRT and the 5-year overall survival (OS) rate was 34.6%. The median OS of patients treated with adjuvant CRT was significantly longer than that of the gastrectomy group (33 months vs 24 months, aHR = 0.71, 95% CI: 0.59, 0.84). Although the crude model showed a significant association between adjuvant CT and total survival (cHR = 0.81, 95% CI: 0.68, 0.96), the effect measure turned null in the multivariable and sub-group analysis. We did not find the significant effect of neoadjuvant RT. CONCLUSIONS: In this study, GSRC patients with stage II-III experienced improved overall survival after receiving adjuvant CRT, which provides several treatment implications. More clinical trials will be needed to verify the conclusion derived from this study.