Prevalence and risk factors of postoperative laryngeal edema in patients undergoing neck dissection.

PURPOSE: Postoperative laryngeal edema (PLE) is a common complication in patients undergoing head and neck surgery, leading to symptoms such as odynophagia, dysphagia, or potential airway obstruction. However, the prevalence and risk factors of PLE in patients undergoing neck dissection (ND) have not been well investigated. METHODS: A retrospective analysis was conducted in three steps. Initially, a pilot study of 50 consecutive ND patients revealed a preliminary PLE prevalence of 0.34. Then, the medical records of an additional 295 ND patients were reviewed to estimate the prevalence of PLE with a total width of 95% confidence interval (CI) of ± 5%. Finally, multivariable logistic regression analyses were performed to identify risk factors for PLE (n = 343). RESULTS: PLE occurred in 29.4% [95%CI 24.4-34.4%] of patients undergoing any type of ND, with the most common symptoms of odynophagia (75.0%) and dyspnea (11.1%). Hospital stay was just one day longer in PLE patients, responding well with short-term steroid treatment (p = 0.0057). In multivariable analyses, no significant association was found between PLE occurrence and airway management. However, body mass index and the American Society of Anesthesiologists classification correlated with PLE. More importantly, surgery for oro-hypopharynx or supraglottis tumors (odds ratio, OR = 3.019, [95%CI 1.166-7.815]) and lymph node level 2(3) ND (OR = 4.214 to 5.279, [95%CI 1.160-20.529]) were significant risk factors for PLE. CONCLUSIONS: PLE developed in approximately 30% of ND patients, causing uncomfortable symptoms. Early diagnosis and intervention of PLE in high-risk patients can improve patient care and outcomes.

A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma.

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.

Extra-Capsular Spread of Lymph Node Metastasis in Oral, Oropharyngeal and Hypopharyngeal Cancer: A Comparative Subsite Analysis.

BACKGROUND: The extra-capsular spread (ECS) of lymph node metastasis (LNM) is a hallmark of aggressive primary tumor phenotype in head and neck cancer (HNC); however, the factors influencing ECS are poorly understood. PATIENTS AND METHODS: This was a retrospective study, including 190 cases of oral tongue cancer (OTC), 148 cases of oropharyngeal cancer (OPC) (118 HPV-positive and 30 HPV-negative), and 100 cases of hypopharyngeal cancer (HPC). Tumor dimension, tumor biological variables (lymphovascular/perineural invasion and histologic grade), and LNM variables (LNM number and size) were analyzed according to the presence of ECS using multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. RESULTS: LNM variables were significant factors for ECS in all subsites of HNC (p < 0.05), except HPV-positive OPC. In OTC, tumor dimensional variables were significantly related to ECS (p < 0.01). Meanwhile, in OPC and HPC, neither the primary tumor dimension nor the T status were significant factors for ECS occurrence. The predictability of ECS by ROC curve using multiple variables was 0.819 [95% confidence interval: 0.759-0.878] in OTC, 0.687 [0.559-0.815] in HPV-positive OPC, 0.823 [0.642-1.000] in HPV-negative OPC, and 0.907 [0.841-0.973] in HPC. CONCLUSION: LNM variables were correlated with ECS occurrence for most HNC subsites, and site-dependent primary tumor characteristics might contribute differentially to the ECS development of LNM in HNC.

Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer.

Early detection and surgical treatment are essential to achieve a good outcome in gastric cancer (GC). Stage IV and recurrent GC have a poor prognosis. Therefore, new treatments for GC are needed. We investigated the intestinal microbiome of GC patients and attempted to reverse the immunosuppression of the immune and cancer cells of GC patients through the modulation of microbiome metabolites. We evaluated the levels of programmed death-ligand 1 (PD-L1) and interleukin (IL)-10 in the peripheral blood immunocytes of GC patients. Cancer tissues were obtained from patients who underwent surgical resection of GC, and stained sections of cancer tissues were visualized via confocal microscopy. The intestinal microbiome was analyzed using stool samples of healthy individuals and GC patients. Patient-derived avatar model was developed by injecting peripheral blood mononuclear cells (PBMCs) from advanced GC (AGC) patients into NSG mice, followed by injection of AGS cells. PD-L1 and IL-10 had higher expression levels in immune cells of GC patients than in those of healthy controls. The levels of immunosuppressive factors were increased in the immune and tumor cells of tumor tissues of GC patients. The abundances of Faecalibacterium and Bifidobacterium in the intestinal flora were lower in GC patients than in healthy individuals. Butyrate, a representative microbiome metabolite, suppressed the expression levels of PD-L1 and IL-10 in immune cells. In addition, the PBMCs of AGC patients showed increased levels of immunosuppressive factors in the avatar mouse model. Butyrate inhibited tumor growth in mice. Restoration of the intestinal microbiome and its metabolic functions inhibit tumor growth and reverse the immunosuppression due to increased PD-L1 and IL-10 levels in PBMCs and tumor cells of GC patients.

Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non-Small Cell Lung Cancer.

PURPOSE: It is unclear whether performing endosonography first in non-small cell lung cancer (NSCLC) patients with radiological N1 (rN1) has any advantages over surgery without nodal staging. We aimed to compare surgery without endosonography to performing endosonography first in rN1 on the overall survival (OS) of patients with NSCLC. MATERIALS AND METHODS: This is a retrospective analysis of patients with rN1 NSCLC between 2013 and 2019. Patients were divided into 'no endosonography' and 'endosonography first' groups. We investigated the effect of nodal staging through endosonography on OS using propensity score matching (PSM) and multivariable Cox proportional hazard regression analysis. RESULTS: In the no endosonography group, pathologic N2 occurred in 23.0% of patients. In the endosonography first group, endosonographic N2 and N3 occurred in 8.6% and 1.6% of patients, respectively. Additionally, 51 patients were pathologic N2 among 249 patients who underwent surgery and mediastinal lymph node dissection (MLND) in endosonography first group. After PSM, the 5-year OSs were 68.1% and 70.6% in the no endosonography and endosonography first groups, respectively. However, the 5-year OS was 80.2% in the subgroup who underwent surgery and MLND of the endosonography first group. Moreover, in patients receiving surgical resection with MLND, the endosonography first group tended to have a better OS than the no endosonography group in adjusted analysis using various models. CONCLUSION: In rN1 NSCLC, preoperative endosonography shows better OS than surgery without endosonography. For patients with rN1 NSCLC who are candidates for surgery, preoperative endosonography may help improve survival through patient selection.

The Prevalence and Clinical Characteristics of Borderline Personality Disorder in South Korea Using National Health Insurance Service Customized Database.

PURPOSE: The purpose of the present study was to identify the prevalence and clinical characteristics of borderline personality disorder (BPD) in South Korea using the Korean National Health Insurance database (DB). MATERIALS AND METHODS: We used the National Health Insurance Service (NHIS)'s research DB (NHIS-2021-1-790) from January 1, 2010 to December 31, 2019, to make customized DB including sociodemographic information and absence or presence of BPD and other psychiatric disorders. The prevalence and the age of onset of BPD was estimated. To compare medical service utilization between the BPD group and the control group, a 1:1:1 propensity score matching was employed, and the regression analysis was conducted. RESULTS: The prevalence of BPD per 10000 people was 0.96 in 2010 and 1.06 in 2019. The prevalence ratio of males to females was 1:1.38 in 2010 and 1:1.65 in 2019, showing that BPD was more prevalent in females. The patients' overall average age of onset was 33.19±14.6 years, with the highest prevalence shown in 8503 people in their 20s. By administrative district, the highest prevalence of BPD per 10000 people was shown in Seoul with 8.71 and the lowest in Jeollanam-do with 2.35. The BPD patients showed a pattern of extensive use of general and mental healthcare services. CONCLUSION: This study identified the prevalence of BPD on a national DB set in South Korea. Although the prevalence of BPD in South Korea was relatively low compared to other countries, there was a steady increase in the number of BPD patients over a decade, which may be possibly due to an increased awareness of mental health and campaigns among healthcare providers and users in the country.

Incorporating axillary-lateral thoracic vessel juncture dosimetric variables improves model for predicting lymphedema in patients with breast cancer: A validation analysis.

Background: A relationship between the axillary-lateral thoracic vessel juncture (ALTJ) dose and lymphedema rate has been reported in patients with breast cancer. The purpose of this study was to validate this relationship and explore whether incorporation of the ALTJ dose-distribution parameters improves the prediction model's accuracy. Methods: A total of 1,449 women with breast cancer who were treated with multimodal therapies from two institutions were analyzed. We categorized regional nodal irradiation (RNI) as limited RNI, which excluded level I/II, vs extensive RNI, which included level I/II. The ALTJ was delineated retrospectively, and dosimetric and clinical parameters were analyzed to determine the accuracy of predicting the development of lymphedema. Decision tree and random forest algorithms were used to construct the prediction models of the obtained dataset. We used Harrell's C-index to assess discrimination. Results: The median follow-up time was 77.3 months, and the 5-year lymphedema rate was 6.8 %. According to the decision tree analysis, the lowest lymphedema rate (5-year, 1.2 %) was observed in patients with ≤ six removed lymph nodes and ≤ 66 % ALTJ V35Gy. The highest lymphedema rate was observed in patients with > 15 removed lymph nodes and an ALTJ maximum dose (Dmax) of > 53 Gy (5-year, 71.4 %). Patients with > 15 removed lymph nodes and an ALTJ Dmax ≤ 53 Gy had the second highest rate (5-year, 21.5 %). All other patients had relatively minor differences, with a rate of 9.5 % at 5 years. Random forest analysis revealed that the model's C-index increased from 0.84 to 0.90 if dosimetric parameters were included instead of RNI (P <.001). Conclusion: The prognostic value of ALTJ for lymphedema was externally validated. The estimation of lymphedema risk based on individual dose-distribution parameters of the ALTJ seemed more reliable than that based on the conventional RNI field design.

Dietary Zinc Intake and All-Cause and Cardiovascular Mortality in Korean Middle-Aged and Older Adults.

We aimed to investigate the association between dietary zinc intake and total deaths, cancer, and cardiovascular disease death. In this prospective, 10-year, community-based cohort analysis, data from 143,050 adult participants (aged 40 years and older) were analyzed. Dietary zinc intake at baseline was assessed using a food frequency questionnaire. Harrell's C-index was used to determine the optimal cut-off of dietary zinc intake with the log-rank test. Using the Cox proportional hazards regression models, the association between dietary zinc intake and all-cause, cancer, and cardiovascular disease mortality was estimated using hazard ratios and 95% confidence intervals. During the mean 10.1 years of follow-up, 5436 participants expired, of whom 2355 died due to cancer and 985 died due to cardiovascular causes. After adjustment for confounders, dietary zinc intake was inversely associated with all-cause mortality (≤5.60 mg/day vs. >7.98 mg/day; hazard ratio, 1.13; 95% confidence interval, 1.01−1.25) and cardiovascular disease mortality (≤5.12 mg/day vs. >7.28 mg/day; hazard ratio, 1.42; 95% confidence interval, 1.11−1.81) but not with cancer mortality (≤5.60 mg/day vs. >10.08 mg/day; hazard ratio, 1.09; 95% confidence interval, 0.90−1.33). Dietary zinc intake was associated with a lower risk of all-cause mortality and cardiovascular disease mortality but not with cancer mortality. Our findings could suggest that recommending optimal dietary zinc intake is helpful for human health.

Association between dietary sodium, potassium, and the sodium-to-potassium ratio and mortality: A 10-year analysis.

There is inconclusive evidence of the association between dietary sodium, potassium, and the sodium-to-potassium ratio and all-cause and cardiovascular disease mortality. To investigate the association between dietary sodium, potassium, and the sodium-to-potassium ratio and all-cause and cardiovascular disease mortality risks. Data from 143,050 adult participants were analyzed from prospective 10-year community-based cohort analysis. Dietary sodium, potassium, and the sodium-to-potassium ratio at baseline were assessed by a food frequency questionnaire. In Cox proportional hazards regression models, the association between dietary sodium, potassium, and their ratio and all-cause and cardiovascular disease mortality was estimated using hazard ratios and 95% confidence intervals, and their predictive ability as mortality predictors was evaluated using Harrell's c-index. During the mean (range) 10.1 (0.2-15.9) years of follow-up, 5,436 participants died, of whom 985 died of cardiovascular causes. After adjustment for age, sex, body mass index, alcohol intake, smoking, regular exercise, total calorie intake, dyslipidemia, hypertension, diabetes, chronic kidney diseases (CKDs), and potassium or sodium intake, respectively, sodium intake was unassociated with all-cause mortality whereas potassium intake was significantly associated inversely with all-cause (Quintile-5 vs. Quintile-1, hazard ratio, 95% confidence interval, 1.09, 0.97-1.22, and 0.79, 0.69-0.91, respectively). The sodium-to-potassium ratio was not significantly associated with all-cause mortality in the adjusted model, and similar trends were observed for cardiovascular disease mortality.

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Clinical Accuracy of Non-Contact Forehead Infrared Thermometer Measurement in Children: An Observational Study.

We evaluated the clinical reliability and utility of temperature measurements using no-contact forehead infrared thermometers (NCFITs) by comparing their temperature measurements with those obtained using infrared tympanic thermometers (IRTTs) in children. In this observational, prospective, and cross-sectional study, we enrolled 255 children (aged 1 month to 18 years) from the pediatric surgery ward at a tertiary medical center in Korea. The mean age of the children was 9.05 ± 5.39 years, and 54.9% were boys. The incidence rate of fever, defined as an IRTT reading of ≥38.0 °C, was 15.7%. The ICC coefficient for the assessment of agreement between temperatures recorded by the NCFIT and IRTT was 0.87, and the κ-coefficient was 0.83. The bias and 95% limits of agreement were 0.15 °C (−0.43 to 0.73). For an accurate diagnosis of fever (≥38 °C), the false-negative rate was much lower, but the false-positive rate was higher, especially in 6-year-old children. Therefore, NCFITs can be used to screen children for fever. However, a secondary check is required using another thermometer when the child's temperature is >38 °C. NCFITs are proposed for screening but not for measuring the temperature. For the latter, an accurate and reliable thermometer shall be used.

RNF213 R4810K Variant in Suspected Unilateral Moyamoya Disease Predicts Contralateral Progression.

Background Early-stage unilateral moyamoya disease (MMD) is difficult to discriminate from isolated intracranial atherosclerotic stenosis, and identification of contralateral progression may aid in the diagnosis of MMD. The RNF213 (ring finger protein 213) R4810K variant is a strong genetic susceptibility factor for MMD; however, the role of contralateral progression in unilateral MMD is unknown. Methods and Results Patients who had undergone RNF213 R4810K genotyping with suspected unilateral MMD between January 2017 and August 2021 from 2 tertiary university hospitals were retrospectively reviewed. We compared the clinical features and radiographic outcomes of patients with and without this variant. The risk factors of contralateral progression in patients with suspected unilateral MMD were evaluated. The RNF213 R4810K variant was observed in 72 of 123 patients with suspected unilateral MMD, all of which were heterozygous. The allele frequency of the R4810K variant was significantly higher in the suspected unilateral MMD group compared with the historical control group (29.3% versus 1.2%; P<0.0001). Family history of MMD was significantly more common in patients with the variant than in those without (17% versus 4%; P=0.003). Eleven of 72 patients with the variant developed contralateral progression, whereas only 1 of 51 patients without the variant developed contralateral progression during a median follow-up period of 28 months (log-rank test; P=0.03). The presence of the RNF213 R4810K variant significantly correlated with contralateral progression (adjusted odds ratio, 6.39 [95% CI, 1.11-36.63]; P=0.04). Conclusions Contralateral progression is more likely to occur in patients with suspected unilateral MMD with the RNF213 R4810K variant than in those without the variant. However, because our study used a small sample size, this finding should be carefully interpreted and requires further studies with more patients and longer follow-up periods.

Dyslipidemia Risk in Thyroid Cancer Patients: A Nationwide Population-Based Cohort Study.

Objective: Thyroid cancer (TC) prevalence has been rapidly increasing. While the relationship between thyroid hormones and lipids has been widely investigated, studies regarding dyslipidemia in patients with TC have been scarce and controversial. We aimed to investigate dyslipidemia risk after TC diagnosis compared to the general population without TC. Method: A population-based prospective study was conducted using data from the Korean National Health Insurance Service-National Sample Cohort Database 2.0 (NHIS-NSC DB 2.0), with health insurance claim data of 1,108,369 subjects between 2002 and 2015. The final study sample comprised 466,735 adult subjects without TC or dyslipidemia diagnoses before the index year, 2009. Bidirectional analyses were performed using prospective and retrospective concepts. In the prospective analysis, Kaplan-Meier estimates were calculated and log-rank tests and univariable and multivariable Cox regression analyses were performed to determine the relationship between TC and dyslipidemia. The retrospective analysis involved 1:5 nested case-control matching based on dyslipidemia status and conditional logistic regression analysis. Results: No significant difference in dyslipidemia incidence was observed between TC patients and the control group, in either the prospective matched (log-rank P = 0.483) or non-matched (log-rank P = 0.424) analyses, or the retrospective analysis (P = 0.3724). In the prospective analysis, 193 patients after TC diagnosis showed similar risk of developing dyslipidemia with the 466,542 controls during the median 7 years of follow-up (unadjusted hazard ratio [HR], 1.102; 95% confidence interval [CI], 0.878-1.383; adjusted HR, 0.932; 95% CI, 0.707-1.230). Multiple propensity score-adjusted models showed similar results, and 114 patients and 570 matched controls showed an HR of 0.818 (95% CI, 0.598-1.120). In the retrospective comparison of dyslipidemia risk in 170 patients and 277,864 controls, the odds ratio was 0.822 (95% CI, 0.534-1.266). Conclusions: Dyslipidemia risk was not significantly different between patients with TC and the general population, in both prospective and retrospective analyses.

Hippocampal Metastasis Rate Based on Non-Small Lung Cancer TNM Stage and Molecular Markers.

Hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) is justified because of low hippocampal brain metastases (BM) rate and its prevention of cognitive decline. However, we hypothesize that the risk of developing BM in the hippocampal-avoidance region (HAR) may differ depending on the lung-cancer stage and molecular status. We retrospectively reviewed 123 patients with non-small cell lung cancer (NSCLC) at the initial diagnosis of BM. The number of BMs within the HAR (5 mm expansion) was counted. The cohort was divided into patients with and without BMs in the HAR, and their clinical variables, TNM stage, and epidermal growth factor receptor (EGFR) status were compared. The most influential variable predicting BMs in the HAR was determined using multi-variable logistic regression, classification and regression tree (CART) analyses, and gradient boosting method (GBM). The feasibility of HAR expansion was tested using generalized estimating equation marginal model. Patients with BMs in the HAR were more frequently non-smokers, and more likely to have extra-cranial metastases and EGFR mutations (p<0.05). Multi-variable analysis revealed that extra-cranial metastases were independently associated with the presence of BM in the HAR (odds ratio=8.75, p=0.04). CART analysis and GBM revealed that the existence of extra-cranial metastasis was the most influential variable predicting BM occurrence in the HAR (variable importance: 23% and relative influence: 37.38). The estmated BM incidence of patients without extra-cranial metastases in th extended HAR (7.5-mm and 10-mm expansion) did not differ significantly from that in the conventional HAR. In conclusion, NSCLC patients with extra-cranial metastases were more likely to have BMs in the HAR than those without extra-cranial metastases.

RT-induced dynamic changes in the lymphocyte-to-monocyte ratio in patients with breast cancer indicate poor prognosis.

PURPOSE: Radiation-induced anti-tumor responses occur in the immune system, particularly in peripheral blood mononuclear cells (PBMCs), which are overly sensitive to ionizing radiation. Irradiation of PBMCs is associated with inflammation. We assessed the association between radiotherapy (RT)-induced changes in peripheral blood cells, utilizing the lymphocyte-to-monocyte ratio (LMR), and survival outcome in breast cancer patients who underwent breast-conserving surgery followed by adjuvant RT. METHODS: LMR values were obtained from retrospective data, and serial sampling of blood before the first and last RT sessions was performed. The cut-off point was analyzed using the Youden index and receiver operating characteristic curve. Recurrence-free survival (RFS) and overall survival (OS) were the main outcomes. RESULTS: Patients with RT-induced low LMR had significantly shorter RFS (hazard ratio [HR] 2.730; 95% confidence interval [CI], 1.607-4.636, P = 0.0002) and OS (HR 2.890; 95% CI 1.410-5.924, P = 0.0038). The results were more robust in the subgroup of patients who received chemotherapy. Multivariate analysis showed that lymph node metastasis and RT-induced low LMR were associated with poor RFS (HR 1.763; 95% CI, 1.017-3.059, P = 0.044) and OS (HR 2.254; 95% CI, 1.060-4.796, P = 0.035). CONCLUSION: This study demonstrates that RT-induced low LMR is a valid prognostic marker for recurrence and survival in breast cancer patients undergoing RT.

Validation of IL-7R as an Immunological Biomarker for Human Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer for which no early diagnostic method is available. The immune surveillance hypothesis suggests that the immune system plays crucial roles in tumor development and progression. We validated a PDAC-specific biomarker derived from peripheral blood mononuclear cells (PBMCs) to facilitate early PDAC diagnosis. mRNA levels of interleukin-7R (IL-7R), reportedly a potential immunological marker for PDAC, were measured in PBMCs isolated prospectively from healthy controls (n = 100) and patients with PDAC (n = 135), pancreatic cysts (n = 82), chronic pancreatitis (n = 42), acute pancreatitis (n = 47), and other malignancies (n = 116). The IL-7R level was significantly higher in patients with PDAC than in healthy controls, patients with benign pancreatic disease, and patients with other malignancies. As diagnostic parameters, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IL-7R were 58.5%, 92%, 90.8%, 62.2%, and 72.8%, respectively. The area under the receiver operating characteristic curve (AUROC) was 0.766. IL-7R levels did not differ between resectable and unresectable PDAC cases. The combined measurement of IL-7R and carbohydrate antigen 19-9 (CA19-9) significantly improved the diagnostic parameters and AUROC compared with the use of IL-7R or CA19-9 alone. IL-7R is significantly upregulated in PBMCs in patients with PDAC, and it may be a novel diagnostic marker for PDAC. The combined use of IL-7R and CA19-9 enhanced the diagnostic performance.

First-trimester screening model for small-for-gestational-age using maternal clinical characteristics, serum screening markers, and placental volume: prospective cohort study.

OBJECTIVE: To examine predictive value of first trimester placental volume, maternal clinical characteristics, and serum biomarkers in predicting small-for-gestational-age (SGA) singleton pregnancy. METHODS: We conducted a prospective study to determine whether SGA is associated with maternal clinical factors. Between November 2016 to May 2018, 351 women were enrolled. We included pregnant women who underwent an integrated test for aneuploidy screening. Placental volume, maternal clinical characteristics, and maternal serum pregnancy-associated plasma protein A (PAPP-A) levels in the first trimester (at 10+0-13+6 weeks) and maternal serum biomarkers after 15+0-22+6 weeks were measured. We measured the width, height, and thickness of the placenta and calculated the placental volume using an established mathematical formula; then, we analyzed the association between SGA at delivery, estimated placental volume (EPV), maternal clinical characteristics, and maternal serum biomarkers by multiple logistic regression analysis. RESULTS: In this study, 12.3% (43/351) neonates were delivered before 37 weeks of gestation, and the birth weight of 23.6% (83/351) was below the 10th percentile according to gestational age. On multivariate logistic regression, the MSAFP multiples of the median (MoM) showed the strongest association with SGA in singleton pregnancy (p < .01), and the PAPP-A MoM showed a weaker association in the multiple logistic regression than in the univariate regression (p = .0073 and .0068, respectively). Our prediction model using maternal age, maternal smoking, PAPP-A, and EPV achieved an area under the curve of 0.668 in singleton pregnancy. CONCLUSION: During the first trimester, maternal clinical characteristics, serum biomarkers, and EPV may be used for predicting the risk of SGA in singleton pregnancy.

Efficacy and safety of temperature-controlled intraductal radiofrequency ablation in advanced malignant hilar biliary obstruction: A pilot multicenter randomized comparative trial.

PURPOSE: We aimed to evaluate the efficacy and safety of temperature-controlled intraductal radiofrequency ablation (ID-RFA) for advanced malignant hilar biliary obstruction (MHBO). METHODS: Patients were randomly assigned to RFA group (ID-RFA and bilateral plastic stent [PS]) or non-RFA group (bilateral PS) at a 1:1 ratio. Exchange to self-expanding metal stent (SEMS) was performed after 3 months or when premature PS occlusion occurred. Total event-free stent patency, overall survival (OS), and adverse events (AEs) were analyzed. RESULTS: A total of 30 patients from three hospitals were enrolled. Stent patency and OS did not differ between the two groups (178 days vs 122 days, P = .154; 230 days vs 144 days, P = .643; respectively). In patients with each stricture length ≥11 mm on both sides, stent patency was longer in the RFA group than in the non-RFA group (175 days vs 121 days, P = .028). More patients received elective exchange to SEMS without PS occlusion in the RFA group than in the non-RFA group (69.2% vs 23.1%, P = .018). AE rates did not differ between the two groups. CONCLUSIONS: Temperature-controlled ID-RFA for advanced MHBO was safe and feasible. It could prevent premature PS occlusion within 3 months.

Comparison of the Clinical Features and Outcomes of Gallbladder Neuroendocrine Carcinoma with Those of Adenocarcinoma: A Propensity Score-Matched Analysis.

Neuroendocrine neoplasms (NENs) of the gallbladder (GB) are extremely rare. We aimed to compare the clinical features, disease progression, management, and prognosis of patients with GB-NENs with those of patients with GB-adenocarcinomas (ADCs). A total of 21 patients with GB-NENs and 206 patients with GB-ADCs, treated at three tertiary medical centers between January 2010 and December 2020, were enrolled. Of the 21 patients with GB-NENs, 20 were diagnosed with poorly differentiated small-cell neuroendocrine carcinomas (NECs), and 1 patient had large-cell NEC. All patients presented with advanced stages of cancer with extensive local extension and/or distant metastasis and non-specific symptoms. Tumor-node-metastasis stage IIIB and IV (A/B) tumors were found in 6 and 15 (1/14) patients, respectively. Nine patients with GB-NEC who underwent surgical resection had a significantly better progression-free survival (PFS) than those who did not undergo surgery. After a propensity score matching with a 1:1 ratio using the American Joint Committee on Cancer stage, age, sex, and operation status, 19 pairs of patients were included. Compared with stage-matched patients with GB-ADC, patients with GB-NEC had similar overall survival and PFS. However, as GB-NEC is rarely diagnosed early, further studies investigating methods for the early diagnosis and improvement in the survival of patients with GB-NEC are needed.

Ability of dynamic preload indices to predict fluid responsiveness in a high femoral-to-radial arterial pressure gradient: a retrospective study.

BACKGROUND: Dynamic preload indices may predict fluid responsiveness in end-stage liver disease. However, their usefulness in patients with altered vascular compliance is uncertain. This study is the first to evaluate whether dynamic indices can reliably predict fluid responsiveness in patients undergoing liver transplantation with a high femoral-to-radial arterial pressure gradient (PG). METHODS: Eighty liver transplant recipients were retrospectively categorized as having a normal (n = 56) or high (n = 24, difference in systolic pressure ≥ 10 mmHg and/or mean pressure ≥ 5 mmHg) femoral-to-radial arterial PG, measured immediately after radial and femoral arterial cannulation. The ability of dynamic preload indices (stroke volume variation, pulse pressure variation [PPV], pleth variability index) to predict fluid responsiveness was assessed before the surgery. Fluid replacement of 500 ml of crystalloid solution was performed over 15 min. Fluid responsiveness was defined as ≥ 15% increase in the stroke volume index. The area under the receiver-operating characteristic curve (AUC) indicated the prediction of fluid responsiveness. RESULTS: Fourteen patients in the normal, and eight in the high PG group were fluid responders. The AUCs for PPV in the normal, high PG groups and total patients were 0.702 (95% confidence interval [CI] 0.553-0.851, P = 0.008), 0.633 (95% CI 0.384-0.881, P = 0.295) and 0.667 (95% CI 0.537-0.798, P = 0.012), respectively. No other index predicted fluid responsiveness. CONCLUSIONS: PPV can be used as a dynamic index of fluid responsiveness in patients with end-stage liver disease but not in patients with altered vascular compliance.