Low-risk Grade Research Articles

A retrospective multicenter study of WHO 2021 classification-diagnosed solitary fibrous tumor of the CNS in a population from Lombardy, Italy.

In this retrospective, multicenter study, we collected patients withsolitary fibrous tumor-SFT-of the CNS followed in eight hospitals in Lombardia from 2004 to 2019, revising the diagnosis according to the WHO 2021 classification. Clinical data were analyzed at diagnosis and during follow-up. Overall, 57 patients were enrolled, of whom 52.6% female. Median age was 54, 91% had an intracranial tumor and 9% a spinal location. 49% patients had grade 1, 31.5% grade 2 and 19% grade 3 tumor. After a median follow-up of84months, 49% of the patients had progressed and 8.7% had died. Gross tumor resection was obtained in 70%, subtotal in 26.3%, partial in 1.7% and biopsy in 1.7%.15.7% (n = 9) of patients developed extra-CNS metastases, mainly involving bone, lung and liver, six of these were grade 3 and 3 were grade 2 at first diagnosis. 14 patients (24.5%) underwent radiation therapy, 3 chemotherapy and one received liver transplant. The 14 radiation-treated patients included all grade 3 and 3 grade 2 with partial or subtotal resection. Only tumor grade had a prognostically significant impact on PFS at univariate analysis, while age had not. All but one case displayed nuclear expression for STAT6, the remaining case showed diffuse expression of CD34. Whereas grade 3 was confirmed as a prognostically relevant factor, partially overlapping behaviours were detected in patients usually considered at low (all grade 1 and grade 2 with gross total resection) versus moderate risk (grade 2 with biopsy or non-gross total resection).

Exploring metastasis and recurrence patterns in low-risk grade 3 endometrial cancer: A multicenter retrospective cohort study

ObjectiveFemales with low-risk endometrial cancer typically have low lymph node metastasis risk and promising prognosis without lymphadenectomy. However, the impact of grade 3 endometrial cancer on nodal involvement, recurrence, and prognosis within this specific subgroup remains unclear. Therefore, in this study, we aimed to investigate the prognosis, patterns of metastasis, and recurrence in a subgroup of females with grade 3 early-stage low-risk endometrioid endometrial cancer. MethodsWe identified patients from the endometrial cancer cohorts of seven institutional hospitals. The study included patients who underwent hysterectomy between January 2013 and December 2021 with preoperative endometrioid histological type, less than half myometrial invasion, no tumor spread outside the corpus on imaging, normal CA-125 level, and histological grade 3. The clinicopathological characteristics and survival outcomes of the patients were collected. Recurrence-free survival was estimated using the Kaplan–Meier method and compared using the log rank test. ResultsOverall, 36 patients were included in this analysis. Of the 33 patients who underwent lymphadenectomy, 1 (1/33, 3.0 %) had lymph node metastasis and 27 (75.0 %) received adjuvant therapy. At a median follow-up of 58 months, three females (8 %) had recurrence and all cases involved lymph nodes. The 5-year recurrence-free survival was 88.7 %. No significant difference was observed in the recurrence-free survival between females who did and did not undergo lymphadenectomy (p = 0.554). ConclusionFemales diagnosed with low-risk grade 3 endometrial cancer typically have favorable prognosis. However, lymph node metastasis and recurrence risks still exist, with all recorded instances of recurrence involving lymph nodes.

Vertical Distribution Characteristics and Ecological Risk Assessment of Mercury and Arsenic in Ice, Water, and Sediment at a Cold-Arid Lake.

Mercury and arsenic are two highly toxic pollutants, and many researchers have explored the effects of the two substances on the environment. However, the research content of toxic substances in frozen periods is relatively small. To explore the spatial and vertical distribution of mercury and arsenic in the ice, water, and sediments of Wuliangsuhai Lake under ice conditions, and to assess the harm degree of the two toxic substances to human beings. We collected the ice, water, and sediments of the lake in December 2020, and tested the contents of Hg and As. The single-factor pollution index method, the local cumulative index method, and the ecological risk coding method were used to assess the pollution status in these three environmental media, and the Monte Carlo simulation combined with the quantitative model recommended by USEPA was used to assess the population health risk. The results showed that (1) The average single-factor pollution values of Hg and As in water were 0.367 and 0.114, both pollutants were at clean levels during the frozen period. (2) The mean Igeo values of Hg and As were 0.657 and -0.948. The bioavailability of Hg in the sediments of Wuliangsuhai Lake during the frozen period was high, and its average value was 7.8%, which belonged to the low-risk grade. The bioavailability of As ranged from 0.2% to 3.7%, with an average value of 1.3%. (3) Monte Carlo simulation results indicate acceptable levels of health risks in both water and ice. This study preliminarily investigated the distribution characteristics of toxic substances and their potential effects on human health in lakes in cold and arid regions during the frozen period. It not only clarified the pollution characteristics of lakes in cold and arid regions during the frozen period, but also provided beneficial supplements for the ecological protection of lake basins. This study lays a foundation for further environmental science research in the region in the future.

Prostate-specific membrane antigen (PSMA) glycoforms in prostate cancer patients seminal plasma.

Prostate-specific membrane antigen (PSMA) is a USFood and Drug Administration-approved theranostic target for prostate cancer (PCa). Although PSMA is known to be glycosylated, the composition and functional roles of its N-linked glycoforms have not been fully characterized. PSMA was isolated from pooled seminal plasma from low-risk grade Groups 1 and 2 PCa patients. Intact glycopeptides were analyzed by mass spectrometry to identify site-specific glycoforms. We observed a rich distribution of PSMA glycoforms in seminal plasma from low and low-intermediate-risk PCa patients. Some interesting generalities can be drawn based on the predicted topology of PSMA on the plasma membrane. The glycoforms at ASN-459, ASN-476, and ASN-638 residues that are located at the basal domain facing the plasma membrane in cells, are predominantly high mannose glycans. ASN-76 which is located in the interdomain region adjacent to the apical domain of the protein shows a mixture of high mannose glycans and complex glycans, whereas ASN-121, ASN-195 and ASN-336 that are located and are exposed at the apical domain of the protein predominantly possess complex sialylated and fucosylated N-linked glycans. These highly accessible glycosites display the greatest diversity in isoforms across the patient samples. Our study provides novel qualitative insights into PSMA glycoforms that are present in the seminal fluid of PCa patients. The presence of a rich diversity of glycoforms in seminal plasmaprovides untapped potential for glycoprotein biomarker discovery and as a clinical sample for noninvasive diagnostics of male urological disorders and diseases including PCa. Specifically, our glycomics approach will be critical in uncovering PSMA glycoforms with utility in staging and risk stratification of PCa.

Explainability of random survival forests in predicting conversion risk from mild cognitive impairment to Alzheimer’s disease

Random Survival Forests (RSF) has recently showed better performance than statistical survival methods as Cox proportional hazard (CPH) in predicting conversion risk from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). However, RSF application in real-world clinical setting is still limited due to its black-box nature.For this reason, we aimed at providing a comprehensive study of RSF explainability with SHapley Additive exPlanations (SHAP) on biomarkers of stable and progressive patients (sMCI and pMCI) from Alzheimer’s Disease Neuroimaging Initiative. We evaluated three global explanations—RSF feature importance, permutation importance and SHAP importance—and we quantitatively compared them with Rank-Biased Overlap (RBO). Moreover, we assessed whether multicollinearity among variables may perturb SHAP outcome. Lastly, we stratified pMCI test patients in high, medium and low risk grade, to investigate individual SHAP explanation of one pMCI patient per risk group.We confirmed that RSF had higher accuracy (0.890) than CPH (0.819), and its stability and robustness was demonstrated by high overlap (RBO > 90%) between feature rankings within first eight features. SHAP local explanations with and without correlated variables had no substantial difference, showing that multicollinearity did not alter the model. FDG, ABETA42 and HCI were the first important features in global explanations, with the highest contribution also in local explanation. FAQ, mPACCdigit, mPACCtrailsB and RAVLT immediate had the highest influence among all clinical and neuropsychological assessments in increasing progression risk, as particularly evident in pMCI patients’ individual explanation. In conclusion, our findings suggest that RSF represents a useful tool to support clinicians in estimating conversion-to-AD risk and that SHAP explainer boosts its clinical utility with intelligible and interpretable individual outcomes that highlights key features associated with AD prognosis.Graphical

CTNI-46. UPFRONT VERSUS DEFERRED TREATMENT IN LOWER GRADE IDH-MUTANT GLIOMAS: A SINGLE-CENTER RETROSPECTIVE ANALYSIS

Abstract BACKGROUND IDH-mutant gliomas are a diverse group of gliomas possessing a mutation in the isocitrate dehydrogenase enzyme. The treatment for both oligodendroglioma (1p/19q co-deleted) and astrocytoma includes resection followed by radiation therapy and chemotherapy. However, there is debate over the optimal timing of adjuvant treatment after surgery. An initial observation approach is sometimes pursued, particularly after gross total resection in young adults. We sought to examine the impact of timing of treatment in order to inform clinical decision-making. METHODS We identified 286 biopsied or resected glial tumors treated at MD Anderson Cancer Center from July 2015 to June 2022. Tumors were categorized using available molecular data based on the WHO 2021 diagnostic criteria. Progression-free survival was analyzed using Kaplan-Meier estimates. RESULTS Of 286 tumors, 232 had identified IDH-mutation, of which 89 were 1p/19q co-deleted and 143 were non-co-deleted. Of oligodendroglioma patients, 71 received either upfront chemotherapy, radiation or both and 18 received treatment upon progression; of astrocytoma patients, 96 were treated upfront and 47 received treatment at progression. Among oligodendroglioma patients, there were no significant differences in PFS between treatment timing groups (75.6 vs 66.7 months, P = 0.18). There was additionally no difference between oligodendroglioma patients treated initially with PC or PCV regimens vs temozolomide (not reached vs 75.4 months, P = 0.24). Among astrocytoma patients, upfront treatment was associated with longer PFS (93.8 vs 45.2 months, P < 0.01). Patients with low-risk grade 2 gliomas (age <40 and gross total resection) also showed longer PFS with upfront treatment (138.0 vs 45.2 months, P = 0.03). CONCLUSION Overall, the results in this molecularly defined cohort suggest a progression-free survival benefit from upfront treatment in IDH-mutant lower grade gliomas, including in low-risk gliomas. The optimal timing and nature of adjuvant treatment for lower grade gliomas remains a matter of debate.

Multimodal recurrence scoring system for prediction of clear cell renal cell carcinoma outcome: a discovery and validation study

Improved markers for predicting recurrence are needed to stratify patients with localised (stage I-III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities-clinical, genomic, and histopathological-to improve the predictive accuracy for localised renal cell carcinoma recurrence. In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI). The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825-0·876 vs 0·608-0·793; p<0·05). The RFI of patients with low stage or grade is usually better than that of patients with high stage or grade; however, the RFI in the multimodal recurrence score-defined high-risk stage I and II group was shorter than in the low-risk stage III group (hazard ratio [HR] 4·57, 95% CI 2·49-8·40; p<0·0001), and the RFI of the high-risk grade 1 and 2 group was shorter than in the low-risk grade 3 and 4 group (HR 4·58, 3·19-6·59; p<0·0001). Our multimodal recurrence score is a practical and reliable predictor that can add value to the current staging system for predicting localised renal cell carcinoma recurrence after surgery, and this combined approach more precisely informs treatment decisions about adjuvant therapy. National Natural Science Foundation of China, and National Key Research and Development Program of China.

Stagnant water environmental management in urban river networks: An integrated risk analysis involving hydraulic potential dissipation

Rapid urbanization has led to water stagnation by temporal and spatial imbalances of the hydrodynamics in urban river networks, which further entails environmental risks to drinking and recreational water supplies. The establishment of a succinct hydraulic potential dissipation (HPD) index to indicate the spatiotemporal stagnant water environmental risks quickly and intuitively is of vital significance to urban river networks with complicated water regimes and diversified water diversion measures. On this basis, an integrated stagnant water environmental risk analysis model (ISWERA) was established by coupling the process-based model and stochastic process to comprehensively and accurately assess risks, which has been calibrated and validated against the real data of 11 monitoring stations from May 3 to May 11 in 2017 and November 28 to December 10 in 2020, respectively. To represent the rationality of stagnant water environmental risks assessment using HPD, ISWERA was used to evaluate the temporal- and spatial-varying stagnant water environmental risk intensity and probability of 270 water diversion schemes formed by the combination of water diversion duration, flow, route, and potential in the Changzhou urban river network along the Yangtze River. For time-varying results, it revealed that cumulative risk intensity was reduced by nearly 15%, and risk probability was significantly reduced by nearly 50% with the increase of diversion duration to 5 days in general. For spatial-varying results, most of the rivers reached the low-risk grade under the optimized diversion duration, flow, route, and potential. While the rivers adjacent to densely populated areas still presented a moderate-risk state. The positive correlation was significant between HPD and stagnant water environmental risk intensity and probability results, with R2 = 0.86 and 0.74 respectively. When the HPD of upstream channels are below 63.4%, 74.1%, and 57.7% and the downstream HPD of S1 to T1, S2 to T2, S2 to T3, and S3 to T4 are below 40.6%, 32.9%, 22.4%, and 19.1%, respectively, the stagnant water environmental risk is lower. Arguably, this study could provide a scientific reference and foundation for water environmental management of similar urban stagnant water systems.

Prevalence of oral behaviours in general dental patients attending a university clinic in Italy.

Oral behaviors represent a diverse array of habits beyond the physiological behaviors of the stomatognathic system. To describe the prevalence of different oral behaviors, as reported with the Oral Behavior Checklist (OBC-21), in a convenience sample of patients attending an Italian university clinic for routine dental cares. In this study, charts of adult patients presenting to the dental department of a regional hospital in Trieste, Italy, from January 2018 and January 2019 were reviewed. Patients with complete files were retrieved, and those with orofacial pain complaints were excluded. OBC-21 scores and grades (score of 0 corresponding to no risk, 1-24 to low risk, and higher than 24 to high risk) were analyzed and stratified according to age and sex. Data from a total of 1424 patients were reported. The overall mean OBC score was 13.3 ± 9.9, with 6.7% no-risk grade, 79.6% low-risk grade, and 13.7% high-risk grade. In general, mean OBC scores decreased with increasing age. Females showed a higher frequency of high-risk grade than males. Most frequent prevalent habits included yawning (73.1%), eating between meals (66.9%) and chewing food on one side only (63.3%). Other behaviors were also highly prevalent, including pressing, touching, or holding teeth together other than while eating (52.7%) and awake clenching (47.5%). A low-risk grade of oral behaviors has been found to be frequent in our sample. Future studies are warranted to confirm these findings in larger, representative general populations and to assess if any of these habits are linked to negative effects on the stomatognathic system.

Risk Stratification for Management of Solitary Fibrous Tumor/Hemangiopericytoma of the Central Nervous System.

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) of the central nervous system (CNS) is a rare meningeal tumor. Given the absence of prospective or randomized data, there are no standard indications for radiotherapy. Recently, the NRG Oncology and EORTC cooperative groups successfully accrued and completed the first prospective trials evaluating risk-adapted adjuvant radiotherapy strategies for meningiomas. Using a similar framework, we sought to develop prognostic risk categories that may predict the survival benefit associated with radiotherapy, using two large national datasets. We queried the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) databases for all newly diagnosed cases of SFT/HPC within the CNS. Risk categories were created, as follows: low risk-grade 1, with any extent of resection (EOR) and grade 2, with gross-total resection; intermediate risk-grade 2, with biopsy/subtotal resection; high risk-grade 3 with any EOR. The Kaplan-Meier method and Cox proportional hazards regressions were used to determine the association of risk categories with overall and cause-specific survival. We then determined the association of radiotherapy with overall survival in the NCDB, stratified by risk group. We identified 866 and 683 patients from the NCDB and SEER databases who were evaluated, respectively. In the NCDB, the 75% survival times for low- (n = 312), intermediate- (n = 239), and high-risk (n = 315) patients were not reached, 86 months (HR 1.60 (95% CI 1.01-2.55)), and 55 months (HR 2.56 (95% CI 1.68-3.89)), respectively. Our risk categories were validated for overall and cause-specific survival in the SEER dataset. Radiotherapy was associated with improved survival in the high- (HR 0.46 (0.29-0.74)) and intermediate-risk groups (HR 0.52 (0.27-0.99)) but not in the low-risk group (HR 1.26 (0.60-2.65)). The association of radiotherapy with overall survival remained significant in the multivariable analysis for the high-risk group (HR 0.55 (0.34-0.89)) but not for the intermediate-risk group (HR 0.74 (0.38-1.47)). Similar results were observed in a time-dependent landmark sensitivity analysis. Risk stratification based on grade and EOR is prognostic of overall and cause-specific survival for SFT/HPCs of the CNS and performs better than any individual clinical factor. These risk categories appear to predict the survival benefit from radiotherapy, which is limited to the high-risk group and, potentially, the intermediate-risk group. These data may serve as the basis for a prospective study evaluating the management of meningeal SFT/HPCs.

PS-C20-11: ANTIHYPERTENSIVE TREATMENT IMPROVES LEFT VENTRICULAR DIASTOLIC FUNCTION AND INDICES OF ARTERIAL STIFFNESS IN YOUNGER MEN WITH GRADE 1 HYPERTENSION

Background: Hypertension is a major risk factor for diastolic dysfunction which, once established, is essentially irreversible. However, it is unclear whether early manifestations of diastolic dysfunction in younger people with mild hypertension can improve with antihypertensive treatment. Objectives: Evaluate whether one-year antihypertensive treatment in younger men (age &lt; 55 years) with low-risk (no evidence of hypertension mediated organ damage) grade 1 hypertension improves diastolic function and indices of arterial stiffness. Methods: 105 treatment-naive men (mean age: 47 ± 6 years) with grade 1 hypertension (confirmed on ABPM) were recruited. Patients were randomised using a PROBE design to one-year antihypertensive treatment (ARB and/or CCB) or no treatment (control). Cardiac function was assessed at baseline and study end via 1.5-Tesla cMRI (MAGNETOM Avanto; Siemens Healthineers AG, Germany) using prospectively gated mid-left-ventricular golden angle tissue phase mapping (primary outcome). Arterial stiffness was measured using CAVI device (VS-1500N; Fukuda Denshi, Japan). Results: Diastolic (longitudinal E/A ratio) and systolic (longitudinal S peak velocity) function improved with treatment (n = 38; 0.11 ± 0.24 and 0.38 ± 1.19 cm.s−1, P = 0.01 and 0.05, respectively) but deteriorated in the control group (n = 44; -0.06 ± 0.33 and -0.13 ± 1.12 cm.s−1, P = 0.01 and 0.05, respectively). Improvement in diastolic function was significantly influenced by baseline bodyfat % and BMI (20 ± 8 versus 27 ± 10%, P = 0.04 and 27.8 ± 3.4 versus 31.0 ± 5.3 kg.m−2, P = 0.03, respectively). CAVI pre-ejection period (-9 ± 15 versus 1 ± 13 ms, P = 0.006), pre-ejection-period.ejection-time−1 (-0.03 ± 0.06 versus 0.00 ± 0.05, P = 0.02), upstroke time (-33 ± 50 versus -8 ± 45 ms, P = 0.03), pulse wave velocity (-0.89 ± 0.64 versus -0.02 ± 0.64 m.s−1, P &lt; 0.001), CAVI (-0.40 ± 0.65 versus 0.03 ± 0.62, P = 0.005) and CAVI estimated vascular age (-3 ± 7 versus 1 ± 7 years old, P = 0.02) all improved with TREATMENT (n = 40) versus CONTROL (n = 44). Conclusions: Early treatment of Grade 1 hypertension improves left ventricular diastolic function. Treated patients with E/A improvements were leaner, which highlights the importance of a healthy lifestyle. Treatment also improved arterial stiffness, however it is unclear whether those changes were predominantly structural and/or functional. Further work is warranted to establish whether an even earlier intervention is needed to restore diastolic function to the level of normotensive age-matched controls.

S1415 Non-Invasive Predictor of High-Risk Esophageal Varices: A Baveno VI Validation Study in Clinical Practice

Introduction: The Baveno VI consensus proposed patients with liver stiffness > 20 Kpa and platelet count < 150.000 have a high risk of moderate to large esophageal varices, therefore endoscopy screening must be done in these patients. On the other hand, patients with liver stiffness < 20 Kpa and platelet count > 150.000 do not need to perform endoscopy screening. This study aims to evaluate the Baveno VI recommendation as a non-invasive method that could predict the presence of high-risk varices. Methods: A cross-sectional study was conducted in a single centre, involving a newly diagnosed non Child-Turcotte-Pugh (CTP) C class liver cirrhosis, without a history of variceal bleeding and beta-blocker consumption. All the subjects underwent endoscopy screening to determine the presence and grading of the esophageal varices. The esophageal varices were graded as low risk (grade < 2) or high risk (grade ⩾2). Liver stiffness and platelet were also measured. The patient was classified according to the Baveno VI criteria. Table 2x2 was used to identify the diagnostic performance of Baveno VI criteria. Results: This study included 103 patients, the mean age was 53 ± 12.09 years and 80.6 % were male. The majority were CTP-A class (55.3%), and 44.7% were CTP-B class. The aetiology of liver disease was hepatitis B in 49 (47.6%), hepatitis C in 25 (24.3%), and other causes in 29 (28.2%). Esophageal varices were found in 59 (57.3%) patients, and the high-risk varices prevalence was 55.3%. Moderate to large varices were detected in 21 (36.8%) and 36 (63.2%) patients with CTP-A and CTP-B classes, respectively. About 83/103 (80.58%) fulfil the Baveno VI criteria, it was correctly predicted that 53.39% (55) of high-risk varices. About 33.7% of patients who did not have oesophageal varices were falsely predicted to have varices. The Baveno VI criteria had a sensitivity 96.49%, specificity 39.13%, positive predictive value 66.26%, negative predictive value 10%, positive likelihood ratio 1.58, and negative likelihood ratio 0.08 to predict high-risk varices. Conclusion: The Baveno VI can be used as a non-invasive method to predict high-risk oesophageal varices, which high sensitivity but low specificity. Further studies are needed in combination with other non-invasive tests to increase specificity so as to avoid unnecessary endoscopic examinations.

Chromium contamination in paddy soil-rice systems and associated human health risks in Pakistan

Chromium (Cr) contamination in paddy soil-rice systems threatens human health through the food chain. This study used a new dataset of 500 paddy soil and plant tissue samples collected in the rice-growing regions of Sindh and Punjab Provinces of Pakistan. Overall, 97.4% of grain samples exceeded the Cr threshold values of 1.0 mg kg−1, determined by the China National Food Standard (CNFS). The Cr in paddy soil, 62.6% samples exceeding the China natural background threshold value (90 mg kg−1) for Cr concentration in paddy soil, and lower than the (pH-dependant > 7.5 threshold value for Cr 350 mg kg−1) as determined by China Environmental Quality Standards (EQSs) for paddy soil (GB15618-2018). Geographically weighted regression (GWR) modelling showed spatially nonstationary correlations, confirming the heterogeneous relationship between dependent (rice grain Cr) and independent paddy soil (pH, SOM, and paddy soil Cr) and plant tissue variables (shoot Cr and root Cr) throughout the study area. The GWR model was then used to determine the critical threshold (CT) for the measured Cr concentrations in the paddy soil system. Overall, 38.4% of paddy soil samples exceeding CT values confirm that the paddy soil Cr risk prevails in the study area. Furthermore, the GWR model was applied to assess the loading capacity (LC), the difference between the CT, and the actual concentration of Cr in paddy soil. Loading capacity identified potential paddy soil Cr pollution risk to rice grain and assessed the risk areas. Overall LC% of samples paddy soil Cr risk areas grade: low-risk grade I (34.6%); moderate-risk grade II (15.8%); high-risk grade III (11.2%); and very high-risk grade IV (38.4%) have been assessed in the study area.The human health index, total hazard quotient (THQ ≪ 1), indicates no potential health risk originating from Cr exposure to the population. However, the excess Cr level in paddy soil and rice grain is still a concern. The current study's results are also valuable for the national decision-making process regarding Cr contamination in the paddy soil-rice system.

Clinicopathological features of hemorrhagic gastrointestinal stromal tumor

In order to demonstrate the bleeding risk factors of GIST (gastrointestinal stromal tumor), we retrospectively investigated clinicopathological features between hemorrhagic (H group, 24 cases) and nonhemorrhagic GIST (NH group, 30 cases). In addition, we investigated features between the E group (6 cases) necessitating TAE (trans-catheter arterial embolization) and NE group (other 48 cases). Whereas H group partly includes high-risk grade GIST with chronic bleeding, meanwhile the E group (reflecting acute bleeding) is characterized by a highly enhanced mass with ulceration, comprising of smaller low-risk grade GIST. Amongst the 29 cases for forceps biopsy, which were 6 cases (21%) including one of E group, needed be hospitalized for postbiopsy bleeding. Acute bleeding in GIST may not be associated with malignant transformation. Postbiopsy bleeding or massive hemorrhage can also be encountered particularly in highly enhanced GIST with ulceration, even with a small and low-risk grade.

Unusual presentations, management and outcomes of gastric stromal tumors: a single-center case series.

BackgroundGastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. This study explores the safety of laparoscopy and the long-term oncological outcome in gastroesophageal GIST treatment.MethodsA prospectively maintained single-institution database was examined. The variables collected were patient demographics and comorbidities, surgical access (laparoscopic/open), type of surgery, length of stay, and complications.ResultsA total of 69 patients underwent GIST resection between January 2011 and June 2018, of whom 56.5% were male; the median age was 68 years (interquartile range 60-76). The majority of patients (78.3%, n=54/69) had a laparoscopic resection. Median length of stay was 6 days in the laparoscopic group and 9 days in the open group (P=0.003). Most patients had wedge excision (n=57/69, 82.6%), while 12 patients (17.4%) required a gastrectomy (one a Merendino type). All patients had an R0 resection and 1 patient (1.4%) had a recurrence, despite having a low-risk grade original tumor with negative margins. Patients in the open group had a significantly higher proportion of patients with a high-risk tumor (50%) compared to the laparoscopic group (3.7%, P=0.001). The mean survival was 92.7 months (95% confidence interval 86.3-99.2). Survival was better in the laparoscopic group (100.4 months) compared with the open group (55.1 months, P<0.001).ConclusionLaparoscopic gastric GIST resection is an oncologically safe alternative to open surgery and is associated with a shorter hospital stay with no difference in complication rates or recurrence rates.

Loss of Phosphatase and Tensin Homologue (PTEN) Expression Associated with Higher Risk Grade Group Gleason Prostate Adenocarcinoma in Sanglah Hospital Denpasar

Background: Prostate cancer is the second most common malignancy in men and the fifth most common cause of death worldwide. In Asia, 59.3% of patients come for the advanced stage treatment. PTEN inactivation is identified in about 20% of primary prostate tumors in radical prostatectomy and the loss of PTEN is associated with poor clinical and pathological outcomes. The purpose of this study is to prove that there is an association between PTEN expression and risk grade group Gleason prostate adenocarcinoma in Sanglah Public Hospital, Denpasar.Methods: This is a cross-sectional study. The sample size of this study was 35 paraffin blocks. These samples were selected by proportional stratified random sampling from hematoxylin-eosin preparation. Prostate adenocarcinoma was regrouped into 3 categories based on NCCN risk stratification: low risk grade group Gleason (Gleason score ≤ 6), intermediate risk grade group Gleason (Gleason score 7), and high-risk grade group Gleason (Gleason score 8–10). Immunohistochemistry examination of PTEN was performed and the expression was evaluated by scoring method. The data were analyzed by Chi-square and logistic regression.Results: The analysis result showed that there is an association between PTEN expression and risk grade group Gleason that is statistically significant. The loss of PTEN expression associated with higher risk grade group Gleason is of the higher proportion with p=0.001; PR 3.339; 95% CI: 1.296–8.599, but there is no association between the proportion loss of PTEN expression heterogeneously or homogeneously and the risk grade group Gleason with p=0.742; PR 0.663; 95% CI: 0.179–2.457.Conclusions: This study has proved that PTEN expression is associated with higher risk grade group Gleason prostate adenocarcinoma.

Clinical characteristics of acute pulmonary embolism at different altitudes in plateau areas

Objective: To analyze the clinical characteristics of pulmonary embolism patients from different altitudes in plateau areas. Methods: A retrospective cross-sectional study was used to analyze the patients with acute pulmonary embolism diagnosed definitely by pulmonary angiography or pulmonary artery CT angiography admitted to Tibet Autonomous Region People's Hospital from August 2014 to December 2018. The subjects were divided into 3 groups according to the altitude of long-term residence before onset, i.e. low-altitude group (group 1, 2 700 m ≤ altitude ≤3 700 m, n=44), medium-altitude group (group 2, 3 700 m<altitude ≤4 000 m, n=30) and high altitude group (group 3, 4 000 m<altitude ≤4 800 m, n=32). The clinical data, auxiliary examination and risk stratification of pulmonary embolism patients at different altitudes were compared and analyzed. Results: The incidence of chest pain, dyspnea and lower limb fracture in the three groups were statistically significant (P<0.05). The incidence of chest pain in group 2 (70%) was higher than that in group 1(40.9%), and dyspnea in group 3 (93.8%) was higher than that in group 2(66.7%), while lower limb fracture in group 3 (43.8%) was higher than that in group 1(15.9%). The differences in arterial oxygen partial pressure, hemoglobin and D-dimer among the three groups were statistically significant (P<0.05). The arterial oxygen partial pressure [52(43.5-63.5)mmHg] in group 3 was lower than that in group 1 [60 (53.25-73) mmHg]. The hemoglobin (163.1±43.3 g/L) and D-dimer [5.6(3.7-12.6)mg/L] in group 3 were higher than those in group 1 [143.5±38.9 g/L and 3.8(2.0-7.5)mg/L respectively]. The risk stratification of the three groups of patients was moderate or low, and there was no statistical difference among the three groups. In patients with the same low-risk grade, the D-dimer in group 3 was higher than that in group 1 [5.8(4.2-14.8)mg/L and 3.6(2.3-5.8)mg/L respectively, P<0.05]. In patients with the same moderate risk level, the arterial oxygen partial pressure in group 3 was lower than that in group 1 [47.0(36.0-58.0)mmHg and 59.5(52.3-68.5)mmHg, respectively, P<0.05]. Conclusion: There was no difference in the risk stratification of pulmonary embolism from different altitudes in plateau areas, but patients who lived at higher altitudes for a long time showed more significant hypoxemia and increased hemoglobin and D-dimer levels.

ALBI-RT as a Radiation Therapy Specific Hepatotoxicity Prediction Model for Hepatocellular Carcinoma Patients

The albumin-bilirubin (ALBI) grading system was developed for predicting hepatotoxicity in hepatocellular carcinoma (HCC) patients; however, its value in patients treated with radiotherapy (RT) remains unclear. We sought to develop a modified ALBI grading system, ALBI-RT, as a novel pre-treatment grading system for stratification of hepatotoxicity risk in HCC patients treated with RT. We performed a retrospective review of 92 consecutive HCC patients treated with RT from 2013 – 2018. Raw ALBI scores and Child-Pugh (CP) scores were calculated. Patient deaths were assessed for association with radiation-induced liver disease (RILD). Using raw ALBI score as a continuous variable, ROC analysis was performed to define risk strata of RILD-specific survival (RILD-SS). Univariate Cox regression models of RILD-SS were generated using raw ALBI score, conventional ALBI grade, ALBI-RT grade, CP score, CP class, and CP score increase of 2 or greater (CP+2). The association of ALBI-RT grade with known predictors of hepatotoxicity was assessed in two bivariate Cox models which adjusted for conventional ALBI grade and CP+2, respectively. The patient cohort was comprised of 67% CP-A and 33% CP-B/C. Median follow-up was 11.5 months for all patients and 15.5 months for alive patients. There were 40 deaths, with 8 attributed to possible RILD. ROC analysis identified raw ALBI (AUC = 0.91, p < 0.001) dichotomization at a score of -1.7 to predict RILD with 100% sensitivity and 80% specificity. Based on this dichotomization, ALBI-RT risk categories were divided into low risk grade A < 1.7 (n = 69) and high risk grade B ≥ 1.7 (n = 23). ALBI-RT grade B identified 6% of CP A patients at increased risk for RILD and conversely, ALBI-RT grade A identified 37% of CP B/C patients with decreased risk. On univariate analysis, ALBI-RT grade B (HR 25.5), CP-A5-B7 vs B8+ (HR 46.8), raw ALBI score (HR 5.3), ALBI grade (HR 8.6), CP score (HR 2.3), CP+2 (HR 11.9) were all significantly associated with a higher relative risk of RILD-SS (p ≤ 0.003). On bivariate analysis, ALBI-RT (HR 14, p = 0.030) was independently predictive for RILD-SS compared to conventional ALBI grade (HR 2.2, p = 0.283); furthermore, ALBI-RT (HR 17.3, p = 0.009) was a more significant predictor of RILD-SS than post-treatment toxicity metric CP+2 (HR 5.1, p = 0.025). ALBI-RT is a novel metric for pre-treatment assessment of HCC patients that predicts risk of RILD-related death. ALBI-RT showed a larger effect size and retained its statistical significance relative to known hepatotoxicity predictors (ALBI grade, CP+2). Multi-institution external validation has the potential to strengthen the generalizability of ALBI-RT and facilitate clinical translation.

Real-world evidence evaluating the use of an NK-1 antiemetic in the systemic chemotherapy treatment of metastatic breast cancer.

e12599 Background: Severe and persistent nausea and vomiting (n/v) impacts quality of life and may lead to treatment discontinuation. While antiemetics assist with minimizing these effects, newer drugs can be expensive and carry their own side effect profile. Prior research has suggested that neurokinin 1 receptor inhibitor(NK-1) antiemetics are overly prescribed. Using the package insert recommendations for aprepitant, an NK-1, we evaluated the frequency of its prophylactic use to prevent emesis in patients receiving systemic chemotherapy(chemo) with moderate to high emetogenic risk. Methods: Patients were identified from a third-party, administrative claims database. Using medical and pharmacy claims, any female with ICD-9/10 codes for both breast cancer and metastases diagnosed between Jan-2013 and Dec-2017, who initiated systemic chemo and received aprepitant prophylactically were selected. Chemo regimen emetogenic potential was scored using the Hesketh scale and aggregated into two cohorts: low risk (grade 1-2 = none- &lt; 30%), and moderate-high risk (grade 3-5: &gt; 30- &gt; 60%). If patients received combination chemo, the assigned risk level was the highest risk of any individual agent. The frequency of NK-1 use for each risk cohort was calculated per line of therapy independent of the previous treatment. Results: 10,342 patients met the selection criteria with 2,868 patients administered moderate-high emetogenic risk chemotherapy regimens. Mean age at initiation of treatment was 61.7 years (SD = 12.12). By line, the aprepitant utilization rate was: 1 line(L) 43% ,2L 27%, 3L 18%, 4L 16%, 5L 11% and 6L 12%. Across all lines of therapy, aprepitant was used prophylactically in 23% of patients treated with high risk chemo regimens and in 2% of patients who had received low risk regimens. Conclusions: Prophylactic use of the NK-1 inhibitor aprepitant was less than 50% in 1L moderate-high emetogenic risk chemotherapy and declined with consecutive lines of treatment. NK-1 use with low risk regimens was minimal. Further research is needed to understand the pattern of use and clinical outcomes between moderate-high emetogenic risk patients who do and don't receive NK-1 antiemetic supportive care.

TREATMENT OF STAGE 1, LOW RISK HYPERTENSION IS ASSOCIATED WITH REDUCTION IN CARDIOVASCULAR MORTALITY

Objective: There is lack of evidence for the benefit of treatment in uncomplicated, low risk grade I hypertension. As such, some of the major guidelines recommend treatment for grade I hypertensives who have underlying cardiovascular disease, or are at high risk. Design and method: From National Health Insurance Service (NHIS) Health Examination Database, subjects with grade I hypertension between 2005 and 2006 were selected and followed-up until December, 2015. The subjects had a SBP of 140–159 mmHg and/or DBP of 90–99 mmHg and were not undergoing treatment at baseline. Subjects were grouped into controlled (<140/90 mmHg; n = 99,301) and uncontrolled group (> = 140/90 mmHg; n = 49,460) according to mean of the BP recorded during follow-up health examination. All-cause death and cardiovascular outcomes including myocardial infarction (MI), ischemic stroke, hemorrhagic stroke, and end stage renal disease (ESRD) were examined by using Cox proportional hazard models with covariate adjustment method using the propensity scores. Results: Median follow-up duration was 124 months (IQR: 116–131). Compared to subjects with uncontrolled BP, controlled group had significantly lower risk of all-cause death (HR, 0.50; 95% CI, 0.48–0.52; p < 0.0001). For non-fatal events, controlled BP was associated with the lower risk of all stroke (HR, 0.88; 95% CI, 0.82–0.93; p < 0.0001), hemorrhagic stroke (HR, 0.75; 95% CI, 0.66–0.85; p < 0.0001), ischemic stroke (HR, 0.91; 95% CI, 0.84–0.98; p = 0.0083), and ESRD (HR, 0.42; 95% CI, 0.30–0.59; p < 0.0001). There was no significant difference between the two groups for non-fatal MI. Importantly, the benefit was evident in young aged hypertensives below the age of 50. The optimal level of BP associated with the lowest risk of all-cause mortality was 120 to < 130 mmHg for SBP and 70 to < 80 mmHg for DBP. However, there was increased risk of MI for subjects with SBP of < 120 mmHg and DBP of 70 to < 80 mmHg. Conclusions: In a large cohort of treated low risk, grade I hypertensive subjects, BP below 140/90 mmHg was associated with significant reduction in the risk of mortality, stroke and ESRD, with the lowest risk of mortality in the range of 120 to < 130 mmHg and 70 to < 80 mmHg.