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Background: Primary adrenal (PA) diffuse large B cell lymphoma (DLBCL) was previously reported as an aggressive subset of DLBCL, but its genetic features were not sufficiently characterized. From our previous study of DLBCL with programmed death-ligand 1 (PD-L1) gene alterations, we focused on PD-L1 gene alterations in PA-DLBCL with clinicopathologic implications. Methods: We performed fluorescence in situ hybridization for PD-L1 gene translocation and amplification in PA-DLBCL (n = 18) and comparatively analyzed clinicopathologic characteristics with systemic non-adrenal (NA)-DLBCL (n = 90). Results: PA-DLBCL harbored distinctive features (vs. NADLBCL), including high international prognostic index score (3–5) (72% [13/18] vs. 38% [34/90], p = .007), poor Eastern Cooperative Oncology Group performance score (≥ 2) (47% [7/15] vs. 11% [10/90], p = .003), elevated serum lactate dehydrogenase (LDH) (78% [14/18] vs. 51% [44/87], p = .035) and MUM1 expression (87% [13/15] vs. 60% [54/90], p = .047). Moreover, PA-DLBCL showed frequent PD-L1 gene alterations (vs. NA-DLBCL) (39% [7/18] vs. 6% [5/86], p = .001), including translocation (22% [4/18] vs. 3% [3/87], p = .016) and amplification (17% [3/18] vs. 2% [2/87], p = .034). Within the PA-DLBCL group, PD-L1 gene–altered cases (vs. non-altered cases) tended to have B symptoms (p = .145) and elevated LDH (p = .119) but less frequent bulky disease (≥ 10 cm) (p = .119). In the survival analysis, PA-DLBCL had a poor prognosis for overall survival (OS) and progression-free survival (PFS) (vs. NA-DLBCL; p = .014 and p = .004). Within the PA-DLBCL group, PD-L1 translocation was associated with shorter OS and PFS (p < .001 and p = .012). Conclusions: PA-DLBCL is a clinically aggressive and distinct subset of DLBCL with frequent PD-L1 gene alterations. PD-L1 gene translocation was associated with poor prognosis in PA-DLBCL.

The diagnostic criteria proposed by the World Health Organization did not consider the discrepancy in diagnosis between lumbar spine (LS) and femoral neck (FN) and the clinical implications is unclear. Therefore, this retrospective study evaluated the probability of fracture risk in postmenopausal women with lumbar spine (LS)–femoral neck (FN) bone mineral density (BMD) discordance or not Patients included 1066 healthy postmenopausal women (median age 55.5 years) who visited our hospital for a health check-up between May 2013 and April 2017. Discordance was defined as a difference of one or two degrees between LS BMD and FN BMD. TBS was calculated from dual energy absorptiometry (DXA) images. Fracture risk was assessed using the Fracture Risk Assessment Tool (FRAX), including TBS-adjusted FRAX Seven hundred and two patients (65.9%) showed concordant LS and FN results, whereas 364 patients (34.1%) exhibited discordance. Normal BMD was found in 519 concordant patients (73.9%). Concordant patients showed significantly higher FRAX scores, including TBS-adjusted FRAX results, than discordant patients with low LS or FN. Furthermore, FRAX results in concordant osteopenia patients were similar to that of osteoporosis patients with osteopenia or a normal result at one site. FRAX and TBS-adjusted FRAX results in concordant osteopenia patients were comparable to that of discordant osteoporosis patients We concluded that patients with colncordant osteopenia in both the FN and LS should be managed in a similar way to patients with discordant osteoporosis.

NUT carcinoma is an aggressive epithelial malignancy defined by NUTM1 translocation, usually arising in the head/neck or thorax regions and showing squamous differentiation. Herein, we describe an extraordinary case of NUT carcinoma in the pelvic cavity. The patient was a 54-yr-old woman who was found to have a large pelvic mass with multiple metastases, suggestive of advanced ovarian cancer. Peritoneal seeding nodules were resected and subjected to pathologic examination. Upon microscopic investigation, infiltration of tumor cells showing monotonous-round morphology without squamous features was observed. Immunohistochemical analysis revealed faint/dot-like expression of cytokeratin, focal expression of vimentin, and diffuse expression of the estrogen receptor, but there was no detection of p40, p63, and Myc. NUT was diffusely and strongly expressed in nuclei, in which it exhibited a speckled pattern. Subsequent dual-color break-apart fluorescence in situ hybridization of NUTM1 confirmed a genetic translocation. Next, target-enriched next-generation sequencing covering ~200 major cancer-associated genes found no other significant alterations. After 2 cycles of chemotherapy, bilateral pleural effusion developed that were diagnosed as metastatic NUT carcinoma. The data suggest that NUT carcinoma should be enlisted in the differential diagnosis of poorly differentiated malignancies arising in the pelvic organs.

To identify features on preoperative MR imaging with diffusion-weighted imaging (DWI) for predicting next-generation sequencing (NGS)-based tumor cellularity and patient outcome after surgical resection of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 105 patients with surgically resected PDAC who underwent preoperative MR imaging with DWI. Tumor cellularity was measured using molecular techniques and bioinformatics methods. Clinico-pathologic findings including tumor T stage for predicting disease-free survival (DFS) and overall survival (OS) were identified using Cox proportional hazards model. Important MR imaging findings including apparent diffusion coefficient (ADC) value of PDAC and modified ADC value (the ratio of the ADC value of PDAC to the ADC value of the spleen) for predicting higher tumor cellularity (≥ 30%) and poor prognosis were also identified. The median DFS and OS were 12.0 months [95% confidence interval (CI), 8.0–17.0] and 22.0 months (95% CI, 18.0–29.0), respectively. Higher T stage (T3/4) [hazard ratio (HR), 7.720, (95% CI 1.072, 55.612); p = 0.048] and higher tumor cellularity [HR, 1.599 (95% CI, 1.003–2.548); p = 0.048] were significantly associated with worse DFS. Among MR imaging features, the modified ADC value was significantly associated with tumor cellularity [odds ratio, 0.068 (95% CI, 0.012–0.372); p = 0.002], and PDAC with lower modified ADC value [≤ 1.40 (cutoff value)] showed significantly shorter median DFS than PDAC with higher modified ADC value [8 months (95% CI, 4–12) vs. 16 months (95% CI, 10–29); HR, 1.713 (95% CI, 1.073–2.735), log-rank p = 0.024]. Higher NGS-based tumor cellularity may be a negative prognostic factor in pancreatic cancer after resection, and modified ADC value derived from DWI could be helpful in predicting tumor cellularity and patient surgical outcome with regard to recurrence.

To determine the appropriate use of ancillary features (AFs) in upgrading LI-RADS category 3 (LR-3) to category 4 (LR-4) for hepatic nodules on gadoxetic acid–enhanced MRI. We retrospectively analyzed MRI features of solid hepatic nodules (≤ 30 mm) categorized as LR-3/4 on gadoxetic acid–enhanced MRI. In LI-RADS diagnostic table-based-LR-3 observations, logistic regression analyses were performed to identify AFs suggestive of hepatocellular carcinomas (HCCs) rather than non-malignant nodules. Using McNemar’s test, the sensitivities and specificities of the final-LR-4 category for HCC diagnosis were compared according to the principles of AF application in category adjustment. A total of 336 hepatic nodules (191 HCCs; 145 non-malignant) in 252 patients were evaluated. Based on major HCC features, 248 nodules (123 HCCs) were assigned as table-based-LR-3 and 88 nodules (68 HCCs) as table-based-LR-4. In table-based-LR-3 observations, mild–moderate T2 hyperintensity was identified as an independent predictor of HCC as opposed to non-malignant nodules (odds ratio = 3.01, p = 0.002). For HCC diagnosis, different criteria of final-LR-4: only table-based-LR-4, allowing category upgrade using only T2 hyperintensity, or using any AFs favoring malignancy resulted in sensitivities of 35.6% (68/191), 53.9% (103/191), and 88.5% (169/191), and specificities of 86.2% (125/145), 75.9% (110/145), and 21.4% (31/145), respectively, which differed from each other (all p < 0.001). While the application of MRI AF in LI-RADS category adjustment increases the sensitivity of LR-4 category for HCC diagnosis, it is accompanied by a significant decrease in specificity. Mild–moderate T2 hyperintensity, a significant AF indicative of HCC, may be more appropriate for upgrading LR-3 to LR-4. • When upgrading from LR-3 to LR-4 using any MRI ancillary features favoring malignancy, LR-4 sensitivity increases but specificity decreased for HCC diagnosis. • By upgrading LR-3 to LR-4 based on MRI ancillary features found to suggest HCC rather than non-malignant nodules in multivariate analysis (i.e., mild–moderate T2 hyperintensity), LR-4 demonstrated a more balanced sensitivity and specificity for HCC diagnosis (53.9% and 75.9%, respectively).

Background Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population. Methods We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250. Findings Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035). Interpretation Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events. Funding ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.

To investigate an additional value of [68Ga]Ga-DOTA-TOC PET/CT for characterizing suspected pancreatic neuroendocrine neoplasms (NENs) in a large study cohort. This retrospective study included 167 patients who underwent [68Ga]Ga-DOTA-TOC PET/CT for suspected pancreatic NENs detected by contrast-enhanced CT (n = 153) and/or MRI (n = 85). Two board-certified radiologists independently reviewed CT and/or MRI as well as [68Ga]Ga-DOTA-TOC PET/CT and scored the probability of NEN on a 5-point scale. Radiologists’ diagnostic performances with and without [68Ga]Ga-DOTA-TOC PET/CT were compared using pathologic findings as the standard of reference. All 167 patients were pathologically diagnosed with NENs (n = 131) or non-NENs (n = 36) by surgery (n = 93) or biopsy (n = 74). The non-NEN group included focal pancreatitis (n = 7), gastrointestinal stromal tumor (n = 6), serous cystadenoma (n = 5), metastatic renal cell carcinoma (n = 4), intrapancreatic accessory spleen (n = 4), ductal adenocarcinoma (n = 3), solid pseudopapillary neoplasm (n = 2), intraductal papillary mucinous carcinoma (n = 1), adenosquamous carcinoma (n = 1), schwannoma (n = 1), paraganglioma (n = 1), and solitary fibrous tumor (n = 1). Radiologists’ diagnostic performance significantly improved after the addition of [68Ga]Ga-DOTA-TOC PET/CT (AUC of CT: 0.737 vs. 0.886 for reviewer 1 [p = 0.0004]; 0.709 vs. 0.859 for reviewer 2 [p = 0.0002], AUC of MRI: 0.748 vs. 0.872 for reviewer 1 [p = 0.023]; 0.670 vs. 0.854 for reviewer 2 [p = 0.001]). [68Ga]Ga-DOTA-TOC PET/CT significantly improved sensitivity (CT: 87.4% vs. 96.6% for reviewer 1 [p = 0.001]; 74.8% vs. 92.5% for reviewer 2 [p = 0.0001], MRI: 86.9% vs. 98.4% for reviewer 1 [p = 0.016]; 70.5% vs. 91.8% for reviewer 2 [p = 0.002]). [68Ga]Ga-DOTA-TOC PET/CT provided an additional value over conventional CT or MRI for the characterization of suspected pancreatic NENs. • [ 68 Ga]Ga-DOTA-TOC PET/CT could provide additional value over conventional CT and/or MRI for the exact characterization of suspected pancreatic NENs by increasing AUC values and sensitivity. • Diagnostic improvement was significant, especially in NENs showing an atypical enhancement pattern. • The inter-observer agreement was improved when [ 68 Ga]Ga-DOTA-TOC PET/CT was added to CT and/or MRI.

Cerebrovascular lesions are widely prevalent in patients with Alzheimer’s disease (AD), but their relationship to the pathophysiology of AD remains poorly understood. An improved understanding of the interaction of cerebrovascular damage with AD is crucial for the development of therapeutic approaches. Herein, we investigated the effects of chronic cerebral hypoperfusion (CCH) in a 5XFAD transgenic (Tg) mouse model of AD. We established CCH conditions in both Tg and non-Tg mice by inducing unilateral common carotid artery occlusion (UCCAO). Cognitive performance in mice was evaluated, and their brain tissue was examined for amyloid-beta (Aβ) pathology to elucidate possible mechanisms. We found that UCCAO-operated Tg mice showed impaired cognitive flexibility in the reversal phase of the hidden-platform water maze task compared to sham-operated Tg mice. Interestingly, UCCAO-operated Tg mice used fewer spatial cognitive strategies than sham-operated Tg mice during reversal learning. These cognitive deficits were accompanied by increased Aβ plaque burden and Aβ42 levels in the hippocampus and prefrontal cortex, 2 regions that play essential roles in the regulation of cognitive flexibility. Furthermore, changes in cognitive flexibility are strongly correlated with the expression levels of enzymes related to Aβ clearance, such as neprilysin and insulin-degrading enzymes. These findings suggest that, in 5XFAD mice, impaired cognitive flexibility is related to CCH, and that Aβ clearance might be involved in this process.

Several patients with chronic kidney disease (CKD) have deteriorated bone status. Estimation of bone status using DXA has limitations especially in patients with CKD accompanying aortic calcifications. Quantitative CT and the trabecular bone score could be more accurate methods to estimate bone status for patients with CKD and vascular calcifications. It remains unclear whether dual-energy absorptiometry (DXA) is appropriate for the assessment of bone status in patients with chronic kidney disease (CKD), a disease that impacts bone health. The aims of this study were to compare DXA and central quantitative computed tomography (cQCT) and to evaluate bone status in patients with pre-dialysis CKD. This retrospective study included 363 healthy control subjects whose bone mineral density (BMD) was evaluated with DXA and 117 CKD patients whose BMD was evaluated using both cQCT and DXA. Diagnostic discordance was assessed between the lumbar spine (LS) and femur neck (FN) from DXA or between two modalities. The trabecular bone score (TBS) was extracted from DXA images. The volume of abdominal aortic calcification (AAC) was calculated using CT images from cQCT. Using LS DXA T-score, osteoporosis was less common in the CKD group than in controls. Patients with normal LS BMD using DXA were reclassified into osteopenia or osteoporosis using cQCT in CKD patients. Among discordant subjects between FN and LS in DXA, a higher BMD of LS was more common in CKD patients than in controls. CKD patients had lower TBS than controls despite having the same diagnosis using DXA. AAC volume negatively correlated with BMD from cQCT and with TBS but not with BMD from DXA. TBS and cQCT could accurately assess bone status in CKD patients since DXA may overestimate LS BMD, likely due to an increased AAC volume.

The purpose of this study was to compare the changes in DXA values including trabecular bone score (TBS) and bone mineral density (BMD) of lumbar spine (LS) and femur according to the hormone therapies including tamoxifen (TMXF) treatment with or without gonadotropin releasing hormone analog (GnRH analog) in women with breast cancer. We enrolled 119 women with breast cancer who had undergone breast-conserving surgery or mastectomy followed by TMXF treatment for postmenopausal women (TMXF group, n = 63, 52.9%) or by combination therapy of TMXF combined with GnRH analog for premenopausal women (TMXF + GnRH group, n = 56, 47.1%) from December 2013 to December 2017. The median follow-up period was 13 months (interquartile range [IQR], 12.0–14.75) for TMXF group and 13.5 months (IQR, 12.00–16.00) for TMXF + GnRH group, respectively. Patients did not receive bone-modifying therapy. The baseline dual-energy X-ray absorptiometry (DXA) scan before breast cancer surgery and follow-up DXA during hormone therapy. Comparing the first and follow-up DXA results, BMD in LS were significantly decreased in both TMXF (P P P = 0.0011, mean difference: − 0.01) and total femur (P P P = 0.095, mean difference: − 0.007). Regarding TBS, no significant change was found in the TMXF (P = 0.574, mean difference: − 0.004) group, whereas there was a significant decrease in TBS in the TMXF + GnRH (P

Tumor immunogenicity is driven by various genomic and transcriptomic factors but the association with the overall status of methylation aberrancy is not well established. We analyzed The Cancer Genome Atlas pan-cancer database to investigate whether the overall methylation aberrancy links to the immune evasion of tumor. We created the definitions of hypermethylation burden, hypomethylation burden and methylation burden to establish the values that represent the degree of methylation aberrancy from human methylation 450 K array data. Both hypermethylation burden and hypomethylation burden significantly correlated with global methylation level as well as methylation subtypes defined in previous literatures. Then we evaluated whether methylation burden correlates with tumor immunogenicity and found that methylation burden showed a significant negative correlation with cytolytic activity score, which represent cytotoxic T cell activity, in pan-cancer (Spearman rho = − 0.37, p

To investigate the utility of MR findings and texture analysis for predicting the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs). Two hundred forty-eight patients with surgically confirmed IPMNs (106 malignant [invasive carcinoma/high-grade dysplasia] and 142 benign [low/intermediate-grade dysplasia]) and who underwent magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) were included. Two reviewers independently analyzed MR findings as proposed by the 2017 international consensus guidelines. Texture analysis of MRCP was also performed. A multivariate logistic regression analysis was used to identify predictors for malignant IPMNs. Diagnostic performance was also analyzed using receiver operating curve analysis. Among MR findings, enhancing mural nodule size ≥ 5 mm, main pancreatic duct (MPD) ≥ 10 mm or MPD of 5 to 9 mm, and abrupt change of MPD were significant predictors for malignant IPMNs (p

To predict poor survival and tumor recurrence in patients with ampullary adenocarcinoma using preoperative clinical and CT findings. A total of 216 patients with ampullary adenocarcinoma who underwent preoperative CT and surgery were retrospectively included. CT was assessed by two radiologists. Clinical and histopathological characteristics including histologic subtypes were investigated. A Cox proportional hazard model and the Kaplan-Meier method were used to identify disease-free survival (DFS) and overall survival (OS). A nomogram was created based on the multivariate analysis. The optimal cutoff size of the tumor was evaluated and validated by internal cross validation. The median OS was 62.8 ± 37.9, and the median DFS was 54.3 ± 41.2 months. For OS, tumor size (hazard ratio [HR] 2.79, p

To compare the diagnostic performances of first and second portal venous phases (PVP1 and PVP2) in revealing washout and capsule appearance for non-invasive HCC diagnoses in gadoxetic acid–enhanced MRI (Gd-EOB-MRI). This retrospective study included 123 at-risk patients with 160 hepatic observations (HCCs, n = 116; non-HCC malignancies, n = 18; benign, n = 26) showing arterial phase hyper-enhancement (APHE) ≥ 1 cm at Gd-EOB-MRI. The mean time intervals from gadoxetic acid injection to PVP1 and PVP2 acquisitions were 53 ± 2 s and 73 ± 3 s, respectively. After evaluating image findings independently, imaging findings and diagnoses were finalized by a consensus of two radiologists using either PVP1 or PVP2 image sets according to the LI-RADS v2018 or EASL criteria. Sensitivity, specificity, and accuracy were compared. Among HCCs, more washout and enhancing capsule were observed in PVP2 (83.6% and 27.6%) than in PVP1 (50.9% and 19.8%) (p

Multiphasic CT or MRI and serum alpha-fetoprotein (AFP) are widely used for posttreatment surveillance of hepatocellular carcinoma (HCC). This study aimed to investigate the clinical outcomes of patients with high posttreatment AFP but without evident recurrence on CT or MRI after curative-intent treatment of HCC. We retrospectively analyzed 121 patients presenting with high posttreatment AFP (> 20 ng/mL) without evident recurrence on multiphasic CT or MRI during surveillance after curative-intent surgical resection or radiofrequency ablation (RFA) for HCC. The time interval from the first event of high posttreatment AFP to imaging-evident recurrence (TimeAFP-Imaging recurrence) was estimated using the Kaplan–Meier method. Cox regression analyses were performed to assess the associated factors with TimeAFP-Imaging recurrence. The median TimeAFP-Imaging recurrence was 20.0 months (95% CI 13.0–28.0 months), and the estimated 6-month and 1-year cumulative incidences of imaging-evident recurrence were 24.4% and 40.1%, respectively. In multivariate Cox analyses, late onset of AFP elevation (> 3 months after treatment) was an independent predictor of shorter TimeAFP-Imaging recurrence (HR 2.11, P = 0.015) if using variables available at the first event of AFP elevation, while non-normalization of AFP at the next follow-up was an independent predictor of shorter TimeAFP-Imaging recurrence (HR 3.65, P

OBJECTIVES The aim of this study was to conduct a radiopathologic evaluation of right-angled traction bronchiectasis to differentiate idiopathic pulmonary fibrosis (IPF) without honeycombing from idiopathic nonspecific interstitial pneumonia (NSIP). MATERIALS AND METHODS The derivation cohort included 78 consecutive patients with idiopathic NSIP (n = 39) or IPF (n = 39) without honeycombing who underwent preoperative thin-section computed tomography scans at a single tertiary hospital. The validation cohort comprised 22 patients (14 IPF and 8 NSIP) from another institution. We assessed conventional computed tomography findings, right-angled traction bronchiectasis on minimum intensity projection (MinIP) images, and pathologic features associated with right-angled bronchiectasis. Right-angled traction bronchiectasis was defined as abrupt kinking of a single bronchus by over 90 degrees or an abrupt angle close to 180 degrees of branching bronchi in the background of fibrosis. In the validation cohort, we evaluated the proportion of correct IPF diagnoses and interobserver agreement of 4 radiologists before and after reviewing MinIP images. RESULTS A probable usual interstitial pneumonia (UIP) pattern (odds ratio [OR], 6.948; 95% confidence interval [CI], 1.525-31.654; P = 0.012) and right-angled traction bronchiectasis (OR, 6.004; 95% CI, 1.980-18.209; P = 0.002) were independently associated with IPF. Patients with right-angled traction bronchiectasis were more likely to have extensive reticular opacity (OR, 1.149; 95% CI, 1.077-1.225; P < 0.001) and pathologically were more likely to have a broad extent of subpleural fibrosis (OR, 4.000; 95% CI, 1.457-10.987; P = 0.007) and relatively thick fibrosis (OR, 7.750; 95% CI, 2.504-23.991; P < 0.001). After reviewing MinIP images, the proportion of correct diagnoses increased from 40.9% to 54.5% to 50.0% to 77.3%. The mean kappa value for right-angled traction bronchiectasis was 0.489 ± 0.192. CONCLUSIONS Right-angled traction bronchiectasis pathologically reflected a subpleural predominance of fibrosis and partly supported the radiologic differentiation of IPF without honeycombing from idiopathic NSIP.

To evaluate diagnostic values of the liver imaging reporting and data system (LI-RADS) M (LR-M) category based on novel explicit criteria that accept both targetoid and nontargetoid LR-M features and the suggested reporting algorithm of LI-RADS v2018 to assess primary liver cancers (PLCs) on gadoxetic acid-enhanced MRI (Gd-EOB-MRI). This retrospective study included 165 patients at high risk for hepatocellular carcinoma (HCC) with pathologically confirmed PLCs (HCC, n = 113; intrahepatic cholangiocarcinoma [iCCA], n = 23; and combined hepatocellular cholangiocarcinoma [cHCC-CCA], n = 29). Two radiologists independently analyzed Gd-EOB-MRI features and determined LI-RADS category for each tumor and categorized the likely etiology either as HCC or non-HCC malignancy if LR-M was assigned. Diagnostic performances for HCC or those for malignancy were compared according to imaging criteria. LR-M was assigned in 95.7%/91.3% of iCCAs; 55.2%/58.6% of cHCC-CCAs; and 21.2%/17.7% of HCCs in reviewers 1/2. Combination of LR-5 plus LR-M resulted in sensitivity of 95.2%/97.6% to diagnose PLCs as malignant, which were significantly higher than that of LR-5 plus “LR-M with ≥ 1 targetoid appearances” (84.8%/91.5%, Ps

Background: Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in pa tients with type 2 diabetes mellitus. Methods: Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeo static model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed. Results: In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P

Follicular lymphoma (FL) with hyaline-vascular Castleman disease (FL-HVCD)-like features is a rare morphologic variant, with fewer than 20 cases in the literature. Herein, we report a case of FL-HVCD in a 37-year-old female who presented with isolated neck lymph node enlargement. The excised lymph node showed features reminiscent of HVCD, including regressed germinal centers (GCs) surrounded by onion skin-like mantle zones, lollipop lesions composed of hyalinized blood vessels penetrating into regressed GCs, and hyalinized interfollicular stroma. In addition, focal areas of abnormally conglomerated GCs composed of homogeneous, small centrocytes with strong BCL2, CD10, and BCL6 expression were observed, indicating partial involvement of the FL. Several other lymphoid follicles showed features of in situ follicular neoplasia. Based on the observations, a diagnosis of FL-HVCD was made. Although FLHVCD is very rare, the possibility of this variant should be considered in cases resembling CD. Identification of abnormal, neoplastic follicles and ancillary immunostaining are helpful for proper diagnosis.

Background: Inhibitors of programmed death-ligand 1 (PD-L1) have potential therapeutic value in gastric cancer. We investigated PD-L1 expression patterns in paired biopsy and resection specimens. Patients and Methods: Thirty-nine formalin-fixed, paraffin-embedded paired samples were assessed using PD-L1 22C3 pharmDx immunohistochemistry technique. Combined positive score (CPS) was calculated as the ratio of PD-L1 stained cells (tumor cells, lymphocytes, and macrophages) to the total number of viable tumor cells, multiplied by 100. The CPS ≥1 indicated PD-L1 positivity. Results: PD-L1 positivity was evident for 33 (84.6%) of 39 resection cases; all displayed low positivity (1≤CPS

This study was conducted in order to assess the performance of the Liver Imaging Reporting and Data System (LI-RADS) treatment response (TR) (LR-TR) categorization on gadoxetic acid-enhanced MRI (Gd-EOB-MRI) for detecting viable tumors in hepatocellular carcinoma (HCC) treated with locoregional treatment (LRT) and to investigate the added value of ancillary features (AFs) to conventional enhancement-based criteria.This retrospective study included 183 patients with Gd-EOB-MRI after LRT for HCC and appropriate reference standards for tumor viability (84 viable and 99 nonviable). Two independent radiologists assigned per-lesion mRECIST and TR categories (TR-nonviable, TR-equivocal, or TR-viable) according to the LR-TR algorithm and modified LR-TR algorithms including mLR-TR(TP) allowing transitional phase (TP) washout and mLR-TR(AF) allowing category adjustment by applying AFs. Diagnostic performances of imaging criteria were compared using the Cochran's Q test with post hoc analysis.For detecting viable tumors, LR-TR-viable resulted in sensitivities of 64.5%/39.3% and specificities of 98.0%/98.0% in reviewers 1/2. In comparison to LR-TR-viable, mRECIST-viable, mLR-TR(TP)-viable, and mLR-TR(AF)-viable showed significantly higher sensitivities (92.9%/94.0%, 77.4%/56.6%, and 86.9%/83.3% in reviewers 1/2) (ps 0.001). The specificity of mRECIST-viable (73.7%/62.6%) was significantly lower than that of LR-TR-viable (ps 0.001), while those of mLR-TR(TP)-viable and mLR-TR(AF)-viable were greater than 95% (98.0%/96.0% and 97.0%/96.0%), statistically equivalent to LR-TR-viable (ps 0.05). TR-equivocal was least assigned on mLR-TR(AF) (1.1%/7.7%) than LR-TR (15.8%/32.2%) or mLR-TR(TP) (6.6%/23.5%) in both reviewers.The LR-TR algorithm on Gd-EOB-MRI provides a specific diagnosis of viable tumor but with limited sensitivity. By applying AFs in the category adjustment, more sensitive and confident diagnosis can be achieved without significant loss of specificity.• The LI-RADS treatment response (LR-TR) algorithm on Gd-EOB-MRI provides a highly specific diagnosis of viable HCC but with limited sensitivity. • The inferior sensitivity of LR-TR-viable category to that of mRECIST can be improved by applying ancillary features in the category adjustment.

BACKGROUND The expression of programmed cell death ligand-1 (PD-L1) is a biomarker in patients with non-small-cell lung carcinoma (NSCLC). Patients with advanced-stage NSCLC receive a variety of molecular genetic tests, possibly resulting in insufficient tissue for immunoassay of PD-L1. Thus, to determine whether effusion fluid specimens are a reliable alternative to tissue specimens for PD-L1 testing, we compared the results of PD-L1 immunostaining using body-fluid cell blocks and tumor tissues. METHODS PD-L1 immunostaining was performed in 62 paired samples of cytology cell blocks (ie, immunocytochemistry) and tumor tissues (ie, immunohistochemistry) from 36 patients using the E1L3N, SP142, and SP263 anti PD-L1 antibody clones. Of the 62 cytology specimens, 50 were from malignant effusion fluid. PD-L1 expression was scored as the percentage of tumor cells with clear membranous staining. RESULTS A strong positive correlation was observed between the immunostains on cytology cell blocks and tumor tissue (Pearson's correlation coefficient, R = .804, P

We examined the effect of TSH-suppressive dose of LT4 on changes in body composition and proinflammatory markers in ovariectomized rats. Bilateral ovariectomy (OVX) and sham operations (Sham) were ...

Background/Aims: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigat ed. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC. Methods: Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this ret rospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were per formed. Results: A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3-4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, perfor mance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respective ly). Furthermore, HPV genotype 18 positivity was also an independent poor prog nostic factor of OS (HR, 10.87, p < 0.001). Conclusions: Non-oropharyngeal cancer, poor performance status, and HPV gen otype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

An inflammatory myofibroblastic tumor (IMT) is a solid tumor of unknown etiology frequently affecting children and young adults and commonly affecting the lung or orbital region. We present a case involving a 41-year-old man who had an IMT combined with Mycobacterium tuberculosis infection in the retroperitoneum. He presented with only pain in the right lower abdomen without accompanying symptoms; a retroperitoneal mass was found on computed tomography. The tumor had invaded the end of the ileum and was attached to the omentum, so mass excision could not be performed. The tumor was completely excised surgically and had histological features diagnostic of an IMT. Histologic findings of the omentum were positive for Ziehl-Nielsen staining for acid-fast bacilli and for a positive polymerase chain reaction for M. tuberculosis. The patient had no apparent immune disorder. These findings made this case exceptional because IMTs, which are mostly due to atypical mycobacteria, have been found mainly in immunocompromised patients.

Fat hypertrophy is a less commonly known complication of autologous fat transfer. We present a 32-year-old female with left hemifacial atrophy associated with systemic sclerosis, who was treated with 7 fat transfer procedures to correct the facial asymmetry. A total of 236.5 mL of fat was injected to the hemiface over a 4-year period to achieve good symmetry. A progressively enlarging, painless, soft mass over the left parotid region was noted at 3 months after the final fat transfer procedure. Magnetic resonance imaging showed a markedly enlarged bulk of subcutaneous fat over the left cheek with no evidence of necrosis, edema, or pathologic enhancement. Concurrent weight gain was noted secondary to additional nutritional input. The patient’s aesthetic, symptomatic, and functional concerns led to the subsequent removal of 115 mL fat by liposuction. Level of Evidence: 5

Purpose: This study aimed to assess the inter-platform reproducibility of ultrasound attenuation examination in patients with nonalcoholic fatty liver disease (NAFLD).Methods: Between March 2021 and April 2021, patients with clinically suspected or known NAFLD were prospectively enrolled; each patient underwent ultrasound attenuation examinations with three different platforms (Attenuation Imaging [ATI], Canon Medical System; Tissue Attenuation Imaging [TAI], Samsung Medison; and Ultrasound-Guided Attenuation Parameter [UGAP], GE Healthcare) on the same day. The mean attenuation coefficient (AC) values of the three platforms were compared using repeated-measures analysis of variance with the Bonferroni correction. To evaluate inter-platform reproducibility, the AC values obtained for each platform were compared using Bland-Altman analysis with the calculation of 95% limits of agreement (LOA), intraclass correlation coefficients (ICCs), and coefficients of variation (CVs).Results: Forty-six patients (23 men; mean age±standard deviation, 52.3±12.4 years) were enrolled. The mean AC values showed significant differences among the three platforms (0.75±0.12, 0.80±0.11, and 0.74±0.09 dB/cm/MHz for ATI, TAI, and UGAP, respectively; P

Aim: There are limited data on the feasibility of programmed death ligand-1 (PD-L1) expression as a prognostic biomarker in metastatic angiosarcoma. Patients & methods: We retrospectively collected and analyzed the data on PD-L1 expression in 70 angiosarcoma patients who were diagnosed at our center between 2005 and 2019. Results: Thirteen (19%) patients had PD-L1 expression. Metastatic angiosarcoma patients who were PD-L1-negative (n = 24) showed longer median progression-free survival (4.9 vs 1.6 months; p = 0.04) and median overall survival (OS; 10.9 vs 5.4 months; p = 0.01) than those who were PD-L1-positive (n = 4). PD-L1 status proved to be a significant factor for OS. Conclusion: Metastatic angiosarcoma patients with PD-L1 expression showed shorter survival. PD-L1 status is an independent prognostic factor for OS in metastatic angiosarcoma patients., Lay abstract Angiosarcoma, a rare subtype of sarcoma, is highly aggressive and has poor prognosis. The majority of patients are diagnosed at advanced and metastatic stages, and treatment options for these subsets of patients are limited to cytotoxic chemotherapy. Validation of prognostic markers including PD-L1 expression remain to be fully carried out in metastatic angiosarcoma. In our study, we assessed the PD-L1 expression in metastatic angiosarcoma and its role as a prognostic biomarker.

Extreme responders to anticancer therapy are rare among advanced breast cancer patients. Researchers, however, have yet to investigate treatment responses therein on the whole exome level. We performed whole exome analysis to characterize the genomic landscape of extreme responders among metastatic breast cancer patients. Clinical samples were obtained from breast cancer patients who showed exceptional responses to anti-HER2 therapy or hormonal therapy and from those who did not. Matched breast tumor tissue (somatic DNA) and blood samples (germline DNA) were collected from a total of 30 responders and 15 non-responders. Whole exome sequencing using Illumina HiSeq2500 was performed for all 45 patients (90 samples). Somatic single nucleotide variants (SNVs), indels, and copy number variants (CNVs) were identified for the genomes of each patient. Group-specific somatic variants and mutational burden were statistically analyzed. Sequencing of cancer exomes for all patients revealed 1839 somatic SNVs (1661 missense, 120 nonsense, 43 splice-site, 15 start/stop-lost) and 368 insertions/deletions (273 frameshift, 95 in-frame), with a median of 0.7 mutations per megabase (range, 0.08 to 4.2 mutations per megabase). Responders harbored a significantly lower nonsynonymous mutational burden (median, 26 vs. 59, P = 0.02) and fewer CNVs (median 13.6 vs. 97.7, P = 0.05) than non-responders. Multivariate analyses of factors influencing progression-free survival showed that a high mutational burden and visceral metastases were significantly related with disease progression. Extreme responders to treatment for metastatic breast cancer are characterized by fewer nonsynonymous mutations and CNVs., Lim, Kim and Jung et al. report a whole-exome sequence analysis of 30 Korean patients showing extreme treatment responses for metastatic breast cancer. They find that compared to non-responders, extreme responders have fewer nonsynonymous mutations and copy number variants.

To determine the relative frequency and change of malignant lymphoma in Korea according to the 4th World Health Organization (WHO) classification and compare with previous reports. Between 2015 and 2016, 7737 new patients with malignant lymphoma were enrolled from 31 institutes, with their clinicopathologic information obtained, and evaluated for the relative frequency of lymphoma subtypes. The relative frequency of non-Hodgkin lymphoma (NHL) was 94.8%, and that of Hodgkin lymphoma (HL) was 5.2%. B cell lymphomas accounted for 83.1% of all NHLs; T/natural killer (NK) cell lymphomas, 16.4%; and immunodeficiency-associated lymphoproliferative disorders, 0.5%. The most common NHL subtypes were diffuse large B cell (41.5%), extranodal marginal zone (MALT, 19.8%), follicular (7.5%), NK/ T cell (4.2%), and peripheral T cell lymphomas, not otherwise specific (PTCL, NOS, 3.4%). Nodular sclerosis was the predominant HL subtype (48.5%), followed by mixed cellularity (28.7%), lymphocyte-rich (6.8%), lymphocyte-depleted (1.5%), lymphocyte-predominant (2.8%), and unclassified HL (11.8%). Compared with a previous report, increased B cell lymphomas (77.6–83.1%) and slightly decreased NK/T cell lymphomas and PTCL were observed. The incidence of follicular lymphoma increased by more than 2.5-fold (2.9–7.5%). Incidence rates of newly diagnosed lymphomas were lower for HL and higher for extranodal NHL, MALT, and nasal type NK/T cell lymphomas in Korea than those in Western countries. A slight increase in the relative frequency of B cell lymphoma and a prominent increase in follicular lymphoma may be attributed to refined diagnostic criteria and Westernized disease patterns.

Background/aims This study was to evaluate the clinical significance of infusion-related reaction (IRR) of rituximab in diffuse large B-cell lymphoma (DLBCL) patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) as a first-line chemotherapy. Methods The medical records of 326 patients diagnosed with DLBCL were re trospectively analyzed. Both doctor's progress records and nursing records were reviewed. IRR was graded according to the National Cancer Institute Common Terminology Criteria. Results IRR was not associated with overall survival (OS) or progression-free survival (PFS) of DLBCL patients as compared to those who did not have IRR (OS: median 78.0 months vs. 69.0 months, p = 0.700; PFS: median 65.4 months vs. 64.0 months, p = 0.901). IRR grade did not affect OS or PFS. B symptoms was independently associated with IRR (hazard ratio [HR], 1.850; 95% confidence interval [CI], 1.041 to 3.290; p = 0.036). Further, bone marrow involvement was independently associated with re-IRR (HR, 4.904; 95% CI, 0.767 to 3.118; p = 0.029). Conclusion Our study shows that IRR of rituximab is not associated with OS or PFS of DLBCL patients who received R-CHOP. Furthermore, our study suggests a need for more careful observation for IRR in patients with B symptoms or bone marrow involvement.

Background There are limited data on the long-term outcome of platinum chromium-based everolimus-eluting stents (PtCr-EES) vs. cobalt chromium-based zotarolimus-eluting stents (CoCr-ZES).Methods and Results:A total of 3,755 patients undergoing percutaneous coronary intervention (PCI) were randomized 2:1 to PtCr-EES or CoCr-ZES, and 96.0% of patients completed the 3-year clinical follow-up. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR). At 3 years, TLF occurred in 5.3% and in 5.4% of the PtCr-EES and CoCr-ZES groups, respectively (hazard ratio 0.978; 95% confidence interval 0.730-1.310, P=0.919). There were no significant differences in the individual components of TLF. Routine angiographic follow-up was performed in 38.9% of the total patients. In a landmark analysis of the subgroup that had follow-up angiography, the clinically-driven TLR rate of CoCr-ZES was significantly higher than PtCr-EES group during the angiography follow-up period (P=0.009). Overall definite and probable stent thrombosis rates were very low in both groups (0.5% vs. 0.6%, P=0.677). Conclusions PtCr-EES and CoCr-ZES had similar and excellent long-term outcomes in both efficacy and safety after PCI in an all-comer population.

BACKGROUND To the authors' knowledge, the indications for radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC) are unclear; treatment decisions are based on physician judgment. The objective of the current study was to identify the degree of concordance between postsurgical RAI therapy recommended by Watson for Oncology (WFO), a clinical decision support system for oncological therapy, and that recommended by physicians for patients with DTC. METHODS The current retrospective cohort study included 207 patients with DTC who underwent thyroidectomy between 2017 and 2018. Treatment recommendations were considered concordant if WFO rendered recommendations consistent with those of the physicians. RESULTS Treatment recommendations were concordant for 160 patients (77%). The concordance rate significantly differed according to the American Thyroid Association (ATA) risk category (P

Background To investigate the prognostic impact of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement for the overall survival (OS) of patients with surgically treated lung adenocarcinomas. Methods A total of 689 patients with stage I–III lung adenocarcinomas (male:female = 334:355; median age, 64 years) underwent complete surgical resection between 2007 and 2013. The prognostic impact of EGFR mutation and ALK rearrangement on OS was analyzed using Cox regression analysis. Certain clinicopathological prognostic factors (i.e., age, sex, smoking status, nodule type, solid portion size, pathologic stage, adenocarcinoma subtype, and history of adjuvant chemotherapy) were included for adjustments of the hazard ratio (HR). Results EGFR mutation was observed in 438 patients (64%) and ALK rearrangement was seen in 28 patients (4%). Multivariable‐adjusted Cox regression demonstrated that the prognostic effect of EGFR mutation on OS differed by age (HR, exp.[−5.199 + 0.064*age]). The adjusted HR for EGFR mutation was 0.14 (95% CI: 0.05–0.36; P 0.05). Conclusions EGFR mutation was independently prognostic of the long‐term outcomes of patients with surgically treated lung adenocarcinomas. A more favorable prognostic effect was seen in younger than in older patients. ALK rearrangement was not associated with OS.

Early detection and accurate monitoring of cancer is important for improving clinical outcomes. Endoscopic biopsy and/ or surgical resection specimens are the gold standard for diagnosing gastric cancer and are also useful for selecting therapeutic strategies based on the analysis of genomic/ immune parameters. However, these approaches cannot be easily performed because of their invasiveness and because these specimens do not always reflect tumor dynamics and drug sensitivities during therapeutic processes, especially chemotherapy. Accordingly, many researchers have tried to develop noninvasive novel biomarkers that can monitor realtime tumor dynamics for early diagnosis, prognostic evaluation, and prediction of recurrence and therapeutic efficacy. Circulating tumor cells (CTCs) are metastatic cells that are released from the primary tumors into the blood stream and comprise a crucial step in hematogenous metastasis. CTCs, as a liquid biopsy, have received a considerable amount of attention from researchers since they are easily accessible in peripheral blood, avoiding the invasiveness associated with traditional biopsy techniques; they can also be used to derive clinical information for monitoring disease status. In this review, with respect to CTCs, we summarize the metastatic cascade, detection methods, clinical applications, and prospects for patients with gastric cancer. (Gut Liver 2019;13:394-401)

BACKGROUND Thyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete. METHODS This study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health. RESULTS At baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL, P

PURPOSE: To examine effects of a postnatal care program on self-efficacy, self-management, and glycemic control in women with gestational diabetes mellitus (GDM). METHODS: A non-equivalent control group non-synchronized quasi-experimental design was used. Sixty-two women with GDM were enrolled and assigned to either an experimental group (n=30) or a control group (n=32). The experimental group received an intervention which was postnatal care program for women with GDM. The postnatal care program for GDM included an individual education with leaflet and mobile web-based video with three times of telephone counseling. Effects of the intervention were measured with self-efficacy, self-management questionnaire, and a 75 g oral glucose tolerance test (75g OGTT). Statistical significance was examined using independent t-test and χ2-test. RESULTS: Although there was no significant difference in 75g OGTT (χ2=.11, p=.748) or self-management (t=−1.28, p=.206), there was a statistically significant increase in self-efficacy (t=−2.02, p=.048) in the experimental group compared to that in the control group. CONCLUSION: A postnatal care program is needed for women with GDM to improve their self-efficacy. Further studies are warranted to improve self-management and glycemic control through tailored education for GDM postpartum women.

Background Pazopanib, a multitargeted tyrosine kinase inhibitor, is recommended as the standard treatment for refractory soft tissue sarcoma (STS). However, there are comparatively few molecular determinants for predicting pazopanib efficacy. Based on correlative studies regarding the predictive impact of PD-L1, we investigated the clinical relevance of PD-L1 expression and evaluated its value for predicting pazopanib efficacy. Methods Tumour tissues from patients with advanced STS who went on to receive pazopanib were assessed for PD-L1 expression. Immunohistochemistry was performed using an anti-PD-L1 antibody, and the PD-L1 tumour proportion score (TPS) was calculated as the percentage of at least 100 viable cells with positive expression, defined as TPS ≥ 1%. Results Among the 67 patients, 8 (11.9%) achieved partial response and a median progression-free survival (PFS) of 4.8 months (95% CI 3.8–5.7). PD-L1 expression in tumour cells was detected in 13 (19.4%) cases and the TPS scores ranged from 1 to 100%, as follows: 0 (n = 54, 80.6%), 1–9% (n = 3, 4.5%), 10–49% (n = 9, 13.4%), and ≥ 50% (n = 1, 1.5%). PD-L1 positive tumours exhibited a poorer response to pazopanib treatment than the PD-L1 negative tumours (0% vs 14.8%, P = 0.07). PD-L1-positive tumours had significantly shorter PFS than the PD-L1-negative tumours (median PFS 2.8 vs 5.1 months, P = 0.003), and PD-L1 positivity was an independent predictor of poor response to pazopanib treatment (HR 2.77, 95% CI; 1.45–5.56, P = 0.006). Conclusion We identified that PD-L1 expression can help predict the clinical outcome of patients with advanced STS treated with pazopanib. Based on our study, stratification should be actively considered in order to identify patients who will benefit from pazopanib or further therapeutic strategies for future clinical trials.

To investigate clinical and CT factors associated with local resectability in patients with nonmetastatic pancreatic cancers after neoadjuvant chemotherapy ± radiation therapy (CRT). This retrospective study included consecutive patients with nonmetastatic pancreatic cancers who underwent neoadjuvant CRT between June 2009 and June 2019. Tumor size, tumor-vascular contact with artery/vein, and local resectability categories (resectable, borderline resectable, or locally advanced) were assessed at baseline and post-CRT CT. Baseline and post-CRT carbohydrate antigen (CA) 19-9 levels were also assessed. Clinical or imaging features related to R0 resection were determined using logistic regression analysis. A total of 179 patients (mean age, 62.4 ± 9.3 years; 92 men) were included. After neoadjuvant CRT, 105 (58.7%) patients received R0 resection, while 74 (41.3%) did not. R0 resection rates were significantly different according to post-CRT CT resectability categories (p < 0.001): 82.8% (48/58), 70.1% (47/67), and 18.5% (10/54) for resectable, borderline resectable, and locally advanced disease, respectively. For post-CRT borderline resectable disease, ≥ 50% decrease in CA 19-9 was significantly associated with R0 resection (odds ratio (OR), 3.160; p = 0.02). For post-CRT locally advanced disease, small post-CRT tumor size ≤ 2 cm (OR, 9.668; p = 0.026) and decreased tumor-arterial contact (OR, 24.213; p = 0.022) were significantly associated with R0 resection. Post-CRT CT resectability categorization may be useful for the assessment of R0 resectability in patients with pancreatic cancer following neoadjuvant CRT. Additionally, ≥ 50% decrease in CA 19-9 was associated with R0 resection in post-CRT borderline resectable disease, while small post-CRT tumor size and decreased tumor-arterial contact were with locally advanced disease. • R0 resection rates following neoadjuvant chemotherapy ± radiation therapy (CRT) were 82.8%, 70.1%, and 18.5% in resectable, borderline resectable, and locally advanced disease, respectively, at post-CRT CT (p < 0.001). • For post-CRT borderline resectable disease, ≥ 50% decrease in carbohydrate antigen (CA) 19-9 was significantly associated with R0 resection. • For post-CRT locally advanced disease, small post-CRT tumor size ≤ 2 cm and decreased tumor-arterial contact were significantly associated with R0 resection.

Background: CD30 is frequently expressed in Epstein-Barr virus (EBV)-infected lymphoid cells and overexpressed in EBV-positive lymphomas. This open-labeled, multi-center, and investigator-initiated phase-II study evaluated the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory EBV-positive and CD30-positive lymphomas (NCT02388490). Methods: Twenty-five patients with relapsed or refractory EBV-positive lymphomas having CD30-positivity (≥ 1% of tumor cells) were administered with 1.8 mg/kg brentuximab vedotin intravenously every 3 weeks up to 16 cycles until disease progression. The primary endpoint was objective response rate and toxicities, duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were the secondary endpoints. Findings: Twenty-two patients (88%), median age of 65 years, were EBV-positive mature T/NK cell neoplasms (angioimmunoblastic T-cell lymphoma, n = 10; EBV-positive peripheral T-cell lymphoma, unspecified, n = 5; extranodal NK/T-cell lymphoma, nasal type, n = 4; and others, n = 3). Most patients (90%) had initial stage III/IV and 15 (60%) received ≥2 prior regimens. The objective response rate was 48% (90% CI, 31·0% to 64·3%; 12 of 25 patients), including five complete responses (20%) and seven partial responses (28%). Median DoR, PFS and OS were 10·1, 6·1, and 15·6 months, respectively. Common adverse events were peripheral neuropathy (48%), neutropenia (40%), thrombocytopenia (20%), and rashes (16%). Grade 3 and 4 adverse events were neutropenia (20%), thrombocytopenia (12%), and anemia (8%). Interpretation: Brentuximab vedotin is active and well tolerated in patients with relapsed or refractory EBV-positive and CD30-positive lymphomas. Trial Registration: (NCT02388490) Funding Statement: Takeda Pharmaceuticals Co. Ltd and Korea Health Industry Development Institute. Declaration of Interests: TMK received a research grant from AstraZeneca-KHIDI outside this work. DWK received travel and accommodation support for advisory board meeting attendance from Amgen and Daiichi-Sankyo outside this work. All other authors declare no competing interests. Seoul National University Hospital received grants from Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery and Yuhan. Ethics Approval Statement: The study was approved by the institutional review board at each participating site and written informed consent was obtained.

To explain the new changes in pathologic diagnoses of biphenotypic primary liver cancer (PLC) according to the updated 2019 World Health Organization (WHO) classification and how it impacts Liver Imaging Reporting and Data System (LI-RADS) classification using gadoxetic acid–enhanced MRI (Gd-EOB-MRI). We retrospectively included 209 patients with pathologically proven biphenotypic PLCs according to the 2010 WHO classification who had undergone preoperative Gd-EOB-MRI between January 2009 and December 2018. Imaging analysis including LI-RADS classification and pathologic review including the proportion of tumor components were performed. Frequencies of each diagnosis and subtype according to the 2010 and 2019 WHO classifications were compared, and changes in LI-RADS classification were evaluated. Univariable and multivariable analysis were performed to determine significant tumor component for LI-RADS classification. Of the 209 biphenotypic PLCs of the 2010 WHO classification, 177 (84.7%) were diagnosed as bipheonotypic PLCs, 25 (12.0%) as hepatocellular carcinomas (HCCs), and 7 (3.3%) as cholangiocarcinomas (CCAs) using the 2019 WHO classification. Of the 177 biphenotypic PLCs, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively. There were no significant differences in the proportion of LR-5 and LR-M categories between the WHO 2010 and 2019 classifications (p = 0.941). Proportion of HCC component was the only independent factor for LI-RADS classification (adjusted odds ratio, 1.02; p < 0.001). According to the 2019 WHO classification, 15% of biphenotypic PLCs from the 2010 WHO classification were re-diagnosed as HCCs or CCAs, and a substantial proportion of biphenotypic PLCs of the 2019 WHO classification could be categorized as LR-4 or LR-5 on Gd-EOB-MRI. • Among 209 diagnosed biphenotypic PLCs according to the 2010 WHO classification, 177 (84.7%) lesions were reclassified as bipheonotypic PLCs, 25 (12.0%) as HCCs, and 7 (3.3%) as CCAs using the 2019 WHO classification. • Of the 177 biphenotypic PLCs at the 2019 WHO classification, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively. • LI-RADS classification relied on the proportion of HCC component (adjusted odds ratio,1.02; p < 0.001).

Diffuse large B-cell lymphoma (DLBCL) patients with MYC/BCL2 double expression (DE) show poor prognosis and their clinical outcomes after R-CHOP therapy vary immensely. We investigated the prognostic value of DE in aggressive B-cell lymphoma patients (n = 461), including those with DLBCL (n = 417) and high-grade B-cell lymphoma (HGBL, n = 44), in a prospectively immunoprofiled cohort. DE was observed in 27.8% of DLBCLs and 43.2% of HGBLs (P = 0.058). DE-DLBCL patients were older (P = 0.040) and more frequently exhibited elevated serum LDH levels (P = 0.002), higher international prognostic index (IPI, P = 0.042), non-germinal-center B-cell phenotype (P &lt, 0.001), and poor response to therapy (P = 0.042) compared to non-DE-DLBCL patients. In R-CHOP-treated DLBCL patients, DE status predicted poor PFS and OS independently of IPI (P &lt, 0.001 for both). Additionally, in DE-DLBCL patients, older age (&gt, 60 years, P = 0.017), involvement of &sup3, 2 extranodal sites (P = 0.021), bone marrow involvement (P = 0.001), high IPI (P = 0.017), CD10 expression (P = 0.006), poor performance status (P = 0.028), and elevated LDH levels (P &lt, 0.001) were significantly associated with poor OS. Notably, DE-DLBCL patients with normal LDH levels exhibited similar PFS and OS to those of patients with non-DE-DLBCL. Our findings suggest that MYC/BCL2 DE predicts poor prognosis in DLBCL. Risk stratification of DE-DLBCL patients based on LDH levels may guide clinical decision-making for DE-DLBCL patients.

Polypharmacy is a growing and major public health issue, particularly in the geriatric population. This study aimed to examine the association between polypharmacy and the risk of hospitalization and mortality. We included 3,007,620 elderly individuals aged ≥ 65 years who had at least one routinely-prescribed medication but had no prior hospitalization within a year. The primary exposures of interest were number of daily prescribed medications (1–2, 3–4, 5–6, 7–8, 9–10, and ≥ 11) and presence of polypharmacy (≥ 5 prescription drugs per day). The corresponding comparators were the lowest number of medications (1–2) and absence of polypharmacy. The study outcomes were hospitalization and all-cause death. The median age of participants was 72 years and 39.5% were men. Approximately, 46.6% of participants experienced polypharmacy. Over a median follow-up of 5.0 years, 2,028,062 (67.4%) hospitalizations and 459,076 (15.3%) all-cause deaths were observed. An incrementally higher number of daily prescribed medications was found to be associated with increasingly higher risk for hospitalization and mortality. These associations were consistent across subgroups of age, sex, residential area, and comorbidities. Furthermore, polypharmacy was associated with greater risk of hospitalization and death: adjusted HRs (95% CIs) were 1.18 (1.18–1.19) and 1.25 (1.24–1.25) in the overall and 1.16 (1.16–1.17) and 1.25 (1.24–1.25) in the matched cohorts, respectively. Hence, polypharmacy was associated with a higher risk of hospitalization and all-cause death among elderly individuals.

Oro-facial fibrosis presents a significant disease burden in patients with systemic sclerosis, but there remains no established treatment modality. Autologous fat grafting is a minimally invasive surgical procedure that is now increasingly recognised for its regenerative capacity, propagating an expansion of heterogeneous indications beyond volume restoration, including fibrotic diseases such as systemic sclerosis. We present a 42-year-old woman with oro-facial involvement of systemic sclerosis leading to severe limitation in mouth opening and closure, with marked retraction of the lower lip and gingival display. We describe the reconstructive journey over a 12-year period, where the antifibrotic effect of autologous fat grafting served as the basis on which a series of surgical procedures were performed to achieve functional and aesthetic improvement. Autologous fat grafting provides a novel treatment modality for oro-facial skin fibrosis, previously considered a non-treatable disease manifestation of systemic sclerosis.

Oxidative stress was implicated in the functional impairment of the frontal cortex observed in early Alzheimer&rsquo, s disease (AD). To elucidate this role in an animal AD model, we assessed cognitive function of 4-month-old five familial AD (5XFAD) transgenic (Tg) mice using a learning strategy-switching task requiring recruitment of the frontal cortex and measuring levels of 4-hydroxy-2-trans-nonenal (4-HNE), a marker of oxidative stress, in their frontal cortex. Mice were sequentially trained in cued/response and place/spatial versions of the water maze task for four days each. 5XFAD and non-Tg mice exhibited equal performance in cued/response training. However, 5XFAD mice used spatial search strategy less than non-Tg mice in the spatial/place training. Immunoblot and immunofluorescence staining showed that 4-HNE levels increased in the frontal cortex, but not in the hippocampus and striatum, of 5XFAD mice compared to those in non-Tg mice. We report early cognitive deficits related to the frontal cortex and the frontal cortex&rsquo, s oxidative damage in 4-month-old 5XFAD mice. These results suggest that 4-month-old 5XFAD mice be a useful animal model for the early diagnosis and management of AD.

BACKGROUND/AIMS Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. METHODS This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher's exact test and log-rank test, were performed. RESULTS Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). CONCLUSION PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.

Highlights • Oro-facial fibrosis presents a significant disease burden in systemic sclerosis. • There is currently no treatment available for oro-facial fibrosis. • Autologous fat grafting is a novel therapeutic method for oro-facial fibrosis., Introduction Oro-facial fibrosis is a common and disabling manifestation of systemic sclerosis (SSc), causing a plethora of functional, aesthetic and social compromise, yet is without effective treatment. Autologous lipotransfer is an established minimally invasive surgical procedure that is postulated to exert anti-fibrotic effects by adipose-derived stem cells, and presents a novel method in the treatment of fibrotic conditions. This study aims to assess the safety and efficacy of autologous lipotransfer for facial involvement in SSc. Methods and analysis This is the first randomised controlled study with an open label design to assess autologous lipotransfer for oro-facial involvement in systemic sclerosis. The goals of this study are to assess the feasibility of using a range of quantitative and qualitative outcome measures to effectively measure disease severity and treatment outcome, and to assess patient acceptability for future multi-centre trials. A total of 50 participants will be randomised to a treatment or control group. The treatment group will receive autologous fat transfer to the peri-oral region by a single surgeon. Dermal fibroblasts and adipose-derived stem cells will be isolated from tissue samples. All outcome measures will be taken at baseline, then at 6 weeks, 3 months and 6 months from the time of intervention in the treatment arm, or from baseline in the control arm. Ethics and dissemination The study has ethical approval (REC reference 19/LO/0718). Results will be available to patients, patient user groups, clinicians and the public through presentations at national and international rheumatology conferences and published in peer reviewed journals. Trial registration Registered on ISRCTN registry (ISRCTN17793055).

We present a 48-year-old female patient who presented with features consistent with acquired partial lipodystrophy (APL) also known as ‘Barraquer-Simons syndrome’. It is a rare disease characterised by a gradual and progressive onset of lipoatrophy limited to the face, neck, upper limbs, thorax and abdomen and sparing the lower extremities. The resultant physical appearance can have significant psychosocial sequelae, further compounded by misdiagnosis and delay in recognition and management. Treatment is aimed at surgical correction of soft tissue destruction. Autologous fat transfer is an established plastic and reconstructive procedure that is safe and minimally invasive and can be used to reconstruct a variety of soft tissue defects and has shown to be an effective treatment modality in patients with APL.