Acoustic radiation force impulse (ARFI) elastography predicts the presence of esophageal varices (EVs). We investigated whether an ARFI-based prediction model can assess EV bleeding (EVB) risk in patients with cirrhosis.The records of 262 patients with cirrhosis who underwent ARFI elastography and endoscopic surveillance at two institutions in 2008 to 2013 were retrospectively reviewed, and ARFI-spleen diameter-to-platelet ratio scores (ASPS) were calculated.The median patient age (165 men, 97 women) was 56 years. The median ARFI velocity, spleen diameter, platelet count, and ASPS were 1.7 m/sec, 10.1 cm, 145×109/L, and 1.16, respectively. During the median 38-month follow-up, 61 patients experienced EVB. Among all patients (179 without EVs and 83 with EVs), the cutoff value that maximized the sum of the sensitivity (73.1%) and specificity (78.4%) (area under receiver operating characteristic curve [AUROC], 0.824) for predicting EVB was 2.60. The cumulative EVB incidence was significantly higher in patients with ASPS ≥2.60 than in those with ASPS <2.60 (p<0.001). Among patients with EVs (n=83), 49 had high-risk EVs (HEVs), and 22 had EVB. The cumulative EVB incidence was significantly higher in HEV patients than in low-risk EV patients (p=0.037). At an ASPS of 4.50 (sensitivity, 66.7%; specificity, 70.6%; AUROC, 0.691), the cumulative EVB incidence was significantly higher in patients with a high ASPS than in those with a low ASPS (p=0.045). A higher ASPS independently predicted EVB (hazard ratio, 4.072; p=0.047).ASPS can assess EVB risk in patients with cirrhosis. Prophylactic management should be considered for patients with HEVs and ASPS ≥4.50.
Abstract Background Despite recent advances in treating non‐small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs), their role in ALK‐positive NSCLC patients is unclear. We investigated the efficacy of ICIs in patients with ALK‐positive NSCLC. Methods Between 2011 and 2018, a total of 14 ALK‐positive NSCLC patients treated with ICIs were evaluated retrospectively. Clinicopathologic features including age, PD‐L1 expression, and treatment outcomes were analyzed. RNA expression level and cytolytic activity by ALK positivity were analyzed using The Cancer Genome Atlas (TCGA) and National Cancer Center Research Institute (NCCRI) data sets. Results A total of 13 patients (92.9%) received ALK inhibitors. Patients received a median of three (range 2–8) courses of therapy. The study included nine patients (64.3%) who were PD‐L1‐high (>50%) and four (28.6%) who were PD‐L1‐low (<50%). The objective response rate was 14.3% (2/14). The median progression‐free survival time was 2.18 months (95% confidence interval [CI] 1.13 months‐not reached [NR]). The median overall survival time was 5.67 months (95% CI 3.00 months‐NR). RNA expression levels of CD274 were similar between the ALK‐positive and negative groups in both TCGA and NCCRI datasets. RNA levels of CD8A in both TCGA and NCCRI data sets were nonsignificantly lower in the ALK‐positive group. Cytolytic activity scores including interferon‐γ‐related response were lower in the ALK‐positive group in the NCCRI but not TCGA dataset. Conclusions Despite high PD‐L1‐positive rates, ICIs show limited efficacy in ALK‐positive NSCLC. Decreased interferon‐γ‐related response may underlie these findings.
Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, "41%, and 36%" for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.
Background Immune checkpoint inhibitors (ICIs) are one of the main pillars of cancer therapy. Since other studies such as clinical trial and retrospective study have limitations for detecting the immune-related adverse events (irAEs) characterized by unpredictable onset, nonspecific symptoms and wide clinical spectrum, we aimed to identify the incidence of irAEs and to detect and evaluate the signals using real-world data. Methods Cancer patients treated with anticancer medications were analyzed using the nationwide health insurance claims database of South Korea from 2017 to 2019, and Clinical Data Warehouse (CDW) database of Asan Medical Center (AMC), a tertiary referral hospital, from 2012 to 2019. AEs of ICI users were compared with those of non-ICI anticancer medication users. PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab) were evaluated. We defined an AE as a newly added diagnosis after the ICI prescription using an ICD-10 diagnostic code. A signal was defined as an AE that was detected by any one of the four indices of data mining: hazard ratio (HR), proportional claims ratio (PCR), claims odds ratio (COR), or information component (IC). All detected signals were reviewed and classified into well-known or potential irAEs. Signal verification was performed for targeted AEs using CDW of AMC using diagnostic codes and text mining. Results We identified 118 significant signals related to ICI use. We detected 31 well-known irAEs, most of which were endocrine diseases and skin diseases. We also detected 33 potential irAEs related to disorders in the nervous system, eye, circulatory system, digestive system, skin and subcutaneous tissues, and bones. Especially, portal vein thrombosis and bone disorders such as osteoporosis with pathological fracture and fracture of shoulder, upper arm, femur, and lower leg showed high HR in ICI users than in non-ICI users. The signals from hospital database were verified using diagnostic codes and text mining. Conclusion This real-world data analysis demonstrated an efficient approach for signal detection and evaluation of ICI use. An effective real-world pharmacovigilance system of the nationwide claims database and the EMR could complement each other in detecting significant AE signals.
Endoscopic bile duct decompression using bilateral self-expandable metallic stents (SEMSs) deployed via a stent-in-stent (SIS) method is considered a preferred procedure for malignant hilar biliary obstruction (MHBO). However, occlusion thereof occurs frequently. Here, we investigated stent patency duration and risk factors related to stent obstruction with bilateral SIS placement for MHBO at two large centers.The present study reviewed data on patients with MHBO who underwent endoscopic biliary drainage using the SIS method. Clinical outcomes, including stent patency duration and patient overall survival, were analyzed. Factors associated with stent patency were evaluated using Cox proportional hazards models.Seventy patients with MHBO underwent endoscopic biliary drainage using the SIS method. Median age was 68 years old, and median follow-up duration was 140 days (interquartile range, 57-329). The proportion of high-grade MHBOs (Bismuth type IV) was 57.1%. Median stent patency duration with the SIS method was 108 days according to Kaplan-Meier curves. Median patient survival analyzed by the Kaplan-Meier method was 181 days. Multivariate analysis indicated that higher baseline bilirubin (> 6.1 mg/dL) as an independent risk factor related to stent patency (p<0.05).In endoscopic biliary decompression using SEMS placed with the SIS method, obstructive jaundice was a risk factor for stent patency. The SIS method for high-grade MHBO showed short stent patency.
Abstract Although immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months [95% confidence interval (CI), 13.4 to not reached (NR)], 11.7 months [95% CI, 9.5–21.1], and 5.4 months [95% CI, 2.6-NR], respectively, P < 0.001). Patients with oligo-progression had significantly longer OS after AR than did the multi-progression patients (18.9 months [95% CI, 10.6-NR] vs. 8.8 months [95% CI, 5.7-NR], P = 0.04). No significant difference in progression-free survival was observed between the subsequent chemotherapy and the ICI after AR groups ( P = 0.723). Patients with AR after ICI treatment had a unique progression pattern with oligo-progression and high rates of progression only in the lymph nodes. Local treatment and/or continuation of ICIs beyond AR might be an effective option.
Abstract Background & Aims Wisteria floribunda agglutinin‐positive human Mac‐2 binding protein ( WFA + ‐M2 BP ) can be used to assess the degree of liver fibrosis, but few studies have investigated its prognostic utility. We evaluated whether serum WFA + ‐M2 BP can predict the development of hepatocellular carcinoma ( HCC ) in chronic hepatitis B ( CHB ) patients. Methods A total of 1323 CHB patients with WFA + ‐M2 BP test results between 2009 and 2011 were included in this retrospective analysis. Results The mean age of patients (793 men) was 51.0 years. During the follow‐up period (median 60.3 months), 52 (3.9%) patients developed HCC . Age, the proportion of male gender, the presence of diabetes and cirrhosis, and levels of aspartate aminotransferase, alpha‐foetoprotein, and WFA + ‐M2 BP were significantly greater in patients with HCC than in those without HCC , whereas serum albumin levels and platelet counts were significantly lower in patients with HCC than in those without HCC (all P <.05). In multivariate analysis, WFA + ‐M2 BP level was an independent predictor of HCC development (adjusted hazard ratio 1.143, 95% CI: 1.139‐1.829), along with male gender and diabetes (all P <.05). In patients without cirrhosis (n=1087), WFA + ‐M2 BP levels ≥1.8 were associated with a higher risk of HCC development ( P <.001 by log‐rank test), whereas WFA + ‐M2 BP levels ≥1.8 tended to be associated with a higher risk of HCC development in patients with cirrhosis (n=236) ( P =.073 by log‐rank test). Conclusions WFA + ‐M2 BP level can independently predict HCC development. Further studies should investigate whether WFA + ‐M2 BP level could be incorporated into surveillance strategies for CHB patients.
Gamma-glutamyl transpeptidase-to-platelet ratio (GPR) can evaluate the degree of liver fibrosis. We investigated whether GPR can predict the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients.We retrospectively evaluated 1109 CHB patients that were enrolled between 2006 and 2012, and all patients had available data for the assessment of GPR at enrollment. Three risk groups were defined according to tertile stratification: GPR < 0.05, low-risk (n = 370 [33.4%]); GPR 0.05-0.24, intermediate-risk (n = 370 [33.4%]); and GPR > 0.24, high-risk (n = 369 [33.2%]). The predictive accuracy of GPR, fibrosis-4 (FIB-4), and aspartate transaminase-to-platelet ratio index (APRI) in predicting HCC development was tested.The median age of the study population (746 men and 363 women) was 50 years. During the follow-up period (median, 32 months; interquartile range, 19-57 months), 69 (6.2%) patients developed HCC. Together with age, male gender, diabetes mellitus, antiviral therapy, serum albumin, and alpha-fetoprotein, the relative risk of HCC development significantly increased from low-risk to high-risk GPR groups (hazard ratio [HR], up to 29.5; adjusted HR, up to 10.6; all P < 0.05). In addition, FIB-4 was calculated to be a significantly high relative risk of HCC development (HR, up to 20.1; adjusted HR, up to 7.3; all P < 0.05), whereas APRI was not (P = 0.168). The cumulative incidence of HCC development was significantly different among three risk groups (P < 0.001, log-rank test).This study suggests that GPR can be used as a noninvasive marker to assess the risk of HCC development in CHB patients.
Abstract Despite the increasing number of female cancer survivors, uncertainty remains regarding potential adverse health outcomes for their offspring. Comprehensive population-based studies would be invaluable for female cancer survivors in making decisions about their future. This study uses the National Health Information Database to investigate perinatal and long-term outcomes of offspring born to mothers with a history of cancer. In a South Korean cohort of 95,264 women aged 15–40 diagnosed with cancer between 2007 and 2010, we evaluated the outcomes of 15,221 children born to 11,092, cancer survivors. We selected 147,727 women without a history of cancer and 201,444 children as a control group. Our study found that children of female cancer survivors have a significantly higher odds ratio of primary outcomes including preterm birth, low birth weight, neonatal intensive care unit admission, and death. While there was no difference in the rate of death within 1 year of birth between the two groups, the total death rate during the follow-up period was significantly higher in children born to mothers with cancer. After adjusting for gestational age and birth weight, there was no statistically significant increased hazard ratio of secondary outcomes including cancer, chromosomal abnormalities, cerebral palsy, delayed development, epilepsy, language disorder, or hearing impairment.
Abstract Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogenous T-cell lymphoid malignancy. The prognostic value of C-reactive protein-to-albumin ratio (CAR) has never been assessed in PTCL. This study retrospectively reviewed the medical records of 76 patients diagnosed with various subtypes of PTCL. The value of 0.794 was identified as the most discriminative point of CAR, and clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), were compared between the high (>0.794, n=25) and low (≤0.794, n=51) CAR groups. After induction therapy, complete response was achieved in 39 patients (76.5%) and 8 patients (32.0%) in the low and high CAR groups, respectively (p<0.001). During the median follow-up of 57.5 months, the high CAR group had significantly worse 5-year PFS (6.6% vs. 43.8%, p<0.0001) and 5-year OS (20.2% vs. 62.2%, p<0.0001) rates. With adjustment for the International Prognostic Index (≥3), Prognostic Index for PTCL-unspecified (≥3), and T cell score (≥2), high CAR remained a significant prognostic factor for PFS (hazard ratio [HR]: 4.01, 95% confidence interval [CI] 2.04–7.86, p<0.001) and OS (HR: 2.97, 95% CI: 1.33–6.64, p=0.008). CAR might play a complementary role in predicting prognosis in patients with PTCL, considering its simplicity, objectivity, and easy accessibility.
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