Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). Conclusions In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

OBJECTIVE: To analyze the complications of percutaneous transthoracic needle biopsy using CT-based imaging modalities for needle guidance in comparison with fluoroscopy in a large retrospective cohort. MATERIALS AND METHODS: This study was approved by multiple Institutional Review Boards and the requirement for informed consent was waived. We retrospectively included 10568 biopsies from eight referral hospitals from 2010 through 2014. In univariate and multivariate logistic analyses, 3 CT-based guidance modalities (CT, CT fluoroscopy, and cone-beam CT) were compared with fluoroscopy in terms of the risk of pneumothorax, pneumothorax requiring chest tube insertion, and hemoptysis, with adjustment for other risk factors. RESULTS: Pneumothorax occurred in 2298 of the 10568 biopsies (21.7%). Tube insertion was required after 316 biopsies (3.0%), and hemoptysis occurred in 550 cases (5.2%). In the multivariate analysis, pneumothorax was more frequently detected with CT {odds ratio (OR), 2.752 (95% confidence interval [CI], 2.325–3.258), p < 0.001}, CT fluoroscopy (OR, 1.440 [95% CI, 1.176–1.762], p < 0.001), and cone-beam CT (OR, 2.906 [95% CI, 2.235–3.779], p < 0.001), but no significant relationship was found for pneumothorax requiring chest tube insertion (p = 0.497, p = 0.222, and p = 0.216, respectively). The incidence of hemoptysis was significantly lower under CT (OR, 0.348 [95% CI, 0.247–0.491], p < 0.001), CT fluoroscopy (OR, 0.594 [95% CI, 0.419–0.843], p = 0.004), and cone-beam CT (OR, 0.479 [95% CI, 0.317–0.724], p < 0.001) guidance. CONCLUSION: Hemoptysis occurred less frequently with CT-based guidance modalities in comparison with fluoroscopy. Although pneumothorax requiring chest tube insertion showed a similar incidence, pneumothorax was more frequently detected using CT-based guidance modalities.
Biopsy ; Biopsy, Needle ; Chest Tubes ; Cohort Studies ; Cone-Beam Computed Tomography ; Ethics Committees, Research ; Fluoroscopy ; Hemoptysis ; Image-Guided Biopsy ; Incidence ; Informed Consent ; Lung Neoplasms ; Multivariate Analysis ; Needles ; Pneumothorax ; Referral and Consultation ; Retrospective Studies ; Risk Factors

On page 323, the grant number was incorrectly numbered as HI15C1234. The correct number is HI15C3390.

OBJECTIVE: To measure the diagnostic accuracy of percutaneous transthoracic needle lung biopsies (PTNBs) on the basis of the intention-to-diagnose principle and identify risk factors for diagnostic failure of PTNBs in a multi-institutional setting. MATERIALS AND METHODS: A total of 9384 initial PTNBs performed in 9239 patients (mean patient age, 65 years [range, 20–99 years]) from January 2010 to December 2014 were included. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PTNBs for diagnosis of malignancy were measured. The proportion of diagnostic failures was measured, and their risk factors were identified. RESULTS: The overall accuracy, sensitivity, specificity, PPV, and NPV were 91.1% (95% confidence interval [CI], 90.6–91.7%), 92.5% (95% CI, 91.9–93.1%), 86.5% (95% CI, 85.0–87.9%), 99.2% (95% CI, 99.0–99.4%), and 84.3% (95% CI, 82.7–85.8%), respectively. The proportion of diagnostic failures was 8.9% (831 of 9384; 95% CI, 8.3–9.4%). The independent risk factors for diagnostic failures were lesions ≤ 1 cm in size (adjusted odds ratio [AOR], 1.86; 95% CI, 1.23–2.81), lesion size 1.1–2 cm (1.75; 1.45–2.11), subsolid lesions (1.81; 1.32–2.49), use of fine needle aspiration only (2.43; 1.80–3.28), final diagnosis of benign lesions (2.18; 1.84–2.58), and final diagnosis of lymphomas (10.66; 6.21–18.30). Use of cone-beam CT (AOR, 0.31; 95% CI, 0.13–0.75) and conventional CT-guidance (0.55; 0.32–0.94) reduced diagnostic failures. CONCLUSION: The accuracy of PTNB for diagnosis of malignancy was fairly high in our large-scale multi-institutional cohort. The identified risk factors for diagnostic failure may help reduce diagnostic failure and interpret the biopsy results.
Biopsy ; Biopsy, Fine-Needle ; Cohort Studies ; Cone-Beam Computed Tomography ; Diagnosis ; Humans ; Image-Guided Biopsy ; Lung Neoplasms ; Lung ; Lymphoma ; Needles ; Odds Ratio ; Risk Factors ; Sensitivity and Specificity

BACKGROUND/AIMS: Fecal calprotectin (FC) is known to correlate with disease activity and can be used as a predictor for relapse or treatment response in inflammatory bowel disease (IBD). We evaluated the usefulness of FC as a biomarker for disease activity in patients with IBD using both enzyme-linked immunosorbent assay (ELISA) and a quantitative point-of-care test (QPOCT). METHODS: Fecal samples and medical records were collected from consecutive patients with IBD. FC levels were measured by both ELISA and QPOCT and patient medical records were reviewed for clinical, laboratory, and endoscopic data. RESULTS: Ninety-three patients with IBD were enrolled, 55 with ulcerative colitis (UC) and 38 with Crohn's disease (CD). The mean FC-ELISA levels were 906.3 ± 1,484.9 μg/g in UC and 1,054.1 ± 1,252.5 μg/g in CD. There was a strong correlation between FC-ELISA level and clinical activity indices (p < 0.05). FC-ELISA level was significantly lower in patients with mucosal healing (MH) compared to those without MH in UC (85.5 ± 55.6 μg/g vs. 1,503.7 ± 2,129.9 μg/g, p = 0.005). The results from the QPOCT corresponded well to those from ELISA. A cutoff value of 201.3 μg/g for FC-ELISA and 150.5 μg/g for FC-QPOCT predicted endoscopic inflammation (Mayo endoscopic subscore ≥ 1) in UC with a sensitivity of 81.8% and 85.8%, respectively, and a specificity of 100% for both. CONCLUSIONS: FC was strongly associated with disease activity indices, serologic markers, and endoscopic activity in patients with IBD. QPOCT can be used more conveniently than ELISA to assess FC in clinical practice.
Colitis, Ulcerative ; Crohn Disease ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Inflammatory Bowel Diseases* ; Leukocyte L1 Antigen Complex* ; Medical Records ; Point-of-Care Systems ; Recurrence ; Sensitivity and Specificity

PURPOSE: The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. MATERIALS AND METHODS: Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m2, and the dose of HM30181A was escalated from 30-210 mg/m2. RESULTS: A total of twenty-four patients were enrolled. Only one patient experienced a dose-limiting toxicity-a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m2 of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m2 and the area under the curve of plasma concentration-time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m2. The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m2. The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m2. Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. CONCLUSION: The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m2.
Absorption ; Humans ; Maximum Tolerated Dose ; Neutropenia ; P-Glycoprotein* ; Paclitaxel* ; Pharmacokinetics ; Plasma

PURPOSE: Renal artery stenosis (RAS) causes or deteriorates hypertension and/or renal insufficiency, and is known as a progressive disease. The aim of this study is to reveal the change of renal function after stenting for RAS. METHODS: We retrospectively analyzed 66 patients between 1999 and 2005 who had stenting for RAS. Renal function was assessed by modified MDRD equation. According to baseline glomerular filtration rate (GFR), patients were divided into subgroups with group A (n=37, GFR > or =60 mL/min/ 1.73m2) or group B (n=29, GFR <60 mL/min/1.73m2). Clinical parameters were compared between two groups. RESULTS: A total of 66 patients (male:female=37:29) were studied. The mean age was 61+/-12 years old and the mean follow-up duration was 54+/-27 months. Sixty-one (92.4%) patients had hypertension, 20 (30.3%) had diabetes, and 48 (73%) had unilateral RAS. Group B was older than group A (65+/-9 vs. 58+/-14 years old). The mean body mass index of group B was higher than that of group A. In group A, there was a decrease in the MDRD GFR (from 75+/-11 to 70+/-15 mL/min/1.73m2; p=0.038). In contrast, in group B there was no significant change in the MDRD GFR (from 48+/-9 to 48+/-15 mL/min/1.73m2). In group A and group B, renal function has been improved in 3% and 24%, and stabilized in 70% and 52%, respectively. CONCLUSION: Stenting for RAS has renal function preserving effect in patients with renal insufficiency. Therefore, stenting should be considered as a treatment modality in RAS patients even with deteriorated renal function.
Body Mass Index ; Constriction, Pathologic ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Hypertension ; Renal Artery ; Renal Artery Obstruction ; Renal Insufficiency ; Retrospective Studies ; Stents