Targetoid Primary Liver Malignancy in Chronic Liver Disease: Prediction of Postoperative Survival Using Preoperative MRI Findings and Clinical Factors

Objective@#We aimed to assess and validate the radiologic and clinical factors that were associated with recurrence and survival after curative surgery for heterogeneous targetoid primary liver malignancies in patients with chronic liver disease and to develop scoring systems for risk stratification. @*Materials and Methods@#This multicenter retrospective study included 197 consecutive patients with chronic liver disease who had a single targetoid primary liver malignancy (142 hepatocellular carcinomas, 37 cholangiocarcinomas, 17 combined hepatocellular carcinoma-cholangiocarcinomas, and one neuroendocrine carcinoma) identified on preoperative gadoxetic acid-enhanced MRI and subsequently surgically removed between 2010 and 2017. Of these, 120 patients constituted the development cohort, and 77 patients from separate institution served as an external validation cohort. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were identified using a Cox proportional hazards analysis, and risk scores were developed. The discriminatory power of the risk scores in the external validation cohort was evaluated using the Harrell C-index. The Kaplan–Meier curves were used to estimate RFS and OS for the different risk-score groups. @*Results@#In RFS model 1, which eliminated features exclusively accessible on the hepatobiliary phase (HBP), tumor size of 2–5 cm or > 5 cm, and thin-rim arterial phase hyperenhancement (APHE) were included. In RFS model 2, tumors with a size of > 5 cm, tumor in vein (TIV), and HBP hypointense nodules without APHE were included. The OS model included a tumor size of > 5 cm, thin-rim APHE, TIV, and tumor vascular involvement other than TIV. The risk scores of the models showed good discriminatory performance in the external validation set (C-index, 0.62–0.76). The scoring system categorized the patients into three risk groups: favorable, intermediate, and poor, each with a distinct survival outcome (all log-rank p < 0.05). @*Conclusion@#Risk scores based on rim arterial enhancement pattern, tumor size, HBP findings, and radiologic vascular invasion status may help predict postoperative RFS and OS in patients with targetoid primary liver malignancies.

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study

Background@#Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size. @*Methods@#We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression. @*Results@#High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC. @*Conclusions@#Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.

Is the Mixed Use of Magnetic Resonance Enterography and Computed Tomography Enterography Adequate for Routine Periodic Follow-Up of Bowel Inflammation in Patients with Crohn’s Disease?

Objective@#Computed tomography enterography (CTE) and magnetic resonance enterography (MRE) are considered substitutes for each other for evaluating Crohn’s disease (CD). However, the adequacy of mixing them for routine periodic follow-up for CD has not been established. This study aimed to compare MRE alone with the mixed use of CTE and MRE for the periodic follow-up of small bowel inflammation in patients with CD. @*Materials and Methods@#We retrospectively compared two non-randomized groups, each comprising 96 patients with CD. One group underwent CTE and MRE (MRE followed by CTE or vice versa) for the follow-up of CD (interval, 13–27 months [median, 22 months]), and the other group underwent MRE alone (interval, 15–26 months [median, 21 months]). However, these two groups were similar in clinical characteristics. Three independent readers from three different institutions determined whether inflammation had decreased, remained unchanged, or increased within the entire small bowel and the terminal ileum based on sequential enterography of the patients after appropriate blinding. We compared the two groups for inter-reader agreement and accuracy (terminal ileum only) using endoscopy as the reference standard for enterographic interpretation. @*Results@#The inter-reader agreement was greater in the MRE alone group for the entire small bowel (intraclass correlation coefficient [ICC]: 0.683 vs. 0.473; p = 0.005) and the terminal ileum (ICC: 0.656 vs. 0.490; p = 0.030). The interpretation accuracy was higher in the MRE alone group without statistical significance (70.9%–74.5% vs. 57.9%–64.9% in individual readers; adjusted odds ratio = 3.21; p = 0.077). @*Conclusion@#The mixed use of CTE and MRE was inferior to MRE alone in terms of inter-reader reliability and could probably be less accurate than MRE alone for routine monitoring of small bowel inflammation in patients with CD. Therefore, the consistent use of MRE is favored for this purpose.

LI-RADS Treatment Response versus Modified RECIST for Diagnosing Viable Hepatocellular Carcinoma after Locoregional Therapy: A Systematic Review and Meta-Analysis of Comparative Studies

Purpose@#To systematically compare the performance of liver imaging reporting and data system treatment response (LR-TR) with the modified Response Evaluation Criteria in Solid Tumors (mRECIST) for diagnosing viable hepatocellular carcinoma (HCC) treated with locoregional therapy (LRT). @*Materials and Methods@#Original studies of intra-individual comparisons between the diagnostic performance of LR-TR and mRECIST using dynamic contrast-enhanced CT or MRI were searched in MEDLINE and EMBASE, up to August 25, 2021. The reference standard for tumor viability was surgical pathology. The meta-analytic pooled sensitivity and specificity of the viable category using each criterion were calculated using a bivariate random-effects model and compared using bivariate meta-regression. @*Results@#For five eligible studies (430 patients with 631 treated observations), the pooled per-lesion sensitivities and specificities were 58% (95% confidence interval [CI], 45%–70%) and 93% (95% CI, 88%–96%) for the LR-TR viable category and 56% (95% CI, 42%–69%) and 86% (95% CI, 72%–94%) for the mRECIST viable category, respectively. The LR-TR viable category provided significantly higher pooled specificity (p < 0.01) than the mRECIST but comparable pooled sensitivity (p = 0.53). @*Conclusion@#The LR-TR algorithm demonstrated better specificity than mRECIST, without a significant difference in sensitivity for the diagnosis of pathologically viable HCC after LRT.

Diagnostic workup of inherited platelet disorders

Inherited platelet disorders (IPDs) can cause mucocutaneous bleeding due to impaired primary hemostatic function of platelets, thrombocytopenia, or both. Recent advances in molecular technology can help identify many genes related to platelet biology, control the overall steps of megakaryopoiesis, and cause IPD. In this article, currently available laboratory tools for diagnosing IPDs with the characteristic laboratory features of each IPD are reviewed, and a general diagnostic approach for the evaluation of IPD patients is presented.

Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background/Aims@#Posthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model. @*Methods@#A total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model. @*Results@#PHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (≤3.8 g/dL; OR 15.89, 95% CI 2.41 to 104.82, p=0.004), major hepatic resection (OR 4.16, 95% CI 1.40 to 12.38, p=0.014), higher albumin-bilirubin score (>–0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum α-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF. @*Conclusions@#Our novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF.

Usefulness of Arterial Subtraction in Applying Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Algorithm to Gadoxetic Acid-Enhanced MRI

Objective@#We aimed to evaluate the usefulness of arterial subtraction images for predicting the viability of hepatocellular carcinoma (HCC) after locoregional therapy (LRT) using gadoxetic acid-enhanced MRI and the Liver Imaging Reporting and Data System treatment response (LR-TR) algorithm. @*Materials and Methods@#This study included 90 patients (mean age ± standard deviation, 57 ± 9 years) who underwent liver transplantation or resection after LRT and had 73 viable and 32 nonviable HCCs. All patients underwent gadoxetic acid-enhanced MRI before surgery. Two radiologists assessed the presence of LR-TR features, including arterial phase hyperenhancement (APHE) and LR-TR categories (viable, nonviable, or equivocal), using ordinary arterial-phase and arterial subtraction images. The reference standard for tumor viability was surgical pathology. The sensitivity of APHE for diagnosing viable HCC was compared between ordinary arterial-phase and arterial subtraction images. The sensitivity and specificity of the LR-TR algorithm for diagnosing viable HCC was compared between the use of ordinary arterial-phase and the use of arterial subtraction images.Subgroup analysis was performed on lesions treated with transarterial chemoembolization (TACE) only. @*Results@#The sensitivity of APHE for viable HCCs was higher for arterial subtraction images than ordinary arterial-phase images (71.2% vs. 47.9%; p 0.999). In a subgroup of 63 lesions treated with TACE only, the use of arterial subtraction images showed a significant increase in sensitivity (81.4% [35/43] vs. 67.4% [29/43]; p = 0.031) without significant decrease in specificity (85.0% [17/20] vs. 90.0% [18/20]; p > 0.999). @*Conclusion@#Use of arterial subtraction images compared with ordinary arterial-phase images improved the sensitivity while maintaining specificity for diagnosing viable HCC after LRT using gadoxetic acid-enhanced MRI and the LR-TR algorithm.

Radiologic Evaluation and Structured Reporting Form for Extrahepatic Bile Duct Cancer: 2019 Consensus Recommendations from the Korean Society of Abdominal Radiology

Radiologic imaging is important for evaluating extrahepatic bile duct (EHD) cancers; it is used for staging tumors and evaluating the suitability of surgical resection, as surgery may be contraindicated in some cases regardless of tumor stage. However, the published general recommendations for EHD cancer and recommendations guided by the perspectives of radiologists are limited.The Korean Society of Abdominal Radiology (KSAR) study group for EHD cancer developed key questions and corresponding recommendations for the radiologic evaluation of EHD cancer and organized them into 4 sections: nomenclature and definition, imaging technique, cancer evaluation, and tumor response. A structured reporting form was also developed to allow the progressive accumulation of standardized data, which will facilitate multicenter studies and contribute more evidence for the development of recommendations.

Usefulness of Arterial Subtraction in Applying Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Algorithm to Gadoxetic Acid-Enhanced MRI

Objective@#We aimed to evaluate the usefulness of arterial subtraction images for predicting the viability of hepatocellular carcinoma (HCC) after locoregional therapy (LRT) using gadoxetic acid-enhanced MRI and the Liver Imaging Reporting and Data System treatment response (LR-TR) algorithm. @*Materials and Methods@#This study included 90 patients (mean age ± standard deviation, 57 ± 9 years) who underwent liver transplantation or resection after LRT and had 73 viable and 32 nonviable HCCs. All patients underwent gadoxetic acid-enhanced MRI before surgery. Two radiologists assessed the presence of LR-TR features, including arterial phase hyperenhancement (APHE) and LR-TR categories (viable, nonviable, or equivocal), using ordinary arterial-phase and arterial subtraction images. The reference standard for tumor viability was surgical pathology. The sensitivity of APHE for diagnosing viable HCC was compared between ordinary arterial-phase and arterial subtraction images. The sensitivity and specificity of the LR-TR algorithm for diagnosing viable HCC was compared between the use of ordinary arterial-phase and the use of arterial subtraction images.Subgroup analysis was performed on lesions treated with transarterial chemoembolization (TACE) only. @*Results@#The sensitivity of APHE for viable HCCs was higher for arterial subtraction images than ordinary arterial-phase images (71.2% vs. 47.9%; p 0.999). In a subgroup of 63 lesions treated with TACE only, the use of arterial subtraction images showed a significant increase in sensitivity (81.4% [35/43] vs. 67.4% [29/43]; p = 0.031) without significant decrease in specificity (85.0% [17/20] vs. 90.0% [18/20]; p > 0.999). @*Conclusion@#Use of arterial subtraction images compared with ordinary arterial-phase images improved the sensitivity while maintaining specificity for diagnosing viable HCC after LRT using gadoxetic acid-enhanced MRI and the LR-TR algorithm.

Reporting Quality of Diagnostic Accuracy Studies in Laboratory Medicine: Adherence to Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015

BACKGROUND: Poor reporting quality in diagnostic accuracy studies hampers an adequate judgment of the validity of the study. The Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was published to improve the reporting quality of diagnostic accuracy studies. This study aimed to evaluate the adherence of diagnostic accuracy studies published in Annals of Laboratory Medicine (ALM) to STARD 2015 and to identify directions for improvement in the reporting quality of these studies.METHODS: Two independent authors assessed articles published in ALM between 2012–2018 for compliance with 30 STARD 2015 checklist items to identify all eligible diagnostic accuracy studies published during this period. We included 66 diagnostic accuracy studies. A total of the fulfilled STARD items were calculated, and adherence was analyzed on an individual-item basis.RESULTS: The overall mean±SD number of STARD items reported for the included studies was 11.2±2.7. Only five (7.6%) studies adhered to more than 50% of the 30 items. No study satisfied more than 80% of the items. Large variability in adherence to reporting standards was detected across items, ranging from 0% to 100%.CONCLUSIONS: Adherence to STARD 2015 is suboptimal among diagnostic accuracy studies published in ALM. Our study emphasizes the necessity of adherence to STARD to improve the reporting quality of future diagnostic accuracy studies to be published in ALM.

Performance Evaluation of the CS-5100 Coagulation Analyzer for Special Coagulation Parameters

Liver Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance

Hepatocellular carcinoma (HCC) surveillance is recommended when the annual incidence of HCC exceeds 1.5%. In 2018, several international guidelines included alternative surveillance modalities, such as computed tomography and magnetic resonance imaging (MRI), as alternatives for patients with inadequate surveillance with an ultrasound. Currently, abbreviated MRI selectively includes several key sequences and is emerging as an effective tool for HCC surveillance with reduced cost and scan time and the required diagnostic performance. The incidence of HCC substantially impacts the benefits of surveillance in terms of cost-effectiveness. Therefore, we need to individualize imaging surveillance of HCC, tailor screening, and determine risk-stratified strategies. The purpose of this article was to present a brief overview of the diagnostic performance and cost-effectiveness of liver MRI as an HCC surveillance tool.

Effects of a Case-Based Sepsis Education Program for General Ward Nurses on Knowledge, Accuracy of Sepsis Assessment, and Self-efficacy

Purpose@#s: Sepsis is a critical condition in which nurses should detect clinical manifestations and provide early intervention to prevent unwanted serious conditions in the patients. The initial occurrence and management of sepsis take place in general units, but there is a lack of knowledge in nurses. The purpose of this study was to examine the effects of a case-based sepsis education program and compare the case-based education program with and without smartphone applications. @*Methods@#A quasi-experimental pre-testpost-test design with a control group was used. We provided a case-based education program with and without smartphone applications to the nurses and tested the effects of the program on knowledge, the accuracy of sepsis assessment, and self-efficacy as outcome variables. A total of 60 nurses in general units participated. To test differences in knowledge, the accuracy of sepsis assessment, and self-efficacy regarding sepsis between the groups over time, a mixed-design ANCOVA was used for parametric analysis, and generalized estimating equations (GEE) were used for nonparametric analysis. @*Results@#There were significant differences in knowledge, the accuracy of sepsis assessment, and self-efficacy between the groups and within the groups over time. The intervention groups treated with the case-based education program showed improved outcome variables compared to the control group. There was no difference between case-based education with the smartphone application or without the application. @*Conclusions@#The case-based education improved knowledge, the accuracy of sepsis assessment, and self-efficacy in the care of sepsis by nurses working in the general wards. The results suggest that the case-based education program for nurses was effective and eventually improved patient health outcomes.

Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer

Purpose@#Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). @*Materials and Methods@#We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. @*Results@#CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively).Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. @*Conclusions@#CLDN18.2 expression was reduced in patients with PM but significantly intactin those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

Characterizing Computed Tomography-Detected Arterial Hyperenhancing-Only Lesions in Patients at Risk of Hepatocellular Carcinoma: Can Non-Contrast Magnetic Resonance Imaging Be Used for Sequential Imaging?

OBJECTIVE: To test the feasibility of non-contrast magnetic resonance imaging (MRI) in a sequential imaging study for characterizing computed tomography (CT)-detected arterial-enhancing nodules that do not washout in patients at risk of hepatocellular carcinoma (HCC).MATERIALS AND METHODS: In this retrospective study, 134 patients (mean age ± standard deviation, 56.8 ± 10.0 years) with 151 arterial enhancing-only nodules measuring up to 2 cm during multiphasic CT that were subsequently evaluated using gadoxetic acid-enhanced MRI in treatment-naïve at-risk patients from three tertiary referral centers were included. Tentative diagnostic criteria for HCC and hepatic malignancy were defined as the presence of one of eight MRI features favoring HCC in combinations of the following sequences: T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), T1-weighted dual gradient-echo in-phase and out-of-phase imaging (Dual-GRE), and hepatobiliary phase imaging (HBP). Typical hemangiomas and arterioportal shunts were excluded from the analysis. Diagnostic performance for HCC and hepatic malignancy was calculated and compared between the abbreviated MRI and full-sequence gadoxetic acid-enhanced MRI.RESULTS: Of 151 nodules (mean size, 1.2 cm) 68 HCCs and 83 non-HCC benignities and malignancies were included. The combination of T2WI, DWI, and Dual-GRE showed per-lesion sensitivity, specificity, and accuracy of 88.2%, 90.4%, and 89.4%, respectively, comparable to those of full-sequence MRI. Applying the same sequence combination to diagnose hepatic malignancy had per-lesion sensitivity, specificity, and accuracy of 86.8%, 97.3%, and 92.1%. In nodules < 1 cm, adding HBP increased sensitivity by up to 13% without compromising the specificity or accuracy.CONCLUSION: The non-contrast MRI protocol comprising T2WI, DWI, and Dual-GRE showed reasonable and comparable performance to full-sequence MRI for discriminating HCC and primary liver malignancies in CT-detected indeterminate arterial enhancing-only nodules in at-risk patients, and can be potentially used for sequential imaging in place of a full-sequence MRI. In nodules < 1 cm, HBP may still be needed to preserve sensitivity.

Clinical significance of myeloproliferative neoplasms with JAK2V617F mutations and major BCR-ABL1 translocations: a literature review with case presentation

No abstract available.

Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer

Purpose@#Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). @*Materials and Methods@#We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. @*Results@#CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively).Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. @*Conclusions@#CLDN18.2 expression was reduced in patients with PM but significantly intactin those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

A Report of Bone Marrow Metastasis of Colon Cancer as a Primary Diagnosis, Supported by Cytokeratin Immunohistochemical Staining

Bone marrow metastasis of colon cancer is rare. Here, we report a 56-year-old female patient who presented with pancytopenia. She was diagnosed with colon cancer accompanied by lung and axial skeleton metastasis. The bone marrow study showed metastatic carcinoma. Immunohistochemical (IHC) staining with anti-cytokeratin 7 (CK7) and anti-cytokeratin 20 (CK20) antibodies showed that the bone marrow samples were negative for CK7 and positive for CK20, consistent with metastatic colon cancer. To the best of our knowledge, there has been only one other reported case of bone marrow metastasis of colon cancer as the primary diagnosis in an adult patient in Korea. Bone and bone marrow metastases of colon cancer are regarded as uncommon. However, for proper management, bone marrows should be promptly examined in patients with solid tumors when unexplained cytopenia is noted, even if the origin of the tumor is known to be rarely metastatic to bone marrow. In addition, the use of cytokeratin IHC staining is helpful for determining the origin of metastatic carcinoma.

Effectiveness of Platelet Function Analyzer-100 for Laboratory Detection of Anti-Platelet Drug-Induced Platelet Dysfunction

BACKGROUND: High on-treatment platelet reactivity (HTPR) is the phenomenon wherein patients exhibit normal platelet activity in laboratory testing despite adequate adherence to anti-platelet treatment. We investigated the detection rates of Platelet Function Analyzer (PFA)-100 (Dade Behring AG, Düdingen, Switzerland) for drug-induced platelet dysfunction and analyzed potential contributors to HTPR with practical PFA-100 data over six years. METHODS: We used data from 6,957 patients who underwent PFA-100 testing after receiving aspirin, clopidogrel, or non-steroidal anti-inflammatory drugs (NSAIDs). Of these, 6,163 patients were tested with only the collagen/epinephrine cartridge (Col/EPI) of PFA-100; 794 were tested with both Col/EPI and the collagen/ADP cartridge (Col/ADP). We calculated PFA-100 closure time (CT) for each drug and compared the clinical and laboratory characteristics of the patients with prolonged CTs and normal CTs (i.e., HTPR). RESULTS: In Col/EPI, 73.2% (365/499), 72.6% (390/537), and 55.3% (3,442/6,228) patients showed prolonged CTs for aspirin, clopidogrel, and NSAIDs, respectively. In Col/ADP, prolonged CTs were observed in 37.4% (34/91), 43.2% (35/81), and 29.6% (200/676) of patients receiving aspirin, clopidogrel, and NSAIDs, respectively. Of the patients tested with both cartridges, 88.9% (48/54), 95.3% (41/43), and 89.0% (577/648) of the patients receiving aspirin, clopidogrel, and NSAIDs had prolonged CTs, and 10.0% (79/794) showed normal CTs regardless of drugs. For clopidogrel users (both cartridges), there were more patients with malignancies in the normal CT than prolonged CT group. CONCLUSIONS: PFA-100 is not sufficiently effective for laboratory screening of drug-induced platelet dysfunction. Malignancy may contribute to clopidogrel-related HTPR in PFA-100.

Multiple Neuroendocrine Tumors in Stomach and Duodenum in a Multiple Endocrine Neoplasia Type 1 Patient

A 67-year-old woman with a history of subtotal parathyroidectomy, distal pancreatectomy, and total splenectomy 23 years prior underwent surgical gastric resection for neuroendocrine tumors of the stomach and duodenum. Meticulous examination of the entire stomach and duodenum revealed multiple scattered, minute neuroendocrine tumors. To the best of our knowledge, this is the first case report of a patient diagnosed with gastroduodenal neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN 1) in whom complete histologic mapping of the whole gastrectomy specimen was performed. The presence of MEN 1–associated neuroendocrine tumors in the stomach is very rare, but should be considered in patients diagnosed with MEN 1 who present with a new tumor in the stomach.