Primary Pulmonary Malignant Melanoma Presenting as Bilateral Multiple Subsolid Nodules: A Case Report.

Primary pulmonary malignant melanoma is an extremely rare type of melanoma. The radiologic features of primary pulmonary malignant melanoma are nonspecific; however, it almost always presents as a well-demarcated round or lobulated solitary solid nodule or mass. Herein, we report the case of a 78-year-old male with primary pulmonary malignant melanoma that was mistaken for primary pulmonary adenocarcinoma with lepidic growth and was seen as bilateral multiple subsolid nodules on CT.

Efficacy and Safety of Percutaneous Transhepatic Cholangioscopy with the Spyglass DS Direct Visualization System in Patients with Surgically Altered Anatomy: A Pilot Study.

BACKGROUND/AIMS: : Percutaneous transhepatic cholangioscopy (PTCS) is used for the diagnosis and treatment of biliary diseases in patients with failed endoscopic retrograde cholangiopancreatography, particularly those with surgically altered anatomy. However, few studies are available on the clinical use of Spyglass DS direct visualization system (SpyDS)-assisted PTCS. This study aimed to assess the efficacy and safety of SpyDS-assisted PTCS in patients with surgically altered anatomy, particularly those with a Roux-en-Y reconstruction. METHODS: Thirteen patients (six women, median age 71.4 years [range, 53 to 83 years]) with surgically altered anatomy (four Roux-en-Y choledochojejunostomies, seven Roux-en-Y hepaticojejunostomies, and two Roux-en-Y esophagojejunostomies) who underwent SpyDS-assisted PTCS between January 2019 and August 2020 were included and the data was acquired by retrospectively reviewing electronic medical record. RESULTS: A total of 19 SpyDS-assisted PTCS procedures were performed in the 13 patients: eight had bile-duct stones, and five had biliary strictures. All SpyDS-assisted PTCS procedures were successfully performed. The total procedure time was 42.42±18.0 minutes (mean±standard deviation). Bile duct clearance was achieved in all bile duct stone cases after a median of 2 (range, 1 to 3) procedures. In the five biliary stricture cases, the results of SpyBite forceps-guided targeted biopsy were consistent with adenocarcinoma (100% accuracy). The median hospitalization duration was 20 days (range, 14 to 30 days). No procedure-related morbidity or mortality occurred. CONCLUSIONS: SpyDS-assisted PTCS may be a safe, feasible, and effective procedure for the diagnosis and treatment of biliary diseases in patients with surgically altered anatomy, particularly in those with the Roux-en-Y reconstruction requiring a percutaneous approach. However, our findings need to be validated in further studies.

Staging of Liver Fibrosis by Means of Semiautomatic Measurement of Liver Surface Nodularity in MRI.

OBJECTIVE. The purposes of this study were to evaluate the accuracy of a semiautomatic method of measuring liver surface nodularity (LSN) on contrast-enhanced MR images and to compare the LSN score with pathologic fibrosis stage. MATERIALS AND METHODS. This retrospective study included patients who had undergone gadoxetate disodium-enhanced liver MRI 6 months before or after histopathologic investigation including percutaneous parenchymal biopsy and surgical biopsy for staging of chronic liver disease between January 2010 and December 2018. Semiautomated LSN quantification software was developed to measure LSN at MRI. Aspartate aminotransferase to platelet ratio index and fibrosis-4 index were derived from serum laboratory test results. The reference standard for staging of liver fibrosis was Metavir score. The accuracy of LSN score for staging of liver fibrosis was evaluated with AUC, and the optimal cutoff value was calculated by Youden index. Spearman correlation coefficient was used for correlation analysis. RESULTS. The study included 132 patients (93 men, 39 women). LSN score was evaluated without technical failure. There was high correlation between LSN score and Metavir score (Spearman ρ = 0.713, p < 0.001). The AUCs of LSN score for distinguishing Metavir score were 0.93 for F0-F1 versus F2-F4 (95% CI, 0.88-0.97; p < 0.001), 0.98 for F0-F2 vs F3-F4 (95% CI, 0.95-1.00; p < 0.001), and 0.83 for F0-F3 versus F4 (95% CI, 0.76-0.90; p < 0.001). The optimal cutoff value for differentiating F0-F2 from F3-F4 was 0.850 with 100% sensitivity and 85.4% specificity. CONCLUSION. LSN score calculated semiautomatically from MR images of the liver has high accuracy and correlates directly with the pathologic fibrosis stage.

An Unusual Presentation of a Solid Pseudopapillary Tumor of the Pancreas Mimicking Adenocarcinoma.

Solid pseudopapillary tumors of the pancreas are rare and typically occur in young women. Compared with pancreatic adenocarcinoma, solid pseudopapillary tumors are characterized by notable indolent biological behavior associated with a favorable prognosis. Despite their large size, these tumors rarely metastasize. Even in cases of hepatic metastasis, most lesions are usually solitary in distribution and are amenable to resection. We report a case of a 55-year-old man with a small solid pseudopapillary tumor (≤3-cm diameter) mimicking a pancreatic adenocarcinoma, with multiple hepatic metastases. The diagnosis was confirmed by endoscopic ultrasound-guided fine-needle biopsy using a 22-G core needle. Unfortunately, rapid tumor progression led to patient mortality 5 months after diagnosis. To our knowledge, this is the first case report that describes a small solid pseudopapillary tumor of the pancreas with multiple hepatic metastasis and poor prognosis in a patient who was diagnosed with this condition at the time of initial diagnosis.

Wound healing effect of regenerated oxidized cellulose versus fibrin sealant patch: An in vivo study.

BACKGROUND: Topical hemostatic agents are used when ligation, electrocauterization, or other conventional hemostatic methods are impractical. Because a hemostatic agent is a foreign body, it can cause foreign body reactions, inflammation, and infections that can interfere with the wound healing process. Therefore, we should select hemostatic agents after considering their effects on wound healing. Here, we compared the effects of hemostatic agents on wound healing in a rectus abdominis muscle defect in rats. METHODS: Twelve Sprague Dawley rats were subjected to creation of a 6 × 6 mm defect in the rectus abdominis muscle and divided into four groups: control group; group A, Tachosil fibrin sealant patch; group B, Surgicel Fibrillar oxidized regenerated cellulose; and group C, Surgicel Snow oxidized regenerated cellulose. For the histologic analysis, biopsies were performed on the 3rd, 7th, and 27th days. RESULTS: The foreign body reaction was the weakest in group A and most significant in group C. The inflammatory cell infiltration was the weakest in group A and similar in groups B and C. Muscle regeneration differed among periods. The rats in group A were the most active initially, while those in group C showed prolonged activity. CONCLUSION: Tachosil and Surgicel administration increased inflammation via foreign body reactions, but the overall wound healing process was not significantly affected. The increased inflammation in the Surgicel groups was due to a low pH. We recommend using Tachosil, because it results in less intense foreign body reactions than Surgicel and faster wound healing due to the fibrin action.

Endoscopic Ultrasound-Guided Liver Biopsy Using a Core Needle for Hepatic Solid Mass.

BACKGROUND/AIMS: This study aimed to evaluate the feasibility and efficacy of endoscopic ultrasound-guided fine needle biopsy (EUSFNB) using a core needle for hepatic solid masses (HSMs). Additionally, the study aimed to assess factors that influence the diagnostic accuracy of EUS-FNB for HSMs. METHODS: A retrospective analysis of patients who underwent EUS-FNB for the pathological diagnosis of HSMs was conducted between January 2013 and July 2017. The procedure had been performed using core needles of different calibers. The assessed variables were mass size, puncture route, needle type, and the number of needle passes. RESULTS: Fifty-eight patients underwent EUS-FNB for the pathologic evaluation of HSMs with a mean mass size of 21.4±9.2 mm. EUSFNB was performed with either a 20-G (n=14), 22-G (n=29) or a 25-G core needle (n=15). The diagnostic accuracy for this procedure was 89.7%, but both specimen adequacy for histology and available immunohistochemistry stain were 91.4%. The sensitivity and specificity of EUS-FNB were 89.7% and 100%, respectively. There was one case involving bleeding as a complication, which was controlled with endoscopic hemostasis. According to the multivariate analysis, no variable was independently associated with a correct final diagnosis. CONCLUSION: EUS-FNB with core biopsy needle is a safe and highly accurate diagnostic option for assessing HSMs. There were no variable factors associated with diagnostic accuracy.

Comparison of cobas EGFR Mutation Test v2 and PANAMutyper-R-EGFR for Detection and Semi-Quantification of Epidermal Growth Factor Receptor Mutations in Plasma and Pleural Effusion Supernatant.

BACKGROUND: Plasma epidermal growth factor receptor (EGFR) mutation tests are less invasive than tissue EGFR mutation tests. We determined which of two kits is more efficient: cobas EGFR Mutation test v2 (cobasv2; Roche Molecular Systems, Pleasanton, CA, USA) or PANAMutyper-R-EGFR (Mutyper; Panagene, Daejeon, Korea). We also evaluated whether pleural effusion supernatant (PE-SUP) samples are assayable, similar to plasma samples, using these two kits. METHODS: We analyzed 156 plasma and PE-SUP samples (31 paired samples) from 116 individuals. We compared the kits in terms of accuracy, assessed genotype concordance (weighted κ with 95% confidence intervals), and calculated Spearman's rho between semi-quantitatively measured EGFR-mutant levels (SQIs) measured by each kit. We also compared sensitivity using 47 EGFR-mutant harboring samples divided into more-dilute and less-dilute samples (dilution ratio: ≥ or <1:1,000). RESULTS: cobasv2 tended to have higher accuracy than Mutyper (73% vs 69%, P=0.53), and PE-SUP samples had significantly higher accuracy than plasma samples (97% vs 55-71%) for both kits. Genotype concordance was 98% (κ=0.92, 0.88-0.96). SQIs showed strong positive correlations (P<0.0001). In less-dilute samples, accuracy and sensitivity did not differ significantly between kits. In more-dilute samples, cobasv2 tended to have higher sensitivity than Mutyper (43% vs 20%, P=0.07). CONCLUSIONS: The kits have similar performance in terms of EGFR mutation detection and semi-quantification in plasma and PE-SUP samples. cobasv2 tends to outperform Mutyper in detecting less-abundant EGFR-mutants. PE-SUP samples are assayable using either kit.

Mucinous Non-neoplastic Cyst of the Pancreas.

Cystic neoplasms of the pancreas consist of a wide range of pathological entities and are being detected more frequently due to advances in cross-sectional imaging modalities and increasing numbers of periodic health checkups. The majority of pancreatic cystic neoplasms are intraductal papillary mucinous neoplasms, serous neoplasms, and mucinous cystic neoplasms, but recently, rare cases of mucinous non-neoplastic cyst of the pancreas (MNCP) have been reported, and despite the availabilities of modern imaging systems, such as MRI and CT, the differentiation of non-neoplastic and neoplastic cysts remains challenging. Herein, we report our experience of a 65-year-old male case with an MNCP.

Expression Profile of Three Splicing Factors in Pleural Cells Based on the Underlying Etiology and Its Clinical Values in Patients with Pleural Effusion.

Splicing factors (SFs) are involved in oncogenesis or immune modulation, the common underlying processes giving rise to pleural effusion (PE). The expression profiles of three SFs (HNRNPA1, SRSF1, and SRSF3) and their clinical values have never been assessed in PE. The three SFs (in pellets of PE) and conventional tumor markers were analyzed using PE samples in patients with PE (N = 336). The sum of higher-molecular weight (Mw) forms of HNRNPA1 (Sum-HMws-HNRNPA1) and SRSF1 (Sum-HMws-SRSF1) and SRSF3 levels were upregulated in malignant PE (MPE) compared to benign PE (BPE); they were highest in cytology-positive MPE, followed by tuberculous PE and parapneumonic PE. Meanwhile, the lowest-Mw HNRNPA1 (LMw-HNRNPA1) and SRSF1 (LMw-SRSF1) levels were not upregulated in MPE. Sum-HMws-HNRNPA1, Sum-HMws-SRSF1, and SRSF3, but neither LMw-HNRNPA1 nor LMw-SRSF1, showed positive correlations with cancer cell percentages in MPE. The detection accuracy for MPE was high in the order of carcinoembryonic antigen (CEA, 85%), Sum-HMws-HNRNPA1 (76%), Sum-HMws-SRSF1 (68%), SRSF3, cytokeratin-19 fragments (CYFRA 21-1), LMw-HNRNPA1, and LMw-SRSF1. Sum-HMws-HNRNPA1 detected more than half of the MPE cases that were undetected by cytology and CEA. Sum-HMws-HNRNPA1, but not other SFs or conventional tumor markers, showed an association with longer overall survival among patients with MPE receiving chemotherapy. Our results demonstrated different levels of the three SFs with their Mw-specific profiles depending on the etiology of PE. We suggest that Sum-HMws-HNRNPA1 is a supplementary diagnostic marker for MPE and a favorable prognostic indicator for patients with MPE receiving chemotherapy.

Hepatic Alanine Differentiates Nonalcoholic Steatohepatitis From Simple Steatosis in Humans and Mice: A Proton MR Spectroscopy Study With Long Echo Time.

PURPOSE: To evaluate the hepatic metabolic alterations in nonalcoholic fatty liver disease (NAFLD) by using 1 H-MRS (proton magnetic resonance spectroscopy) with long echo time and to test the reproducibility of human study in an animal model. Liver biopsy is the gold standard for diagnosing NAFLD but with practical constraints. 1 H-MRS allows in vivo assessment of hepatocellular metabolism and has shown potential for biochemical differentiation in diffuse liver disease. MATERIALS AND METHODS: In all, 32 subjects (11 patients with nonalcoholic steatohepatitis [NASH], 15 with simple steatosis [SS], and six healthy controls) were studied. For test reproducibility, 36 C57BL/6 mice, including 10 mice with streptozotocin-induced NASH, 15 with SS, and 11 high-fat diet controls, were studied. 1 H-MRS measurements at 3T and 4.7T MRI were performed on a localized voxel of the liver using PRESS sequence. Hepatic alanine (Ala), lactate+triglyceride (Lac+TG), and TG levels were compared between NASH, SS, and control groups using analysis of variance (ANOVA) tests. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolite levels and pathologic grades or NAFLD activity scores (NAS) were assessed using Pearson's correlation. RESULTS: NASH patients had higher levels of Ala (P < 0.001), Lac+TG (P < 0.001), and TG (P < 0.05) than SS patients or controls. The AUROC curve to distinguish NASH from SS was 1.00 (95% confidence interval [CI] 1.00-1.00) for Ala and 0.782 (95% CI 0.61-0.96) for Lac+TG. Ala and Lac+TG concentrations were positively correlated with steatosis grade (Ala Pearson's r = 0.723; Lac+TG r = 0.446), lobular inflammation (Ala r = 0.513), and NAS (Ala r = 0.743; Lac+TG r = 0.474). CONCLUSION: 1 H-MRS is potentially useful for noninvasive diagnosis of NASH and simple steatosis by hepatic metabolite quantification. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1298-1310.

HNRNPA1, a Splicing Regulator, Is an Effective Target Protein for Cervical Cancer Detection: Comparison With Conventional Tumor Markers.

OBJECTIVE: Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), serine/arginine-rich splicing factor 1 (SRSF1), and SRSF3 are splicing regulators associated with oncogenesis. However, the alterations of SF proteins and their diagnostic values in cervical cancer are unclear. To apply SFs clinically, effective marker selection and characterization of the target organ properties are essential. MATERIALS AND METHODS: We concurrently analyzed HNRNPA1, SRSF1, SRSF3, and the conventional tumor markers squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) in cervical tissue samples (n = 127) using semiquantitative immunoblotting. In addition, we compared them with p16 (cyclin-dependent kinase inhibitor 2A [CDKN2A]), which has shown high diagnostic efficacy in immunohistochemical staining studies and has been proposed as a candidate protein for point-of-care screening biochemical tests of cervical neoplasia. RESULTS: HNRNPA1, higher molecular weight forms of SRSF1 (SRSF1-HMws), SRSF3, CEA, and p16 levels were higher (P < 0.05) in cervical carcinoma tissue samples than in nontumoral cervical tissue samples. However, the levels of SRSF1-Total (sum of SRSF1-HMws and a lower molecular weight form of SRSF1) and SCCA, a commonly used cervical tumor marker, were not different between carcinoma and nontumoral tissue samples. In paired sample comparisons, HNRNPA1 (94%) showed the highest incidence of up-regulation (carcinoma/nontumor, >1.5) in cervical carcinoma, followed by p16 (84%), SRSF1-HMws (69%), SRSF3 (66%), CEA (66 %), SCCA (32%), and SRSF1-Total (31%). HNRNPA1 (92%) and p16 (91%) presented the two highest diagnostic accuracies for cervical carcinoma, which were superior to those of SRSF3 (75%), SRSF1-HMws (72%), CEA (72%), SCCA (59%), and SRSF1-Total (55%). CONCLUSIONS: Our results identified that HNRNPA1 is the best diagnostic marker among the SFs and conventional markers given its excellent diagnostic efficacy for cervical carcinoma, and it has a p16-comparable diagnostic value. We suggest that HNRNPA1 is an additional effective target protein for developing cervical cancer detection tools.

SRSF5: a novel marker for small-cell lung cancer and pleural metastatic cancer.

OBJECTIVES: SR-splicing factors (SRSFs) play important roles in oncogenesis. However, the expression of SRSF 5-7 proteins in lung cancer (LC) is unclear, and their use in the diagnosis of pleural diseases has never been assessed. We evaluated SRSF 5-7 protein levels in LC and their diagnostic potential for cancer cells in lung and pleural effusion (PE) and, for the dysregulated SRSFs, investigated their neutralization effect on LC. MATERIALS AND METHODS: SRSF 5-7 levels in lung tissue and PE cell lysate samples (n=453) were compared with the results of conventional tumor markers. Knockdown of SRSF gene expression was performed using small interfering RNAs on small-cell LC (SCLC) cell lines. RESULTS: In lung tissue analysis, SRSF 5-7 levels were up-regulated in LC samples compared with non-tumoral lung tissue samples; they were markedly higher in SCLC than in adenocarcinoma or squamous cell carcinoma. SRSF5 showed the highest detection accuracy (89%) for total LC, and it was superior to that (74%) of carcinoembryonic antigen [CEA, a commonly used non-SCLC (NSCLC) marker]. Notably, the detection accuracies of the three SRSFs for SCLC were all 100% and higher than that (69%) of a pro-gastrin-releasing peptide (a well-known SCLC marker). In PE cell analysis, the detection accuracy (86%) of SRSF5 for malignant cells was highest among SRSFs and comparable to that (83%) of CEA. SRSF5 additionally detected 70% of CEA-missed non-NSCLC cases. Down-regulation of the SRSFs induced mild (SRSF5 and SRSF7) to remarkably (SRSF6) reduced cell proliferation. CONCLUSIONS: Our results demonstrated the up-regulated expression of SRSF 5-7 proteins in LC with much more profound up-regulation in SCLC than in NSCLC and suggest that up-regulation of the SRSFs is related to SCLC proliferation. Moreover, we identified SRSF5 as a novel detection marker for SCLC and pleural metastatic cancer cells.

Comparative expression patterns and diagnostic efficacies of SR splicing factors and HNRNPA1 in gastric and colorectal cancer.

BACKGROUND: Serine/arginine-rich splicing factors (SRSFs) and HNRNPA1 have oncogenic properties. However, their proteomic expressions and practical priority in gastric cancer (GC) and colorectal cancer (CRC) are mostly unknown. To apply SFs in clinics, effective marker selection and characterization of properties in the target organ are essential. METHODS: We concurrently analyzed SRSF1, 3, and 5-7, and HNRNPA1, together with the conventional tumor marker carcinoembryonic antigen (CEA), in stomach and colorectal tissue samples (n = 420) using semiquantitative immunoblot, subcellular fractionation, and quantitative real-time polymerase chain reaction methods. RESULTS: In the semiquantitative immunoblot analysis, HNRNPA1 and SRSF7 levels were significantly higher in GC than in gastric normal mucosa, and SRSF7 levels were higher in intestinal-type compared with diffuse-type of gastric adenocarcinoma. Of the SFs, only HNRNPA1 presented greater than 50 % upregulation (cancer/normal mucosa > 2-fold) incidences and CEA-comparable, acceptable (>70 %) detection accuracy (74 %) for GC. All SF protein levels were significantly higher in CRC than in colorectal normal mucosa, and HNRNPA1 levels were higher in low-stage CRC compared with high-stage CRC. Among the SFs, HNRNPA1 and SRSF3 presented the two highest upregulation incidences (88 % and 74 %, respectively) and detection accuracy (90 % and 84 %, respectively) for CRC. The detection accuracy of HNRNPA1 was comparable to that of CEA in low (≤ II)-stage CRC but was inferior to that of CEA in high (>II)-stage CRC. Extranuclear distributions of HNRNPA1 and SRSF6 (cytosol/microsome) differed from those of other SRSFs (membrane/organelle) in both cancers. In an analysis of the six SF mRNAs, all mRNAs presented unacceptable detection accuracies (≤70 %) in both cancers, and all mRNAs except SRSF6 were disproportionate to the corresponding protein levels in GC. CONCLUSION: Our results provide a comprehensive insight into the six SF expression profiles in GC and indicate that, among the SFs, HNRNPA1, but not HNRNPA1 mRNA, is the most effective, novel GC marker. Regardless of the good to excellent detection accuracy of SRSF3 and HNRNPA1 in CRC, the SFs have lower practical priority than CEA, especially for high-stage CRC detection.