BACKGROUND: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method.
METHODS: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method.
RESULTS: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes.
CONCLUSIONS: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

Cervical lymph node (LN) metastasis is common in differentiated thyroid cancer (DTC). This study evaluated the utility of the washout CYFRA 21-1 level, combined with the thyroglobulin (Tg) concentration, in terms of diagnosis of LN metastasis. We prospectively enrolled 53 patients who underwent thyroid surgery to treat DTC with lateral cervical LN metastases. Preoperative ultrasound guided needle localization was used to surgical sampling of specific LNs during the operation. The intraoperative washout Tg and CYFRA 21-1 levels were measured in such LNs. The Tg and CYFRA 21-1 levels differed significantly between metastatic and benign LNs. The cutoff values were 2.63 ng/mL for washout CYFRA 21-1 and 22.62 ng/mL for Tg. Combined use of the washout Tg and CYFRA 21-1 levels afforded the highest diagnostic accuracy (92.5%), better than that of individual markers. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were 94.6%, 90.0%, 91.4%, 93.8%, respectively. The conjunction of the washout CYFRA21-1 and Tg levels enhances the diagnostic accuracy of LN metastasis in DTC patients. The washout CYFRA 21-1 level may be useful when malignancy is suspected, especially in cases where the cytology and washout Tg findings do not provide definitive results.

BACKGROUND: Pancreatic cancer is a challenging disease, often requiring invasive procedures for diagnosis. Reliable tumour markers are essential for ensuring early detection and better patient outcomes. Although Carbohydrate Antigen 19-9 is the most commonly used marker, it is marred by low predictive accuracy and high false positivity. Carcino Embryonic Antigen also has limited practical use. A novel antigen, Cytokeratin fragment 21-1, is gaining significance for its diagnostic value in various tumours.
METHODS: This prospective study aimed to evaluate the potential of Cytokeratin fragment 21-1 in comparison with Carbohydrate Antigen 19-9 and Carcino Embryonic Antigen in diagnosing pancreatic cancer. From January 2016 to December 2019, 45 patients with confirmed pancreatic ductal adenocarcinoma were included in this cross-sectional study.
RESULTS: Carbohydrate Antigen 19-9 was raised in 22 patients, Carcino Embryonic Antigen was elevated in 17, and Cytokeratin fragment 21-1 was elevated in 30 cases. Carbohydrate Antigen 19-9 was found to be elevated in the presence of jaundice. Both Carbohydrate Antigen 19-9 and Cytokeratin fragment 21-1 had good correlation with stage of cancer, while Carcino Embryonic Antigen had very minimal correlation.
CONCLUSIONS: In this study, Cytokeratin fragment 21-1 was elevated in a higher number of cases than Carbohydrate Antigen 19-9 and Carcino Embryonic Antigen. Both Cytokeratin fragment 21-1 and Carbohydrate Antigen 19-9 correlated well with cancer stage. Also Cytokeratin fragment 21-1 was not affected by jaundice, unlike Carbohydrate Antigen 19-9. Therefore, Cytokeratin fragment 21-1 has the potential to be an effective individual tumour marker in pancreatic cancer.

OBJECTIVE: Cytokeratin 19 fragment 21-1 (CYFRA 21-1) and cytokeratin 19 fragment 2G2 (CK 19-2G2) are two soluble fragments of cytokeratin 19 (CK 19) that can be detected in serum. CK 19-positive hepatocellular carcinoma (HCC) is characterized by an aggressive behavior and a poor outcome. This study aimed to assess the prognostic value of serum CYFRA 21-1 and CK 19-2G2 in predicting tumor aggressiveness and overall survival (OS) in patients with hepatic C virus (HCV)-related HCC.
METHODS: The current study included 138 patients with HCV-related HCC recruited from the Hepatobiliary and Interventional Radiology Units at Alexandria\'s main university hospitals and 40 healthy individuals as controls. Patients were assessed for clinical, radiological tumor characteristics, and aggressiveness index. Baseline serum CYFRA 21-1 and CK 19-2G2 levels were measured by enzyme-linked immunosorbent assay.
RESULTS: Elevated CYFRA 21-1 levels were associated with tumors size ≥ 5 cm (p < 0.001), malignant portal vein thrombosis (mPVT) (p < 0.001), distant metastasis (p = 0.030), ill-defined/infiltrative pattern (p = 0.010), and aggressiveness index > 4 (p = 0.045). Elevated CK19-2G2 levels were not associated with any clinical or radiological characteristics. Either or both elevated serum CYFRA 21-1 and CK 19-2G2 in combination with alpha-feto protein (AFP) ≥ 400 ng/ml have a better predictability for mPVT and ill-defined/infiltrative patterns (sensitivity (10-25%) and specificity (96-100%)). Elevated levels of CYFRA 21-1, CK 19-2G2, or AFP ≥ 400 ng/ml were associated with decreased 1-year OS.
CONCLUSIONS: Either or both elevated serum CYFRA 21-1 and CK 19-2G2 levels when added to AFP ≥ 400 ng/ml are specific but less sensitive biomarkers for predicting tumor aggressiveness. These biomarkers can be used independently to predict reduced 1-year OS in Egyptian patients with HCV-related HCC.

BACKGROUND: Serum tumor markers have not yet been developed for the clinical diagnosis and treatment of sinonasal inverted papilloma (SNIP), one of the most significant sinonasal tumors. Therefore, this study aimed to determine the diagnostic value of serum squamous cell carcinoma antigen (SCCA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) for SNIP.
METHODS: Clinical data were obtained from 101, 56, and 116 patients with SNIP, sinonasal squamous cell carcinoma (SNSCC), and unilateral chronic rhinosinusitis (CRS), respectively. Preoperative serum SCCA and CYFRA 21-1 levels were compared, and logistic regression analyses were performed to screen serum tumor markers, which may be used to diagnose SNIP. Diagnostic cut-off values were determined using receiver operating characteristic (ROC) curves, and their diagnostic power was verified.
RESULTS: Serum SCCA and CYFRA 21-1 differentiated SNIP from CRS with the cut-off values of 1.97 ng/mL and 2.64 ng/mL and the areas under the ROC curves (AUC) of 0.895 and 0.766, respectively, and the AUC of the combination of the two markers was 0.909. CYFRA 21-1 differentiated SNIP with malignant transformation from that without malignant transformation with a cut-off value of 3.51 ng/mL and an AUC of 0.938. CYFRA 21-1 distinguished SNIP with malignant transformation from SNSCC with a cut-off value of 3.55 ng/mL and an AUC of 0.767.
CONCLUSIONS: This study provides novel potential diagnostic tools for SNIP by demonstrating the use of serum SCCA and CYFRA 21-1 in the diagnosis of SNIP.

Organoids are novel in vitro models to study intercellular cross talk between the different types of cells in disease pathophysiology. To better understand the underlying mechanisms driving the progression of primary sclerosing cholangitis (PSC), scaffold-free multicellular three-dimensional cholangiocyte organoids (3D-CHOs) were developed using primary liver cells derived from normal subjects and patients with PSC. Human liver samples from healthy donors and patients with PSC were used to isolate primary cholangiocytes [epithelial cell adhesion molecule (EpCam)+/ cytokeratin-19+], liver endothelial cells (CD31+), and hepatic stellate cells (HSCs; CD31-/CD68-/desmin+/vitamin A+). 3D-CHOs were formed using cholangiocytes, HSCs, and liver endothelial cells, and kept viable for up to 1 month. Isolated primary cell lines and 3D-CHOs were further characterized by immunofluorescence, quantitative RT-PCR, and transmission electron microscopy. Transcription profiles for cholangiocytes (SOX9, CFTR, EpCAM, AE, SCT, and SCTR), fibrosis (ACTA2, COL1A1, DESMIN, and TGFβ1), angiogenesis (PECAM, VEGF, CDH5, and vWF), and inflammation (IL-6 and TNF-α) confirmed PSC phenotypes of 3D-CHOs. Because cholangiocytes develop a neuroendocrine phenotype and express neuromodulators, confocal immunofluorescence was used to demonstrate localization of the neurokinin-1 receptor within cytokeratin-19+ cholangiocytes and desmin+ HSCs. Moreover, 3D-CHOs from patients with PSC confirmed PSC phenotypes with up-regulated neurokinin-1 receptor, tachykinin precursor 1, and down-regulated membrane metalloendopeptidase. Scaffold-free multicellular 3D-CHOs showed superiority as an in vitro model in mimicking PSC in vivo phenotypes compared with two-dimensional cell culture, which can be used in PSC disease-related research.

This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers.
Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-μm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance.
A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance.
The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.

BACKGROUND: The OSNA technique is based on reverse transcription loop-mediated DNA amplification for the detection of cytokeratin 19 (CK19) messen-ger RNA (mRNA). The purpose of our paper, which represents the first study in the literature, is to test the accuracy of this method in the detection of lymph node metastases in patients undergoing robotic radical prostatectomy with lymph node dis-section.
METHODS: Our cohort consisted of patients that have undergone robotic radical prostatectomy with extended lymph node dissec-tion. Lymph nodes were evaluated with imprint technique and then with frozen section examination. The remaining tissue was evaluated by OSNA method. Lymph nodes were defined as \'neg-ative\' or \'positive\' according to mRNA copy number.
RESULTS: 7 patients and 25 lymph nodes were included in our cohort. Two patients were found negative with all pathology methods. In one patient the standard stains revealed a suspi-cious outcome but it was positive for micrometastasis with OSNA. In another patient the outcome was positive for standard stains and negative for OSNA. Finally, 2 patients were found positive for OSNA and negative for imprint methods.
CONCLUSIONS: One Step Nucleic Acid Amplification (OSNA) method using CK19 seems to fail in detection of lymph node metastases in prostate cancer patients undergoing radical prostatectomy and lymph node dissection.

UNASSIGNED: Peripherally inserted central catheter (PICC), as one of the important intravenous routes for the rescue and treatment of critically ill patients, has been widely used in the fluid resuscitation of critically ill patients in intensive care. In particular, PICC can be widely used in the treatment of cancer patients. With the wide application of peripheral central venous catheterization, the clinical findings of bloodstream infection complications caused by PICC have gradually attracted the attention of doctors and patients.
UNASSIGNED: To investigate the effect of specialized placement and PICC placement care on patients with lung cancer who underwent PICC puncture. Patients were selected and divided into a comparison group and an observation group of 40 patients each according to the randomized residual grouping method. In the comparison group, routine PICC placement and catheter maintenance were performed, while the observation group was provided with specialized placement and PICC placement care. The differences in immune and tumor marker levels and nursing compliance between the two groups were observed and compared before and after nursing care.
UNASSIGNED: There was no significant difference in the comparison of tumor marker levels between the two groups of patients before care, while the levels of CYFRA21-1, CA125, and VGEF in the observation group were significantly lower than those in the comparison group after care, and this difference was statistically significant (P < 0.05). There was no statistically significant difference in the comparison of immune levels between the two groups before care (P > 0.05), while the comparison of CD4+, CD3+, and CD4+/CD8+ after care was significantly different and higher in the observation group than in the comparison group, and the comparison was statistically significant (P < 0.05). The compliance rate of 93.8% in the observation group was significantly higher than that of 77.9% in the comparison group, and this difference was statistically significant for comparison (P < 0.05).
UNASSIGNED: PICC placement care is more effective in patients with lung cancer and performing PICC puncture, significantly improves patients\' immune and tumor marker levels, improves patients\' negative emotions, reduces disease uncertainty, and improves nursing compliance.

UNASSIGNED: Ascertaining the role of cytokeratin-19 (CK19) and its staining pattern helps to differentiate papillary carcinoma from other thyroid lesions.
UNASSIGNED: To correlate fine needle aspiration cytology (FNAC) and cell block study of equivocal cases (Category III, IV, and V) with the role of CK19 staining in it.
UNASSIGNED: A hospital-based cross-sectional observational study was designed and conducted at North Bengal Medical College and Hospital, Shusrutnagar, Darjeeling.
UNASSIGNED: The FNAC performed and reported as per TBSRTC-2017.50 cases of Category III, IV, and V was selected for cell block study and CK19 staining followed by immunohistochemical scoring.
UNASSIGNED: Out of 50 cases, 17 were follicular neoplasm, 21 papillary carcinoma, 6 lymphocytic thyroiditis, 1 Hürthle cell adenoma, 1 medullary carcinoma, 1 lymphoma, and 3 undifferentiated carcinomas. Among cases of papillary carcinoma, 10 showed 4+ positivity, 9 showed 3+ positivity, 2 showed focal 1+ and 2+ positivity. In the case of follicular neoplasm, 1 showed 3+ positivity, 3 cases had 1+ 2+ positivity, and 13 cases revealed negative staining.
UNASSIGNED: Role of CK19 in distinguishing papillary carcinoma of thyroid from other lesions in cytologically diagnosed Category III, IV, and V (TBSRTC-2017) cases can be demonstrated.