The aim of this study was to evaluate the cutoff value for identifying malignance in main pancreatic duct (MPD)-involved intraductal papillary mucinous neoplasm (IPMN) with an MPD diameter ranging from 5 to 10 mm. Clinical-radiological characteristics of 142 patients, including MPD-involved IPMNs (n = 53) and branch-duct (BD)-IPMNs (n = 89) were analyzed. Logistic regression analysis was used to determine the risk factors of malignant IPMNs and invasive carcinoma. ROC curves were used to identify different cutoffs in terms of preoperative MPD values to predict the presence of invasive carcinoma as well as malignant IPMNs, and the prediction performance was evaluated. For MPD-involved IPMNs (5 mm < MPD < 10 mm), MPD diameter of 7.5 mm for discriminating malignant IPMNs (area under curve [AUC] = 0.67) and 7.7 mm for discriminating invasive IPMNs (AUC = 0.56) were found to be the optimal cutoff values at receiver operating characteristic curve (ROC) analysis. MPD > 7.5 mm and carbohydrate antigen19-9 (Ca19-9) > 37 U/ml were found to be predictors of malignant IPMNs at univariate, and MPD > 7.5 mm was a predictor in multivariate analysis in MPD-involved IPMNs. The AUC of the ROC curve of MPD (7.5 mm) combined with Ca19-9 in identifying malignant IPMNs was 0.73 in MPD-involved IPMNs. MPD (7.5 mm) combined with Ca19-9 performed well in identifying malignant IPMNs in MPD-involved IPMNs.

BACKGROUND: Pancreatic cancer (PaCa) is one of the most intractable and fatal malignancies and is associated with the dysregulation of long noncoding RNAs (lncRNAs), which are a large class of noncoding RNAs larger than 200 nt that act as competing endogenous RNAs or sponges for miRNAs to induce tumour biological behaviours. However, their clinical value in treating pancreatic cancer has been poorly explained, but they are essential for improving the prognosis of PaCa patients.
METHODS: We analysed the plasma-derived exosomal lncRNA profiles of PaCa patients by using whole-transcriptome sequencing analysis and identified significantly differentially expressed lncRNAs, including LINC01268, LINC02802, AC124854.1, and AL132657.1. In the current study, the expression levels of four plasma-derived exosomal lncRNAs in PaCa plasma were validated via quantitative real-time polymerase chain reaction (qRT‒PCR). The relationship between the expression of the four lncRNAs and the clinicopathological features of patients with PaCa was also evaluated.
RESULTS: We demonstrated that exosomal LINC01268, LINC02802, AC124854.1 and AL132657.1 were highly expressed in PaCa plasma compared with those in normal controls; moreover, they were positively correlated with the serum expression of carbohydrate antigen 19-9 (CA19-9). The receiver operating characteristic curves (AUCs) of the four lncRNAs were 0.8421, 0.6544, 0.7190, and 0.6321, and the AUC value of the combination of the four exosomal lncRNAs increased to 0.8476, with a sensitivity of 0.72 and specificity of 0.89. These results suggested that the plasma-derived exosomal genes LINC01268, LINC02802, AC124854.1, and AL132657.1 may be novel diagnostic markers for PaCa.
CONCLUSIONS: Our research demonstrated that the plasma-derived exosomal lncRNAs of PaCa patients are novel blood-based biomarkers of disease.

BACKGROUND: This study was designed to compare the diagnostic efficacy of mSEPT9 to four blood markers (CEA, CA19-9, platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR)). In addition, we aimed to determine the combined diagnostic efficacy of mSEPT9, CEA, CA19-9, PLR and NLR in colorectal cancer.
METHODS: A total of 567 participants were enrolled in the study, including 308 CRC patients, 61 colorectal polyp patients and 198 healthy subjects confirmed by colonoscopy and/or tissue biopsy. Plasma samples were collected for tests.
RESULTS: The positive rate of mSEPT9 in CRC (71.8%) was markedly higher than that in either the colorectal polyps group (27.9%) or the healthy controls (6.1%) (P < 0.001). The levels of CEA, CA19-9, NLR and PLR in the CRC group were significantly higher than those in the non-CRC groups (P < 0.05). ROC curves comparison analyses showed that the diagnostic efficacy of mSEPT9 alone in CRC was significantly higher than CEA, CA19-9, NLR and PLR alone. The combination of mSEPT9 with CEA, CA19-9 and PLR showed superior diagnostic value. In addition, binary logistic regression was also used to build a better model for clinical diagnosis of CRC. On univariable analyses, age, mSEPT9, CEA, CA 19-9, PLR and NLR were independent predictors of CRC. When these covariates were fitted in multivariable models, the ones with positive detection of mSEPT9, CEA, CA 19-9 and PLR were more likely to have CRC.
CONCLUSIONS: This research revealed a significant association between mSEPT9 status and the clinicopathological characteristics of CRC patients, and the combination of mSEPT9, CEA, CA19-9 and PLR could significantly improve diagnostic efficacy in CRC.

Biomarkers screening is a benefit approach for early diagnosis of major diseases. In this study, magnetic nanoparticles (MNPs) have been utilized as labels to establish a multi-line immunochromatography (MNP-MLIC) for simultaneous detection of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA 19-9), and alpha-fetoprotein (AFP) in a single serum sample. Under the optimal parameters, the three biomarkers can be rapidly and simultaneously qualitative screening within 15 min by naked eye. As for quantitative detection, the MNP-MLIC test strips were precisely positioned and captured by a smartphone, and signals on the test and control lines were extracted by ImageJ software. The signal ratio of test and control lines has been calculated and used to plot quantitative standard curves with the logarithmic concentration, of which the correlation coefficients are more than 0.99, and the limit of detection for CEA, CA 19-9, and AFP were 0.60 ng/mL, 1.21 U/mL, and 0.93 ng/mL, respectively. The recoveries of blank serum were 75.0 ~ 112.5% with the relative standard deviation ranging from 2.5 to 15.3%, and the specificity investigation demonstrated that the MNP-MLIC is highly specific to the three biomarkers. In conclusion, the developed MNP-MLIC offers a rapid, simple, accurate, and highly specific method for simultaneously detecting multiple biomarkers in serum samples, which provides an efficient and accurate approach for the early diagnosis of diseases.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients.
METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness.
RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort.
CONCLUSIONS: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

OBJECTIVE: We sought to investigate whether the addition of nimotuzumab to gemcitabine would improve the treatment efficacy of advanced pancreatic cancer.
METHODS: This retrospective analysis involved a total of 98 hospitalized patients harboring advanced pancreatic cancer. Depending on the specific treatment, patients were divided into study groups and control groups. The clinical efficacy, adverse reactions, and follow-up results of the 2 groups were compared, and the physical status, CA724, CA19-9, and CEA levels before and after treatment were monitored and recorded.
RESULTS: After treatment, PR ratio, SD ratio, ORR, and DCR in the study group were significantly higher than those in the control group, and PD ratio was significantly lower than that in the control group (P < 0.05) the KPS score after treatment in the study group was markedly higher than that of the control group (P < 0.05). After treatment, however, significantly lower levels of the 3 indicators were observed when compared with the control group (P < 0.05).
CONCLUSIONS: Our study highlights a more superior combined efficacy of nimotuzumab and gemcitabine than the control regimen, exhibiting improved survival and reduced levels of CA724, CA19-9, and CEA in patients with advanced pancreatic cancer.

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.

The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 (<37 U/mL), which introduces additional limitations to their accurate diagnosis and treatment. Hence, improved methods to accurately detect PC stages in CA19-9-negative patients are warranted. In this study, tumor-proximal liquid biopsy and inertial microfluidics were coupled to enable high-throughput enrichment of portal venous circulating tumor cells (CTCs) and support the effective diagnosis of patients with early-stage PC. The proposed inertial microfluidic system was shown to provide size-based enrichment of CTCs using inertial focusing and Dean flow effects in slanted spiral channels. Notably, portal venous blood samples were found to have twice the yield of CTCs (21.4 cells per 5 mL) compared with peripheral blood (10.9 CTCs per 5 mL). A combination of peripheral and portal CTC data along with CA19-9 results showed to greatly improve the average accuracy of CA19-9-negative PC patients from 47.1% with regular CA19-9 tests up to 87.1%. Hence, portal venous CTC-based microfluidic biopsy can be used with high sensitivity and specificity for the diagnosis of early-stage PC, particularly in CA19-9-negative patients.

BACKGROUND: Angiogenesis is a critical step in colorectal cancer growth, progression and metastasization. CT are routine imaging examinations for preoperative clinical evaluation in colorectal cancer patients. This study aimed to investigate the predictive value of preoperative CT enhancement rate (CER) and CT perfusion parameters on angiogenesis in colorectal cancer, as well as the association of preoperative CER and CT perfusion parameters with serum markers.
METHODS: This retrospective analysis included 42 patients with colorectal adenocarcinoma. Median of microvessel density (MVD) as the cut-off value, it divided 42 patients into high-density group (MVD ≥ 35/field, n = 24) and low-density group (MVD < 35/field, n = 18), and 25 patients with benign colorectal lesions were collected as the control group. Statistical analysis of CER, CT perfusion parameters, serum markers were performed in all groups. Receiver operating curves (ROC) were plotted to evaluate the diagnostic efficacy of relevant CT perfusion parameters for tumor angiogenesis; Pearson correlation analysis explored potential association between CER, CT perfusion parameters and serum markers.
RESULTS: CER, blood volume (BV), blood flow (BF), permeability surface (PS) and carbohydrate antigen 19 - 9 (CA19-9), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), trefoil factor 3 (TFF3), vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma were significantly higher than those in the control group, the parameters in high-density group were significantly higher than those in the low-density group (P < 0.05); however, the time to peak (TTP) of patients in colorectal adenocarcinoma were significantly lower than those in the control group, and the high-density group showed a significantly lower level compared to the low-density group (P < 0.05). The combined parameters BF + TTP + PS and BV + BF + TTP + PS demonstrated the highest area under the curve (AUC), both at 0.991. Pearson correlation analysis showed that the serum levels of CA19-9, CA125, CEA, TFF3, and VEGF in patients showed positive correlations with CER, BV, BF, and PS (P < 0.05), while these indicators exhibited negative correlations with TTP (P < 0.05).
CONCLUSIONS: Some single and joint preoperative CT perfusion parameters can accurately predict tumor angiogenesis in colorectal adenocarcinoma. Preoperative CER and CT perfusion parameters have certain association with serum markers.

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.
目的： 探讨胃癌骨转移的临床特点及预后，分析发生骨转移的影响因素及不同治疗方式的效果，为胃癌骨转移的早期发现和治疗优化提供依据。 方法： 纳入2011年1月至2021年12月兰州大学第一医院收治的胃癌骨转移患者142例，其中单纯骨转移60例，骨转移合并骨外转移82例。纳入同期无远处转移的Ⅲ期胃癌患者和单纯内脏转移的胃癌患者各142例。采用logistic回归分析确定胃癌骨转移的影响因素，采用Cox比例风险回归模型评估胃癌骨转移患者总生存时间（OS）的影响因素。 结果： 142例胃癌骨转移患者，以低分化腺癌为主（123例），45例患者为同时骨转移，肋骨转移（100例）、脊柱转移（88例）和骨盆转移（84例）多见，110例患者为多发骨转移，82例合并骨外其他部位转移。Ⅲ期胃癌组、单纯内脏转移组、单纯骨转移组和骨转移合并骨外转移组4组比较，患者年龄、分化程度、Borrmann分型、碱性磷酸酶、乳酸脱氢酶、血钙、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肌酸激酶同工酶、淋巴细胞、血红蛋白、血小板、癌胚抗原、糖类抗原19-9（CA19-9）和糖类抗原724差异有统计学意义（均P＜0.05）。多因素logistic回归分析显示，Borrmann分型是胃癌骨转移的独立保护因素（3型：OR=0.07，95% CI：0.01～0.64，P=0.018），碱性磷酸酶（OR=2.54，95% CI：1.07～6.01，P=0.034）、血钙（OR=2.71，95% CI：1.15～6.41，P=0.023）、肌酸激酶同工酶（OR=16.33，95% CI：1.83～145.58，P=0.012）、血小板（OR=10.08，95% CI：1.89～53.85，P=0.007）、CA19-9（OR=2.40，95% CI：1.14～5.05，P=0.021）是胃癌骨转移的独立危险因素。Ⅲ期胃癌组、单纯内脏转移组、单纯骨转移组和骨转移合并骨外转移组患者的中位OS分别为47、13、18和6个月，差异有统计学意义（P＜0.001）。单纯骨转移患者行原发肿瘤手术治疗的中位OS为中位OS为33个月，优于未手术患者（6个月，P=0.048）。多因素Cox回归分析显示，有骨外转移（HR=2.45，95% CI：1.56～3.85，P＜0.001）、血红蛋白降低（HR=1.54，95% CI：1.02～2.34，P=0.042）是胃癌骨转移患者OS的独立危险因素。 结论： 胃癌单纯骨转移患者的预后明显优于其他Ⅳ期患者，对此类患者，在充分评估后行原发部位手术联合化疗可能延长生存时间。.