Tumor-Specific miRNA Signatures in Combination with CA19−9 for Liquid Biopsy-Based Detection of PDAC

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most aggressive malignancies and has high mortality and poor survival rates. Therefore, there is an urgent need to discover non-invasive biomarkers for early detection before PDAC reaches the incurable stage. We hypothesized that liquid biopsy of PDAC-derived extracellular vesicles (PDEs) containing abundant microRNAs (miRNAs) could be used for early diagnosis of PDAC because they can be selectively enriched and because they are biologically stable. We isolated PDEs by immunocapture using magnetic beads, and we identified 13 miRNA candidates in 20 pancreatic cancer patients and 20 normal controls. We found that expression of five miRNAs, including miR−10b, miR−16, miR−155, miR−429, and miR−1290, was markedly higher in PDEs. Furthermore, the miRNA signatures along with serum carbohydrate antigen 19−9 (CA19−9) were optimized by logistic regression, and the miRNA signature and CA19−9 combination markers (CMs) were effective at differentiating PDAC patients from normal controls. As a result, the CMs represented a high sensitivity (AUC, 0.964; sensitivity, 100%; specificity, 80%) and a high specificity (AUC, 0.962; sensitivity, 85.71%; specificity, 100%). These findings suggest that five miRNAs expressed in PDEs and CA19−9 are valuable biomarkers for screening and diagnosis of pancreatic cancer by liquid biopsy.

High Serum Carbohydrate Antigen (CA) 125 Level Is Associated With Poor Prognosis in Patients With Light-Chain Cardiac Amyloidosis

Background and Aims: Patients with light-chain cardiac amyloidosis (AL-CA) are characterized by high levels of serum carbohydrate antigen 125 (CA 125). However, studies have not explored the correlation between CA 125 and AL-CA. The aim of this study was to explore the clinical implications of an increase in CA 125 in patients with AL-CA.Methods and Results: A total of 95 patients diagnosed with AL-CA at the Second Xiangya Hospital were enrolled in this study. Out of the 95 patients with AL-CA, 57 (60%) patients had elevated serum CA 125 levels. The mean age was 59.7 ± 10.0 years with 44 (77.2%) men in the high serum CA 125 group, and 61.8 ± 9.6 years with 28 (73.7%) men in the normal group. Patients with high CA 125 showed higher rates of polyserositis (79.3% vs. 60.5%, p = 0.03), higher levels of hemoglobin (117.4 ± 21.9 g/L vs. 106.08 ± 25.1 g/L, p = 0.03), serum potassium (4.11 ± 0.47 mmol/L vs. 3.97 ± 0.40 mmol/L, p = 0.049), low-density lipoprotein-cholesterol (3.0 ± 1.6 mmol/L vs. 2.3 ± 1.10 mmol/L, p = 0.01), and cardiac troponin T (96.0 pg/mL vs. 91.9 pg/mL, p = 0.005). The median overall survival times for patients with high or normal serum CA 125 were 5 and 25 months, respectively (p = 0.045). Multivariate Cox hazard analysis showed that treatment without chemotherapy (HR 1.694, 95% CI 1.121–2.562, p = 0.012) and CA 125 (HR 1.002, 95% CI 1.000–1.004, p = 0.020) was correlated with high all-cause mortality. The time-dependent receiver operating characteristic (t-ROC) curve showed that the prediction accuracy of CA 125 was not inferior to that of cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and lactate dehydrogenase (LDH) based on the area under the curve.Conclusions: CA 125 is a novel prognostic predictor. High serum CA 125 values are correlated with low overall survival, and the accuracy of predicting prognosis is similar to that of traditional biomarkers in AL-CA.

Irreversible Electroporation Treatment With Intraoperative Biliary Stenting for Unresectable Perihilar Cholangiocarcinoma: A Pilot Study

BackgroundTreating perihilar cholangiocarcinoma (PHCC) is particularly difficult due to the fact that it is usually in an advanced stage at the time of diagnosis. Irreversible electroporation treatment (IRE) involves the local administration of a high-voltage electric current to target lesions without causing damage to surrounding structures. This study investigated the safety and efficacy of using IRE in conjunction with intraoperative biliary stent placement in cases of unresectable PHCC.MethodsThis study enrolled 17 patients with unresectable Bismuth type III/IV PHCC who underwent IRE in conjunction with intraoperative biliary stent placement (laparotomic) in two medical centers in Asia between June 2015 and July 2018. Analysis focused on the perioperative clinical course, the efficacy of biliary decompression, and outcomes (survival).ResultsMean total serum bilirubin levels (mg/dL) on postoperative day (POD) 7, POD30, and POD90 were significantly lower than before IRE (respectively 3.46 vs 4.54, p=0.007; 1.21 vs 4.54, p<0.001; 1.99 vs 4.54, p<0.001). Mean serum carbohydrate antigen 19-9 (CA19-9, U/ml) levels were significantly higher on POD3 than before the operation (518.8 vs 372.4, p=0.001) and significantly lower on POD30 and POD90 (respectively 113.7 vs 372.4, p<0.001; 63.9 vs 372.4, p<0.001). No cases of Clavien-Dindo grade III/IV adverse events or mortality occurred within 90 days post-op. The median progression-free survival was 21.5 months, and the median overall survival was 27.9 months. All individuals who survived for at least one year did so without the need to carry percutaneous biliary drainage (PTBD) tubes.ConclusionsIt appears that IRE treatment in conjunction with intraoperative biliary stent placement is a safe and effective approach to treating unresectable PHCC. The decompression of biliary obstruction without the need for PTBD tubes is also expected to improve the quality of life of patients.

Correlation between serum carbohydrate antigen 19-9 levels and computed tomography severity score in patients with nontuberculous mycobacterial pulmonary disease

There is no validated clinical biomarker for disease severity or treatment response for nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the correlation between elevated serum carbohydrate antigen (CA) 19-9 levels and NTM-PD disease activity, defined using an imaging severity score based on chest computed tomography (CT). We retrospectively examined 79 patients with NTM-PD who underwent serum CA19-9 level assessments and chest CT less than 1 month apart. NTM-PD severity was rated using a CT-based scoring system. The correlation between the CT score and serum CA19-9 levels was evaluated. Chest CT revealed nodular bronchiectasis without cavitation in most patients (78.5%). Serum CA19-9 levels were elevated in 19 (24%) patients. Serum CA19-9 levels were positively correlated with the total CT score and bronchiectasis, bronchiolitis, cavity, and consolidation subscores. Partial correlation analysis revealed a significant positive correlation between serum CA19-9 levels and CT scores for total score and bronchiectasis, bronchiolitis, cavitation, and consolidation subscores after controlling for age, sex, and BMI. Serum CA19-9 levels were positively correlated with the CT severity score for NTM-PD. Serum CA19-9 may be useful in evaluating disease activity or therapeutic response in patients with NTM-PD.

Decreased mean platelet volume predicts poor prognosis in patients with pancreatic cancer

Background Decreased mean platelet volume (MPV) predicts poor prognosis in some cancers. However, its significance as a prognostic indicator in pancreatic cancer (PC) remains unclear. Methods A total of 91 PC patients who underwent pancreatectomy were included in this study. MPV and serum carbohydrate antigen 19-9 (CA19-9) were measured within 1 week before surgery. Results We divided patients into MPVhigh (≥ 8.65; n = 40), MPVlow (< 8.65; n = 51), CA19-9high (≥ 66.3; n = 47), and CA19-9low (< 66.3; n = 44) groups based on the optimal cut-off values determined from receiver operating characteristic curve analysis. The 5-year overall survival (OS) rates were significantly lower in the MPVlow than in the MPVhigh group (16.9% and 56.3%, respectively; P = 0.0038), and the 5-year disease-specific survival (DSS) rates in the MPVlow group and MPVhigh group were 20.5% and 62.2%, respectively (P = 0.0031). Multivariate analysis identified MPV as an independent prognostic indicator for both OS and DSS. The patients were then divided into groups A (MPVhigh and CA19-9low), B (MPVhigh and CA19-9high), C (MPVlow and CA19-9low), and D (MPVlow and CA19-9high), with 5-year OS rates of 73.2%, 40.4%, 25.8%, and 10.3%, respectively (P = 0.0002), and 5-year DSS rates of 80.8%, 44.9%, 27.3%, and 16.4%, respectively (P = 0.0003). Conclusions Classification based on MPV and CA19-9 might be useful for predicting long-term outcomes in patients with PC.

Management of pancreatic cysts and guidelines: what the gastroenterologist needs to know

The prevalence of pancreatic cysts has increased significantly over the last decade, partly secondary to increased quality and frequency of cross-sectional imaging. While the majority never progress to cancer, a small number will and need to be followed. The management of pancreatic cysts can be both confusing and intimidating due to the multiple guidelines with varying recommendations. Despite the differences in the specifics of the guidelines, they all agree on several high-risk features that should get the attention of any clinician when assessing a pancreatic cyst: presence of a mural nodule or solid component, dilation of the main pancreatic duct (or presence of main duct intraductal papillary mucinous neoplasm), pancreatic cyst size ⩾3–4 cm, or positive cytology on pancreatic cyst fluid aspiration. Other important criteria to consider include rapid cyst growth (⩾5 mm/year), elevated serum carbohydrate antigen 19-9 levels, new-onset diabetes mellitus, or acute pancreatitis thought to be related to the cystic lesion.

A case of elevated carbohydrate antigen 19-9 with a benign cause

Serum carbohydrate antigen 19-9 (CA 19-9), a marker of malignant tumors, is generally slightly elevated in benign conditions. We report a case of cholecystitis with perforated gall bladder with significantly elevated level of serum CA 19-9 based on abdomen computed tomography and intra operative findings. A 70 years diabetic and hypertensive female presented with right hypochondriac pain associated with occasional itching and nausea without vomiting with markedly raised CA 19-9 (1554 U/ml) with CECT abdomen suggestive of perforated gall bladder with cholecystitis. Patient electively operated for open cholecystectomy and per operative findings were distended gall bladder with multiple calculi within with edematous gall bladder wall and adhesions between gall bladder and omentum and colon. Gall bladder removed and biopsy suggestive of chronic calculus cholecystitis. On post-operative day 5th and 7th CA 19-9 was repeated twice and drastic fall to 5 U/ml and 12 U/ml respectively. Chronic calculus cholecystitis with high elevation of CA 19-9 is rare.