Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better than alpha-fetoprotein in diagnosis of hepatitis B virus-related hepatocellular carcinoma patients.

Prognostic and recurrent significance of SII in patients with pancreatic head cancer undergoing pancreaticoduodenectomy.

Background: To investigate the clinical significance of preoperative inflammatory status in patients with pancreatic head carcinoma (PHC), we performed a single-center study to assess it. Method: We studied a total of 164 patients with PHC undergoing PD surgery (with or without allogeneic venous replacement) from January 2018 to April 2022. Systemic immune-inflammation index (SII) was the most important peripheral immune index in predicting the prognosis according to XGBoost analysis. The optimal cutoff value of SII for OS was calculated according to Youden index based on the receiver operating characteristic (ROC) curve and the cohort was divided into Low SII group and High SII group. Demographic, clinical data, laboratory data, follow-up data variables were obtained and compared between the two groups. Kaplan-Meier curves, univariable and multivariable Cox regression models were used to determine the association between preoperative inflammation index, nutritional index and TNM staging system with OS and DFS respectively. Results: The median follow-up time was 16 months (IQR 23), and 41.4% of recurrences occurred within 1 year. The cutoff value of SII was 563, with a sensitivity of 70.3%, and a specificity of 60.7%. Peripheral immune status was different between the two groups. Patients in High SII group had higher PAR, NLR than those in Low SII group (P <0.01, <0.01, respectively), and lower PNI (P <0.01). Kaplan-Meier analysis showed significantly poorer OS and DFS (P < 0.001, <0.001, respectively) in patients with high SII. By using the multivariable Cox regression model, high SII (HR, 2.056; 95% CI, 1.082-3.905, P=0.028) was significant predictor of OS. Of these 68 high-risk patients who recurrence within one year, patients with widespread metastasis had lower SII and worse prognosis (P <0.01). Conclusion: High SII was significantly associated with poor prognosis in patients with PHC. However, in patients who recurrence within one year, SII was lower in patients at TNM stage III. Thus, care needs to be taken to differentiate those high-risk patients.

Clinical characteristics, treatment patterns and survival outcomes of early-onset pancreatic adenocarcinoma: a population-based study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a rare and refractory malignancy. Early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed before the age of 50 years, is very rare. Clinical presentation and oncological outcomes of EOPC are confusing according to previous studies. METHODS: We performed a retrospective, population-based study by querying the SEER database to analyze patients with PDAC from 2004 to 2018. Data on demographics, pathological characteristics, treatment patterns, and survival outcomes were compared between EOPC and pancreatic cancer in older patients. Propensity score matching (PSM) was used to minimize the potential bias of baseline characteristics between the two groups. The effect of age on changes in treatment modalities was evaluated using the Cochran-Armitage trend test. RESULTS: The entire study enrolled 42,414 patients, including 2,916 (6.9%) patients with EOPC. Patients with EOPC were more likely to be male (56.6% vs. 51.0%, P < 0.001) and more frequently to present with a larger tumor size (40 mm vs. 37 mm, P < 0.001), vascular invasion (28.6% vs. 25.9%, P = 0.022) and distant metastasis (56.2% vs. 50.8%, P < 0.001) compared with older group. However, surgical resection rates (29.3% vs. 28.3%, P = 0.284) were fairly comparable, and most clinicopathologic characteristics were similar in the patients underwent resection. Younger patients had longer 5-year overall survival (6.9% vs. 5.5%, P < 0.001) and 5-year cancer-specific survival (8.4% vs. 7.3%, P < 0.001) among the overall cohort but had comparable prognosis among patients received surgery (both P > 0.05). Similar survival outcomes were obtained after PSM. In addition, operated patients tended to receive fewer systemic treatments at an increasing age (Ptrend < 0.001). The survival analysis, which was stratified by age groups, suggested that younger patients only had a better prognosis than those over 70. CONCLUSIONS: Patients with EOPC exhibited an advanced stage and a male predilection at diagnosis in the overall cohort but broadly similar clinicopathologic characteristics in the operated patients. In the surgical cohort, although younger patients were more likely to receive systemic treatment, patients with EOPC presented comparable outcomes compared with elderly patients. We suggest that more research should be conducted to uncover the unique characteristics of EOPC for better clinical management.

The expression characteristics of transmembrane protein genes in pancreatic ductal adenocarcinoma through comprehensive analysis of bulk and single-cell RNA sequence.

Background: Transmembrane (TMEM) protein genes are a class of proteins that spans membranes and function to many physiological processes. However, there is very little known about TMEM gene expression, especially in cancer tissue. Using single-cell and bulk RNA sequence may facilitate the understanding of this poorly characterized protein genes in PDAC. Methods: We selected the TMEM family genes through the Human Protein Atlas and characterized their expression by single-cell and bulk transcriptomic datasets. Identification of the key TMEM genes was performed through three machine learning algorithms: LASSO, SVM-RFE and RF-SRC. Then, we established TMEM gene riskscore and estimate its implication in predicting survival and response to systematic therapy. Additionally, we explored the difference and impact of TMEM gene expression in PDAC through immunohistochemistry and cell line research. Results: 5 key TMEM genes (ANO1, TMEM59, TMEM204, TMEM205, TMEM92) were selected based on the single-cell analysis and machine learning survival outcomes. Patients stratified into the high and low-risk groups based on TMEM riskscore, were observed with distinct overall survival in internal and external datasets. Moreover, through bulk RNA-sequence and immunohistochemical staining we verified the protein expression of TMEM genes in PDAC and revealed TMEM92 as an essential regulator of pancreatic cancer cell proliferation, migration, and invasion. Conclusion: Our study on TMEM gene expression and behavior in PDAC has revealed unique characteristics, offering potential for precise therapeutic approaches. Insights into molecular mechanisms expand understanding of PDAC complexity and TMEM gene roles. Such knowledge may inform targeted therapy development, benefiting patients.

Clinicopathological Characteristics of Nonfunctional Pancreatic Neuroendocrine Neoplasms and the Effect of Surgical Treatment on the Prognosis of Patients with Liver Metastases: A Study Based on the SEER Database.

Background: The incidence of nonfunctional pancreatic neuroendocrine neoplasms (NF-pNENs) has been increasing annually. This study is aimed at investigating the clinicopathological characteristics and high-risk factors of NF-pNENs and the influence of surgical treatment on the prognosis of NF-pNEN patients with liver metastases. Methods: pNEN patients in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. This study analyzed patients diagnosed with NF-pNENs from 2000 to 2017 who met the inclusion criteria. A retrospective analysis of the clinicopathological characteristics of NF-pNEN patients was conducted. Kaplan-Meier method was used to calculate the survival time. A multivariate Cox regression model was used to analyze the survival outcomes and risk factors. Results: From 2000 to 2017, the SEER database registered 10576 patients with pNENs and 1774 patients with liver metastases. Cox analysis revealed that age, sex, primary site, grade, tumor stage, surgery, tumor size, and liver metastasis were risk factors of prognosis, with grade being the most influential index. Patients with NF-pNENs with liver metastasis and no metastasis had different primary site, grade, and tumor size. In general, a higher grade was associated with a larger tumor and a greater risk of liver metastasis. Meanwhile, patients with liver metastasis showed that those with tumors originated from the tail of the pancreas had better prognoses than those with tumors originated from other parts. Surgical treatment can improve the prognosis of patients with liver metastases, despite the tumor grade. Conclusions: The incidence of pNENs has been increasing annually, and the liver has been the most common site of metastasis. Liver metastasis in patients with NF-pNENs, related to tumor size and grade, affected their long-term survival. Surgery significantly improved the prognosis of patients with liver metastases secondary to NF-pNENs with different grades.

The prognostic value of CA19-9 response after neoadjuvant therapy in patients with pancreatic cancer: a systematic review and pooled analysis.

BACKGROUND: Pancreatic cancer (PC) is a highly aggressive and refractory disease, with disappointing 5-year survival rates. Regarding the wide application of neoadjuvant treatment in patients with PC, how the post-neoadjuvant Carbohydrate antigen 19-9 (CA19-9) response could translate into a survival benefit is not clearly understood. We aimed to evaluate the correlation of the CA19-9 response with overall survival (OS) in patients with PC receiving neoadjuvant therapy. METHODS: An extensive electronic search in PubMed, Embase, and the Cochrane Library was performed to identify relevant articles, from which data relevant to independent correlations of the CA19-9 response with overall survival (OS) were extracted for analysis. A random-effects model was used to calculate the pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). RESULTS: Altogether, 17 eligible studies were identified in the systematic review. Pooled analysis showed that CA19-9 response > 50% (HR, 0.43; 95% CI 0.29-0.56; P < 0.001) and normalization of CA19-9 (HR, 0.52; 95% CI 0.42-0.63; P < 0.001) after neoadjuvant treatment are significantly associated with promising overall survival. The results also showed that optimal CA19-9 response after neoadjuvant treatment was significantly related to a favorable prognosis (HR = 0.49, 95% CI 0.42-0.55, P < 0.001; I2 = 45.1%, P = 0.04). Subgroup analysis revealed there were no prognostic difference between CA19-9 > 50% and normalization of CA19-9 after neoadjuvant treatment (P = 0.338), but the duration of neoadjuvant chemotherapy over 4 months was significantly associated with expanded postoperative survival (P = 0.013). CONCLUSIONS: Serum CA19­9 is valuable in determining the effect of neoadjuvant treatment in patients with PC. Post-neoadjuvant CA19-9 response > 50% or CA19-9 normalization was related to a more promising overall survival, suggesting that optimal CA19-9 response may be a suitable prognostic index to guide treatment decisions.