Jin-Zhi Xu

Infiltrating immune cells and gene mutations in pancreatic ductal adenocarcinoma

The aim of this study was to assess the immune profile within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and to investigate the prognostic value of intratumoral infiltrating immune/inflammatory cells (IICs) in patients after surgery.

Intratumoral infiltrating immune cells and gene mutations in pancreatic ductal adenocarcinoma

The aim of this study was to assess the immune profile within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and to investigate the prognostic value of intratumoral infiltrating immune/inflammatory cells (IICs) in patients after surgery.

Revised nodal stage for pancreatic neuroendocrine tumors

BACKGROUND Previously we have proposed a modified European Neuroendocrine Tumor Society (mENETS) staging system for pNETs, which is more suitable than either the American Joint Committee on Cancer (AJCC) or the European Neuroendocrine Tumor Society (ENETS) systems. However, it is necessary to revise the nodal stage of the mENETS system for the under representation of stage III diseases. METHODS Nodal substages of the upper gastrointestinal organs (N0: 0 node, N1: 1-2 nodes; N2: ≥3 nodes) or the lower gastrointestinal organs (0: 0 node, N1: 1-3 nodes, and N2:≥ 4 nodes) were incorporated into the mENETS system and evaluated using the Surveillance, Epidemiology, and End Results (SEER) registry series. RESULTS The mENETS classification with the upper gastrointestinal N-stage revision (stage III, 17.1%) had better proportional distribution than the mENETS classification (stage III, 8.7%) or the lower gastrointestinal N-stage revision (stage III, 14.5%). N-stage revision (N0: 0 node, N1: 1-2 nodes; N2: ≥3 nodes) was incorporated in the mENETS staging definition for further analysis. Survival curves were well separated by nodal substages. HRs of stage IIA (T3N0M0) and IIB (T1-3N1M0) of the mENETS classification with N-stage revision were similar, indicating these two substages should be attributed to stage II. Survival curves were well separated by stage using the mENETS classification with N-stage revision. CONCLUSIONS The mENETS classification with N-stage revision (N0: 0 node, N1: 1-2 nodes; N2: ≥3 nodes) had better prognostic value and proportional distribution than the mENETS classification for pNETs and can be used in clinical practice.

Tryptase expression as a prognostic marker in patients with resected gastric cancer

Mast cells play important roles in the progression of various malignancies, but their prognostic value in gastric cancer is unknown. Tryptase expression, as an indicator of mast cell activity, was therefore evaluated to see whether this could be incorporated usefully into a prognostic nomogram after surgery in patients with gastric cancer.

Tumor-Infiltrating Platelets Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma

BackgroundPlatelets are believed to promote tumor growth and metastasis in several tumor types. The prognostic role of blood platelets in pancreatic ductal adenocarcinoma (PDAC) remains controversial, and the prognostic value of tumor-infiltrating platelets (TIPs) remains unknown.MethodsA total of 303 patients who underwent curative pancreatectomy for PDAC were enrolled from two independent centers in China and divided into three cohorts. Paired preoperative blood samples and surgical specimens from all patients were analyzed. The correlations between patient outcomes and preoperative blood platelet counts and the presence of TIPs, respectively, were analyzed. TIPs were identified by immunohistochemical staining of CD42b. Prognostic accuracy was estimated by concordance index (C-index) and Akaike information criterion (AIC).ResultsTIPs, but not preoperative blood platelet counts, were associated with overall survival (OS; all P < 0.001) and recurrence-free survival (RFS; all P < 0.001) in the training, testing, and validation sets. Positive CD42b expression predicted poor postsurgical survival. Incorporation of TIPs improved the predictive accuracy of the 8th edition American Joint Committee on Cancer (AJCC) tumor–node–metastasis (TNM) staging system for OS in each of the three cohorts (C-index: 0.7164, 0.7569, and 0.7050, respectively; AIC: 472, 386, and 1019, respectively). The new predictor system was validated by incorporating TIPs with the 7th edition AJCC TNM staging system (C-index: 0.7052, 0.7623, and 0.7157; AIC: 476, 386, and 1015).ConclusionTIPs were an independent prognostic factor that could be incorporated into the AJCC TNM staging system to refine risk stratification and predict surgical outcomes of patients with PDAC.

Postoperative serum CA19-9, CEA and CA125 predicts the response to adjuvant chemoradiotherapy following radical resection in pancreatic adenocarcinoma

OBJECTIVE To evaluate the prediction of benefits from adjuvant chemoradiotherapy by postoperative serum CA19-9, CA125 and CEA. METHODS The relations between benefits from adjuvant chemoradiotherapy and levels of postoperative serum CA19-9, CA125 and CEA were investigated in 804 pancreatic adenocarcinoma patients who received radical resection. RESULTS Adjuvant chemoradiotherapy was an independent factor for late recurrence [12.2 vs. 8.5 months, P = 0.001 for recurrence free survival (RFS)] and long survival [23.7 vs. 17.0 months, P < 0.001 for overall survival (OS)] in resected pancreatic adenocarcinoma. Postoperative serum CA19-9, CA125 and CEA were independent risk predictors for poor surgical outcome in pancreatic adenocarcinoma (P < 0.001 for all). Adjuvant chemradiotherapy (hazard ratio: 0.359, 95% confidence interval: 0.253-0.510, P < 0.001 for OS; hazard ratio: 0.522, 95% confidence interval: 0.387-0.705, P < 0.001 for RFS) were confirmed to improve the surgical outcome in patients with abnormal levels of any one of the three postoperative markers, but not in patients with normal levels of the three postoperative markers. In the subgroup of patients with negative lymph node, its improvement of surgical outcome was also significant in patients with abnormal levels of any one of postoperative serum CA19-9, CA125 and CEA (hazard ratio: 0.412, 95% confidence interval: 0.244-0.698, P = 0.001 for OS; hazard ratio: 0.546, 95% confidence interval: 0.352-0.847, P = 0.007 for RFS). CONCLUSION Postoperative serum CA19-9, CA125 and CEA could serve as predictors of response for adjuvant chemoradiotherapy even if the status of lymph nodes is negative.

The Significance of Liquid Biopsy in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer. The 5-year survival rate for PDAC remains low because it is always diagnosed at an advanced stage and it is resistant to therapy. A biomarker, which could detect asymptomatic premalignant or early malignant tumors and predict the response to treatment, will benefit patients with PDAC. However, traditional biopsy has its limitations. There is an urgent need for a tumor biomarker that could easily and repeatedly sample and monitor, in real time, the progress of tumor development. Liquid biopsy could be a tool to assess potential biomarkers. In this review, we focused on the latest discoveries and advancements of liquid biopsy technology in pancreatic cancer research and demonstrated how this technology is being used in clinical applications.

Neoadjuvant Therapy Is Essential for Resectable Pancreatic Cancer

BACKGROUND Awareness of the benefits of neoadjuvant therapy is increasing, but its use as an initial therapeutic option for patients with resectable pancreatic cancer remains controversial, especially for those patients without high-risk prognostic features. Even for patients with high-risk features who are candidates to receive neoadjuvant therapy, no standard regimen exists. METHODS In this review, we examined available data on neoadjuvant therapy in patients with resectable pancreatic cancer, including prospective studies, retrospective studies, and ongoing clinical trials, by searching PubMed/MEDLINE, ClinicalTrials.gov, Web of Science, and Cochrane Library. The characteristics and results of screened studies were described. RESULTS Retrospective and prospective studies with reported results and ongoing randomized studies were included. For patients with resectable pancreatic cancer, neoadjuvant therapy provides benefits such as increased survival, decreased risk of comorbidities and mortality, and improved cost-effectiveness due to increased completion rate of multimodal treatment. Highly active regimens such as FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine plus nab-paclitaxel are considered acceptable therapeutic regimens. Additionally, platinum-containing regimens other than FOLFIRINOX are acceptable for select patients. Other therapies, such as chemoradiation treatment, immuno-oncology agents, and targeted therapies are being explored and the results are highly anticipated. CONCLUSION This review highlights the benefits of neoadjuvant therapy for resectable pancreatic cancer. Some regimens are currently acceptable, but need more evidence from well-designed clinical trials or should be used on after being carefully examined by a multidisciplinary team.

ASO Author Reflections: Contact Between T and N Classifications in Pancreatic Neuroendocrine Neoplasms

Lymph node metastasis (LNM) is common in pancreatic neuroendocrine neoplasms (pNENs), but its prognostic value is controversial. Some studies show that LNM affects the prognosis of patients with pNENs, whereas other studies reveal that LNM is not associated with patients’ outcomes. Nowadays, various prognostication systems containing LNM have been proposed for pNENs, among which the tumor-node-metastasis (TNM) classification systems of the American Joint Committee on Cancer (AJCC) or the European Neuroendocrine Tumor Society (ENETS) are most commonly used. However, the controversy over which staging system was superior remained unsolved until a modified ENETS (mENETS) staging system was proposed in our previous study, which implied that the prognostic value of LNM may be related to T classification. The objective of our study was to identify whether factors determining T classification were related to N classification and to examine the impact of N1 classification on survival based on T classification. PRESENT

Angiogenesis in pancreatic cancer: current research status and clinical implications

Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of < 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors. However, clinical outcomes are far from satisfying for pancreatic cancer patients receiving anti-angiogenic therapies. In this review, we summarize the current status of angiogenesis in pancreatic cancer research and explore the reasons for the poor efficacy of anti-angiogenic therapies, aiming to identify some potential therapeutic targets that may enhance the effectiveness of anti-angiogenic treatments.