Predictive Factors for Differentiating Pancreatic Cancer-Associated Diabetes Mellitus from Common Type 2 Diabetes Mellitus for the Early Detection of Pancreatic Cancer.

BACKGROUND: The purpose of this study was to find the factors that may be helpful for differentiating pancreatic cancer-associated diabetes mellitus (PC + DM) from common type 2 diabetes for the early diagnosis of pancreatic cancer. METHODS: From January 2008 to August 2013, 171 patients with pancreatic cancer and new-onset diabetes were recruited for the study; 242 age- and gender-matched patients with common type 2 diabetes were also identified as control during the same period. The patient's characteristics and laboratory parameters were compared between the 2 groups. RESULTS: By multivariate logistic regression analysis, we found that body mass index (BMI), the age of onset of diabetes, hepatitis B virus (HBV) infection, total bilirubin (TBIL), alanine aminotransferase (ALT), creatinine (Cr), apolipoprotein-A1 (APO-A1), and white blood cell (WBC) were independent predictive factors for differentiating PC + DM from common type 2 diabetes; the areas under receiver operating characteristic curves were up to 0.815 for the combination of these 8 markers. CONCLUSIONS: These results suggest that BMI, the age of onset of diabetes, HBV infection, TBIL, ALT, Cr, APO-A1, and WBC are factors that could differentiate PC + DM from common type 2 -diabetes and may be used for early diagnosis of pancreatic cancer.

Successful outcome of neoadjuvant PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy for potentially unresectable esophagogastric junctional squamous cell carcinoma: a case report.

Background: Esophagogastric junctional squamous cell carcinoma (EJSCC) is quite rare among all gastric carcinoma, its potential resectable rate is low due to the late diagnosis. Recently, programmed death-1 (PD-1) blockade combined with anti-angiogenesis have gained accumulated clinical experiences in treating solid tumors. This is the first reported case with EJSCC who achieved a partial remission (PR) after neoadjuvant PD-1 blockade, vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor plus chemotherapy. Case Description: We present an EJSCC case treated with novel neoadjuvant treatment. A 64-year-old Chinese male had the symptom of chocking for 3 months. An enhanced abdominal computed tomography (CT) scan found a locally advanced, potentially unresectable esophagogastric junctional (EGJ) mass, and the preoperative immunohistochemistry result exhibited a highly positive programmed death-ligand 1 (PD-L1) expression, so the patient received three courses of neoadjuvant camrelizumab (200 mg/day), apatinib (750 mg/day), albumin paclitaxel (200 mg/day) and nedaplatin (70 mg/day), he was well tolerant without any adverse event, and he underwent radical surgery after a significant tumor shrinkage. The patient recovered well after surgery, and he has received four cycles of camrelizumab and apatinib as maintenance treatment. There is no recurrence 7 months after surgery. Conclusions: PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy is effective and safe for the patient with EJSCC.

Efficacy and safety of long-term transcutaneous electroacupuncture versus sham transcutaneous electroacupuncture for delayed gastric emptying after distal gastrectomy: study protocol for a randomized, patient-assessor blinded, controlled trial.

BACKGROUND: Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS: A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION: The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.

Novel blood biomarkers of pancreatic cancer-associated diabetes mellitus identified by peripheral blood-based gene expression profiles.

OBJECTIVES: The prognosis of pancreatic cancer is still very poor, and the ability to detect pancreatic cancer in high-risk groups at an early stage is therefore essential for improving its long-term survival. The purpose of this study was to explore specific biomarkers that can differentiate pancreatic cancer-associated diabetes from type 2 diabetes, for the early detection of pancreatic cancer. METHODS: From January 2006 to July 2008, 102 peripheral blood samples were collected from 25 patients diagnosed with pancreatic cancer and diabetes, 27 patients with pancreatic cancer without diabetes, 25 patients with diabetes mellitus >5 years, and 25 healthy controls. Thirty-two samples were used in microarray experiments to find differentially expressed genes specific for pancreatic cancer-associated diabetes. The results were further validated by quantitative real-time PCR for 101 blood samples. Protein expression of selected genes in serum and tissues was also detected. RESULTS: Using microarray analysis, we found 58 genes to be unique in patients with pancreatic cancer-associated diabetes, including 23 upregulated genes and 35 downregulated genes. Eleven upregulated genes were further validated by RT-PCR, and two of these genes-vanin-1 (VNN1) and matrix metalloproteinase 9 (MMP9)-were selected for logistic regression analysis. The combination of VNN1 and MMP9 showed the best discrimination of pancreatic cancer-associated diabetes from type 2 diabetes. The protein expression of MMP9 and VNN1 was in accordance with the gene expression. CONCLUSIONS: Our results indicate that the combination of VNN1 and MMP9 may be used as a novel blood biomarker panel for the discrimination of pancreatic cancer-associated diabetes from type 2 diabetes.

Pancreatic cancer-derived exosomes promoted pancreatic stellate cells recruitment by pancreatic cancer.

Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been identified in the blood circulation of patients with cancer metastasis, and metastatic cancer cells can recruit circulating CAFs. However, primary carcinoma sites usually regulate the behavior of metastatic cancer cells through exosomes. Here, we hypothesized that cancer-derived exosomes could enhance CAF recruitment. Exosomes secreted by pancreatic cancer cells (PANC-1 and MIA PaCa-2) were isolated and characterized. The ability of pancreatic cancer to recruit pancreatic stellate cells (PSCs) was assessed with Transwell assays in vitro and bioluminescent imaging in a mouse model in vivo, and the underlying molecular mechanism was also investigated. The results showed that pancreatic cancer cell-derived exosomes (Exo-Pan and Exo-Mia) promoted the pancreatic cancer recruitment of PSCs. This effect was mediated partially by the transfer of the exosomal protein Lin28B to the recipient cells to activate the Lin28B/let-7/HMGA2/PDGFB signaling pathway. These results suggested that exosomes derived from local cancer could promote the formation of distant metastases through transferring the exosomal protein Lin28B to the metastatic cancer cells.

MACC1: A potential molecule associated with pancreatic cancer metastasis and chemoresistance.

It has been suggested that the newly identified metastasis-associated in colon cancer-1 (MACC1) oncogene is involved in the progression and metastasis of cancer. Several studies have indicated that MACC1 has potential as a novel biomarker. In this study, we aimed to investigate the functions and serum expression levels of MACC1 in pancreatic cancer patients. Blood serum samples from 60 cancer patients and 49 controls were analyzed for serum MACC1 by ELISA. The results revealed that high expression levels of MACC1 were correlated with lymph node metastasis, distant metastasis and a later TNM stage. Inhibition of MACC1 by siRNAs significantly suppressed pancreatic cancer cell proliferation and migration. Furthermore, it was found that the downregulation of MACC1 sensitized pancreatic cancer cells to gemcitabine treatment through the inhibition of the Ras/ERK signaling pathway. Our findings suggest that MACC1 may aid in the diagnosis of pancreatic cancer and serve as a potential therapeutic target.

Analysis of pancreatic fistula according to the International Study Group on Pancreatic Fistula classification scheme for 294 patients who underwent pancreaticoduodenectomy in a single center.

OBJECTIVES: The purposes of this study were to validate the value of the International Study Group on Pancreatic Fistula (ISGPF) classification scheme for pancreatic fistula (PF) and to identify predictive factors for clinically significant PF. METHODS: From January 2000 to December 2007, 294 consecutive patients underwent pancreaticoduodenectomy in a single medical center. Pancreatic fistula was evaluated by the ISGPF criteria and Johns Hopkins Hospital's definition (JHH). Then, logistic regression analysis was performed to identify predictive factors for PF development. Our own management strategies with PF were also discussed. RESULTS: The overall incidence of PF was 19.4% (57/294) according to the ISGPF criteria, and 8.8% (26/294) using the JHH definition. Thirty-one patients with PF classified by the ISGPF were missed by the JHH definition. By logistic regression analysis, we found that besides the lack of cardiovascular disease and malignant diseases, our single-layer continuous circular invaginated pancreaticojejunostomy was another independent factor for the lowered incidence of PF. CONCLUSIONS: The ISGPF classification scheme was accurate for evaluating PF. Single-layer continuous circular invaginated pancreaticojejunostomy may be a promising method that may have been responsible for the lower incidence of PF in this study.