Serum JAK/STAT profile is related to the IL expression but not with the outcome in pancreatic adenocarcinoma patients.

Current genetic characterization of pancreatic ductal adenocarcinoma (PDAC) does not integrate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. The JAK/STAT pathway is an important factor of cytokine-mediated cancer inflammation, but its relationship with pancreatic carcinogenesis and the role of potential biomarkers is not established yet. Our study aimed to assess the significance of serum levels of JAK/STAT3 expression and inflammatory cytokines in PDAC in relation to the clinicopathological features and prognosis. This prospective cohort study included patients with proven adenocarcinoma and a matched group of controls without any malignancies. There were evaluated the serum expression of IL2, 6, 8, 17, JAK2, and STAT3 by ELISA assays in these two groups. The PDAC patients were followed up for 24 months. A Cox regression multivariate analysis model was used to determine factors influencing survival. The study comprised 56 patients with PDAC and 56 controls. The upregulated serum JAK2/STAT3 or cytokines were present in about half of the patients with PDAC, similar to controls. The expression of JAK2 in serum of PDAC patients was significantly associated with the expression of IL2 (p=0.03) and IL6 (p=0.02) but not with survival or metastasis development. Only age and the presence of lymph node metastases were associated with reduced survival in multivariate analyses. The STAT 3/JAK2 expression, although correlated with inflammatory status (IL2, IL6) was not overexpressed in PDAC compared to controls and proved no prognostic value.

Endoscopic ultrasonography-fine needle aspiration of solid pancreatic masses: Do we need the fourth pass? A prospective study.

BACKGROUND: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) is important for the differential diagnosis of solid pancreatic lesions. Sample adequacy is related to the number of needle passes, and European guidelines recommend three to four needle passes with a standard EUS-FNA needle. We aimed to evaluate the optimal number of passes with standard EUS-FNA needles in solid pancreatic lesions. METHODS: Patients with solid pancreatic masses without cystic component >20% on computed tomography scan, and without biliary metallic stents, or coagulation problems were included prospectively. Standard 22G needles were used (maximum four passes); each sample was paraffin-embedded and analyzed separately. Final diagnosis was established by EUS-FNA, repeat EUS-FNA, surgery, or follow-up. RESULTS: Sixty-one of 65 patients were included. The final diagnoses were adenocarcinoma (n = 44, 72%), neuroendocrine tumor (NET) (n = 10, 16%), metastasis (n = 1, 4%) and nonmalignant lesion (n = 6, 10%). Immunohistochemical staining was possible in 17 cases. The diagnosis was established by the first pass in 62% of cases (n = 38), by the second in 15% (n = 9), by the third in 15% (n = 9), and by the fourth in 3% (n = 2). The diagnostic accuracy for all four passes compared to the first three passes was 95% vs 92% (P = .5). The contribution of the fourth pass was not different between adenocarcinoma and NET (2% vs 10%, respectively; P = .667). CONCLUSION: Three passes with standard EUS-FNA was optimal for a specific diagnosis of solid pancreatic masses, regardless of the histological type of the lesion.

Risk Factors in Pancreatic Adenocarcinoma: the Interrelation with Familial History and Predictive Role on Survival.

BACKGROUND AND AIMS: Pancreatic cancer is associated with poor survival and quality of life. In Romania the prognostic influence of known risk factors for pancreatic adenocarcinoma, such as age, smoking, chronic pancreatitis, diabetes mellitus, and obesity is little known. Their importance in developing cancer in families with a history of adenocarcinoma is less studied. This study aims to assess the risk factors in pancreatic ductal adenocarcinoma, in familial pancreatic adenocarcinoma, in neuroendocrine tumors and to evaluate their predictive role on survival. METHODS: We performed a prospective bicentric study of patients with pancreatic tumors detected in transabdominal imaging; we assessed the risk factors and their possible association with survival. RESULTS: 312 pancreatic cancer patients (279 with pancreatic ductal adenocarcinoma and 24 patients with neuroendocrine tumors, and nine patients with other malignant types) and 312 controls were included. The median body mass index was significantly higher in patients with neuroendocrine tumors. Positive family history for pancreatic cancer was found in 4% of patients with pancreatic cancer. The risk for familial pancreatic carcinoma was associated with the presence of new-onset diabetes (OR: 4.64, p=0.018). The multivariate logistic analysis suggested that advanced age (OR: 1.67), smoking (OR: 1.67), low body mass index (OR: 12.07), and diabetes (OR: 3.91) were risk factors for pancreatic cancer. The overall survival analysis after adjustment for age and tumor stage showed only advanced tumoral stage (HR=1.6, p=0.003) and metastasis as independent predicting factors (HR=1.67, p<0.001). CONCLUSION: Our study suggests that diabetes, smoking, underweight, and age over 60 years are risk factors for pancreatic cancer. Patients with a family history of pancreatic cancer, especially those with new-onset diabetes, should be followed carefully and considered for screening. Only an advanced tumor stage was associated with poor overall survival for patients with pancreatic ductal adenocarcinoma.

Relationship between cachexia and perineural invasion in pancreatic adenocarcinoma.

BACKGROUND: Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma (PDAC). The rapid disease progression and patient deterioration seems related to perineural invasion, but the relationship between cachexia and perineural invasion for the evolution of the disease has been rarely studied. As perineural invasion is difficult to be highlighted, a biomarker such as the neurotrophic factor Midkine (MK) which promotes the neuronal differentiation and the cell migration could be helpful. Also, Activin (ACV) has been described as cachexia related to PDAC. However, their role for assessing and predicting the disease course in daily practice is not known. AIM: To assess the relationship between perineural invasion and cachexia and their biomarkers, MK and ACV, respectively, and their prognostic value. METHODS: This study included prospectively enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies. Patients with other causes of malnutrition were excluded. The plasma levels of ACV and MK were analyzed using western blotting and were correlated with the clinicopathological features and survival data. These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the patients included in the study and a supplementary group of surgically resected specimens from patients with a benign disease. RESULTS: The study comprised 114 patients with PDAC, 125 controls and a supplementary group of 14 benign pancreatic tissue samples. ACV and MK were both overexpressed more frequently in the plasma of patients with PDAC than in the controls (63% vs 32% for ACV, P < 0.001; 47% vs 16% for MK, P < 0.001), with similar levels in pancreatic tissue the MK protein expression was closely related to the advanced clinical stage (P = 0.006), the presence of metastasis (P = 0.04), perineural invasion (P = 0.03) and diabetes (P = 0.002), but with no influence on survival. No correlation between clinicopathological factors and ACV expression was noted. Cachexia, present in 19% of patients, was unrelated to ACV or MK level. Higher ACV expression was associated with a shorter survival (P = 0.008). CONCLUSION: The MK was a biomarker of perineural invasion, associated with tumor stage and diabetes, but without prognostic value as ACV. Cachexia was unrelated to perineural invasion, ACV level or survival.

New targeted therapies in pancreatic cancer.

Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.