Catecholamines stimulate epithelial proliferation, but the role of sympathetic nerve signaling in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Catecholamines promoted ADRB2-dependent PDAC development, nerve growth factor (NGF) secretion, and pancreatic nerve density. Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras;Pdx1-Cre (KC) mice. ADRB2 blockade together with gemcitabine reduced NGF expression and nerve density, and increased survival of LSL-Kras;LSL-Trp53;Pdx1-Cre (KPC) mice. Therapy with a Trk inhibitor together with gemcitabine also increased survival of KPC mice. Analysis of PDAC patient cohorts revealed a correlation between brain-derived neurotrophic factor (BDNF) expression, nerve density, and increased survival of patients on nonselective β-blockers. These findings suggest that catecholamines drive a feedforward loop, whereby upregulation of neurotrophins increases sympathetic innervation and local norepinephrine accumulation.

Neoadjuvant chemoradiation was feasible, safe, and efficacious, although non-significant results were obtained as a result of the underpowered data due to the difficulty in recruiting patients. Additional multicenter RCTs are needed in the future.

Patients treated with platinum compounds are subject to hypersensitivity reactions. Our study has highlighted the reactions related to oxaliplatin (OHP) infusion. One hundred and twenty-four patients affected by advanced colorectal cancer were treated with different schedules containing OHP, at the Institute of Haematology and Medical Oncology 'L. and A. Seragnoli' of Bologna and at the Medical Oncology Division of Livorno Hospital. Seventeen patients (13%) showed hypersensitivity reactions after a few minutes from the start of the OHP infusion. Usually, these reactions were seen after 2 -17 exposures to OHP (Mean7s.e.: 9.471.07). No patient experienced allergic reactions at his/her first OHP infusion. Eight patients developed a mild reaction consisting of flushing and swelling of the face and hands, itching, sweating and lachrymation. The remaining nine patients showed a moderatesevere reaction with dyspnoea, wheezing, laryngospasm, psycho-motor agitation, tachycardia, precordial pain, diffuse erythema, itching and sweating. Six patients out of 17 were re-exposed to the drug with premedication of steroids and all except one developed the hypersensitivity reaction again. The cumulative dose, the time of exposure to OHP and the clinical features are variable and unpredictable. The risk of developing hypersensitivity reactions in patients treated with a short infusion of OHP cannot be underestimated.

Even if the number of patients compared is underpowered, the laparoscopic approach in the treatment of PDAC seems to be safe and efficacious. However, additional prospective, randomised, multicentric trials are needed to correctly evaluate the laparoscopic approach in PDAC.

From this study, it seems reasonable to suggest that total pancreatectomy can be considered as safe, feasible, and efficacious as PD and acceptable in terms of cost-effectiveness.

No abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a five-year survival rate of approximately 5%. Several target agents have been tested in PDAC, but almost all have failed to demonstrate efficacy in late phase clinical trials, despite the better understanding of PDAC molecular biology generated by large cancer sequencing initiatives in the past decade. Eroltinib (a small-molecule tyrosine-kinase inhibitor of epidermal growth factor receptor) plus gemcitabine is the only schedule with a biological agent approved for advanced pancreatic cancer, but it has resulted in a very modest survival benefit in unselected patients. In our work, we report a summary of the main clinical trials (closed and ongoing) that refer to biological therapy evaluation in pancreatic cancer treatment.

Aim: The purpose of the present multicentric study was to review stereotactic body radiotherapy (SBRT) with or without chemotherapy (CHT) experience in locally advanced pancreatic cancer (LAPC). Endpoints were overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). Several parameters' impact on these outcomes was assessed. Materials and Methods: Fifty-six patients with LAPC undergoing SBRT+/-CHT were included. SBRT median BED α/β10Gy was 48.0 Gy (range=28.0-78.7). Survival curves were calculated by Kaplan-Meier method. A Cox regression model was fitted. Results: At a median follow-up of 15.0 months, 2-year OS, LC, DMFS were: 33.8% 55.4%, and 22.9%, respectively. Patients treated with BED α/β10Gy ≥48 Gy showed improved OS (p=0.020) and LC (p=0.024). At multivariate analysis, BED α/β10Gy ≥48 Gy was significantly associated to both higher OS (p=0.042) and LC (p=0.045), while post-SBRT CHT improved DMFS (p=0.003). Conclusion: SBRT proved to be tolerable and effective in LAPC. Moreover, BED α/β10Gy ≥48 Gy was significantly correlated with improved OS and LC. Pancreatic cancer (Pca) is projected to become the second cancer killer in the United States by 2030 (1). Overall, 5-year survival in Pca patients is only 8% (2). Radical surgery achieving negative margins is the only treatment able to gain long-term survival (3, 4). Unfortunately, only a small percentage of patients (around 20%) present with a resectable tumor at diagnosis, while 30-40% of them have unresectable locally advanced disease (5). Moreover, these patients represent a category with an intermediate prognosis between resectable and metastatic disease (6), with a median overall survival (OS) ranging from 9 to 11 months (5). Nowadays, a therapeutic standard approach for Pca is missing and therefore the treatment is frequently institution 465 This article is freely accessible online.