Alessandro Giardino

Combined modality treatment for patients with locally advanced pancreatic adenocarcinoma.

Radiofrequency ablation (RFA) is an emerging treatment for patients with locally advanced pancreatic carcinoma, and can be combined with radiochemotherapy and intra‐arterial plus systemic chemotherapy.

Triple approach strategy for patients with locally advanced pancreatic carcinoma

BACKGROUND Radiofrequency ablation (RFA) is a relatively new technique, applied to metastatic solid tumours which, in recent studies, has been shown to be feasible and safe on locally advanced pancreatic carcinoma (LAPC). RFA can be combined with radio-chemotherapy (RCT) and intra-arterial plus systemic chemotherapy (IASC). The aim of this study was to investigate the impact on the prognosis of a multimodal approach to LAPC and define the best timing of RFA. METHODS This is a retrospective observational study of patients who have consecutively undergone RFA associated with multiple adjuvant approaches. RESULTS Between February 2007 and December 2011, 168 consecutive patients were treated by RFA, of which 107 were eligible for at least 18 months of follow-up. Forty-seven patients (group 1) underwent RFA as an up-front treatment and 60 patients as second treatment (group 2) depending on clinician choice. The median overall survival (OS) of the whole series was 25.6 months: 14.7 months in the group 1 and 25.6 months in the group 2 (P = 0.004). Those patients who received the multimodal treatment (RFA, RCT and IASC-triple approach strategy) had an OS of 34.0 months. CONCLUSIONS The multimodal approach seems to be feasible and associated with an improved longer survival rate.

Local Ablative Strategies for Ductal Pancreatic Cancer (Radiofrequency Ablation, Irreversible Electroporation): A Review.

Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Locally advanced pancreatic cancer (LAPC) accounts for the 40% of the new diagnoses. Current treatment options are based on chemo- and radiotherapy regimens. Local ablative techniques seem to be the future therapeutic option for stage-III patients with PDAC. Radiofrequency Ablation (RFA) and Irreversible Electroporation (IRE) are actually the most emerging local ablative techniques used on LAPC. Initial clinical studies on the use of these techniques have already demonstrated encouraging results in terms of safety and feasibility. Unfortunately, few studies on their efficacy are currently available. Even though some reports on the overall survival are encouraging, randomized studies are still required to corroborate these findings. This study provides an up-to-date overview and a thematic summary of the current available evidence on the application of RFA and IRE on PDAC, together with a comparison of the two procedures.

Immunomodulation after radiofrequency ablation of locally advanced pancreatic cancer by monitoring the immune response in 10 patients

OBJECTIVE/BACKGROUND RFA of pancreatic cancer has been demonstrated to be feasible and safe with a positive impact on survival. The aim was to investigate whether an immune reaction is activated after locally advanced pancreatic cancer (LAPC) ablation. METHODS Peripheral Blood samples were obtained preoperatively and on post-operative days 3-30. Evaluated parameters were: cells [CD4+, CD8+ and activated subsets, T-Reg, Monocytes, myeloid and plasmocytoid Dendritic cells (mDC and pDC)] and cytokines [Interleukin (IL)-6, Stromal-cells derived factor (SDF)-1, IL-1β, Tumour-Necrosis Factor (TNF)-α, Interferon (IFN)-γ, Vascular Endothelial Growth Factor (VEGF), chemokine (C-C motif) ligand 5 (CCL-5), Transforming-Growth Factor (TGF)-β]. RESULTS Ten patients were enrolled. CD4+, CD8+ and TEM increased from day 3 suggesting the activation of the adaptive response. Immunosuppressive T-Reg cells were stable despite the possibility that laparotomy and heating might favour their expansion. Myeloid DCs, that present tumour-associated antigens, increased at day 30. RFA dramatically increased circulating IL-6 at day 3 but this decreased to baseline by day 30, consistent with the supposed anti-tumour effect. RFA did not significantly modulate essential chemokines, such as CCL-5 and SDF1, VEGF, TGF-β and TNF-α, that favour tumour-growth by sustaining cancer angiogenesis and fuelling tumour-associated inflammation. CONCLUSIONS This study provides the first evidence of RFA-based immunomodulation in LAPC. We observed a general activation of adaptive response along with a decrease of immunosuppression. Furthermore, most cells showed prolonged activation some weeks after the procedure, suggesting true immunomodulation rather than a normal inflammatory response.

Tumor thrombosis: a peculiar finding associated with pancreatic neuroendocrine neoplasms. A pictorial essay

While abutment, encasement or vessel occlusion are identified in most patients with a pancreatic tumor, tumor thrombosis is an uncommon finding. In particular, there are no description in the literature of tumor thrombosis associated with ductal adenocarcinoma, the most common pancreatic tumor. On the other hand, surgical series reveal that tumor thrombosis is associated with about 5% of pancreatic neuroendocrine neoplasms (PanNENs), and literature data suggest that this finding is frequently underreported on pre-operative imaging examinations. Tumor thrombosis may be clinically relevant, causing splenoportomesenteric hypertension, possibly responsible for life-threatening upper gastrointestinal bleeding. Bland thrombosis caused by direct infiltration of peri-pancreatic vessels frequently determines surgical unresectability, even in neuroendocrine tumors; on the opposite, tumor thrombosis associated with PanNENs do not exclude surgery per se, even though both morbidity and mortality can be increased by such condition. Considering the favorable prognosis of PanNENs and the frequent need to treat tumor thrombosis in order to prevent complications or to relieve symptoms, it is of paramount importance for radiologists the knowledge of the variety of findings associated with tumor thrombosis in PanNENs.

Role of local ablative techniques (Radiofrequency ablation and Irreversible Electroporation) in the treatment of pancreatic cancer

Thanks to continuous research and investment in technology, the ablation of tumors has become common. Through the application of different types of energy is possible to induce cellular injury of the neoplastic tissue, leading to cellular death. Radiofrequency ablation (RFA) and irreversible electroporation (IRE) represent the most applied ablative techniques on pancreatic cancer. RFA and IRE, causing necrosis and apoptosis of neoplastic cells, are able to destroy neoplastic tissue, to drastically modify the neoplastic microenvironment and, possibly, to stimulate both directly and indirectly the anti-tumor immune system. This article provides part of our experience with the application of RFA and IRE on pancreatic adenocarcinoma (PDAC).

Radiofrequency Ablation of Pancreatic Mass

Stage III pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and no gold standard treatment has been established so far. Radiofrequency ablation (RFA) is a new treatment option for locally advanced pancreatic cancer (LAPC), but its application is still very limited. We report our experience on 200 patients treated with pancreatic RFA as cytoreductive intent associated with chemoradiotherapy in a multimodal setting. In our series, median survival was 19 months and progression-free survival was 13 months. The results do not seem to depend on the rate of the ablated area. Postoperative course was uneventful in 76 % of cases, abdominal complications occurred in 23 % of patients, and the mortality rate was 2 %. However, after the last technical changes (temperature 80 °C, limited ablation, use of single cool-tip needle, safety distance from the duodenum), we found a significant reduction of morbidity (from 25% to 13%) and mortality (from 2% to 0%). RFA with endoscopic ultrasound approach (EUS-RFA) has been recently proposed, but the experience is still very limited. The advantages of EUS-RFA are being a less invasive approach, more precise placement of the needle due to high-resolution images, and short hospital stay. Moreover, the procedure is potentially repeatable.