Paolo Regi

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.

Pancreatic neuroendocrine neoplasms: Magnetic resonance imaging features according to grade and stage

AIM To describe magnetic resonance (MR) imaging features of pancreatic neuroendocrine neoplasms (PanNENs) according to their grade and tumor-nodes-metastases stage by comparing them to histopathology and to determine the accuracy of MR imaging features in predicting their biological behavior. METHODS This study was approved by our institutional review board; requirement for informed patient consent was waived due to the retrospective nature of the study. Preoperative MR examinations of 55 PanNEN patients (29 men, 26 women; mean age of 57.6 years, range 21-83 years) performed between June 2013 and December 2015 were reviewed. Qualitative and quantitative features were compared between tumor grades and stages determined by histopathological analysis. RESULTS Ill defined margins were more common in G2-3 and stage III-IV PanNENs than in G1 and low-stage tumors (P < 0.001); this feature had high specificity in the identification of G2-3 and stage III-IV tumors (90.3% and 96%, 95%CI: 73.1-97.5 and 77.7-99.8). The mean apparent diffusion coefficient value was significantly lower in G2-3 and stage III-IV lesions compared to well differentiated and low-stage tumors (1.09 × 10-3 mm2/s vs 1.45 × 10-3 mm2/s and 1.10 × 10-3 mm2/s vs 1.53 × 10-3 mm2/s, P = 0.003 and 0.001). Receiving operator characteristic analysis determined optimal cut-offs of 1.21 and 1.28 × 10-3 mm2/s for the identification of G2-3 and stage III-IV tumors, with sensitivity and specificity values of 70.8/80.7% and 64.5/64% (95%CI: 48.7-86.6/60-92.7 and 45.4-80.2/42.6-81.3). CONCLUSION MR features of PanNENs vary according to their grade of differentiation and their stage at diagnosis and could predict the biological behavior of these tumors.

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.

Can histogram analysis of MR images predict aggressiveness in pancreatic neuroendocrine tumors

ObjectivesTo evaluate MRI derived whole-tumour histogram analysis parameters in predicting pancreatic neuroendocrine neoplasm (panNEN) grade and aggressiveness.MethodsPre-operative MR of 42 consecutive patients with panNEN >1 cm were retrospectively analysed. T1-/T2-weighted images and ADC maps were analysed. Histogram-derived parameters were compared to histopathological features using the Mann-Whitney U test. Diagnostic accuracy was assessed by ROC-AUC analysis; sensitivity and specificity were assessed for each histogram parameter.ResultsADCentropy was significantly higher in G2-3 tumours with ROC-AUC 0.757; sensitivity and specificity were 83.3 % (95 % CI: 61.2–94.5) and 61.1 % (95 % CI: 36.1–81.7). ADCkurtosis was higher in panNENs with vascular involvement, nodal and hepatic metastases (p= .008, .021 and .008; ROC-AUC= 0.820, 0.709 and 0.820); sensitivity and specificity were: 85.7/74.3 % (95 % CI: 42–99.2 /56.4–86.9), 36.8/96.5 % (95 % CI: 17.2–61.4 /76–99.8) and 100/62.8 % (95 % CI: 56.1–100/44.9–78.1). No significant differences between groups were found for other histogram-derived parameters (p >.05).ConclusionsWhole-tumour histogram analysis of ADC maps may be helpful in predicting tumour grade, vascular involvement, nodal and liver metastases in panNENs. ADCentropy and ADCkurtosis are the most accurate parameters for identification of panNENs with malignant behaviour.Key Points• Whole-tumour ADC histogram analysis can predict aggressiveness in pancreatic neuroendocrine neoplasms.• ADC entropy and kurtosis are higher in aggressive tumours.• ADC histogram analysis can quantify tumour diffusion heterogeneity.• Non-invasive quantification of tumour heterogeneity can provide adjunctive information for prognostication.

Digital Subtraction of Magnetic Resonance Images Improves Detection and Characterization of Pancreatic Neuroendocrine Neoplasms

Objective The aim of this study was to evaluate the usefulness of digital image subtraction of contrast-enhanced magnetic resonance (MR) images for detection and characterization of pancreatic neuroendocrine neoplasms (PanNENs). Methods Magnetic resonance examinations of 50 histologically verified PanNENs were retrospectively evaluated by 2 radiologists; 50 ductal adenocarcinomas were included as a control group. Late arterial phase images and correspondent subtracted images were analyzed. Tumor detectability on a subjective 3-point scale and contrast-to-noise ratios were compared across sequences using paired Student t tests. Tumor signal intensity was compared between sequences using &khgr;2 or Fisher exact tests. Results Subjective conspicuity and contrast-to-noise ratios of PanNENs were significantly higher on subtracted images compared with correspondent late arterial phase images (P < 0.001 and P = 0.002). The rate of clearly hyperenhancing PanNENs was higher on subtracted images compared with arterial phase images (76% vs 36%). Conclusions Digital image subtraction improves tumor conspicuity and allows better characterization of PanNENs compared with late arterial phase images.

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.

Rare Variants of Ductal Adenocarcinoma of the Pancreas

Histologic variants of ductal adenocarcinoma are neoplasms characterized by a specific histological pattern different from that of conventional pancreatic cancer, which is typically an adenocarcinoma. It has been estimated that these variants account for 2–10% of all pancreatic ductal cancers.

Do antibiotics have a role in the management of severe pancreatitis

Severe pancreatitis is almost always characterized by the presence of glandular necrosis, which determines a clear worsening in the prognosis of the patients in terms of either complications or mortality. Necrotic infection is the single factor able to triple mortality in severe pancreatitis and is strictly correlated with the amount of necrosis. In this regard it is of great importance to identify patients affected by pancreatic necrosis as soon as possible in order to make every effort to prevent necrotic infection. Determination of C-reactive protein in serum and a contrast-enhanced CT scan 48–72 h after the onset of symptoms are two easily performed procedures for the detection of necrosis. Total enteral nutrition and early antibiotic treatment are the only therapeutic options to prevent necrotic infection but some authors have expressed concerns about antibiotic prophylaxis because of the role of antibiotics in the selection of multiresistant pathogens and fungi. However, it is recommended nowadays t...