Background and aims
Radiofrequency ablation (RFA) is a well-recognized local ablative technique applied in the treatment of different solid tumors. Intraoperative RFA has been used for non-metastatic ...unresectable pancreatic ductal adenocarcinoma (PDAC), showing increased overall survival in retrospective studies. A novel RFA probe has recently been developed, allowing RFA under endoscopic ultrasound (EUS) guidance. Aim of the present study was to assess the feasibility and safety of EUS-guided RFA for unresectable PDACs.
Methods
Patients with unresectable non-metastatic PDAC were included in the study following neoadjuvant chemotherapy. EUS-guided RFA was performed using a novel monopolar 18-gauge electrode with a sharp conical 1 cm tip for energy delivery. Pre- and post-procedural clinical and radiological data were prospectively collected.
Results
Ten consecutive patients with unresectable PDAC were enrolled. The procedure was successful in all cases and no major adverse events were observed. A delineated hypodense ablated area within the tumor was observed at the 30-day CT scan in all cases.
Conclusions
EUS-guided RFA is a feasible and safe minimally invasive procedure for patients with unresectable PDAC. Further studies are warranted to demonstrate the impact of EUS-guided RFA on disease progression and overall survival.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Recent papers consider surgery as an option for synchronous liver oligometastatic patients metastatic pancreatic ductal adenocarcinoma (mPDAC). In this study, we present our series of ...resected mPDACs after neoadjuvant chemotherapy (nCT).
Patients and methods
All patients resected after downstaging of mPDAC were included in this study. Downstaging criteria were disappearance of liver metastasis and a decrease in cancer antigen (CA) 19-9. The type and duration of nCT, last nCT surgery interval, histology, morbidity, and mortality were recorded, and overall survival (OS) and disease-free survival (DFS) were analyzed.
Results
Overall, 24 of 535 patients (4.5%) observed with mPDAC were included. These patients received gemcitabine alone (5/24), gemcitabine + nanoparticle albumin-bound (nab)−paclitaxel (3/24), and FOLFIRINOX (16/24). Primary tumor size decreased from 31 to 19 mm (
p
< 0.001), and serum CA19-9 decreased from 596 to 18 U/mL (
p
< 0.001). In 14/24 patients, the tumor was located in the head. Median interval nCT surgery was 2 months, there were no mortalities, and the postoperative course was uneventful in 34% of cases. Grade B/C pancreatic fistula, postoperative bleeding, and sepsis occurred in 17/4, 4, and 12% of cases, respectively, and reoperation rate was 4%. R0 resection was achieved in 88% of cases, with 17% complete pathological response. Positive nodes were found in 9/24 patients with a median node ratio of 0.37, and OS and DFS was 56 and 27 months, respectively.
Conclusions
Patients with mPDAC who were fully responsive to nCT may be cautiously considered for surgery, with potential benefit in survival compared with palliative chemotherapy alone. This is supported by results of our retrospective study, which is the largest ever reported.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives
To evaluate MRI derived whole-tumour histogram analysis parameters in predicting pancreatic neuroendocrine neoplasm (panNEN) grade and aggressiveness.
Methods
Pre-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.
Results
ADC
entropy
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). ADC
kurtosis
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).
Conclusions
Whole-tumour histogram analysis of ADC maps may be helpful in predicting tumour grade, vascular involvement, nodal and liver metastases in panNENs. ADC
entropy
and ADC
kurtosis
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
.
AIM To describe magnetic resonance(MR) imaging features of pancreatic neuroendocrine neoplasms(Pan NENs) according to their grade and tumor-nodes-metastases stage by comparing them to histopathology ...and todetermine 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 Pan NEN 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 PanN ENs 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 cutoffs 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 PanN ENs vary according to their grade of differentiation and their stage at diagnosis and could predict the biological behavior of these tumors.
Background
Resection of initially oligometastatic pancreatic ductal adenocarcinoma (PDAC) following response to first-line chemotherapy is controversial. We herein updated a previous case series to ...investigate the oncologic outcomes and preoperative factors that could drive the decision-making process.
Methods
This retrospective analysis was limited to patients with liver-only synchronous metastases who experienced complete regression of the metastatic component and underwent pancreatectomy between October 2008 and July 2020 at two high-volume institutions. Clinical-pathologic variables were captured, and inflammation-based prognostic scores were calculated. Recurrence and survival analyses were performed using standard statistical methods.
Results
Overall, 52 patients were included. FOLFIRINOX was the most employed chemotherapy regimen (63.5%). Post-treatment tumor size, serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were significantly decreased relative to baseline evaluation. The median time from diagnosis to pancreatectomy was 10.2 months, while the median time from chemotherapy completion to pancreatectomy was 2 months. Major postoperative complications occurred in 26.9% of patients, while postoperative mortality was nil. The median disease-free survival (DFS) and overall survival (OS) from pancreatectomy were 16.5 and 23.0 months, respectively, and the median OS from diagnosis was 37.2 months. At multivariable analysis, vascular resection, operative time, prognostic nutrition index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were associated with OS. Operative time, platelet × neutrophil/lymphocyte count (SII), and PNI were associated with DFS.
Conclusions
We confirm promising outcomes of selected patients who underwent pancreatectomy following downstaging of liver metastases. The absence of vascular involvement of the primary tumor, good nutritional status, and low inflammatory index scores could be useful to select candidates for resection.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Pancreatic cancer, most frequently as ductal adenocarcinoma (PDAC), is the third leading cause of cancer death. Clear-cell primary adenocarcinoma of the pancreas (CCCP) is a rare, aggressive, still ...poorly characterized subtype of PDAC. We report here a case of a 65-year-old male presenting with pancreatic neoplasia. A histochemical examination of the tumor showed large cells with clear and abundant intracytoplasmic vacuoles. The clear-cell foamy appearance was not related to the hyperproduction of mucins. Ultrastructural characterization with transmission electron microscopy revealed the massive presence of mitochondria in the clear-cell cytoplasm. The mitochondria showed disordered cristae and various degrees of loss of structural integrity. Immunohistochemistry staining for NADH dehydrogenase ubiquinone 1 alpha subcomplex, 4-like 2 (NDUFA4L2) proved specifically negative for the clear-cell tumor. Our ultrastructural and molecular data indicate that the clear-cell nature in CCCP is linked to the accumulation of disrupted mitochondria. We propose that this may impact on the origin and progression of this PDAC subtype.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
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.
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.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Neo-adjuvant chemotherapy (CHT) has gained increasing importance in resectable and borderline resectable pancreatic cancer leading to a better performing surgery when we look at negative ...resection margins and selection of patients with less aggressive disease. We apply this principle to patients with Stage III (LAC) pancreatic cancer undergoing RFA and try to select patients who may benefit from a local treatment.
Methods
All patients affected by LAC were treated with RFA for a stable disease after a short CHT. Postoperative morbidity and mortality were evaluated together with overall survival (OS) and disease specific survival (DSS).
Results
We consecutively treated 57 patients affected by LAC. Median duration of CHT before RFA was 5 months. The postoperative mortality rate was zero. Overall morbidity was 14 % with RFA-related morbidity of 3.5 %. The OS and DSS were 19 months and when compared to a similar population who received RFA as up front treatment, there was no difference.
Conclusions
Our results do not support the adoption of a short CHT as a way to identify patients to treat with RFA with the most benefit. Based on this and by knowing the role of immune modulation after RFA and its specific involvement in pancreatic carcinoma, we can propose RFA as upfront treatment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Stage III pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with the results of chemoradiation being disappointing. Radiofrequency is an ablation technique employed in many ...unresectable solid tumours, but its application to pancreatic cancer is limited. We report our experience of radiofrequency ablation (RFA) with cytoreductive intent in stage III PDAC.
Patients and methods
One hundred consecutive patients affected by stage III PDAC received RFA combined with chemoradiotherapy. Follow-up was planned on a 3-month basis including clinical evaluation, serum markers and computed tomography scan or MRI. Short-term outcomes and survival data were evaluated.
Results
Forty-eight patients received upfront RFA, and 52 had associated palliative surgery. Abdominal complications occurred in 24 patients, and in 15 cases, they were related to RFA. The mortality rate was 3 %. At a median follow-up of 12 months, 55 patients had died of disease and four patients due to unknown causes. Nineteen patients are alive with disease progression, and 22 are alive and progression free.
Conclusions
We presented the broadest experience of RFA in stage III PDAC, focusing on the rationale of its application and considering the advanced stage of disease and the cytoreductive purpose of the procedure. The critical aspects of the technique, along with the unexpected results in efficacy, were discussed.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background:
Up-front surgery followed by postoperative chemotherapy remains the standard paradigm for the treatment of patients with resectable pancreatic cancer. However, the risk for positive ...surgical margins, the poor recovery after surgery that often impairs postoperative treatment, and the common metastatic relapse limit the overall clinical outcomes achieved with this strategy. Polychemotherapeutic combinations are valid options for postoperative treatment in patients with good performance status. liposomal irinotecan (Nal-IRI) is a novel nanoliposome formulation of irinotecan that accumulates in tumor-associated macrophages improving the therapeutic index of irinotecan and has been approved for the treatment of patients with metastatic pancreatic cancer after progression under gemcitabine-based therapy. Thus, it remains of the outmost urgency to investigate introduction of the most novel agents, such as nal-IRI, in perioperative approaches aimed at increasing the long-term effectiveness of surgery.
Methods:
The nITRO trial is a phase II, single-arm, open-label study to assess the safety and the activity of nal-IRI with fluorouracil/leucovorin (5-FU/LV) and oxaliplatin in the perioperative treatment of patients with resectable pancreatic cancer. The primary tumor must be resectable with no involvement of the major arteries and no involvement or <180° interface between tumor and vessel wall of the major veins. A total of 72 patients will be enrolled to receive a perioperative treatment of three cycles before and three cycles after surgical resection with nal-IRI 50 mg/m2, oxaliplatin 60 mg/m2, leucovorin 200 mg/m2, and 5-fluorouracil 2400 mg/m2, days 1 and 15 of a 28-day cycle. The primary objective is to improve from 40% to 55% the proportion of patients achieving R0 resection after preoperative treatment.
Discussion:
The nITRO trial will contribute to strengthen the clinical evidence supporting perioperative strategies in resectable pancreatic cancer patients. Moreover, this study represents a unique opportunity for translational analyses aimed to identify novel immune-related prognostic and predictive factors in this setting.
Trial registration
Clinicaltrial.gov: NCT03528785. Trial registration data: 1 January 2018
Protocol number: CRC 2017_01
EudraCT Number: 2017-000345-46
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