Background
Surgery remains the only treatment for the cure of pancreatic neuroendocrine tumors (PanNETs). Biomarkers to identify the completeness of resection and predict recurrence are lacking.
...Objective
The aims of this study were to evaluate if the blood measurement of neuroendocrine gene transcripts (NETest) was diagnostic of PanNETs, and whether NETest blood levels could identify complete resection. We compared transcript analysis with the biomarker chromogranin A (CgA).
Methods
This was a prospective, longitudinal, single-center study including 30 patients with a postoperative histological confirmation of PanNET. Blood for NETest and CgA was collected preoperatively and on postoperative day (POD) 1, POD5, and POD30. Transcripts were measured by real-time quantitative reverse transcription polymerase chain reaction and multianalyte algorithmic analysis (NETest; normal < 20), and CgA was measured by enzyme-linked immunosorbent assay (ELISA; normal < 109 ng/mL). Data are expressed as mean ± standard deviation (SD).
Results
Pancreatic surgical resections (
n
= 30) were
R
0, 26;
R
1, 2; and
R
2, 2. Preoperatively, NETest score was elevated in all 30 patients (44.7 ± 27), but postoperatively, NETest scores significantly decreased (
p
= 0.006) to POD30 (24.7 ± 24). The proportion of patients (15/30) with an elevated score significantly decreased by POD30 (
p
< 0.0001). CgA levels were elevated preoperatively (184 ± 360 ng/mL) in only 9/30 patients, but did not decrease significantly postoperatively at POD30 (260 ± 589 ng/mL,
p
= 0.398). The number of patients with elevated CgA levels remained unchanged (9/30).
Conclusions
The NETest is an accurate diagnostic biomarker for PanNETs (100%). A decrease in NETest levels after radical resection suggests this blood test provides early assessment of surgical efficacy. CgA had no clinical utility.
Perineural invasion (PNI) is defined as the presence of neoplastic cells along nerves and/or within the different layers of nervous fibers: epineural, perineural and endoneural spaces. In pancreatic ...cancer-particularly in pancreatic ductal adenocarcinoma (PDAC)-PNI has a prevalence between 70 and 100%, surpassing any other solid tumor. PNI has been detected in the early stages of pancreatic cancer and has been associated with pain, increased tumor recurrence and diminished overall survival. Such an early, invasive and recurrent phenomenon is probably crucial for tumor growth and metastasis. PNI is a still not a uniformly characterized event; usually it is described only dichotomously ("present" or "absent"). Recently, a more detailed scoring system for PNI has been proposed, though not specific for pancreatic cancer. Previous studies have implicated several molecules and pathways in PNI, among which are secreted neurotrophins, chemokines and inflammatory cells. However, the mechanisms underlying PNI are poorly understood and several aspects are actively being investigated. In this review, we will discuss the main molecules and signaling pathways implicated in PNI and their roles in the PDAC.
Abstract Background The highly metastatic nature of pancreatic ductal adenocarcinoma (PDAC) and the difficulty to achieve favorable patient outcomes emphasize the need for novel therapeutic ...solutions. For preclinical evaluations, genetically engineered mouse models are often used to mimic human PDAC but frequently fail to replicate synchronous development and metastatic spread. This study aimed to develop a transplantation model to achieve synchronous and homogenous PDAC growth with controlled metastatic patterns in the liver. Methods To generate an orthotopic PDAC model, the DT6606 cell line was injected into the pancreas head of C57BL/6 mice, and their survival was monitored over time. To generate a heterotopic transplantation model, growing doses of three PDAC cell lines (DT6606, DT6606lm, and K8484) were injected into the portal vein of mice. Magnetic resonance imaging (MRI) was used to monitor metastatic progression, and histologic analysis was performed. Results Orthotopically injected mice succumbed to the tumor within an 11-week period (average survival time, 78.2 ± 4.45 days). Post-mortem examinations failed to identify liver metastasis. In the intraportal model, 2 × 10 5 DT6606 cells resulted in an absence of liver metastases by day 21, whereas 5 × 10 4 DT6606lm cells and 7 × 10 4 K8484 cells resulted in steady metastatic growth. Higher doses caused significant metastatic liver involvement. The use of K8484 cells ensured the growth of tumors closely resembling the histopathologic characteristics of human PDAC. Conclusions This report details the authors’ efforts to establish an “optimal” murine model for inducing metastatic PDAC, which is critical for advancing our understanding of the disease and developing more effective treatments.
Objective:
To determine the accuracy of preoperative imaging, including contrast-enhanced computed tomography (CE-CT), endoscopic ultrasound (EUS), and
68
Gallium-DOTATOC positron emission tomography ...(
68
Ga-DOTATOC PET), in identifying nodal metastases (N+) in sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs).
Background:
An accurate preoperative identification of N+ in NF-PanNETs is critical for surgical planning. The accuracy of different imaging techniques in detecting lymph node (LN) metastases in NF-PanNETs has been poorly investigated.
Methods:
All consecutive patients undergoing surgery for sporadic NF-PanNETs (2018–2021) were enrolled in a prospective study (DETECTYON; NCT03918759). The accuracy of preoperative imaging techniques in detecting N+ was assessed through sensitivity, specificity positive and negative predictive values.
Results:
Overall, 100 patients with NF-PanNETs underwent CE-CT, EUS, and
68
Ga-DOTATOC PET before pancreatic resection. LN metastases were found in 42 cases (42%). Sensitivity, specificity, positive predictive value, and negative predictive value of different imaging techniques were 26%, 95%, 79%, 64% for CE-CT, 19%, 98%, 89%, 63% for EUS, and 12%, 95%, 63%, 60% for
68
Ga-DOTATOC PET, respectively. Radiologic tumor size >4 cm and the presence of radiologic N+ at ≥1 imaging were independent predictors of N+ at pathology. The identification of N+ at ≥1 imaging technique was associated with a higher number of positive LNs compared with negative imaging (4 vs 2) (
P
=0.012).
Conclusions:
CE-CT, EUS, and
68
Ga-DOTATOC PET are poorly sensitive in predicting nodal status in NF-PanNETs despite a high specificity.
Peptide receptor radionuclide therapy is a valid therapeutic option for pancreatic neuroendocrine neoplasms. The aim of this study was to describe an initial experience with the use of peptide ...receptor radionuclide therapy as a neoadjuvant agent for resectable or potentially resectable pancreatic neuroendocrine neoplasms.
The postoperative outcomes of 23 patients with resectable or potentially resectable pancreatic neuroendocrine neoplasms at high risk of recurrence who underwent neoadjuvant peptide receptor radionuclide therapy (peptide receptor radionuclide therapy group) were compared with 23 patients who underwent upfront surgical operation (upfront surgery group). Patients were matched for tumor size, grade, and stage. Median follow-up was 61 months.
The size (median greatest width) of the primary pancreatic neuroendocrine neoplasms decreased after neoadjuvant peptide receptor radionuclide therapy (59 to 50 mm; P = .047). There were no differences in intraoperative and postoperative outcomes and there were no operative deaths, but the risk of developing a pancreatic fistula tended to be less in the peptide receptor radionuclide therapy group when compared to the upfront surgery group (0/23 vs 4/23; P < .02). The incidence of nodal metastases at the time of resection was also less in the peptide receptor radionuclide therapy group (n = 9/23 vs 17/23; P < .02). Neither median disease-specific survival (not reached in either group; P = .411) nor progression-free survival (52 vs 37 months; P > .2) differed between groups, but progression-free survival in the 31 patients who had an R0 resection seemed to be greater in the 15 patients in the peptide receptor radionuclide therapy group versus 16 patients the upfront group (median progression-free survival not reached vs 36 months; P < .05).
Neoadjuvant peptide receptor radionuclide therapy for resectable or potentially resectable pancreatic neuroendocrine neoplasms in patients with high-risk features of recurrence seems to be beneficial, but well-designed and much larger prospective trials are needed to confirm the safety and the oncologic value of this approach.
Pancreatic cystic neoplasms (PCNs) represent a difficult preoperative diagnosis despite improvements in imaging. In this study, we compared preoperative and final pathologic diagnosis in a large ...cohort of resected PCNs, evaluating diagnostic accuracy with a specific focus on the value of EUS.
A retrospective analysis of patients undergoing resection between 2009 and 2019 for presumed PCNs was performed. Preoperative workup was reviewed by analyzing the role of imaging and EUS. Patients with a benign histology who did not show absolute indication were categorized as “delayable surgery.”
Of 585 patients who were retrospectively analyzed, in 108 (18.5%) final histology did not confirm preoperative diagnosis. EUS was associated with a lower rate of incorrect diagnosis (16%; P = .03), but the risk of overtreatment was similar regardless of instrumental diagnostic path (33/131 vs 68/328, P = .298). Dilatation of the main pancreatic duct and cytologic sampling were the only variables independently associated with a correct diagnosis (P < .001 and P = .041, respectively). Based on clinical presentation and final histology, pancreatic resection could have been spared or delayed in 101 of 459 patients (22%), and this was influenced by age (odds ratio OR, .97; P = .002), cyst larger than 30 mm (OR, 1.89; P = .005), and type of operation (OR, 3.46 P < .001 and 3.18 P = .023 for distal pancreatectomies and other resections, respectively).
The overall risk of unnecessary immediate surgery for PCNs is about 22% in a high-volume referral center. EUS with cytologic sampling is a useful procedure in the diagnostic management of PCNs, improving their diagnostic accuracy.
Wilms tumors growing in a botryoid fashion into the renal pelvis have been reported since the 1960s as a rare tumor type usually associated with stromal histology and a good prognosis. However, the ...true frequency, association with Wilms tumor subtypes, and stage have never been comprehensively studied. We analyzed all Wilms tumors enrolled into the International Society of Paediatric Oncology (SIOP) United Kingdom 2001 Trial (2001–2011), which showed botryoid growth. In addition, we reviewed published series reporting papers on botryoid Wilms tumors. 77/739 patients (10.4%) showed at least one Wilms tumor with a botryoid pattern, and they were sub-classified according to the SIOP criteria as follows: 28 stromal, 21 mixed, 7 regressive, 3 completely necrotic, 4 blastemal, 2 epithelial, 3 diffuse anaplasia, 1 focal anaplasia, and 10 non-anaplastic type (treated with primary surgery). Stage was as follows: 25 stage I, 21 stage II, 12 stage III, 11 stage IV, and 8 stage V. In six cases, local pathologists incorrectly upstaged the tumor from stage I to stage II based on botryoid growth. The event-free and overall survivals were 90 and 96%, respectively. We concluded that botryoid growth pattern is a common finding in Wilms tumor and that all histological types and stages can share this feature. The botryoid growth itself is not a criterion for stage II. Botryoid Wilms tumor is not an entity but merely represents a pattern of tumor growth; such tumors should be sub-classified according to their overall histological features, which will determine treatment and prognosis.
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