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Cancers
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Pancreatic Neuroendocrine Tumors
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Pancreatic Neuroendocrine Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 6535

Special Issue Editors

Prof. Dr. Patrick Michl

E-Mail Website
Guest Editor
Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany
Interests: pancreatic neuroendocrine tumors; tumor microenvironment; macrophages; pancreatic adenocarcinoma; inflammation-induced carcinogenesis; microbiome; clinical studies
Prof. Dr. Sebastian Krug

E-Mail Website
Guest Editor
Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany
Interests: neuroendocrine neoplasms; epigenetics; tumor-associated macrophages; in vitro models; translational studies; RIP1Tag2 mouse model
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the new insights and advances in the field of targeted therapies that have taken place in recent years, the successful treatment of pancreatic neuroendocrine neoplasms (PanNEN) remains a challenge, and the development towards more personalized medicine has been inadequate so far. The current therapy recommendations are mainly based on clinical parameters and patient-related risk constellations, and do not consider molecular genetic aspects. Therefore, the existing guidelines do not adequately reflect the complex tumor characteristics that should be included in the process of treatment decisions. One reason for this is the lack of understanding of tumor biology to identify subgroups, which in turn would benefit from specific and individualized therapeutic approaches. In addition, the low incidence of this entity as well as the heterogenous tumor character impede the collection of sufficiently large patient cohorts, which are necessary for scientific investigations and clinical trials. Thus, there is a lack of studies which analyze corresponding biomarkers and the efficacy of potential new individual therapies. This Special Issue aims to publish original research, expert opinions, commentaries, and reviews. The focus of the Special Issue includes basic, translational, and clinical research aiming to enhance the understanding of tumor biology, diagnostics, and the medical treatment of PanNEN.

Prof. Dr. Patrick Michl
Prof. Dr. Sebastian Krug
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pancreatic neuroendocrine neoplasms
  • tumor biology
  • systemic treatment
  • functionality
  • tumor progression
  • metastasis
  • prognosis
  • biomarkers

Published Papers (5 papers)

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Research

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12 pages, 1465 KiB  
Article
When Should Lymphadenectomy Be Performed in Non-Metastatic Pancreatic Neuroendocrine Tumors? A Population-Based Analysis of the German Clinical Cancer Registry Group
by Thaer S. A. Abdalla, Louisa Bolm, Monika Klinkhammer-Schalke, Sylke Ruth Zeissig, Kees Kleihues van Tol, Peter Bronsert, Stanislav Litkevych, Kim C. Honselmann, Rüdiger Braun, Judith Gebauer, Richard Hummel, Tobias Keck, Ulrich Friedrich Wellner and Steffen Deichmann
Cancers 2024, 16(2), 440; https://doi.org/10.3390/cancers16020440 - 19 Jan 2024
Viewed by 855
Abstract
Background: Patient selection for lymphadenectomy remains a controversial aspect in the treatment of pancreatic neuroendocrine tumors (pNETs), given the growing importance of parenchyma-sparing resections and minimally invasive procedures. Methods: This population-based analysis was derived from the German Cancer Registry Group during the period [...] Read more.
Background: Patient selection for lymphadenectomy remains a controversial aspect in the treatment of pancreatic neuroendocrine tumors (pNETs), given the growing importance of parenchyma-sparing resections and minimally invasive procedures. Methods: This population-based analysis was derived from the German Cancer Registry Group during the period from 2000 to 2021. Patients with upfront resected non-functional non-metastatic pNETs were included. Results: Out of 5520 patients with pNET, 1006 patients met the inclusion criteria. Fifty-three percent of the patients were male. The median age was 64 ± 17 years. G1, G2, and G3 pNETs were found in 57%, 37%, and 7% of the patients, respectively. Lymph node metastasis (LNM) was present in 253 (24%) of all patients. LNM was an independent prognostic factor (HR 1.79, CI 95% 1.21–2.64, p = 0.001) for disease-free survival (DFS). The 3-, 5-, and 10-year disease-free survival in nodal negative tumors compared to nodal positive was 82% vs. 53%, 75% vs. 38%, and 48% vs. 16%. LNM was present in 5% of T1 tumors, 25% of T2 tumors, and 49% of T3–T4 tumors. In T1 tumors, G1 was the most predominant tumor grade (80%). However, in T2 tumors, G2 and G3 represented 44% and 5% of all tumors. LNM was associated with tumors located in the pancreatic head (p < 0.001), positive resection margin (p < 0.001), tumors larger than 2 cm (p < 0.001), and higher tumor grade (p < 0.001). The multivariable analysis showed that tumor size, tumor grade, and location were independent prognostic factors associated with LNM that could potentially be used to predict LNM preoperatively. Conclusion: LNM is an independent negative prognostic factor for DFS in pNETs. Due to the low incidence of LNM in T1 tumors (5%), parenchyma-sparing surgery seems oncologically adequate in small G1 pNETs, while regional lymphadenectomy should be recommended in T2 or G2/G3 pNETs. Full article
(This article belongs to the Special Issue Pancreatic Neuroendocrine Tumors)
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19 pages, 1784 KiB  
Article
Generation of an Obese Diabetic Mouse Model upon Conditional Atrx Disruption
by Tiago Bordeira Gaspar, Tito Teles Jesus, Maria Teresa Azevedo, Sofia Macedo, Mariana Alves Soares, Rui Sousa Martins, Rúben Leite, Lia Rodrigues, Daniela Ferreira Rodrigues, Luís Cardoso, Inês Borges, Sule Canberk, Fátima Gärtner, Leandro Miranda-Alves, José Manuel Lopes, Paula Soares and João Vinagre
Cancers 2023, 15(11), 3018; https://doi.org/10.3390/cancers15113018 - 1 Jun 2023
Viewed by 1149
Abstract
Atrx loss was recently ascertained as insufficient to drive pancreatic neuroendocrine tumour (PanNET) formation in mice islets. We have identified a preponderant role of Atrx in the endocrine dysfunction in a Rip-Cre;AtrxKO genetically engineered mouse model (GEMM). To validate the impact of [...] Read more.
Atrx loss was recently ascertained as insufficient to drive pancreatic neuroendocrine tumour (PanNET) formation in mice islets. We have identified a preponderant role of Atrx in the endocrine dysfunction in a Rip-Cre;AtrxKO genetically engineered mouse model (GEMM). To validate the impact of a different Cre-driver line, we used similar methodologies and characterised the Pdx1-Cre;AtrxKO (P.AtrxKO) GEMM to search for PanNET formation and endocrine fitness disruption for a period of up to 24 months. Male and female mice presented different phenotypes. Compared to P.AtrxWT, P.AtrxHOM males were heavier during the entire study period, hyperglycaemic between 3 and 12 mo., and glucose intolerant only from 6 mo.; in contrast, P.AtrxHOM females started exhibiting increased weight gains later (after 6 mo.), but diabetes or glucose intolerance was detected by 3 mo. Overall, all studied mice were overweight or obese from early ages, which challenged the histopathological evaluation of the pancreas and liver, especially after 12 mo. Noteworthily, losing Atrx predisposed mice to an increase in intrapancreatic fatty infiltration (FI), peripancreatic fat deposition, and macrovesicular steatosis. As expected, no animal developed PanNETs. An obese diabetic GEMM of disrupted Atrx is presented as potentially useful for metabolic studies and as a putative candidate for inserting additional tumourigenic genetic events. Full article
(This article belongs to the Special Issue Pancreatic Neuroendocrine Tumors)
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Review

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17 pages, 947 KiB  
Review
Prognostic Implications of PET-Derived Tumor Volume and Uptake in Patients with Neuroendocrine Tumors
by Manuel Weber, Tugce Telli, David Kersting and Robert Seifert
Cancers 2023, 15(14), 3581; https://doi.org/10.3390/cancers15143581 - 12 Jul 2023
Cited by 2 | Viewed by 1573
Abstract
Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS [...] Read more.
Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided. Full article
(This article belongs to the Special Issue Pancreatic Neuroendocrine Tumors)
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Other

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13 pages, 1636 KiB  
Perspective
Relevance of Endoscopic Ultrasound in Endocrinology Today: Multiple Endocrine Neoplasia Type 1, Insulinoma, Primary Aldosteronism—An Expert’s Perspective Based on Three Decades of Scientific and Clinical Experience
by Peter Herbert Kann
Cancers 2023, 15(13), 3494; https://doi.org/10.3390/cancers15133494 - 4 Jul 2023
Cited by 2 | Viewed by 1151
Abstract
In endocrinology, endoscopic ultrasound (EUS) may be used to image the adrenals, the endocrine pancreas, and other organs where endocrine neoplasms may occur. During the recent decades, EUS has been established predominantly to assess multiple endocrine neoplasia type 1, to localize insulinomas, and [...] Read more.
In endocrinology, endoscopic ultrasound (EUS) may be used to image the adrenals, the endocrine pancreas, and other organs where endocrine neoplasms may occur. During the recent decades, EUS has been established predominantly to assess multiple endocrine neoplasia type 1, to localize insulinomas, and to identify aldosterone-producing adenomas. EUS in endocrinology requires special skills and individual experience in order to provide reliable diagnostic information. Full article
(This article belongs to the Special Issue Pancreatic Neuroendocrine Tumors)
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15 pages, 652 KiB  
Systematic Review
Clinical Prediction Models for Recurrence in Patients with Resectable Grade 1 and 2 Sporadic Non-Functional Pancreatic Neuroendocrine Tumors: A Systematic Review
by Jeffrey W. Chen, Charlotte M. Heidsma, Anton F. Engelsman, Ertunç Kabaktepe, Susan van Dieren, Massimo Falconi, Marc G. Besselink and Els J. M. Nieveen van Dijkum
Cancers 2023, 15(5), 1525; https://doi.org/10.3390/cancers15051525 - 28 Feb 2023
Cited by 1 | Viewed by 1321
Abstract
Recurrence after resection in patients with non-functional pancreatic neuroendocrine tumors (NF-pNET) has a considerable impact on overall survival. Accurate risk stratification will tailor optimal follow-up strategies. This systematic review assessed available prediction models, including their quality. This systematic review followed PRISMA and CHARMS [...] Read more.
Recurrence after resection in patients with non-functional pancreatic neuroendocrine tumors (NF-pNET) has a considerable impact on overall survival. Accurate risk stratification will tailor optimal follow-up strategies. This systematic review assessed available prediction models, including their quality. This systematic review followed PRISMA and CHARMS guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2022 for studies that developed, updated, or validated prediction models for recurrence in resectable grade 1 or 2 NF-pNET. Studies were critically appraised. After screening 1883 studies, 14 studies with 3583 patients were included: 13 original prediction models and 1 prediction model validation. Four models were developed for preoperative and nine for postoperative use. Six models were presented as scoring systems, five as nomograms, and two as staging systems. The c statistic ranged from 0.67 to 0.94. The most frequently included predictors were tumor grade, tumor size, and lymph node positivity. Critical appraisal deemed all development studies as having a high risk of bias and the validation study as having a low risk of bias. This systematic review identified 13 prediction models for recurrence in resectable NF-pNET with external validations for 3 of them. External validation of prediction models improves their reliability and stimulates use in daily practice. Full article
(This article belongs to the Special Issue Pancreatic Neuroendocrine Tumors)
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