| 1. |
- Ambrosini, Valentina, et al.
(författare)
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Consensus on molecular imaging and theranostics in neuroendocrine neoplasms
- 2021
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 146, s. 56-73
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Forskningsöversikt (refereegranskat)abstract
- Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro-2-deoxyglucose ([18F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[68Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [68Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [18F]FDG and [68Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
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| 2. |
- Crippa, Stefano, et al.
(författare)
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A tug-of-war in intraductal papillary mucinous neoplasms management : Comparison between 2017 International and 2018 European guidelines
- 2021
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Ingår i: Digestive and Liver Disease. - : Elsevier. - 1590-8658 .- 1878-3562. ; 53:8, s. 998-1003
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 2017 International and 2018 European guidelines are the most recent guidelines for intraductal papillary mucinous neoplasms management.AIM: to evaluate the diagnostic accuracy of these guidelines in identifying malignant IPMN.METHODS: data from resected patients with IPMN were collected in two referral centers. Features of risk associated to cancerous degeneration described in International and European guidelines were retrospectively applied. Sensitivity, specificity, positive and negative predictive value in detecting malignant disease were calculated.RESULTS: the study includes 627 resected patients. European guidelines suggest resection in any patient with at least one feature of moderate-risk. International guidelines suggest that patients with moderate-risk features undergo endoscopic ultrasound before surgery. European guidelines had a higher sensitivity (99.2% vs. 83%) but a lower positive predictive value (59.5% vs. 65.8%) and Specificity (2% vs. 37.5%). European guidelines detected almost all malignancies, but 40% of resected patients had low-grade dysplasia. 297 patients underwent endoscopic ultrasound before surgery. 31/116 (26.7%) tumors radiologically classified as "worrisome features" were reclassified as "high-risk stigmata" by endoscopic ultrasound and 24/31 were malignant IPMN.CONCLUSIONS: European and International guidelines have a relatively low diagnostic accuracy, being European guidelines more aggressive. Endoscopic ultrasound can improve guidelines accuracy in patients with moderate-risk features.
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| 3. |
- Maggino, Laura, et al.
(författare)
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Reappraisal of a 2-Cm Cut-off Size for the Management of Cystic Pancreatic Neuroendocrine Neoplasms : A Multicenter International Study
- 2021
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Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 273:5, s. 973-981
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to characterize an international cohort of resected cystic pancreatic neuroendocrine neoplasms (cPanNENs) and identify preoperative predictors of aggressive behavior.BACKGROUND: The characteristics of cPanNENs are unknown and their clinical management remains unclear. An observational strategy for asymptomatic cPanNENs ≤2 cm has been proposed by recent guidelines, but evidence is scarce and limited to single-institutional series.METHODS: Resected cPanNENs (1995-2017) from 16 institutions worldwide were included. Solid lesions (>50% solid component), functional tumors, and MEN-1 patients were excluded. Aggressiveness was defined as lymph node (LN) involvement, G3 grading, distant metastases, and/or recurrence.RESULTS: Overall, 263 resected cPanNENs were included, among which 177 (63.5%) were >2 cm preoperatively. A preoperative diagnosis of cPanNEN was established in 162 cases (61.6%) and was more frequent when patients underwent endoscopic ultrasound [EUS, odds ratio (OR) 2.69, 95% confidence interval (CI) 1.52-4.77] and somatostatin-receptor imaging (OR 3.681, 95% CI 1.809-7.490), and for those managed in specialized institutions (OR 3.12, 95% CI 1.57-6.21). Forty-one cPanNENs (15.6%) were considered aggressive. In the whole cohort, LN involvement on imaging, age >65 years, preoperative size >2 cm, and pancreatic duct dilation were independently associated with aggressive behavior. In asymptomatic patients, older age and a preoperative size >2 cm remained independently associated with aggressiveness. Only 1 of 61 asymptomatic cPanNENs ≤2 cm displayed an aggressive behavior.CONCLUSIONS: The diagnostic accuracy of cPanNENs is increased by the use of EUS and somatostatin-receptor imaging and is higher in specialized institutions. Preoperative size >2 cm is independently associated with aggressive behavior. Consequently, a watch-and-wait policy for sporadic asymptomatic cPanNENs ≤2 cm seems justified and safe for most patients.
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| 4. |
- Modlin, Irvin M., et al.
(författare)
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Early Identification of Residual Disease After Neuroendocrine Tumor Resection Using a Liquid Biopsy Multigenomic mRNA Signature (NETest)
- 2021
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Ingår i: Annals of Surgical Oncology. - : Springer. - 1068-9265 .- 1534-4681. ; 28:12, s. 7506-7517
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence. Methods This was a multicenter evaluation of surgically treated primary NETs (n = 153). Blood sampling was performed at day 0 and postoperative day (POD) 30. Follow-up included computed tomography/magnetic resonance imaging (CT/MRI), and messenger RNA (mRNA) quantification was performed by polymerase chain reaction (PCR; NETest score: 0-100; normal <= 20). Statistical analyses were performed using the Mann-Whitney U-test, Chi-square test, Kaplan-Meier survival, and area under the receiver operating characteristic curve (AUROC), as appropriate. Data are presented as mean +/- standard deviation. Results The NET cohort (n = 153) included 57 patients with pancreatic cancer, 62 patients with small bowel cancer, 27 patients with lung cancer, 4 patients with duodenal cancer, and 3 patients with gastric cancer, while the surgical cohort comprised patients with R0 (n = 102) and R1 and R2 (n = 51) resection. The mean follow-up time was 14 months (range 3-68). The NETest was positive in 153/153 (100%) samples preoperatively (mean levels of 68 +/- 28). In the R0 cohort, POD30 levels decreased from 62 +/- 28 to 22 +/- 20 (p < 0.0001), but remained elevated in 30% (31/102) of patients: 28% lung, 29% pancreas, 27% small bowel, and 33% gastric. By 18 months, 25/31 (81%) patients with a POD30 NETest >20 had image-identifiable recurrence. An NETest score of >20 predicted recurrence with 100% sensitivity and correlated with residual disease (Chi-square 17.1, p < 0.0001). AUROC analysis identified an AUC of 0.97 (p < 0.0001) for recurrence-prediction. In the R1 (n = 29) and R2 (n = 22) cohorts, the score decreased (R1: 74 +/- 28 to 45 +/- 24, p = 0.0012; R2: 72 +/- 24 to 60 +/- 28, p = non-significant). At POD30, 100% of NETest scores were elevated despite surgery (p < 0.0001). Conclusion The preoperative NETest accurately identified all NETs (100%). All resections decreased NETest levels and a POD30 NETest score >20 predicted radiologically recurrent disease with 94% accuracy and 100% sensitivity. R0 resection appears to be ineffective in approximately 30% of patients. NET mRNA blood levels provide early objective genomic identification of residual disease and may facilitate management.
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| 5. |
- Niederle, Bruno, et al.
(författare)
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Multiple Endocrine Neoplasia Type 1 and the Pancreas : Diagnosis and Treatment of Functioning and Non-Functioning Pancreatic and Duodenal Neuroendocrine Neoplasia within the MEN1 Syndrome - An International Consensus Statement
- 2021
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Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 111:7, s. 609-630
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Forskningsöversikt (refereegranskat)abstract
- The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a revision of previously published guidelines. Duodenopancreatic neuroendocrine neoplasias (DP-NENs) are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to reevaluate recommendations for their diagnosis and treatment. Especially over the last 2 years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology, and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syndrome in an effort to further standardize and improve treatment and follow-up, as well as to establish a "logbook" for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guidelines of 2001 and 2012 and attempts to supplement the recommendations issued by various national and international societies.
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| 6. |
- Rodriguez-Freixinos, Victor, et al.
(författare)
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Practical recommendations for the management of patients with gastroenteropancreatic and thoracic (carcinoid) neuroendocrine neoplasms in the COVID-19 era
- 2021
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 144, s. 200-214
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Forskningsöversikt (refereegranskat)abstract
- Neuroendocrine neoplasms (NENs) are a heterogeneous family of uncommon tumours with challenging diagnosis, clinical management and unique needs that almost always requires a multidisciplinary approach. In the absence of guidance from the scientific literature, along with the rapidly changing data available on the effect of COVID-19, we report how 12 high-volume NEN centres of expertise in 10 countries at different stages of the evolving COVID-19 global pandemic along with members of international neuroendocrine cancer patient societies have suggested to preserve high standards of care for patients with NENs. We review the multidisciplinary management of neuroendocrine neoplasms during the COVID-19 pandemic, and we suggest potential strategies to reduce risk and aid multidisciplinary treatment decision-making. By sharing our joint experiences, we aim to generate recommendations for proceeding to other institutions facing the same challenges. (C) 2020 Elsevier Ltd. All rights reserved.
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| 7. |
- Siriwardena, Ajith K., et al.
(författare)
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Standards for reporting on surgery for chronic pancreatitis : a report from the International Study Group for Pancreatic Surgery (ISGPS)
- 2020
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Ingår i: Surgery (United States). - : Elsevier BV. - 0039-6060. ; 168:1, s. 101-105
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Tidskriftsartikel (refereegranskat)abstract
- Background: The International Study Group for Pancreatic Surgery provides globally accepted definitions for reporting of complications after pancreatic surgery. This International Study Group for Pancreatic Surgery project aims to provide a standardized framework for reporting of the results of operative treatment for chronic pancreatitis. Methods: An International Study Group for Pancreatic Surgery project circulation list was created with pre-existing and new members and including gastroenterologists in addition to surgeons. A computerized search of the literature was undertaken for articles reporting the operative treatment of chronic pancreatitis. The results of the literature search were presented at the first face-to-face meeting of this International Study Group for Pancreatic Surgery project group. A document outlining proposed reporting standards was produced by discussion during an initial meeting of the International Study Group for Pancreatic Surgery. An electronic questionnaire was then sent to all current members of the International Study Group for Pancreatic Surgery. Responses were collated and further discussed at international meetings in North America, Europe, and at the International Association of Pancreatology World Congress in 2019. A final consensus document was produced by integration of multiple iterations. Results: The International Study Group for Pancreatic Surgery consensus standards for reporting of surgery in chronic pancreatitis recommends 4 core domains and the necessary variables needed for reporting of results: clinical baseline before operation; the morphology of the diseased gland; a new, standardized, operative terminology; and a minimum outcome dataset. The 4 domains combine to give a comprehensive framework for reports. Conclusion: Adoption of the 4 domains of the International Study Group for Pancreatic Surgery reporting standards for surgery for chronic pancreatitis will facilitate comparison of results between centers and help to improve the care for patients with this debilitating disease.
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| 8. |
- van Hilst, Jony, et al.
(författare)
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Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA) : study protocol for a randomized controlled trial
- 2021
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Ingår i: Trials. - : BMC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin >= 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (alpha), 80% power (1-beta), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. Discussion: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting.
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