Luca Landoni

Background and Clinical Significance: Pancreatic neuroendocrine tumors (pNETs) rarely exhibit intraductal growth, a pattern that may mimic intraductal papillary mucinous neoplasms (IPMNs) or pancreatic ductal adenocarcinoma (PDAC). Preoperative recognition is challenging, particularly when associated with anatomic variants such as pancreas divisum. Case Presentation: A 63-year-old man with a history of pancreatic duct dilation presented with pruritus, weight loss, and lymphadenopathy. Cross-sectional imaging revealed a cephalopancreatic mass with upstream ductal dilatation. EUS demonstrated a hypervascular lesion with intraductal extension into the dorsal duct in the setting of pancreas divisum. EUS-FNB confirmed a well-differentiated pNET (G1) with loss of DAXX expression and preserved ATRX. Ga-68 PET/CT showed intense uptake in the primary lesion and lower-grade uptake in two additional nodules, later proven non-neoplastic. A multidisciplinary tumor board recommended preoperative optimization with somatostatin analog therapy and supervised weight reduction, followed by pylorus-preserving duodenocephalopancreatectomy. Final pathology confirmed NET G1 with intraductal growth and full concordance with preoperative EUS-FNB findings. Conclusions: in this case, a pNET showed intraductal growth within the dorsal duct in the context of pancreas divisus, further expanding the range of its reported presentations. It underscores the diagnostic value of EUS-FNB for morphologic, proliferative, and molecular characterization, and highlights the importance of multidisciplinary evaluation in guiding preoperative optimization and tailored surgical management.

Introduction: Minimally invasive pancreatoduodenectomy (MIPD), including laparoscopic (LPD) and robotic approaches (RPD), has gained increasing attention as an alternative to open pancreatoduodenectomy (OPD). Despite rapid technological progress, concerns persist regarding safety, reproducibility, and oncological adequacy. The publication of randomized controlled trials (RCTs) provides essential high-level evidence to reassess the true benefits and limitations of MIPD. Methods: This narrative review synthesizes all available RCTs comparing LPD and RPD with OPD. Major domains evaluated include mortality, major morbidity, intraoperative parameters, postoperative recovery, oncological outcomes, conversion, costs, and the influence of surgeon experience and institutional volume. The objective is to contextualize RCT findings rather than perform a quantitative meta-analysis. Discussion: Across studies, LPD demonstrates comparable mortality and complication rates to OPD in high-volume centers, with consistent reductions intraoperative blood loss (IBL) and shorter recovery or length of stay (LOS). RPD shows more heterogeneous results: one large trial reported improved postoperative recovery, whereas the EUROPA trial identified higher rates of pancreatic fistula (POPF) and delayed gastric emptying (DGE) alongside significantly increased costs. Both LPD and RPD achieve oncological outcomes equivalent to OPD, and 3-year survival data confirm the long-term non-inferiority of LPD. However, operative time remains longer for all minimally invasive approaches, and conversion persists as a marker of technical difficulty and incomplete learning curve. Conclusions: Current RCT evidence indicates that MIPD is safe, feasible, and oncologically sound only when performed by surgeons who have surpassed the demanding learning curve within specialized, high-volume centers. The benefits, mainly reduced IBL and faster recovery, must be weighed against longer operative times, conversion risks, and substantially higher costs for RPD. MIPD should therefore be considered an advanced option rather than a universal standard, and its broader implementation requires structured training pathways, appropriate patient selection, and institutional readiness.

In patients with gastroenteric and pancreatic neuroendocrine neoplasms (GEP‐NENs), the risk of liver metastases is high, but the accuracy of standard imaging for detecting small hepatic nodules is limited. This raises concerns about the adequacy of staging in cM0 patients. This study aims to determine the percentage of cM0 GEP‐NEN patients with occult liver metastases that can be identified using intraoperative ultrasound (IOUS) during surgery for the primary tumor. A prospective study was conducted at three high‐volume centers between October 2020 and December 2023. Patients who underwent surgery for GEP‐NENs staged as cM0 based on CT and PET/CT (MRI in selected cases) were included. IOUS was systematically performed, in combination with contrast‐enhanced IOUS (CE‐IOUS) and biopsy when necessary. The ground truth was the result of a contrast‐enhanced CT or MRI performed 6 months after surgery. A total of 51 cM0 GEP‐NEN patients were enrolled. IOUS detected suspicious liver nodules in seven patients (14%). Three were classified as metastatic based on the IOUS pattern, CE‐IOUS pattern, and biopsy, respectively, while four were classified as non‐metastatic based on biopsy ( n = 2) or CE‐IOUS pattern ( n = 2). At six‐month follow‐up imaging, two patients (4%) were confirmed as metastatic (the suspicious metastasis at CE‐IOUS was not confirmed). GEP‐NENs G3 and those with necrosis had a higher risk of metastases (one‐third of patients, p < 0.05 compared to G1‐2 and non‐necrotic neoplasms). IOUS, combined with CE‐IOUS and biopsy, achieved 100% sensitivity, 98% accuracy, and 100% negative predictive value. IOUS, along with CE‐IOUS and biopsy, provides accurate staging in GEP‐NENs, identifying occult metastases in approximately 4% of cM0 cases. Due to the low incidence of occult metastases, routine use of IOUS cannot be recommended. It should be considered selectively in aggressive tumors, which have shown a significantly higher risk of liver involvement.

Aims Death domain-associated protein (DAXX) and/or α-thalassemia/mental retardation X-linked (ATRX) genes mutations and alternative lengthening of telomeres (ALT) activation are associated with more aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-pNETs)[1] [2]. We aimed to evaluate their reliability on EUS-FNB specimens. Methods Patients who underwent EUS-FNB and subsequent surgical resection for PNETs between 2017 and 2019 were identified. Immunohistochemistry was performed to evaluate DAXX/ATRX expression and fluorescence in situ hybridization (FISH) for ALT status. The primary outcome was the concordance rate of markers expression between EUS-FNB and surgical specimens. Secondary aims were association between markers and aggressive lesions and their diagnostic performance in predicting aggressiveness. Results 41 NF-pNETs (mean diameter 36.1±26.5mm) were included. 24 showed features of lesion aggressiveness. Concordance of expressions of DAXX, ATRX, and ALT status between EUS-FNB and surgical specimens were 95.1% (κ=0.828; p<0.001), 92.7% (κ=0.626; p<0.001), and 100% (κ=1; p<0.001), respectively. DAXX/ATRX loss and ALT-positivity were significantly (p<0.05) associated with metastatic lymphnodes and lymphovascular invasion. The combination of all tumor markers (DAXX/ATRX loss + ALT-positivity + grade 2) reached an accuracy of 73.2% (95%CI 57.1–85.8) in identifying aggressive lesions (Table). Pre- and post-operative ki-67-based grading was concordant in 80.5% of cases (k=0.573; p<0.001) ([Table 1]). Conclusions DAXX/ATRX expression and ALT status can be accurately evaluated on EUS-FNB samples, potentially improving the identification of patients with increased risk and poorer prognosis. Article published online: 14 April 2023 © 2023. European Society of Gastrointestinal Endoscopy. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Introduction The COVID-19 pandemic has severely limited the access to cancer surgery, but it is not known to what extent referral centers for pancreatic diseases were affected by its outbreak. The aim of this study is to describe the effect of COVID-19 pandemic on a third-level referral center for pancreatic surgery in Italy. Methods The 2020 activity of The Pancreas Institute of the University of Verona was reviewed, comparing different phases of the COVID-19 pandemic outbreaks using the pre-COVID era as a control. Endpoints were the overall caseload of pancreatic resections, surgical waiting list, administration of preoperative therapy, major morbidity and mortality, residents’ training; number of inpatients beds, outpatient visits/procedures/diagnostics. Results In 2020, there was an overall significant reduction of pancreatic resections performed (394 vs. 506 in 2019), particularly during the first (March–May) and second (October–December) COVID-19 outbreaks, with an all-time-low of 16 resections/months in April (compared to 43 average resection/month in 2019). The rates of major morbidity (Clavien–Dindo ≥ 3) and mortality were similar to 2019 (16 vs 12%, p = 0.11 and 3 vs 2%, p = 0.29, respectively). During the first and second outbreaks resident’s training, inpatient beds, outpatient visits, diagnostics, and procedures were severely impaired, while the waiting list for up-front cancer resections and the use of preoperative chemotherapy concomitantly raised. Conclusion The COVID-19 pandemic has severely disrupted the activity of a third-level referral center for pancreatic surgery, affecting the access to cancer surgical procedures and raising concerns regarding the solidity of the current centralization model.