Nodal metastases (N+) are one of the most powerful predictors of disease recurrence after surgery for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs). However, the prognostic role of nodal metastases < 5 mm, defined as micrometastases, has been poorly investigated so far. The aim of this study was to compare clinico-pathological features and survival outcomes between patients with NF-PanNETs without nodal involvement (N0), with nodal micrometastases (microN+) and with nodal macrometastases (macroN+). Consecutive patients who underwent a formal pancreatic resection for NF-PanNETs at San Raffaele Hospital (Milan, Italy) between 2018 and 2021 and were enrolled in the DETECTYON trial were considered (NCT03918759). Nodal metastases were further classified as microN+ when their maximum diameter was < 5 mm, or as macroN+ when their maximum diameter was ≥ 5 mm. Overall, 100 patients were included. Of these, 58 had N0 PanNETs, 15 had microN+ and 27 had macroN+. Patients with macroN+ had significantly larger tumors [median 35 mm (IQR 28-47)] as compared to patients with microN+ [25 mm (IQR 24-35), p=0.040] and N0 neoplasms (26 mm (IQR 18-34), p=0.003]. The rate of G2-G3 neoplasms was comparable between patients with N0 and microN+ PanNETs (45% versus 27%, p=0.203), whereas it was significantly higher among subjects with macroN+ tumors (n=21/27 - 78%). Median Ki67 was 2% in patients with N0 and microN+ neoplasms (p=0.429), whereas it increased to 6% in patients with macroN+ (p=0.006). After a median follow-up of 37 months, 16 patients (16%) experienced disease relapse. Patients with N0 PanNETs had a 4-year DFS rate of 97% as compared with 88% and 43% in patients with microN+ (p=0.152) and macroN+ (p<0.001), respectively. At multivariable analysis, distant metastases (HR 5.826, p=0.026) and macroN+ (HR 6.281, p=0.034) were identified as independent determinants of disease relapse. NF-PanNETs with microN+ seem to be associated with a risk of recurrence similar to N0 neoplasms. MicroN+ may be regarded as a clinicopathological entity separate from macroN+, with a possible impact on postoperative surveillance protocols.

Purpose: Despite initial nihilism and restraint, the idea of surgical treatment of liver metastasis from pancreatic adenocarcinoma (LM-PDAC) has been reported with some satisfactory outcomes. The aim of the present study is to analyze outcome of surgical resection for LM-PDAC within a national cohort of patients with both synchronous and metachronous presentation of the hepatic disease. The secondary endpoint is to discriminate factors potentially associated with oncological outcome and construct a nomogram to predict survival. Methods: Prospectively collected data of LM-PDAC from Italian centers with high volume of pancreatic and/or hepatic activity were retrospectively reviewed for the purposed of the study. Patients were classified according to these settings: 1. PDAC and synchronous LM-PDAC undergoing upfront surgery; 2. PDAC and synchronous LM-PDAC undergoing surgery after neoadjuvant chemotherapy 3. Metachronous LM-PDAC. Factors resulting significantly associated with OS at multivariate analysis were used to construct the model for estimation of OS and consequently predict the risk for these patients. Results: 165 patients were resected for LM-PDAC and included in the analysis: 39 patients (23.6%) were classified in setting 1, 78 (47.3%) in setting 2 and 48 (29.1%) in setting 3. Rate of severe (Dindo>=3) postoperative morbidity was 36.9% and mortality was 0.6%. The median disease-free survival (DFS) and overall survival (OS) from LM-PDAC surgery were 18 and 28 months, respectively. Multivariable analysis identified classification in setting 2 or 3 (HR = 2.229, p <0.001), metachronous presentation (HR= 2.107, p= 0.034, preoperative chemotherapy ((HR= 1.920, p= 0.029), CA19-9 level before surgery (hazard ratio [HR]= 1.016, p <0.001), number of liver lesions <4 (HR= 1.710, p= 0.010) and postoperative major morbidity (HR= 1.013, p <0.033) as independent predictors of survival. The performance of the nomogram built on these factors was assessed using the concordance index, showing good performance (c-index 0.777). Conclusion: Surgical treatment may constitute a valid option in the multidisciplinary management of LM-PDAC. Within adequate selection criteria and supported in clinical decision making using the nomogram, oncological outcomes reported in the present series support the value surgery combined with chemotherapy. Center expertise is a key point in defining the optimal patient-tailored strategy and assuring adequate perioperative results.

Purpose: Variables associated with recurrence and survival in pancreatic ductal adenocarcinoma (PDAC) are well known in case of upfront resection but their role in the neoadjuvant setting is debated. The aim of this study is to assess the strongest prognostic factors in patients presenting a resectable or borderline resectable (BR) disease undergoing chemotherapy before resection. Method: This is a retrospective study including all consecutive pancreatoduodenectomies (PD) or total pancreatectomies (TP) performed after neoadjuvant therapy for an initially resectable or BR PDAC. All variables influencing disease-free survival (DFS) and overall-survival (OS) were examined through a cox regression analysis. Results: Among the 240 patients included in the cohort, 46 (n= 19.2%) were classified as resectable at diagnosis whereas 194 (n= 80.8%) were BR. Beyond the well-established pathologic features, margin status and tumor regression grade revealed to be significantly associated with DFS (p= 0.046 and p= 0.001) and OS (p= 0.002 and p <0.001) at univariate analysis. Preoperative resectability status influenced OS (p= 0.046) but not DFS (p= 0.129). When adjusted for all covariates, factors independently associated with long-term outcomes were more than 3 positive nodes for DFS and OS (p <0.001) and resectability status (p= 0.037), tumor regression grade (p= 0.018) and post-operative severe complications (p <0.001) for OS. Conclusion: In patient undergoing pancreatic resection after neoadjuvant therapy for a resectable or BR PDAC, only nodal status among the well-known pathologic features is an independent prognostic factor. Furthermore, resectability status at diagnosis and tumor regression grade are significantly associated with survival.PBP-112. TableUnivariate and Multivariate Cox Regression Analysis of Prognostic Factors for Disease Specific Survival in the whole cohortVariableCategoryUnivariate AnalysisHazard Ratio (95% CI)PMultivariate AnalysisHazard Ratio (95% CI)PStatus at diagnosisAnatomic Borderline vs Resectable1.75 (1–3.06)0.0461.83 (1.04–3.24)0.037Post-operative severe complicationsYes vs No1.65 (1.09–2.51)0.0172.18 (1.41–3.37)<0.001ypT (TNM, 8th ed.)ypT2 vs ypT0/11.77 (1.18–2.66)0.0050.95 (0.59–1.52)0.823ypT3 vs ypT0/12.48 (1.04–5.89)0.0401.52 (0.62–3.74)0.364ypN (TNM, 8th ed.)ypN1 vs ypN01.58 (0.98–2.54)0.0611.33 (0.82–2.16)0.240ypN2 vs ypN03.7 (2.24–6.11)<0.0012.81 (1.65–4.79)<0.001GradingG3 vs CR-G1/21.51 (1.04–2.21)0.0321.42 (0.96–2.11)0.076R statusR1 vs R01.76 (1.21–2.57)0.0021.2 (0.78–1.83)0.407Perineural InvasionYes vs No2.09 (1.26–3.44)0.0030.98 (0.55–1.75)0.948Microvascular InvasionYes vs No1.83 (1.19–2.82)0.0051.02 (0.6–1.71)0.947TRGMinimal vs poor response0.6 (0.4–0.9)0.0130.83 (0.55–1.27)0.398Moderate vs poor response0.28 (0.15–0.53)<0.0010.44 (0.22–0.86)0.018Marked vs poor response–––– Open table in a new tab

Currently availbale preoperative prognostic factors for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs) still struggle to predict tumor aggressiveness, making an adequate management of these lesions hard to be achieved. Aims of this study were: i) to evaluate treatment appropriateness in patients submitted to surgery for NF-PanNETs, and ii) to investigate preoperative features predicting undertreatment or overtreatment in this setting. Patients who underwent curative surgery (R0-R1) for NF-PanNETs at San Raffaele Hospital (2002-2022) were retrospectively analysed. Treatment appropriateness was categorized as appropriate treatment, overtreatment, and undertreatment. The presence of histological features of aggressiveness and the occurrence of disease relapse within one year from surgery were considered to define treatment appropriateness. Overall, 384 patients were included. Of these, 230 (60%) received an appropriate treatment, 129 (34%) an overtreatment and 25 (6%) an undertreatment. Treatment appropriateness was significantly associated with radiological tumor size (p<0.001), tumor site (p=0.012), surgical technique employed (p<0.001), and year of surgical resection (p<0.001). Surgery performed before 2015 (p<0.001), radiological tumor diameter <25.5mm (p<0.001) and pancreatic body/tail location (p=0.018) were identified as independent predictors of overtreatment. Radiological tumor size was the only independent determinant of undertreatment (p=0.016). Significantly poorer disease-free survival (p<0.001), overall survival (p<0.001) and disease-specific survival (p<0.001) were observed among undertreated patients. Overtreatment occured in almost one-third of patients undergoing surgery for NF-PanNETs. However, over the last decade, the percentage of appropriately treated patients has been steadily increasing. Surgical management should be carefully considered in presence of lesions located in the pancreatic body-tail and/or measuring <25.5 mm, in order to further improve treatment appropriateness.

Aims Describe the experience of a Multidisciplinary team meetings (MTM) tertiary referral center for pancreatic diseases for the management of acute and chronic pancreatitis (AP/CP).

Aims Intraductal papillary neoplasm of the pancreas (IPMN) are common in general population. IPMNs can be classified into three morphological types (Main-duct/MD, Branch-duct/BD and Mixed-type/MT) and ranging from low grade dysplasia (LGD) to invasive carcinoma (IC). Identification of high-grade dysplasia (HGD)/IC has a strong clinical value. The aim of this study is to evaluate the accuracy of endoscopic ultrasound (EUS) to predict malignancy.

Background: Mucinous cystic neoplasms (MCN) of the pancreas are characterized by an inner layer of mucin-secreting cells and an ovarian-like stroma expressing estrogen and progesterone receptors. MCN have a potential for invasive degeneration and surgical resection is recommended by the international guidelines. Several case reports available in literature describe MCN undergoing a rapid increase in size during gestation. These case reports together with their histological characteristics created speculation about the possible interaction of MCN with hormones of gestation and systemic contraceptives. The aim of this study is to assess if pregnancy is a risk factor for malignant degeneration pancreatic MCN.

No single reliable biomarker is available for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). Vasostatin-1 (VS-1), the N-terminal fragment of chromogranin A (CgA), seems to be a more accurate biomarker compared to its precursor. Primary aim was to investigate the ability of VS-1, compared to total-CgA, to assess the effectiveness of surgical resection performed for NF-PanNETs. Secondary aim was to evaluate two additional CgA-derived fragments, pancreastatin (PST) and vasostatin-2 (VS-2), as possible biomarkers for NF-PanNETs. Consecutive patients who underwent surgery for NF-PanNETs at San Raffaele Scientific Institute were included (n = 35). Plasma levels of CgA and CgA-derived fragments were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA), preoperatively and postoperatively. Preoperative VS-1 was significantly higher compared to VS-1 measured on postoperative day 5 (POD5) (pre: 0.338 nM versus POD5: 0.147 nM, P < 0.001), whereas total-CgA significantly increased after surgery (pre: 1.123 nM versus POD5: 1.949 nM, P = 0.006). Overall, 24 patients showed ≥ 1 feature of tumor aggressiveness (T3-T4, nodal/distant metastases, Ki67 > 5%, microvascular/perineural invasion, necrosis). The median percentage decrease in VS-1 plasma levels was 63% (IQR 28–88%) among patients with aggressive tumors, compared to 13% (IQR 0–57%) in the remaining population (P = 0.033). No significant differences in terms of PST (P = 0.870) and VS-2 (P = 0.909) were observed between preoperative and postoperative time. VS-1 provides an early assessment of surgical efficacy in patients who undergo resection for NF-PanNETs, especially in those with aggressive neoplasms. Total-CgA, PST and VS-2 have no clinical utility in this setting.

Our aim was to evaluate the perioperative morbidity and survival of a selected group of patients with locally advanced pancreatic ductal adenocarcinoma (PDAC) and malignant obstruction of portal axis inducing portal hypertension (PH) who underwent a curative intent pancreatic resection, after neoadjuvant chemotherapy, adopting a new type of temporary intraoperative mesentericoportal shunt (TMPS).We analyzed the perioperative data and survival outcome of 15 patients with locally advanced PDAC and PH who underwent pancreatoduodenectomy combined with vascular resections between October 2008 and October 2012 using this TMPS.There was no perioperative mortality. Postoperative morbidity occurred in 7 patients without any postoperative liver failure. All patients underwent mesentericoportal venous resection, 11 of whom had a concomitant arterial resection. The mean ± SD follow-up was 16 ± 10 months (range, 4–40; median 15). Overall survival rates of patients were 78% and 11% at 1 and at 3 years, respectively. Median survival was 17 months. The 1-year disease-free survival was 36%.The use of this form of TMPS allowed us to achieve PD or total pancreatectomy in patients with locally advanced PDAC and PH without postoperative mortality but with increased morbidity. The relevance of such an aggressive approach is yet to be determined.

This paper examines efforts by teacher educators in the US to address student diversity, educational equity, and social justice through teacher education to draw lessons that may be of value globally. We begin by considering what teacher educators mean by “student diversity,” then review and critique the primary methods teacher educators have attempted to prepare teachers who can work with and for a diverse student population to achieve educational equity and social justice. We end by considering the common features of the challenges and failures of these approaches to teacher education, and suggest a transformative teacher education framework.