Italian survey about intraperitoneal drain use in distal pancreatectomy.

Intraperitoneal prophylactic drain (IPD) use in distal pancreatectomy (DP) is still controversial. A survey was carried out through the Italian community of pancreatic surgeons using institutional emails, Twitter, and Facebook accounts of the Italian Association for the Study of the Pancreas (AISP) and the Italian Association of Hepato-biliary-pancreatic Surgery (AICEP). The survey was structured to learn surgeons' practice in using IPD through questions and one clinical vignette. Respondents were asked to report their regrets for omission and commission regarding the IPD use for the clinical scenario, eliciting a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were built to identify respondents' attitudes. One hundred six surgeons completed the survey. Sixty-three (59.4%) respondents confirmed using at least 1 drain, while 43 (40.6%) placed 2 IPDs. Only 13 respondents (12.3%) declared a change in IPD strategy in patients at high risk of clinically relevant postoperative pancreatic fistula (CR-POPF), while 9 (9.4%) respondents changed their strategy in low-risk POPF situations. Thirty-five (35.5%) respondents declared they would remove the IPD within the third postoperative day (POD) in the absence of CR-POPF suspicion. The median omission regret, which proved to be the wrong decision, was 80 (50-100, IQR). The median regret due to the commission of IPD, which turned out to be useless, was 2.5 (1-20, IQR). The CR-POPF probability threshold at which drainage omission was the less regrettable choice was 7% (1-35, IQR). The threshold to perceive drain omission as the least regrettable choice was higher in female surgeons (P < 0.001), in surgeons who modulated the strategies based on the risk of CR-POPF, and in high volume centers (p = 0.039). The threshold was lower in surgeons who performed minimally invasive distal pancreatectomy (P < 0.001), adopted a closed system (P < 0.001), placed two IPDs (P < 0.001), or perceived the IPD as important to prevent reintervention (p = 0.047). Drain management after DP remains very heterogeneous among surgeons. The regret model suggested that IPD omission could be performed in low-risk patients (7% of CR-POPF), leading to low regret in the case of the wrong decision, making it an acceptable clinical decision.

Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study.

BACKGROUND: Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients. The potential benefits of neoadjuvant treatments have, however, never been explored. The primary aim of this study was to evaluate the safety of neoadjuvant 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) followed by surgery in patients with NF-PanNETs. METHODS: NEOLUPANET was a multicentre, single-arm, phase II trial of patients with sporadic, resectable or potentially resectable NF-PanNETs at high-risk of recurrence; those with positive 68Ga-labelled DOTA PET were eligible. All patients were candidates for neoadjuvant 177Lu-DOTATATE followed by surgery. A sample size of 30 patients was calculated to test postoperative complication rates against predefined cut-offs. The primary endpoint was safety, reflected by postoperative morbidity and mortality within 90 days. Secondary endpoints included rate of objective radiological response and quality of life. RESULTS: From March 2020 to February 2023, 31 patients were enrolled, of whom 26 completed 4 cycles of 177Lu-DOTATATE. A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed. Twenty-four R0 resections and 4 R1 resections were performed in 29 patients who underwent surgery. One tumour was unresectable owing to vascular involvement. There was no postoperative death. Postoperative complications occurred in 21 of 29 patients. Severe complications were observed in seven patients. Quality of life remained stable after 177Lu-DOTATATE and decreased after surgery. CONCLUSION: Neoadjuvant treatment with 177Lu-DOTATATE is safe and effective for patients with NF-PanNETs.

Surgical removal of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) can often cure patients. However, it is not known whether treating patients before surgery provides additional benefits. The main aim of the study was to investigate safety of treatment called peptide receptor radionuclide therapy with 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) before surgery in patients with NF-PanNETs. The NEOLUPANET study was conducted from March 2020 to February 2023 across multiple centres. Patients with NF-PanNETs that were at high risk of recurrence after surgery were included. All patients received 177Lu-DOTATATE before surgery. The main measure of success was safety, reflected by complications or death within 90 days after surgery. The study enrolled 31 patients and 26 completed four cycles of 177Lu-DOTATATE. Tumours shrank partially in 18 patients, and in 13 patients the tumour remained the same. No tumours increased in size. The entire tumour was removed in 28 of 29 patients. No patients died, but 72% had some complications (severe in 7 patients). The study found that using 177Lu-DOTATATE before surgery is safe and useful for treating patients with NF-PanNETs.

Pathologic complete response following neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma: Impact on survival and recurrence.

BACKGROUND: Pathologic complete response after neoadjuvant treatment in pancreatic ductal adenocarcinoma is a rare occurrence. Similar to other malignancies, achieving a pathologic complete response in pancreatic ductal adenocarcinoma seems to correlate with improved survival. However, because of the rarity of such events, the true significance of pathologic complete response in pancreatic cancer remains unclear. The aim of the present study was to investigate the impact of pathologic complete response on survival and recurrence. METHODS: In a single-center retrospective study, pathologic complete response was defined as no evidence of viable tumor cells in resected specimen entirely sampled according to a rigorous protocol and in which a residual tumor bed was identified. Disease-specific survival and disease-free survival were measured from surgery. Independent predictors for disease-specific survival and disease-free survival were examined. RESULTS: Overall, 403 patients were included. Pathologic complete response was found in 15 patients (3.8%), after chemotherapy alone. After a median follow-up of 42 months (95% CI 38-45), 3-year disease-specific survival was 87% in pathologic complete response patients vs 43% in those without pathologic complete response (P = .014). The recurrence rate was 40% (n = 6/15) in the pathologic complete response group compared with 69.8% (n = 271/388) in those without pathologic complete response. Disease-free survival was longer in the pathologic complete response group, with higher 1- and 3-year rates compared with the no-pathologic complete response group (80% vs 60% and 48% vs 24%, respectively). Pathologic complete response was found to be an independent protective factor for disease-specific survival (P = .035) but not for disease-free survival (P = .052). CONCLUSION: Pathologic complete response in pancreatic ductal adenocarcinoma is not synonymous of cure but ensure a prolonged survival. Nevertheless, recurrence remains a significant concern, with high rates observed even among these exceptional responders.

The Impact of Postoperative Complications on Recovery of Health-Related Quality of Life and Functional Capacity after Pancreatectomy: Findings From a Prospective Observational Study.

OBJECTIVE: To evaluate the extent to which postoperative complications impact on patient health-related quality of life (HRQoL) and survival after pancreatic surgery. SUMMARY BACKGROUND DATA: Pancreatectomy is frequently associated with severe postoperative morbidity, which can affect patient recovery. Few and conflicting data are available regarding the effect of post-pancreatectomy complications on patient reported HRQoL. METHODS: This is an observational cohort study including consecutive patients enrolled in a prospective clinical trial (NCT04431076) who underwent elective pancreatectomy (2020-2022). Before surgery and on postoperative days (PODs) 15, 30, 90, 180, patients completed PROMIS-29 profile and Duke Activity Status Index questionnaires to assess their HRQoL and functional capacity. Mean differences in HRQoL scores were obtained using multivariable linear regression adjusting for preoperative scores and confounders. RESULTS: Of 528 patients, 370 (70%) experienced morbidity within 90 days, 154 (29%) severe complications (Clavien-Dindo grade >2). Delayed gastric emptying had the greatest impact on HRQoL, showing decreased mental health up to POD90 and physical health up to POD180 compared to uncomplicated patients. An inverse relationship between complication severity grade and HRQoL was evident for most domains, with Clavien-Dindo grade 3b-4 patients showing worse HRQoL and functional capacity scores up to 6 months after surgery. In 235 pancreatic cancer patients, grade 3b and 4 complications were associated with reduced disease specific survival (median 25 versus 41 mo, P<0.001). CONCLUSION: In patients undergoing pancreatic resection, postoperative complications significantly impact on all domains of patient quality of life with a dose-effect relationship between complication severity and impairment of HRQoL and functional capacity.

Critical appraisal of the adequacy of surgical indications for non-functioning pancreatic neuroendocrine tumours.

BACKGROUND: The lack of preoperative prognostic factors to accurately predict tumour aggressiveness in non-functioning pancreatic neuroendocrine tumours may result in inappropriate management decisions. This study aimed to critically evaluate the adequacy of surgical treatment in patients with resectable non-functioning pancreatic neuroendocrine tumours and investigate preoperative features of surgical appropriateness. METHODS: A retrospective study was conducted on patients who underwent curative surgery for non-functioning pancreatic neuroendocrine tumours at San Raffaele Hospital (2002-2022). The appropriateness of surgical treatment was categorized as appropriate, potential overtreatment and potential undertreatment based on histologic features of aggressiveness and disease relapse within 1 year from surgery (early relapse). RESULTS: A total of 384 patients were included. Among them, 230 (60%) received appropriate surgical treatment, whereas the remaining 154 (40%) underwent potentially inadequate treatment: 129 (34%) experienced potential overtreatment and 25 (6%) received potential undertreatment. The appropriateness of surgical treatment was significantly associated with radiological tumour size (P < 0.001), tumour site (P = 0.012), surgical technique (P < 0.001) and year of surgical resection (P < 0.001). Surgery performed before 2015 (OR 2.580, 95% c.i. 1.570 to 4.242; P < 0.001), radiological tumour diameter < 25.5 mm (OR 6.566, 95% c.i. 4.010 to 10.751; P < 0.001) and pancreatic body/tail localization (OR 1.908, 95% c.i. 1.119 to 3.253; P = 0.018) were identified as independent predictors of potential overtreatment. Radiological tumour size was the only independent determinant of potential undertreatment (OR 0.291, 95% c.i. 0.107 to 0.791; P = 0.016). Patients subjected to potential undertreatment exhibited significantly poorer disease-free survival (P < 0.001), overall survival (P < 0.001) and disease-specific survival (P < 0.001). CONCLUSIONS: Potential overtreatment occurs in nearly one-third of patients undergoing surgery for non-functioning pancreatic neuroendocrine tumours. Tumour diameter emerges as the sole variable capable of predicting the risk of both potential surgical overtreatment and undertreatment.

Implications of noncoding regulatory functions in the development of insulinomas.

Insulinomas are rare neuroendocrine tumors arising from pancreatic ß cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development, and epigenetic modifying genes, including polycomb complex components. Chromatin remodeling is apparent in insulinoma-selective domains shared across patients, containing a specific set of regulatory sequences dominated by the SOX17 binding motif. Moreover, many of these regions are H3K27me3 repressed in ß cells, suggesting that tumoral transition involves derepression of polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements affecting the function and fate of ß cells in their progression to insulinomas and a framework to identify coding and noncoding driver mutations.

European Neuroendocrine Tumor Society (ENETS) 2024 guidance paper for the management of well-differentiated small intestine neuroendocrine tumours.

Both the incidence and prevalence of well-differentiated neuroendocrine tumours from the small intestine (Si-NET) are gradually increasing. Most patients have non-functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment-related decision-making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si-NET grade (G) 1-3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making.

Exploring definitions of graft pancreatitis following pancreas transplantation: A scoping review.

Despite the clinical relevance of graft pancreatitis (GP) after pancreas transplantation (PT), a universally accepted definition is lacking. Aim of this scoping review was to provide a systematic overview of GP definitions reported in the literature. MEDLINE, Web of Science and Embase were searched for relevant articles. Prospective/retrospective studies reporting a GP definition were included. The included series (n = 20) used four main criteria (clinical, biochemical, radiological and pathological) to define GP. Overall, 9 studies defined GP using a single criterion (n = 8 biochemical, n = 1 pathological), 7 series using two criteria (n = 3 clinical + biochemical, n = 3 biochemical + radiological, n = 1 clinical + radiological), 3 series using three criteria (n = 3 clinical + biochemical + radiological), and 1 series using four criteria. Overall, 20 definitions of GP were found. GP rate was reported by 19 series and ranged between 0% and 87%. This scoping review confirms that a universally accepted definition of GP is absent, and there is no consensus on the criteria on which it should be grounded. Future research should focus on developing a validated definition of GP.

Preoperative assessment of lymph nodal metastases with [68Ga]Ga-DOTATOC PET radiomics for improved surgical planning in well-differentiated pancreatic neuroendocrine tumours.

PURPOSE: Accurate identification of lymph node (LN) metastases is pivotal for surgical planning of pancreatic neuroendocrine tumours (PanNETs); however, current imaging techniques have sub-optimal diagnostic sensitivity. Aim of this study is to investigate whether [68Ga]Ga-DOTATOC PET radiomics might improve the identification of LN metastases in patients with non-functioning PanNET (NF-PanNET) referred to surgical intervention. METHODS: Seventy-two patients who performed preoperative [68Ga]Ga-DOTATOC PET between December 2017 and March 2022 for NF-PanNET. [68Ga]Ga-DOTATOC PET qualitative assessment of LN metastases was measured using diagnostic balanced accuracy (bACC), sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). SUVmax, SUVmean, Somatostatin receptor density (SRD), total lesion SRD (TLSRD) and IBSI-compliant radiomic features (RFs) were obtained from the primary tumours. To predict LN involvement, these parameters were engineered, selected and used to train different machine learning models. Models were validated using tenfold repeated cross-validation and control models were developed. Models' bACC, SN, SP, PPV and NPV were collected and compared (Kruskal-Wallis, Mann-Whitney). RESULTS: LN metastases were detected in 29/72 patients at histology. [68Ga]Ga-DOTATOC PET qualitative examination of LN involvement provided bACC = 60%, SN = 24%, SP = 95%, PPV = 78% and NPV = 65%. The best-performing radiomic model provided a bACC = 70%, SN = 77%, SP = 61%, PPV = 60% and NPV = 83% (outperforming the control model, p < 0.05*). CONCLUSION: In this study, [68Ga]Ga-DOTATOC PET radiomics allowed to increase diagnostic sensitivity in detecting LN metastases from 24 to 77% in NF-PanNET patients candidate to surgery. Especially in case of micrometastatic involvement, this approach might assist clinicians in a better patients' stratification.

Intraperitoneal prophylactic drain after pancreaticoduodenectomy: an Italian survey.

Intraperitoneal prophylactic drain (IPD) use in pancreaticoduodenectomy (PD) is still controversial. A survey was designed to investigate surgeons' use of IPD in PD patients through 23 questions and one clinical vignette. For the clinical scenario, respondents were asked to report their regret of omission and commission regarding the use of IPD elicited on a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were applied. One hundred three (97.2%) respondents confirmed using at least two IPDs. The median regret due to the omission of IPD was 84 (67-100, IQR). The median regret due to the commission of IPD was 10 (3.5-20, IQR). The CR-POPF probability threshold at which drainage omission was the less regrettable choice was 3% (1-50, IQR). The threshold was lower for those surgeons who performed minimally invasive PD (P = 0.048), adopted late removal (P = 0.002), perceived FRS able to predict the risk (P = 0.006), and IPD able to avoid relaparotomy P = 0.036). Drain management policies after PD remain heterogeneous among surgeons. The regret model suggested that IPD omission could be performed in low-risk patients.

Recent developments in the diagnosis of pancreatic neuroendocrine neoplasms.

INTRODUCTION: Pancreatic Neuroendocrine Neoplasms (PanNENs) are characterized by a highly heterogeneous clinical and biological behavior, making their diagnosis challenging. PanNENs diagnostic work-up mainly relies on biochemical markers, pathological examination, and imaging evaluation. The latter includes radiological imaging (i.e. computed tomography [CT] and magnetic resonance imaging [MRI]), functional imaging (i.e. 68Gallium [68 Ga]Ga-DOTA-peptide PET/CT and Fluorine-18 fluorodeoxyglucose [18F]FDG PET/CT), and endoscopic ultrasound (EUS) with its associated procedures. AREAS COVERED: This review provides a comprehensive assessment of the recent advancements in the PanNENs diagnostic field. PubMed and Embase databases were used for the research, performed from inception to October 2023. EXPERT OPINION: A deeper understanding of PanNENs biology, recent technological improvements in imaging modalities, as well as progresses achieved in molecular and cytological assays, are fundamental players for the achievement of early diagnosis and enhanced preoperative characterization of PanNENs. A multimodal diagnostic approach is required for a thorough disease assessment.

Very Early Recurrence After Curative Resection for Pancreatic Ductal Adenocarcinoma: Proof of Concept for a "Biological R2 Definition".

PURPOSE: Very early recurrence after radical surgery for pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study was designed to evaluate this group of patients who developed recurrence, within 12 weeks after surgery, defined as "biological R2 resections (bR2)." METHODS: Data from patients who underwent surgical resection as upfront procedure or after neoadjuvant treatment for PDAC between 2015 and 2019 were analyzed. Disease-free, disease-specific survival, and independent predictors of early recurrence were examined. The same analysis was performed separately for upfront and neoadjuvant treated patients. RESULTS: Of the 573 patients included in the study, 63 (11%) were classified as bR2. The rate of neoadjuvant treatment was similar in bR2 and in the remaining patients (44 vs. 42%, p = 0.78). After a median follow-up of 27 months, median DFS and DSS for the entire cohort were 17 and 43 months, respectively. Median DSS of bR2 group was 13 months. The only preoperative identifiable independent predictor of very early recurrence was body-tail site lesion, whereas all other were pathological: higher pT (8th classification), G3 differentiation, and high lymph node ratio. These predictors were confirmed for patients undergoing upfront surgery, whereas in the neoadjuvant group the only independent predictor was pT. CONCLUSIONS: One of ten patients with "radical" resected PDAC relapses very early after surgery (bR2); hence, imaging must be routinely repeated within 12 weeks. Despite higher biological aggressiveness and worse pathology, this bR2 cluster eludes our preoperative examinations.

The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). PATIENTS AND METHODS: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested. RESULTS: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival.

Are enhanced recovery protocols after pancreatoduodenectomy still efficient when applied in elderly patients? A systematic review and individual patient data meta-analysis.

BACKGROUND: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD). METHODS: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70-79 years) and older patients (≥80 years). RESULTS: IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65-1.29], p = .596 and OR 1.22 [95% CI: 0.61-2.46], p = .508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (-0.14 days [95% CI: -0.29 to 0.01], p = .071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (-0.28 days [95% CI: -0.62 to 0.05], p = .069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (-0.36 days [95% CI: -0.71 to -0.004], p = .048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group. CONCLUSION: ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers.

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database.

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083).

Exploring the optimal therapeutic management of stage ypIA pancreatic ductal adenocarcinoma patients in the era of primary chemotherapy.

BACKGROUND: Data on the proper post-surgical chemotherapy (PSC) in pancreatic ductal adenocarcinoma (PDAC) patients already treated with neoadjuvant therapy (NAT) are lacking, especially for stage ypIA. AIM AND METHODS: We retrospectively analyzed ypT1N0M0 (ypIA) PDAC patients resected after NAT between 2015 and 2020 at our Institution. Primary endpoint was median disease free-survival (DFS) according to PSC treatment. RESULTS: Seventy-five out of 363 patients achieved a pathological ypIA after NAT (20.6%) and 72 were analyzed. Among the study population 34 patients (47%) were treated with NAT ≤4 months and 38 (53%) >4 months. After surgery, 10 patients (14%) received PSC using the same multidrug NAT regimen (Group A); 35 (49%) received PSC with a different regimen (Group B), with either single agents in 24 patients (68.5%) or combination schedules in 11 (31.5%); 27 patients (14%) did not receive any PSC (Group C). DFS was longer in group A and C as opposed to group B (p = 0.006). CONCLUSION: Patients affected by ypIA PDAC treated with a proper multi-agent chemotherapy for more than 4 months show an improved DFS, regardless of the peri­operative or totally pre-surgical administration of treatment.