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Simple Summary: Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving neoadjuvant therapy (NAT) with the aim of improving patient care. However, complete tumor regression remains rare, and there is a dire need for biomarkers that can predict responses to NAT. SMAD4 is a protein that is inactivated in about half of PDACs and has been described as associated with metastasis and resistance to therapy. The aim of our study is to investigate whether SMAD4 status is a prognostic and predictive factor in patients with pancreatic cancer receiving NAT. In our cohort of patients, SMAD4 loss was associated with quicker progression and metastasis development. When patients were subgrouped depending on their type of neoadjuvant treatment, those receiving FOLFIRINOX-based NAT and presenting SMAD4-positive tumors showed the best outcome. This result suggests that SMAD4 may be a potential biomarker for patients with pancreatic cancer receiving NAT and may help improve patient care. Background: SMAD4 is inactivated in 50–55% of pancreatic ductal adenocarcinomas (PDACs). SMAD4 loss of expression has been described as a negative prognostic factor in PDAC associated with an increased rate of metastasis and resistance to therapy. However, the impact of SMAD4 inactivation in patients receiving neoadjuvant therapy (NAT) is not well characterized. The aim of our study was to investigate whether SMAD4 status is a prognostic and predictive factor in patients receiving NAT. Methods: We retrospectively analyzed 59 patients from a single center who underwent surgical resection for primary PDAC after NAT. SMAD4 nuclear expression was assessed by immunohistochemistry, and its relationship to clinicopathologic variables and survival parameters was evaluated. Interaction testing was performed between SMAD4 status and the type of NAT. Results: 49.15% of patients presented loss of SMAD4. SMAD4 loss was associated with a higher positive lymph node ratio (p = 0.03), shorter progression-free survival (PFS) (p = 0.02), and metastasis-free survival (MFS) (p = 0.02), but it was not an independent prognostic biomarker in multivariate analysis. Interaction tests demonstrated that patients with SMAD4-positive tumors receiving FOLFIRINOX-based NAT showed the best outcome. Conclusion: This study highlights the potential prognostic and predictive role of SMAD4 status in PDAC patients receiving FOLFIRINOX-based NAT. [ABSTRACT FROM AUTHOR]

Background: Opioid-free anesthesia (OFA) is associated with significantly reduced cumulative postoperative morphine consumption in comparison with opioid-based anesthesia (OBA). Whether OFA is feasible and may improve outcomes in pancreatic surgery remains unclear. Methods: Perioperative data from 77 consecutive patients who underwent pancreatic resection were included and retrospectively reviewed. Patients received either an OBA with intraoperative remifentanil (n = 42) or an OFA (n = 35). OFA included a combination of continuous infusions of dexmedetomidine, lidocaine, and esketamine. In OBA, patients also received a single bolus of intrathecal morphine. All patients received intraoperative propofol, sevoflurane, dexamethasone, diclofenac, neuromuscular blockade. Postoperative pain management was achieved by continuous wound infiltration and patient-controlled morphine. The primary outcome was postoperative pain (Numerical Rating Scale, NRS). Opioid consumption within 48 h after extubation, length of stay, adverse events within 90 days, and 30-day mortality were included as secondary outcomes. Episodes of bradycardia and hypotension requiring rescue medication were considered as safety outcomes. Results: Compared to OBA, NRS (3 [2–4] vs 0 [0–2], P < 0.001) and opioid consumption (36 [24–52] vs 10 [2–24], P = 0.005) were both less in the OFA group. Length of stay was shorter by 4 days with OFA (14 [7–46] vs 10 [6–16], P < 0.001). OFA (P = 0.03), with postoperative pancreatic fistula (P = 0.0002) and delayed gastric emptying (P < 0.0001) were identified as only independent factors for length of stay. The comprehensive complication index (CCI) was the lowest with OFA (24.9 ± 25.5 vs 14.1 ± 23.4, P = 0.03). There were no differences in demographics, operative time, blood loss, bradycardia, vasopressors administration or time to extubation among groups. Conclusions: In this series, OFA during pancreatic resection is feasible and independently associated with a better outcome, in particular pain outcomes. The lower rate of postoperative complications may justify future randomized trials to test the hypothesis that OFA may improve outcomes and shorten length of stay. [ABSTRACT FROM AUTHOR]