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Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15–60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated tumor histology (p = 0.006), more positive lymph nodes (p = 0.04), higher ypN stage (p = 0.002), and higher positive lymph node ratio (p = 0.03). The long-term survivor group had smaller tumor size (p = 0.001), lower ypT stage (p = 0.001), fewer positive lymph nodes (p < 0.001), lower ypN stage (p < 0.001), lower positive lymph node ratio (p < 0.001), lower rate of lymphovascular invasion (p = 0.001) and perineural invasion (p < 0.001), better tumor response grading (p < 0.001), and less frequent recurrence/metastasis (p < 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data.

OBJECTIVES: The initial settings on an intravenous patient-controlled analgesia (IV-PCA) pump can represent a significant source of postoperative opioid exposure. The primary aim of this study was to evaluate the impact of first day IV-PCA use on total inpatient opioid use after open pancreatectomy, before and after standardization of initial dosing. METHODS: Inpatient oral morphine equivalents (OME) were reviewed for pancreatectomy patients treated with IV-PCA at a single institution before and after (3/2016–8/2017 vs. 3/2019–11/2020) implementation of a standardized initial IV-PCA dosing regimen (initial limit 0.1mg hydromorphone, or 1mg OME, every 10 min as needed). IV-PCA OME in the first 24 hours and total inpatient OME were compared between cohorts. RESULTS: Of 220 total patients, 132 were in the pre-standardization historical cohort. First-24-hour IV-PCA use was different (pre-standardization median 95mg vs. post-standardization 15mg, p

The Borrmann classification system is widely used to classify advanced gastric cancer (GC). No studies have focused on the relationship between Borrmann type and response to preoperative therapy.Patients with advanced GC who received preoperative therapy followed by curative-intent gastrectomy from September 2016 through September 2021 were identified. Clinicopathologic characteristics were compared by Borrmann type. Logistic regression models were fit to analyze the relationship between Borrmann type and pCR rate.Of the 227 patients who underwent gastrectomy during the period studied, 73 had pretreatment endoscopic images available for analysis. We classified the tumors as follows: Borrmann type 1, 4 (6%); type 2, 17 (23%); type 3, 33 (45%); and type 4, 19 (26%). Nine patients (12%) achieved pCR; 6 of these (67%) had type 1/2 GC and 3 (33%) had type 3. Multivariable logistic regression showed that Borrmann type 3/4 was the only independent factor associated with pCR (odds ratio 0.12; p = 0.023), but 2-year overall survival rates did not differ by Borrmann type (p = 0.216).Patients with Borrmann type 3/4 advanced GC have a lower likelihood of achieving pCR after preoperative therapy than those with type 1/2 GC. Determining the Borrmann type preoperatively can guide treatment decision-making.

Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies.

PURPOSE The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC. METHODS PDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (HNF4A) expression in PDAC tissues was evaluated by immunohistochemical and Western blot analysis. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and hemoglobin A1C (HbA1C) levels in patients who underwent neoadjuvant FOLFIRINOX treatment. RESULTS High CES2 activity in PDAC PDXs was associated with increased sensitivity to irinotecan. Integrated gene expression, proteomic analyses, and in vitro genetic experiments revealed that nuclear receptor HNF4A, which is upregulated in diabetes, is the upstream transcriptional regulator of CES2 expression. Elevated CES2 protein expression in PDAC tissues was positively associated with a history of type 2 diabetes (odds ratio, 4.84; P = .02). High HbA1C levels were associated with longer overall survival in patients who received neoadjuvant FOLFIRINOX treatment ( P = .04). CONCLUSION To our knowledge, we provide, for the first time, evidence that CES2 expression is associated with a history of type 2 diabetes in PDAC and that elevated HbA1C, by predicting tumor CES2 expression, may represent a novel marker for stratifying patients most likely to respond to FOLFIRINOX therapy.

Background: This study aimed to determine the clinical relevance of putative radiographic and serologic metrics of chemotherapy response in patients with localized pancreatic cancer (LPC) who do not undergo pancreatectomy. Studies evaluating the response of LPC to systemic chemotherapy have focused on histopathologic analyses of resected specimens, but such specimens are not available for patients who do not undergo resection. We previously showed that changes in tumor volume and CA 19-9 levels provide a clinical readout of histopathologic response to preoperative therapy. Methods: Our institutional database was searched for patients with LPC who were treated with first-line chemotherapy between January 2010 and December 2017 and did not undergo pancreatectomy. Radiographic response was measured using RECIST 1.1 and tumor volume. The volume of the primary tumor was compared between pretreatment and posttreatment images. The percentage change in tumor volume (%Δvol) was calculated as a percentage of the pretreatment volume. Serologic response was measured by comparing pretreatment and posttreatment CA 19-9 levels. We established 3 response groups by combining these metrics: (1) best responders with a decline in %Δvol in the top quartile and in CA 19-9, (2) nonresponders with an increase in %Δvol and in CA 19-9, and (3) other patients. Results: This study included 329 patients. Individually, %Δvol and change in CA 19-9 were associated with overall survival (OS) (P≤.1), but RECIST 1.1 was not. In all, 73 patients (22%) were best responders, 42 (13%) were nonresponders, and there were 214 (65%) others. Best responders lived significantly longer than nonresponders and others (median OS, 24 vs 12 vs 17 months, respectively; PConclusions: Changes in tumor volume and serum levels of CA 19-9—but not RECIST 1.1—represent reliable metrics of response to systemic chemotherapy. They can be used to counsel patients and families on survival expectations even if pancreatectomy is not performed.

Background: The value of neoadjuvant radiotherapy (RT) after 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan, with or without dose modifications [(m)FOLFIRINOX], for patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is uncertain. Methods: We conducted an international retrospective cohort study including consecutive patients with BR PDAC who received (m)FOLFIRINOX as initial treatment (2012–2019) from the Trans-Atlantic Pancreatic Surgery Consortium. Because the decision to administer RT is made after chemotherapy, patients with metastases or deterioration after (m)FOLFIRINOX or a performance score ≥2 were excluded. Patients who received RT after (m)FOLFIRINOX were matched 1:1 by nearest neighbor propensity scores with patients who did not receive RT. Propensity scores were calculated using sex, age (≤70 vs >70 years), WHO performance score (0 vs 1), tumor size (0–20 vs 21–40 vs >40 mm), tumor location (head/uncinate vs body/tail), number of cycles (1–4 vs 5–8 vs >8), and baseline CA 19-9 level (≤500 vs >500 U/mL). Primary outcome was overall survival (OS) from diagnosis. Results: Of 531 patients who received neoadjuvant (m)FOLFIRINOX for BR PDAC, 424 met inclusion criteria and 300 (70.8%) were propensity score–matched. After matching, median OS was 26.2 months (95% CI, 24.0–38.4) with RT versus 32.8 months (95% CI, 25.3–42.0) without RT (P=.71). RT was associated with a lower resection rate (55.3% vs 72.7%; P=.002). In patients who underwent a resection, RT was associated with a comparable margin-negative resection rate (>1 mm) (70.6% vs 64.8%; P=.51), more node-negative disease (57.3% vs 37.6%; P=.01), and more major pathologic response with P=.006). The OS associated with conventional and stereotactic body RT approaches was similar (median OS, 25.7 vs 26.0 months; P=.92). Conclusions: In patients with BR PDAC, neoadjuvant RT following (m)FOLFIRINOX was associated with more node-negative disease and better pathologic response in patients who underwent resection, yet no difference in OS was found. Routine use of RT cannot be recommended based on these data.

Background: With increasing implementation of enhanced recovery programs (ERPs) in clinical practice, standardised data collection and reporting have become critical in addressing the heterogeneity of metrics used for reporting outcomes. Opportunities exist to leverage electronic health record (EHR) systems to collect, analyse, and disseminate ERP data. Objectives: (i) To consolidate relevant ERP variables into a singular data universe; (ii) To create an accessible and intuitive query tool for rapid data retrieval. Method: We reviewed nine established individual team databases to identify common variables to create one standard ERP data dictionary. To address data automation, we used a third-party business intelligence tool to map identified variables within the EHR system, consolidating variables into a single ERP universe. To determine efficacy, we compared times for four experienced research coordinators to use manual, five-universe, and ERP Universe processes to retrieve ERP data for 10 randomly selected surgery patients. Results: The total times to process data variables for all 10 patients for the manual, five universe, and ERP Universe processes were 510, 111, and 76 min, respectively. Shifting from the five-universe or manual process to the ERP Universe resulted in decreases in time of 32% and 85%, respectively. Conclusion: The ERP Universe improves time spent collecting, analysing, and reporting ERP elements without increasing operational costs or interrupting workflow. Implications: Manual data abstraction places significant burden on resources. The creation of a singular instrument dedicated to ERP data abstraction greatly increases the efficiency in which clinicians and supporting staff can query adherence to an ERP protocol.

The primary aim was to compare overall survival (OS) between neoadjuvant therapy (NT) and surgery-first (SF) patients with pancreatic adenocarcinoma (PDAC) by nodal stage using the American Joint Commission on Cancer 8th Edition (AJCC8).Rates of nodal positivity are consistently lower following NT versus SF sequencing. It's unclear whether post-NT nodal stage (ypNx) has similar survival compared to SF (pNx) using AJCC8.This is a single-institution retrospective cohort study with routine consideration of NT. Patients undergoing PDAC resection from 2010 to 2018 were analyzed and OS compared by nodal stage using AJCC8.Of 450 total patients, 24% were treated with SF and 76% NT. SF patients had potentially resectable disease in 97% of the cases, whereas NT patients had more advanced clinical stages at diagnosis: borderline resectable 34%, locally advanced 5%. NT patients had higher rates of node-negativity (52.4% vs 22.7%) and lower rates of pathologic N2 disease (19.1% vs 43.6%) vs. SF (p 0.001). For each pathologic nodal stage, SF and NT groups had similar 5-year OS [pN0/ypN0 52.7% vs. 53.6%, p = 0.723], [pN1/ypN1 37.0% vs. 36.7%, p = 0.872], and [pN2/ypN2 16.6% vs. 21.0%, p = 0.508].AJCC8 stratifies outcomes for each post-NT nodal stage similar to SF counterparts. Despite presenting with more advanced clinical stage, NT patients had lower rates of nodal metastases yet comparable OS when stratified by final nodal status. These data provide both hope for patients with obvious radiographic nodal disease at presentation and further support for considering NT sequencing for most patients diagnosed with localized PDAC.