Faculty Bibliography

OBJECTIVES/OBJECTIVE:To evaluate patient preferences for decision-making role in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and to identify individual characteristics associated with those preferences. BACKGROUND:Management of IPMNs is rooted in uncertainty with current guidelines failing to incorporate patients' preferences and values. METHODS:A representative sample of participants aged 40-70 were recruited to evaluate a clinical vignette where they were given the option to undergo surveillance or surgical resection of their IPMN. Their preferred role in the decision-making process for the vignette was evaluated using the Control Preference Scale. The relationship between control preference and variables including cancer anxiety, health literacy, and education level was analyzed. RESULTS:Of the 520 participants in the study, most preferred an active role (65%), followed by shared (29%), and passive roles (6%) in the decision-making process. Lower health literacy was significantly associated with a more passive control preference (p = 0.003). Non-active preference was significantly associated with Latino race compared to White race (odds ratio = 0.52, p = 0.009) in multivariate analysis. We found no significant association between control preference and education level or cancer anxiety. CONCLUSIONS:Most patients preferred an active role in IPMN treatment decisions. Lower health literacy and Latino race were associated with a preference for non-active decision roles. Clinicians should strive to align patient involvement in IPMN treatment decisions with their patient's preferred role.

OBJECTIVE:To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others. SUMMARY BACKGROUND DATA/BACKGROUND:Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking. METHODS:International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored six standardized case vignettes. This variability and the 'within centers' variability were calculated for twofold scoring (no complication/grade A vs grade B/C) and threefold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula (POPF), post-pancreatoduodenectomy hemorrhage (PPH), chyle leak (CL), bile leak (BL), and delayed gastric emptying (DGE). Interobserver variability is presented with Gwet's AC-1 measure for agreement. RESULTS:Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for twofold scoring was 68% (95%-CI: 55%-81%, AC1 score: moderate agreement) and for threefold scoring 55% (49%-62%, AC1 score: fair agreement). The mean 'within centers' agreement for twofold scoring was 84% (80%-87%, AC1 score; substantial agreement). CONCLUSION/CONCLUSIONS:The interobserver variability for the ISGPS defined complications of pancreatoduodenectomy was too high even though the 'within centers' agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability.

BACKGROUND AND AIM/OBJECTIVE:Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) management is generally extrapolated from pancreatic intraepithelial neoplasia (PanIN)-derived PDAC guidelines. However, these are biologically divergent, and heterogeneity further exists between tubular and colloid subtypes. METHODS:Consecutive upfront surgery patients with PanIN-derived and IPMN-derived PDAC were retrospectively identified from international centers (2000-2019). One-to-one propensity score matching for clinicopathologic factors generated three cohorts: IPMN-derived versus PanIN-derived PDAC, tubular IPMN-derived versus PanIN-derived PDAC, and tubular versus colloid IPMN-derived PDAC. Overall survival (OS) was compared using Kaplan-Meier and log-rank tests. Multivariable Cox regression determined corresponding hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS:The median OS (mOS) in 2350 PanIN-derived and 700 IPMN-derived PDAC patients was 23.0 and 43.1 months (P < 0.001), respectively. PanIN-derived PDAC had worse T-stage, CA19-9, grade, and nodal status. Tubular subtype had worse T-stage, CA19-9, grade, nodal status, and R1 margins, with a mOS of 33.7 versus 94.1 months (P < 0.001) in colloid. Matched (n = 495), PanIN-derived and IPMN-derived PDAC had mOSs of 30.6 and 42.8 months (P < 0.001), respectively. In matched (n = 341) PanIN-derived and tubular IPMN-derived PDAC, mOS remained poorer (27.7 vs 37.4, P < 0.001). Matched tubular and colloid cancers (n = 112) had similar OS (P = 0.55). On multivariable Cox regression, PanIN-derived PDAC was associated with worse OS than IPMN-derived (HR: 1.66, 95% CI: 1.44-1.90) and tubular IPMN-derived (HR: 1.53, 95% CI: 1.32-1.77) PDAC. Colloid and tubular subtype was not associated with OS (P = 0.16). CONCLUSIONS:PanIN-derived PDAC has worse survival than IPMN-derived PDAC supporting distinct outcomes. Although more indolent, colloid IPMN-derived PDAC has similar survival to tubular after risk adjustment.

PURPOSE/OBJECTIVE:Dynamics of carbohydrate antigen 19-9 (CA19-9) often inform treatment decisions during and after neoadjuvant chemotherapy (NAT) of patients with pancreatic ductal adenocarcinoma (PDAC). However, considerable dispute persists regarding the clinical relevance of specific CA19-9 thresholds and dynamics. Therefore, we aimed to define optimal thresholds for CA19-9 values and create a biochemically driven composite score to predict survival in CA19-9-producing patients with PDAC after NAT. METHODS:Patients with PDAC who underwent NAT and surgical resection from 2012 to 2022 were retrospectively identified from three high-volume centers. CA19-9 nonproducers and patients with 90-day mortality, and macroscopically incomplete resections were excluded. A composite score was created on the basis of relative CA19-9 change and newly defined optimal thresholds of pre- and postneoadjuvant values for overall survival (OS) using patients from two centers and validated using data from the third center. RESULTS:< .001). Major serological response (90% decrease of CA19-9) had a positive and negative predictive value of 32% and 88%, respectively. CONCLUSION/CONCLUSIONS:The composite score consisting of CA19-9 levels at diagnosis, after neoadjuvant treatment, and its dynamics demonstrates prognostic discrimination between low and high scores. However, better predictive biomarkers are needed to facilitate treatment decisions during neoadjuvant treatment.

The majority of patients diagnosed with pancreatic cancer already have metastatic disease at the time of presentation, which results in a 5-year survival rate of only 13%. However, multiagent chemotherapy regimens can stabilize the disease in select patients with limited metastatic disease. For such patients, a combination of curative-intent therapy and systemic therapy may potentially enhance outcomes compared to using systemic therapy alone. Of note, the evidence supporting this approach is primarily derived from retrospective studies and may carry a significant selection bias. Looking ahead, ongoing prospective trials are exploring the efficacy of curative-intent therapy in managing oligometastatic pancreatic cancer and the implementation of treatment strategies based on specific biomarkers. The emergence of these trials, coupled with the development of less invasive therapeutic modalities, provides hope for patients with oligometastatic pancreatic cancer.

BACKGROUND OBJECTIVES/OBJECTIVE:The aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value. METHODS:We examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016-2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression. RESULTS:Median overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001). CONCLUSION/CONCLUSIONS:While synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.

OBJECTIVE:To analyze postrecurrence progression in the context of recurrence sites and assess implications for postrecurrence treatment. BACKGROUND:Most patients with resected pancreatic ductal adenocarcinoma (PDAC) recur within 2 years. Different survival outcomes for location-specific patterns of recurrence are reported, highlighting their prognostic value. However, a lack of understanding of postrecurrence progression and survival remains. METHODS:This retrospective analysis included surgically treated patients with PDAC at NYU Langone Health (2010-2021). Sites of recurrence were identified at the time of diagnosis and further follow-up. Kaplan-Meier curves, log-rank test, and Cox regression analyses were applied to assess survival outcomes. RESULTS:Recurrence occurred in 57.3% (196/342) patients with a median time to recurrence of 11.3 months (95% CI: 12.6-16.5). The first site of recurrence was local in 43.9% of patients, liver in 23.5%, peritoneal in 8.7%, lung in 3.6%, whereas 20.4% had multiple sites of recurrence. Progression to secondary sites was observed in 11.7%. Only lung involvement was associated with significantly longer survival after recurrence compared with other sites (16.9 vs 8.49 months, P = 0.003). In local recurrence, 21 (33.3%) patients were alive after 1 year without progression to secondary sites. This was associated with a CA19-9 of <100 U/mL at the time of primary diagnosis ( P = 0.039), nodal negative disease ( P = 0.023), and well-moderate differentiation ( P = 0.042) compared with patients with progression. CONCLUSION/CONCLUSIONS:Except for lung recurrence, postrecurrence survival after PDAC resection is associated with poor survival. A subset of patients with local-only recurrence do not quickly succumb to systemic spread. This is associated with markers for favorable tumor biology, making them candidates for potential curative re-resections when feasible.

BACKGROUND:The appropriate surgical approach for pancreatic ductal adenocarcinoma (PDAC) is determined by the tumor's relation to the porto-mesenteric axis. Although the extent and location of lymphadenectomy is dependent on the type of resection, a pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) are considered equivalent oncologic operations for pancreatic neck tumors. Therefore, we aimed to assess differences in histopathological and oncological outcomes for surgical approaches in the treatment of pancreatic neck tumors. METHODS:Patients with resected PDAC located in the pancreatic neck were identified from the National Cancer Database (2004-2020). Patients with metastatic disease were excluded. Furthermore, patients with 90-day mortality and R2-resections were excluded from the multivariable Cox-regression analysis. RESULTS:Among 846 patients, 58% underwent PD, 25% DP, and 17% TP with similar R0-resection rates (p = 0.722). Significant differences were observed in nodal positivity (PD:44%, DP:34%, TP:57%, p < 0.001) and mean-number of examined lymph nodes (PD:17.2 ± 10.4, DP:14.7 ± 10.5, TP:21.2 ± 11.0, p < 0.001). Furthermore, inadequate lymphadenectomy (< 12 nodes) was observed in 30%, 44%, and 19% of patients undergoing PD, DP, and TP, respectively (p < 0.001). Multivariable analysis yielded similar overall survival after DP (HR:0.83, 95%CI:0.63-1.11), while TP was associated with worse survival (HR:1.43, 95%CI:1.08-1.89) compared to PD. CONCLUSION/CONCLUSIONS:While R0-rates are similar amongst all approaches, DP is associated with inadequate lymphadenectomy which may result in understaging disease. However, this had no negative influence on survival. In the premise that an oncological resection of the pancreatic neck tumor is feasible with a partial pancreatectomy, no benefit is observed by performing a TP.

OBJECTIVE:We aimed to better understand patients' treatment preferences and quantify the level of cancer risk at which treatment preferences change (risk threshold) to inform better counseling of patients with intraductal papillary mucinous neoplasms (IPMNs). SUMMARY BACKGROUND DATA/BACKGROUND:The complexity of IPMN management provides an opportunity to align treatment with individual preference. METHODS:We surveyed a sample of healthy volunteers simulating a common scenario: undergoing an imaging study that incidentally identifies an IPMN. In the scenario, the estimated risk of cancer in the IPMN was 5%. Patients were asked their treatment preference (surgery or surveillance), to quantify the level of cancer risk in the IPMN at which their treatment preference would change (i.e. risk threshold), and their level of cancer anxiety as measured on a 5-point Likert scale. We examined associations between participant characteristics, treatment preferences, and risk threshold using multivariable linear regression. RESULTS:The median risk threshold among the 520 participants was 25% (IQR 2.3-50%). The risk threshold had a bimodal distribution: 40% of participants had a risk threshold between 0-10% and 47% had a risk threshold above 30%. When informed that the risk of cancer was 5%, 62% of participants (n=323) preferred surveillance, and the remaining 38% (n=197) preferred surgery. After adjusting for potential confounders, participants who expressed "worry" or "extreme worry" about the malignancy risk of IPMN had significantly lower risk thresholds than participants who were "not at all worried" (Coefficient -12, 95%CI -21 to -2, P=0.015 and Coefficient -18, 95%CI -29 to -8, P<0.001, respectively). CONCLUSIONS:Participants varied in treatment preference and risk threshold of incidentally identified IPMNs. Given the uncertainty in estimating the true malignant potential of IPMNs, a better understanding of a patient's risk threshold, as influenced by patient concern about malignancy, will help inform the shared decision-making process.

OBJECTIVE:To establish minimal and optimal lymphadenectomy thresholds for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and evaluate their prognostic value. BACKGROUND:Current guidelines recommend a minimum of 12-15 lymph nodes (LNs) in PDAC. This is largely based on pancreatic intraepithelial neoplasia (PanIN)-derived PDAC, a biologically distinct entity from IPMN-derived PDAC. METHODS:Multicenter retrospective study including consecutive patients undergoing upfront surgery for IPMN-derived PDAC was conducted. The minimum cut-off for lymphadenectomy was defined as the maximum number of LNs where a significant node positivity difference was observed. Maximally selected log-rank statistic was used to derive the optimal lymphadenectomy cut-off (maximize survival). Kaplan-Meier curves and log-rank tests were used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariable Cox-regression was used to determine hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS:In 341 patients with resected IPMN-derived PDAC, the minimum number of LNs needed to ensure accurate nodal staging was 10 (P=0.040), whereas ≥20 LNs was the optimal number associated with improved OS (80.3 vs. 37.2 mo, P<0.001). Optimal lymphadenectomy was associated with improved OS [HR:0.57 (95%CI 0.39-0.83)] and RFS [HR:0.70 (95%CI 0.51-0.97)] on multivariable Cox-regression. On sub-analysis the optimal lymphadenectomy cut-offs for pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were 20 (P<0.001), 23 (P=0.160), and 25 (P=0.008). CONCLUSION/CONCLUSIONS:In IPMN-derived PDAC, lymphadenectomy with at least 10 lymph nodes mitigates under-staging, and at least 20 lymph nodes is associated with the improved survival. Specifically, for pancreatoduodenectomy and total pancreatectomy, 20 and 25 lymph nodes were the optimal cut-offs.