Faculty Bibliography

BACKGROUND:The National Comprehensive Cancer Network guidelines consider pancreatic cancer with celiac axis (CA), proper hepatic artery (PHA), and superior mesenteric artery (SMA) involvement unresectable. Thus, technical reports and video illustrations of these operations are rare. We report the stepwise management of multivascular reconstruction for Mayo Clinic class IIIb CA resections at New York University Langone Health, a dedicated center of excellence in pancreatic surgery. METHODS:We illustrated the management of a 56-year-old patient with biopsy-confirmed pancreatic ductal adenocarcinoma arising from the pancreatic body and involving the CA, PHA, SMA, and mesentericoportal venous axis. PERIOPERATIVE MANAGEMENT/UNASSIGNED:The preoperative stepwise considerations include: 1) mandatory patient selection; 2) planning vascular reconstructability; 3) tailoring risk assessment while carefully considering the need for total pancreatectomy, total gastrectomy, and mesenteric/hepatic revascularization; and 4) 3D-reconstruction for arterial evaluation. The key intraoperative considerations include: 1) selective and sequential clamping for vascular reconstruction in a "domino" fashion, to minimize warm ischemic time 2) a combined multi-surgeon approach to comprehensively tackle vascular reconstructions; 3) a low threshold for total pancreatectomy to avoid pancreatic leak; and 4) two-stage surgery to reassess the blood supply to the liver and stomach for on-demand gastric preservation instead of a theoretically advised total gastrectomy. CONCLUSION/CONCLUSIONS:Liver, stomach, and bowel vascularization present life-threatening risks that require an extensive preoperative evaluation and a multidisciplinary approach. Our stepwise management for these extensive operations includes total pancreatectomy, "domino" vascular reconstruction, and two-stage surgery.

BACKGROUND:Current guidelines recommend the resection of main duct- (MD) and mixed-type (MT) intraductal papillary mucinous neoplasms (IPMN) based on specific risk criteria to prevent or treat pancreatic cancer in selected patients. This paradigm follows high rates of malignancy observed in published surgical series. The aim of this systematic review and meta-analysis was to provide robust, pooled rates of invasive carcinoma (IC) and high-grade dysplasia (HGD) in resected MD- and MT-IPMNs of the pancreas. METHODS:The PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were systematically searched. Studies that reported rates of IC or HGD, diagnosed by histopathology of surgical specimens, in MD- or MT-IPMNs were included. Pooled prevalence with 95 % confidence interval (95 % CI) was calculated using a random effects model. Galbraith plots were used to evaluate heterogeneity. Risk of bias was assessed using the National Institutes of Health Quality Assessment Tool. RESULTS:Based on 51 studies, 59 % (95 % CI: 54 %, 64 %) of resected MD- and MT-IPMN had IC or HGD, with IC in up to 39 % (95 % CI: 33 %, 44 %) of lesions and HGD in 20 % (95 % CI: 16 %, 25 %). Most studies were deemed to be of good quality and Galbraith plots demonstrated high concordance. CONCLUSIONS:These results confirm the rates of IC and HGD in resected MD/MT-IPMNs. However, a significant proportion of patients have benign lesions, and future research is needed to develop precise diagnostics to distinguish between patients with and without high-risk or cancerous disease.

SUMMARY OF BACKGROUND DATA/BACKGROUND:Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is typically managed like pancreatic intraepithelial neoplasia (PanIN)-derived pancreatic cancer. However, in IPMN-derived pancreatic cancer, the role of chemotherapy remains controversial, particularly in the neoadjuvant setting (NAT). OBJECTIVE:To evaluate the role of neoadjuvant chemotherapy in IPMN-derived pancreatic cancer. METHODS:Patients with IPMN-derived pancreatic cancer treated with either upfront surgery (US) or NAT were identified from eight international centers (2000-2023). Clinicopathologic data were compared. Date of first treatment was used for Kaplan-Meier and log-rank tests to compare overall (OS) and recurrence free survival (RFS). Multivariable Cox-regression was performed in patients that underwent NAT. RESULTS:In 1,019 patients, 76 (7%) underwent NAT. Patients who received NAT had higher baseline CA19-9 levels (P<0.001). Of these 76 patients, 27 (36%), 20 (26%), and 29 (38%) had resectable, borderline resectable, or locally advanced pancreatic cancer at diagnosis, respectively. Advanced resectability stage was significantly more common in the NAT patients as compared to those who underwent US (P<0.001). OS for US patients was 38.0 months (95%CI: 33.7.1-44.3), which was not statistically different than those that received NAT [27.5 mo (95%CI: 23.1-46.7), P=0.121]. This was also valid for patients with resectable disease [US: 38.1 mo vs. NAT: 35.6 mo, P=0.920)]. Complete or marked pathological treatment response (P=0.046) and serological CA19-9 normalization after NAT (P=0.017) were associated with improved survival. On Cox-regression for OS, N2 disease [HR: 4.15 (95%CI: 1.71-10.10)], elevated CA19-9 [HR: 2.02 (95%CI:1.06-3.85)] and R1 margin [HR: 2.36 (95%CI:1.20-4.61)] was independently associated with OS after NAT, while resectability status was not. CONCLUSION/CONCLUSIONS:After NAT and resection, advanced resectability stage was not associated with worse OS indicating the value of this approach for borderline resectable and locally advanced IPMN-derived pancreatic cancer. The benefit of NAT in resectable disease is unclear and may require an individualized approach. Biological treatment effect can be assessed with CA19-9 and confirmed by pathologic response.

BACKGROUND:The current evaluation of surgical resident operative autonomy consists primarily of self-report and is prone to bias. Objective performance indicators (OPIs) generated from the da Vinci Surgical System capture objective intraoperative data providing an opportunity to evaluate the intraoperative resident experience more accurately. This study investigates the ability of OPIs to describe resident autonomy during robotic cholecystectomy. METHODS:The Intuitive Data Recorder captured OPI data during 82 robotic cholecystectomies performed at a single high-volume academic center between July 1st, 2020, and April 30th, 2023. Autonomy was characterized by evaluating surgeon-specific OPIs: instrument active time (AT) and path length (PL). OPIs were evaluated for the overall procedure, the hepatocystic triangle dissection, and the gallbladder fossa dissection. Analysis was stratified by trainee level and case complexity as defined by the Parkland Grading Scale. RESULTS:Of the 82 cholecystectomies, surgical trainees participated in 77 cases, 59.7% (n = 46) involved senior trainees (PGY 4-7), and 40.3% (n = 31) involved junior trainees (PGY 2-3). By median AT, senior trainees performed 60% of the cholecystectomy (median AT 0.6 [IQR, 0.5 - 0.8]), significantly more compared to junior trainees at 40% (AT 0.4 [IQR 0.3 - 0.5]; P < 0.001). Junior residents had the least autonomy during the hepatocystic triangle dissection (P < 0.05) whereas no significant difference was present between annotated steps for senior trainees (P > 0.05). Resident autonomy did not vary significantly based on case complexity (P > 0.05). Overall, 76.1% of senior residents performed at least half of the cholecystectomy, significantly more compared to 32.3% of junior trainees (P < 0.001). CONCLUSION/CONCLUSIONS:OPIs differentiated the surgical trainee experience during a robotic cholecystectomy. While senior trainees performed more of the procedure, there was significant within-group heterogeneity regarding the level of autonomy allotted. Moving forward, OPIs can be a valuable tool for characterizing resident autonomy and objectively informing surgical training curricula.

BACKGROUND:To improve outcomes for patients with pancreatic ductal adenocarcinoma, a complete resection is crucial. However, evidence regarding the impact of microscopically positive surgical margins (R1) on recurrence is conflicting due to varying definitions and limited populations of patients with borderline-resectable and locally advanced pancreatic cancer. Therefore, we aimed to determine the impact of the resection margin status on recurrence and survival in patients with pancreatic ductal adenocarcinoma stratified by local tumor stage. METHODS:We performed a retrospective cohort study on patients with nonmetastatic pancreatic ductal adenocarcinoma undergoing pancreatectomy at a high-volume academic center (2012-2022). R1 was subclassified into microscopic invasion of the margin (R1 direct) or carcinoma present within 1 mm but not directly involving the margin (R1 <1 mm). Overall survival and time to recurrence were assessed by log-rank test and multivariable Cox regression. RESULTS:Of 472 included patients, 154 (33%) had an R1 resection. Of those 50 (32%) had R1 <1 mm and 104 (68%) R1 direct. The most commonly involved margin was the uncinate (41%) followed by the pancreatic neck (16%) and vascular margins (9%). Overall, a stepwise shortening of time to recurrence and overall survival was observed with an increasing degree of margin involvement (median time to recurrence: R0 39.3 months, R1 <1 mm 16.0 months, and R1 direct 13.4 months, all comparisons P < .05). Multivariable analyses confirmed the independent prognostic value of R1 direct across all surgical stages. CONCLUSION/CONCLUSIONS:The resection margin status portends an independent prognostic value. Moreover, this association persists in patients with borderline-resectable and locally advanced pancreatic cancer. Increasing the R0-resection rate is the most important potentially influenceable prognostic factor for improving surgery-related outcomes.

BACKGROUND:IPMN consensus guidelines make implicit judgments on what cancer risk level should prompt surgery. We used decision modeling to estimate this cancer risk threshold (CRT) for BD-IPMN patients. METHODS:We created a decision model to compare quality-adjusted life years (QALYs) following surgery or surveillance for BD-IPMNs. We simulated treatment decisions for hypothetical patients, varying age, comorbidities and lesion location (pancreatic head/tail). The base case was a 60-year-old patient with mild comorbidities and pancreatic head IPMN. Probabilities, life expectancies, and utilities were incorporated from literature/public datasets. CRT was defined as the level of cancer risk at which the expected value of QALYs for surgery first exceeded that of surveillance. RESULTS:In the base case, surgery was preferred over surveillance, yielding 21.90 vs. 21.88 QALYs. The optimal CRT for a BD-IPMN patient depended on age, comorbidities, and location. CRT in the base case was 20 % and 3 % for an IPMN in the head and tail of the pancreas, respectively. Other drivers of preferred treatment were age and likelihood of postoperative mortality. CONCLUSION/CONCLUSIONS:For BD-IPMNs, the optimal CRT varies depending on patient age and risk of surgical complications. Personalized risk threshold values could guide treatment decisions and inform future treatment consensus guidelines.

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.

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.