Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer.

Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland "units." Tumor gland typing provided an additional layer of intratumoral heterogeneity that was associated with differences in stromal abundance and clinical outcomes. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.

Caregiver-reported quality of communication in pancreatic and periampullary cancer.

BACKGROUND: Communication between caregivers and clinical team members is critical for transitional care, but its quality and potential impact on outcomes are not well understood. This study reports on caregiver-reported quality of communication with clinical team members in the postpancreatectomy period and examines associations of these reports with patient and caregiver outcomes. METHODS: Caregivers of patients with pancreatic and periampullary malignancies who had undergone pancreatectomy were surveyed. Instrument measures assessed care experiences using the Caregiver Perceptions About Communication with Clinical Team Members (CAPACITY) instrument. The instrument has two main subscales: communication, assessing the extent to which providers helped caregivers comprehend details of clinical visits, and capacity, defined as the extent to which providers assessed whether caregivers were able to care for patients. RESULTS: Of 265 caregivers who were approached, 240 (90.6%) enrolled in the study. The mean communication and capacity subscale scores were 2.7 ± 0.6 and 1.5 ± 0.6, respectively (range, 0-4 [higher = better]). Communication subscale scores were lower among caregivers of patients who experienced (vs. those who did not experience) a 30-day readmission (2.6 ± 0.5 vs. 2.8 ± 0.6, respectively; p = .047). Capacity subscale scores were inversely associated with restriction in patient daily activities (a 0.04 decrement in the capacity score for every 1 point in daily activity restriction; p = .008). CONCLUSIONS: After pancreatectomy, patients with pancreatic and periampullary cancer whose caregivers reported worse communication with care providers were more likely to experience readmission. Caregivers of patients with greater daily activity restrictions were less likely to report being asked about the caregiver's skill and capacity by clinicians. PLAIN LANGUAGE SUMMARY: This prospective study used a validated survey instrument and reports on the quality of communication between health care providers and caregivers as reported by caregivers of patients with pancreatic and periampullary cancer after pancreatectomy. In an analysis of 240 caregivers enrolled in the study, lower communication scores (the extent to which providers helped caregivers understand clinical details) were associated with higher odds of 30-day patient readmission to the hospital. In addition, lower capacity scores (the extent to which providers assessed caregivers' ability to care for patients) were associated with greater impairment in caregivers. The strikingly low communication quality and capacity assessment scores suggest substantial room for improvement, with the potential to improve both caregiver and patient outcomes.

The Revised R Status is an Independent Predictor of Postresection Survival in Pancreatic Cancer After Neoadjuvant Treatment.

OBJECTIVE: To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1 mm) after neoadjuvant therapy (NAT). BACKGROUND: The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1 mm margin clearance after NAT remains controversial. METHODS: Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases. Clinicopathological and survival data were analyzed. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), and pattern of recurrence in association with R 0 >1 mm and R 1 ≤1 mm resections. RESULTS: Three hundred fifty-seven patients with PDAC were included after NAT and subsequent pancreatic resection. Two hundred eight patients (58.3%) received FOLFIRINOX, 41 patients (11.5%) received gemcitabine-based regimens, and 299 individuals (83.8%) received additional radiotherapy. R 0 resections were achieved in 272 patients (76.2%) and 85 patients (23.8%) had R 1 resections. Median OS after R 0 was 41.0 months, compared with 20.6 months after R 1 resection ( P = 0.002), and even longer after additional adjuvant chemotherapy ( R 0 44.8 vs R1 20.1 months; P = 0.0032). Median RFS in the R 0 subgroup was 17.5 months versus 9.4 months in the R 1 subgroup ( P < 0.0001). R status was confirmed as an independent predictor for OS ( R 1 hazard ratio: 1.56, 95% CI: 1.07-2.26) and RFS ( R 1 hazard ratio: 1.52; 95% CI: 1.14-2.0). In addition, R 1 resections were significantly associated with local but not distant recurrence ( P < 0.0005). CONCLUSIONS: The revised R status is an independent predictor of postresection survival and local recurrence in PDAC after NAT. Achieving R 0 resection with a margin of at least 1 mm should be a primary goal in the surgical treatment of PDAC after NAT.

Lymph Node Yield is Associated with Improved Overall Survival and Increased Time to Recurrence in Node-Negative Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy.

OBJECTIVE: To determine if lymph node yield (LNY) is associated with improved overall survival (OS) and time to recurrence (TTR) in patients with node-negative pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant therapy (NAT). BACKGROUND: Lymph node yield has been associated with survival in solid gastrointestinal cancers, including PDAC. METHODS: Patients with pathological T stage I-III, node-negative (N0), PDAC treated with NAT followed by pancreatoduodenectomy were identified in the Massachusetts General Hospital (MGH) pancreatectomy database and the National Cancer Database (NCDB). A cutoff point of 22 nodes was identified in the NCDB using the point with the optimal (log-rank test) split. Overall survival and TTR were evaluated using univariate and multivariable analyses. RESULTS: In the MGH cohort, 233 node-negative patients following NAT were included. A LNY ≥ 22 was associated with prolonged median OS (59 months vs. 25 months, P<0.001) and prolonged TTR (32 months vs. 14 months, P=0.019). On multivariable analysis, LNY was an independent predictor of survival (HR 0.97, 95% CI 0.95-0.99, P=0.034) per sampled node. In the NCDB, 2,029 node-negative patients following NAT were included. A LNY ≥ 22 was associated with prolonged median OS (49 months vs. 33 months, P<0.001). On multivariable analysis, LNY was an independent predictor of survival (HR 0.99, 95% CI 0.98-0.99, P<0.001) per sampled node. CONCLUSION: Lymph node yield was associated with improved oncologic outcomes in patients treated with NAT followed by pancreatoduodenectomy in two independent datasets. Responsible mechanisms by which LNY impacts the outcomes of node-negative patients following NAT warrant further exploration.

Reappraising the Role of Intraoperative Neck Margin Revision in Post-Neoadjuvant Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Multi-Institutional Analysis.

OBJECTIVE: To investigate whether revision of pancreatic neck margin based on intraoperative frozen section analysis has oncologic value in post-neoadjuvant pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: The role of intraoperative neck margin revision has been controversial, with little information specific to post-neoadjuvant PD. METHODS: Patients who underwent post-neoadjuvant PD (2013-2019) for conventional PDAC with frozen section analysis of neck margin at three academic institutions were included. Overall survival (OS) and recurrence-free survival (RFS) were compared across three groups: complete resection achieved en-bloc (CR-EB), complete resection achieved non-en-bloc (CR-NEB), and incomplete resection (IR). RESULTS: Among the 671 patients included, 524 (78.1%) underwent CR-EB, 119 (17.7%) CR-NEB and 28 (4.2%) IR. Patients undergoing CR-NEB and IR exhibited larger tumors and lower rates of RECIST response, requiring vascular resections more often. Likewise, CR-NEB and IR were associated with a worse pathological profile than CR-EB. The incidence of postoperative complications and access to adjuvant treatment were comparable among groups. A CR-EB was associated with the longest OS duration (34.3 mo). In patients with positive neck margin, obtaining a CR-NEB via re-excision was associated with a comparable OS relative to patients with an IR (26.9 vs. 27.1 mo, P=0.901). Similar results were observed for RFS. At multivariable analysis, neck margin status was not independently associated with survival and recurrence. CONCLUSION: Conversion of an initially positive pancreatic neck margin by additional resection is not associated with oncologic benefits in post-neoadjuvant PD and cannot be routinely recommended.

Interobserver Variability in the International Study Group for Pancreas Surgery (ISGPS)-Defined Complications After Pancreatoduodenectomy: An International Cross-Sectional Multicenter Study.

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: 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: 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.

Complexity and Experience Grading to Guide Patient Selection for Minimally-invasive Pancreatoduodenectomy: An ISGPS Consensus.

OBJECTIVE: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD). BACKGROUND: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience. METHODS: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions. RESULTS: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification. CONCLUSION: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries.

Clinical and Financial Validation of the International Study Group for Pancreatic Surgery (ISGPS) Definition of Post-Pancreatectomy Acute Pancreatitis (PPAP): International Multicenter Prospective Study.

OBJECTIVE: To validate the ISGPS definition and grading system of PPAP after pancreatoduodenectomy (PD). SUMMARY BACKGROUND DATA: In 2022, the International Study Group for Pancreatic Surgery (ISGPS) defined post-pancreatectomy acute pancreatitis (PPAP) and recommended a prospective validation of its diagnostic criteria and grading system. METHODS: This was a prospective, international, multicenter study including patients undergoing PD at 17 referral pancreatic centers across Europe, Asia, Oceania, and the United States. PPAP diagnosis required the following three parameters: (1) postoperative serum hyperamylasemia /hyperlipasemia (POH) persisting on postoperative days 1 and 2, (2) radiologic alterations consistent with PPAP, and (3) a clinically relevant deterioration in the patient's condition. To validate the grading system, clinical and economic parameters were analyzed across all grades. RESULTS: Among 2902 patients undergoing PD, 7.5% (n=218) developed PPAP (6.3% grade B and 1.2% grade C). POH occurred in 24.1% of patients. Hospital stay was associated with PPAP grades (No POH/PPAP 10 days (IQR 7-17) days, grade B 22 days (IQR 15-34) days, and grade C 43 days (IQR 27-54) days; P<0.001), as well as intensive care unit admission (No POH/PPAP 5.4%, grade B 12.6%, grade C 82.9%; P<0.010), and hospital readmission rates (No POH/PPAP 7.3%, grade B 16.1%, grade C 18.5%; P<0.05). Costs of grade B and C PPAP were 2 and 11 times greater than uncomplicated clinical course, resp. (P<0.001). CONCLUSIONS: This first prospective, international validation study of the ISGPS definition and grading system for PPAP highlighted the relevant clinical and financial implications of this condition. These results stress the importance of routine screening for PPAP in patients undergoing PD.

Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Impact of neoadjuvant chemoradiotherapy on pathologic response in pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: The impact of chemoradiotherapy on pathologic response, resection margin, and survival benefit is still debated. The aim of this study was to compare the rate of pathologic complete response (pCR) in surgical resection following neoadjuvant chemotherapy vs. chemoradiotherapy, and secondarily, to compare the rate of R0 resection and Overall Survival (OS). METHODS: A systematic review on MEDLINE/PubMed, Embase, Cochrane, Web of Science and Google Scholar was conducted for studies published between 2012 and 2024 (PROSPERO CRD42022341467). All studies reporting clinical outcomes of patients with Pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant therapy were considered eligible for inclusion. A meta-analysis comparing the rate of pCR, R0 resection rate, and 3-year OS following Chemotherapy vs chemoradiotherapy in patients was performed. The overall quality of evidence was evaluated using a GRADE approach. RESULTS: Out of 5194 potentially relevant studies, 29 studies were considered eligible for full-text assessment, and 11 studies were included in the systematic review and in the meta-analysis. Of these, five were retrospective single-center, five retrospective multi-center studies, and one was a phase II multi-center RCT. Overall, 1830 Chemotherapy patients and 2299 Chemoradiotherapy patients were included in the meta-analysis. A statistically significant increased rate of pCR and R0 resections were found in chemoradiotherapy patients (OR 3.58, 95 % CI 2.47-5.18, p ≤ 0.00001) (OR 1.49, 95 % CI 1.17-1.90, p = 0.001), whereas 3-year OS (OR 1.07, 95 % CI 0.84-1.36, p = 0.6) did not differ significantly. CONCLUSIONS: Chemoradiotherapy may have a positive impact on pathologic response and R0 resection rate, whereas a survival benefit was not reported.

Long-term overall survival in patients undergoing liver resection for metastatic anal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: There is limited research on management of metastatic anal canal squamous cell carcinoma (SCC) to the liver. This study aimed to describe outcomes for patients undergoing liver resection of anal SCC metastases. METHODS: A multicenter, retrospective cohort study was conducted by three tertiary-referral centers. Patients undergoing liver surgery between 2008 and 2022 were included. Cox regression analysis was performed to evaluate predictors of recurrence and survival and Kaplan-Meier analysis was performed for 1-, 3-, and 5-year survival. RESULTS: Twenty-one patients underwent liver resection and/or ablation. None were HIV positive and 24% had known HPV infection. 20/21(95%) patients had undergone Nigro protocol for management of the primary tumor with 12/21 (57%) patients experiencing complete response. 4/21 (19%) patients had synchronous liver metastases at time of diagnosis. Median tumor size was 5.0 cm and median tumor number was one. At analysis, 52% remained alive. Median overall survival was 32.2 months. 5-year overall survival was 50%. Median recurrence-free survival was 7.7 months and 5-year recurrence-free survival was 30%. Need for salvage abdominoperineal resection was negatively associated with recurrence-free survival. The most common site of recurrence was the liver. CONCLUSIONS: Liver resection for metastatic anal SCC can be beneficial for appropriately selected patients.

Author Correction: High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.

In Fig. 4e of this Article, the labels for 'Control' and 'HFD' were reversed ('Control' should have been labelled blue rather than purple, and 'HFD' should have been labelled purple rather than blue). Similarly, in Fig. 4f of this Article, the labels for 'V' and 'GW' were reversed ('V' should have been labelled blue rather than purple, and 'GW' should have been labelled purple instead of blue). The original figure has been corrected online.

Imaging of Neuroendocrine Neoplasms; Principles of Treatment Strategies. What Referring Clinicians Want to Know.

ABSTRACT: Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings. Treatment strategies vary depending on the specific subtype of NEN. In this review, we will focus on treatment strategies and therapies including the information relevant to clinicians in order to undertake optimal management and treatment decisions, the implications of different therapies on imaging, and how to ascertain their possible complications and treatment effects.

Immune microenvironment and lymph node yield in colorectal cancer.

BACKGROUND: Lymph node (LN) harvesting is associated with outcomes in colonic cancer. We sought to interrogate whether a distinctive immune milieu of the primary tumour is associated with LN yield. METHODS: A total of 926 treatment-naive patients with colorectal adenocarcinoma with more than 12 LNs (LN-high) were compared with patients with 12 or fewer LNs (LN-low). We performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2MG), CD8, CD163, LAG3, PD-L1, FoxP3, and BRAF V600E. RESULTS: The LN-high group was comprised of younger patients, longer resections, larger tumours, right-sided location, and tumours with deficient mismatch repair (dMMR). The tumour microenvironment showed higher CD8+ cells infiltration and B2MG expression on tumour cells in the LN-high group compared to the LN-low group. The estimated mean disease-specific survival was higher in the LN-high group than LN-low group. On multivariate analysis for prognosis, LN yield, CD8+ cells, extramural venous invasion, perineural invasion, and AJCC stage were independent prognostic factors. CONCLUSION: Our findings corroborate that higher LN yield is associated with a survival benefit. LN yield is associated with an immune high microenvironment, suggesting that tumour immune milieu influences the LN yield.

Association Between Intraoperative Dexamethasone and Postoperative Mortality in Patients Undergoing Oncologic Surgery: A Multicentric Cohort Study.

OBJECTIVE: We examined the effects of dexamethasone on postoperative mortality, recurrence-free survival, and side effects in patients undergoing oncologic operations. BACKGROUND: Dexamethasone prevents nausea and vomiting after anesthesia and may affect cancer proliferation. METHODS: A total of 30,561 adult patients undergoing solid cancer resection between 2005 and 2020 were included. Multivariable logistic regression was applied to investigate the effect of dexamethasone on 1-year mortality and recurrence-free survival. Effect modification by the cancer's potential for immunogenicity, defined as a recommendation for checkpoint inhibitor therapy based on the National Comprehensive Cancer Network guidelines, was investigated through interaction term analysis. Key safety endpoints were dexamethasone-associated risk of hyperglycemia >180 mg/dL within 24 hours and surgical site infections within 30 days after surgery. RESULTS: Dexamethasone was administered to 38.2% (11,666/30,561) of patients (6.5±2.3 mg). Overall, 3.2% (n=980/30,561) died and 15.4% (n=4718/30,561) experienced cancer recurrence within 1 year of the operation. Dexamethasone was associated with a -0.6% (95% confidence interval: -1.1, -0.2, P =0.007) 1-year mortality risk reduction [adjusted odds ratio (OR adj ): 0.79 (0.67, 0.94), P =0.009; hazard ratio=0.82 (0.69, 0.96), P =0.016] and higher odds of recurrence-free survival [OR adj : 1.28 (1.18, 1.39), P <0.001]. This effect was only present in patients with solid cancers who were defined as not to respond to checkpoint inhibitor therapy [OR adj : 0.70 (0.57, 0.87), P =0.001 vs OR adj : 1.13 (0.85, 1.50), P =0.40]. A high (>0.09 mg/kg) dose of dexamethasone increased the risk of postoperative hyperglycemia [OR adj : 1.55 (1.32, 1.82), P <0.001], but not for surgical site infections [OR adj : 0.84 (0.42, 1.71), P =0.63]. CONCLUSIONS: Dexamethasone is associated with decreased 1-year mortality and cancer recurrence in patients undergoing surgical resection of cancers that are not candidates for immune modulators. Dexamethasone increased the risk of postoperative hyperglycemia, however, no increase in surgical site infections was identified.

Uncinate Duct Dilatation Predicts Additional Risk for High-Grade Dysplasia or Invasive Carcinoma Among Fukuoka-Positive Intraductal Papillary Mucinous Neoplasms.

OBJECTIVE: To determine whether uncinate duct dilatation (UDD) increases the risk of high-grade dysplasia or invasive carcinoma (HGD/IC) in Fukuoka-positive intraductal papillary mucinous neoplasms (IPMNs). BACKGROUND: Though classified as a branch duct, the uncinate duct is the primary duct of the pancreatic ventral anlage. We hypothesized that UDD, like main duct dilatation, confers additional risk for HGD/IC. METHODS: A total of 467 patients met inclusion criteria in a retrospective cohort study of surgically resected IPMNs at the Massachusetts General Hospital. We used multivariable logistic regression to analyze the association between UDD (defined as ≥4 mm) and HGD/IC, controlling for Fukuoka risk criteria. In a secondary analysis, the modeling was repeated in the 194 patients with dorsal branch duct IPMNs (BD-IPMNs) in the pancreatic neck, body, or tail. RESULTS: Mean age at surgery was 70, and 229 (49%) patients were female. In total, 267 (57%) patients had only worrisome features and 200 (43%) had at least 1 high-risk feature. UDD was present in 164 (35%) patients, of whom 118 (73%) had HGD/IC. On multivariable analysis, UDD increased the odds of HGD/IC by 2.8-fold, even while controlling for Fukuoka risk factors (95% CI: 1.8-4.4, P <0.001). Prevalence of HGD/IC in all patients with UDD was 73%, compared with 74% in patients with high-risk stigmata and 73% in patients with main duct IPMNs. In the secondary analysis, UDD increased the odds of HGD/IC by 3.2-fold in patients with dorsal BD-IPMNs (95% CI: 1.3-7.7, P =0.010). CONCLUSIONS: UDD confers additional risk for HGD/IC unaccounted for by current Fukuoka criteria. Further research can extend this study to Fukuoka-negative patients, including unresected patients.

Enhanced Recovery After Surgery Patients Are Prescribed Fewer Opioids at Discharge: A Propensity-score Matched Analysis.

OBJECTIVE: We aimed to compare discharge opioid prescriptions pre- and post-ERAS implementation. SUMMARY OF BACKGROUND DATA: ERAS programs decrease inpatient opioid use, but their relationship with postdischarge opioids remains unclear. METHODS: All patients undergoing hysterectomy between October 2016 and November 2020 and pancreatectomy or hepatectomy between April 2017 and November 2020 at 1 tertiary care center were included. For each procedure, ERAS was implemented during the study period. PSM was performed to compare pre - versus post-ERAS patients on discharge opioids (number of pills and oral morphine equivalents). Patients were matched on age, sex, race, payor, American Society of Anesthesiologists score, prior opioid use, and procedure. Sensitivity analyses in open versus minimally invasive surgery cohorts were performed. RESULTS: A total of 3983 patients were included (1929 pre-ERAS; 2054 post-ERAS). Post-ERAS patients were younger (56.0 vs 58.4 years; P < 0.001), more often female (95.8% vs 78.1%; P < 0.001), less often white (77.2% vs 82.0%; P < 0.001), less often had prior opioid use (20.1% vs 28.1%; P < 0.001), and more often underwent hysterectomy (91.1% vs 55.7%; P < 0.001). After PSM, there were no significant differences between cohorts in baseline characteristics. Matched post-ERAS patients were prescribed fewer opioid pills (17.4 pills vs 22.0 pills; P < 0.001) and lower oral morphine equivalents (129.4 mg vs 167.6 mg; P < 0.001) than pre-ERAS patients. Sensitivity analyses confirmed these findings [open (18.8 pills vs 25.4 pills; P < 0.001 \ 138.9 mg vs 198.7 mg; P < 0.001); minimally invasive surgery (17.2 pills vs 21.1 pills; P < 0.001 \ 127.1 mg vs 160.1 mg; P < 0.001). CONCLUSIONS: Post-ERAS patients were prescribed significantly fewer opioids at discharge compared to matched pre-ERAS patients.

Underlying Bias in the Treatment of Pancreatic Cancer: Minorities Treated at the Same Facilities are Less Likely to Receive Neoadjuvant Therapy.

OBJECTIVE: To identify disparities in access to NAT for PDAC at the prehospital and intrahospital phases of care. SUMMARY OF BACKGROUND DATA: Delivery of NAT in PDAC is susceptible to disparities in access. There are limited data that accurately locate the etiology of disparities at the prehospital and intrahospital phases of care. METHODS: Retrospective cohort of patients ≥18 years old with clinical stage I-II PDAC from the 2010-2016 National Cancer Database. Multiple logistic regression was used to assess 2 sequential outcomes: (1) access to an NAT facility (prehospital phase) and (2) receipt of NAT at an NAT facility (intrahospital phase). RESULTS: A total of 36,208 patients were included for analysis in the prehospital phase of care. Higher education, longer travel distances, being treated at academic/research or integrated network cancer programs, and more recent year of diagnosis were independently associated with receipt of treatment at an NAT facility. All patients treated at NAT facilities (31,099) were included for the second analysis. Higher education level and receiving care at an academic/research facility were independently associated with increased receipt of NAT. NonBlack racial minorities (including American Indian, Asian, Pacific Islanders), being Hispanic, being uninsured, and having Medicaid insurance were associated with decreased receipt of NAT at NAT facilities. CONCLUSIONS: Non-Black racial minorities and Hispanic patients were less likely to receive NAT at NAT facilities compared to White and non-Hispanic patients, respectively. Discrepancies in administration of NAT while being treated at NAT facilities exist and warrant urgent further investigation.

Feasibility, Safety, and Efficacy of Aggressive Multimodal Management of Elderly Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: We aimed to evaluate the safety and efficacy of NAT followed by surgical resection in patients with PDAC aged ≥75 years. SUMMARY BACKGROUND DATA: Whether administration of neoadjuvant therapy (NAT) followed by surgical resection in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is safe and effective is unknown. METHODS: The present study is a three-part comparison of older (≥ 75 years) versus younger (< 75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with non-metastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older vs. younger patients who underwent NAT followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT followed by surgical resection vs. upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR), were compared. Propensity-score matching (PSM) analysis was performed to adjust for potential confounders. RESULTS: In the first analysis, a lower proportion of older patients (n=40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared to younger patients (n=214) (65.0% vs. 81.4%, P=0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P=0.89) as well as surgical resection (57.5% vs 55.6%, P=0.70). In the second analysis, PSM was conducted to compare older (n=54) vs. younger patients (n=54) who underwent NAT followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in overall survival (OS) between older and younger patients (median OS: 16.43 months vs. 30.83 months, P=0.002), importantly, there was no significant difference in time to recurrence (TTR, median: 7.65 months vs. 11.83 months, P=0.215). In the third analysis, older patients who underwent NAT followed by surgical resection (n=48) were compared with similar older patients who underwent upfront surgical resection (n=48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs. 11.51 months, P=0.037) as well as TTR (median TTR: 8.81 months vs. 7.10 months, P=0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone. CONCLUSIONS: This comprehensive three-part study showed that administration of NAT followed by surgical resection appears to be safe and effective among patients ≥ 75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma after Curative Resection.

OBJECTIVE: Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). SUMMARY BACKGROUND DATA: DAC and iAC share a similar histological differentiation but the benefit of adjuvant therapy remains unclear. METHODS: Patients undergoing curative-intent surgical resection for DAC and iAC between 2010 and 2021 at five high-volume centers were included. Patient baseline, perioperative and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). RESULTS: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in DAC patients was 101 months versus 155 months for iAC patients (P=0.098). DAC had a higher rate of local (14.1% vs. 1.2%, P<0.001) and systemic recurrence (30.4% vs. 3.5%, P<0.001). Adjuvant therapy failed to improve overall survival in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors had improved OS rates with adjuvant therapy (72 m vs. 44 m, P=0.044). IAC patients with N+ (190 m vs. 57 m, P=0.003), T3-4 (177 m vs. 59 m, P=0.050) and perineural invasion (150 m vs. 59 m, P=0.019) had improved OS rates with adjuvant therapy. CONCLUSION: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved overall survival in DAC patients with perineural invasion and in iAC patients with T3-4 tumors, positive lymph nodes, and perineural invasion.