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Intraductal papillary mucinous neoplasms (IPMNs) resection margins are assessed intraoperatively using frozen section (IFS) pathology. We conducted a systematic review to evaluate the concordance of IFS with permanent histopathology and the association between IFS margin status and recurrence. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We queried PubMed, Embase, Scopus, and Google Scholar for studies reporting IFS in patients undergoing resection for IPMN. Data, including IFS margin status, recurrence rates, and final pathology, were extracted. Positive margins were defined as high-grade dysplasia or invasive cancer. Seven studies, with a total of 706 patients, met the inclusion criteria. Positive IFS margins were reported in 9.4% of cases, with a high correlation (98%) between IFS and final pathology. Recurrence occurred in 15.4% of patients. Fifty-nine of 85 (69.4%) patients with recurrence of IPMN or intraductal papillary mucinous carcinoma (IPMC) had negative IFS margins. IFS accurately predicts final pathology and is a valuable tool for guiding intraoperative decision-making. A sizeable number of patients experienced recurrence despite negative margins, highlighting the need for adjunct diagnostic modalities and continued surveillance following resection, regardless of margin status.

Background: Chyle leak after pancreatic surgery is linked to malnutrition, but its impact on oncological outcomes is unclear. This study assessed if postoperative clinically relevant chyle leak (CR-chyle leak) affects adjuvant chemotherapy receipt rates and overall survival (OS) in pancreatic cancer patients.

Methods: Patients who underwent resection for localized pancreatic ductal adenocarcinoma at the University of Colorado Hospital (2015–2023) were included. Year of surgery was divided in two time periods based on changes in dissection techniques, increased neoadjuvant therapies, and more surgeries for advanced disease in 2019. Risk factors for CR-chyle leak (grade B–C) and their relation to OS and adjuvant chemotherapy were analyzed using logistic and Cox regression models.

Results: Among 487 patients, 93 (19.5 %) developed CR-chyle leak. Patients with CR-chyle leak more often had borderline/locally advanced disease, neoadjuvant chemotherapy, vascular resections, longer surgeries, and operated in 2019–2023. There were no differences in hospital stay (median 10 vs 10 days), adjuvant chemotherapy rates (70.5 % vs 70.2 %, p = 0.917), or median OS (28.5 vs 29.9 months, p = 0.477). CR-chyle leak was not associated with OS (HR 0.81; 95 % CI: 0.57–1.16) in the adjusted model.

Conclusion: CR-chyle leak is common after pancreatic cancer surgery but does not negatively impact oncological outcomes.

Background: Randomized studies comparing neoadjuvant therapy and upfront surgery for primary resectable pancreatic cancer are conflicting. We aimed to determine whether multidisciplinary conference (MDC) recommendation of neoadjuvant multiagent chemotherapy is associated with survival benefits compared to upfront surgery.

Methods: This retrospective study included patients with treatment-naive, biopsy-proven, primary resectable pancreatic adenocarcinoma discussed on MDCs at the University of Colorado Hospital in 2013–2021. Overall survival was compared by intention-to-treat, with Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models.

Results: Among the 221 patients included, 116 were recommended neoadjuvant multiagent chemotherapy and 105 were recommended upfront surgery. In the neoadjuvant group, 106 patients (91.4%) completed at least two months of multiagent chemotherapy. The resection rates were 87/116 (75.0%) in the neoadjuvant group and 94/105 (89.5%) in the upfront surgery group (P= 0.005). The median overall survival was 41.9 months (95% CI 23.2–62.0) in the neoadjuvant group and 23.3 months (95% CI 19.0–31.6) in the upfront surgery group. Neoadjuvant therapy recommendation was associated with improved overall survival in the adjusted Cox model (HR: 0.65; 95% CI 0.44–0.95, P= 0.027).

Conclusion: Neoadjuvant therapy is associated with high multiagent chemotherapy completion rates and with improved overall survival compared to upfront surgery.

Background: Invasive intraductal papillary mucinous neoplasms (I-IPMNs) are considered more indolent than conventional pancreatic ductal adenocarcinoma (PDAC). Although neoadjuvant therapy (NAT) is widely adopted in PDAC, its role in I-IPMN remains unclear. This study aimed to evaluate the impact of NAT on survival in I-IPMN compared with PDAC.

Methods: The study enrolled I-IPMN and PDAC patients undergoing resection at the University of Colorado Hospital between 2013 and 2023. Prognostic factors for overall survival (OS) were identified using Cox models. OS was compared between histology/NAT subgroups using the Kaplan-Meier method and the log-rank test, stratified by resectability.

Results: Of 500 patients (413 PDAC, 87 I-IPMN), 289 PDAC and 34 I-IPMN patients received NAT, and the I-IPMN patients showed slightly longer median OS than the PDAC patients (30.2 vs 28.1 months; p = 0.04). In the entire cohort, worse OS was associated with borderline resectable (BR)/locally advanced (LA) disease, elevated cancer antigen 19-9 (CA19-9), node-positive disease, lymphovascular invasion, perineural invasion, and absence of adjuvant therapy. In the resectable cohort (n = 311), NAT was associated with longer OS in PDAC (61.9 vs 34.2 months; p < 0.001), but not in I-IPMN (not reached vs 47.9 months; p = 0.74). Survival did not differ between NAT-treated resectable I-IPMN and PDAC (p = 0.95). In the BR/LA cohort treated with NAT (n = 183), OS was similar between I-IPMN and PDAC (17.1 vs 22.0 months; p = 0.69).

Conclusions: In resectable I-IPMN, NAT was not associated with improved survival. Comparable survival between NAT-treated BR/LA I-IPMN and PDAC suggests a need for further research on treatment outcomes.

Background: Treatment options for pancreatic cancer with major arterial involvement has evolved in the last decades with the introduction of multi-agent chemotherapies. This study aimed to explore treatment patterns of surgical and oncological treatment for clinical stage T4 pancreatic cancer in the United States.

Methods: The study included clinical T4M0 pancreatic cancer cases treated between 2004 and 2021 in the US National Cancer Database. Treatment patterns and overall survival were evaluated and divided into three time periods (2004–2010, 2011–2016, 2017–2021). Odds of resection were assessed with multivariable logistic regression.

Results: In total, 47,345 cases were analyzed, of which 4222 (8.9 %) underwent surgery. The median age was 68 years, 49 % were male and 77.0 % reported non-hispanic white race. The proportion of patients that received no treatment decreased from 31.2 % to 23.6 % and the proportion that received both chemotherapy and surgery increased from 4.4 % to 11.1 %. Among patients that received upfront chemotherapy (n = 28,445), single-agent chemotherapy dominated in 2004 but was almost completely replaced by multi-agent chemotherapy by 2021. Median overall survival improved; for non-resected patients from 10.8 months in 2004–2010 to 14.9 months in 2017–2021 (p ' .001), and for resected patients from 25.2 to 32.7 months (p ' .001). Variables associated with higher odds of resection included private insurance and center volume, whereas age, race/ethnicity, clinical N1-2 and a body/tail tumor location was associated with lower odds.

Conclusions: Treatment for pancreatic cancer with major arterial involvement has shifted towards an increased use of multi-agent chemotherapy and surgical resection, with an associated improved overall survival.

Background Excess body adiposity is an established cause of renal cancer, but underlying molecular pathways mediating this relationship remain unclear. This study aimed to systematically evaluate a panel of obesity-related risk factors as potential mediators in renal cancer etiology. Methods and findings We used two complementary approaches to evaluate obesity-related risk factors in renal cancer etiology: (i) direct risk factor assessment in longitudinal cohorts and (ii) genetically proxied risk factors through two-sample mendelian randomization (MR). Direct risk-factor association-analyses (i.e., cohort analyses) were based on the UK Biobank cohort study (472,337 cohort participants, including 1,382 incident renal cancer cases diagnosed during 5,586,414 person years of follow-up) and the Northern Sweden Health and Disease Study (NSHDS) for fasting insulin (204 pairs of cases and controls, ongoing recruitment and follow-up since 1985). We used Cox proportional hazards regression models to evaluate the association between risk factors and renal cancer risk with adjustment for age, sex, center of recruitment, education, smoking and alcohol drinking status. Two-sample MR analyses were based on a genome-wide association study (GWAS) of renal cancer (27,213 cases, 486,846 controls). We used the inverse-variance weighted (IVW) approach to estimate the association between risk factors and renal cancer risk. Mediation analyses were performed for traits displaying directionally consistent associations with renal cancer risk in both the cohort and MR analyses using the product method. We found consistent positive associations with renal cancer risk for fasting insulin (odds ratio per standard deviation increment [ORMR]: 2.24, 95% confidence interval [95% CI]: 1.19, 4.22; p=0.01; hazard ratio per standard deviation increment [HRcohort]: 1.43, 95% CI: 1.02, 2.00; p=0.04), triglycerides (ORMR: 1.11, 95% CI: 1.05, 1.17; p<0.001, HRcohort: 1.23, 95% CI: 1.11, 1.38; p<0.001), diastolic blood pressure (DBP) (ORMR: 1.14, 95% CI: 1.04, 1.26; p<0.001, HRcohort: 1.11, 95% CI: 1.05, 1.17; p<0.001) and consistent inverse associations with renal cancer risk for sex-hormone binding globulin (SHBG) (ORMR: 0.80, 95% CI: 0.70, 0.90; p<0.001, HRcohort: 0.67, 95% CI: 0.58, 0.76; p<0.001) and high-density lipoprotein (HDL) cholesterol (ORMR: 0.93, 95% CI: 0.88, 0.98; p<0.001, HRcohort: 0.72, 95% CI: 0.66, 0.77; p<0.001). The main limitation of this study was that we had limited statistical power to evaluate some risk factors. Conclusions Our study highlights roles for fasting insulin, HDL cholesterol, DBP, triglycerides and SHBG in mediating the relationship between body adiposity and renal cancer risk.

Importance: The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Objective: To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Design, Setting, and Participants: This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018. Patients who died within 3 months after surgery were excluded (landmark). Data were analyzed from February 1 to December 31, 2023.

Exposures: Preoperative (m)FOLFIRINOX chemotherapy followed by resection and eventually followed by adjuvant chemotherapy.

Main Outcomes and Measures: The primary outcome was OS, calculated from the 3-month landmark. Cox regression analysis, including interaction analyses, was performed to investigate the association of adjuvant chemotherapy with OS.

Results: Overall, 767 patients were included after resection of pancreatic adenocarcinoma (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant chemotherapy was independently associated with prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed by adjusted OS curves. The interaction analysis to assess estimated treatment effect across subgroups was not statistically significant. The forest plot and interaction test suggest that the association of adjuvant chemotherapy was lower among patients receiving 8 or more cycles of preoperative (m)FOLFIRINOX, those who had radiological response, and those with ypNO disease. Compared to no adjuvant chemotherapy, both adjuvant (m)FOLFIRINOX (HR, 0.57; 95% CI, 0.40-0.80) and other multiagent adjuvant regimens (HR, 0.61; 95% CI, 0.41-0.92) were associated with prolonged OS, whereas single-agent adjuvant chemotherapy was not (HR, 0.75; 95% CI, 0.55-1.03).

Conclusions and Relevance: In this cohort study, adjuvant (m)FOLFIRINOX and other multiagent chemotherapy regimens were associated with improved OS following resection of localized pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX, whereas single-agent adjuvant chemotherapy was not. The impact of adjuvant chemotherapy on OS may be lower in subgroups such as patients with 8 or more preoperative cycles of (m)FOLFIRINOX, those having radiological response, and those with ypNO.