BACKGROUND:Total neoadjuvant therapy for localized rectal cancer entails delivery of all systemic chemotherapy and pelvic radiation before proctectomy to improve pathologic response, disease-free survival, and potentially organ preservation. In patients who develop liver metastases during or after total neoadjuvant therapy, the effects of total neoadjuvant therapy on patient outcomes and chemotherapy-associated liver injury are unknown. METHODS:A single-institution prospectively maintained database was queried for patients who underwent hepatectomy for metastatic rectal cancer, with or without total neoadjuvant therapy between 2014 and 2024. Surgical pathology reports were reviewed for histologic changes in the background liver. RESULTS:Among 286 patients undergoing hepatectomy for metastatic rectal cancer, 30 patients received total neoadjuvant therapy, and 256 patients did not receive total neoadjuvant therapy. Overall survival was significantly lower among patients in the total neoadjuvant therapy group (median overall survival 48.7 months, total neoadjuvant therapy vs 99.5 months, non-total neoadjuvant therapy, P = .01). On multivariable analysis, total neoadjuvant therapy remained an independent predictor of worse overall survival (hazard ratio 0.41, 95% confidence interval 0.22-0.79, P = .008). Sinusoidal injury rates were not significantly different with or without total neoadjuvant therapy (26.9% total neoadjuvant therapy vs 32.9% non-total neoadjuvant therapy, P = .69). Patients who received total neoadjuvant therapy had significantly higher rates of steatosis or steatohepatitis (30.8% total neoadjuvant therapy vs 8.7% non-total neoadjuvant therapy, P = .002). CONCLUSION:In this preliminary analysis, patients who developed liver metastases during or after total neoadjuvant therapy for rectal cancer had significantly worse overall survival after hepatectomy than patients who did not receive total neoadjuvant therapy. Steatosis and steatohepatitis rates were higher with total neoadjuvant therapy. Further study is needed to identify factors associated with worse outcomes in patients who undergo hepatectomy after total neoadjuvant therapy.

662 Background: Survival disparities by race and ethnicity in pancreatic cancer are often attributed to delayed access to specialized centers and differential treatment receipt. Whether these patterns persist among patients receiving care at high-volume centers remains unclear. Methods: We identified patients with pancreatic adenocarcinoma diagnosed from 2016-2024 who received chemotherapy or radiation or underwent a curative-intent pancreatectomy at an NCI-designated Comprehensive Cancer Center. Data were extracted from the institutional cancer registry, pharmacy database, and electronic health record and harmonized using Palantir Foundry. Treatment receipt by self-reported race and ethnicity was compared using chi-squared tests corrected for multiple comparisons. Cox models for overall survival (OS) and time to treatment were adjusted for age, performance status, stage at diagnosis, comorbidities, and treatment-specific variables. Results: Among 3249 patients (median follow-up 33.1 months), median OS from diagnosis across all stages was 20.7 months for non-Hispanic White (NHW), 18.6 for Hispanic, 26.6 for Asian, and 17.4 for Black patients ( p <0.001). Non-White patients were more likely to be seen within 3 months after diagnosis compared to White patients (adjusted ORs: Hispanic 1.72, Asian 2.06, Black 1.67; p <0.05 for all). Among patients with metastatic disease, receipt of chemotherapy varied across groups ( p <0.001), highest for Asian patients (92%) and lowest for Black patients (83%). Median OS from initiation of chemotherapy ranged from 9.8 months in Black patients to 11.2 months in Asian patients ( p =0.120). In patients initially diagnosed with localized disease, rates of pancreatectomy were similar: 33% for NHW, 26% for Hispanic, 28% for Asian, and 24% for Black patients ( p =0.074). Median OS after pancreatectomy was 43.9 months for NHW, 48.7 for Hispanic, 57.7 for Asian, and 39.3 for Black patients ( p =0.570). Interventional clinical trial enrollment rates were lower for Black (25%; p < 0.001) and Hispanic patients (30%; p =0.043) compared to NHW patients (38%). Post-treatment survival did not differ significantly after adjustment for first-line chemotherapy agents in patients with metastatic disease or tumor location in patients with localized disease. Conclusions: At a high-volume academic center, patients from minoritized groups receive timely evaluation and standard of care treatment at similar rates to NHW patients. Nevertheless, survival disparities persist for Black and Hispanic patients, while Asian patients experience a survival advantage. After accounting for patient and disease characteristics, survival outcomes were largely similar across groups, but lower chemotherapy rates among Black patients with metastatic disease and lower trial enrollment among Black and Hispanic patients highlight areas where treatment inequities persist.

BACKGROUND:The AJCC staging system has assigned variable prognostic weight to multifocal disease across versions for intrahepatic cholangiocarcinoma (iCCA). We aimed to better delineate how multifocality influences survival in patients with resectable iCCA to refine clinical staging and better inform treatment sequencing. PATIENTS AND METHODS:We retrospectively identified patients undergoing curative-intent hepatectomy for iCCA between 2000 and 2024 from 6 international, high-volume hepatobiliary centers. Patients were stratified by multifocality, T classification, and N classification. Overall survival (OS) was evaluated using Kaplan-Meier and Cox regression analyses, and a novel modified system was proposed based on current AJCC groupings. RESULTS:A total of 731 patients met the study inclusion criteria. Multifocal disease was present in 36% of patients with T2-T4 tumors and was independently associated with worse OS (hazard ratio, 1.64; 95% CI, 1.21-2.22; P=.002) compared with solitary tumors on multivariable analysis. This survival disadvantage persisted across T2 classification (28.8 vs 44.8 months; P=.001) and T3 classification (21.2 vs 36.5 months; P=.003), and remained significant after adjustment for nodal status (P=.003 and P=.017, respectively). Compared with solitary disease, multifocality also conferred worse OS in patients with node-negative (36.0 vs 58.9 months; P=.003) and regionally node-positive disease (19.2 vs 23.8 months; P=.016). Current AJCC staging failed to distinguish prognostic differences between stage II and stage IIIA disease (48.3 vs 46.9 months; P=.190). However, our proposed modifications, which classify multifocal tumors as T3 and upstage multifocality from stage II to stage IIIA in node-negative disease and from stage IIIB to a newly defined stage IIIC in node-positive disease, better stratified overall risk (P<.001). CONCLUSIONS:Multifocality independently predicts poor prognosis in resectable iCCA. Refining the current staging system by reclassifying multifocal tumors as T3 may improve prognostic stratification and better inform treatment sequencing.

PURPOSE:The incidence of young-onset pancreatic cancer (YO-PC) has risen over the past two decades, yet its molecular characteristics and long-term outcomes remain poorly defined. METHODS:We retrospectively evaluated patients with PC treated at a tertiary referral center from 2016 to 2022 who had available molecular data. Patients were classified as YO-PC (≤50 years) or average-onset PC (AO-PC, >50 years). A subset analysis examined outcomes in those who underwent curative-intent pancreatectomy. Primary end points included overall survival (OS) and recurrence-free survival (RFS). RESULTS:Among 511 patients, 10.9% had YO-PC (n = 56; median age 44 years). Patients with YO-PC more commonly self-identified as non-White compared with patients with AO-PC (41.1% v 26.4%, P = .03). BMI, anatomic stage, and CA19-9 level at presentation were similar between groups. KRAS mutations were the most prevalent somatic alterations in both the YO-PC and AO-PC cohorts (87.0% v 88.0%, P = .83), followed by TP53 (73.5% v 74.1%, P = .93), CDKN2A (14.6% v. 23.6%, P = .20), and SMAD4 (18.2% v 12.9%, P = .34). KRAS-specific allele subtypes were also similar (P = .38). A subset analysis in the surgical cohort (n = 167) yielded similar results. OS was similar for YO-PC and AO-PC (18.7 v 21.7 months; P = .29). In the surgical cohort, OS and RFS for YO-PC and AO-PC were also similar (OS, 31.2 v 47.1 months, P = .34; RFS, 10.3 v 14.7 months, P = .10). CONCLUSION:In this single-institution study, patients with YO-PC and AO-PC demonstrated similar clinicopathologic and molecular profiles; however, the study population to date may be underpowered. Routine molecular testing on all patients diagnosed with PC will be critical to better understand its clinical and molecular heterogeneity and to inform design of practice-changing clinical trials.

Background: Risk-stratified pancreatectomy pathways improve short-term outcomes, reduce cost, and decrease opioid use in patients with pancreatic adenocarcinoma (PDAC); however, the association with overall survival (OS) in the modern era of chemotherapy remains unknown. Methods: Patients with resected PDAC, identified from a prospectively maintained database, treated after pathway implementation (10/2016–12/2022, “POST”) were compared to pre-pathway patients (7/2011–9/2016, “PRE”) and assessed for complications >2 ACCORDION. OS was measured from diagnosis and compared with Cox regression models. Results: Among 550 patients, 34% (189/550) were treated in the PRE and 66% POST pathway era. ACCORDION grade >2 complications (PRE-59% [112/189]; POST-51% [184/361]; p=0·064), clinically relevant fistula (PRE–5%, POST–8%; p=0·33), and adjuvant therapy rates (PRE–71%, POST–77%; p=0·085) were similar. PRE cohort had higher rates of surgery-first (PRE–38%, POST–17%; p<0·001).Median OS was 50-months in the POST cohort vs. 38-months in PRE cohort (p=0·006). When stratified by ACCORDION grade ≥2, POST patients with grade ≥2 complications had similar OS to POST patients with grade 0-1 complications. On Cox regression, POST-pathway care was independently associated with improved OS (HR-0·69, 95% CI 0·54–0·89; p=0·004). More advanced nodal and tumor stage and omission of adjuvant chemotherapy were associated with worse OS. Perioperative chemotherapy vs. surgery-first sequencing with intended adjuvant therapy was not associated with OS difference (HR 1·04, 95% CI 0·78–1·40; p=0·77). Conclusion: Programmatic and iterative efforts to standardize and optimize perioperative care for patients undergoing pancreatectomy were associated with improved OS after PDAC resection. Despite similar serious complications and adjuvant therapy rates in PRE/POST cohorts, long-term outcomes have improved over time with an inflection point at the initiation of the first iteration. Bundled, pathway-driven care may be associated with oncologic benefits beyond short-term outcomes.

INTRODUCTION:Unplanned, delayed readmissions (>30 ds) following oncologic surgeries can increase mortality and care costs and affect hospital quality indices. However, there is a dearth of literature on rectal cancer surgery. Hence, we aimed to assess the risk factors associated with delayed readmissions following rectal cancer surgery to improve targeted interventions, patient outcomes, and quality indices. METHODS:For this case-control study, all adult patients in the US Rectal Cancer Consortium database who underwent surgery and subsequent readmission were included. Multivariable logistic regression described the association of factors associated with delayed readmission. Descriptive statistics were used to ascertain the most common causes of readmission. RESULTS:Of the 1417 patients included in the analysis, 403 (28.4%) patients were readmitted postoperatively. Among these, 101 (25.1%) patients had delayed readmission. The median length of stay for early readmission was significantly longer when compared to delayed readmission (4 versus 2 ds, P < 0.01). American Society of Anesthesiologists-Physical Status score > II [odds ratio = 1.81] was associated with an increased risk of delayed readmissions, while intraoperative pelvic drain placement [odds ratio = 0.57] was associated with a reduced risk. Surgical site infection was the most common cause of delayed (18.4%) and early readmissions (27.4%). CONCLUSIONS:The risk of readmission following surgery for rectal cancer extends beyond the commonly tracked 30 ds, with up to a quarter of readmissions happening more than 30 ds after surgery. Surgical site infection continues to be the leading cause of both early and delayed readmission, underscoring the need to double down on infection prevention bundles.

143 Background: The use of neoadjuvant chemoradiation (NCRT) for upper rectal cancer remains controversial. Our aim was to determine whether NCRT was associated with improved outcomes. Methods: The US Rectal Cancer Consortium was queried for patients who underwent resection of non-metastatic upper rectal cancer (≥12cm from anal verge) from 2007-2017. Primary outcomes were recurrence-free (RFS) and overall survival (OS). Secondary outcomes were postoperative complications. Results: 193 pts met inclusion criteria; 100 (52%) did not receive NCRT and 93 (48%) did. Median age was similar between groups (non-NCRT: 62 yrs; NCRT: 57 yrs; p=0.71). Patients in each group had similar gender and pathological stage (non-NCRT: 22% stage I, 32% stage II, 36% stage III; NCRT: 21% stage I, 23% stage II, 33% stage III; p=0.143). Median follow-up was 31 months (non-NCRT) and 34 months (NCRT). On Kaplan-Meier analysis, NCRT was not associated with improved RFS compared to non-NCRT (3-year RFS 85% vs. 80%; p=0.34) or OS (3-year OS 88% vs. 90%; p=0.49). This finding persisted on multivariable cox regression. R0 resection rate was similar between groups at 99% (non-NCRT) and 97% (NCRT; p=0.27). Anastomotic leak occurred in 11% of both cohorts. Creation of a diverting loop ileostomy (DLI) was nearly 3 times higher in NCRT (82%) versus non-NCRT patients (29%; p<0.001). Conclusions: Among patients with non-metastatic upper rectal cancer, NCRT did not improve survival or recurrence rates, but was associated with a nearly threefold higher DLI rate. Although NCRT is a mainstay of treatment for lower rectal cancer, our results do not support its use in upper rectal cancer. [Table: see text]

Pancreatic cancer is a highly aggressive disease with a poor prognosis. In advanced stages, symptoms such as biliary and gastric outlet obstructions frequently occur and can be managed through techniques such as advanced endoscopy, interventional radiology, and surgery. A multidisciplinary team, including oncologists, gastroenterologists, surgical specialists, and palliative care providers, is crucial to tailor and select treatment strategies that align with the individual goals and preferences of each patient.

BACKGROUND:Postoperative urinary retention warrants catheterization. A bladder scan helps check for postoperative urinary retention before catheterization. There is a paucity of data about its reliability in postoperative obese patients. Our study assesses its reliability in this patient population. METHODS:All patients in the postoperative ward of one hospital who underwent surgery during their current admission were included in our prospective cohort study. Patients were catheterized on the basis of the clinical judgment of the treating physician. The nurses collected bladder scan readings before catheterizing patients. Final analysis excluded patients with nongastrointestinal surgeries, record of fewer than 3 bladder scans readings, and missing urinary catheterized volume. The mean bladder scan readings (minimum = 3) were compared with the catheterized volume using intraclass correlation coefficient analysis. RESULTS:Of 100 patients, 65 met our selection criteria. Bladder scan reliability was good (intraclass correlation coefficient. 0.69; 95% confidence interval, 0.55-0.80) in the overall study cohort. A strong linear relationship was noted between bladder scan and catheterized volumes (r = 0.774, P < .001). Excellent reliability was noted in body mass index <30 subgroup (n = 43, intraclass correlation coefficient, 0.76, 95% confidence interval, 0.61-0.86), whereas the reliability was fair in body mass index ≥30 subgroup (n = 20, intraclass correlation coefficient, 0.55, 95% confidence interval, 0.26-0.81). Patients with body mass index ≥30 had a larger median difference between scan and catheterized volumes compared to patients with body mass index <30 (94.2 mL vs 34.8 mL). CONCLUSION:Our study demonstrates the accuracy and reliability of portable ultrasound bladder scans, especially in patients with healthy weight and overweight with postoperative urinary retention. The reliability may be suboptimal in obese patients.

Background and Objectives: The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both. Methods: The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response. Results: Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS. Conclusions: SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone.