Background/Objectives: Stereotactic body radiotherapy (SBRT) aims to prolong overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) with vascular contact without progression of disease after (m)FOLFIRINOX. The primary objective of this study was to determine the potential value of SBRT. Methods: This nationwide, retrospective cohort study included patients with PDAC without progression of disease after at least four cycles of (m)FOLFIRINOX. The study comprised two cohorts, the SBRT and the No SBRT group. A landmark analysis excluded patients with a follow-up or OS time less than 12 months to minimize immortal time bias in the SBRT group. The primary outcome was OS from diagnosis. Secondary outcomes were the histopathological characteristics after resection. Results: Overall, 331 patients were included, of whom 231 were in the landmark analysis. In the overall cohort, the median OS was 20.7 months in the SBRT group versus 15.7 months in the No SBRT group (p = 0.004). In the landmark analysis, the median OS was 23.2 months in the SBRT group compared to 22.3 months in the No SBRT group (p = 0.554). These results indicate the presence of immortal time bias in the overall cohort in favor of the SBRT group. In the subgroup after resection, ypT0-2 (95% versus 76.5% [p = 0.026]), ypN0 (75% versus 37.3% [p < 0.004]), and absence of perineural invasion (50% versus 68.6% [p = 0.015]) were more prevalent in the SBRT group. Conclusions: In a landmark analysis, including only patients who survived at least 12 months after diagnosis, we found no difference in median OS between (m)FOLFIRINOX-only and (m)FOLFIRINOX with consecutive SBRT.

BACKGROUND:Optimizing antibiotic prophylaxis might improve outcomes after pancreatoduodenectomy. Current guidelines lack clear recommendations regarding the type and duration of prophylaxis. This survey evaluated global practices for antibiotic prophylaxis in pancreatoduodenectomy. METHODS:An online survey among members of international surgical associations was distributed from April to September 2024. Sixteen questions addressed intraoperative and prolonged antibiotic prophylaxis practices. Responses were analyzed descriptively and compared across continents and center volumes. RESULTS:A total of 215 surgeons participated. Piperacillin-tazobactam was the most commonly used intraoperative antibiotic (44%), with variations across continents (North America: 68%, Europe: 29%, Asia: 22%). Prolonged prophylaxis was always used by 13% and selectively used by 66% of the surgeons with indications being mainly perioperative signs of infection (45%) or preoperative biliary drainage (55%). Piperacillin-tazobactam was preferred as prolonged prophylaxis (47%), mostly during five days (25%). Bile cultures were routinely obtained by 47% of the surgeons. Antibiotic prophylaxis was routinely adjusted based on bile culture results by 22% of the surgeons. CONCLUSION:Global variations in perioperative antibiotic practices indicate a lack of consensus regarding antibiotic prophylaxis for pancreatoduodenectomy. Further research is required to clarify the effect of targeted antibiotic prophylaxis for patients with contaminated bile, while preserving antibiotic stewardship.

INTRODUCTION:Most present-day survival-models of patients with cancer do not account for tumor-host interactions. We hypothesized that host phenotypes based on systemic inflammation and body composition are prognostic of overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS:We performed a post-hoc analysis of the nationwide PORSCH-trial, including all patients undergoing pancreatoduodenectomy for PDAC. Primary outcome was OS. Body composition analysis was performed using automatic segmentation (Mosamatic™) of preoperative abdominal computed tomography scans. Low muscle mass and myosteatosis were defined using log-rank stratification of sex-standardized Z-values of skeletal muscle index and radiation attenuation, respectively. Patients were clustered in eight host phenotypes based on combinations of adverse host factors: [1] low muscle mass, [2] myosteatosis, [3] systemic inflammation (C-reactive protein >6mg/L). Their association with OS was tested using multivariable-adjusted Cox-proportional hazard-analysis. Distinct combinations of adverse host factors were stratified into low-, intermediate-, and high-risk phenotypes according to k-means clustering based on log hazard-ratio's. RESULTS:549 patients were included. The high-risk phenotype, characterized by the presence of all adverse host factors, showed lower median OS than intermediate ([1], [2], [1 +2], [1 +3], [2 +3]) and low-risk ([3]; none) phenotypes (13.0 months [95%CI 11.4-19.3] vs. 21.9 months [95%CI 19.3-24.7] vs. 35.2 months [95%CI 29.2-45.3], respectively; p < 0.001). In multivariable analysis, host phenotypes were associated with OS (adjusted [a]HR 1.39 [95%CI 1.08-1.80, p = 0.01; aHR 2.10 [95%CI 1.53-2.88], p < 0.01, for intermediate- and high-risk respectively), independent of tumor stage. DISCUSSION:Host phenotypes based on body composition and systemic inflammation predict OS independent of tumor stage in patients with resected PDAC, underscoring the importance of tumor-host interactions for clinical survival prediction.

BACKGROUND:Benchmarking of surgical outcomes across institutions requires adjustment for established risk factors. Although pathological diagnosis is recognized as a determinant of postoperative morbidity after pancreatoduodenectomy, its independent impact on outcomes has not been systematically quantified at a national level. This study aimed to investigate the impact of pathological diagnosis on postoperative outcomes after pancreatoduodenectomy and to assess inter-hospital variation in case-mix. METHODS:Data were obtained from the nationwide Dutch Pancreatic Cancer Audit. Postoperative complications were compared for pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), ampullary adenocarcinoma (AAC), duodenal adenocarcinoma (DAC), non-invasive intraductal papillary mucinous neoplasm (IPMN), pancreatic neuroendocrine tumors (PanNET), chronic pancreatitis (CP), and Other Pathology. Multivariable logistic regression was used to identify independent risk factors for major complications (Clavien-Dindo grade ≥3). RESULTS:Between 2014 and 2020, 4152 patients underwent pancreatoduodenectomy. The three most common diagnoses were PDAC (n = 1778; 42.8%), dCCA (n = 544; 13.1%), and AAC (n = 541; 13.0%). The rate of major complications differed between diagnoses (P < 0.001), and was lowest for CP at 21.8% and highest for PanNET at 43.9%. All diagnoses except CP showed a higher risk of major complications compared with PDAC, with CP showing no significant difference. The adjusted odds ratio for major complications was the highest for PanNET (2.59; 95% CI: 1.84-3.65) and DAC (2.32; 95% CI: 1.77-3.03). CONCLUSIONS:Pathological diagnosis is an independent risk factor for complications after pancreatoduodenectomy, with PanNET and DAC carrying the highest risk. Given the substantial inter-hospital variation in case-mix, audits comparing postoperative outcomes across institutions should incorporate pathological diagnosis as a covariate.

Background Resection margin status and lymph node involvement are well-established predictors of recurrence following resection of perihilar cholangiocarcinoma (pCCA). However, even patients with favorable pathology including negative surgical margins (R0) and node-negative disease (N0) may experience recurrence. We sought to develop a clinically relevant tool to risk stratify patients relative to tumor recurrence following an R0N0 resection of pCCA. Methods pCCA patients undergoing curative-intent resection with R0 and N0 tumor were identified from an international multi-institutional database. A pathology-based risk score was developed to predict recurrence-free survival (RFS). In addition, genomic profiling was performed in a subset of patients to evaluate the prognostic relevance of genetic alterations. Results Among 298 patients with resected R0N0 pCCA, 131 (44.0%) developed disease recurrence. Multivariable analysis identified advanced AJCC T category (T2b or T3/T4), perineural invasion, and poor tumor differentiation as independent predictors of inferior RFS. Based on these factors, a three-variable pathology-based risk score stratified patients into low-, intermediate-, and high-risk groups with corresponding 3-year RFS of 85%, 31%, and 27%, respectively. Both intermediate- and high-risk patients had worse RFS versus low-risk patients (high-risk vs. low-risk: median RFS, 15.0 vs. 92.9 months; intermediate-risk vs. low-risk: median RFS, 23.0 vs. 92.9 months; both p < 0.001). KRAS mutations occurred in 29% of profiled patients, which was associated with reduced RFS (mutant vs. wild-type KRAS: median RFS, 11.0 vs. 24.0 months, p = 0.011). Conclusions Recurrence risk among patients with R0N0 pCCA was heterogeneous. The proposed risk score stratified patients into markedly different risk categories relative to recurrence, which may help guide utilization of adjuvant therapy as well as surveillance in the postoperative setting.

INTRODUCTION:Cholestasis prevents optimal treatment of perihilar cholangiocarcinoma (pCCA). To counteract this, biliary drainage (BD) has long been regarded as mandatory prior to any treatment. However, increasing evidence has highlighted the risks associated with BD, notably cholangitis, indicating that while often necessary, drainage requires careful clinical judgment. AREAS COVERED:This narrative literature review outlines the historical development of BD and its rationales, including the restoration of liver function, a prerequisite for liver hypertrophy-inducing procedures, and improvement of performance status. The review also addresses its drawbacks, particularly the risk of cholangitis due to bacterial colonization of the biliary tree and summarizes the evidence shaping contemporary clinical practice. EXPERT OPINION:Once regarded as mandatory, BD can no longer be justified as a routine intervention for every pCCA patient, given the associated risks. Undrained partial hepatectomy should be considered in patients with moderate bilirubin levels, adequate future liver remnant volume, absence of cholangitis, normal performance status, and preserved liver and renal function. Still, this applies to only a minority of patients. Similarly, systemic therapy may be feasible without BD in highly selected patients. Future research should focus on defining selection criteria, investigating new biomarkers of cholestasis, and refining drainage techniques to minimize complications of BD.

PURPOSE:Intrahepatic cholangiocarcinoma (iCCA) has been a contraindication for liver transplantation due to frequent recurrence and poor survival. We sought to determine the true proportion of transplantation-eligible iCCA patients and their outcomes without transplantation. METHODS:Data from patients evaluated for iCCA at two academic medical centers between 2008 and 2018 were analyzed retrospectively. Overall survival was determined for patients categorized as eligible for liver transplantation based on six criteria: unresectability, no extrahepatic disease, stable disease after chemotherapy, functional status (maximum age, 72 years), no major comorbidity, and no involvement of major vasculature. RESULTS:Of 1407 iCCA patients with sufficient data, 327 (23%) had advanced liver-confined disease. Most (n = 180 [55%]) progressed or died before 6 months of therapy. Others were ineligible owing to resection after pretreatment (n = 47), poor performance status (n = 8), advanced age (n = 32), comorbidity (n = 19), or extensive extrahepatic vascular involvement (n = 2). Only 39 patients (12% of 327; 2.8% of 1,407; 95% confidence interval [CI] 2-3.8%) met eligibility, with more than half (n = 22 [56%]) treated with hepatic arterial infusion pump chemotherapy. Their median survival from diagnosis was 39 months (95% CI 28-62 months); 3-year survival from estimated eligibility was 46% (95% CI 32-65%). CONCLUSIONS:Patients who meet stringent eligibility criteria for liver transplantation constitute approximately 3% of patients with iCCA. The observed survival exceeds benchmarks established for systematic therapy alone and is likely attributable to favorable tumor biology and hepatic artery infusion chemotherapy.

598 Background: Mutations in isocitrate dehydrogenase 1 and 2 ( IDH1 , IDH2 ) are common in intrahepatic cholangiocarcinoma (ICC), but their prognostic value is unclear. Using a large, clinically annotated dataset, we assessed their impact in resected and non-resected ICC. Methods: This was a retrospective study of ICC patients who underwent next-generation sequencing from 2008-2022. Adults treated with curative intent resection (resected) or managed nonoperatively (unresectable) were analyzed. Results: Of 795 patients, 25% had IDH1/2 mutations (80% IDH1 , 20% IDH2 ) ( IDH mut) and 43% underwent resection. High-risk genetic alterations ( TP53 mut, KRAS mut, CDKN2A del) were more frequent in IDH wild-type ( IDH wt) ( IDH mut, OR 2.26; q <0.001) (Table 1). In the entire cohort, median overall survival (OS) was 32 months in IDH mut and 28 months for IDH wt (p=0.2); by contrast, OS was 19 months in patients with high-risk alterations compared to 40 months without (p<0.001). In resected patients, recurrence free survival (RFS) in IDH mut was 20 months vs. 14 months for IDH wt (p=0.018), and OS was 69 months vs. 50 months, respectively (p=0.2); however, after controlling for high-risk genetic alterations, any benefit of IDH mut disappeared (RFS: HR 0.78; p=0.095; OS: HR 0.88; p=0.4). In unresectable patients, progression free survival (PFS) in IDH mut was 9.4 months compared to 9.1 months for IDH wt (p=0.7), and OS was 22 months vs. 18 months, respectively (p=0.13) There remained no significant differences after controlling for high-risk alterations (PFS: HR 1.03; p=0.8; OS: HR 0.94; p=0.6). IDH mutational status was not a significant survival predictor in multivariable models for both resected and non-resected patients. In 42 patients with unresectable IDH mut treated with IDH inhibitors, median OS was 12 months. Conclusions: In this large cohort of resected and non-resected ICC patients, IDH mutations were not an independent predictor of survival, after controlling for high-risk genetic alterations and clinical variables. Thus, IDH status should not be used in isolation to guide prognosis. Gene Mutation OverallN = 795 1 IDH mutN = 202 1 IDH wtN = 593 1 OR 95% CI q-value 2 TP53 151 (19%) 19 (9.4%) 132 (22%) 2.76 1.69, 4.73 <0.001 ARID1A 142 (18%) 51 (25%) 91 (15%) 0.54 0.37, 0.79 0.004 CDKN2A 136 (17%) 24 (12%) 112 (19%) 1.73 1.09, 2.83 0.043 BAP1 121 (15%) 39 (19%) 82 (14%) 0.67 0.44, 1.03 0.069 FGFR2 119 (15%) 6 (3.0%) 113 (19%) 7.69 3.62, 19.9 <0.001 CDKN2B 104 (13%) 20 (9.9%) 84 (14%) 1.50 0.91, 2.58 0.12 PBRM1 89 (11%) 36 (18%) 53 (8.9%) 0.45 0.29, 0.72 0.002 KRAS 83 (10%) 14 (6.9%) 69 (12%) 1.77 1.00, 3.34 0.069 CDKN2Adel 114 (14%) 20 (9.9%) 94 (16%) 1.71 1.05, 2.93 0.054 TP53, KRAS, or CDKN2Adel 288 (36%) 47 (23%) 241 (41%) 2.26 1.58, 3.28 <0.001 1 n (%); Median (Q1,Q3). 2 False discovery rate correction for multiple hypothesis testing.

BACKGROUND:Primary Percutaneous Stenting (PPS) is a novel drainage technique for malignant hilar biliary obstruction (MHBO), typically caused by perihilar cholangiocarcinoma. During PPS, the percutaneous tract is sealed with Avitene™ Microfibrillar Collagen Hemostat (MCH) to avoid an external drain. This report describes the radiological, intraoperative, and histopathological appearance of MCH following PPS in resectable MHBO. METHODS:We reviewed all patients with MHBO who underwent PPS and surgical exploration at two Dutch academic hospitals between 2022-2025. Macroscopic findings were documented by the surgeon, and tissue from suspicious lesions was evaluated with frozen section and definitive histology to differentiate malignant lesions from reactive ones due to MCH deposits. RESULTS:Twenty-one patients underwent surgical exploration after PPS. In fourteen patients, white-yellow capsular lesions were identified at the PPS puncture site that were macroscopically suspicious for peritoneal metastases. Histology revealed foreign body reactions with eosinophils, giant cells, amorphous material, and focal necrosis. No malignant cells were identified. Two patients had peritoneal metastases, yet the lesions along the PPS tract were negative for malignancy. DISCUSSION:MCH deposits along the PPS puncture tract can resemble PM during surgical exploration. Recognizing this characteristic appearance is important to prevent misinterpretation and alter surgical decision making.

LBA3506 Background: Recurrence after local treatment for colorectal liver metastases (CLM) occurs in up to 70% of patients, frequently confined to the liver. Dutch guidelines do not recommend adjuvant chemotherapy, because three randomized controlled trials (RCTs) have shown no overall survival (OS) benefit of perioperative systemic chemotherapy in resectable CLM. Hepatic arterial infusion pump (HAIP) chemotherapy delivers high doses of floxuridine directly to the liver. This trial evaluated the effectiveness of adjuvant HAIP chemotherapy with floxuridine compared to resection alone in patients with resectable CLM and a low clinical risk score (CRS). Methods: This is an open-label, investigator-initiated, multicenter, randomized phase III trial. Adult patients with resectable CLM, no extrahepatic disease, and CRS 0–2 were randomized 1:1 to resection plus adjuvant HAIP chemotherapy with floxuridine versus resection alone, both without adjuvant systemic chemotherapy. Preoperative systemic chemotherapy prior to randomization was allowed. Patients in both groups who signed informed consent but did not fulfill inclusion criteria at the time of surgery were excluded and replaced. Patients were scheduled for 6 cycles of HAIP chemotherapy with floxuridine (0.12 mg/kg/day) that was initiated 4–12 weeks after placement of a Tricumed constant flow pump. The primary endpoint was progression-free survival (PFS) calculated from the date of surgery to the date of a recurrence or death. Secondary endpoints included hepatic PFS (hPFS) and ninety-day mortality. Survival was estimated using Kaplan-Meier method and compared using a log-rank test. Results: Between August 2018 and March 2026, 243 patients were randomized to resection followed by adjuvant HAIP (n=120) or resection alone (n=123). At time of surgery, 25 patients were excluded due to presence of extrahepatic disease, unresectable CLM or histopathological confirmation of benign disease. In this analyses, 110 patients were included in the resection and adjuvant HAIP group and 108 patients in the resection alone group. In the HAIP group, 100 patients (91%) initiated HAIP chemotherapy, and the median number of administered cycles was 5 [IQR 3-6]. Treatment was discontinued in 8 patients (8%) due to recurrence and in 32 patients (32%) due to toxicity. The median PFS was 15.0 months in HAIP group vs 16.0 months in resection alone group (HR 0.88; 95% CI 0.62–1.25; p=0.48). The median hPFS was 37.6 months in HAIP group vs 21.8 months in resection alone group (HR 0.80; 95% CI 0.54–1.17; p=0.25). Ninety-day postoperative mortality was observed in 4 patients (3.3%) in the HAIP group and in 1 patient (0.8%) after resection alone. No mortality was attributed to pump placement or HAIP chemotherapy. Conclusion: In patients with resectable CLM and a low CRS, no improvement in PFS after adjuvant HAIP chemotherapy with floxuridine compared to resection alone could be demonstrated. Mature results for overall survival are expected in 2029. EudraCT number: 2018-001696-21. Clinical trial information: 2018-001696-21.

Importance Total pancreatectomy (TP) is indicated for advanced pancreatic cancer or multifocal tumors. Furthermore, TP may be performed to avoid the risk of pancreatic fistula in selected patients to improve the perioperative risk profile. Objective To define reference values for TP based on a low-risk cohort treated at expert centers. Design, Setting, and Participants This multicenter study analyzed outcomes from patients undergoing primary TP for malignant or benign lesions from 25 international expert centers from January 2017 to November 2023. Low-risk patients undergoing TP (LR-TP) were without vascular resections or significant comorbidities. Exposures TP. Main Outcomes and Measures Twenty reference values were derived from the 75th or the 25th percentile of the median values of all centers. Outcomes of LR-TP were compared with a cohort of TP with vascular resection, TP due to high-risk pancreatic anastomosis, and the benchmark values for low-risk pancreatoduodenectomy. Results Of 994 patients, 333 (33.5%; median [IQR] age, 66 [58-72] years; 171 male [51.4%]) qualified as the LR-TP cohort. Reference values included blood loss (≤1000 mL), major complications (≤37%), 3-month postoperative mortality (<6%), and retrieved lymph nodes (≥29). Compared with TP with vascular resections, reference cutoffs were not met for major complications (51% vs LR-TP ≤37%) and 90-day mortality (11% vs LR-TP ≤6%). For TP due to high-risk anastomosis, failure to rescue rate (38% vs ≤6%) and 90-day mortality (11% vs LR-TP ≤6%) were not met. Compared with pancreatoduodenectomy, reference values for postoperative mortality were 3 times higher for LR-TP (≤2% vs ≤6%) and less for resected lymph nodes (≥16 vs ≥29). Conclusions and Relevance This case-control study provided global reference values for TP, indicating significantly higher postoperative morbidity and mortality compared with pancreatoduodenectomy. Perioperative morbidity of TP was especially increased in patients with vascular resections. These reference values can serve for quality control of pancreatic surgery.

BACKGROUND AND AIMS:Cholangiocarcinoma (CCA) is an aggressive cancer with rising incidence and mortality worldwide. Chronic liver disease (CLD) is a well-recognized risk factor, but its influence on tumor presentation and clinical outcomes remains unclear. We aimed to compare the clinical course of CCA in patients with and without CLD. METHODS:We retrospectively analyzed 3,743 patients diagnosed with CCA between 2010 and 2024 across international centers. CLD was defined by documented primary sclerosing cholangitis, cirrhosis, viral hepatitis, or other chronic liver disorders; remaining patients were classified as non-CLD. Demographic, clinical, biochemical, treatment, and survival features were compared. RESULTS:Among the CCA cohort, 993 patients had CLD. Compared with non-CLD patients (n=2,750), those with CLD were more frequently male (67% vs. 53%) and younger (median age 63 vs. 66 years). CLD-CCA patients more often presented with intrahepatic tumors (64% vs. 42%), better performance status (ECOG 0: 53% vs. 35%), lower CA19.9 levels (56 vs. 135 U/mL), and earlier-stage disease (localized: 57% vs. 43%; metastatic: 23% vs. 31%). In propensity score-matched analyses, patients with prior CLD were diagnosed at earlier CCA stages than non-CLD controls. Consequently, curative-intent tumor surgery was performed more frequently in CLD patients (60% vs. 48%), resulting into longer median overall survival (mOS 12.2 vs. 11.1 months; HR 0.88, 95%CI 0.80-0.98) and higher 5-year survival (OR 1.70, 95%CI 1.37-2.11), particularly in intrahepatic CCA (mOS: 14.2 vs. 11.1 months; HR 0.77, 95%CI 0.68-0.87; 5-year survival OR 2.19, 95%CI 1.60-3.01). Treatment responses across modalities were comparable between groups. CONCLUSION:Pre-existing CLD is associated with earlier-stage CCA diagnosis and improved survival, supporting the implementation of structured surveillance strategies in high-risk CLD populations. IMPACT AND IMPLICATIONS:This international multicenter study show that pre-existing CLD is associated with earlier-stage CCA diagnosis, likely due to closer clinical surveillance, greater eligibility for curative-intent surgery, and improved survival. Treatment responses were similar regardless of CLD status. These findings support established surveillance in high-risk groups and highlight the need to optimize strategies for selected moderate-to-high risk CLD populations, alongside prospective evaluation of their clinical utility, cost-effectiveness, and potential refinement through more accurate non-invasive biomarkers.

BACKGROUND:Although robot-assisted pancreatoduodenectomy (RPD) enhances patient recovery, it could be associated with higher costs than open pancreatoduodenectomy (OPD), potentially limiting its widespread adoption. High-level evidence comparing costs of RPD and OPD is lacking. This analysis in a randomized trial compared costs and cost-effectiveness between RPD and OPD. METHODS:Predefined cost-effectiveness analysis in the international randomized DIPLOMA-2 trial (ISRCTN27483786) comparing RPD and OPD in patients with primary resectable neoplasm in 14 centers in 6 European countries (2022-2023). Primary outcomes were mean total hospital costs (euro) at 6 months postoperatively and cost-effectiveness based on costs per quality-adjusted life year (QALY; incremental cost-utility ratio). Three analyses were performed: (1) costs, (2) QALYs including Health-Related Quality of Life (HR-QoL), and (3) cost-effectiveness with probabilities at various willingness-to-pay (WTP) thresholds. RESULTS:Overall, 268 patients were included (170 RPD, 98 OPD). No significant difference in total hospital costs was found between RPD and OPD (€30,956 vs. €28,271, P=0.538). The intraoperative costs were €5,491 higher with RPD (€11,906 vs. €6,451, P<0.001), whereas postoperative costs were €2806 lower (€19,051 vs. €21,856, P=0.518). The HR-QoL index scores were comparable at 1 and 3 months, but worse at 6 months with RPD (Δ-0.08 [-0.15 to -0.001]). Consequently, over 6 months a QALY loss was observed with RPD (Δ-0.02 [-0.07 to 0.01]) with a <30% probability of RPD being cost-effective across various WTP thresholds. CONCLUSION:This analysis in a randomized trial found no significant differences in costs between RPD and OPD up to 6 months. Nonsignificantly lower QALYs at 6 months with RPD resulted in a <30% probability that RPD is cost-effective compared with OPD within 6 months after surgery in selected patients in high-volume centers.

BACKGROUND AND AIMS:Liver resection (LR) and orthotopic liver transplantation (OLT) are therapeutic options for locally advanced perihilar cholangiocarcinoma (pCCA) requiring hepatic artery reconstruction (HAR). This study aimed to compare short- and long-term outcomes of LR and OLT. Outcomes were major vascular complications, 90-day mortality, overall survival (OS) and recurrence-free survival (RFS). METHODS:A cohort of patients undergoing LR with HAR from 10 Western centres was compared with an OLT cohort comprising patients who received or did not receive neoadjuvant chemoradiotherapy (NACR). RESULTS:109 patients, 60 LR and 49 OLT (22 OLT no-NACR and 27 OLT NACR) were included. LR patients were older and had fewer Bismuth type 4 tumours (38.3% vs. 69.4%, p = 0.009). Positive margins (49.2% vs. 6.5%, p < 0.001) and lymph nodes (54.2% vs. 32.4%, p = 0.058) were found more frequently in LR patients. No differences were found between LR and OLT in major (40% vs. 46.9%, p = 0.56) and vascular complications (23.3% vs. 28.6%, p = 0.66); NACR was an independent prognostic factor for vascular complications (OR 2.63, 95% CI 1.03-6.70, p = 0.043). 90-day mortality (15% for LR vs. 10.2% for OLT, p = 0.57) and 5-year OS (HR 0.68, 95% CI 0.40-1.17, p = 0.17) were similar. Median OS after LR versus OLT was higher but not significant (24 vs. 40 months, p = 0.13). OLT had better 5-year RFS (HR 0.52, 95% CI 0.29-0.96, p = 0.035) than LR. R1 resection (HR 2.07, 95% CI 1.03-4.18, p = 0.041) and perineural invasion (HR 3.64, 95% CI 1.09-12.16, p = 0.035) were independent prognostic factors for RFS. CONCLUSIONS:LR and OLT for locally advanced pCCA had similar rates of major complications and post-operative mortality, but NACR was associated with increased vascular complications. Survival was difficult to compare in the groups due to their heterogeneity, but OLT, especially with NACR, seems to give better results than LR.

Background Intrahepatic cholangiocarcinoma (iCCA) is a rare liver malignancy with poor prognosis. This study assessed how case discussion of patients at expert centers within multidisciplinary team meetings (MDTs) is associated with treatment and survival in iCCA patients in the Netherlands. Methods This retrospective cohort study analyzed data registered in the Netherlands Cancer Registry between 2017 and 2021 on all consecutive patients diagnosed with iCCA. Data included patient demographics, tumor characteristics, and the involvement of a member of an expert center at case discussions. Outcomes included overall survival and treatment type, which was specified as tumor-directed (e.g., resection, ablation, systemic treatment, or other treatment modalities) vs. supportive care only. Results Among the 1.622 patients included, median overall survival was 5.4 months, and 825 (50.9%) underwent tumor-directed therapy. Patients discussed at expert centers (59.6%) were more likely to receive tumor-directed therapy (58.8% vs. 37.2%, P < 0.001) and undergo surgery (20.3% vs. 5.7%, P < 0.001). In the multivariable analysis, patients discussed at expert centers had better overall survival (hazard ratio 0.69 (0.62-0.78)). Conclusions Centralized care through MDT discussion at expert centers was associated with increased likelihood of receiving tumor-directed therapy and improved survival in iCCA patients. This study highlights the potential for improved patient outcomes through structured expert consultations.

Models that predict the survival and quality of life (QoL) in patients with malignancies can support prognostic counselling and patient-centered evaluation of disease trajectories. Challenges in the development of such models include incomplete data in real-world registries, including missing baseline measurements and irregular, sparse availability of longitudinal QoL outcomes during treatment. These limitations complicate the incorporation of QoL into survival prediction and the reliable modeling of QoL over time. We address these limitations with a novel framework to predict survival and quality of life in the face of sparse data. The framework consists of a regularized missingness-avoiding random survival forest (MA-RSF) for survival prediction, and a conditional diffusion-based approach to predict QoL at various follow-up intervals. We apply the approach to a pancreatic cancer use-case, and evaluate it on a nationwide Dutch cohort. We find that our approach maintains high predictive accuracy (C-index 0.77) for survival prediction and minimizes reliance on sparse pre-treatment data, including QoL PROMs. In addition, we demonstrate that the QoL prediction expressed as the Static-Dynamic diffusion architecture reduces trajectory prediction error (RMSE) at key follow-up intervals compared to standard conditional generation (e.g. 12.9 vs 14.0 RMSE at 7 months). The proposed framework facilitates the prediction of survival and QoL outcomes in settings characterized by incomplete data and could enhance prognostic counseling in patients with malignancies, including pancreatic cancer.