Immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is a rare condition with symptoms often mimicking malignancy, infection, or other autoimmune diseases. This case report describes the unique case of a 62-year-old male initially diagnosed with IgG4-SC, followed by subsequent diagnosis of cholangiocarcinoma. Biliary tract cancer in the setting of IgG4 related disease has been previously described; however, this patient course is novel as it encompasses the spectrum of challenges in IgG4-SC management, including diagnostic uncertainty, risk of infection with immunosuppressive agents, and development of malignancy diagnosed shortly following IgG4-SC diagnosis. We review the literature of management, outcomes, and malignancy risk and furthermore, highlight a promising recent therapy in treatment of IgG4 related disease, inebilizumab.

BACKGROUND:Hepatic artery infusion with floxuridine is a treatment option for patients with colorectal liver metastases or intrahepatic cholangiocarcinoma. Outcomes from newer centers are understudied. Predictive markers are needed, and quantitative circulating tumor DNA is an emerging candidate method for predicting response in patients receiving hepatic artery infusion. We aimed to describe safety, feasibility, early oncologic outcomes, and quantitative circulating tumor DNA dynamics in patients treated with hepatic artery infusion at a newly established program. METHODS:Single-institution analysis of patients who underwent hepatic artery infusion pump placement (April 2022-April 2024) was conducted. Primary outcomes included safety and feasibility (receiving ≥1 cycle of floxuridine). Secondary outcomes included radiographic response (Response Evaluation Criteria in Solid Tumors 1.1), relative dose intensity of floxuridine received, and quantitative circulating tumor DNA response. RESULTS:A total of 36 patients underwent hepatic artery infusion pump placement (colorectal liver metastases: 32; cholangiocarcinoma: 4). Technical success was 100%. Feasibility was 97%. One patient experienced mortality at 90 days from disease progression. Three patients (8%) experienced a total of 5 hepatic artery infusion pump-specific complications (pump pocket [n = 3], hemorrhage [n = 1], biliary sclerosis [n = 1]). Median relative dose intensity was 68.5% (colorectal liver metastases: 68.3%; cholangiocarcinoma 72.5.0%). For the 27 patients who underwent floxuridine therapy with available postoperative imaging, disease control rate was 97% (partial response: n = 15; stable disease: n = 11). Quantitative circulating tumor DNA was obtained from 16 patients (44%). Circulating tumor DNA dynamics appeared to correlate with and precede radiographic response. CONCLUSIONS:Implementation of a new hepatic artery infusion program is safe and feasible with promising early oncologic outcomes. Circulating tumor DNA tracking is achievable and dynamic changes in circulating tumor DNA may correlate with radiographic response to treatment.

Background: Prior studies have shown that achievement of textbook oncologic outcomes (TOO) after pancreatectomy for pancreatic adenocarcinoma (PDAC) is associated with better survival outcomes. However, the associations between TOO, procedure type, and treatment sequence has not been examined. Methods: Patients with resected PDAC were identified within the National Cancer Database (2010-2018). We analyzed rates of TOO (defined as no 30-day readmission, no 90-day mortality, no prolonged length of stay, negative surgical margins, receipt of multi-agent chemotherapy, and nodal yield >= 12) stratified by procedure (pancreatoduodenectomy vs. distal pancreatectomy vs. total pancreatectomy) and treatment sequence (up-front surgery vs. neoadjuvant therapy). Results: A total of 20,155 patients were identified. Patients who underwent distal pancreatectomy were less likely to have TOO compared to pancreatoduodenectomy (12.6% vs. 17.5%; OR=0.77, 95% CI: 0.68-0.88). There was no difference in TOO between patients who underwent total pancreatectomy compared to pancreatoduodenectomy (16.4% vs. 17.5%; OR=0.96, 95% CI: 0.84-1.11). Neoadjuvant chemotherapy was associated with a 5-fold increase in the odds of TOO (OR=5.07, 95% CI: 4.35-5.91). TOO was associated with improved OS regardless of surgical procedure (pancreatoduodenectomy: median OS: 33.7 vs. 20.5mo; HR=0.69, 95% CI: 0.65-0.73; distal pancreatectomy: median OS: 35.8 vs. 23.9mo; HR=0.73, 95% CI: 0.64-0.84; total pancreatectomy: median OS: 30.1 vs. 19.9mo; HR=0.69, 95% CI: 0.61-0.79). Conclusions: The rate of TOO was lower for distal pancreatectomy as compared to pancreatoduodenectomy or total pancreatectomy. Neoadjuvant therapy was associated with higher likelihood of TOO. Regardless of pancreatectomy type, TOO was associated with improved OS.

Background: Survival data on patients with locally advanced rectal cancer (LARC) undergoing non-operative management (NOM) in a real-world setting are lacking. Methods: We analyzed LARC patients from the National Cancer Database with the following features: treated between 2010 and 2020, age 18–65 years, Charlson comorbidity index (CCI) ≤ 1, received neoadjuvant multiagent chemotherapy plus radiation ≥ 45 Gray, and underwent surgery or NOM. Patients were stratified into two groups: (A) clinical T1-3 tumors with positive nodes (cT1-3N+) and (B) clinical T4 tumors, N+/− (cT4N+/−). We performed a comparative analysis of overall survival (OS) with NOM versus surgery by the Kaplan–Meier method and propensity score matching. Additionally, a multivariable analysis explored the association between NOM and OS. Results: NOM exhibited significantly lower OS than surgery in both groups. In cT1-3N+ patients, NOM resulted in a 5-year OS of 73.9% (95% confidence interval [CI] = 69.7–77.6%) versus 84.5% (95% CI = 83.6–85.3%) with surgery (p < 0.001). In the cT4N+/− group, NOM yielded a 5-year OS of 44.5% (95% CI = 37.0–51.8%) versus 72.5% (95% CI = 69.9–74.8%) with surgery (p < 0.001). Propensity score matching and multivariable analyses revealed similar conclusions. Conclusion: Patients with LARC undergoing NOM versus surgery in real-world settings appear to have inferior survival.

Background: We examined differences in receipt of guideline-compliant care in patients with early-onset versus average-onset biliary tract cancers (BTC) in localized or metastatic settings. Additionally, we examined associations between guideline compliance and overall survival (OS), stratified by age of onset and clinical stage. Methods: Patients with BTC [intrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, extrahepatic cholangiocarcinoma] were identified within the National Cancer Database (2010-2018). Early onset was defined as diagnosis at < 50 and average onset at >= 70 years. Guideline-compliant care was defined as surgical resection +/- chemotherapy for localized disease and multi-agent chemotherapy for metastatic disease. Results: A total of 32,247 patients were identified, of whom 2855 patients (8.9%) had early-onset disease. Earlyonset patients were more likely to have metastatic disease at presentation. Early-onset patients were more likely to receive guideline-compliant care in both localized (OR=2.24, 95% CI: 1.93-2.60) and metastatic (OR=4.40, 95% CI: 3.72-5.21) settings. Among patients with localized BTC, guideline compliance was associated with improved OS in both early (median OS: 51.9 vs. 13.5 months; HR=0.31, 95% CI: 0.27-0.37) and average-onset (median OS: 25.9 vs. 6.1 months; HR=0.31, 95% CI: 0.30-0.32) disease. Among patients with metastatic BTC, guideline compliance was associated with improved OS in both early (median OS: 10.1 vs. 3.5 months; HR=0.52, 95% CI: 0.43-0.62) and average-onset (median OS: 8.6 vs. 2.2 months; HR=0.45, 95% CI: 0.43-0.48) disease. Conclusions: Early-onset BTC is associated with more frequent guideline-compliant care regardless of clinical stage. Guideline compliance is associated with improved OS regardless of age of onset or clinical stage.

Retrospective analyses investigating intraoperative margin revision in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing pancreatectomy have yielded conflicting results.Some studies have reported that additional resection to achieve an R0 margin on permanent section was not associated with higher overall survival (OS) or recurrence-free survival (RFS). 1,2Other studies have suggested that intraoperative revision of positive neck margins may lead to prolonged survival. 3To date, no studies have examined the frequency of isolated margin positivity (IMP) in patients with localized PDAC who underwent pancreatectomy (pancreatoduodenectomy, distal pancreatectomy, or total pancreatectomy) and determined the fraction of patients that would potentially derive a survival benefit from revising positive neck or surgical margins; conceptually, these would be patients with no adverse pathologic features (nodal positivity, perineural invasion, and lymphovascular invasion) besides margin positivity, and revision of this isolated margin would result in absence of any adverse pathologic feature and theoretically higher survival.

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) occurs in 10% to 40% of patients after pancreatic resection. Pancreatic exocrine insufficiency (PEI) is thought to be closely associated with NAFLD; however, the mechanism of NAFLD is not clearly understood. We perform a systematic review and meta-analysis to better understand the risk factors of NAFLD. METHODS:A systematic literature search was performed in the MEDLINE database. Studies focused on the risk factors associated with NAFLD in patients undergoing pancreatectomy. The odds ratios (ORs) denoting the association of risk factors with NAFLD after resection were curated. RESULTS:Of 814 published articles, 26 studies met the inclusion criteria. Combined, these studies included clinical data on 4055 patients. The pooled incidence of NAFLD was 29% (23%-35%). Among the various risk factors analyzed, the following had a significant likelihood of NAFLD on forest plot analysis: female gender (OR, 2.44), pancreatic ductal adenocarcinoma (OR, 2.11), portal vein or superior mesenteric vein resection (OR, 1.99), dissection of nerve plexus around the superior mesenteric artery (OR, 1.93), and adjuvant chemotherapy (OR, 1.58). Only 2 studies investigated 2 different measurements of quantitative PEI, which could not be used for analysis. Owing to heterogeneity of studies, pancreatic remanent volume, which is considered a marker for PEI could not be evaluated. Pancreatic enzyme replacement therapy (PERT) was not associated with NAFLD. CONCLUSION:Numerous factors are associated with NAFLD after pancreatectomy. Previous research shows that PEI may be associated with NAFLD; however, this could not be compared in our meta-analysis. Further research is required to study the role of PERT in NAFLD.

Objectives: We used a novel combined analysis to evaluate various factors associated with failure to undergo surgery in non-metastatic pancreatic cancer. Methods: We identified rates of surgery and reasons for surgical attrition from clinical trials, which studied neoadjuvant therapy in resectable pancreatic cancer. Next, we queried the National Cancer Database (NCDB) for Stage I-III, T1-3 pancreatic adenocarcinoma patients. We investigated the rates and factors associated with the receipt of surgery. Finally, we evaluated variable importance predicting the receipt of surgery. Results: In clinical trials, 25-30 % of patients did not undergo surgery, mostly due to disease progression. In the NCDB, the overall surgical rate was only 49 %, but increased to 67 % in a curated cohort meant to mirror clinical trial patients. Patients treated at low-volume institutions (OR = 0.64, 95 % CI: 0.61-0.67) and who were uninsured (OR = 0.56, 95 % CI: 0.52-0.62) and Medicaid-insured (OR = 0.67, 95 % CI: 0.64-0.71) were less likely to receive potentially curative surgery. Conclusion: We have identified a realistic target surgery rate of 70%-75 % in potentially-resectable pancreatic cancer. While attrition to pancreatic cancer surgery is mostly due to tumor biology, our study identified the most important non-medical barriers, such as facility volume and insurance, affecting pancreatic cancer surgery.

Background We previously reported that an extended antibiotic mitigation pathway following pancreatoduodenectomy in patients with intermediate-/high-risk glands is associated with 83 % lower odds of clinically relevant postoperative pancreatic fistula (CR-POPF). We now describe associations between the pathway, resource utilization, and hospital charges. Methods We performed a retrospective cohort study of patients who underwent elective pancreatoduodenectomy with soft gland texture and fistula risk score (FRS) ≥3 who received standard or extended antibiotics. Hospital charges and resource utilization within 90 days of surgery were compared by CR-POPF status and antibiotic pathway. Results A total of 34 patients received extended antibiotics and 53 received standard antibiotics. In patients with CR-POPF, patients who received extended antibiotics had lower likelihood of surgical or percutaneous reintervention (75.0 % vs. 100.0 %, p = 0.022). Ninety-day postoperative charges associated with CR-POPF were higher than no CR-POPF ($60,527 vs. $25,631, p = 0.028). Our risk-based model predicted a $15,825 decrease in hospital charges per patient receiving extended antibiotics. Conclusions CR-POPF is associated with higher 90-day hospital charges. Extended antibiotic therapy following pancreatoduodenectomy in patients with soft gland texture and FRS ≥3 is associated with fewer reinterventions in patients who develop CR-POPF. These outcomes will be formally tested in a randomized controlled trial (NCT05753735).

Background: The frequency of major cancer surgery in the elderly (≥80 years) has increased concomitantly with the rise in average age of the population. We assessed early postoperative mortality following hepato-pancreato-biliary (HPB) and gastrointestinal (GI) procedures for common malignancies stratified by age. Methods: The National Cancer Database (2004-2017) was queried for patients who underwent resection for GI (gastroesophageal and colorectal) or HPB (pancreatic adenocarcinoma, biliary tract, and primary liver) cancers. We compared early postoperative mortality (30 d and 90 d) stratified by age (65-79 vs ≥80 years) and procedure, and compared survival outcomes by age and operative vs nonoperative management. Results: A total of 709,358 patients were included. The 30-day mortality ranged from 1.8% to 5.8% among patients 65-79 years and from 3.2% to 12.4% among patients ≥80 years depending on procedure. The 90-day mortality ranged from 3.6% to 10.6% in patients 65-79 years compared to 8.4%-21.0% among patients ≥80 years. The overall 90-day mortality was 5.2% for patients 65-79 years and 12.0% for patients ≥80 years ( P < .001). Age ≥80 was associated with worse survival among operatively managed patients with each upper GI, HPB, and lower GI malignancy relative to younger patients on multivariable analysis. However, operative management of patients ≥80 years was associated with improved survival relative to nonoperative management. Discussion: Elderly patients suffer higher postoperative mortality after major GI and HPB cancer surgery, but operative management is associated with improved survival among patients ≥80 years as compared to nonoperative management. These data are important to contextualize when counseling elderly patients on their treatment options for localized GI and HPB cancers.

Centralization of hepatopancreatobiliary procedures to more experienced centers has been recommended but remains controversial. Hospital volume and risk-stratified mortality rates (RSMR) are metrics for interhospital comparison. We compared facility operative volume with facility RSMR as a proxy for hospital quality. Patients who underwent surgery for liver (LC), biliary tract (BTC), and pancreatic (PDAC) cancer were identified in the National Cancer Database (2004–2018). Hierarchical logistic regression was used to create facility-specific models for RSMR. Volume (high versus low) was determined by quintile. Performance (high versus low) was determined by RSMR tercile. Primary outcomes included median facility RSMR and RSMR distributions. Volume- and RSMR-based redistribution was simulated and compared for reductions in 90-day mortality. A total of 106,217 patients treated at 1282 facilities were included; 17,695 had LC, 23,075 had BTC, and 65,447 had PDAC. High-volume centers (HVC) had lower RSMR compared with medium-volume centers and low-volume centers for LC, BTC, and PDAC (all p < 0.001). High-performance centers (HPC) had lower RSMR compared with medium-performance centers and low-performance centers for LC, BTC, and PDAC (all p < 0.001). Volume-based redistribution required 16.0 patients for LC, 11.2 for BTC, and 14.9 for PDAC reassigned to 15, 22, and 20 centers, respectively, per life saved within each US census region. RSMR-based redistribution required 4.7 patients for LC, 4.2 for BTC, and 4.9 for PDAC reassigned to 316, 403, and 418 centers, respectively, per life saved within each US census region. HVC and HPC have the lowest overall and risk-standardized 90-day mortality after oncologic hepatopancreatobiliary procedures, but RSMR may outperform volume as a measure of hospital quality.

BACKGROUND:Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed.OBJECTIVE:A systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI).METHODS:Outcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR).RESULTS:A total of 32, 7, 9, and 14 publications were included in the HAI-S, TACE-S, and TARE-S chemotherapy arms. The 6/12/24/36-month OS estimates for HAI-S, TACE-S, TARE-S, FOLFOX, FOLFIRI, and FOLFOXIRI were 97%/80%/54%/35%, 100%/83%/40%/14%, 82%/61%/34%/21%, 96%/83%/53%/36%, and 96%/93%/72%/55%. Similarly, the 6/12/24/36-month PFS estimates were 74%/44%/19%/14%, 66%/20%/9%/3%, 57%/23%/10%/3%, 69%/30%/12%/7%, and 88%/55%/18%/11%. The corresponding CTR and RR rates were 31, 20%, unmeasurable (TARE-S), 35, 53; and 49, 45, 45, 50, 80%, respectively. The majority of chemotherapy studies included first-line therapy and liver-only metastases, whereas most HAI-S studies were pretreated. On subgroup analysis in first-line setting with liver-only metastases, the HAI-S arm had comparable outcomes to FOLFOXIRI and outperformed doublet chemotherapy regimens. Although triplet chemotherapy appeared to outperform other arms, high toxicity and inclusion of potentially resectable patients must be considered while interpreting results.CONCLUSIONS:HAI-S and multiagent chemotherapy are effective therapies for UCRLM. To make definitive conclusions, a randomized trial with comparable patient characteristics and line of therapy will be required. The upcoming EA2222 PUMP trial may help to address this question.

Background: The surgical management of 1- to 2-cm neuroendocrine tumors of the appendix is an area of debate. We analyzed the clinical outcomes of appendectomy and compared them to right hemicolectomy. Methods: We queried the National Cancer Database to identify patients treated for 1- to 2-cm ANETs from 2004 to 2018. Patients were stratified by surgical approach (appendectomy vs. hemicolectomy). Multivariable models were used to identify factors associated with the choice of surgical approach and the association between surgical approach and overall survival. Results: Of the 3,189 patients we included, 1,573 (49.3%) underwent right hemicolectomy and 1,616 (50.7%) appendectomy. The appendectomy rate increased from 37.7% in 2004 to 58.9% in 2018. On multivariable analysis, patients with grade 2 and 3 tumors were less likely to undergo appendectomy alone (odds ratio = 0.41, 95% confidence interval = 0.26-0.66). Longer travel distance was associated with a higher likelihood of undergoing appendectomy (odds ratio = 2.52, 95% confidence interval = 1.15 -5.51). After adjusting for tumor grade, appendectomy alone had similar survival to hemicolectomy (hazard ratio = 1.03, 95% confidence interval = 0.67-1.59). Conclusion: In this updated analysis of the National Cancer Database, right hemicolectomy was not associated with improved overall survival compared to appendectomy alone for 1- to 2-cm neuroendocrine tumors of the appendix. Although patients with grade 2 or 3 tumors are more likely to undergo right hemicolectomy, this procedure may not improve their treatment or overall outcome. (c) 2023 Elsevier Inc. All rights reserved.