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The therapeutic role of lymphadenectomy (LND) for intrahepatic cholangiocarcinoma (ICC) patients remains ill-defined. We sought to analyze the therapeutic value of LND relative to tumor location and preoperative lymph node metastasis (LNM) risk. Patients who underwent curative-intent hepatic resection of ICC between 1990 and 2020 were included from a multi-institutional database. Therapeutic LND (tLND) was defined as LND that harvested ≥3 lymph nodes. Among 662 patients, 178 (26.9%) individuals received tLND. Patients were categorized into central type ICC (n = 156, 23.6%) and peripheral type ICC (n = 506, 76.4%). Central type harbored multiple adverse clinicopathologic factors and worse overall survival (OS) compared with peripheral type (5-year OS, central: 27.0% vs. peripheral: 47.2%, p < 0.001). After consideration of preoperative LNM risk, patients with central type and high-risk LNM who underwent tLND survived longer than individuals who did not (5-year OS, tLND: 27.9% vs. non-tLND: 9.0%, p = 0.001), whereas tLND was not associated with better survival among patients with peripheral type ICC or low-risk LNM. The therapeutic index of hepatoduodenal ligament (HDL) and other regions was higher in central type than in peripheral type, which was more pronounced among high-risk LNM patients. Central type ICC with high-risk LNM should undergo LND involving regions beyond the HDL. [ABSTRACT FROM AUTHOR]

Background: The prognostic role of tumor burden score (TBS) relative to albumin-bilirubin (ALBI) grade among patients undergoing curative-intent resection of ICC has not been examined. Methods : We identified patients who underwent curative-intent resection for ICC between 1990 and 2017 from a multi-institutional database. Multivariable analysis was performed to assess the effect of TBS relative to ALBI grade on both short- and long-term outcomes. Results: Among 724 patients, 360 (49.7%) patients had low TBS and low ALBI grade, 142 (19.6%) patients had low TBS and high ALBI grade, 138 (19.1%) patients had high TBS and low ALBI grade, and 84 patients (11.6%) had high TBS and high ALBI grade. Decreased tumor burden was associated with better long-term outcomes among patients with both low (5-year OS; low TBS vs. high TBS: 52.4% vs 21.4%; p < 0.001) and high ALBI grade (5-year OS; low TBS vs. high TBS: 40.7% vs 12.0%; p < 0.001). On multivariable analysis, higher ALBI grade was associated with greater odds of an extended hospital LOS (> 10 days) (OR 2.80, 95%CI 1.62–4.82; p < 0.001), perioperative transfusion (OR 2.04, 95%CI 1.25–3.36; p = 0.005), 90-day mortality (OR 2.56, 95%CI 1.12–5.81; p = 0.025), as well as a major complication (OR 1.99, 95%CI 1.13–3.49; p = 0.016) among patients with similar tumor burden. Of note, patients with high TBS and high ALBI grade had markedly worse overall survival compared with patients who had low TBS and low ALBI grade disease (HR 2.27; 95%CI 1.44–3.59; p < 0.001). Importantly, high TBS and high ALBI grade were strongly associated with both early recurrence (88.1%%) and 5-year risk of death (96.4%). Conclusion: Both TBS (i.e., tumor morphology) and ALBI grade (i.e., hepatic function reserve) were strong predictors of outcomes among patients undergoing ICC resection. There was an interplay between TBS and ALBI grade relative to patient prognosis after hepatic resection of ICC with high ALBI grade predicting worse outcomes among ICC patients with different TBS. [ABSTRACT FROM AUTHOR]

This study aimed to develop a holistic risk score incorporating preoperative tumor, liver, nutritional, and inflammatory markers to predict overall survival (OS) after hepatectomy for hepatocellular carcinoma (HCC). Patients who underwent curative-intent surgery for HCC between 2000 and 2020 were identified using an international multi-institutional database. Preoperative predictors associated with OS were selected and a prognostic risk score model (PreopScore) was developed and validated using cross-validation. A total of 1676 patients were included. On multivariable analysis, preoperative parameters associated with OS included α-feto protein (hazard ratio [HR]1.17, 95%CI 1.03–1.34), neutrophil-to-lymphocyte ratio (HR2.62, 95%CI 1.30–5.30), albumin (HR0.49, 95%CI 0.34–0.70), gamma-glutamyl transpeptidase (HR1.00, 95%CI 1.00–1.00), as well as vascular involvement (HR3.52, 95%CI 2.10–5.89) and tumor burden score (medium, HR3.49, 95%CI 1.62–7.58; high, HR3.21, 95%CI 1.40–7.35) on preoperative imaging. A weighted PreopScore was devised and made available online (https://yutaka-endo.shinyapps.io/PrepoScore%5fShiny/). Patients with a PreopScore 0–2, 2–3.5, and >3.5 had incrementally worse 5-year OS of 85.8%, 70.7%, and 52.4%, respectively (p < 0.001). The c-index of the test and validation cohort were 0.75 and 0.71, respectively. The PreopScore outperformed individual parameters and previous HCC staging systems. The PreopScore can be used as a better guide to preoperatively identify patients and individualize pre-/post-operative strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: The interplay of carbohydrate antigen 19-9 (CA19-9) and tumor burden score (TBS) within intrahepatic cholangiocarcinoma remains ill-defined. We evaluated the roles of TBS and CA19-9 relative to overall survival (OS) and recurrence, as well as the predictive ability of the combined TBS and CA19-9 (CTC) grading system. STUDY DESIGN: Patients undergoing liver resection for intrahepatic cholangiocarcinoma between 2000 and 2020 were identified using a multi-institutional database. The impact of CA19-9 and TBS on 5-year OS and 3-year recurrence was assessed, along with the prognostic accuracy of the CTC grading system (ie the composite score of CA19-9 level and TBS). RESULTS: Among 831 patients, the median age was 58.2 years and 482 (58.0%) were male. The median [IQR] CA19-9 level was 49.7 [17.0, 221.0] U/mL and TBS was 6.1 [4.1, 8.3]. Median [IQR] and 5-year OS were 36.9 [32.3, 43.1] months and 38.9%, respectively; 3-year recurrence was 68.9%. Five-year survival varied relative to CA19-9 (low vs high, 49.0% vs 19.7%) and TBS (low vs high, 53.6% vs 26.9%) (p < 0.001 for both). On multivariable analysis, high CA19-9 (hazard ratio [HR] 2.02, 95% CI 1.64 to 2.49) and high TBS (HR 1.64, 95% CI 1.32 to 2.06) remained independently associated with OS. In turn, the CTC grading score stratified 5-year OS (low vs intermediate vs high CTC, 57.7% vs 39.9% vs 12.6%; p < 0.001) and remained an independent prognostic factor (referent, low CTC; [intermediate CTC] HR 1.54, 95% CI 1.18 to 2.01; [high CTC] HR 3.28, 95% CI 2.47 to 4.36). CONCLUSIONS: The interplay between tumor morphology and biology dictates long-term prognosis after liver resection for intrahepatic cholangiocarcinoma. Prognostic models such as the CTC grading system may inform discussions around prognosis, as well as help identify which patients with ICC may benefit more from neoadjuvant chemotherapy rather than up-front surgery. [ABSTRACT FROM AUTHOR]

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend adjuvant therapy for patients with resectable cholangiocarcinoma (CCA). The trends in utilization and receipt of adjuvant therapy and its association with overall survival have not been well studied among patients with low-risk CCA. Methods: Patients who received systemic chemotherapy for low-risk CCA after surgical resection (2010–2017) were identified in the National Cancer Database. Low-risk CCA was defined according to NCCN guidelines as patients with R0 margins and negative regional lymph nodes. Multivariable analysis was performed to assess predictors of NCCN guideline concordance and its association with overall survival. Results: Among 4519 patients who underwent resection for low-risk CCA, 55.5% (n = 2510) had intrahepatic, 15.0% (n = 680) had perihilar, and 29.4% (n = 1329) had distal cholangiocarcinoma. Adherence to NCCN guidelines increased from 27.7% in 2010 to 41.6% in 2017 (ptrend < 0.001) for low-risk CCA. On multivariable analysis, receipt of NCCN guideline-concordant care was associated with a nearly 15% decrease in mortality hazards (HR 0.86, 95%CI 0.78–0.95, p < 0.05 ). Increased distance travelled (Ref < 12.5 miles, 50–249 miles: OR 0.55, 95%CI 0.49–0.69; ≥ 250 miles: OR 0.41, 95%CI 0.25–0.6), and care in the South (OR 0.78, 95%CI 0.64–0.95) or Midwest (OR 0.66, 95%CI 0.53–0.81) of the United States versus the Northeast was associated with not receiving guideline-concordant care. Conclusion: Adherence to evidence-based NCCN guidelines was associated with improved survival among low-risk CCA patients. Geographical disparities in the receipt of NCCN guideline-concordant care exist and may influence long-term outcomes among CCA patients. [ABSTRACT FROM AUTHOR]

The efficacy of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs), trans-arterial chemoembolization (TACE), and radiotherapy to treat hepatocellular carcinoma (HCC) has not been well-defined. We performed a meta-analysis to characterize tumor response and survival associated with multimodal treatment of HCC. PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (1990–2022). Random-effect meta-analysis was conducted to compare efficacy of treatment modalities. Odds ratios (OR) and standardized mean difference (SMD) were reported. Thirty studies (4170 patients) met inclusion criteria. Triple therapy regimen (ICI + TKI + TACE) had the highest overall disease control rate (DCR) (87%, 95% CI 83–91), while ICI + radiotherapy had the highest objective response rate (ORR) (72%, 95% CI 54%–89%). Triple therapy had a higher DCR than ICI + TACE (OR 4.49, 95% CI 2.09–9.63), ICI + TKI (OR 3.08, 95% CI 1.63–5.82), and TKI + TACE (OR 2.90, 95% CI 1.61–5.20). Triple therapy demonstrated improved overall survival versus ICI + TKI (SMD 0.72, 95% CI 0.37–1.07) and TKI + TACE (SMD 1.13, 95% CI 0.70–1.48) (both p < 0.05). Triple therapy had a greater incidence of adverse events (AEs) compared with ICI + TKI (OR 0.59, 95% CI 0.29–0.91; p = 0.02), but no difference in AEs versus ICI + TACE or TKI + TACE (both p > 0.05). The combination of ICIs, TKIs and TACE demonstrated superior tumor response and survival and should be considered for select patients with advanced HCC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Behavioral health disorders (BHDs) can often be exacerbated in the setting of cancer. We sought to define the prevalence of BHD among cancer patients and characterize the association of BHD with surgical outcomes. STUDY DESIGN: Patients diagnosed with lung, esophageal, gastric, liver, pancreatic, and colorectal cancer between 2018 and 2021 were identified within Medicare Standard Analytic Files. Data on BHD defined as substance abuse, eating disorder, or sleep disorder were obtained. Postoperative textbook outcomes (ie no complications, prolonged length of stay, 90-day readmission, or 90-day mortality), as well as in-hospital expenditures and overall survival were assessed. RESULTS: Among 694,836 cancer patients, 46,719 (6.7%) patients had at least 1 BHD. Patients with BHD were less likely to undergo resection (no BHD: 23.4% vs BHD: 20.3%; p < 0.001). Among surgical patients, individuals with BHD had higher odds of a complication (odds ratio [OR] 1.32 [1.26 to 1.39]), prolonged length of stay (OR 1.36 [1.29 to 1.43]), and 90-day readmission (OR 1.57 [1.50 to 1.65]) independent of social vulnerability or hospital-volume status resulting in lower odds to achieve a TO (OR 0.66 [0.63 to 0.69]). Surgical patients with BHD also had higher in-hospital expenditures (no BHD: $16,159 vs BHD: $17,432; p < 0.001). Of note, patients with BHD had worse long-term postoperative survival (median, no BHD: 46.6 [45.9 to 46.7] vs BHD: 37.1 [35.6 to 38.7] months) even after controlling for other clinical factors (hazard ratio 1.26 [1.22 to 1.31], p < 0.001). CONCLUSIONS: BHD was associated with lower likelihood to achieve a postoperative textbook outcome, higher expenditures, as well as worse prognosis. Initiatives to target BHD are needed to improve outcomes of cancer patients undergoing surgery. [ABSTRACT FROM AUTHOR]