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Purpose: Hepatic veno-occlusive disease (HVOD) after liver transplantation (LT) is almost always a fatal complication. We assessed the outcomes of HVOD in a single institute and analyzed a literature-based cohort. Methods: We reviewed the medical records of recipients of LT performed between 1995 and 2020 at our institute and the literature on HVOD after LT. We then analyzed the clinical features based on a "pooled" cohort of cases identified in our institute and reported in the literature. Results: HVOD was diagnosed in 3 of 331 LT recipients, all of whom died in hospital, on days 164, 12, and 13, respectively. Our comprehensive review of the literature, as well as our cases, identified eight cases of HVOD that developed within 14 days after LT (early-onset type). Early-onset HVOD had a significantly worse prognosis than HVOD that developed beyond 2 weeks after LT (non-early-onset type), which was identified in 22 cases (25.0% vs. 86.1% of the 3-month graft survival rate). The most common causes of early-onset and non-early-onset types were acute cellular rejection (50%) and drug-induced disease (50%), respectively. Conclusion: Early-onset HVOD developing within 14 days after LT has a poor prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer presents a challenge due to its high mortality rates and limited treatment options. In an effort to improve patient outcomes, neoadjuvant treatment (NAT) has emerged as a promising approach for both resectable and borderline resectable pancreatic cancer. This scoping review provides a comprehensive overview of evidence from published (n = 14) and ongoing (n = 12) randomized Phase II and III trials, shedding light on the current status of NAT. The efficacy of NAT in terms of survival benefits for patients with resectable pancreatic cancer has been still controversial. However, the efficacy of NAT has been affirmed in cases of borderline resectable pancreatic cancer, although the ideal treatment regimens remain subject to debate. Ongoing trials are actively exploring novel approaches, including immunotherapy, underscoring the dynamic nature of pancreatic cancer treatment. Future efforts aim to refine treatment strategies by integrating systemic chemotherapy with immunotherapy, guided by molecular-based biomarkers to achieve precision oncology. Pancreatic cancer (PC) is a lethal disease that requires innovative therapeutic approaches to enhance the survival outcomes. Neoadjuvant treatment (NAT) has gained attention for resectable and borderline resectable PC, offering improved resection rates and enabling early intervention and patient selection. Several retrospective studies have validated its efficacy. However, previous studies have lacked intention-to-treat analyses and appropriate resectability classifications. Randomized comparative trials may help to enhance the clinical applicability of evidence. Therefore, after searching the MEDLINE database, this scoping review presents a comprehensive summary of the evidence from published (n = 14) and ongoing (n = 12) randomized Phase II and III trials. Diverse regimens and their outcomes were explored for both resectable and borderline resectable PC. While some trials have supported the efficacy of NAT, others have demonstrated no clear survival benefits for patients with resectable PC. The utility of NAT has been confirmed in patients with borderline resectable PC, but the optimal regimens remain debatable. Ongoing trials are investigating novel regimens, including immunotherapy, thereby highlighting the dynamic landscape of PC treatment. Studies should focus on biomarker identification, which may enable precision in oncology. Future endeavors aim to refine treatment strategies, guided by precision oncology. [ABSTRACT FROM AUTHOR]

The aMAP score is a proposed model to predict the development of hepatocellular carcinoma (HCC) among high-risk patients with chronic hepatitis. The role of the aMAP score to predict long-term survival among patients following resection of HCC has not been determined. Patients undergoing resection for HCC between 2000 and 2020 were identified using a multi-institutional database. The impact of the aMAP score on long-term outcomes following HCC resection was assessed. Among 1377 patients undergoing resection for HCC, a total of 972 (70.6 %) patients had a low aMAP score (≤63), whereas 405 (29.4 %) individuals had a high aMAP score (≥64). aMAP score was associated with 5-year OS in the entire cohort (low vs high aMAP score:66.5 % vs. 54.3 %, p < 0.001). aMAP score predicted 5-year OS following resection among patients with HBV-HCC (low vs. high aMAP:68.8 % vs. 55.6 %, p = 0.01) and NASH/other-HCC (64.7 % vs. 53.7, p = 0.04). aMAP score could sub-stratify 5-year OS among patients undergoing HCC resection within (low vs. high aMAP:81.5 % vs. 67.4 %, p < 0.001) and beyond (55.9 % vs. 38.8 %, p < 0.001) Milan criteria. The aMAP score predicted postoperative outcomes following resection of HCC within and beyond Milan criteria. Apart from a surveillance tool, the aMAP score can also be used as a prognostic tool among patients undergoing resection of HCC. [ABSTRACT FROM AUTHOR]

Background: Over the last decade there has been a surge in overdose deaths due to the opioid crisis. We sought to characterize the temporal change in overdose donor (OD) use in liver transplantation (LT), as well as associated post‐LT outcomes, relative to the COVID‐19 era. Methods: LT candidates and donors listed between January 2016 and September 2022 were identified from the Scientific Registry of Transplant Recipients database. Trends in LT donors and changes related to OD were assessed pre‐ versus post‐COVID‐19 (February 2020). Results: Between 2016 and 2022, most counties in the United States experienced an increase in overdose‐related deaths (n = 1284, 92.3%) with many counties (n = 458, 32.9%) having more than a doubling in drug overdose deaths. Concurrently, there was an 11.2% increase in overall donors, including a 41.7% increase in the number of donors who died from drug overdose. In pre‐COVID‐19 overdose was the 4th top mechanism of donor death, while in the post‐COVID‐19 era, overdose was the 2nd most common cause of donor death. OD was younger (OD: 35 yrs, IQR 29–43 vs. non‐OD: 43 yrs, IQR 31–56), had lower body mass index (≥35 kg/cm2, OD: 31.2% vs. non‐OD: 33.5%), and was more likely to be HCV+ (OD: 28.9% vs. non‐OD: 5.4%) with lower total bilirubin (≥1.1 mg/dL, OD: 12.9% vs. non‐OD: 20.1%) (all p <.001). Receipt of an OD was not associated with worse graft survival (HR.94, 95% CI.88–1.01, p =.09). Conclusions: Opioid deaths markedly increased following the COVID‐19 pandemic, substantially altering the LT donor pool in the United States. [ABSTRACT FROM AUTHOR]

We report a case of reactive lymphoid hyperplasia (RLH) mimicking colorectal liver metastases (CRLM) on preoperative workup that was clinically indistinguishable. A 78-year-old woman was found to have locally-advanced sigmoid cancer (T4), and then treated with radical sigmoidectomy. One year after the surgery, plain computed tomography (CT) revealed a low-density area in the right hepatic lobe. Metastatic liver tumors could not be ruled out with CT/ magnetic resonant imaging (MRI) and positron emission tomography–CT. Based on these findings, the patient was diagnosed with CRLM at S7 of the liver. The patient underwent right posterior sectionectomy. The tumor was adjacent to the right hepatic vein; however, no invasion was observed. The patient was pathologically diagnosed as having RLH. The patient showed no signs of recurrence 16 months after initial surgery. RLH is clinically indistinguishable from CRLM. Further evaluation is required to elucidate the effective strategies of detecting and treating hepatic RLH. [ABSTRACT FROM AUTHOR]

BACKGROUND: Social determinants of health can impact the quality of liver transplantation (LT) care. We sought to assess whether the association between neighborhood deprivation and transplant outcomes can be mitigated by receiving care at high-quality transplant centers. STUDY DESIGN: In this population-based cohort study, patients who underwent LT between 2004 and 2019 were identified in the Scientific Registry of Transplant Recipients. LT-recipient neighborhoods were identified at the county level and stratified into quintiles relative to Area Deprivation Index (ADI). Transplant center quality was based on the Scientific Registry of Transplant Recipients 5-tier ranking using standardized transplant rate ratios. Multivariable Cox regression was used to assess the relationship between ADI, hospital quality, and posttransplant survival. RESULTS: A total of 41,333 recipients (median age, 57.0 [50.0 to 63.0] years; 27,112 [65.4%] male) met inclusion criteria. Patients residing in the most deprived areas were more likely to have nonalcoholic steatohepatitis, be Black, and travel further distances to reach a transplant center. On multivariable analysis, post-LT long-term mortality was associated with low-vs high-quality transplant centers (hazard ratio [HR] 1.19, 95% CI 1.07 to 1.32), as well as among patients residing in high-vs low-ADI neighborhoods (HR 1.25, 95% CI 1.16 to 1.34; both p = 0.001). Of note, individuals residing in high- vs low-ADI neighborhoods had a higher risk of long-term mortality after treatment at a low-quality (HR 1.31, 95% CI 1.06 to 1.62, p = 0.011) vs high-quality (HR 1.12, 95% CI 0.83 to 1.52, p = 0.471) LT center. CONCLUSIONS: LT at high-quality centers may be able to mitigate the association between posttransplant survival and neighborhood deprivation. Investments and initiatives that increase access to referrals to high-quality centers for patients residing in higher deprivation may lead to better outcomes and help mitigate disparities in LT. [ABSTRACT FROM AUTHOR]

This study aimed to develop a tool based on preoperative factors to predict the risk of perioperative complications based on the Comprehensive Complication Index (CCI) and long-term survival outcomes after liver resection for primary liver cancer. Patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent hepatectomy between 1990 and 2020 were identified using a multi-institutional international database. Among 1411 patients who underwent curative-intent hepatic resection (HCC: 997, 70.7%; ICC: 414, 29.3%), median patient age was 66.0 years (IQR, 57.0–73.0), and most patients were male (n = 1001, 70.9%). In the postoperative setting, 699 patients (49.5%) experienced a complication; moreover, 112 patients (7.9%) had major complications. Although most patients had a favorable risk complication-overall survival (CompOS) profile (CCI score > 40 risk of <30% and median survival of >5 years: n = 778, 55.1%), 553 patients (39.2%) had an intermediate-risk profile, and 80 patients (5.7%) had a very unfavorable risk profile (CCI score > 40 risk of ≥30% and/or median survival of ≤1.5 years). The areas under the curve of the test and validation cohorts were 0.73 and 0.76, respectively. The CompOS risk model accurately stratified patients relative to short- and long-term risks, identifying a subset of patients at a high risk of major complications and poor overall survival. [ABSTRACT FROM AUTHOR]

The internet is a common source of health information for patients. Interactive online artificial intelligence (AI) may be a more reliable source of health-related information than traditional search engines. This study aimed to assess the quality and perceived utility of chat-based AI responses related to 3 common gastrointestinal (GI) surgical procedures. A survey of 24 questions covering general perioperative information on cholecystectomy, pancreaticoduodenectomy (PD), and colectomy was created. Each question was posed to Chat Generative Pre-trained Transformer (ChatGPT) in June 2023, and the generated responses were recorded. The quality and perceived utility of responses were independently and subjectively graded by expert respondents specific to each surgical field. Grades were classified as "poor," "fair," "good," "very good," or "excellent." Among the 45 respondents (general surgeon [n = 13], surgical oncologist [n = 18], colorectal surgeon [n = 13], and transplant surgeon [n = 1]), most practiced at an academic facility (95.6%). Respondents had been in practice for a mean of 12.3 years (general surgeon, 14.5 ± 7.2; surgical oncologist, 12.1 ± 8.2; colorectal surgeon, 10.2 ± 8.0) and performed a mean 53 index operations annually (cholecystectomy, 47 ± 28; PD, 28 ± 27; colectomy, 81 ± 44). Overall, the most commonly assigned quality grade was "fair" or "good" for most responses (n = 622/1080, 57.6%). Most of the 1080 total utility grades were "fair" (n = 279, 25.8%) or "good" (n = 344, 31.9%), whereas only 129 utility grades (11.9%) were "poor." Of note, ChatGPT responses related to cholecystectomy (45.3% ["very good"/"excellent"] vs 18.1% ["poor"/"fair"]) were deemed to be better quality than AI responses about PD (18.9% ["very good"/"excellent"] vs 46.9% ["poor"/"fair"]) or colectomy (31.4% ["very good"/"excellent"] vs 38.3% ["poor"/"fair"]). Overall, only 20.0% of the experts deemed ChatGPT to be an accurate source of information, whereas 15.6% of the experts found it unreliable. Moreover, 1 in 3 surgeons deemed ChatGPT responses as not likely to reduce patient-physician correspondence (31.1%) or not comparable to in-person surgeon responses (35.6%). Although a potential resource for patient education, ChatGPT responses to common GI perioperative questions were deemed to be of only modest quality and utility to patients. In addition, the relative quality of AI responses varied markedly on the basis of procedure type. [ABSTRACT FROM AUTHOR]

Metastatic disease in the regional lymph nodes (LNs) is a strong indicator of worse outcomes among patients after curative-intent resection of ampullary cancer (AC). This study aimed to ascertain the threshold number of examined LNs (ELNs) for AC to compare the prognosis accuracy of various nodal classification schemes relative to long-term prognosis. Patients who underwent pancreatoduodenectomy (PD) for AC (2004–2019) were identified using the National Cancer Database. Locally weighted regression scatter plot smoothing (LOWESS) curves were used to ascertain the optimal cut point for ELNs. The accuracy of the American Joint Committee on Cancer N classification, LN ratio, and log odds transformation (LODDS) ratio to stratify patients relative to survival was examined. Among 8127 patients with AC, 67% were male with a median age of 67 years (IQR, 59–74). Tumors were most frequently classified as T3 (34.9%), followed by T2 (30.6%); T1 (12.9%) and T4 (17.6%) were less common. LN metastasis was identified in 4606 patients (56.7%). Among patients with nodal disease, 37.0% and 19.7% had N1 and N2 disease, respectively. The LOWESS curves identified an inflection cutoff point in the hazard of survival at 20 ELNs. The survival benefit of 20 ELNs was more pronounced among patients without LN metastasis vs patients with N1 disease (median overall survival [OS]: 54.1 months [IQR, 45.9–62.1] in ≥20 ELNs vs 39.0 months [IQR, 35.8–42.2] in <20 ELNs; P <.001) or N2 disease (median OS: 22.5 months [IQR, 18.9–26.2] in ≥20 ELNs vs 25.4 months [IQR, 23.3–27.6] in <20 ELNs; P <.001). When comparing the 4 different N classification schemes, the LODDS classification scheme yielded the highest predictive ability. Evaluation of a minimum of 20 LNs was needed to stratify patients with AC relative to the prognosis and to minimize stage migration. The LODDS nodal classification scheme had the highest prognostic accuracy to differentiate survival among patients after PD for AC. [ABSTRACT FROM AUTHOR]

A preoperative predictive score for hepatocellular carcinoma (HCC) can help stratify patients who undergo resection relative to long-term outcomes and tailor treatment strategies. Patients who underwent curative-intent hepatectomy for HCC between 2000 and 2020 were identified from an international multi-institutional database. A risk score (mFIBA) was developed using an Eastern cohort and then validated using a Western cohort. Among 957 patients, 443 and 514 patients were included from the Eastern and Western cohorts, respectively. On multivariable analysis, alpha-feto protein (HR1.97, 95%CI 1.42–2.72), neutrophil-to-lymphocyte ratio (HR1.74, 95%CI 1.28–2.38), albumin-bilirubin grade (HR1.66, 95%CI 1.21–2.28), and imaging tumor burden score (HR1.25, 95%CI 1.12–1.40) were associated with OS. The c-index in the Eastern test and Western validation cohorts were 0.69 and 0.67, respectively. Notably, mFIBA score outperformed previous HCC staging systems. 5-year OS incrementally decreased with an increase in mFIBA. On multivariable Cox regression analysis, the mFIBA score was associated with worse OS (HR1.18, 95%CI 1.13–1.23) and higher risk of recurrence (HR1.16, 95%CI 1.11–1.20). An easy-to-use calculator of the mFIBA score was made available online (https://yutaka-endo.shinyapps.io/mFIBA%5fscore/). The online mFIBA calculator may help surgeons with clinical decision-making to individualize perioperative treatment strategies for patients undergoing resection of HCC. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation (LT) has been considered a potential curative treatment for patients with very early intrahepatic cholangiocarcinoma (ICC) and cirrhosis, yet the survival benefit of LT has not been well defined. This study aimed to compare the long-term survival outcomes of patients who underwent LT with that of individuals who received resection and non-curative intent treatment (non-CIT). Methods: Patients who underwent LT, hepatectomy, and non-CIT between 2004 and 2018 were included in the National Cancer Database. Survival benefits of LT over resection and non-CIT were analyzed relative to overall survival (OS). Results: Among 863 patients, 54 (6.3%) underwent LT, while 342 (39.6%) underwent surgical resection, and 467 (54.1%) received non-CIT, respectively. While the rates of non-CIT increased over time, the percentages of LT remained consistent during the study period. LT patients had similar 5-year OS to individuals who underwent resection (referent, resection: LT, HR 0.95, 95%CI 0.84–1.58, p=0.84). In contrast, 5-year OS was better among patients who underwent LT versus individuals who had non-CIT after controlling other variables using propensity score overlapping weighting (5-year OS, LT 57.1% vs. LR 25.8%, p<0.001). Conclusions: The outcomes of very early ICC patients who underwent LT were similar to individuals who underwent hepatectomy, but better than patients treated with non-CIT. LT should be may be a consideration as a treatment option for patients with early stage ICC who are unsuitable candidates for resection. [ABSTRACT FROM AUTHOR]

Introduction: The reasons for the geographic disparities in liver‐related mortality across the US remain ill‐defined. We sought to investigate the impact of travel distance to liver transplantation (LT) programs and social vulnerability on county differences in liver‐related mortality. Methods: Data on LT registrants were obtained from the Scientific Registry of Transplant Recipients Standard Analytic Files (SRTR SAFs) between 2004 and 2019. Liver‐related mortality data were obtained from the Center for Disease Control and Prevention's Wide‐ranging Online Data for Epidemiologic Research (CDC WONDER) platform. Spatial epidemiological clustering of county‐level LT registration and liver‐related mortality rates was determined using local Moran's I. Comparison analyses assessed social vulnerability index (SVI) and travel distance within various county clusters. Results: Among 151 864 LT waitlist registrants who were diagnosed with liver disease due to hepatitis C virus (HCV) or hepatitis B virus (HBV) (n = 68 479, 45.1%), alcohol (n = 38 328, 25.2%), non‐alcoholic steatohepatitis (NASH) (n = 17 485, 11.5%), liver tumors (n = 16 644, 11.0%), and other diseases (n = 10 928, 7.2%), median SVI was 59.3 (IQR, 40.1–83.4). SVI (76.2 vs. 24.3, p <.001) was greater in the highest versus lowest liver‐related mortality quartiles. The travel distances to LT centers (143.1 miles vs. 107.2 miles, p <.001) was longer in the lowest versus highest LT registration quartiles. Counties with low LT registration rates and high liver‐related mortality rates were associated with long travel distances and high SVI. In contrast, while counties with high LT registration rates and high liver‐related mortality rates had comparable SVI, travel distance was relatively shorter. Conclusion: Counties with greater SVIs were associated with higher liver‐related mortality, with the highest SVI counties having the highest overall liver‐related mortality. Longer travel distances were associated with higher liver‐related mortality. These findings highlight the impact of social determinants of health (SDOH) on liver disease outcomes. [ABSTRACT FROM AUTHOR]

Background: The prognostic impact of major postoperative complications (POCs) for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. We sought to analyze the relationship between POCs and outcomes relative to lymph node metastases (LNM) and tumor burden score (TBS). Methods: Patients who underwent resection of ICC between 1990–2020 were included from an international database. POCs were defined according to Clavien-Dindo classification ≥ 3. The prognostic impact of POCs was estimated relative to TBS categories (i.e., high and low) and lymph node status (i.e., N0 or N1). Results: Among 553 patients who underwent curative-intent resection for ICC, 128 (23.1%) individuals experienced POCs. Low TBS/N0 patients who experienced POCs presented with a higher risk of recurrence and death (3-year cumulative recurrence rate; POCs: 74.8% vs. no POCs: 43.5%, p = 0.006; 5-year overall survival [OS], POCs 37.8% vs. no POCs 65.8%, p = 0.003), while POCs were not associated with worse outcomes among high TBS and/or N1 patients. The Cox regression analysis confirmed that POCs were significant predictors of poor outcomes in low TBS/N0 patients (OS, hazard ratio [HR] 2.91, 95%CI 1.45–5.82, p = 0.003; recurrence free survival [RFS], HR 2.42, 95%CI 1.28–4.56, p = 0.007). Among low TBS/N0 patients, POCs were associated with early recurrence (within 2 years) (Odds ratio [OR] 2.79 95%CI 1.13–6.93, p = 0.03) and extrahepatic recurrence (OR 3.13, 95%CI 1.14–8.54, p = 0.03), in contrast to patients with high TBS and/or nodal disease. Conclusions: POCs were independent, negative prognostic determinants for both OS and RFS among low TBS/N0 patients. Perioperative strategies that minimize the risk of POCs are critical to improving prognosis, especially among patients harboring favorable clinicopathologic features. [ABSTRACT FROM AUTHOR]

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: Hospital volume affects outcomes of patients who underwent resection for hepatocellular carcinoma (HCC). We sought to assess the impact of minimally invasive hepatectomy (MIH) volume on short- and long-term outcomes among patients with HCC. Methods: Patients who underwent MIH for HCC from 2010 to 2018 were identified from the National Cancer Database. Multivariable modeling with restricted cubic splines (RCS) was utilized to identify the MIH hospital volume threshold. Textbook outcome (TO) was defined as no conversion to open resection, negative margins after resection (R0), no extended length-of-stay, no readmission, and no 90-day mortality. Results: Among 3268 patients who underwent MIH for HCC, median age was 65.0 (IQR 59.0–72.0) and the majority was male (n = 2308, 70.6%). MIH hospital volume ranged from 1 to 87 cases, with a median of 13 (IQR 7–23). Overall, 2151 (60.9%) patients achieved TO after resection. While particularly high rates of achievement were found for no 90-day mortality (n = 3106, 95.0%), no readmission (n = 3153, 96.5%), and R0 resection (n = 3,017, 92.3%), other TO components including no conversion to open (n = 2778, 85.0%) and no prolonged LOS (n = 2584, 79.1%) were achieved less frequently. Patients treated at high-volume centers (≥50 MIH cases) were more likely to experience TO (high volume centers, n = 334, 68.7% vs. low volume centers, n = 1656, 59.5%, p < 0.001) and better long-term survival (5-year OS; high volume centers, 64.7% vs. low volume centers, 54.6%, p < 0.001). Conclusions: MIH hospital volume was associated with a higher likelihood of achieving TO and improved long-term survival among patients undergoing resection of HCC. [ABSTRACT FROM AUTHOR]

A difference in OS among patients who underwent LDLT versus DDLT was also observed, depicted by a flat hazard curve for LDLT versus a multi-peak curve for DDLT. Keywords: Liver transplantation; Colorectal liver metastases; Hazard function EN Liver transplantation Colorectal liver metastases Hazard function 1720 1722 3 08/11/23 20230801 NES 230801 Introduction Few studies regarding liver transplantation (LT) for unresectable colorectal liver metastases (urCRLM) have been published.[1]-[3] Due to the paucity of literature, dynamic changes in risk of death and recurrence have been poorly documented. Although undoubtedly multifactorial, this difference in OS may have been attributable to patients undergoing DDLT who had a longer waitlist duration; however, the data do not inform which type of LT (i.e., LDLT vs. [Extracted from the article]

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]

Purpose: The postoperative mortality rate of distal pancreatectomy is lower than that of pancreaticoduodenectomy, although persistent complications may occur after distal pancreatectomy. Fluid collection (FC) is frequently observed after distal pancreatectomy; however, FC may occasionally progress to postoperative intra-abdominal abscess (PIAA), which requires conservative or progressive interventional treatment. This study aimed to compare the status between patients with or without PIAA, identify predictive factors for PIAA and clinically relevant postoperative pancreatic fistula, and investigate the clinical characteristics of patients with PIAA with interventional drainage. Methods: We retrospectively reviewed data of patients who underwent distal pancreatectomy between January 2012 and December 2019 at two high-volume centers, where hepatobiliary-pancreatic surgeries were performed by expert specialist surgeons. Logistic regression analysis was performed to determine the predictive factors for PIAA. Results: Overall, 242 patients were analyzed, among whom 49 (20.2%) had PIAA. The median postoperative period of PIAA formation was 9 (range: 3–49) days. Among the 49 patients with PIAA, 25 (51.0%) underwent percutaneous ultrasound, computed tomography, or endoscopic ultrasound-guided interventions for PIAA. In the univariate analysis, preoperative indices representing abdominal fat mass (i.e., body mass index, subcutaneous fat area, and visceral fat area) were identified as predictive factors for PIAA; in the multivariate analysis, C-reactive protein (CRP) level (continuous variable) on postoperative day (POD) 3 (odds ratio: 1.189, 95.0% confidence interval: 1.111 − 1.274; P < 0.001) was the only independent and significant predictive factor for PIAA. Conclusions: CRP level on POD 3 was an independent and significant predictive factor for PIAA after distal pancreatectomy. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a predictive model to identify individuals most likely to derive overall survival (OS) benefit from adjuvant chemotherapy (AC) after hepatic resection of intrahepatic cholangiocarcinoma (ICC). Patients who underwent hepatic resection of ICC between 1990 and 2020 were identified from a multi-institutional database. Factors associated with worse OS were identified and incorporated into an online predictive model to identify patients most likely to benefit from AC. Among 726 patients, 189 (26.0%) individuals received AC. Factors associated with OS on multivariable analysis included CA19-9 (Hazard Ratio [HR]1.17, 95%CI 1.04–1.31), tumor burden score (HR1.09, 95%CI 1.04–1.15), T-category (T2/3/4, HR1.73, 95%CI 1.73–2.64), nodal disease (N1, HR3.80, 95%CI 2.02–7.15), tumor grade (HR1.88, 95%CI 1.00–3.55), and morphological subtype (HR2.19, 95%CI 1.08–4.46). A weighted predictive score was devised and made available online (https://yutaka-endo.shinyapps.io/ICCrisk%5fmodel%5ffor%5fAC/). Receipt of AC was associated with a survival benefit among patients at high/medium-risk (high: no AC, 0% vs. AC, 20.6%; medium: no AC, 36.4% vs. 40.8%; both p < 0.05) but not low-risk (low: no AC, 65.1% vs. AC, 65.1%; p = 0.73) tumors. An online predictive model based on tumor characteristics may help identify which patients may benefit the most from AC following resection of ICC. [ABSTRACT FROM AUTHOR]

Background: Resection of Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) remains controversial. While not recommended by the BCLC algorithm, some patients may indeed benefit from hepatectomy. We sought to identify that subset of patients who might derive long-term survival benefit from resection. Methods: Intermediate-stage HCC patients who underwent curative-intent resection were identified from an international multi-institutional database. Factors associated with long-term prognosis were identified using multivariate analysis and a risk score was developed and assessed. Results: Among 194 patients, most individuals had two tumors (n = 123, 63.4%) with a median size of 6.0 cm (IQR, 4.0–8.4) for a median tumor burden score (TBS) of 6.5 (IQR, 5.0–9.1); median alpha-fetoprotein (AFP) was 23.9 ng/mL (IQR, 5.0–503.2), and median overall survival (OS) was 69 months (IAR, 60.7–77.3). Factors associated with OS included AFP (referent ≤ 20 ng/mL, > 20 ng/mL: HR 1.78 95%CI, 1.09–2.89) and TBS (referent TBS ≤ 8.0, TBS > 8.0: HR 1.72 95%CI, 1.07–2.75). While 71 (36.6%) patients had neither risk factor, 79 (40.7%) and 44 (22.7%) had 1 or 2, respectively. A simplified score stratified patients relative to recurrence-free survival (RFS) (0: 33.6% vs. 1: 18.0% vs. 2: 14.7%) (AUC 0.60) and recurrence time (i.e., < 6 months after surgery) (0: 21.3% vs. 1: 43.1% vs. 2: 68.6%) (AUC 0.69) (both p < 0.001). Of note, a higher score was also associated with incrementally worse 5-year OS (0: 68.1% vs. 1: 61.0% vs. 2: 29.9%) (AUC 0.62) (p < 0.001). Conclusion: Long-term OS and RFS outcomes varied considerably. Using a simple risk score, patients with low AFP and low TBS were identified as the subset of individuals most likely to benefit from resection. [ABSTRACT FROM AUTHOR]

Background: Post-hepatectomy liver failure (PHLF) is a dreaded complication following liver resection for hepatocellular carcinoma (HCC) with a high mortality rate. We sought to develop a score based on preoperative factors to predict PHLF.Methods: Patients who underwent resection for HCC between 2000 and 2020 were identified from an international multi-institutional database. Factors associated with PHLF were identified and used to develop a preoperative comorbidity-tumor burden-liver function (CTF) predictive score.Results: Among 1785 patients, 106 (5.9%) experienced PHLF. On multivariate analysis, several factors were associated with PHLF including high Charlson comorbidity index (CCI ≥ 5) (OR 2.80, 95%CI, 1.08-7.26), albumin-bilirubin (ALBI) (OR 1.99, 95%CI, 1.10-3.56), and tumor burden score (TBS) (OR 1.06, 95%CI, 1.02-1.11) (all p < 0.05). Using the beta-coefficients of these variables, a weighted predictive score was developed and made available online ( https://alaimolaura.shinyapps.io/PHLFriskCalculator/ ). The CTF score (c-index = 0.67) performed better than Child-Pugh score (CPS) (c-index = 0.53) or Barcelona clinic liver cancer system (BCLC) (c-index = 0.57) to predict PHLF. A high CTF score was also an independent adverse prognostic factor for survival (HR 1.61, 95%CI, 1.12-2.30) and recurrence (HR 1.36, 95%CI, 1.08-1.71) (both p = 0.01).Conclusion: Roughly 1 in 20 patients experienced PHLF following resection of HCC. Patient (i.e., CCI), tumor (i.e., TBS), and liver function (i.e., ALBI) factors were associated with risk of PHLF. These preoperative factors were incorporated into a novel CTF tool that was made available online, which outperformed other previously proposed tools. [ABSTRACT FROM AUTHOR]

Purpose. In the Philippines, drug-resistant tuberculosis (DRTB) is a growing concern. Healthcare workers face challenges in retaining patients with DRTB in care. This study intends to understand their perspectives on the factors that influence patient treatment outcomes and to propose potential programmatic solutions for strengthening care services for the patients. Methods. A mixed-methods study was conducted in the Philippines between December 2017 and March 2018 to understand the major barriers for healthcare workers to provide quality care to DRTB patients across the care continuum. In the quantitative phase, healthcare workers participated in an online survey; in the qualitative phase, in-depth interviews were conducted with a select number of the survey respondents to better understand their survey responses. Results. 272 healthcare workers participated in the survey, and of those, 11 were interviewed. Survey results identified economic constraints, patient perceptions of care, family-related concerns, and limited accessibility to healthcare services as the major patient-related barriers across the care continuum. Major health-system-related barriers were insufficient human resources, lack of financial and political support, and limited knowledge about DRTB by healthcare providers. Interviews revealed more elaborate, contextualized, and nuanced aspects of each of the major challenges. The elaborated patient-related barriers included expenses needed during treatment (e.g., transportation); fear of being stigmatized by family, community, or healthcare staff; worries about adverse drug reactions from medication; a lack of family support; and the location of patients' homes. The health-system-related barriers revealed through interviews included the limited capacities of facility staff to provide DRTB care due to insufficient human resources; the shortage of funds to support treatment completion (e.g., transportation allowance and food package for patients, service vehicles and mobile phone costs for outreach actions at the facility level); and discrimination by healthcare staff against patients with DRTB attributed to the staff's limited knowledge and experiences of treating the patients. Conclusion. This study identified the main barriers for DRTB facility staff in the Philippines from the perspectives of providers. Further exploration of the barriers and best practices in facilities may be useful for improving DRTB care in the Philippines. [ABSTRACT FROM AUTHOR]

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life‐saving procedure and to correct the underlying enzymatic defect, respectively. Case presentation: We report a 20‐year‐old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP‐induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late‐onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high‐risk situation for bile leakage from the non‐communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. Conclusion: Physicians should recognize the potentially rapid and life‐threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post‐transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft. [ABSTRACT FROM AUTHOR]

Background: Pancreatic fistulas remain a significant concern after pancreatectomy owing to the associated high risk of mortality and high costs. It is not possible to perform preoperative risk stratification for all patients. This study aimed to evaluate the usefulness of the measurement of portal vein (PV) distance as a predictive indicator of pancreatic fistula development after pancreatoduodenectomy and compare it with the usefulness of other indicators such as body mass index (BMI), and abdominal fat area. Methods: Patient characteristics, preoperative laboratory data, radiographic findings, and their association with pancreatic fistula development after pancreatoduodenectomy were analyzed for 157 patients who underwent resection during 2011–2017. Clinically relevant postoperative pancreatic fistulas (CR-POPF) were defined as Grade B or C fistulas based on the International Study Group of Pancreatic Surgery (ISGPS) 2016 consensus. Results: CR-POPF developed in 38 patients (24.2%). Multivariate logistic regression indicated that PV distance and BMI were potential candidates for predictive models for pancreatic fistula development, and small pancreatic duct diameter, diabetes mellitus development, and pathology of non-pancreatic cancers were independent factors for CR-POPF. When comparing the two risk models (PV distance- and BMI-based models), the PV distance-derived risk model was compatible to the BMI-based stratification models (area under the curve 0.831 vs. 0.830). Conclusions: PV distance was confirmed to be a useful risk predictor for CR-POPF. This research highlighted the efficacy of abdominal thickness measurement, which is simple and easily applicable in the clinical setting. [ABSTRACT FROM AUTHOR]

Social determinants of health can play an important role in patient health. Privilege is a right, benefit, advantage, or opportunity that can positively affect all social determinants of health. We sought to assess variations in the prevalence of privilege among patient populations and define the association of privilege on postoperative surgical outcomes. Medicare beneficiaries who underwent elective coronary artery bypass grafting, abdominal aortic aneurysm repair, total hip arthroplasty, total knee arthroplasty, colectomy, and lung resection were identified. The Index of Concentration of Extremes (ICE), a validated metric of both social spatial polarization and privilege was calculated and merged with county-level data obtained from the American Community Survey. Textbook outcome (TO) was defined as absence of postoperative complications, extended length of stay, 90-day mortality, and 90-day readmission. Multivariable regression analysis was performed to assess the relationship between ICE and TO. Among 1,885,889 Medicare beneficiaries who met inclusion criteria, 655,980 (34.8%) individuals resided in areas with the highest privilege (i.e., White, high-income homogeneity), whereas 221,314 (11.7%) individuals resided in areas of the lowest privilege (i.e., Black, low-income homogeneity). The overall incidence of TO was 66.2% (n = 1,247,558). On multivariable regression, residence in the most advantaged neighbourhoods was associated with a lower chance of surgical complications (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.88-0.91), a prolonged length of stay (OR 0.81, 95% CI 0.79-82), 90-day readmission (OR 0.94, 95% CI 0.92-0.95), and 90-day mortality (OR 0.71, 95% CI 0.68-0.74) (all P < 0.001). Residence in the most privileged areas was associated with 19% increased odds of achieving TO (OR 1.19, 95% CI 1.18-1.21), as well as a 6% reduction in Medicare expenditures versus individuals in the least privileged counties (OR 0.94, 95% CI 0.94-0.94) (both P < 0.001). Privilege, based on the ICE joint measure of racial/ethnic and economic spatial concentration, was strongly associated with the likelihood to achieve an "optimal" TO following surgery. As healthcare is a basic human right, privilege should not be associated with disparities in surgical care. [ABSTRACT FROM AUTHOR]

Although receipt of neoadjuvant chemotherapy has been identified to improve unfavorable survival outcomes among patients with locally advanced gastric cancer (LAGC), several randomized controlled trials have not demonstrated a difference in oncological outcomes/overall survival (OS) among patients undergoing minimally invasive surgery (MIS) versus open gastrectomy. This study aimed to investigate National Comprehensive Cancer Network (NCCN) guideline adherence and textbook oncological outcome (TOO) among patients undergoing MIS versus open surgery for LAGC. In this cross-sectional study, patients with stage II/III LAGC (cT2-T4N0-3M0) who underwent curative-intent treatment between 2013 and 2019 were evaluated using the National Cancer Database. Multivariable analysis was performed to assess the association between surgical approach, NCCN guideline adherence, TOO, and OS. The study was registered on the International Standard Randomised Controlled Trial Number registry (registration number: ISRCTN53410429) and conducted according to the Strengthening The Reporting Of Cohort Studies in Surgery and Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Among 13,885 patients, median age at diagnosis was 68 years (IQR, 59-76); most patients were male (n = 9887, 71.2%) and identified as White (n = 10,295, 74.1%). Patients who underwent MIS (n = 4692, 33.8%) had improved NCCN guideline adherence and TOO compared with patients who underwent open surgery (51.3% vs 43.5% and 36.7% vs 27.3%, respectively; both P <.001). Adherence to NCCN guidelines and likelihood to achieve TOO increased from 2013 to 2019 (35.6% vs 50.9% and 31.4% vs 46.4%, respectively; both P <.001). Moreover, improved median OS was observed among patients with NCCN guideline adherence and TOO undergoing MIS versus open surgery (57.3 vs 49.8 months [ P =.041] and 68.4 vs 60.6 months [ P =.025], respectively). An overall increase in guideline-adherent treatment and achievement of TOO among patients with LAGC undergoing multimodal and curative-intent treatment in the United States was observed. Adoption of minimally invasive gastrectomy may result in improved short- and long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Both textbook outcome (TO) and hospital volume have been identified as quality metrics following cancer surgery. We sought to examine whether TO or hospital volume is more important relative to long-term survival following surgical resection of hepatocellular carcinoma (HCC). Methods: Patients who underwent surgery for HCC between 2004 and 2018 were identified using the National Cancer Database. TO was defined as R0 margin resection, no extended length of stay, no 30-day readmissions, and no 90-day mortality. The impact of TO and hospital case volume on long-term survival was determined using multivariable Cox regression. Results: Among 24,895 patients who underwent HCC resection, 9.0% (n = 2,252), 79.5% (n = 19,787), and 11.5% (n = 2,856) of patients were operated on at low-, medium-, and high-volume hospitals, respectively. Treatment at high-volume hospitals and achievement of a post-operative TO were independently associated with improved 5-year overall survival (OS). Pairwise comparison demonstrated that patients treated at high-volume hospitals who did not achieve a TO still had a better 5-year OS versus individuals treated at low-volume hospitals who did achieve a TO (5-year OS, no TO vs. TO: low-volume hospitals, 26.5% vs. 48.6%; high volume hospitals: 62.6% vs. 74.9%, respectively; p < 0.001). Overall, resection of HCC at a high-volume hospital was independently associated with a 54% reduction in mortality. Conclusion: Long-term survival following HCC resection was largely associated with hospital case volume rather than TO. The effect of TO on long-term outcomes was largely mediated by hospital case volume highlighting the importance of centralization of care for patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Malnutrition has been linked to the development of hepatopancreatobiliary (HPB) cancer. We sought to examine the association between food swamps and food deserts on surgical outcomes of patients with HPB cancer. Methods: Patients who underwent surgery for HPB cancer between 2014 and 2020 were identified from the Medicare Standard Analytic Files. Patient-level data were linked to the United States Department of Agriculture data on food swamps and deserts. Multivariable regression was performed to examine the association between the food environment and outcomes. Results: Among 53,426 patients, patients from the worse food environment were more likely to be Black, have a higher Charlson Comorbidity Index, and reside in areas with high social vulnerability. Following surgery, the overall incidence of textbook outcome (TO) was 41.6% (n = 22,220). Patients residing in the worse food environments less often achieved a TO versus individuals residing in the healthiest food environments (food swamp: 39.4% vs. 43.9%; food desert: 38.5% vs 42.2%; p < 0.05). On multivariable analysis, individuals residing in the poorest food environments were associated with lower odds of achieving TO compared with individuals living in healthiest food environments (food swamp: OR 0.83, 95%CI 0.75–0.92, food desert: OR 0.86, 95%CI 0.76–0.97; both p < 0.05). Conclusion: The surrounding food environment of patients may serve as a modifiable socio-demographic risk factor that contributes to disparities in surgical outcomes of HPB cancer. [ABSTRACT FROM AUTHOR]

Background: Patients with hepatocellular carcinoma (HCC) may have a heterogeneous presentation, as well as different long-term outcomes following surgical resection. We sought to use machine learning to cluster patients into different prognostic groups based on preoperative characteristics. Methods: Patients who underwent curative-intent liver resection for HCC between 2000 and 2020 were identified from a large international multi-institutional database. A hierarchical cluster analysis was performed based on preoperative factors to characterize patterns of presentation and define disease-free survival (DFS). Results: Among 966 with HCC, 3 distinct clusters were identified: Cluster 1 (n = 160, 16.5%), Cluster 2 (n = 537, 55.6%) and Cluster 3 (n = 269, 27.8%). Cluster 1 (n = 160, 16.5%) consisted of female patients (n = 160, 100%), low inflammation-based scores, intermediate tumor burden score (TBS) (median: 4.71) and high alpha-fetoprotein (AFP) levels (median 41.3 ng/mL); Cluster 2 consisted of male individuals (n = 537, 100%), mainly with a history of HBV infection (n = 429, 79.9%), low inflammation-based scores, intermediate AFP levels (median 26.0 ng/mL) and lower TBS (median 4.49); Cluster 3 was comprised of older patients (median age 68 years) predominantly male (n = 248, 92.2%) who had low incidence of HBV/HCV infection (7.1% and 8.2%, respectively), intermediate AFP levels (median 16.8 ng/mL), high inflammation-based scores and high TBS (median 6.58). Median DFS worsened incrementally among the three different clusters with Cluster 3 having the lowest DFS (Cluster 1: median not reached; Cluster 2: 34 months, 95% CI 23.0–48.0, Cluster 3: 19 months, 95% CI 15.0–29.0, p < 0.05). Conclusion: Cluster analysis classified HCC patients into three distinct prognostic groups. Cluster assignment predicted DFS following resection of HCC with the female cluster having the most favorable prognosis following HCC resection. [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]

Background: The Affordable Care Act (ACA) transformed the US healthcare system, expanding healthcare insurance coverage. However, its impact on rare malignancies that lack an established screening strategy such as intrahepatic cholangiocarcinoma (ICC) remains ill-defined.Methods: Patients diagnosed with ICC were identified from the National Cancer Database and divided relative to ACA implementation. Multivariate logistic regression analyses were performed to evaluate association with stage at diagnosis, receipt of surgical and multimodal treatments, and survival.Results: Among the 9095 patients, 5636 (62.0%) were diagnosed before and 3459 (38.0%) after the implementation of the ACA. Across US regions, rates of early-stage diagnosis increased in the post-ACA era (Northeast, 62.9% vs. 85.2%; South, 63.7% vs. 78.5%; Midwest, 62.1% vs. 83.4%; West, 55.5% vs. 75.4%; p < 0.001). On multivariate analyses, the post-ACA era was associated with increased early-stage diagnosis (OR = 2.19; 95% CI 1.79-2.69), and receipt of surgical treatment (OR = 1.19, 95% CI 1.03-1.38) (both p < 0.01). Furthermore, the ACA's Medicaid expansion (ME) was also associated with improved overall survival (HR = 0.89, 95% CI 0.80-0.99, p = 0.038). Of note, although the odds of receiving surgical treatment increased after ACA for non-Hispanic White patients (OR = 1.34; 95% CI 1.20-1.49; p < 0.001), no such effect was observed in non-Hispanic Black (OR = 1.01, 95% CI 0.71-1.45), Hispanic (OR = 1.44, 95% CI 0.99-2.09), or others (OR = 1.43, 95% CI 0.98-2.10) (all p > 0.05).Conclusions: The implementation of the ACA increased rates of early diagnosis and receipt of surgical treatment. Additionally, ME improved short- and long-term outcomes. However, racial and socioeconomic disparities persist, resulting in inequitable access to care and outcomes for patients with ICC. [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: We sought to define surgical outcomes among elderly patients with Alzheimer's disease and related dementias (ADRD) following major thoracic and gastrointestinal surgery. Methods: A retrospective cohort study was used to identify patients who underwent coronary artery bypass grafting (CABG), abdominal aortic aneurysm (AAA) repair, pneumonectomy, pancreatectomy, and colectomy. Individuals were identified from the Medicare Standard Analytic Files and multivariable regression was utilized to assess the association of ADRD with textbook outcome (TO), expenditures, and discharge disposition. Results: Among 1,175,010 Medicare beneficiaries, 19,406 (1.7%) patients had a preoperative diagnosis of ADRD (CABG: n = 1,643, 8.5%; AAA repair: n = 5,926, 30.5%; pneumonectomy: n = 590, 3.0%; pancreatectomy: n = 181, 0.9%; and colectomy: n = 11,066, 57.0%). After propensity score matching, patients with ADRD were less likely to achieve a TO (ADRD: 31.2% vs. no ADRD: 40.1%) or be discharged to home (ADRD: 26.7% vs. no ADRD: 46.2%) versus patients who did not have ADRD (both p < 0.001). Median index surgery expenditures were higher among patients with ADRD (ADRD: $28,815 [IQR $14,333–$39,273] vs. no ADRD: $27,101 [IQR $13,433–$38,578]; p < 0.001) (p < 0.001). On multivariable analysis, patients with ADRD had higher odds of postoperative complications (OR 1.32, 95% CI 1.25–1.40), extended length‐of‐stay (OR 1.26, 95% CI 1.21–1.32), 90‐day readmission (OR 1.37, 95% CI 1.31–1.43), and 90‐day mortality (OR 1.76, 95% CI 1.66–1.86) (all p < 0.001). Conclusion: Preoperative diagnosis of ADRD was an independent risk factor for poor postoperative outcomes, discharge to non‐home settings, as well as higher healthcare expenditures. These data should serve to inform discussions and decision‐making about surgery among the growing number of older patients with cognitive deficits. [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]

Introduction: The role of surgery in stage IV gastric cancer with peritoneal metastasis (PM) remains unclear. The objective of the current single-center study was to define the impact of gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on outcomes among Central European GC patients with limited peritoneal disease progression after neoadjuvant chemotherapy (NAC). Methods: Patients with histologically confirmed GC who underwent curative-intent multimodal treatment between 2013 and 2023 were included. Patients without adenocarcinoma, who did not undergo gastrectomy, had early (cT1) or metastatic GC at the time of initial diagnosis, who underwent multivisceral resection, incomplete cytoreduction or palliative care, died before planned curative-intent treatment, or had incomplete clinical or pathological missing information were excluded. Results: A total of 74 patients who underwent curative-intent treatment for GC with PM were included in the final analytic cohort. Patients who underwent gastrectomy with CRS+HIPEC were less likely to achieve TOO (CRS+HIPEC: 28% vs. CRS: 57.1%, p = 0.033) compared with individuals after CRS alone. Specifically, patients who underwent gastrectomy with CRS+HIPEC had a higher likelihood of postoperative complications (CRS+HIPEC: 48% vs. CRS: 20.4%, p = 0.018) and longer hospital LOS (median, CRS+HIPEC: 12 vs. CRS: 10, p = 0.019). While administration of HIPEC did not impact long-term survival (median OS, CRS+HIPEC: 16 months vs. CRS: 12 months, p = 0.55), postoperative complications (median OS, CCI < 30:16 months vs. CCI > 30:5 months, p = 0.024) and ICU stay (median OS, no ICU stay: 16 months vs. ICU stay: 5 months, p = 0.008) were associated with worsened long-term survival among GC patients with PM. Conclusions: Data from the current study demonstrated a lack of survival benefit among advanced GC patients with PM undergoing gastrectomy with CRS+HIPEC when compared with individuals after gastrectomy with CRS alone. Administration of perioperative chemotherapy and achievement of TO failed to withstand the peritoneal disease progression during NAC. [ABSTRACT FROM AUTHOR]

Background: The composition of the US healthcare workforce relative to citizenship status remains ill-defined. We sought to characterize practice patterns among US doctors relative to citizenship status. Materials and Methods: Data were extracted from the 2008–2019 American Community Surveys, and citizenship was stratified as: citizens by birth, naturalized citizens for ≥ 10 years or < 10 years, and non-citizens. Multinomial logistic regression models and inverse probability weighting were employed. The data were reported as differences in proportions/means with 95% confidence intervals. Results: Among 97,775,606 respondents, 113,638 were identified as doctors (0.12%). Among the surveyed doctors, 72.4% (95% CI 72.1–72.8%) were citizens by birth, followed by naturalized citizens ≥ 10 years [14.4% (95% CI 14.1–14.6%)], non-citizens [7.2% (95% CI 7.0–7.4%)], and naturalized citizens < 10 years [6.0% (95% CI 5.8–6.1%)]. Naturalized citizens ≥ 10 and < 10 years worked 40.4 (95% CI 12.6–68.2) and 38.2 (95% CI 4.8–71.6) more hours annually compared with citizens by birth, respectively (both p < 0.05). While 22.7% of doctors who were citizens by birth worked in high socially vulnerable counties, immigrant doctors were more likely to work in these areas (difference (95% CI); naturalized citizens ≥ 10 years, 7.7% (6.1–9.4) vs. naturalized citizens < 10 years, 8.0% (5.9–10.1) vs. non-citizens, 4.1% (2.0–6.1)). Furthermore, naturalized citizens ≥ 10 years and < 10 years worked in lower physician density counties that had 29.6 (14.4–44.8) and 59.9 (42.3–77.5) more people, respectively, relative to doctors (all p < 0.001). Conclusions: Immigrant doctors play a vital role in addressing US healthcare needs. Policies that encourage the increased integration and utilization of immigrant doctors and physicians-in-training may help to foster a sustainable healthcare workforce over the coming decades. [ABSTRACT FROM AUTHOR]

We sought to evaluate the association of county-level poverty duration and cardiac surgical outcomes. Patients who underwent coronary artery bypass graft, surgical aortic valve replacement, and mitral valve repair and replacement between 2016 and 2020 were identified using the Medicare Standard Analytical Files Database. County-level poverty data were acquired from the American Community Survey and US Department of Agriculture (1980-2015). High poverty was defined as ≥19.5% of residents in poverty. Patients were stratified into never-high poverty (NHP), intermittent low poverty, intermittent high poverty, and persistent poverty (PP). A mixed-effect hierarchical generalized linear model and Cox regression models that adjusted for patient-level covariates were used to evaluate outcomes. Among 237,230 patients, 190,659 lived in NHP counties, while 10,273 resided in PP counties. Compared with NHP patients, PP patients were more likely to present at a younger median age (NHP: 75 y versus PP: 74 y), be non-Hispanic Black (5388, 2.9% versus PP: 1030, 10.1%), and live in the south (NHP: 66,012, 34.6% versus PP: 87,815, 76.1%) (all P < 0.001). PP patients also had more nonelective surgical operations (NHP: 58,490, 30.8% versus 3645, 35.6%, P < 0.001). Notably, PP patients had increased odds of 30-d mortality (odds ratio 1.13, 95% confidence interval [CI] 1.02-1.26), 90-d mortality (odds ratio 1.14, 95% CI 1.05-1.24), and risk of long-term mortality (hazard ratio 1.13, 95% CI 1.09-1.19) compared with patients in NHP counties (all P < 0.05). County-level poverty was associated with a greater risk of short- and long-term mortality among cardiac surgical patients. [ABSTRACT FROM AUTHOR]

Background: Patients with mental illnesses face unique disparities in access to liver transplantation. We sought to compare rates of evaluation, transplantation, and post-transplant outcomes among patients with and without mental illnesses. Methods: Patients aged 18–75 with decompensated cirrhosis or hepatocellular carcinoma were identified from the Medicare Standard Analytic Files from 2014-2020. Regression analyses were used to examine the association between mental illness and evaluation by a transplant surgeon, receipt of transplant, and post-transplant outcomes. Results: Among 274,252 liver transplant candidates, 34,269 (12.5%) patients had depression and/or anxiety disorders and 8,184 (3.0%) had severe mental illnesses. The proportion of patients evaluated by a transplant surgeon was lower among patients with severe mental illnesses (14.1%), as well as individuals with depression and/or anxiety disorders (16.0%) versus the general population (18.5%) (p < 0.001). Similarly, utilization of transplantation rates was lower among patients with severe mental illness (1.1%) compared with depression and/or anxiety disorders (2.0%), as well as individuals without mental illnesses (3.8%) (p < 0.001). On multivariable regression analyses, mental illness remained independently associated with lower odds of evaluation and transplantation among patients with mental illnesses. In contrast, on adjusted analyses there were no differences in postoperative outcomes including perioperative complications, biliary complications, graft rejection, graft failure, and overall survival. Conclusion: Despite lower rates of evaluation and transplant, patients with mental illnesses did not experience differences in most postoperative outcomes compared with patients without a mental illness. [ABSTRACT FROM AUTHOR]

Background: Access to high-quality cancer care is affected by environmental exposures and structural inequities. This study sought to investigate the association between the environmental quality index (EQI) and achievement of textbook outcomes (TO) among Medicare beneficiaries over the age of 65 who underwent surgical resection for early-stage pancreatic adenocarcinoma (PDAC). Methods: Patients diagnosed with early-stage PDAC from 2004 to 2015 were identified using the SEER-Medicare database and combined with the US Environmental Protection Agency's EQI data. High EQI category indicated poor environmental quality, whereas low EQI indicated better environmental conditions. Results: A total of 5,310 patients were included, of which 45.0% (n = 2,387) patients achieved TO. Median age was 73 years and more than half were female (n = 2,807, 52.9%), married (n = 3,280, 61.8%), and resided in the Western region of the US (n = 2,712, 51.1%). On multivariable analysis, patients residing in moderate and high EQI counties were less likely to achieve a TO (referent: low EQI; moderate EQI: OR 0.66, 95% CI 0.46–0.95; high EQI: OR 0.65, 95% CI 0.45–0.94; p < 0.05). Increasing age (OR 0.98, 95%CI 0.97–0.99), racial minorities (OR 0.73, 95% CI 0.63–0.85), having a Charlson co-morbidity index > 2 (OR 0.54, 95%CI 0.47–0.61) and stage II disease (OR 0.82, 95%CI 0.71–0.96) were also associated with not achieving a TO (all p < 0.001). Conclusion: Older Medicare patients residing in moderate or high EQI counties were less likely to achieve an "optimal" TO after surgery. These results demonstrate that environmental factors may drive post-operative outcomes among patients with PDAC. [ABSTRACT FROM AUTHOR]

Introduction: Telemedicine may serve as an important avenue to address disparities in access to cancer care. We sought to define factors associated with telemedicine use among Medicare beneficiaries who underwent hepatopancreatic (HP) surgery, as well as characterize trends in telemedicine usage relative to community vulnerability based on the enactment of the Medicare telemedicine coverage waiver. Methods: Patients who underwent HP surgery between 2013–2020 were identified from the Medicare Standard Analytic Files (SAF). Telemedicine utilization was assessed pre- versus post- implementation of the Medicare telemedicine coverage waiver; the county-level social vulnerability index (SVI) was obtained from the Center for Disease Control. Interrupted time series analysis with negative binomial and multivariable logistic regression methods were used to assess changes in telemedicine utilization after the implementation of the Medicare telemedicine coverage waiver relative to SVI. Results: Pre-waiver telemedicine visits were scarce among 16,690 patients (0.2%, n = 28), while post-waiver telemedicine adoption was substantial among 3,301 patients (45.8%, n = 1,388). Post-waiver, the median patient age was 70 years (IQR, 66–74) with the majority of patients being age 65–69 (n = 994, 32.8%); 1,599 (52.8%) were female. Most patients self-identified as White (n = 2641, 87.1%), while a minority of patients self-identified as Black (n = 190, 6.3%), Asian (n = 18, 0.6%), Hispanic (n = 35, 1.2%), or Other/unknown (n = 147, 4.9%). On multivariable regression analysis, patients who lived in highly vulnerable counties (referent Low SVI; moderate SVI: OR 1.09, 95% CI 0.86–1.39, p = 0.449; high SVI: OR 0.72, 95% CI 0.55–0.94, p = 0.001) and individuals with advancing age (referent 18–64; 65–69, OR 0.68, 95%CI 0.54–0.86; 70–74, OR 0.56, 95%CI 0.44–0.71; 75–79, OR 0.57, 95%CI 0.44–0.75; 80–84, OR 0.43, 95%CI 0.30–0.61; 85 + , OR 0.25, 95%CI 0.13–0.49) had lower odds of utilizing telemedicine. In contrast, Black patients (referent White; OR 2.26, 95% CI 1.65–3.10) and patients with a higher CCI score > 2 (referent ≤ 2; OR 1.49, 95% CI 1.28–1.71) were more likely to use telemedicine (all p < 0.001). Conclusions: Medicare beneficiaries residing in counties with extreme vulnerability, as well as elderly individuals, were markedly less likely to use telemedicine services related to HP surgical episodes of care. The lower utilization of telemedicine in areas of high social vulnerability was attributable to concomitant lower rates of internet access in these areas. [ABSTRACT FROM AUTHOR]

Background: Hepatopancreatic (HP) surgeon and hospital procedural volume may vary relative to liver or pancreas cases. We sought to investigate the impact of surgeon and hospital pancreatic subspecialization on patient outcomes. Methods: Patients who underwent pancreatic surgery between 2013–2017 were identified from the Medicare Standard Analytic Files. The surgery subspecialization index (SSI) was calculated to signify surgeon and hospital pancreatic subspecialization, and categorized as low, intermediate, and high SSI. The association of SSI with Textbook Outcome (TO) and its components, failure to rescue (FTR), discharge to home and index admission expenditures was assessed with mixed-effects multivariable logistic regression. Results: Among 19,625 patients, most pancreatic procedures were characterized by high SSI (Low SSI: 27.7%, Intermediate SSI: 34.7%, High SSI: 37.7%). Notably, higher SSI was associated with greater odds of achieving a TO [Intermediate SSI: OR 1.16 (95%CI 1.06–1.27); High SSI: OR 1.23 (95%CI 1.11–1.35)] as well as being discharged home, and lower odds of experiencing FTR. Furthermore, this association persisted in both low-volume [referent: Low SSI; Intermediate SSI: OR 1.14 (95%CI 1.01–1.28); High SSI: OR 1.15 (95%CI 1.02–1.31)] and high-volume hospitals [referent: Low SSI; Intermediate SSI: OR 1.16 (95%CI 1.01–1.32); High SSI: OR 1.26 (95%CI 1.09–1.45)]. Conclusions: Greater pancreatic subspecialization was associated with improved postoperative outcomes following pancreatic resection. Amidst increasing efforts to improve quality of care, surgical subspecialization may play a role in determining patient outcomes regardless of total surgeon or hospital volume. [ABSTRACT FROM AUTHOR]

Defining patterns and risk of recurrence can help inform surveillance strategies and patient counselling. We sought to characterize peak hazard rates (pHR) and peak time of recurrence among patients who underwent resection of hepatocellular carcinoma (HCC). 1434 patients who underwent curative-intent resection of HCC were identified from a multi-institutional database. Hazard, patterns, and peak rates of recurrence were characterized. The overall hazard of recurrence peaked at 2.4 months (pHR: 0.0384), yet varied markedly. The incidence of recurrence increased with Barcelona Clinic Liver Cancer (BCLC) stage 0 (29%), A (54%), and B (64%). While the hazard function curve for BCLC 0 patients was relatively flat (pHR: <0.0177), BCLC A patients recurred with a peak at 2.4 months (pHR: 0.0365). Patients with BCLC B had a bimodal recurrence with a peak rate at 4.2 months (pHR: 0.0565) and another at 22.8 months. The incidence of recurrence also varied according to AFP level (≤400 ng/mL: 52.6% vs. >400 ng/mL: 36.3%) and Tumor Burden Score (low: 73.7% vs. medium: 50.6% vs. high: 24.2%) (both p < 0.001). Recurrence hazard rates for HCC varied substantially relative to both time and intensity/peak rates. TBS and AFP markedly impacted patterns of hazard risk of recurrence. [ABSTRACT FROM AUTHOR]