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Background: The impact of tumor burden score (TBS) on conditional survival (CS) among patients undergoing curative-intent resection of hepatocellular carcinoma (HCC) has not been examined to date., Methods: Patients who underwent liver resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS and other clinicopathologic factors on 3-year conditional survival (CS 3 ) was examined., Results: Among 1,040 patients, 263 (25.3%) patients had low TBS, 668 (64.2%) had medium TBS and 109 (10.5%) had high TBS. TBS was strongly associated with OS; 5-year OS was 39.0% among patients with high TBS compared with 61.1% and 79.4% among patients with medium and low TBS, respectively (p < 0.001). While actuarial survival decreased as time elapsed from resection, CS increased over time irrespective of TBS. The largest differences between 3-year actuarial survival and CS 3 were noted among patients with high TBS (5-years postoperatively; CS 3 : 78.7% vs. 3-year actuarial survival: 30.7%). The effect of adverse clinicopathologic factors including high TBS, poor/undifferentiated tumor grade, microvascular invasion, liver capsule involvement, and positive margins on prognosis decreased over time., Conclusions: CS rates among patients who underwent resection for HCC increased as patients survived additional years, irrespective of TBS. CS estimates can be used to provide important dynamic information relative to the changing survival probability after resection of HCC., (© 2021. Société Internationale de Chirurgie.)

Introduction: Intrahepatic cholangiocarcinoma (ICC) remains an uncommon disease with a rising incidence worldwide. We sought to identify trends in therapeutic approaches and differences in patient outcomes based on facility types., Methods: Between January 1, 2004, and December 31, 2015, a total of 27,120 patients with histologic diagnosis of ICC were identified in the National Cancer Database and were enrolled in this study., Results: The incidence of ICC patients increased from 1194 in 2004 to 3821 in 2015 with an average annual increase of 4.16% (p < 0.001). Median survival of the cohort improved over the last 6 years of the study period (2004-2009: 8.05 months vs. 2010-2015: 9.49 months; p < 0.001). Among surgical patients (n = 5943, 21.9%), the incidence of R0 resection, lymphadenectomy and harvest of ≥6 lymph nodes increased over time (p < 0.001). Positive surgical margins (referent R0: R1, HR 1.49, 95% CI 1.24-1.79, p < 0.001) and treatment at community cancer centers (referent academic centers; HR 1.24, 95% CI 1.04-1.49, p = 0.023) were associated with a worse prognosis. Patients treated at academic centers had higher rates of R0 resection (72.4% vs. 67.7%; p = 0.006) and lymphadenectomy (55.6% vs. 49.5%, p = 0.009) versus community cancer centers. Overall survival was also better at academic versus community cancer programs (median OS: 11 months versus 6 months, respectively; p < 0.001)., Conclusions: The incidence of ICC has increased over the last 12 years in the USA with a moderate improvement in survival over time. Treatment at academic cancer centers was associated with higher R0 resection and lymphadenectomy rates, as well as improved OS for patients with ICC.

Background: The effect of various hospital characteristics on failure to rescue (FTR) after liver surgery has not been well examined. We sought to examine the relationship between hospital characteristics and FTR after liver surgery., Methods: The 2013-2015 Medicare-Provider Analysis and Review (MEDPAR) database was used to identify Medicare beneficiaries who underwent liver surgery. The effect of various hospital characteristics on FTR was compared among the highest mortality hospitals (HMH) and the lowest mortality hospitals (LMH)., Results: Among 4902 patients undergoing hepatectomy, patients treated at HMH had a higher risk of FTR (OR 3.08, 95% CI 2.03-4.66). Hospital factors such as total number of beds (OR 0.80, 95% 0.56-1.15), operating rooms (OR 0.81, 95% 0.57-1.14), and overall hospital surgical volume (OR 0.88, 95% 0.61-1.25) were not associated with FTR (all p > 0.05). In contrast, hospitals with a greater nurse-to-patient ratio had a markedly lower risk of FTR following a complication (OR 0.70, 95% CI 0.54-0.91; p = 0.007) (Table 3). As volume of liver operations and nurse-to-patient ratio decreased the risk of FTR increased (p > 0.001). After risk-adjusting for patient characteristics, both the effect of surgical volume (adjusted OR 0.66, 95% CI 0.46-0.94; p = 0.022) and nurse-to-patient ratio (adjusted OR 0.68, 95% CI 0.51-0.90; p = 0.008) remained strongly associated with FTR., Conclusion: FTR rates varied considerably among hospital performing hepatectomy. Higher procedure-specific hepatectomy volume, as well as a higher nurse-to-patient ratio, accounted for a reduction in the FTR rates. These data highlight the importance of not only procedure volume, but also adequate nurse staffing in reducing FTR and improving mortality following complex procedures such as hepatectomy.

Background: The impact of time to readmission (TTR) on post-discharge mortality has not been well examined. We sought to define the impact of TTR on postoperative mortality after liver or pancreas surgery., Methods: A retrospective cohort analysis of liver and pancreas surgical patients was conducted using 2013-2015 Medicare Provider Analysis and Review database. Patients were subdivided into TTR groups: 1-5 days, 6-15, 15-30, 31-60, 61-90, and no readmission. The association of index complication, readmission causes, TTR, and mortality was assessed., Results: Among 18,177 patients, a total of 4485 (24.7%) patients were readmitted within 90 days of discharge. Major causes for readmission differed across TTR groups. Patients readmitted within 1-15 days were more likely to be readmitted for postoperative infection compared with patients who had a late readmission (1-5 days: 63.1% vs. 6-15 days: 65.0% vs. 61-90 days: 39.3%; P < 0.001). In contrast, causes of late readmissions were more likely related to gastrointestinal complications (1-5 days: 28.9% vs. 61-90 days: 39.7%; P < 0.001). Compared with no readmission, 180-day mortality was highest among patients readmitted within 16-30 days (aOR 3.60; 95% CI 2.94-4.41). Among patients with index complications, patients who were readmitted within 1-5 days had a higher risk-adjusted 180-day mortality than late readmission (1-5 days: 37.3% vs. 61-90 days: 27.1%) (P < 0.001)., Conclusions: Among patients who were readmitted, the incidence of mortality increased with TTR up to 60 days after discharge yet decreased thereafter. The relation of TTR and mortality was particularly pronounced among those patients who had an index complication. Future efforts should consider TTR when identifying specific approaches to decrease readmission.

Background: The association of hospital teaching status and overall expenditures has not been studied among patients undergoing hepato-pancreato-biliary (HPB) surgery. We sought to define the impact of hospital teaching intensity on payments and charges associated with (HPB) surgery from the payer perspective., Methods: Surgical patients undergoing HPB procedures were identified using 2013-2015 Medicare Provider Analysis and Review (MEDPAR) data. Hospital teaching intensity was categorized based on hospital resident-to-bed ratio: non-teaching (NTH: 0), minor teaching (minor-TH: 0-0.363), and major teaching (major-TH:  > 0.363). Risk-adjusted price-standardized Medicare payments were assessed and compared among HPB surgical patients at NTH versus major-TH., Results: A total of 8863 patients underwent HPB (NTH: n = 1239, 14.0%; minor-TH: n = 3202, 36.1%; major-TH: n = 4422, 49.9%). Patient comorbidities did not vary across hospital according to teaching intensity (p = 0.27). Mean risk-adjusted Medicare payment at a major-TH was $29,541 versus $19,345 at a NTH (Δ-payment: + $10,195; p < 0.001). Differences in Medicare payments associated with hospital teaching status persisted when the risk-adjusted price was standardized to remove social subsidies and regional variation in costs (NTH: $19,760 vs. major-TH: $28,382; Δ-payment:  + $8623). Major-TH had higher total charges submitted to Medicare versus NTH (NTH: $100,583 vs. major-TH: $120,498; Δ-charge = + $19,915), including charges for accommodations, laboratory, and blood utilization (all p < 0.05). Compared with NTH, major-TH had lower morbidity (22.6 vs. 19.0%), serious complications (13.0 vs. 10.5%) and 30-day mortality (4.8 vs. 2.3%) (all p < 0.05)., Conclusions: Major-TH was associated with higher Medicare expenditures than NTH among HPB surgical patients. These differences were attributable, in part, to higher submitted charges for hospital-based services. While associated with higher payments and charges, TH did have better short-term outcomes compared with NTH.

Background: The consequences of lymphadenectomy (LND) on cirrhotic patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) have not been investigated. We sought to analyze the impact of LND on morbidity among patients undergoing resection for ICC., Methods: A total of 1005 patients who underwent hepatectomy for ICC at one of the 14 participating institutions between 1990 and 2015 were identified. A propensity score match analysis was performed to reduce confounding biases between cirrhosis and non-cirrhosis groups., Results: Cirrhosis was diagnosed in 118 (11.7%) patients. Among non-cirrhotic patients, 63% underwent major liver resection versus only 20% among patients with cirrhosis (p < 0.001). LND was also less common among cirrhotic versus non-cirrhotic patients (19 vs. 50%, p < 0.001). The incidence of complications was 41 and 30% among patients who did not and did have cirrhosis, respectively (p = 0.022). The propensity-matched cohort included 150 patients. The incidence of complications was 71% among patients who underwent lymphadenectomy versus 23% among patients who did not undergo lymphadenectomy (OR 8.39) (p < 0.001). In the propensity-matched analysis, the median HLN was comparable among patients independent of cirrhosis status (median HLN: non-cirrhosis, 2.5 vs. cirrhosis, 2) (p = 0.95). While lymphadenectomy was associated with a higher risk of infections (non-cirrhosis, 0% vs. cirrhosis, 21%, p < 0.001) among patients with cirrhosis, infections were not associated with lymphadenectomy among non-cirrhotic patients (p = 0.19)., Conclusion: Lymphadenectomy was associated with an increased risk of complications among patients with cirrhosis undergoing surgery for ICC. The benefit of lymphadenectomy in cirrhotic patients should be considered in light of the higher risk of postoperative complications compared with non-cirrhotic patients.

Extranodal extension (ENE) of nodal metastasis is defined as the extension of metastatic cells through the nodal capsule into the perinodal tissue. This morphological parameter, recently proposed as an important prognostic factor in different types of malignancy, has not been included in the TNM staging system for non-small cell lung cancer (NSCLC). In this systematic review with meta-analysis, we weighted the prognostic role of ENE in patients with lymph node-positive NSCLC. Two independent authors searched SCOPUS and PubMed through 28 February 2017. Prospective and retrospective studies on NSCLC, comparing patients with presence of ENE (ENE+) ENE+) vs. only intranodal extension (ENE-) and including data regarding prognosis, were considered as eligible. Data were summarized using risk ratios (RR) for the number of deaths/recurrences, and hazard ratios (HR) with 95% confidence intervals (CI) for time-dependent risk related to ENE+, adjusted for potential confounders. We identified 13 studies, including 1709 patients (573 ENE+ and 1136 ENE-) with a median follow-up of 60 months. ENE was associated with a significantly increased risk of mortality of all causes (RR = 1.39, 95% CI: 1.18-1.65, P < 0.0001, I 2  = 70%; HR = 1.30, 95% CI: 1.01-1.67, P = 0.04, I 2  = 0%) and of disease recurrence (RR = 1.32, 95% CI: 1.04-1.68, P = 0.02, I 2  = 42%; HR = 1.93, 95% CI: 1.53-2.44, P < 0.0001, I 2  = 0%). We conclude that in NSCLC, requirements for assessment of ENE should be included in gross sampling and ENE status should be included in the pathology report. Inclusion of ENE status in oncology staging systems will allow further assessment of its role as prognostic parameter.

Background: We sought to investigate the prognosis of patients following curative-intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV-ICC), hepatolithiasis (Stone-ICC), and no identifiable cause (conventional ICC) etiologic subtype., Methods: 986 patients with HBV-ICC (n = 201), stone-ICC (n = 103), and conventional ICC (n = 682) who underwent curative-intent resection were identified from a multi-institutional database. Propensity score matching (PSM) was used to mitigate residual bias., Results: HBV-ICC patients more often had cirrhosis, earlier stage tumors, a mass-forming lesion, well-to-moderate tumor differentiation, and an R0 resection versus stone-ICC or conventional ICC patients. Five-year recurrence-free survival among HBV-ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence-free of only 8.3% among patients with stone-ICC. Similarly, 5-year overall survival among patients with stone-ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV-ICC and conventional ICC, respectively. On PSM, patients with stone-ICC group had equivalent long-term outcomes as HBV-ICC patients. In contrast, on PSM, stone-ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic-only recurrence among patients who had stone-ICC (6.0 months) was worse than OS among HBV-ICC (13.0 months) or conventional ICC (12.0 months) (p = 0.006 and p = 0.082, respectively)., Conclusions: While HBV-ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage-for-stage differences in outcomes compared with stone-ICC or conventional ICC. In contrast, patients with stone-ICC had worse long-term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC.

Background: While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC)., Methods: Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age., Results: The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9-4.9) and 23.9 % (95 % CI, 19.6-28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7-23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p ≤ 0.05). The cure fraction for patients with a CA 19.9 < 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 ≥ 50 who also had lymph node metastasis., Conclusions: Examining an "all comer" cohort, <15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship.

Background: Nomograms may be important clinical tools to estimate the preoperative risk of transfusion and allow for preemptive arrangements for alternatives to allogeneic blood transfusions., Methods: A multicentric international cohort of 1345 patients who underwent hepatectomy for benign or malign liver diseases was used to validate a nomogram developed by the Memorial Sloan-Kettering Cancer Center., Results: A total of 449 (33.3 %) patients received a blood transfusion after hepatectomy. Several variables were associated with the need of transfusion on univariate analysis: age, BMI, hemoglobin, PT-INR, bilirubin, AST, ALT, GGT, albumin, primary liver cancer, and number of segments resected. The MSKCC nomogram, including the number of segments resected, diagnosis (primary vs. non-primary), extrahepatic organ resection, as well as platelet and hemoglobin levels, had a good predictive ability (AUC = 0.69). The frequency of patients transfused ranged from 19 % for patients who were at "low risk" (<20 % risk to be transfused) up to 68 % for patients at "high risk" (>70 % risk to be transfused). The nomogram was tested in a multivariable model including other factors associated with risk of transfusion. The final model included age (OR 1.02, 95 % CI 1.01-1.03, p < 0.001), PT-INR (OR 1.54, 95 % CI 1.01-2.36, p = 0.048), and bilirubin (OR 1.86, 95 % CI 1.09-3.18, p = 0.021). The prediction ability for the integrated prediction model was AUC = 0.73., Conclusion: The MSKCC nomogram was an effective clinical tool able to predict the perioperative risk of transfusion in our independent external validation. The inclusion of patient age, as well as factors associated with liver functional status (bilirubin and PT-INR), improved the predictive ability of the MSKCC nomogram.