Prognostic factors of overall survival in patients with recurrent disease following liver resection for colorectal cancer metastases: A multicenter external validation study

Background: The clinical course of patients experiencing recurrence following hepatectomy for colorectal cancer metastases (CRM) is poorly defined. Previous studies associated shorter time to recurrence (TTR) in months, node-positive primary tumor, and more than one site of recurrence with worse outcomes. Methods: We conducted a retrospective cohort study across four Canadian institutions to externally validate previously established prognostic factors of overall survival (OS). We included consecutive adult patients who had a recurrence following curative-intent liver resection for CRM. Prognostic factors were explored using a multivariable Cox regression model. Risk group cutoffs were identified through recursive partitioning. OS between low- and high-risk groups was compared using the Kaplan–Meier method. Results: This study included 471 patients. Shorter TTR in months (hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.93–0.97), presence of extrahepatic disease at first hepatectomy (HR: 2.54, 95% CI: 1.18–5.50), and larger tumor size in millimetres (HR: 1.01, 95% CI: 1.00–1.02) were associated with worse OS. Median OS in the high- and low-risk groups were 40.5 (95% CI: 34.0–45.7 months) versus 64.7 months (95% CI: 57.9–72.3 months; p < 0.001), respectively. Conclusions: We externally validated the prognostic significance of shorter TTR (<8.5 months) as a predictor of worse OS in patients who recur the following hepatectomy for CRM

Point-of-care haemoglobin accuracy and transfusion outcomes in non-cardiac surgery at a Canadian tertiary academic hospital: protocol for the PREMISE observational study

Introduction Transfusions in surgery can be life-saving interventions, but inappropriate transfusions may lack clinical benefit and cause harm. Transfusion decision-making in surgery is complex and frequently informed by haemoglobin (Hgb) measurement in the operating room. Point-of-care testing for haemoglobin (POCT-Hgb) is increasingly relied on given its simplicity and rapid provision of results. POCT-Hgb devices lack adequate validation in the operative setting, particularly for Hgb values within the transfusion zone (60–100 g/L). This study aims to examine the accuracy of intraoperative POCT-Hgb instruments in non-cardiac surgery, and the association between POCT-Hgb measurements and transfusion decision-making.Methods and analysis PREMISE is an observational prospective method comparison study. Enrolment will occur when adult patients undergoing major non-cardiac surgery require POCT-Hgb, as determined by the treating team. Three concurrent POCT-Hgb results, considered as index tests, will be compared with a laboratory analysis of Hgb (lab-Hgb), considered the gold standard. Participants may have multiple POCT-Hgb measurements during surgery. The primary outcome is the difference in individual Hgb measurements between POCT-Hgb and lab-Hgb, primarily among measurements that are within the transfusion zone. Secondary outcomes include POCT-Hgb accuracy within the entire cohort, postoperative morbidity, mortality and transfusion rates. The sample size is 1750 POCT-Hgb measurements to obtain a minimum of 652 Hgb measurements &lt;100 g/L, based on an estimated incidence of 38%. The sample size was calculated to fit a logistic regression model to predict instances when POCT-Hgb are inaccurate, using 4 g/L as an acceptable margin of error.Ethics and dissemination Institutional ethics approval has been obtained by the Ottawa Health Science Network—Research Ethics Board prior to initiating the study. Findings from this study will be published in peer-reviewed journals and presented at relevant scientific conferences. Social media will be leveraged to further disseminate the study results and engage with clinicians

Long-term outcomes after curative resection of HCV-positive versus non-hepatitis related hepatocellular carcinoma: an international multi-institutional analysis

BACKGROUND: To define the chronological changes of long-term survival among patients with non-hepatitis-related hepatocellular carcinoma (Non-Hep-HCC) versus hepatitis C-related HCC (HCV-HCC) over the last two decades.METHODS: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Overall (OS) and recurrence-free survival (RFS) were analyzed and compared among Non-Hep-HCC versus HCV-HCC patients. Propensity score matching (PSM) was utilized to mitigate residual bias.RESULTS: Among 617 patients, 196 (31.8%) patients had HCV-HCC, whereas 421 (68.2%) patients had Non-Hep-HCC. While patients with HCV-HCC had an improvement in OS over time (5-year OS, 2000-2009 55% vs. 2010-2017 67%, p = 0.034), OS among patients with Non-Hep-HCC remain unchanged (5-year OS, 2000-2009 53% vs. 2010-2017 52%, p = 0.905). In the matched cohort, patients with HCV-HCC had a worse OS versus patients with Non-Hep-HCC during 2000 and 2009 (5-year OS, 12% vs. 63%, p = 0.029), but significantly better OS from 2010 to 2017 than patients with Non-Hep-HCC (5-year OS, 86% vs. 73%, p = 0.035). The recurrence timing, patterns and re-treatments were comparable among Non-Hep-HCC and HCV-HCC patients.CONCLUSION: While OS of patients with HCV-HCC improved over time, the long-term survival of patients with Non-Hep-HCC patients remained unchanged and was more unfavorable

Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma

Introduction Although preoperative alpha-fetoprotein (AFP) has been recognized as an important tumor marker among patients with hepatocellular carcinoma (HCC), the predictive value of AFP levels at the time of recurrence (rAFP) on post-recurrence outcomes has not been well examined. Methods Patients undergoing curative-intent resection of HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of rAFP on post-recurrence survival, as well as the impact of rAFP relative to the timing and treatment of HCC recurrence were examined. Results Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8 ng/mL (interquartile range 3-100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP &gt; 10 ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP &lt; 10 ng/mL (28.7% vs. 65.5%, p &lt; 0.001). rAFP correlated with survival among patients who had early (3-year survival; rAFP &gt; 10 vs. &lt; 10 ng/mL: 30.1% vs. 60.2%, p &lt; 0.001) or late (18.0% vs. 78.7%, p = 0.03) recurrence. Furthermore, rAFP levels predicted 3-year post-recurrence survival among patients independent of the therapeutic modality used to treat the recurrent HCC (rAFP &gt; 10 vs. &lt; 10 ng/mL; ablation: 41.1% vs. 76.0%; intra-arterial therapy: 12.9% vs. 46.1%; resection: 37.5% vs. 100%; salvage transplantation: 60% vs. 100%; all p &lt; 0.05). After adjusting for competing risk factors, patients with rAFP &gt; 10 ng/mL had a twofold higher hazard of death in the post-recurrence setting (hazard ratio 1.96, 95% confidence interval 1.26-3.04). Conclusion AFP levels at the time of recurrence following resection of HCC predicted post-recurrence survival independent of the secondary treatment modality used. Evaluating AFP levels at the time of recurrence can help inform post-recurrence risk stratification of patients with recurrent HCC

Prediction of tumor recurrence by \u3b1-fetoprotein model after curative resection for hepatocellular carcinoma

BACKGROUND: Preoperative alpha-fetoprotein (AFP) level levels may help select patients with hepatocellular carcinoma (HCC) for surgery. The objective of the current study was to assess an AFP model to predict tumor recurrence and patient survival after curative resection for HCC.METHODS: Patients undergoing curative-intent resection for HCC between 2000 and 2017 were identified from a multi-institutional database. AFP score was calculated based on the last evaluation before surgery. Probabilities of tumor recurrence and overall survival (OS) were compared according to an AFP model.RESULTS: A total of 825 patients were included. An optimal cut-off AFP score of 2 was identified with an AFP score 653 versus 642 independently predicting tumor recurrence and OS. Net reclassification improvements indicated the AFP model was superior to the Barcelona Clinic Liver Cancer (BCLC) system to predict recurrence (p&lt;0.001). Among patients with BCLC B-C, AFP score 642 identified a subgroup of patients with AFP levels of 64100ng/mL with a low 5-year recurrence risk ( 642 45.2% vs. 653 61.8%, p=0.046) and favorable 5-year OS ( 642 54.5% vs. 653 39.4%, p=0.035). In contrast, among patients within BCLC 0-A, AFP score 653 identified a subgroup of patients with AFP values&gt;1000ng/mL with a high 5-year recurrence ( 653 47.9% vs. 642% 38.4%, p=0.046) and worse 5-year OS ( 653 47.8% vs. 642 65.9%, p&lt;0.001). In addition, the AFP score independently correlated with vascular invasion, tumor differentiation and capsule invasion.CONCLUSIONS: The AFP model was more accurate than the BCLC system to identify which HCC patients may benefit the most from surgical resection

Non-transplantable Recurrence After Resection for Transplantable Hepatocellular Carcinoma: Implication for Upfront Treatment Choice

Objectives To identify the preoperative risk factors for prediction of non-transplantable recurrence (NTR) after tumor resection for early-stage hepatocellular carcinoma (HCC) to assist in patient selection relative to upfront liver resection (LR) versus liver transplantation (LT). Methods Patients who underwent curative resection for transplantable HCC and chronic liver disease were identified from an international multi-institutional database. NTR was defined as recurrence beyond the Milan or UCSF criteria, and the preoperative risk factors of NTR were investigated. Results Among 293 patients with transplantable HCC within Milan criteria and 320 within UCSF criteria, 113 (38.6%) and 131 (40.9%) patients developed tumor recurrence, respectively. Among patients who recurred, NTR was present in 32 (28.3%) patients within Milan and 35 (26.7%) within UCSF criteria. When either Milan or UCSF criteria was adopted, three preoperative risk factors including liver cirrhosis, tumor size &gt; 3 cm, and multiple lesions were consistently identified as risk factors associated with NTR after curative resection. By summing up the three factors, a scoring model was established and the incidence of NTR among patients with 0, 1 or &gt;= 2 risk factors incrementally increased from 4.5%, 13.3% to 20.5% when Milan criteria was used, and from 4.5%, 12.4% to 33.9% when UCSF criteria was adopted. The model demonstrated very good discriminatory power on internal validation (n = 5,000) (c-index 0.689 for Milan criteria, and 0.715 for UCSF criteria). Conclusions Whereas surgical resection may be optimal first-line treatment for patients with no or one risk factor, patients with &gt;= 2 risk factors should be considered for upfront liver transplantation

Impact of Tumor Burden Score on Conditional Survival after Curative-Intent Resection for Hepatocellular Carcinoma: A Multi-Institutional Analysis

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 (CS3) 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 &lt; 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 CS3 were noted among patients with high TBS (5-years postoperatively; CS3: 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

Tumor Necrosis Impacts Prognosis of Patients Undergoing Curative-Intent Hepatocellular Carcinoma

Background The impact of tumor necrosis relative to prognosis among patients undergoing curative-intent resection for hepatocellular carcinoma (HCC) remains ill-defined. Methods Patients who underwent curative-intent resection for HCC without any prior treatment between 2000 and 2017 were identified from an international multi-institutional database. Tumor necrosis was graded as absent, moderate (&lt; 50% area), or extensive (&gt;= 50% area) on histological examination. The relationship between tumor necrosis, clinicopathologic characteristics, and long-term survival were analyzed. Results Among 919 patients who underwent curative-intent resection for HCC, the median tumor size was 5.0 cm (IQR, 3.0-8.5). Tumor necrosis was present in 367 (39.9%) patients (no necrosis: n = 552, 60.1% vs &lt; 50% necrosis: n = 256, 27.9% vs &gt;= 50% necrosis: n = 111, 12.1%). Extent of tumor necrosis was also associated with more advanced tumor characteristics. HCC necrosis was associated with OS (median OS: no necrosis, 84.0 months vs &lt; 50% necrosis, 73.6 months vs &gt;= 50% necrosis: 59.3 months; p &lt; 0.001) and RFS (median RFS: no necrosis, 49.6 months vs &lt; 50% necrosis, 38.3 months vs &gt;= 50% necrosis: 26.5 months; p &lt; 0.05). Patients with T1 tumors with extensive &gt;= 50% necrosis had an OS comparable to patients with T2 tumors (median OS, 62.9 vs 61.8 months; p = 0.645). In addition, patients with T2 disease with necrosis had long-term outcomes comparable to patients with T3 disease (median OS, 61.8 vs 62.4 months; p = 0.713). Conclusion Tumor necrosis was associated with worse OS and RFS, as well as T-category upstaging of patients. A modified AJCC T classification that incorporates tumor necrosis should be considered in prognostic stratification of HCC patients

Early Versus Late Recurrence of Hepatocellular Carcinoma After Surgical Resection Based on Post-recurrence Survival: an International Multi-institutional Analysis

Background To define early versus late recurrence based on post-recurrence survival (PRS) among patients undergoing curative resection for hepatocellular carcinoma (HCC). Methods Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The optimal cut-off time point to discriminate early versus late recurrence was determined relative to PRS. Results Among 1004 patients, 443 (44.1%) patients experienced recurrence with a median recurrence-free survival time of 12 months. A cut-off time point of 8 months was defined as the optimal threshold based on sensitivity analyses relative to PRS for early (n = 165, 37.2%) versus late relapse (n = 278, 62.8%) (p = 0.008). Early recurrence was associated with worse PRS (median PRS, 27.0 vs. 43.0 months, p = 0.019), as well as overall survival (OS) (median OS, 32.0 versus 74.0 months, p &lt; 0.001) versus late recurrence. In addition, patients who recurred early were more likely to recur at extra- +/- intrahepatic (35.5% vs. 19.8%, p = 0.003) sites and were less likely to have the recurrence treated with curative intent (33.8% vs. 45.7%, p = 0.08). Patients undergoing curative re-treatment of late recurrence had a comparable OS with patients who had no recurrence (median OS, 139.0 vs. 140.0 months); patients with early recurrence had inferior OS after curative re-treatment versus patients with no recurrence (median OS, 69.0 vs. 140.0 months, p = 0.036), yet still better than patients who received palliative treatment for early recurrence (median OS, 69.0 vs. 21.0 months, p &lt; 0.001). Conclusions Eight months was identified as the cut-off value to differentiate early versus late recurrence. Curative-intent treatment for recurrent intrahepatic tumors was associated with reasonable long-term outcomes

Postoperative Infectious Complications Worsen Long-Term Survival After Curative-Intent Resection for Hepatocellular Carcinoma

Background: Postoperative infectious complications may be associated with a worse long-term prognosis for patients undergoing surgery for a malignant indication. The current study aimed to characterize the impact of postoperative infectious complications on long-term oncologic outcomes among patients undergoing resection for hepatocellular carcinoma (HCC). Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The relationship between postoperative infectious complications, overall survival (OS), and recurrence-free survival (RFS) was analyzed. Results: Among 734 patients who underwent HCC resection, 269 (36.6%) experienced a postoperative complication (Clavien-Dindo grade 1 or 2 [n = 197, 73.2%] vs grade 3 and 4 [n = 69, 25.7%]). An infectious complication was noted in 81 patients (11.0%) and 188 patients (25.6%) had non-infectious complications. The patients with infectious complications had worse OS (median: infectious complications [46.5 months] vs no complications [106.4 months] [p &lt; 0.001] and non-infectious complications [85.7 months] [p &lt; 0.05]) and RFS (median: infectious complications [22.1 months] vs no complications [45.5 months] [p &lt; 0.05] and non-infectious complications [38.3 months] [p = 0.139]) than the patients who had no complication or non-infectious complications. In the multivariable analysis, infectious complications remained an independent risk factor for OS (hazard ratio [HR], 1.7; p = 0.016) and RFS (HR, 1.6; p = 0.013). Among the patients with infectious complications, patients with non-surgical-site infection (SSI) had even worse OS and RFS than patients with SSI (median OS: 19.5 vs 70.9 months [p = 0.010]; median RFS: 12.8 vs 33.9 months [p = 0.033]). Conclusion: Infectious complications were independently associated with an increased long-term risk of tumor recurrence and death. Patients with non-SSI versus SSI had a particularly worse oncologic outcome