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The \Odessey\ : the Zombies, in words and images
\"To mark the fiftieth anniversary of the recording of their classic Odessey and Oracle album, The Zombies have assembled an eclectic collection of rare and unseen photos, original artwork, and personal memories that offer readers an intimate snapshot of one of the more influential bands to emerge from the UK music scene of the 1960s.\" -- From publisher's website.
Book
Prognosis After Resection of Barcelona Clinic Liver Cancer (BCLC) Stage 0, A, and B Hepatocellular Carcinoma: A Comprehensive Assessment of the Current BCLC Classification
Background
Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have questioned the prognostic stratification of this classification schema, as well as the proposed treatment allocation of patients with a single large tumor.
Methods
Patients who underwent curative-intent hepatectomy for histologically proven hepatocellular carcinoma (HCC) between 1998 and 2017 were identified using an international multi-institutional database. Overall survival (OS) among patients with BCLC stage 0, A, and B was examined. Patients with a single large tumor were classified as BCLC stage A1 and were independently assessed.
Results
Among 814 patients, 68 (8.4%) were BCLC-0, 310 (38.1%) were BCLC-A, 279 (34.3%) were BCLC-A1, and 157 (19.3%) were BCLC-B. Five-year OS among patients with BCLC stage 0, A, A1, and B HCC was 86.2%, 69.0%, 56.9%, and 49.9%, respectively (
p
< 0.001). Among patients with very early- and early-stage HCC (BCLC 0, A, and A1), patients with BCLC stage A1 had the worst OS (
p
= 0.0016). No difference in survival was noted among patients undergoing surgery for BCLC stage A1 and B HCC (5-year OS: 56.9% vs. 49.9%;
p
= 0.259) even after adjusting for competing factors (hazard ratio 0.83, 95% confidence interval 0.54–1.28;
p
= 0.40).
Conclusion
Prognosis following liver resection among patients with BCLC-A1 HCC was similar to patients presenting with BCLC-B tumors. Surgery provided acceptable long-term outcomes among select patients with BCLC-B HCC. Designation into BCLC stage B should not be considered an a priori contraindication to surgery.
Journal Article
Recurrence Patterns and Outcomes after Resection of Hepatocellular Carcinoma within and beyond the Barcelona Clinic Liver Cancer Criteria
BackgroundSeveral investigators have advocated for extending the Barcelona Clinic Liver Cancer (BCLC) resection criteria to select patients with BCLC-B and even BCLC-C hepatocellular carcinoma (HCC). The objective of the current study was to define the outcomes and recurrence patterns after resection within and beyond the current resection criteria.Patients and MethodsPatients who underwent resection for HCC within (i.e., BCLC 0/A) and beyond (i.e. BCLC B/C) the current resection criteria between 2005 and 2017 were identified from an international multi-institutional database. Overall survival (OS), disease-free survival (DFS), as well as patterns of recurrence of patients undergoing HCC resection within and beyond the BCLC guidelines were examined.ResultsAmong 756 patients, 602 (79.6%) patients were BCLC 0/A and 154 (20.4%) were BCLC B/C. Recurrences were mostly intrahepatic (within BCLC: 74.3% versus beyond BCLC: 70.8%, p = 0.80), with BCLC B/C patients more often having multiple tumors at relapse (69.6% versus 49.4%, p = 0.001) and higher rates of early (< 2 years) recurrence (88.0% versus 75.5%, p = 0.011). During the first postoperative year, annual recurrence was 38.3% and 21.3% among BCLC B/C and BCLC 0/A patients, respectively; 5-year OS among BCLC 0/A and BCLC B/C patients was 76.9% versus 51.6% (p = 0.003). On multivariable analysis, only a-fetoprotein (AFP) > 400 ng/mL (HR = 1.84, 95% CI 1.07–3.15) and R1 resection (HR = 2.36, 95% CI 1.32–4.23) were associated with higher risk of recurrence among BCLC B/C patients.ConclusionsSurgery can provide acceptable outcomes among select patients with BCLC B/C HCC. The data emphasize the need to further refine the BCLC treatment algorithm as well as highlight the need for surveillance protocols with a particular focus on the liver, especially for patients undergoing resection outside the BCLC criteria.
Journal Article
Assessing Textbook Outcomes Following Liver Surgery for Primary Liver Cancer Over a 12-Year Time Period at Major Hepatobiliary Centers
IntroductionThe objective of the current study was to comprehensively assess the change of practice in hepatobiliary surgery by determining the rates and the trends of textbook outcomes (TO) among patients undergoing surgery for primary liver cancer over time.MethodsPatients undergoing curative-intent resection for primary liver malignancies, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) between 2005 and 2017 were analyzed using a large, international multi-institutional dataset. Rates of TO were assessed over time. Factors associated with achieving a TO and the impact of TO on long-term survival were examined.ResultsAmong 1829 patients, 944 (51.6%) and 885 (48.4%) individuals underwent curative-intent resection for HCC and ICC, respectively. Over time, patients were older, more frequently had ASA class > 2, albumin-bilirubin grade 2/3, major vascular invasion and more frequently underwent major liver resection (all p < 0.05). Overall, a total of 1126 (62.0%) patients achieved a TO. No increasing trends in TO rates were noted over the years (ptrend = 0.90). In addition, there was no increasing trend in the TO rates among patients undergoing either major (ptrend = 0.39) or minor liver resection (ptrend = 0.63) over the study period. Achieving a TO was independently associated with 26% and 37% decreased hazards of death among ICC (HR 0.74, 95%CI 0.56–0.97) and HCC patients (HR 0.63, 95%CI 0.46–0.85), respectively.ConclusionApproximately 6 in 10 patients undergoing surgery for primary liver tumors achieved a TO. While TO rates did not increase over time, TO was associated with better long-term outcomes following liver resection for both HCC and ICC.
Journal Article
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 (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.
Journal Article
Postoperative Infectious Complications Worsen Long-Term Survival After Curative-Intent Resection for Hepatocellular Carcinoma
BackgroundPostoperative 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). MethodsPatients 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. ResultsAmong 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 < 0.001] and non-infectious complications [85.7 months] [p < 0.05]) and RFS (median: infectious complications [22.1 months] vs no complications [45.5 months] [p < 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]). ConclusionInfectious 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.
Journal Article
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
< 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
< 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.
Journal Article
Tumor Necrosis Impacts Prognosis of Patients Undergoing Curative-Intent Hepatocellular Carcinoma
BackgroundThe impact of tumor necrosis relative to prognosis among patients undergoing curative-intent resection for hepatocellular carcinoma (HCC) remains ill-defined.MethodsPatients 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 (< 50% area), or extensive (≥ 50% area) on histological examination. The relationship between tumor necrosis, clinicopathologic characteristics, and long-term survival were analyzed.ResultsAmong 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 < 50% necrosis: n = 256, 27.9% vs ≥ 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 < 50% necrosis, 73.6 months vs ≥ 50% necrosis: 59.3 months; p < 0.001) and RFS (median RFS: no necrosis, 49.6 months vs < 50% necrosis, 38.3 months vs ≥ 50% necrosis: 26.5 months; p < 0.05). Patients with T1 tumors with extensive ≥ 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).ConclusionTumor 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.
Journal Article
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 > 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 ≥ 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 ≥ 2 risk factors should be considered for upfront liver transplantation.
Journal Article
Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma
IntroductionAlthough preoperative α-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.MethodsPatients 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.ResultsAmong 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 > 10 ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP < 10 ng/mL (28.7% vs. 65.5%, p < 0.001). rAFP correlated with survival among patients who had early (3-year survival; rAFP > 10 vs. < 10 ng/mL: 30.1% vs. 60.2%, p < 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 > 10 vs. < 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 < 0.05). After adjusting for competing risk factors, patients with rAFP > 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).ConclusionAFP 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.
Journal Article