Browsing by Author "Tsilimigras, DI"
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- Impact of Time‐to‐Surgery on Outcomes of Patients Undergoing Curative‐Intent Liver Resection for BCLC‐0, A and B Hepatocellular CarcinomaPublication . Tsilimigras, DI; Hyer, JM; Diaz, A; Moris, D; Bagante, F; Ratti, F; Pinto Marques, H; Soubrane, O; Lam, V; Poultsides, GA; Popescu, I; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Pawlik, TMBackground: The impact of a prolonged time-to-surgery (TTS) among patients with resectable hepatocellular carcinoma (HCC) is not well defined. Methods: Patients who underwent curative-intent hepatectomy for BCLC-0, A and B HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of prolonged TTS on overall survival (OS) and disease-free survival (DFS) was examined. Results: Among 775 patients who underwent resection for HCC, 537 (69.3%) had early surgery (TTS < 90 days) and 238 (30.7%) patients had a delayed surgery (TTS ≥ 90 days). Patient- and tumor-related characteristics were similar between the two groups except for a higher proportion of patients undergoing major liver resection in the early surgery group (31.3% vs. 23.8%, p = .04). The percentage of patients with delayed surgery varied from 8.8% to 59.1% among different centers (p < .001). Patients with TTS < 90 days had similar 5-year OS (63.7% vs. 64.9; p = .79) and 5-year DFS (33.5% vs. 42.4; p = .20) with that of patients with TTS ≥ 90 days. On multivariable analysis, delayed surgery was not associated with neither worse OS (BCLC-0/A: adjusted hazards ratio [aHR] = 0.90; 95% confidence interval [CI]: 0.65-1.25 and BCLC-B: aHR = 0.72; 95%CI: 0.30-1.74) nor DFS (BCLC-0/A: aHR = 0.78; 95%CI: 0.60-1.01 and BCLC-B: aHR = 0.67; 95% CI: 0.36-1.25). Conclusion: Approximately one in three patients diagnosed with resectable HCC had a prolonged TTS. Delayed surgery was not associated with worse outcomes among patients with resectable HCC.
- Impact of Tumor Burden Score on Conditional Survival after Curative-Intent Resection for Hepatocellular Carcinoma: A Multi-Institutional AnalysisPublication . Elfadaly, AN; Tsilimigras, DI; Hyer, JM; Paro, A; Bagante, F; Ratti, F; Marques, HP; Soubrane, O; Lam, V; Poultsides, GA; Popescu, I; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Pawlik, TMBackground: 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 < 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.
- Predicting Lymph Node Metastasis in Intrahepatic CholangiocarcinomaPublication . Tsilimigras, DI; Sahara, K; Paredes, AZ; Moro, A; Mehta, R; Moris, D; Guglielmi, A; Aldrighetti, L; Weiss, M; Bauer, TW; Alexandrescu, S; Poultsides, GA; Maithel, SK; Marques, HP; Martel, G; Pulitano, C; Shen, F; Soubrane, O; Koerkamp, BG; Endo, I; Pawlik, TMBackground: The objective of the current study was to develop a model to predict the likelihood of occult lymph node metastasis (LNM) prior to resection of intrahepatic cholangiocarcinoma (ICC). Methods: Patients who underwent hepatectomy for ICC between 2000 and 2017 were identified using a multi-institutional database. A novel model incorporating clinical and preoperative imaging data was developed to predict LNM. Results: Among 980 patients who underwent resection of ICC, 190 (19.4%) individuals had at least one LNM identified on final pathology. An enhanced imaging model incorporating clinical and imaging data was developed to predict LNM ( https://k-sahara.shinyapps.io/ICC_imaging/ ). The performance of the enhanced imaging model was very good in the training data set (c-index 0.702), as well as the validation data set with bootstrapping resamples (c-index 0.701) and outperformed the preoperative imaging alone (c-index 0.660). The novel model predicted both 5-year overall survival (OS) (low risk 48.4% vs. high risk 18.4%) and 5-year disease-specific survival (DSS) (low risk 51.9% vs. high risk 25.2%, both p < 0.001). When applied among Nx patients, 5-year OS and DSS of low-risk Nx patients was comparable with that of N0 patients, while high-risk Nx patients had similar outcomes to N1 patients (p > 0.05). Conclusion: This tool may represent an opportunity to stratify prognosis of Nx patients and can help inform clinical decision-making prior to resection of ICC.
- Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular CarcinomaPublication . Tsilimigras, DI; Moris, D; Hyer, JM; Bagante, F; Ratti, F; Marques, HP; Soubrane, O; Lam, V; Poultsides, GA; Popescu, I; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Pawlik, TMIntroduction: Although 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. 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 > 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). 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.
- Synergistic Impact of Alpha-Fetoprotein and Tumor Burden on Long-Term Outcomes Following Curative-Intent Resection of Hepatocellular CarcinomaPublication . Tsilimigras, DI; Hyer, JM; Diaz, A; Bagante, F; Ratti, F; Marques, HP; Soubrane, O; Lam, V; Poultsides, GA; Popescu, I; Alexandrescu, S; Martel, G; Workneh, A; Guglielmi, A; Hugh, T; Aldrighetti, L; Endo, I; Pawlik, TMIntroduction: The prognostic role of tumor burden score (TBS) relative to pre-operative α -fetoprotein (AFP) levels among patients undergoing curative-intent resection of HCC has not been examined. Methods: Patients who underwent curative-intent resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS on overall survival (OS) and cumulative recurrence relative to serum AFP levels was assessed. Results: Among 898 patients, 233 (25.9%) patients had low TBS, 572 (63.7%) had medium TBS and 93 (10.4%) had high TBS. Both TBS (5-year OS; low TBS: 76.9%, medium TBS: 60.9%, high TBS: 39.1%) and AFP (>400 ng/mL vs. <400 ng/mL: 48.5% vs. 66.1%) were strong predictors of outcomes (both p < 0.001). Lower TBS was associated with better OS among patients with both low (5-year OS, low-medium TBS: 68.0% vs. high TBS: 47.7%, p < 0.001) and high AFP levels (5-year OS, low-medium TBS: 53.7% vs. high TBS: not reached, p < 0.001). Patients with low-medium TBS/high AFP had worse OS compared with individuals with low-medium TBS/low AFP (5-year OS, 53.7% vs. 68.0%, p = 0.003). Similarly, patients with high TBS/high AFP had worse outcomes compared with patients with high TBS/low AFP (5-year OS, not reached vs. 47.7%, p = 0.015). Patients with high TBS/low AFP and low TBS/high AFP had comparable outcomes (5-year OS, 47.7% vs. 53.7%, p = 0.24). The positive predictive value of certain TBS groups relative to the risk of early recurrence and 5-year mortality after HCC resection increased with higher AFP levels. Conclusion: Both TBS and serum AFP were important predictors of prognosis among patients with resectable HCC. Serum AFP and TBS had a synergistic impact on prognosis following HCC resection with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class.
- Tumor Burden Dictates Prognosis Among Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma: A Tool to Guide Post-Resection Adjuvant Chemotherapy?Publication . Tsilimigras, DI; Hyer, JM; Paredes, AZ; Moris, D; Sahara, K; Guglielmi, A; Aldrighetti, L; Weiss, M; Bauer, TW; Alexandrescu, S; Poultsides, GA; Maithel, SK; Pinto Marques, H; Martel, G; Pulitano, C; Shen, F; Soubrane, O; Koerkamp, BG; Endo, I; Sasaki, K; Aucejo, F; Zhang, XF; Pawlik, TMIntroduction: While tumor burden (TB) has been associated with outcomes among patients with hepatocellular carcinoma, the role of overall TB in intrahepatic cholangiocarcinoma (ICC) remains poorly defined. Methods: Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified from a multi-institutional database. The impact of TB on overall (OS) and disease-free survival (DFS) was evaluated in the multi-institutional database and validated externally. Results: Among 1101 patients who underwent curative-intent resection of ICC, 624 (56.7%) had low TB, 346 (31.4%) medium TB, and 131 (11.9%) high TB. OS incrementally worsened with higher TB (5-year OS; low TB: 48.3% vs medium TB: 29.8% vs high TB: 17.3%, p < 0.001). Similarly, patients with low TB had better DFS compared with medium and high TB patients (5-year DFS: 38.3% vs 18.7% vs 6.9%, p < 0.001). On multivariable analysis, TB was independently associated with OS (medium TB: HR = 1.40, 95% CI 1.14-1.71; high TB: HR = 1.89, 95% CI 1.46-2.45) and DFS (medium TB, HR = 1.61, 95% CI 1.33-1.96; high TB: HR = 2.03, 95% CI 1.56-2.64). Survival analysis revealed an excellent prognostic discrimination using the TB among the external validation cohort (3-year OS; low TB: 44.8%, medium TB: 29.3%; high TB: 23.3%, p = 0.03; 3-year DFS: low TB: 32.7%, medium TB: 10.7%; high TB: 0%, p < 0.001). While neoadjuvant chemotherapy was not associated with survival across the TB groups, receipt of adjuvant chemotherapy was associated with increased survival among patients with high TB (5-year OS: 24.4% vs 13.4%, p = 0.02). Conclusion: Overall TB dictated prognosis among patients with resectable ICC. TB may be used as a tool to help guide post-resection treatment strategies.
- Tumor Necrosis Impacts Prognosis of Patients Undergoing Resection for T1 Intrahepatic CholangiocarcinomaPublication . Tsilimigras, DI; Ejaz, A; Cloyd, J; Guglielmi, A; Aldrighetti, L; Weiss, M; Bauer, TW; Alexandrescu, S; Poultsides, GA; Maithel, SK; Pinto Marques, H; Martel, G; Pulitano, C; Shen, F; Soubrane, O; Koerkamp, BG; Endo, I; Pawlik, TMBackground: The prognostic impact of tumor necrosis among patients undergoing resection for intrahepatic cholangiocarcinoma (ICC) remains ill-defined. Methods: Patients who underwent curative-intent resection for ICC between 2000 and 2017 were identified using a multi-institutional database. The association of pathologic tumor necrosis with overall survival (OS) and recurrence-free survival (RFS) was examined. Results: Among 757 patients who underwent resection for ICC, tumor necrosis was present in 384 (50.7%) patients (no necrosis: n = 373, 49.3%; <50% necrosis: n = 291, 38.4%; ≥50% necrosis: n = 93, 12.3%). Tumor necrosis was associated with worse OS (5-year OS: no necrosis 39.3% vs. <50% necrosis 34.7% and ≥50% necrosis 24.0%; p = 0.03) and RFS (5-year RFS: no necrosis 25.7% vs. <50% necrosis 13.9% and ≥50% necrosis 18.8%; p < 0.001). After stratifying by T stage, tumor necrosis was able to further stratify prognosis among patients with T1a ICC (5-year RFS: T1a and no necrosis 46.7% vs. T1a and necrosis 36.1%; p = 0.02), and T1b ICC (5-year RFS: T1b and no necrosis 31.1% vs. T1b and necrosis 11.2%; p = 0.006), but was not associated with outcomes among patients with more advanced T2-T3 disease. Patients with T1a ICC and tumor necrosis had similar 5-year RFS as individuals with T1b ICC and no tumor necrosis (36.1% vs. 31.1%; p = 0.66). Conclusion: Tumor necrosis was associated with worse prognosis among patients with T1 ICC. Tumor necrosis for T1 ICC should be considered as an important factor to further stratify outcomes of patients with early T-stage ICC.
- Updates and Critical Insights on Glissonian Approach in Liver SurgeryPublication . Moris, D; Rahnemai-Azar, AA; Tsilimigras, DI; Ntanasis-Stathopoulos, I; Pinto Marques, H; Spartalis, E; Felekouras, E; Pawlik, TMRecent advances in surgical techniques have broadened the indications of surgical management of liver malignancies. Intraoperative bleeding is one of the known predictors of postoperative outcomes following liver surgery, signifying the importance of vascular control during liver resection. Furthermore, preservation of future liver remnant plays a critical role in prevention of post-hepatectomy liver failure as one of the main causes of postoperative morbidity and mortality. Glissonian approach liver resection offers an effective method for vascular inflow control while protecting future liver remnant from ischemia-reperfusion injury. Several studies have demonstrated the feasibility of Glisson's pedicle resection technique in modern liver surgery with an acceptable safety profile. Moreover, with increasing popularity of minimally invasive surgery, laparoscopic liver resection via Glissonian approach has been shown to be superior to standard laparoscopic hepatectomy. Herein, we systematically review the role of Glissonian approach hepatectomy in current practice of liver surgery, highlighting its advantages and disadvantaged over other methods of vascular control.