Liver transplantation (LT) for hepatocellular carcinoma (HCC) within Milan criteria is a widely accepted optimal therapy. Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent drop...Liver transplantation (LT) for hepatocellular carcinoma (HCC) within Milan criteria is a widely accepted optimal therapy. Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent dropout during the waiting period and as a down-staging method for the patient with intermediate HCC to qualify for liver transplantation. Transarterial chemoembolization and radiofrequency ablation are the most commonly used method for locoregional therapy. The data associated with newer modalities including drug-eluting beads, radioembolization with Y90, stereotactic radiation therapy and sorafenib will be discussed as a tool for converting advanced HCC to LT candidates. The concept “ablate and wait” has gained the popularity where mandated observation period after neo-adjuvant therapy allows for tumor biology to become apparent, thus has been recommended after down-staging. The role of neo-adjuvant therapy with conjunction of “ablate and wait” in living donor liver transplantation for intermediate stage HCC is also discussed in the paper.展开更多
Liver transplantation(LT) for hepatocellular carcinoma(HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria(MC...Liver transplantation(LT) for hepatocellular carcinoma(HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria(MC)(single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy(LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCCLT criteria models and pre-LT treatment strategies are required.展开更多
BACKGROUND:Locoregional therapies(LRTs) are treatments to achieve local control of hepatocellular carcinoma(HCC).Correlation between radiologic response to LRT and degree of induced tumor necrosis is not well understo...BACKGROUND:Locoregional therapies(LRTs) are treatments to achieve local control of hepatocellular carcinoma(HCC).Correlation between radiologic response to LRT and degree of induced tumor necrosis is not well understood.The aim of this study was to evaluate different levels of radiologic response after pre-liver transplant(LT) LRT and its correlation with percentage of tumor necrosis on explanted histopathology.METHODS:Institutional Review Board approved LT database was queried for treated HCC in patients undergoing LT.Radiologic response was evaluated to predict tumor necrosis in the explanted liver.Tumor response was evaluated 1 to 3 months after LRT with computed tomography or MRI via Response Evaluation Criteria in Solid Tumors(RECIST),and European Association for the Study of the Liver(EASL) guidelines.LRT was repeated as needed until time of LT.Histological tumor necrosis was graded as complete(100%),partial(50%-99%),or poor(【50%).RESULTS:Between 2002 and 2011,128 patients(97 men and 31 women) received pre-LT LRT including transarterial therapy(93),radiofrequency ablation(20),or combination of both(15).The mean age of the patients was 58±9 years.Their mean follow-up was 35±27 months.The median waitlist time was 55 days.One hundred(78%) patients had HCC within the Milan criteria at the initial radiologic diagnosis.Nineteen(15%) of the patients had complete tumor necrosis on histopathology analysis.Fifty(39%) of the patients exhibited partial necrosis,52(41%) showed poor or no necrosis and 7(5%) showed progressive disease.The overall pre-LT radiologic staging was correlated with explant pathology in 73(57%) of the patients.Underestimated tumor stage was noted in 49(38%) patients,and overestimated tumor stage in 6(5%) patients.The post-LT 3-year overall survival and disease free survival were 82% and 80%,and the rates for complete and partial tumor necrosis were 100% vs 78%(P=0.02) and 100% vs 75%(P=0.03),respectively.CONCLUSIONS:In the current era,interpretation of radiologic response after LRT for HCC does not correlate accurately with histologic tumor necrosis.Total tumor necrosis is the goal of LRT;therefore,evolution in its performance is needed.Similarly,ways to predict therapy induced tumor necrosis via radiological investigation need to be improved.展开更多
Background:Although offering the best chance of potential cure for patients with localized perihilar cholangiocarcinoma(pCCA),resection has been associated with high morbidity and sometimes poor long-term outcomes due...Background:Although offering the best chance of potential cure for patients with localized perihilar cholangiocarcinoma(pCCA),resection has been associated with high morbidity and sometimes poor long-term outcomes due to recurrence.We sought to develop a predictive model to identify individuals at high risk for very early recurrence(VER)after curative-intent surgery for pCCA.Methods:Patients who underwent curative-intent surgery for pCCA between 2000-2023 were identified from a multi-institutional database.An eXtreme Gradient Boosting(XGBoost)model was developed to estimate the risk of VER,defined as recurrence within 6 months after resection.The relative importance of clinicopathologic factors was determined using SHapley Additive exPlanations(SHAP)values.Results:Among 434 patients undergoing curative-intent resection for pCCA,65(15.0%)patients developed VER.Median overall survival(OS)among patients with and without VER was 8.4[interquartile range(IQR)6.6-11.3]versus 38.5(IQR 31.9-45.7)months(P<0.001).An XGBoost model was able to stratify patients relative to the risk of VER[low-risk:6-month recurrence-free survival(RFS)94.6%vs.intermediate-risk:6-month RFS 88.3%vs.high-risk:6-month RFS 40.0%;P<0.001].Similarly,3-year OS incrementally worsened based on VER risk(low-risk:75.3%vs.intermediate-risk:19.5%vs.high-risk:4.6%;P<0.001).The SHAP algorithm identified age,preoperative carbohydrate antigen 19-9(CA19-9)levels,tumor size and differentiation/grade,as well as lymph node metastasis as the five most important predictors of VER.The predictive accuracy of the model was good in the training[c-index:0.74,95%confidence interval(CI):0.67-0.81]and internal validation(c-index:0.77,95%CI:0.71-0.83)cohorts.An easy-to-use risk calculator for VER was developed and made available online at:https://junkawashima.shinyapps.io/VER_hilar/.Conclusions:A novel,machine learning based model was able to predict accurately the chance of VER after curative-intent resection of pCCA.In turn,the tool may help surgeons in the selection of patients likely to benefit the most from resection,as well as counsel individuals about the anticipated risk of recurrence in the early post-operative period.展开更多
Background and aims:Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors.Rapid progression of disease and delays in diagnosis restrict the number of patients ...Background and aims:Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors.Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy.The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma.Methods:All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors,laboratory data,symptoms and radiological characteristics at presentation.Results:A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis.Patients with a serum albumin level>3.0 g/dL(P<0.01),cancer antigen 19-9≤200U/mL(P=0.03),carcinoembryonic antigen≤10g/L(P<0.01)or patients without a history of cirrhosis(P<0.01)or diabetes(P=0.02)were associated with a greater length of overall survival.A serum albumin level>3.0 g/dL was identified as an independent predictor of overall survival(hazard ratio 0.31;95%confidence interval 0.14–0.70)with a survival benefit of 44 weeks.Conclusion:This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma.A serum albumin level>3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival.展开更多
Background:We sought to assess the overall benefit of laparoscopic versus open hepatectomy for treatment of colorectal liver metastases(CRLMs)using the win ratio,a novel methodological approach.Methods:CRLM patients u...Background:We sought to assess the overall benefit of laparoscopic versus open hepatectomy for treatment of colorectal liver metastases(CRLMs)using the win ratio,a novel methodological approach.Methods:CRLM patients undergoing curative-intent resection in 2001-2018 were identified from an international multi-institutional database.Patients were paired and matched based on age,number and size of lesions,lymph node status and receipt of preoperative chemotherapy.The win ratio was calculated based on margin status,severity of postoperative complications,90-day mortality,time to recurrence,and time to death.Results:Among 962 patients,the majority underwent open hepatectomy(n=832,86.5%),while a minority underwent laparoscopic hepatectomy(n=130,13.5%).Among matched patient-to-patient pairs,the odds of the patient undergoing laparoscopic resection“winning”were 1.77[WR:1.77,95%confidence interval(CI):1.42-2.34].The win ratio favored laparoscopic hepatectomy independent of low(WR:2.94,95%CI:1.20-6.39),medium(WR:1.56,95%CI:1.16-2.10)or high(WR:7.25,95%CI:1.13-32.0)tumor burden,as well as unilobar(WR:1.71,95%CI:1.25-2.31)or bilobar(WR:4.57,95%CI:2.36-8.64)disease.The odds of“winning”were particularly pronounced relative to short-term outcomes(i.e.,90-day mortality and severity of postoperative complications)(WR:4.06,95%CI:2.33-7.78).Conclusions:Patients undergoing laparoscopic hepatectomy had 77%increased odds of“winning”.Laparoscopic liver resection should be strongly considered as a preferred approach to resection in CRLM patients.展开更多
文摘Liver transplantation (LT) for hepatocellular carcinoma (HCC) within Milan criteria is a widely accepted optimal therapy. Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent dropout during the waiting period and as a down-staging method for the patient with intermediate HCC to qualify for liver transplantation. Transarterial chemoembolization and radiofrequency ablation are the most commonly used method for locoregional therapy. The data associated with newer modalities including drug-eluting beads, radioembolization with Y90, stereotactic radiation therapy and sorafenib will be discussed as a tool for converting advanced HCC to LT candidates. The concept “ablate and wait” has gained the popularity where mandated observation period after neo-adjuvant therapy allows for tumor biology to become apparent, thus has been recommended after down-staging. The role of neo-adjuvant therapy with conjunction of “ablate and wait” in living donor liver transplantation for intermediate stage HCC is also discussed in the paper.
文摘Liver transplantation(LT) for hepatocellular carcinoma(HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria(MC)(single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy(LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCCLT criteria models and pre-LT treatment strategies are required.
文摘BACKGROUND:Locoregional therapies(LRTs) are treatments to achieve local control of hepatocellular carcinoma(HCC).Correlation between radiologic response to LRT and degree of induced tumor necrosis is not well understood.The aim of this study was to evaluate different levels of radiologic response after pre-liver transplant(LT) LRT and its correlation with percentage of tumor necrosis on explanted histopathology.METHODS:Institutional Review Board approved LT database was queried for treated HCC in patients undergoing LT.Radiologic response was evaluated to predict tumor necrosis in the explanted liver.Tumor response was evaluated 1 to 3 months after LRT with computed tomography or MRI via Response Evaluation Criteria in Solid Tumors(RECIST),and European Association for the Study of the Liver(EASL) guidelines.LRT was repeated as needed until time of LT.Histological tumor necrosis was graded as complete(100%),partial(50%-99%),or poor(【50%).RESULTS:Between 2002 and 2011,128 patients(97 men and 31 women) received pre-LT LRT including transarterial therapy(93),radiofrequency ablation(20),or combination of both(15).The mean age of the patients was 58±9 years.Their mean follow-up was 35±27 months.The median waitlist time was 55 days.One hundred(78%) patients had HCC within the Milan criteria at the initial radiologic diagnosis.Nineteen(15%) of the patients had complete tumor necrosis on histopathology analysis.Fifty(39%) of the patients exhibited partial necrosis,52(41%) showed poor or no necrosis and 7(5%) showed progressive disease.The overall pre-LT radiologic staging was correlated with explant pathology in 73(57%) of the patients.Underestimated tumor stage was noted in 49(38%) patients,and overestimated tumor stage in 6(5%) patients.The post-LT 3-year overall survival and disease free survival were 82% and 80%,and the rates for complete and partial tumor necrosis were 100% vs 78%(P=0.02) and 100% vs 75%(P=0.03),respectively.CONCLUSIONS:In the current era,interpretation of radiologic response after LRT for HCC does not correlate accurately with histologic tumor necrosis.Total tumor necrosis is the goal of LRT;therefore,evolution in its performance is needed.Similarly,ways to predict therapy induced tumor necrosis via radiological investigation need to be improved.
文摘Background:Although offering the best chance of potential cure for patients with localized perihilar cholangiocarcinoma(pCCA),resection has been associated with high morbidity and sometimes poor long-term outcomes due to recurrence.We sought to develop a predictive model to identify individuals at high risk for very early recurrence(VER)after curative-intent surgery for pCCA.Methods:Patients who underwent curative-intent surgery for pCCA between 2000-2023 were identified from a multi-institutional database.An eXtreme Gradient Boosting(XGBoost)model was developed to estimate the risk of VER,defined as recurrence within 6 months after resection.The relative importance of clinicopathologic factors was determined using SHapley Additive exPlanations(SHAP)values.Results:Among 434 patients undergoing curative-intent resection for pCCA,65(15.0%)patients developed VER.Median overall survival(OS)among patients with and without VER was 8.4[interquartile range(IQR)6.6-11.3]versus 38.5(IQR 31.9-45.7)months(P<0.001).An XGBoost model was able to stratify patients relative to the risk of VER[low-risk:6-month recurrence-free survival(RFS)94.6%vs.intermediate-risk:6-month RFS 88.3%vs.high-risk:6-month RFS 40.0%;P<0.001].Similarly,3-year OS incrementally worsened based on VER risk(low-risk:75.3%vs.intermediate-risk:19.5%vs.high-risk:4.6%;P<0.001).The SHAP algorithm identified age,preoperative carbohydrate antigen 19-9(CA19-9)levels,tumor size and differentiation/grade,as well as lymph node metastasis as the five most important predictors of VER.The predictive accuracy of the model was good in the training[c-index:0.74,95%confidence interval(CI):0.67-0.81]and internal validation(c-index:0.77,95%CI:0.71-0.83)cohorts.An easy-to-use risk calculator for VER was developed and made available online at:https://junkawashima.shinyapps.io/VER_hilar/.Conclusions:A novel,machine learning based model was able to predict accurately the chance of VER after curative-intent resection of pCCA.In turn,the tool may help surgeons in the selection of patients likely to benefit the most from resection,as well as counsel individuals about the anticipated risk of recurrence in the early post-operative period.
文摘Background and aims:Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors.Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy.The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma.Methods:All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors,laboratory data,symptoms and radiological characteristics at presentation.Results:A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis.Patients with a serum albumin level>3.0 g/dL(P<0.01),cancer antigen 19-9≤200U/mL(P=0.03),carcinoembryonic antigen≤10g/L(P<0.01)or patients without a history of cirrhosis(P<0.01)or diabetes(P=0.02)were associated with a greater length of overall survival.A serum albumin level>3.0 g/dL was identified as an independent predictor of overall survival(hazard ratio 0.31;95%confidence interval 0.14–0.70)with a survival benefit of 44 weeks.Conclusion:This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma.A serum albumin level>3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival.
文摘Background:We sought to assess the overall benefit of laparoscopic versus open hepatectomy for treatment of colorectal liver metastases(CRLMs)using the win ratio,a novel methodological approach.Methods:CRLM patients undergoing curative-intent resection in 2001-2018 were identified from an international multi-institutional database.Patients were paired and matched based on age,number and size of lesions,lymph node status and receipt of preoperative chemotherapy.The win ratio was calculated based on margin status,severity of postoperative complications,90-day mortality,time to recurrence,and time to death.Results:Among 962 patients,the majority underwent open hepatectomy(n=832,86.5%),while a minority underwent laparoscopic hepatectomy(n=130,13.5%).Among matched patient-to-patient pairs,the odds of the patient undergoing laparoscopic resection“winning”were 1.77[WR:1.77,95%confidence interval(CI):1.42-2.34].The win ratio favored laparoscopic hepatectomy independent of low(WR:2.94,95%CI:1.20-6.39),medium(WR:1.56,95%CI:1.16-2.10)or high(WR:7.25,95%CI:1.13-32.0)tumor burden,as well as unilobar(WR:1.71,95%CI:1.25-2.31)or bilobar(WR:4.57,95%CI:2.36-8.64)disease.The odds of“winning”were particularly pronounced relative to short-term outcomes(i.e.,90-day mortality and severity of postoperative complications)(WR:4.06,95%CI:2.33-7.78).Conclusions:Patients undergoing laparoscopic hepatectomy had 77%increased odds of“winning”.Laparoscopic liver resection should be strongly considered as a preferred approach to resection in CRLM patients.
