目的探讨联合肝脏离断和门静脉结扎的2步肝切除新技术在提高结直肠癌肝转移患者可切除的意义.方法结直肠癌肝转移患者接受联合肝脏离断和门静脉结扎的2步肝切除,手术第1步,门静脉右支结扎后离断右三肝和左外侧叶肝实质,待健侧肝组织增...目的探讨联合肝脏离断和门静脉结扎的2步肝切除新技术在提高结直肠癌肝转移患者可切除的意义.方法结直肠癌肝转移患者接受联合肝脏离断和门静脉结扎的2步肝切除,手术第1步,门静脉右支结扎后离断右三肝和左外侧叶肝实质,待健侧肝组织增生后再行右三肝切除.结果第1步手术后7 d,残肝体积从313.5 m L增加到559.1 m L,并在第1步手术后8 d,第2步手术行右三肝切除.第2步手术后8 d患者顺利出院,肝功能恢复基本正常,联合肝脏离断和门静脉结扎的二步肝切除诱导了残肝组织快速的增生.结论联合肝脏离断和门静脉结扎的二步肝切除提高了结直肠癌肝转移患者的可切除率.联合肝脏离断和门静脉结扎的二步肝切除有较高的并发症率和死亡率,因此需要仔细选择手术患者;该术式的可行性、安全性还需要进一步研究评估.展开更多
目的:评价结直肠癌肝转移(colorectal cancer liver metastases,CRLM)射频消融(radiofrequency ablation,RFA)治疗的可行性。方法:2003年12月至2008年11月67例结直肠癌肝转移患者在西安交通大学医学院第一附属医院接受了RFA治疗。根据实...目的:评价结直肠癌肝转移(colorectal cancer liver metastases,CRLM)射频消融(radiofrequency ablation,RFA)治疗的可行性。方法:2003年12月至2008年11月67例结直肠癌肝转移患者在西安交通大学医学院第一附属医院接受了RFA治疗。根据实施RFA治疗的方法将患者分成3组:经皮穿刺RFA(第1组)、开腹RFA(第2组)或经皮RFA与手术相结合的方法(第3组)。结果:RFA后90天,3组的死亡率均为零。一半的患者(34/67)出现手术后轻度发热。1/4的患者(17/67)有右肩部与右季肋部疼痛或不适。1例并发结肠瘘。随访显示1年、3年和5年生存率分别是100%、34.3%和4.5%。结论:对CRLM的患者,RFA或结合肝切除手术是相对微创、安全可行的方法,而且致死率低。展开更多
Colorectal cancer is the leading cause of cancer-related death globally.The liver is the most predominant site for metastatic disease.Approximately 20-30%of patients diagnosed with colorectal cancer develop liver meta...Colorectal cancer is the leading cause of cancer-related death globally.The liver is the most predominant site for metastatic disease.Approximately 20-30%of patients diagnosed with colorectal cancer develop liver metastases.Surgical resection is considered the only potentially curative treatment for colorectal liver metastases(CRLM)(1).Several studies have indicated that liver resection provides favorable long-term survival for patients with CRLM.Both open liver resection(OLR)and laparoscopic liver resection(LLR)are used to treat CRLM,and the incidence of LLR has been increasing.LLR is a minimally invasive technique that has become predominantly used for treating CRLM.The first international consensus conference in Louisville in 2008 recommended LLR for solitary tumors measuring≤5 cm in the anterolateral segments(2).The second international consensus conference in Morioka established minor LLR as a standard procedure(3).Recently,short-term outcomes have demonstrated that LLR leads to lower morbidity,less blood losses,fewer transfusions,and shorter hospital stays compared to OLR.展开更多
The dual centre retrospective study by Chávez-Villa et al.assessed the rate of radiologically missed,occult colorectal liver metastases(CRLM)on pathologic evaluation of total hepatectomy specimens(1).Of the 14 pa...The dual centre retrospective study by Chávez-Villa et al.assessed the rate of radiologically missed,occult colorectal liver metastases(CRLM)on pathologic evaluation of total hepatectomy specimens(1).Of the 14 patients who underwent liver transplantation for unresectable CRLM,7(50%)patients were deemed to have radiographically viable tumours,as defined by fluorodeoxyglucose positron emission tomography(FDG-PET)avidity;the remainder had complete radiographic response.However,on pathologic assessment,11(78.6%)were noted to have viable tumours,with a median of two viable tumours,ranging from 0.2 to 6.5 cm in size.Three(21.4%)patients had complete radiological and pathological responses.展开更多
Colorectal cancer is the second leading cause of cancer-related death globally.Approximately half of colorectal cancer patients develop liver metastasis,and the overall prognosis is significantly influenced by the ext...Colorectal cancer is the second leading cause of cancer-related death globally.Approximately half of colorectal cancer patients develop liver metastasis,and the overall prognosis is significantly influenced by the extent of these liver metastases(1).Multiple studies have investigated the risk factors affecting survival in colorectal liver metastasis(CRLM),and have found that Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation,v-Raf murine sarcoma viral oncogene homolog B1(BRAF)mutation,tumor morphology,carcinoembryonic antigen(CEA)levels,primary lymph node metastases,surgical margin width,primary tumor site(right or left),and the presence of extrahepatic disease influence survival following curative resection(1).展开更多
Background:In patients with colorectal liver metastases(CRLM),preoperative chemotherapy may increase resectability and survival outcomes.However,cytotoxic agents can also cause chemotherapy-associated liver injury(CAL...Background:In patients with colorectal liver metastases(CRLM),preoperative chemotherapy may increase resectability and survival outcomes.However,cytotoxic agents can also cause chemotherapy-associated liver injury(CALI),leading to increased rates of postoperative complications.This study evaluates the association between splenic hypertrophy(SH)after preoperative chemotherapy and postoperative liver-specific complications(LSC),in patients undergoing major liver resection for CRLM.Methods:This retrospective study included patients who underwent major curative liver resection of CRLM following preoperative chemotherapy at the University Hospital RWTH Aachen(UH-RWTH)between 2010-2021.Patients with missing radiological images,incomplete data on chemotherapy regimens,or prior splenectomy were excluded.Volumetric measurements of the spleen were performed on preoperative computerized tomography(CT)and magnetic resonance imaging(MRI)images,using segmentation software(3D-Slicer).Receiver-operating characteristic(ROC)analysis was performed to determine the optimal SH cut-off for predicting postoperative LSC.Independent risk factors of postoperative LSC were examined using logistic regression.Results:A total of 115 patients were included in the study,of which 78(68%)received oxaliplatin as part of their preoperative chemotherapy regimen.A threshold of 8.6%SH(Youden Index=0.25)was identified as predictive of postoperative LSC.Patients with SH>8.6%(n=62)received oxaliplatin significantly more often(84%vs.49%;P<0.001)and exhibited higher rates of liver fibrosis(72%vs.52%,P=0.03)and LSC(63%vs.38%,P=0.007).Multivariable logistic regression analysis identified SH>8.6%as an independent risk factor for LSC(odds ratio 2.86,95%confidence interval:1.104-7.402,P=0.03).Conclusions:Preoperative SH may be a valuable predictor of postoperative LSC in patients undergoing major liver resection for CRLM,following chemotherapy.Further studies are necessary to investigate the impact on a larger cohort and find preventive strategies to mitigate and treat CALI.展开更多
Surgical margin is an important prognosticator in patients undergoing hepatectomy for colorectal liver metastases(CRLM)(1).However,the incidence of cut-end recurrence is relatively low,approximately 5-20%,even in pati...Surgical margin is an important prognosticator in patients undergoing hepatectomy for colorectal liver metastases(CRLM)(1).However,the incidence of cut-end recurrence is relatively low,approximately 5-20%,even in patients with pathologically positive(R1)resection(1).Therefore,cut-end recurrence is not an underlying cause of poor prognosis in patients with narrow surgical margin,but it is thought to reflect tumor progression and biology(1,2).展开更多
The TransMet trial is a multicenter,prospective,randomized controlled study aimed at comparing the efficacy of liver transplantation combined with chemotherapy(LT+CT)versus chemotherapy(CT)alone in patients with unres...The TransMet trial is a multicenter,prospective,randomized controlled study aimed at comparing the efficacy of liver transplantation combined with chemotherapy(LT+CT)versus chemotherapy(CT)alone in patients with unresectable colorectal liver metastases(CRLM)(1).Patient enrollment took place between February 2016 and July 2021.This study enrolled patients aged 18 to 65 years with liver-confined metastases who demonstrated either a partial response or disease stabilization after at least 3 months of CT.The primary objective of the study was to assess 5-year overall survival(OS),with secondary outcomes including 3-year OS,3-and 5-year progression-free survival(PFS),as well as recurrence rates.展开更多
We enjoyed the article by Kampf et al.(1)on obesity and its association with fatty liver and post-hepatectomy liver failure(PHLF).They concluded that obesity,defined by body mass index(BMI),was associated with liver s...We enjoyed the article by Kampf et al.(1)on obesity and its association with fatty liver and post-hepatectomy liver failure(PHLF).They concluded that obesity,defined by body mass index(BMI),was associated with liver steatosis and fibrosis;however,postoperative complications,including PHLF after liver resection,were comparable regardless of BMI,suggesting that liver resection is safely performed in obese patients.However,the surgical method for obese patients is also important,and Inoue et al.have reported that open liver resection for colorectal liver metastases(CRLM)in obese patients resulted in a significantly higher risk of infectious complications than laparoscopic liver resection(2).展开更多
Excessive fructose diet is closely associated with colorectal cancer(CRC)progression.Nevertheless,fructose’s specific function and precise mechanism in colorectal cancer liver metastasis(CRLM)is rarely known.Here,thi...Excessive fructose diet is closely associated with colorectal cancer(CRC)progression.Nevertheless,fructose’s specific function and precise mechanism in colorectal cancer liver metastasis(CRLM)is rarely known.Here,this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM,and the expression of KHK-A,not KHK-C,in liver metastasis was higher than in paired primary tumors.Furthermore,KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at Ser37.PKM2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of PKM2.EMT and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells’migration ability and anoikis resistance during CRLM progression.TEPP-46 treatment,targeting the phosphorylation of PKM2,inhibited the pro-metastatic effect of KHK-A.Besides,c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A,forming a positive feedback loop.展开更多
Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors ...Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM.Methods:This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1,2012,to December 31,2020.Propensity score matching with 1:1 ratio matching was performed.The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status.Moreover,whole-exome sequencing(WES)of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles.Results:The median follow-up was 68 months.Matching yielded 481 pairs of patients.Compared to right-sided CRLM,left-sided patients experienced with better 5-year overall survival(OS)in surgery responsiveness,with a 14.6 lower risk of death[hazard ratio(HR),1.36,95%confidence interval(CI),1.10-1.69,P=0.004].Interaction between tumor sidedness and KRAS status was statistically significant:left-sidedness was associated with better prognosis among KRAS wild-type patients(HR 1.71;95%CI:1.20-2.45;P=0.003),but not among KRAS mutated-type patients.Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53,APC,KRAS,and BRAF alterations,and identified a critical role of KRAS mutation in correlation with their survival differences.Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors(29.3%vs.15.5%,P=0.03).Conclusions:We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors.Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.展开更多
Colorectal cancer represents the third most common cancer and about 20%are diagnosed with synchronous metastatic disease.From a historical point of view,surgery remains the mainstream treatment for resectable colorect...Colorectal cancer represents the third most common cancer and about 20%are diagnosed with synchronous metastatic disease.From a historical point of view,surgery remains the mainstream treatment for resectable colorectal liver metastases(CRLM).Furthermore,disease outcomes are improving due significant advances in systemic treatments and diagnostic methods.However,the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open question.Thus,patient selection combining image workouts,time of recurrence,positive lymph nodes,and molecular biomarkers can improve the decision-making process.Nevertheless,molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of treatment.Tumor biomakers,genetic profiling,and circulating tumor DNA have been used to offer as much personalized treatment as possible,based on the precision oncology concept of tailored care rather than a guideline-based therapy.This review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.展开更多
With great interest,we read the article by Lam et al.(1)entitled“A machine learning model for colorectal liver metastasis post-hepatectomy prognostications”.In this study,the authors included colorectal liver metast...With great interest,we read the article by Lam et al.(1)entitled“A machine learning model for colorectal liver metastasis post-hepatectomy prognostications”.In this study,the authors included colorectal liver metastasis(CRLM)patients from four hospitals in Hong Kong who underwent hepatic resection,and developed a survival prediction model based on the patients’demographic,oncologic,clinicopathologic,and therapeutic characteristics using machine learning.Through Cox proportional hazards and least absolute shrinkage and selection operator(LASSO)regression analyses,the authors successfully developed a predictive model consisting of eight predictors that could accurately predict overall survival(OS)and recurrence-free survival(RFS)after hepatectomy in patients with CRLM.This is an intriguing study with significant clinical value,and the authors deserve to be commended for their efforts.However,there are still several issues that need to be addressed in this study.展开更多
Approximately half of individuals diagnosed with colorectal cancer(CRC)will develop colorectal liver metastasis(CRLM)during the course of their disease(1,2).Liver resection is the only potentially curative treatment f...Approximately half of individuals diagnosed with colorectal cancer(CRC)will develop colorectal liver metastasis(CRLM)during the course of their disease(1,2).Liver resection is the only potentially curative treatment for patients with CRLM,yet less than 20%of individuals are candidates for resection due to the extent or location of liver disease,underlying liver function and/or presence of extrahepatic metastases(1,2).In addition,the oncologic benefit of liver resection for CRLM is limited by recurrence rates than can be as high as 70%(3).Liver transplantation(LT)for CRLM was initially proposed as an alternative treatment strategy in the early 1990s but was abandoned due to the initial poor outcomes(3,4).The concept of transplantation for CRLM was later revisited in the 2000s by a group in Oslo,Norway that reported promising results in the SECA-I pilot study(5).Since the completion of the SECA-I study,the Norwegian group has also published other promising data from the SECA-II study(6).In addition,other notable outcomes have been reported in the RAPID study(7),as well as another study from specialized centers in North America(8),both of which have revitalized the concept of LT for CRLM.展开更多
文摘目的探讨联合肝脏离断和门静脉结扎的2步肝切除新技术在提高结直肠癌肝转移患者可切除的意义.方法结直肠癌肝转移患者接受联合肝脏离断和门静脉结扎的2步肝切除,手术第1步,门静脉右支结扎后离断右三肝和左外侧叶肝实质,待健侧肝组织增生后再行右三肝切除.结果第1步手术后7 d,残肝体积从313.5 m L增加到559.1 m L,并在第1步手术后8 d,第2步手术行右三肝切除.第2步手术后8 d患者顺利出院,肝功能恢复基本正常,联合肝脏离断和门静脉结扎的二步肝切除诱导了残肝组织快速的增生.结论联合肝脏离断和门静脉结扎的二步肝切除提高了结直肠癌肝转移患者的可切除率.联合肝脏离断和门静脉结扎的二步肝切除有较高的并发症率和死亡率,因此需要仔细选择手术患者;该术式的可行性、安全性还需要进一步研究评估.
文摘目的:评价结直肠癌肝转移(colorectal cancer liver metastases,CRLM)射频消融(radiofrequency ablation,RFA)治疗的可行性。方法:2003年12月至2008年11月67例结直肠癌肝转移患者在西安交通大学医学院第一附属医院接受了RFA治疗。根据实施RFA治疗的方法将患者分成3组:经皮穿刺RFA(第1组)、开腹RFA(第2组)或经皮RFA与手术相结合的方法(第3组)。结果:RFA后90天,3组的死亡率均为零。一半的患者(34/67)出现手术后轻度发热。1/4的患者(17/67)有右肩部与右季肋部疼痛或不适。1例并发结肠瘘。随访显示1年、3年和5年生存率分别是100%、34.3%和4.5%。结论:对CRLM的患者,RFA或结合肝切除手术是相对微创、安全可行的方法,而且致死率低。
文摘Colorectal cancer is the leading cause of cancer-related death globally.The liver is the most predominant site for metastatic disease.Approximately 20-30%of patients diagnosed with colorectal cancer develop liver metastases.Surgical resection is considered the only potentially curative treatment for colorectal liver metastases(CRLM)(1).Several studies have indicated that liver resection provides favorable long-term survival for patients with CRLM.Both open liver resection(OLR)and laparoscopic liver resection(LLR)are used to treat CRLM,and the incidence of LLR has been increasing.LLR is a minimally invasive technique that has become predominantly used for treating CRLM.The first international consensus conference in Louisville in 2008 recommended LLR for solitary tumors measuring≤5 cm in the anterolateral segments(2).The second international consensus conference in Morioka established minor LLR as a standard procedure(3).Recently,short-term outcomes have demonstrated that LLR leads to lower morbidity,less blood losses,fewer transfusions,and shorter hospital stays compared to OLR.
文摘The dual centre retrospective study by Chávez-Villa et al.assessed the rate of radiologically missed,occult colorectal liver metastases(CRLM)on pathologic evaluation of total hepatectomy specimens(1).Of the 14 patients who underwent liver transplantation for unresectable CRLM,7(50%)patients were deemed to have radiographically viable tumours,as defined by fluorodeoxyglucose positron emission tomography(FDG-PET)avidity;the remainder had complete radiographic response.However,on pathologic assessment,11(78.6%)were noted to have viable tumours,with a median of two viable tumours,ranging from 0.2 to 6.5 cm in size.Three(21.4%)patients had complete radiological and pathological responses.
文摘Colorectal cancer is the second leading cause of cancer-related death globally.Approximately half of colorectal cancer patients develop liver metastasis,and the overall prognosis is significantly influenced by the extent of these liver metastases(1).Multiple studies have investigated the risk factors affecting survival in colorectal liver metastasis(CRLM),and have found that Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation,v-Raf murine sarcoma viral oncogene homolog B1(BRAF)mutation,tumor morphology,carcinoembryonic antigen(CEA)levels,primary lymph node metastases,surgical margin width,primary tumor site(right or left),and the presence of extrahepatic disease influence survival following curative resection(1).
基金supported by the START-Program(#01/23)of the Faculty of Medicine of the RWTH Aachen University,Aachen,Germany。
文摘Background:In patients with colorectal liver metastases(CRLM),preoperative chemotherapy may increase resectability and survival outcomes.However,cytotoxic agents can also cause chemotherapy-associated liver injury(CALI),leading to increased rates of postoperative complications.This study evaluates the association between splenic hypertrophy(SH)after preoperative chemotherapy and postoperative liver-specific complications(LSC),in patients undergoing major liver resection for CRLM.Methods:This retrospective study included patients who underwent major curative liver resection of CRLM following preoperative chemotherapy at the University Hospital RWTH Aachen(UH-RWTH)between 2010-2021.Patients with missing radiological images,incomplete data on chemotherapy regimens,or prior splenectomy were excluded.Volumetric measurements of the spleen were performed on preoperative computerized tomography(CT)and magnetic resonance imaging(MRI)images,using segmentation software(3D-Slicer).Receiver-operating characteristic(ROC)analysis was performed to determine the optimal SH cut-off for predicting postoperative LSC.Independent risk factors of postoperative LSC were examined using logistic regression.Results:A total of 115 patients were included in the study,of which 78(68%)received oxaliplatin as part of their preoperative chemotherapy regimen.A threshold of 8.6%SH(Youden Index=0.25)was identified as predictive of postoperative LSC.Patients with SH>8.6%(n=62)received oxaliplatin significantly more often(84%vs.49%;P<0.001)and exhibited higher rates of liver fibrosis(72%vs.52%,P=0.03)and LSC(63%vs.38%,P=0.007).Multivariable logistic regression analysis identified SH>8.6%as an independent risk factor for LSC(odds ratio 2.86,95%confidence interval:1.104-7.402,P=0.03).Conclusions:Preoperative SH may be a valuable predictor of postoperative LSC in patients undergoing major liver resection for CRLM,following chemotherapy.Further studies are necessary to investigate the impact on a larger cohort and find preventive strategies to mitigate and treat CALI.
文摘Surgical margin is an important prognosticator in patients undergoing hepatectomy for colorectal liver metastases(CRLM)(1).However,the incidence of cut-end recurrence is relatively low,approximately 5-20%,even in patients with pathologically positive(R1)resection(1).Therefore,cut-end recurrence is not an underlying cause of poor prognosis in patients with narrow surgical margin,but it is thought to reflect tumor progression and biology(1,2).
文摘The TransMet trial is a multicenter,prospective,randomized controlled study aimed at comparing the efficacy of liver transplantation combined with chemotherapy(LT+CT)versus chemotherapy(CT)alone in patients with unresectable colorectal liver metastases(CRLM)(1).Patient enrollment took place between February 2016 and July 2021.This study enrolled patients aged 18 to 65 years with liver-confined metastases who demonstrated either a partial response or disease stabilization after at least 3 months of CT.The primary objective of the study was to assess 5-year overall survival(OS),with secondary outcomes including 3-year OS,3-and 5-year progression-free survival(PFS),as well as recurrence rates.
文摘We enjoyed the article by Kampf et al.(1)on obesity and its association with fatty liver and post-hepatectomy liver failure(PHLF).They concluded that obesity,defined by body mass index(BMI),was associated with liver steatosis and fibrosis;however,postoperative complications,including PHLF after liver resection,were comparable regardless of BMI,suggesting that liver resection is safely performed in obese patients.However,the surgical method for obese patients is also important,and Inoue et al.have reported that open liver resection for colorectal liver metastases(CRLM)in obese patients resulted in a significantly higher risk of infectious complications than laparoscopic liver resection(2).
基金funded by the National Natural Science Foundation(Grant Number 82273406)Basic Research Program of Jiangsu Province(Grant No.BK20201491,China)+2 种基金Nature Key Research and Development Program of Jiangsu Province(BE2021742,China)Jiangsu Province Capability Improvement Project through Science,Technology and Education(Jiangsu Provincial Medical Key Discipline,ZDXK202222,China)the National Natural Science Foundation(Grant Number 82203656,China).
文摘Excessive fructose diet is closely associated with colorectal cancer(CRC)progression.Nevertheless,fructose’s specific function and precise mechanism in colorectal cancer liver metastasis(CRLM)is rarely known.Here,this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM,and the expression of KHK-A,not KHK-C,in liver metastasis was higher than in paired primary tumors.Furthermore,KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at Ser37.PKM2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of PKM2.EMT and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells’migration ability and anoikis resistance during CRLM progression.TEPP-46 treatment,targeting the phosphorylation of PKM2,inhibited the pro-metastatic effect of KHK-A.Besides,c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A,forming a positive feedback loop.
基金supported by National Natural Science Foundation of China(81874182,M-0334)Natural Science Foundation of Shanghai(22ZR1413300)+2 种基金National Science and Technology Major Project(2017ZX10203204-007-004)Shanghai Municipal Health Bureau(201940043)Shanghai Hospital Development Center(SHDC12019X19).
文摘Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM.Methods:This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1,2012,to December 31,2020.Propensity score matching with 1:1 ratio matching was performed.The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status.Moreover,whole-exome sequencing(WES)of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles.Results:The median follow-up was 68 months.Matching yielded 481 pairs of patients.Compared to right-sided CRLM,left-sided patients experienced with better 5-year overall survival(OS)in surgery responsiveness,with a 14.6 lower risk of death[hazard ratio(HR),1.36,95%confidence interval(CI),1.10-1.69,P=0.004].Interaction between tumor sidedness and KRAS status was statistically significant:left-sidedness was associated with better prognosis among KRAS wild-type patients(HR 1.71;95%CI:1.20-2.45;P=0.003),but not among KRAS mutated-type patients.Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53,APC,KRAS,and BRAF alterations,and identified a critical role of KRAS mutation in correlation with their survival differences.Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors(29.3%vs.15.5%,P=0.03).Conclusions:We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors.Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.
文摘Colorectal cancer represents the third most common cancer and about 20%are diagnosed with synchronous metastatic disease.From a historical point of view,surgery remains the mainstream treatment for resectable colorectal liver metastases(CRLM).Furthermore,disease outcomes are improving due significant advances in systemic treatments and diagnostic methods.However,the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open question.Thus,patient selection combining image workouts,time of recurrence,positive lymph nodes,and molecular biomarkers can improve the decision-making process.Nevertheless,molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of treatment.Tumor biomakers,genetic profiling,and circulating tumor DNA have been used to offer as much personalized treatment as possible,based on the precision oncology concept of tailored care rather than a guideline-based therapy.This review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.
基金Key University Natural Science Research Project of Anhui Province(No.2023AH053416)partly supported by the Open Funds of the Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation(No.2023KF012)Anhui Provincial Postdoctoral Scientific Foundation(No.2023A660).
文摘With great interest,we read the article by Lam et al.(1)entitled“A machine learning model for colorectal liver metastasis post-hepatectomy prognostications”.In this study,the authors included colorectal liver metastasis(CRLM)patients from four hospitals in Hong Kong who underwent hepatic resection,and developed a survival prediction model based on the patients’demographic,oncologic,clinicopathologic,and therapeutic characteristics using machine learning.Through Cox proportional hazards and least absolute shrinkage and selection operator(LASSO)regression analyses,the authors successfully developed a predictive model consisting of eight predictors that could accurately predict overall survival(OS)and recurrence-free survival(RFS)after hepatectomy in patients with CRLM.This is an intriguing study with significant clinical value,and the authors deserve to be commended for their efforts.However,there are still several issues that need to be addressed in this study.
文摘Approximately half of individuals diagnosed with colorectal cancer(CRC)will develop colorectal liver metastasis(CRLM)during the course of their disease(1,2).Liver resection is the only potentially curative treatment for patients with CRLM,yet less than 20%of individuals are candidates for resection due to the extent or location of liver disease,underlying liver function and/or presence of extrahepatic metastases(1,2).In addition,the oncologic benefit of liver resection for CRLM is limited by recurrence rates than can be as high as 70%(3).Liver transplantation(LT)for CRLM was initially proposed as an alternative treatment strategy in the early 1990s but was abandoned due to the initial poor outcomes(3,4).The concept of transplantation for CRLM was later revisited in the 2000s by a group in Oslo,Norway that reported promising results in the SECA-I pilot study(5).Since the completion of the SECA-I study,the Norwegian group has also published other promising data from the SECA-II study(6).In addition,other notable outcomes have been reported in the RAPID study(7),as well as another study from specialized centers in North America(8),both of which have revitalized the concept of LT for CRLM.
