Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is ...Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.展开更多
Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence,treatment options r...Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence,treatment options remain limited for advanced HCC,and as a result prognosis continues to be poor. Current therapeutic options,surgery,chemotherapy and radiotherapy,have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising,novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here,we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies,such as tumor-associated antigen therapy,immune checkpoint inhibitors and cell transfer immunotherapy,have demonstrated safety and feasibility in HCC patients. Unfortunately,immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this chal lenge will place immunotherapy at the forefront of HCC treatment,possibly in the near future.展开更多
A 84-year-old man with a surgical history of subtotal gastrectomy for gastric cancer was transferred to our department because of a disorder of consciousness. Septic shock due to obstructive suppurative cholangitis se...A 84-year-old man with a surgical history of subtotal gastrectomy for gastric cancer was transferred to our department because of a disorder of consciousness. Septic shock due to obstructive suppurative cholangitis secondary to choledocholithiasis was diagnosed. Anemia was also present,and upper gastrointestinal tract endoscopy revealed blood emerging from the Papilla of Vater.The cause of the anemia was identified as haemobilia.Angiography showed a small aneurysm over the artery on segment 3(A3) .The cause of the haemobilia was suspected to be the bleeding into the biliary tree from this aneurysm.Because the patient's general condition was poor,minimally invasive therapy was needed.Transcatheter arterial embolization(TAE) was selected initally.Later,lateral sectionectomy was performed in order to remove the aneurysm on A3. No surgical complication occurred and,after surgery,no haemobilia was identified.In conclusion,a twostage treatment,namely,surgery following TAE,is recommended for patients in a physically poor condition who have haemobilia due to intrahepatic aneurysm.展开更多
BACKGROUND The liver is the most common metastatic site of colorectal cancer.Hepatectomy is the mainstay of treatment for patients with colorectal liver metastases(CRLMs).However,there are cases of early recurrence af...BACKGROUND The liver is the most common metastatic site of colorectal cancer.Hepatectomy is the mainstay of treatment for patients with colorectal liver metastases(CRLMs).However,there are cases of early recurrence after upfront hepatectomy alone.In selected high-risk patients,neoadjuvant chemotherapy(NAC)may improve longterm survival.AIM To determine the efficacy of NAC for initially resectable CRLMs.METHODS Among 644 patients who underwent their first hepatectomy for CRLMs at our institution,297 resectable cases were stratified into an upfront hepatectomy group(238 patients)and a NAC group(59 patients).Poor prognostic factors for upfront hepatectomy were identified using multivariate logistic regression analysis.Propensity score matching was used to compare clinical outcomes between the upfront hepatectomy and NAC groups,according to the number of poor prognostic factors.Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS Preoperative carcinoembryonic antigen levels(≥10 ng/mL)(P=0.003),primary histological type(other than well/moderately differentiated)(P=0.04),and primary lymph node metastases(≥1)(P=0.04)were identified as independent poor prognostic factors for overall survival(OS)in the upfront hepatectomy group.High-risk status was defined as the presence of two or more risk factors.After propensity score matching,50 patients were matched in each group.Among high-risk patients,the 5-year OS rate was significantly higher in the NAC group(13 patients)than in the upfront hepatectomy group(18 patients)(100%vs 34%;P=0.02).CONCLUSION NAC may improve the prognosis of high-risk patients with resectable CRLMs who have two or more risk factors.展开更多
Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The pr...Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft(PDOX)model.This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S.typhimurium A1-R with first-line chemotherapy using the CUP PDOX model.The present study is the first to use a CUP PDOX model,which was able to precisely distinguish the chemotherapeutic course.We found that a carboplatinum(CAR)-based regimen was effective for this CUP patient.We also demonstrated that S.typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy.Our results indicate that S.typhimurium A1-R has clinical potential for CUP,a resistant disease that requires effective therapy.展开更多
Background: Patients with advanced hepatobiliary cancer (HBC) have a dismal prognosis and limited treatment options. Immunotherapy has been considered as a promising treatment, especially for cancers not amenable to s...Background: Patients with advanced hepatobiliary cancer (HBC) have a dismal prognosis and limited treatment options. Immunotherapy has been considered as a promising treatment, especially for cancers not amenable to surgery. Methods: Between 2004, and 2015, patients diagnosed with hepatocellular carcinoma (HCC), intra- and extrahepatic cholangiocarcinoma and gallbladder cancer (GBC) were identified in the National Cancer Database. Results: Among 249,913 patients with HBC, only 585 (0.2%) patients received immunotherapy. Among patients who received immunotherapy, most patients were diagnosed between 2012 and 2015, had private insurance, as well as an income ≥$46,000 and were treated at an academic facility. The use of immunotherapy among HBC patients varied by diagnosis (HCC, 67.7%;bile duct cancer, 14%). On multivariable analysis, a more recent period of diagnosis (OR 1.80, 95% CI: 1.44-2.25), median income >$46,000 (OR 1.43, 95% CI: 1.11-1.87), and higher tumor stage (stage III, OR 2.22, 95% CI: 1.65-3.01;stage IV, OR 3.24, 95% CI:2.41-4.34) were associated with greater odds of receiving immunotherapy. Conclusions: Overall utilization of immunotherapy in the US among patients with HBC was very low, yet has increased over time. Certain socioeconomic factors were associated with an increased likely of receiving immunotherapy, suggesting disparities in access of patients with lower socioeconomic status.展开更多
Background:Machine learning to predict morbidity and mortality-especially in a population traditionally considered low risk-has not been previously examined.We sought to characterize the incidence of death among patie...Background:Machine learning to predict morbidity and mortality-especially in a population traditionally considered low risk-has not been previously examined.We sought to characterize the incidence of death among patients with a low estimated morbidity and mortality risk based on the National Surgical Quality Improvement Program(NSQIP)estimated probability(EP),as well as develop a machine learning model to identify individuals at risk for“unpredicted death”(UD)among patients undergoing hepatopancreatic(HP)procedures.Methods:The NSQIP database was used to identify patients who underwent elective HP surgery between 2012-2017.The risk of morbidity and mortality was stratified into three tiers(low,intermediate,or high estimated)using a k-means clustering method with bin sorting.A machine learning classification tree and multivariable regression analyses were used to predict 30-day mortality with a 10-fold cross validation.C statistics were used to compare model performance.Results:Among 63,507 patients who underwent an HP procedure,median patient age was 63(IQR:54-71)years.Patients underwent either pancreatectomy(n=38,209,60.2%)or hepatic resection(n=25,298,39.8%).Patients were stratified into three tiers of predicted morbidity and mortality risk based on the NSQIP EP:low(n=36,923,58.1%),intermediate(n=23,609,37.2%)and high risk(n=2,975,4.7%).Among 36,923 patients with low estimated risk of morbidity and mortality,237 patients(0.6%)experienced a UD.According to the classification tree analysis,age was the most important factor to predict UD(importance 16.9)followed by preoperative albumin level(importance:10.8),disseminated cancer(importance:6.5),preoperative platelet count(importance:6.5),and sex(importance 5.9).Among patients deemed to be low risk,the c-statistic for the machine learning derived prediction model was 0.807 compared with an AUC of only 0.662 for the NSQIP EP.Conclusions:A prognostic model derived using machine learning methodology performed better than the NSQIP EP in predicting 30-day UD among low risk patients undergoing HP surgery.展开更多
文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.
文摘Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence,treatment options remain limited for advanced HCC,and as a result prognosis continues to be poor. Current therapeutic options,surgery,chemotherapy and radiotherapy,have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising,novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here,we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies,such as tumor-associated antigen therapy,immune checkpoint inhibitors and cell transfer immunotherapy,have demonstrated safety and feasibility in HCC patients. Unfortunately,immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this chal lenge will place immunotherapy at the forefront of HCC treatment,possibly in the near future.
文摘A 84-year-old man with a surgical history of subtotal gastrectomy for gastric cancer was transferred to our department because of a disorder of consciousness. Septic shock due to obstructive suppurative cholangitis secondary to choledocholithiasis was diagnosed. Anemia was also present,and upper gastrointestinal tract endoscopy revealed blood emerging from the Papilla of Vater.The cause of the anemia was identified as haemobilia.Angiography showed a small aneurysm over the artery on segment 3(A3) .The cause of the haemobilia was suspected to be the bleeding into the biliary tree from this aneurysm.Because the patient's general condition was poor,minimally invasive therapy was needed.Transcatheter arterial embolization(TAE) was selected initally.Later,lateral sectionectomy was performed in order to remove the aneurysm on A3. No surgical complication occurred and,after surgery,no haemobilia was identified.In conclusion,a twostage treatment,namely,surgery following TAE,is recommended for patients in a physically poor condition who have haemobilia due to intrahepatic aneurysm.
文摘BACKGROUND The liver is the most common metastatic site of colorectal cancer.Hepatectomy is the mainstay of treatment for patients with colorectal liver metastases(CRLMs).However,there are cases of early recurrence after upfront hepatectomy alone.In selected high-risk patients,neoadjuvant chemotherapy(NAC)may improve longterm survival.AIM To determine the efficacy of NAC for initially resectable CRLMs.METHODS Among 644 patients who underwent their first hepatectomy for CRLMs at our institution,297 resectable cases were stratified into an upfront hepatectomy group(238 patients)and a NAC group(59 patients).Poor prognostic factors for upfront hepatectomy were identified using multivariate logistic regression analysis.Propensity score matching was used to compare clinical outcomes between the upfront hepatectomy and NAC groups,according to the number of poor prognostic factors.Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS Preoperative carcinoembryonic antigen levels(≥10 ng/mL)(P=0.003),primary histological type(other than well/moderately differentiated)(P=0.04),and primary lymph node metastases(≥1)(P=0.04)were identified as independent poor prognostic factors for overall survival(OS)in the upfront hepatectomy group.High-risk status was defined as the presence of two or more risk factors.After propensity score matching,50 patients were matched in each group.Among high-risk patients,the 5-year OS rate was significantly higher in the NAC group(13 patients)than in the upfront hepatectomy group(18 patients)(100%vs 34%;P=0.02).CONCLUSION NAC may improve the prognosis of high-risk patients with resectable CRLMs who have two or more risk factors.
文摘Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy.CUP consists of diverse malignancy groups,making personalized precision therapy essential.The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft(PDOX)model.This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S.typhimurium A1-R with first-line chemotherapy using the CUP PDOX model.The present study is the first to use a CUP PDOX model,which was able to precisely distinguish the chemotherapeutic course.We found that a carboplatinum(CAR)-based regimen was effective for this CUP patient.We also demonstrated that S.typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy.Our results indicate that S.typhimurium A1-R has clinical potential for CUP,a resistant disease that requires effective therapy.
文摘Background: Patients with advanced hepatobiliary cancer (HBC) have a dismal prognosis and limited treatment options. Immunotherapy has been considered as a promising treatment, especially for cancers not amenable to surgery. Methods: Between 2004, and 2015, patients diagnosed with hepatocellular carcinoma (HCC), intra- and extrahepatic cholangiocarcinoma and gallbladder cancer (GBC) were identified in the National Cancer Database. Results: Among 249,913 patients with HBC, only 585 (0.2%) patients received immunotherapy. Among patients who received immunotherapy, most patients were diagnosed between 2012 and 2015, had private insurance, as well as an income ≥$46,000 and were treated at an academic facility. The use of immunotherapy among HBC patients varied by diagnosis (HCC, 67.7%;bile duct cancer, 14%). On multivariable analysis, a more recent period of diagnosis (OR 1.80, 95% CI: 1.44-2.25), median income >$46,000 (OR 1.43, 95% CI: 1.11-1.87), and higher tumor stage (stage III, OR 2.22, 95% CI: 1.65-3.01;stage IV, OR 3.24, 95% CI:2.41-4.34) were associated with greater odds of receiving immunotherapy. Conclusions: Overall utilization of immunotherapy in the US among patients with HBC was very low, yet has increased over time. Certain socioeconomic factors were associated with an increased likely of receiving immunotherapy, suggesting disparities in access of patients with lower socioeconomic status.
文摘Background:Machine learning to predict morbidity and mortality-especially in a population traditionally considered low risk-has not been previously examined.We sought to characterize the incidence of death among patients with a low estimated morbidity and mortality risk based on the National Surgical Quality Improvement Program(NSQIP)estimated probability(EP),as well as develop a machine learning model to identify individuals at risk for“unpredicted death”(UD)among patients undergoing hepatopancreatic(HP)procedures.Methods:The NSQIP database was used to identify patients who underwent elective HP surgery between 2012-2017.The risk of morbidity and mortality was stratified into three tiers(low,intermediate,or high estimated)using a k-means clustering method with bin sorting.A machine learning classification tree and multivariable regression analyses were used to predict 30-day mortality with a 10-fold cross validation.C statistics were used to compare model performance.Results:Among 63,507 patients who underwent an HP procedure,median patient age was 63(IQR:54-71)years.Patients underwent either pancreatectomy(n=38,209,60.2%)or hepatic resection(n=25,298,39.8%).Patients were stratified into three tiers of predicted morbidity and mortality risk based on the NSQIP EP:low(n=36,923,58.1%),intermediate(n=23,609,37.2%)and high risk(n=2,975,4.7%).Among 36,923 patients with low estimated risk of morbidity and mortality,237 patients(0.6%)experienced a UD.According to the classification tree analysis,age was the most important factor to predict UD(importance 16.9)followed by preoperative albumin level(importance:10.8),disseminated cancer(importance:6.5),preoperative platelet count(importance:6.5),and sex(importance 5.9).Among patients deemed to be low risk,the c-statistic for the machine learning derived prediction model was 0.807 compared with an AUC of only 0.662 for the NSQIP EP.Conclusions:A prognostic model derived using machine learning methodology performed better than the NSQIP EP in predicting 30-day UD among low risk patients undergoing HP surgery.
