Cholangiocarcinoma(CCA)is an aggressive malignancy arising from the biliary epithelium.It may occur at any location along the biliary tree with the perihilar area being the most common.Prognosis is poor with 5-year ov...Cholangiocarcinoma(CCA)is an aggressive malignancy arising from the biliary epithelium.It may occur at any location along the biliary tree with the perihilar area being the most common.Prognosis is poor with 5-year overall survival at less than 10%,typically due to unresectable disease at presentation.Radical surgical resection with clear margins offers a chance of cure in patients with resectable tumours,but is frequently not possible due to locally advanced disease.On the other hand,orthotopic liver transplantation(LT)allows for a radical and potentially curative resection for these patients,but has been historically controversial due to the limited supply of donor grafts and previously poor outcomes.In patients with perihilar CCA,within specific criteria and following the implementation of a protocol combining neoadjuvant chemoradiation and LT,excellent results have been achieved in the last decades,resulting in its increasing acceptance as an indication for LT and the standard of care in several centres with significant experience.However,in intrahepatic CCA,the role of LT remains controversial and owing to dismal previous results it is not an accepted indication.Nevertheless,more recent studies have demonstrated favourable results with LT in early intrahepatic CCA,indicating that,under defined criteria,its role may increase in the future.This review highlights the history and contemporary advances of LT in CCA,with particular focus on the improving outcomes of LT in intrahepatic and perihilar CCA and future perspectives.展开更多
Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow po...Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor unresectable.The median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are necessary.Vascular resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal tumors.Thus,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.展开更多
Over the past decade,enhanced preoperative imaging and visualization,improved delineation of the complex anatomical structures of the liver and pancreas,and intra-operative technological advances have helped deliver t...Over the past decade,enhanced preoperative imaging and visualization,improved delineation of the complex anatomical structures of the liver and pancreas,and intra-operative technological advances have helped deliver the liver and pancreatic surgery with increased safety and better postoperative outcomes.Artificial intelligence(AI)has a major role to play in 3D visualization,virtual simulation,augmented reality that helps in the training of surgeons and the future delivery of conventional,laparoscopic,and robotic hepatobiliary and pancreatic(HPB)surgery;artificial neural networks and machine learning has the potential to revolutionize individualized patient care during the preoperative imaging,and postoperative surveillance.In this paper,we reviewed the existing evidence and outlined the potential for applying AI in the perioperative care of patients undergoing HPB surgery.展开更多
BACKGROUND The global incidence of intrahepatic cholangiocarcinoma(ICCA)is soaring.Due to often delayed presentation,only a narrow spectrum of the disease is usually surgically resectable.To more accurately stage the ...BACKGROUND The global incidence of intrahepatic cholangiocarcinoma(ICCA)is soaring.Due to often delayed presentation,only a narrow spectrum of the disease is usually surgically resectable.To more accurately stage the disease,reduce recurrence,and improve overall survival,surgical teams are increasingly performing intraoperative lymph node dissection(LND)as well.This procedure has its associated morbidity,while there is no consensus or formal guidelines on its role in this setting.Hence,there is a need to better delineate the evidence for performing LND alongside surgical resection of the ICCA.AIM To perform a systematic review and meta-analysis on the role of LND in improving prognostication and survival post-resection of ICCA.METHODS We performed a systematic literature search using Pubmed,Medline,Embase,and the Cochrane Library,for all studies involving LND,ICCA,and surgical resection using several keywords,Medical Subject Headings(MeSH)tags,and appropriate synonyms.All clinical studies comparing curative intent resection of ICCA with LND vs resection without LND were included,while single-arm case series,studies with insufficient data,and duplicates were excluded.We included all English-language studies from the different academic databases up till early December 2022.The primary outcome measures were set for overall survival(OS)and disease-free survival(DFS).RESULTS This systematic review and meta-analysis included 15 studies that fulfilled the selection criteria comprising 11413 patients with surgically-resectable ICCA,of whom 6424(56.3%)underwent hepatectomy with LND while the remainder underwent hepatectomy only.In patients who underwent LND,on average,27.7%of the resected lymph nodes were positive for metastatic disease.Overall,the results showed that performing LND did not significantly improve OS or DFS.However,the effect of LND on OS showed a degree of variability by geographical region,in Eastern and Western countries.As LND is increasingly being performed,further time-based analysis was undertaken to identify time-dependent changes in the role of LND.An increasing adoption of LND was not associated with improved OS.Furthermore,no roles were identified for neoadjuvant/adjuvant chemotherapy or increasing lymph node retrieval in improving OS either.CONCLUSION LND might aid in staging,prognosticating,and deciding further management of resected ICCA,but does not improve OS and DFS and is unsuitable for high-risk patients unlikely to benefit from further treatments.展开更多
AIM： To investigate a dual labeling technique, which would enable real-time monitoring of transplanted em- bryonic stem cell （ESC） kinetics, as well as long-term tracking. METHODS： Liver damage was induced in C57/...AIM： To investigate a dual labeling technique, which would enable real-time monitoring of transplanted em- bryonic stem cell （ESC） kinetics, as well as long-term tracking. METHODS： Liver damage was induced in C57/BL6 male mice （n = 40） by acetaminophen （APAP） 300 mg/kg administered intraperitoneally. Green fluores- cence protein （GFP） positive C57/BL6 mouse ESCs were stained with the near-infrared fluorescent lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbo- cyanine iodide （DiR） immediately before transplantationinto the spleen. Each of the animals in the cell therapy group （n = 20） received 5 x 106 ESCs 4 h following treatment with APAP. The control group （n = 20） re- ceived the vehicle only. The distribution and dynamics of the cells were monitored in real-time with the IVIS lumina-2 at 30 rain post transplantation, then at 3, 12, 24, 48 and 72 h, and after one and 2 wk. Immunohisto- chemical examination of liver tissue was used to identify expression of GFP and albumin. Plasma alanine amino- transferase （ALT） was measured as an indication of liver damage.RESULTS： DiR-stained ESCs were easily tracked with the IVIS using the indocyanine green filter due to its high background passband with minimal background autofluorescence. The transplanted cells were confined inside the spleen at 30 min post-transplantation, gradu- ally moved into the splenic vein, and were detectable in parts of the liver at the 3 h time-point. Within 24 h of transplantation, homing of almost 90% of cells was confirmed in the liver. On day three, however, the DiR signal started to fade out, and ex vivo IVIS imaging of different organs allowed signal detection at time-points when the signal could not be detected by in vivo imag- ing, and confirmed that the highest photon emission was in the liver （P 〈 0.0001）. At 2 wk, the DiRsignal was no longer detectable in vivo; however, immuno- histochemistry analysis of constitutively-expressed GFP was used to provide an insight into the distribution of the cells. GFP ＋ve cells were detected in tissue sections resembling hepatocytes and were dispersed throughout the hepatic parenchyma, with the presence of a larger number of GFP ＋ve cells incorporated within the sinu- soidal endothelial lining. Very faint albumin expression was detected in the transplanted GFP ＋re cells at 72 h; however at 2 wk, few cells that were positive for GFP were also strongly positive for albumin. There was a significant improvement in serum levels of ALT, albumin and bilirubin in both groups at 2 wk when compared with the 72 h time-point. In the cell therapy group, serum ALT was significantly （P = 0.016） lower and al- bumin （P = 0.009） was significantly higher when com- pared with the control group at the 2 wk time-point;however there was no difference in mortality between the two groups. CONCLUSION： Dual labeling is an easy to use and cheap method for longitudinal monitoring of distribu- tion, survival and engraftment of transplanted cells, and could be used for cell therapy models.展开更多
Intrahepatic cholangiocarcinoma(iCCA)is an aggressive malignancy with an increasing incidence worldwide and poor prognosis,despite several advances and continuous efforts to develop effective treatments.Complete surgi...Intrahepatic cholangiocarcinoma(iCCA)is an aggressive malignancy with an increasing incidence worldwide and poor prognosis,despite several advances and continuous efforts to develop effective treatments.Complete surgical resection is the mainstay of treatment and offers a potentially curative option,but is only possible in less than a third of patients,owing to advanced disease.Chemotherapy is a well-established treatment in the adjuvant and palliative setting,however,confers limited benefit.Conventional radiotherapy is challenging due to local toxicity.With recent advances in stereotactic ablative radiotherapy(SABR),it is now possible to focus ablative beams of radiotherapy precisely aimed at tumours to minimise damage to surrounding viscera.This review details the history,technical background and application of SABR to iCCA,with directions for future research suggested.展开更多
文摘Cholangiocarcinoma(CCA)is an aggressive malignancy arising from the biliary epithelium.It may occur at any location along the biliary tree with the perihilar area being the most common.Prognosis is poor with 5-year overall survival at less than 10%,typically due to unresectable disease at presentation.Radical surgical resection with clear margins offers a chance of cure in patients with resectable tumours,but is frequently not possible due to locally advanced disease.On the other hand,orthotopic liver transplantation(LT)allows for a radical and potentially curative resection for these patients,but has been historically controversial due to the limited supply of donor grafts and previously poor outcomes.In patients with perihilar CCA,within specific criteria and following the implementation of a protocol combining neoadjuvant chemoradiation and LT,excellent results have been achieved in the last decades,resulting in its increasing acceptance as an indication for LT and the standard of care in several centres with significant experience.However,in intrahepatic CCA,the role of LT remains controversial and owing to dismal previous results it is not an accepted indication.Nevertheless,more recent studies have demonstrated favourable results with LT in early intrahepatic CCA,indicating that,under defined criteria,its role may increase in the future.This review highlights the history and contemporary advances of LT in CCA,with particular focus on the improving outcomes of LT in intrahepatic and perihilar CCA and future perspectives.
文摘Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor unresectable.The median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are necessary.Vascular resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal tumors.Thus,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.
文摘Over the past decade,enhanced preoperative imaging and visualization,improved delineation of the complex anatomical structures of the liver and pancreas,and intra-operative technological advances have helped deliver the liver and pancreatic surgery with increased safety and better postoperative outcomes.Artificial intelligence(AI)has a major role to play in 3D visualization,virtual simulation,augmented reality that helps in the training of surgeons and the future delivery of conventional,laparoscopic,and robotic hepatobiliary and pancreatic(HPB)surgery;artificial neural networks and machine learning has the potential to revolutionize individualized patient care during the preoperative imaging,and postoperative surveillance.In this paper,we reviewed the existing evidence and outlined the potential for applying AI in the perioperative care of patients undergoing HPB surgery.
文摘BACKGROUND The global incidence of intrahepatic cholangiocarcinoma(ICCA)is soaring.Due to often delayed presentation,only a narrow spectrum of the disease is usually surgically resectable.To more accurately stage the disease,reduce recurrence,and improve overall survival,surgical teams are increasingly performing intraoperative lymph node dissection(LND)as well.This procedure has its associated morbidity,while there is no consensus or formal guidelines on its role in this setting.Hence,there is a need to better delineate the evidence for performing LND alongside surgical resection of the ICCA.AIM To perform a systematic review and meta-analysis on the role of LND in improving prognostication and survival post-resection of ICCA.METHODS We performed a systematic literature search using Pubmed,Medline,Embase,and the Cochrane Library,for all studies involving LND,ICCA,and surgical resection using several keywords,Medical Subject Headings(MeSH)tags,and appropriate synonyms.All clinical studies comparing curative intent resection of ICCA with LND vs resection without LND were included,while single-arm case series,studies with insufficient data,and duplicates were excluded.We included all English-language studies from the different academic databases up till early December 2022.The primary outcome measures were set for overall survival(OS)and disease-free survival(DFS).RESULTS This systematic review and meta-analysis included 15 studies that fulfilled the selection criteria comprising 11413 patients with surgically-resectable ICCA,of whom 6424(56.3%)underwent hepatectomy with LND while the remainder underwent hepatectomy only.In patients who underwent LND,on average,27.7%of the resected lymph nodes were positive for metastatic disease.Overall,the results showed that performing LND did not significantly improve OS or DFS.However,the effect of LND on OS showed a degree of variability by geographical region,in Eastern and Western countries.As LND is increasingly being performed,further time-based analysis was undertaken to identify time-dependent changes in the role of LND.An increasing adoption of LND was not associated with improved OS.Furthermore,no roles were identified for neoadjuvant/adjuvant chemotherapy or increasing lymph node retrieval in improving OS either.CONCLUSION LND might aid in staging,prognosticating,and deciding further management of resected ICCA,but does not improve OS and DFS and is unsuitable for high-risk patients unlikely to benefit from further treatments.
基金Supported by Citadel Capital Scholarship Foundation,EgyptDr. Leslie Borthwick/Ms. Anita Holme,Charitable Research Fund East and North Herts NHS TrusHertfordshire,United Kingdom
文摘AIM： To investigate a dual labeling technique, which would enable real-time monitoring of transplanted em- bryonic stem cell （ESC） kinetics, as well as long-term tracking. METHODS： Liver damage was induced in C57/BL6 male mice （n = 40） by acetaminophen （APAP） 300 mg/kg administered intraperitoneally. Green fluores- cence protein （GFP） positive C57/BL6 mouse ESCs were stained with the near-infrared fluorescent lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbo- cyanine iodide （DiR） immediately before transplantationinto the spleen. Each of the animals in the cell therapy group （n = 20） received 5 x 106 ESCs 4 h following treatment with APAP. The control group （n = 20） re- ceived the vehicle only. The distribution and dynamics of the cells were monitored in real-time with the IVIS lumina-2 at 30 rain post transplantation, then at 3, 12, 24, 48 and 72 h, and after one and 2 wk. Immunohisto- chemical examination of liver tissue was used to identify expression of GFP and albumin. Plasma alanine amino- transferase （ALT） was measured as an indication of liver damage.RESULTS： DiR-stained ESCs were easily tracked with the IVIS using the indocyanine green filter due to its high background passband with minimal background autofluorescence. The transplanted cells were confined inside the spleen at 30 min post-transplantation, gradu- ally moved into the splenic vein, and were detectable in parts of the liver at the 3 h time-point. Within 24 h of transplantation, homing of almost 90% of cells was confirmed in the liver. On day three, however, the DiR signal started to fade out, and ex vivo IVIS imaging of different organs allowed signal detection at time-points when the signal could not be detected by in vivo imag- ing, and confirmed that the highest photon emission was in the liver （P 〈 0.0001）. At 2 wk, the DiRsignal was no longer detectable in vivo; however, immuno- histochemistry analysis of constitutively-expressed GFP was used to provide an insight into the distribution of the cells. GFP ＋ve cells were detected in tissue sections resembling hepatocytes and were dispersed throughout the hepatic parenchyma, with the presence of a larger number of GFP ＋ve cells incorporated within the sinu- soidal endothelial lining. Very faint albumin expression was detected in the transplanted GFP ＋re cells at 72 h; however at 2 wk, few cells that were positive for GFP were also strongly positive for albumin. There was a significant improvement in serum levels of ALT, albumin and bilirubin in both groups at 2 wk when compared with the 72 h time-point. In the cell therapy group, serum ALT was significantly （P = 0.016） lower and al- bumin （P = 0.009） was significantly higher when com- pared with the control group at the 2 wk time-point;however there was no difference in mortality between the two groups. CONCLUSION： Dual labeling is an easy to use and cheap method for longitudinal monitoring of distribu- tion, survival and engraftment of transplanted cells, and could be used for cell therapy models.
文摘Intrahepatic cholangiocarcinoma(iCCA)is an aggressive malignancy with an increasing incidence worldwide and poor prognosis,despite several advances and continuous efforts to develop effective treatments.Complete surgical resection is the mainstay of treatment and offers a potentially curative option,but is only possible in less than a third of patients,owing to advanced disease.Chemotherapy is a well-established treatment in the adjuvant and palliative setting,however,confers limited benefit.Conventional radiotherapy is challenging due to local toxicity.With recent advances in stereotactic ablative radiotherapy(SABR),it is now possible to focus ablative beams of radiotherapy precisely aimed at tumours to minimise damage to surrounding viscera.This review details the history,technical background and application of SABR to iCCA,with directions for future research suggested.
