Liver transplantation(LT)remains the optimal life-saving intervention for patients with end-stage liver disease.Despite the recent advances in LT several barriers,including organ allocation,donor-recipient matching,an...Liver transplantation(LT)remains the optimal life-saving intervention for patients with end-stage liver disease.Despite the recent advances in LT several barriers,including organ allocation,donor-recipient matching,and patient education,persist.With the growing progress of artificial intelligence,particularly large language models(LLMs)like ChatGPT,new applications have emerged in the field of LT.Current studies demonstrating usage of ChatGPT in LT include various areas of application,from clinical settings to research and education.ChatGPT usage can benefit both healthcare professionals,by decreasing the time spent on non-clinical work,but also LT recipients by providing accurate information.Future potential applications include the expanding usage of ChatGPT and other LLMs in the field of LT pathology and radiology as well as the automated creation of discharge summaries or other related paperwork.Additionally,the next models of ChatGPT might have the potential to provide more accurate patient education material with increased readability.Although ChatGPT usage presents promising applications,there are certain ethical and practical limitations.Key concerns include patient data privacy,information accuracy,misinformation possibility and lack of legal framework.Healthcare providers and policymakers should collaborate for the establishment of a controlled framework for the safe use of ChatGPT.The aim of this minireview is to summarize current literature on ChatGPT in LT,highlighting both opportunities and limitations,while also providing future possible applications.展开更多
BACKGROUND Kidney and liver transplantation are two sub-specialized medical disciplines,with transplant professionals spending decades in training.While artificial intelligencebased(AI-based)tools could potentially as...BACKGROUND Kidney and liver transplantation are two sub-specialized medical disciplines,with transplant professionals spending decades in training.While artificial intelligencebased(AI-based)tools could potentially assist in everyday clinical practice,comparative assessment of their effectiveness in clinical decision-making remains limited.AIM To compare the use of ChatGPT and GPT-4 as potential tools in AI-assisted clinical practice in these challenging disciplines.METHODS In total,400 different questions tested ChatGPT’s/GPT-4 knowledge and decision-making capacity in various renal and liver transplantation concepts.Specifically,294 multiple-choice questions were derived from open-access sources,63 questions were derived from published open-access case reports,and 43 from unpublished cases of patients treated at our department.The evaluation covered a plethora of topics,including clinical predictors,treatment options,and diagnostic criteria,among others.RESULTS ChatGPT correctly answered 50.3%of the 294 multiple-choice questions,while GPT-4 demonstrated a higher performance,answering 70.7%of questions(P<0.001).Regarding the 63 questions from published cases,ChatGPT achieved an agreement rate of 50.79%and partial agreement of 17.46%,while GPT-4 demonstrated an agreement rate of 80.95%and partial agreement of 9.52%(P=0.01).Regarding the 43 questions from unpublished cases,ChatGPT demonstrated an agreement rate of 53.49%and partial agreement of 23.26%,while GPT-4 demonstrated an agreement rate of 72.09%and partial agreement of 6.98%(P=0.004).When factoring by the nature of the task for all cases,notably,GPT-4 demonstrated outstanding performance,providing a differential diagnosis that included the final diagnosis in 90%of the cases(P=0.008),and successfully predicting the prognosis of the patient in 100%of related questions(P<0.001).CONCLUSION GPT-4 consistently provided more accurate and reliable clinical recommendations with higher percentages of full agreements both in renal and liver transplantation compared with ChatGPT.Our findings support the potential utility of AI models like ChatGPT and GPT-4 in AI-assisted clinical practice as sources of accurate,individualized medical information and facilitating decision-making.The progression and refinement of such AI-based tools could reshape the future of clinical practice,making their early adoption and adaptation by physicians a necessity.展开更多
Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global hea...Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies.This review critically assesses the dynamic treatment panorama for HCC,focusing specifically on the burgeoning role of immunotherapy in two key contexts:early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy.It delves into the unique immunobiology of the liver and HCC,highlighting tumor-mediated immune evasion mechanisms.Analyzing the diverse immunothera-peutic approaches including checkpoint inhibitors,cytokine modulators,vaccines,oncolytic viruses,antigen-targeting antibodies,and adoptive cell therapy,this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring.Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC,current research is actively exploring the safety and effectiveness of diverse immunothera-peutic approaches through ongoing clinical trials.The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant,highlighting the need for careful patient selection,meticulous monitoring,and novel strategies to mitigate post-transplant complications.Finally,this review delves into the latest findings from the clinical research landscape and future directions in HCC management,paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.展开更多
BACKGROUND Hepatic ischemia-reperfusion injury(HIRI)remains one of the major causes of postoperative liver dysfunction following extensive hepatectomy and liver transplantation.Owing to its progressive and dynamic nat...BACKGROUND Hepatic ischemia-reperfusion injury(HIRI)remains one of the major causes of postoperative liver dysfunction following extensive hepatectomy and liver transplantation.Owing to its progressive and dynamic nature,HIRI may lead to multiple organ failure and a worsened outcome.Treprostinil is a relatively new synthetic prostacyclin analog with a potential beneficial effect against HIRI.Ischemic preconditioning(IP)is a promising method to protect against HIRI.AIM To investigate HIRI biomarkers,their effects on liver and heart,and the effects of treprostinil and IP on these processes.METHODS Forty male Wistar albino rats aged 3-4 months were randomly assigned to four groups of ten,subjected to a 3-hour surgical intervention,and then sacrificed.Hepatic ischemia was induced by clamping the hepatoduodenal ligament for 30 minutes,followed by reperfusion for 120 minutes.Treprostinil(100 ng/kg/minute for 24 hours)or IP before HIRI,no protection,and a sham operation were applied accordingly in each group.Liver and heart histopathology and specific serum and hepatic tissue biomarkers were assessed.RESULTS HIRI deteriorated hepatocellular function and exacerbated liver and myocardial damage in the control group.Furthermore,HIRI triggered cytokine overexpression and protein carbonyl content(P<0.001).Compared with those in the HIRI group,lower troponin I,tumor necrosis factor-α,endothelin-1,and interleukin-1βin serum and liver tissue were significantly correlated with reduced cellular necrosis and improved hepatocellular function in the treprostinil group(P<0.001).Similar but less pronounced effects were observed in the IP group.Both treprostinil and IP had protective effects in hepatic and cardiac tissues.However,treprostinil showed slightly superior cardioprotective efficacy,as evidenced by a statistically significant difference in troponin I levels(P<0.05)and histopathological scoring of myocardium samples,but there were no differences in the other parameters.CONCLUSION HIRI results in oxidative stress and cytokine overexpression,which deteriorate hepatic function and accelerates myocardial damage.Treprostinil and IP are promising strategies for preventing reperfusion-induced cellular and systemic damage.展开更多
Treprostinil is a relatively new tricyclic prostacyclin analog with a stable str-ucture,extended half-life and improved potency.Currently,treprostinil is indicated by the Food and Drug Administration in the United Sta...Treprostinil is a relatively new tricyclic prostacyclin analog with a stable str-ucture,extended half-life and improved potency.Currently,treprostinil is indicated by the Food and Drug Administration in the United States for the treatment of pulmonary arterial hypertension(group 1 in the pulmonary hy-pertension classification of the World Health Organization).It has a potent vasodilating effect along with the inhibition of platelet aggregation and the attenuation of the inflammatory response in pulmonary and systemic circulation.It is available in the following formulations:Subcutaneous,intravenous,inhaled and oral.Although unknown to many clinicians,several encouraging reports of off-label treprostinil use in the adult population suggest its potential effectiveness in other clinical conditions.Currently under investigation are digital ischemia secondary to systemic sclerosis,chronic limb ischemia,hepatic ischemia-reper-fusion injury and group 3 and 4 pulmonary hypertension.Based on review and analysis of the available literature,this article provides a thorough update on the off-label use of treprostinil in adult patients.展开更多
Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcome...Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcomes.The underlying cellular and molecular reactions are extremely complex and not completely understood.Anaerobic metabolism,ATP depletion,intracellular acidosis,calcium overload,mitochondrial dysfunction,oxidative stress,activation of Kupffer cells and neutrophils,platelet aggregation,nitric oxide production,activation of the complement system and overexpression of cytokines and chemokines constitute the main pathophysiological actions and pathways for possible therapeutic strategies.Prostaglandins(PGs)are a group of biologically active lipid compounds called eicosanoids with many physiological activities.Prostacyclin(PGI_(2))is a member of the PGs family with an unstable chemical structure and a very short half-life.PGI_(2)has potent vasodilating activity,inhibits platelet activation and exerts anti-inflammatory effects.PGI_(2)has been evaluated in chronic liver disease as a mediator of hepatic stellate cell function,an antiproliferative and antifibrotic agent and a regulator of the hepatic microcirculation.In recent decades,the cytoprotective effects of PGI_(2)analogs on hepatic ischemiareperfusion injury have been experimentally and clinically studied.Moreover,the administration of synthetic PGI_(2)analogs to patients who underwent liver transplantation produced very encouraging results.The downregulation of PGE_(2) production,reduction of neutrophil aggregation in liver lobules,regulation of local microcirculatory homeostasis,improvement in mitochondrial function,alleviation of hepatic oxidative stress,suppression of the c-Jun N-terminal kinase and p38 cascades and downregulation of tumor necrosis factor-alpha and interleukin-1βproduction constitute some of the underlying physiological mechanisms of the beneficial effects of PGI_(2)on hepatic ischemia-reperfusion injury.Thus,PGI_(2)analogs appear to hold great promise for the management of hepatic ischemia-reperfusion injury,but further research is needed.展开更多
BACKGROUND Enhanced recovery after surgery(ERAS)started a revolution that changed age-old surgical stereotypical practices regarding the overall management of the surgical patient.In the last decade,ERAS has gained si...BACKGROUND Enhanced recovery after surgery(ERAS)started a revolution that changed age-old surgical stereotypical practices regarding the overall management of the surgical patient.In the last decade,ERAS has gained significant acceptance in the community of general surgery,in addition to several other surgical specialties,as the evidence of its advantages continues to grow.One of the last remaining fields,given its significant complexity and intricate nature,is liver transplantation(LT).AIM To investigate the existing efforts at implementing ERAS in LT.METHODS We conducted a systematic review of the existing studies that evaluate ERAS in orthotopic LT,with a multimodal approach and focusing on measurable clinical primary endpoints,namely length of hospital stay.RESULTS All studies demonstrated a considerable decrease in length of hospital stay,with no readmission or negative impact of the ERAS protocol applied to the postoperative course.CONCLUSIONS ERAS is a well-validated multimodal approach for almost all types of surgical procedures,and its future in selected LT patients seems promising,as the preliminary results advocate for the safety and efficacy of ERAS in the field of LT.展开更多
Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities,such as major hepatic resections...Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities,such as major hepatic resections and liver transplantation.In addition to the organ’s post reperfusion injury,this syndrome appears to play a central role in the dysfunction of distant tissues and systems.Thus,continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates.Treprostinil is a synthetic analog of prostaglandin I2,and its experimental administration has shown encouraging results.It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation,where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min.Treprostinil improves renal and hepatic function,diminishes hepatic oxidative stress and lipid peroxidation,reduces hepatictoll-like receptor 9 and inflammation,inhibits hepatic apoptosis and restores hepatic adenosine triphosphate(ATP)levels and ATP synthases,which is necessary for functional maintenance of mitochondria.Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflam-matory cytokines;therefore,it can potentially minimize ischemia-reperfusion injury.Additionally,it may have beneficial effects on cardiovascular parameters,and much current research interest is concentrated on this compound.展开更多
The number of solid organ transplantations performed annually is increasing and are increasing in the following order:Kidney,liver,heart,lung,pancreas,small bowel,and uterine transplants.However,the outcomes of transp...The number of solid organ transplantations performed annually is increasing and are increasing in the following order:Kidney,liver,heart,lung,pancreas,small bowel,and uterine transplants.However,the outcomes of transplants are impro-ving(organ survival>90%after the 1st year).Therefore,there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen.Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems.The perioperative regulation of immunosuppression,the treatment of accompanying problems of immunosuppression,the administration of cortisol and,above all,the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients.The perioperative assessment and preparation includes evaluation of the patient’s cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis,or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes.Immunosuppression in transplant patients is associated with the use of calci-neurin inhibitors,corticosteroids,and antiproliferation agents.Many times,the clinical picture is atypical,resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality.Multidetector computed tomo-graphy is of utmost importance for early diagnosis and management.Transplant recipients are prone to infections,especially specific infections caused by cytomegalovirus and Clostridium difficile,and they are predisposed to intraop-erative or postoperative complications that require great care and vigilance.It is necessary to follow evidence-based therapeutic protocols.Thus,it is required that the clinician choose the correct therapeutic plan for the patient(conservative,emergency open surgery or minimally invasive surgery,including laparoscopic or even robotic surgery).展开更多
Liver transplantation is a major abdominal operation and the intimate anatomic relation of the liver with the right hemidiaphragm predisposes the patient to various manifestations in the chest cavity.Furthermore,chron...Liver transplantation is a major abdominal operation and the intimate anatomic relation of the liver with the right hemidiaphragm predisposes the patient to various manifestations in the chest cavity.Furthermore,chronic liver disease affects pulmonary function before and after liver transplantation resulting in a considerable percentage of patients presenting with morbidity related to chest complications.This review aims to identify the potential chest complications of surgical interest during or after liver transplantation.Complications of surgical interest are defined as those conditions that necessitate an invasive procedure(such as thoracocentesis or a chest tube placement)in the chest or a surgical intervention performed by a thoracic surgeon.These complications will be classified as perioperative and postoperative;the latter will be categorized as early and late.Although thoracocentesis or a chest tube placement is usually sufficient when invasive measures are deemed necessary,in some patients,thoracic surgical interventions are warranted.A high index of suspicion is needed to recognize and treat these conditions promptly.A close collaboration between abdominal surgeons,intensive care unit physicians and thoracic surgeons is of paramount importance.展开更多
BACKGROUND Liver transplantation has evolved into a safe life-saving operation and remains the golden standard in the treatment of end stage liver disease.The main limiting factor in the application of liver transplan...BACKGROUND Liver transplantation has evolved into a safe life-saving operation and remains the golden standard in the treatment of end stage liver disease.The main limiting factor in the application of liver transplantation is graft shortage.Many strategies have been developed in order to alleviate graft shortage,such as living donor partial liver transplantation and split liver transplantation for adult and pediatric patients.In these strategies,liver volume assessment is of paramount importance,as size mismatch can have severe consequences in the success of liver transplantation.AIM To evaluate the safety,feasibility,and accuracy of light detection and ranging(LIDAR)3D photography in the prediction of whole liver graft volume and mass.METHODS Seven liver grafts procured for orthotopic liver transplantation from brain deceased donors were prospectively measured with an LIDAR handheld camera and their mass was calculated and compared to their actual weight.RESULTS The mean error of all measurements was 17.03 g(range 3.56-59.33 g).Statistical analysis of the data yielded a Pearson correlation coefficient index of 0.9968,indicating a strong correlation between the values and a Student’s t-test P value of 0.26.Mean accuracy of the measurements was calculated at 97.88%.CONCLUSION Our preliminary data indicate that LIDAR scanning of liver grafts is a safe,cost-effective,and feasible method of ex vivo determination of whole liver volume and mass.More data are needed to determine the precision and accuracy of this method.展开更多
This review aims to present the developments occurring in the field of artificial organs and particularly focuses on the presentation of developments in artificial kidneys.The challenges for biomedical engineering inv...This review aims to present the developments occurring in the field of artificial organs and particularly focuses on the presentation of developments in artificial kidneys.The challenges for biomedical engineering involved in overcoming the potential difficulties are showcased,as well as the importance of interdisciplinary collaboration in this marriage of medicine and technology.In this review,modern artificial kidneys and the research efforts trying to provide and promise artificial kidneys are presented.But what are the problems faced by each technology and to what extent is the effort enough to date?展开更多
BACKGROUND Liver transplantation is the most important therapeutic intervention for end-stage liver disease(ELD).The prioritization of these patients is based on the model for end-stage liver disease(MELD),which can s...BACKGROUND Liver transplantation is the most important therapeutic intervention for end-stage liver disease(ELD).The prioritization of these patients is based on the model for end-stage liver disease(MELD),which can successfully predict short-term mortality.However,despite its great validity and value,it cannot fully incorporate several comorbidities of liver disease,such as sarcopenia and physical frailty,variables that can sufficiently influence the survival of such patients.Subsequently,there is growing interest in the importance of physical frailty in regard to mortality in liver transplant candidates and recipients,as well as its role in improving their survival rates.AIM To evaluate the effects of an active lifestyle on physical frailty on liver transplant candidates.METHODS An observational study was performed within the facilities of the Department of Transplant Surgery of Aristotle University of Thessaloniki.Twenty liver transplant candidate patients from the waiting list of the department were included in the study.Patients that were bedridden,had recent cardiovascular incidents,or had required inpatient treatment for more than 5 d in the last 6 mo were excluded from the study.The following variables were evaluated:Activity level via the International Physical Activity Questionnaire(IPAQ);functional capacity via the 6-min walking test(6MWT)and cardiopulmonary exercise testing;and physical frailty via the Liver Frailty Index(LFI).RESULTS According to their responses in the IPAQ,patients were divided into the following two groups based on their activity level:Active group(A,10 patients);and sedentary group(S,10 patients).Comparing mean values of the recorded variables showed the following results:MELD(A:12.05±5.63 vs S:13.99±3.60;P>0.05);peak oxygen uptake(A:29.78±6.07 mL/kg/min vs S:18.11±3.39 mL/kg/min;P<0.001);anaerobic threshold(A:16.71±2.17 mL/kg/min vs S:13.96±1.45 mL/kg/min;P<0.01);6MWT(A:458.2±57.5 m vs S:324.7±55.8 m;P<0.001);and LFI(A:3.75±0.31 vs S:4.42±0.32;P<0.001).CONCLUSION An active lifestyle can be associated with better musculoskeletal and functional capacity,while simultaneously preventing the evolution of physical frailty in liver transplant candidates.This effect appears to be independent of the liver disease severity.展开更多
文摘Liver transplantation(LT)remains the optimal life-saving intervention for patients with end-stage liver disease.Despite the recent advances in LT several barriers,including organ allocation,donor-recipient matching,and patient education,persist.With the growing progress of artificial intelligence,particularly large language models(LLMs)like ChatGPT,new applications have emerged in the field of LT.Current studies demonstrating usage of ChatGPT in LT include various areas of application,from clinical settings to research and education.ChatGPT usage can benefit both healthcare professionals,by decreasing the time spent on non-clinical work,but also LT recipients by providing accurate information.Future potential applications include the expanding usage of ChatGPT and other LLMs in the field of LT pathology and radiology as well as the automated creation of discharge summaries or other related paperwork.Additionally,the next models of ChatGPT might have the potential to provide more accurate patient education material with increased readability.Although ChatGPT usage presents promising applications,there are certain ethical and practical limitations.Key concerns include patient data privacy,information accuracy,misinformation possibility and lack of legal framework.Healthcare providers and policymakers should collaborate for the establishment of a controlled framework for the safe use of ChatGPT.The aim of this minireview is to summarize current literature on ChatGPT in LT,highlighting both opportunities and limitations,while also providing future possible applications.
文摘BACKGROUND Kidney and liver transplantation are two sub-specialized medical disciplines,with transplant professionals spending decades in training.While artificial intelligencebased(AI-based)tools could potentially assist in everyday clinical practice,comparative assessment of their effectiveness in clinical decision-making remains limited.AIM To compare the use of ChatGPT and GPT-4 as potential tools in AI-assisted clinical practice in these challenging disciplines.METHODS In total,400 different questions tested ChatGPT’s/GPT-4 knowledge and decision-making capacity in various renal and liver transplantation concepts.Specifically,294 multiple-choice questions were derived from open-access sources,63 questions were derived from published open-access case reports,and 43 from unpublished cases of patients treated at our department.The evaluation covered a plethora of topics,including clinical predictors,treatment options,and diagnostic criteria,among others.RESULTS ChatGPT correctly answered 50.3%of the 294 multiple-choice questions,while GPT-4 demonstrated a higher performance,answering 70.7%of questions(P<0.001).Regarding the 63 questions from published cases,ChatGPT achieved an agreement rate of 50.79%and partial agreement of 17.46%,while GPT-4 demonstrated an agreement rate of 80.95%and partial agreement of 9.52%(P=0.01).Regarding the 43 questions from unpublished cases,ChatGPT demonstrated an agreement rate of 53.49%and partial agreement of 23.26%,while GPT-4 demonstrated an agreement rate of 72.09%and partial agreement of 6.98%(P=0.004).When factoring by the nature of the task for all cases,notably,GPT-4 demonstrated outstanding performance,providing a differential diagnosis that included the final diagnosis in 90%of the cases(P=0.008),and successfully predicting the prognosis of the patient in 100%of related questions(P<0.001).CONCLUSION GPT-4 consistently provided more accurate and reliable clinical recommendations with higher percentages of full agreements both in renal and liver transplantation compared with ChatGPT.Our findings support the potential utility of AI models like ChatGPT and GPT-4 in AI-assisted clinical practice as sources of accurate,individualized medical information and facilitating decision-making.The progression and refinement of such AI-based tools could reshape the future of clinical practice,making their early adoption and adaptation by physicians a necessity.
文摘Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies.This review critically assesses the dynamic treatment panorama for HCC,focusing specifically on the burgeoning role of immunotherapy in two key contexts:early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy.It delves into the unique immunobiology of the liver and HCC,highlighting tumor-mediated immune evasion mechanisms.Analyzing the diverse immunothera-peutic approaches including checkpoint inhibitors,cytokine modulators,vaccines,oncolytic viruses,antigen-targeting antibodies,and adoptive cell therapy,this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring.Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC,current research is actively exploring the safety and effectiveness of diverse immunothera-peutic approaches through ongoing clinical trials.The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant,highlighting the need for careful patient selection,meticulous monitoring,and novel strategies to mitigate post-transplant complications.Finally,this review delves into the latest findings from the clinical research landscape and future directions in HCC management,paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.
文摘BACKGROUND Hepatic ischemia-reperfusion injury(HIRI)remains one of the major causes of postoperative liver dysfunction following extensive hepatectomy and liver transplantation.Owing to its progressive and dynamic nature,HIRI may lead to multiple organ failure and a worsened outcome.Treprostinil is a relatively new synthetic prostacyclin analog with a potential beneficial effect against HIRI.Ischemic preconditioning(IP)is a promising method to protect against HIRI.AIM To investigate HIRI biomarkers,their effects on liver and heart,and the effects of treprostinil and IP on these processes.METHODS Forty male Wistar albino rats aged 3-4 months were randomly assigned to four groups of ten,subjected to a 3-hour surgical intervention,and then sacrificed.Hepatic ischemia was induced by clamping the hepatoduodenal ligament for 30 minutes,followed by reperfusion for 120 minutes.Treprostinil(100 ng/kg/minute for 24 hours)or IP before HIRI,no protection,and a sham operation were applied accordingly in each group.Liver and heart histopathology and specific serum and hepatic tissue biomarkers were assessed.RESULTS HIRI deteriorated hepatocellular function and exacerbated liver and myocardial damage in the control group.Furthermore,HIRI triggered cytokine overexpression and protein carbonyl content(P<0.001).Compared with those in the HIRI group,lower troponin I,tumor necrosis factor-α,endothelin-1,and interleukin-1βin serum and liver tissue were significantly correlated with reduced cellular necrosis and improved hepatocellular function in the treprostinil group(P<0.001).Similar but less pronounced effects were observed in the IP group.Both treprostinil and IP had protective effects in hepatic and cardiac tissues.However,treprostinil showed slightly superior cardioprotective efficacy,as evidenced by a statistically significant difference in troponin I levels(P<0.05)and histopathological scoring of myocardium samples,but there were no differences in the other parameters.CONCLUSION HIRI results in oxidative stress and cytokine overexpression,which deteriorate hepatic function and accelerates myocardial damage.Treprostinil and IP are promising strategies for preventing reperfusion-induced cellular and systemic damage.
文摘Treprostinil is a relatively new tricyclic prostacyclin analog with a stable str-ucture,extended half-life and improved potency.Currently,treprostinil is indicated by the Food and Drug Administration in the United States for the treatment of pulmonary arterial hypertension(group 1 in the pulmonary hy-pertension classification of the World Health Organization).It has a potent vasodilating effect along with the inhibition of platelet aggregation and the attenuation of the inflammatory response in pulmonary and systemic circulation.It is available in the following formulations:Subcutaneous,intravenous,inhaled and oral.Although unknown to many clinicians,several encouraging reports of off-label treprostinil use in the adult population suggest its potential effectiveness in other clinical conditions.Currently under investigation are digital ischemia secondary to systemic sclerosis,chronic limb ischemia,hepatic ischemia-reper-fusion injury and group 3 and 4 pulmonary hypertension.Based on review and analysis of the available literature,this article provides a thorough update on the off-label use of treprostinil in adult patients.
文摘Hepatic ischemia-reperfusion injury is an important mechanism of liver failure that occurs in many clinical conditions,including massive hemorrhage,major hepatectomy and liver transplantation,and leads to poor outcomes.The underlying cellular and molecular reactions are extremely complex and not completely understood.Anaerobic metabolism,ATP depletion,intracellular acidosis,calcium overload,mitochondrial dysfunction,oxidative stress,activation of Kupffer cells and neutrophils,platelet aggregation,nitric oxide production,activation of the complement system and overexpression of cytokines and chemokines constitute the main pathophysiological actions and pathways for possible therapeutic strategies.Prostaglandins(PGs)are a group of biologically active lipid compounds called eicosanoids with many physiological activities.Prostacyclin(PGI_(2))is a member of the PGs family with an unstable chemical structure and a very short half-life.PGI_(2)has potent vasodilating activity,inhibits platelet activation and exerts anti-inflammatory effects.PGI_(2)has been evaluated in chronic liver disease as a mediator of hepatic stellate cell function,an antiproliferative and antifibrotic agent and a regulator of the hepatic microcirculation.In recent decades,the cytoprotective effects of PGI_(2)analogs on hepatic ischemiareperfusion injury have been experimentally and clinically studied.Moreover,the administration of synthetic PGI_(2)analogs to patients who underwent liver transplantation produced very encouraging results.The downregulation of PGE_(2) production,reduction of neutrophil aggregation in liver lobules,regulation of local microcirculatory homeostasis,improvement in mitochondrial function,alleviation of hepatic oxidative stress,suppression of the c-Jun N-terminal kinase and p38 cascades and downregulation of tumor necrosis factor-alpha and interleukin-1βproduction constitute some of the underlying physiological mechanisms of the beneficial effects of PGI_(2)on hepatic ischemia-reperfusion injury.Thus,PGI_(2)analogs appear to hold great promise for the management of hepatic ischemia-reperfusion injury,but further research is needed.
文摘BACKGROUND Enhanced recovery after surgery(ERAS)started a revolution that changed age-old surgical stereotypical practices regarding the overall management of the surgical patient.In the last decade,ERAS has gained significant acceptance in the community of general surgery,in addition to several other surgical specialties,as the evidence of its advantages continues to grow.One of the last remaining fields,given its significant complexity and intricate nature,is liver transplantation(LT).AIM To investigate the existing efforts at implementing ERAS in LT.METHODS We conducted a systematic review of the existing studies that evaluate ERAS in orthotopic LT,with a multimodal approach and focusing on measurable clinical primary endpoints,namely length of hospital stay.RESULTS All studies demonstrated a considerable decrease in length of hospital stay,with no readmission or negative impact of the ERAS protocol applied to the postoperative course.CONCLUSIONS ERAS is a well-validated multimodal approach for almost all types of surgical procedures,and its future in selected LT patients seems promising,as the preliminary results advocate for the safety and efficacy of ERAS in the field of LT.
文摘Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities,such as major hepatic resections and liver transplantation.In addition to the organ’s post reperfusion injury,this syndrome appears to play a central role in the dysfunction of distant tissues and systems.Thus,continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates.Treprostinil is a synthetic analog of prostaglandin I2,and its experimental administration has shown encouraging results.It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation,where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min.Treprostinil improves renal and hepatic function,diminishes hepatic oxidative stress and lipid peroxidation,reduces hepatictoll-like receptor 9 and inflammation,inhibits hepatic apoptosis and restores hepatic adenosine triphosphate(ATP)levels and ATP synthases,which is necessary for functional maintenance of mitochondria.Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflam-matory cytokines;therefore,it can potentially minimize ischemia-reperfusion injury.Additionally,it may have beneficial effects on cardiovascular parameters,and much current research interest is concentrated on this compound.
文摘The number of solid organ transplantations performed annually is increasing and are increasing in the following order:Kidney,liver,heart,lung,pancreas,small bowel,and uterine transplants.However,the outcomes of transplants are impro-ving(organ survival>90%after the 1st year).Therefore,there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen.Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems.The perioperative regulation of immunosuppression,the treatment of accompanying problems of immunosuppression,the administration of cortisol and,above all,the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients.The perioperative assessment and preparation includes evaluation of the patient’s cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis,or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes.Immunosuppression in transplant patients is associated with the use of calci-neurin inhibitors,corticosteroids,and antiproliferation agents.Many times,the clinical picture is atypical,resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality.Multidetector computed tomo-graphy is of utmost importance for early diagnosis and management.Transplant recipients are prone to infections,especially specific infections caused by cytomegalovirus and Clostridium difficile,and they are predisposed to intraop-erative or postoperative complications that require great care and vigilance.It is necessary to follow evidence-based therapeutic protocols.Thus,it is required that the clinician choose the correct therapeutic plan for the patient(conservative,emergency open surgery or minimally invasive surgery,including laparoscopic or even robotic surgery).
文摘Liver transplantation is a major abdominal operation and the intimate anatomic relation of the liver with the right hemidiaphragm predisposes the patient to various manifestations in the chest cavity.Furthermore,chronic liver disease affects pulmonary function before and after liver transplantation resulting in a considerable percentage of patients presenting with morbidity related to chest complications.This review aims to identify the potential chest complications of surgical interest during or after liver transplantation.Complications of surgical interest are defined as those conditions that necessitate an invasive procedure(such as thoracocentesis or a chest tube placement)in the chest or a surgical intervention performed by a thoracic surgeon.These complications will be classified as perioperative and postoperative;the latter will be categorized as early and late.Although thoracocentesis or a chest tube placement is usually sufficient when invasive measures are deemed necessary,in some patients,thoracic surgical interventions are warranted.A high index of suspicion is needed to recognize and treat these conditions promptly.A close collaboration between abdominal surgeons,intensive care unit physicians and thoracic surgeons is of paramount importance.
基金the European Union and Greek national funds through the Operational Program Competitiveness,Entrepreneurship and Innovation,No.T1EDK-03599.
文摘BACKGROUND Liver transplantation has evolved into a safe life-saving operation and remains the golden standard in the treatment of end stage liver disease.The main limiting factor in the application of liver transplantation is graft shortage.Many strategies have been developed in order to alleviate graft shortage,such as living donor partial liver transplantation and split liver transplantation for adult and pediatric patients.In these strategies,liver volume assessment is of paramount importance,as size mismatch can have severe consequences in the success of liver transplantation.AIM To evaluate the safety,feasibility,and accuracy of light detection and ranging(LIDAR)3D photography in the prediction of whole liver graft volume and mass.METHODS Seven liver grafts procured for orthotopic liver transplantation from brain deceased donors were prospectively measured with an LIDAR handheld camera and their mass was calculated and compared to their actual weight.RESULTS The mean error of all measurements was 17.03 g(range 3.56-59.33 g).Statistical analysis of the data yielded a Pearson correlation coefficient index of 0.9968,indicating a strong correlation between the values and a Student’s t-test P value of 0.26.Mean accuracy of the measurements was calculated at 97.88%.CONCLUSION Our preliminary data indicate that LIDAR scanning of liver grafts is a safe,cost-effective,and feasible method of ex vivo determination of whole liver volume and mass.More data are needed to determine the precision and accuracy of this method.
文摘This review aims to present the developments occurring in the field of artificial organs and particularly focuses on the presentation of developments in artificial kidneys.The challenges for biomedical engineering involved in overcoming the potential difficulties are showcased,as well as the importance of interdisciplinary collaboration in this marriage of medicine and technology.In this review,modern artificial kidneys and the research efforts trying to provide and promise artificial kidneys are presented.But what are the problems faced by each technology and to what extent is the effort enough to date?
文摘BACKGROUND Liver transplantation is the most important therapeutic intervention for end-stage liver disease(ELD).The prioritization of these patients is based on the model for end-stage liver disease(MELD),which can successfully predict short-term mortality.However,despite its great validity and value,it cannot fully incorporate several comorbidities of liver disease,such as sarcopenia and physical frailty,variables that can sufficiently influence the survival of such patients.Subsequently,there is growing interest in the importance of physical frailty in regard to mortality in liver transplant candidates and recipients,as well as its role in improving their survival rates.AIM To evaluate the effects of an active lifestyle on physical frailty on liver transplant candidates.METHODS An observational study was performed within the facilities of the Department of Transplant Surgery of Aristotle University of Thessaloniki.Twenty liver transplant candidate patients from the waiting list of the department were included in the study.Patients that were bedridden,had recent cardiovascular incidents,or had required inpatient treatment for more than 5 d in the last 6 mo were excluded from the study.The following variables were evaluated:Activity level via the International Physical Activity Questionnaire(IPAQ);functional capacity via the 6-min walking test(6MWT)and cardiopulmonary exercise testing;and physical frailty via the Liver Frailty Index(LFI).RESULTS According to their responses in the IPAQ,patients were divided into the following two groups based on their activity level:Active group(A,10 patients);and sedentary group(S,10 patients).Comparing mean values of the recorded variables showed the following results:MELD(A:12.05±5.63 vs S:13.99±3.60;P>0.05);peak oxygen uptake(A:29.78±6.07 mL/kg/min vs S:18.11±3.39 mL/kg/min;P<0.001);anaerobic threshold(A:16.71±2.17 mL/kg/min vs S:13.96±1.45 mL/kg/min;P<0.01);6MWT(A:458.2±57.5 m vs S:324.7±55.8 m;P<0.001);and LFI(A:3.75±0.31 vs S:4.42±0.32;P<0.001).CONCLUSION An active lifestyle can be associated with better musculoskeletal and functional capacity,while simultaneously preventing the evolution of physical frailty in liver transplant candidates.This effect appears to be independent of the liver disease severity.
