Artificial kidney: Challenges and opportunities

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?

Critical considerations for the management of acute abdomen in transplant patients

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).

Global dissemination of minimally invasive living donor hepatectomy: What are the barriers?

Minimally invasive donor hepatectomy(MIDH)is a relatively novel procedure that can potentially increase donor safety and contribute to faster rehabilitation of donors.After an initial period in which donor safety was not effectively validated,MIDH currently seems to provide improved results,provided that it is conducted by experienced surgeons.Appropriate selection criteria are crucial to achieve better outcomes in terms of complications,blood loss,operative time,and hospital stay.Beyond a pure laparoscopic technique,various approaches have been recommended such as hand-assisted,laparoscopic-assisted,and robotic donation.The latter has shown equal outcomes compared to open and laparoscopic approaches.A steep learning curve seems to exist in MIDH,mainly due to the fragility of the liver parenchyma and the experience needed for adequate control of bleeding.This review investigated the challenges and the opportunities of MIDH and the barriers to its global dissemination.Surgeons need expertise in liver transplantation,hepatobiliary surgery,and minimally invasive techniques to perform MIDH.Barriers can be categorized into surgeon-related,institutionalrelated,and accessibility.More robust data and the creation of international registries are needed for further evaluation of the technique and the acceptance from more centers worldwide.

Exploring the use of virtual reality in surgical education

Virtual reality(VR)technologies have rapidly developed in the past few years.The most common application of the technology,apart from gaming,is for educational purposes.In the field of healthcare,VR technologies have been applied in several areas.Among them is surgical education.With the use of VR,surgical pathways along with the training of surgical skills can be explored safely,in a cost-effective manner.The aim of this mini-review was to explore the use of VR in surgical education and in the 3D reconstruction of internal organs and viable surgical pathways.Finally,based on the outcomes of the included studies,an ecosystem for the implementation of surgical training was proposed.

Challenges involved in the application of artificial intelligence in gastroenterology:The race is on!

Gastroenterology is a particularly data-rich field,generating vast repositories of data that are a fruitful ground for artificial intelligence(AI)and machine learning(ML)applications.In this opinion review,we initially elaborate on the current status of the application of AI/ML-based software in gastroenterology.Currently,AI/ML-based models have been developed in the following applications:Models integrated into the clinical setting following real-time patient data flagging patients at high risk for developing a gastrointestinal disease,models employing non-invasive parameters that provide accurate diagnoses aiming to either replace,minimize,or refine the indications of endoscopy,models utilizing genomic data to diagnose various gastrointestinal diseases,computer-aided diagnosis systems facilitating the interpretation of endoscopy images,models to facilitate treatment allocation and predict the response to treatment,and finally,models in prognosis predicting complications,recurrence following treatment,and overall survival.Then,we elaborate on several challenges and how they may negatively impact the widespread application of AI in healthcare and gastroenterology.Specifically,we elaborate on concerns regarding accuracy,cost-effectiveness,cybersecurity,interpretability,oversight,and liability.While AI is unlikely to replace physicians,it will transform the skillset demanded by future physicians to practice.Thus,physicians are expected to engage with AI to avoid becoming obsolete.

Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog

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.

Translational research and innovation in modern transplant practice:Paradigms from Greece and around the world

The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of Transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.

Analysis of the effects of donor and recipient hepatitis C infection on kidney transplant outcomes in the United States

BACKGROUND As Hepatitis C virus infection(HCV+)rates in kidney donors and transplant recipients rise,direct-acting antivirals(DAA)may affect outcomes.AIM To analyze the effects of HCV+in donors,recipients,or both,on deceased-donor(DD)kidney transplantation(KT)outcomes,and the impact of DAAs on those effects.METHODS The Organ Procurement and Transplantation Network data of adult first solitary DD-KT recipients 1994-2019 were allocated into four groups by donor and recipient HCV+status.We performed patient survival(PS)and death-censored graft survival(DCGS)pairwise comparisons after propensity score matching to assess the effects of HCV+in donors and/or recipients,stratifying our study by DAA era to evaluate potential effect modification.RESULTS Pre-DAA,for HCV+recipients,receiving an HCV+kidney was associated with 1.28-fold higher mortality(HR 1.151.281.42)and 1.22-fold higher death-censored graft failure(HR 1.081.221.39)compared to receiving an HCV-kidney and the absolute risk difference was 3.3%(95%CI:1.8%-4.7%)for PS and 3.1%(95%CI:1.2%-5%)for DCGS at 3 years.The HCV dual-infection(donor plus recipient)group had worse PS(0.56-fold)and DCGS(0.71-fold)than the dual-uninfected.Donor HCV+derived worse post-transplant outcomes than recipient HCV+(PS 0.36-fold,DCGS 0.34-fold).In the DAA era,the risk associated with HCV+in donors and/or recipients was no longer statistically significant,except for impaired PS in the dual-infected vs dual-uninfected(0.43-fold).CONCLUSION Prior to DAA introduction,donor HCV+negatively influenced kidney transplant outcomes in all recipients,while recipient infection only relatively impaired outcomes for uninfected donors.These adverse effects disappeared with the introduction of DAA.

Advances and challenges in laparoscopic surgery in the management of hepatocellular carcinoma

Hepatocellular carcinoma is the fifth most common malignancy and the third most common cause of cancer-related mortality worldwide. From the wide variety of treatment options, surgical resection and liver transplantation are the only therapeutic ones. However, due to shortage of liver grafts, surgical resection is the most common therapeutic modality implemented. Owing to rapid technological development, minimally invasive approaches have been incorporated in liver surgery. Liver laparoscopic resection has been evaluated in comparison to the open technique and has been shown to be superior because of the reported decrease in surgical incision length and trauma, blood loss, operating theatre time, postsurgical pain and complications, R0 resection, length of stay, time to recovery and oral intake. It has been reported that laparoscopic excision is a safe and feasible approach with near zero mortality and oncologic outcomes similar to open resection. Nevertheless, current indications include solid tumors in the periphery < 5 cm, especially in segments Ⅱ through Ⅵ, while according to the consensus laparoscopic major hepatectomy should only be performed by surgeons with high expertise in laparoscopic and hepatobiliary surgery in tertiary centers. It is necessary for a surgeon to surpass the 60-cases learning curve observed in order to accomplish the desirable outcomes and preserve patient safety. In this review, our aim is to thoroughly describe the general principles and current status of laparoscopic liver resection for hepatocellular carcinoma, as well as future prospects.

Surgical treatment of hepatic metastases from colorectal cancer

Colorectal carcinoma is one of the most frequent cancers in Western societies with an incidence of around 700 per million people.About half of the patients develop metastases from the primary tumor and liver is the primary metastatic site.Improved survival rates after hepatectomy for metastatic colorectal cancer have been reported in the last few years and these may be the result of a variety of factors,such as advances in systemic chemotherapy,radiographic imaging techniques that permit more accurate determination of the extent and location of the metastatic burden,local ablation methods,and in surgical techniques of hepatic resection.These have led to a more aggressive approach towards liver metastatic disease,resulting in longer survival.The goal of this paper is to review the role of various forms of surgery in the treatment of hepatic metastases from colorectal cancer.

Evolving role of Sorafenib in the management of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common malignant diseases worldwide and comes third in cancer-related mortality.Although there is a broad spectrum of treatment options to choose from,only a few patients are eligible candidates to receive a curative therapy according to their stage of disease,and thus palliative treatment is implemented in the majority of the patients suffering from liver cancer.Sorafenib,a multikinase inhibitor,is the only currently approved agent for systemic therapy in patients with advanced stage HCC and early stage liver disease.It has been shown to improve the overall survival,but with various side effects,while its cost is not negligible.Sorafenib has been in the market for a decade and has set the stage for personalized targeted therapy.Its role during this time has ranged from monotherapy to neoadjuvant and adjuvant treatment with surgical resection,liver transplantation and chemoembolization or even in combination with other chemotherapeutic agents.In this review our aim is to highlight in depth the current position of Sorafenib in the armamentarium against HCC and how that has evolved over time in its use either as a single agent or in combination with other therapies.

Challenges and opportunities in the application of artificial intelligence in gastroenterology and hepatology

Artificial intelligence(AI)is an umbrella term used to describe a cluster of interrelated fields.Machine learning(ML)refers to a model that learns from past data to predict future data.Medicine and particularly gastroenterology and hepatology,are data-rich fields with extensive data repositories,and therefore fruitful ground for AI/ML-based software applications.In this study,we comprehensively review the current applications of AI/ML-based models in these fields and the opportunities that arise from their application.Specifically,we refer to the applications of AI/ML-based models in prevention,diagnosis,management,and prognosis of gastrointestinal bleeding,inflammatory bowel diseases,gastrointestinal premalignant and malignant lesions,other nonmalignant gastrointestinal lesions and diseases,hepatitis B and C infection,chronic liver diseases,hepatocellular carcinoma,cholangiocarcinoma,and primary sclerosing cholangitis.At the same time,we identify the major challenges that restrain the widespread use of these models in healthcare in an effort to explore ways to overcome them.Notably,we elaborate on the concerns regarding intrinsic biases,data protection,cybersecurity,intellectual property,liability,ethical challenges,and transparency.Even at a slower pace than anticipated,AI is infiltrating the healthcare industry.AI in healthcare will become a reality,and every physician will have to engage with it by necessity.

Role of innovative 3D printing models in the management of hepatobiliary malignancies

Three-dimensional (3D) printing has recently emerged as a new technique in various liver-related surgical fields. There are currently only a few systematic reviews that summarize the evidence of its impact. In order to construct a systematic literature review of the applications and effects of 3D printing in liver surgery, we searched the PubMed, Embase and ScienceDirect databases for relevant titles, according to the PRISMA statement guidelines. We retrieved 162 titles, of which 32 met the inclusion criteria and are reported. The leading application of 3D printing in liver surgery is for preoperative planning. 3D printing techniques seem to be beneficial for preoperative planning and educational tools, despite their cost and time requirements, but this conclusion must be confirmed by additional randomized controlled trials.

Hepatocellular carcinoma and metabolic syndrome: The times are changing and so should we

Although hepatocellular carcinoma (HCC) is as prevalent as ever as a cancerrelated mortality, and some would even argue that it is increasing, the pattern of its etiologies has been changing. Specifically, the domination of viral hepatitis C virus is being overcome, partly because of the emergence of the antiviral treatments, and partly because of the significant increase, especially in developed countries, of the combination of obesity, diabetes, metabolic syndrome, nonalcoholic fatty liver disease and non-alcoholic steatohepatitis. This editorial will explore the interconnection of this group of diseases and how they are linked to HCC. More importantly, it will argue that this shift in HCC etiology essentially means that we have to change how we approach the treatment of HCC, by changing our focus (and resources) to earlier stages of the disease development in order to prevent the appearance and progression of HCC.

Role of three-dimensional printing and artificial intelligence in the management of hepatocellular carcinoma:Challenges and opportunities

Hepatocellular carcinoma(HCC)constitutes the fifth most frequent malignancy worldwide and the third most frequent cause of cancer-related deaths.Currently,treatment selection is based on the stage of the disease.Emerging fields such as three-dimensional(3D)printing,3D bioprinting,artificial intelligence(AI),and machine learning(ML)could lead to evidence-based,individualized management of HCC.In this review,we comprehensively report the current applications of 3D printing,3D bioprinting,and AI/ML-based models in HCC management;we outline the significant challenges to the broad use of these novel technologies in the clinical setting with the goal of identifying means to overcome them,and finally,we discuss the opportunities that arise from these applications.Notably,regarding 3D printing and bioprinting-related challenges,we elaborate on cost and cost-effectiveness,cell sourcing,cell viability,safety,accessibility,regulation,and legal and ethical concerns.Similarly,regarding AI/ML-related challenges,we elaborate on intellectual property,liability,intrinsic biases,data protection,cybersecurity,ethical challenges,and transparency.Our findings show that AI and 3D printing applications in HCC management and healthcare,in general,are steadily expanding;thus,these technologies will be integrated into the clinical setting sooner or later.Therefore,we believe that physicians need to become familiar with these technologies and prepare to engage with them constructively.

Detection of human papillomavirus DNA in esophageal carcinoma in Greece

AIM:To detect human papillomavirus(HPV)in theesophageal mucosa and the possible relationship with esophageal cancer in Greece.METHODS:Forty-nine patients underwent esophagogastroduodenoscopy(EGD)and esophageal biopsy at a university hospital that acts as a referral center for Northern Greece.Nineteen of these patients(14 male and 5 female)had esophageal squamous cell carcinoma(ESCC)and 30(15 male and 15 female)did not have any reported esophageal malignancy.Histopathological assessment was followed by polymerase chain reaction analysis of all the samples.Patient demographic data(age,sex,and place of birth)and information regarding smoking habits,alcohol consumption or sexual habits were collected.A method of statistical interference,verification of hypotheses based on homogeneity and independentχ2 test,was used.RESULTS:From the 49 patients that underwent EGD and biopsy,19 had ESCC and 30 had normal esophageal mucosa,with a mean age of 65.2 years.Regarding the prevalence of oncogenic risk factors for esophageal carcinoma,an interesting conclusion was that 78%of the patients used tobacco and almost one-third had multiple sexual partners,whereas only 20%of the patients consumed alcohol,which was not statistically significant,when compared to the control group.In the ESCC group,the only two positive samples were among the male patients(2/14 male patients with ESCC,14.5%).No HPV was identified in the control group.The predominant HPV types identified were 11 and 31,which have a low malignancy potential.The presence of HPV DNA in the ESCC group was not statistically significant,95%confidence interval(χ2=3.292,P=0.07).CONCLUSION:This is the first relevant study in Greece,and despite the lack of statistical significance,the issue of HPV infection and ESCC does merit further investigation.

Metabolic syndrome and liver disease in the era of bariatric surgery: What you need to know!

Metabolic syndrome(MS)is defined as the constellation of obesity,insulin resistance,high serum triglycerides,low high-density lipoprotein cholesterol,and high blood pressure.It increasingly affects more and more people and progressively evolves into a serious issue with widespread healthcare,cost,and quality of life associated consequences.MS is associated with increased morbidity and mortality due to cardiovascular or chronic liver disease.Conservative treatment,which includes diet,exercise,and antidiabetic agents,is the mainstay of treatment,but depends on patient compliance to medical treatment and adherence to lifestyle modification recommendations.Bariatric surgery has recently emerged as an appropriate alternative treatment with promising longterm results.Sleeve gastrectomy and Roux-en-Y gastric bypass constitute the most commonly performed procedures and have been proven both cost-effective and safe with low complication rates.Liver transplantation is the only definitive treatment for end-stage liver disease and its utilization in patients with nonalcoholic steatohepatitis has increased more than fivefold over the past 15 years.In this review,we summarize current state of evidence on the surgical treatment of MS.

Immunotherapy for advanced hepatocellular carcinoma:From clinical trials to real-world data and future advances

Hepatocellular carcinoma(HCC)is a leading cause of cancer-associated mortality worldwide.HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers.Advanced HCC is managed with systemic therapies;the tyrosine kinase inhibitor(TKI)sorafenib has been used in 1st-line setting since 2007.Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors(ICIs)are licensed in 1st-and 2nd-line treatment setting.The treatment field of advanced HCC is continuously evolving.Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents,such as other ICIs,TKIs,and anti-angiogenics.Novel immunotherapies including adoptive cell transfer,vaccine-based approaches,and virotherapy are also being brought to the fore.Yet,despite advances,several challenges persist.Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort.Consequently,issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications,comorbidities,or poor performance status;lack of response,efficacy,and safety data;and cost-effectiveness.Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making.This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC,with a focus on ICIs,as well as novel immunotherapy strategies underway.

Role of liver transplantation in the management of colorectal liver metastases:Challenges and opportunities

The liver is the most common site of colorectal cancer metastasis.Complete resection of the metastatic tumor is currently the only treatment modality available with a potential for cure.However,only 20%of colorectal liver metastases(CRLM)are considered resectable at the time of presentation.Liver transplantation(LT)has been proposed as an alternative oncologic treatment for patients with unresectable CRLM.This review summarizes the published experiences of LT in the setting of unresectable CRLM from the previous decades and discusses the challenges and future horizons in the field.Contemporary experiences that come mostly from countries with broader access to liver grafts are also explored and their promising findings in terms of overall survival(OS)and disease-free survival(DFS)are outlined along with their study design and methods.The rationale of establishing specific patient selection criteria and the dilemmas around immunosuppressive regimens in patients undergoing LT for CRLM are also highlighted.Additionally,this review describes the findings of studies comparing LT vs chemotherapy alone and LT vs portal vein embolization plus resection for CRLM in terms of OS and DFS.Last but not least,we present current perspectives and ongoing prospective trials that try to elucidate the role of LT for CRLM.

Enhanced recovery after surgery in liver transplantation:Challenges and feasibility

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.