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.

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.

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.

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.

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.

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.

Obstetrical and gynecologic challenges in the liver transplant patient

An increasing number of childbearing agewomen undergo liver transplantation(LT)in the United States.Transplantation in this patient subgroup poses a significant challenge regarding the plans for future fertility,particularly in terms of immunosuppression and optimal timing of conception.Intrapartum LT is only rarely performed as the outcome is commonly dismal for the mother or more commonly the fetus.On the other hand,the outcomes of pregnancy in LT recipients are favorable,and children born to LT recipients are relatively healthy.Counseling on pregnancy should start before LT and continue after LT up until pregnancy,while all pregnant LT recipients must be managed by amultidisciplinary team,including both an obstetrician and a transplant hepatologist.Additionally,an interval of at least 1-2 years after successful LT is recommended before considering pregnancy.Pregnancy-induced hypertension,pre-eclampsia,and gestational diabetes mellitus are reported more commonly during the pregnancies of LT recipients than in the pregnancies of non-transplant patients.As adverse fetal outcomes,such asmiscarriage,abortion,stillbirth,or ectopic pregnancy,may occur more often than in the non-transplant population,early planning or delivery either through a planned induction of labor or cesarean section is critical to minimize the risk of complications.No significant long-term physical or phycological abnormalities have been reported in children born to LT recipients.

Pediatric surgery during the COVID-19 pandemic

The coronavirus disease 2019(COVID-19)pandemic has had a major impact on pediatric surgery.The infection is often asymptomatic and atypical in children,while overlapping presentations with other infectious diseases generate additional diagnostic challenges.The high probability of missed pediatric cases and the invasive nature of surgery generate great concern for widespread transmission in this setting.Current guidelines suggest that triage of cases should be made on a case-by-case basis by a multidisciplinary team of experts.Decisionmaking can be assisted by classifying cases as elective,urgent,or an emergency according to the risks of delaying their surgical management.A workflow diagram should ideally guide the management of all cases from admission to discharge.When surgery is necessary,all staff should use appropriate personal protective equipment,and high-risk practices,such as aerosol-generating tools or procedures,should be avoided if possible.Furthermore,carefully designed organizational protocols should be established to minimize transmission while ensuring the uninterrupted operation of pediatric surgery units.For example,surgical teams can be divided into small weekly rotating groups,and healthcare workers should be continuously monitored for COVID-19 symptoms.Additionally,team protocols in the operating room can optimize communication and improve adherence to personal protective equipment use.Isolated operating rooms,pediatric intensive care units,and surgical wards should be specifically designed for suspected or confirmed COVID-19 cases.Finally,transportation of patients should be minimal and follow designated short routes.All these measures can help mitigate the effects of the COVID-19 pandemic on pediatric surgery units.

Pediatric transplantation during the COVID-19 pandemic

Children infected by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)seem to have a better prognosis than adults.Nevertheless,pediatric solid organ transplantation(SOT)has been significantly affected by the unprecedented coronavirus disease 2019(COVID-19)pandemic during the pre-,peri-,and posttransplant period.Undoubtedly,immunosuppression constitutes a real challenge for transplant clinicians as increased immunosuppression may prolong disease recovery,while its decrease can contribute to more severe symptoms.To date,most pediatric SOT recipients infected by SARS-CoV-2 experience mild disease with only scarce reports of life-threatening complications.As a consequence,after an initial drop during the early phase of the pandemic,pediatric SOTs are now performed with the same frequency as during the pre-pandemic period.This review summarizes the currently available evidence regarding pediatric SOT during the COVID-19 pandemic.

Management of biliary atresia:To transplant or not to transplant

Kasai procedure(KP)and liver transplantation(LT)represent the only therapeutic options for patients with biliary atresia(BA),the most common indication for LT in the pediatric population.However,KP represents by no means a radical option but rather a bridging one,as nearly all patients will finally require a liver graft.More and more experts in the field of transplant surgery propose that maybe it is time for a paradigm change in BA treatment and abandon KP as transplantation seems inevitable.Inadequacy of organs yet makes this option currently not feasible,so it seems useful to find ways to maximize the efficacy of KP.In previous decades,multiple studies tried to identify these factors which opt for better results,but in general,outcomes of KP have not improved to the level that was anticipated.This review provides the framework of conditions which favor native liver survival after KP and the ones which optimize a positive LT outcome.Strategies of transition of care at the right time are also presented,as transplantation plays a key role in the surgical treatment of BA.Future studies and further organization in the transplant field will allow for greater organ availability and better outcomes to be achieved for BA patients.

Rapid right ventricular pacing for balloon valvuloplasty in congenital aortic stenosis:A systematic review

BACKGROUND Balloon aortic valvuloplasty(BAV)is a well-established treatment modality for congenital aortic valve stenosis.AIM To evaluate the role of rapid right ventricular pacing(RRVP)in balloon stabilization during BAV on aortic regurgitation(AR)in pediatric patients.METHODS A systematic review of the MEDLINE,Cochrane Library,and Scopus databases was conducted according to the PRISMA guidelines(end-of-search date:July 8,2020).The National Heart,Lung,and Blood Institute and Newcastle-Ottawa scales was utilized for quality assessment.RESULTS Five studies reporting on 72 patients were included.The studies investigated the use of RRVP-assisted BAV in infants(>1 mo)and older children,but not in neonates.Ten(13.9%)patients had a history of some type of aortic valve surgical or catheterization procedure.Before BAV,58(84.0%),7(10.1%),4(5.9%)patients had AR grade 0(none),1(trivial),2(mild),respectively.After BAV,34(49.3%),6(8.7%),26(37.7%),3(4.3%),patients had AR grade 0,1,2,and 3(moderate),respectively.No patient developed severe AR after RRVP.One(1.4%)developed ventricular fibrillation and was defibrillated successfully.No additional arrhythmias or complications occurred during RRVP.CONCLUSION RRVP can be safely used to achieve balloon stability during pediatric BAV,which could potentially decrease AR rates.

Liver transplantation during COVID-19: Adaptive measures with future significance

Following the outbreak of coronavirus disease 2019(COVID-19),a disease caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the field of liver transplantation,along with many other aspects of healthcare,underwent drastic changes.Despite an initial increase in waitlist mortality and a decrease in both living and deceased donor liver transplantation rates,through the implementation of a series of new measures,the transplant community was able to recover by the summer of 2020.Changes in waitlist prioritization,the gradual implementation of telehealth,and immunosuppressive regimen alte-rations amidst concerns regarding more severe disease in immunocompromised patients,were among the changes implemented in an attempt by the transplant community to adapt to the pandemic.More recently,with the advent of the Pfizer BNT162b2 vaccine,a powerful new preventative tool against in-fection,the pandemic is slowly beginning to subside.The pandemic has cert-ainly brought transplant centers around the world to their limits.Despite the unspeakable tragedy,COVID-19 constitutes a valuable lesson for health systems to be more prepared for potential future health crises and for life-saving tran-splantation not to fall behind.