Assessment of pathogens and risk factors associated with bloodstream infection in the year after pediatric liver transplantation

BACKGROUND Bloodstream infection(BSI)is one of the most significantly adverse events that can occur after liver transplantation(LT)in children.AIM To analyze the profile of BSI according to the postoperative periods and assess the risk factors after pediatric LT.METHODS Clinical data,collected from medical charts of children(n=378)who underwent primary LT,were retrospectively reviewed.The primary outcome considered was BSI in the first year after LT.Univariate and multivariate analyses were performed to identify risk factors for BSI and respective odds ratios(ORs).RESULTS Of the examined patients,106(28%)experienced 162 episodes of pathogen-confirmed BSI during the first year after LT.There were 1.53±0.95 episodes per children(mean±SD)among BSIcomplicated patients with a median onset of 0.4 mo post-LT.The most common pathogenic organisms identified were Coagulase-negative staphylococci,followed by Enterococcus spp.and Streptococcus spp.About half(53%)of the BSIs were of unknown origin.Multivariate analysis demonstrated that young age(≤1.3 year;OR=2.1,P=0.011),growth failure(OR=2.1,P=0.045),liver support system(OR=4.2,P=0.008),and hospital stay of>44 d(OR=2.3,P=0.002)were independently associated with BSI in the year after LT.CONCLUSION BSI was frequently observed in patients after pediatric LT,affecting survival outcomes.The profile of BSI may inform clinical treatment and management in high-risk children after LT.

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.

A surgical technique using the gastroepiploic vein for portal inflow restoration in living donor liver transplantation in a patient with diffuse portomesenteric thrombosis

Portal vein thrombosis(PVT)is no longer a definitive contraindication in liver transplants(LTs)[1].Complex vascular reconstructions such as cavoportal hemitransposition(CPHT)[2–5],renoportal anastomosis(RPA)[6,7],and use of sizable collaterals(pericholedochal varix[8,9],coronary vein,peripancreatic or perigastroesophageal varices[10],right superior colic vein[11],ileocolic vein[12],and left gastric vein[13]),or combined liverpancreas-small bowel transplant[14]are required for portal inflow in patients with total portosplenomesenteric thrombosis.

Feasibility of ABO-incompatible adult living donor liver transplantation for acute-on-chronic liver failure

To the Editor:In Korea,the annual number of deceased donors for or gan transplantation per million people is still less than10.Thus,approximately 40%of patients with acute liver failure or acute-on-chronic liver failure undergo living donor liver transplantation（LDLT）.;Although the use of ABO-incompatible（ABOi）living donors is an attrac tive option,ABOi LDLT has very restricted applications

Morbidity analysis of left hepatic trisectionectomy for hepatobiliary disease and live donor

Background:Despite remarkable advances in surgical techniques and perioperative management,left hepatic trisectionectomy(LHT)remains a challenging procedure with a somewhat high postoperative morbidity rate compared with less-extensive resections.This study aimed to analyze the short-and long-term outcomes of LHT and identify factors associated with the postoperative morbidity of this technically demanding surgical procedure.Methods:The medical records of 53 patients who underwent LHT between June 2005 and October 2019 at a single institution were retrospectively reviewed.The independent prognostic factor of postoperative morbidity was analyzed using the logistic regression model.Results:Hepatocellular carcinoma was the most common indication for surgery(n=21),followed by hilar cholangiocarcinoma(n=14),intrahepatic cholangiocarcinoma(n=10),and other pathologies(including colorectal liver metastasis,hepatolithiasis,gallbladder cancer,living donor,hemangioma,and multilocular biliary cyst;n=8).The rates of postoperative morbidities of Clavien-Dindo grade 3 or higher and 90-day mortality were 39.6% and 1.9%,respectively.The 1-,3-,and 5-year overall survival rates were 81.1%,61.4%,and 44.6%,respectively.Multivariate analysis revealed that preoperative jaundice[hazard ratio(HR)=6.15,95%confidence interval(CI):1.57-24.17,P=0.009]and operative time>420 min(HR=4.66,95%CI:1.27–17.17,P=0.021)were independent predictors of postoperative morbidity.Conclusions:The in-hospital mortality of LHT surgery can be minimalized by a reliable preoperative evaluation of liver function and selection of the dominant anatomic features of right posterior sector,active and appropriate preoperative management for obstructive cholangitis and compensatory hypertrophy of the future remnant posterior sector,and the experience of the surgeon.

Salvage living donor liver transplantation for recurrent hepatocellular carcinoma after prior laparoscopic hepatectomy

Salvage liver transplantation(LT)is frequently performed on patients who experience recurrent hepatocellular carcinoma(HCC)after primary hepatectomy for HCC[1,2].The main concern in these patients is the technical feasibility of salvage LT,especially as prior hepatectomy may result in heavy adhesions[3,4].Salvage living donor LT(LDLT)is a more demanding procedure than salvage deceased donor LT(DDLT)using an entire donor graft with a long vascular pedicle[5,6].Because less than optimal dissection of perihepatic adhesions could result in uncontrollable pinpoint bleedings at the dissection surface[1,5],many transplant surgeons avoid performing salvage LDLT.Minimally invasive laparoscopic hepatectomy(LH)results in fewer intraperitoneal adhesions than the open method,reducing the difficulty of surgical dissection during future LT[7–10].To date,however,no study has compared salvage LDLT for recurrent HCC after LH to that after open hepatectomy(OH).

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.

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.

Surgical treatment of liver metastasis with uveal melanoma:A case report

BACKGROUND Uveal melanoma is the most common primary intraocular malignant tumor affecting the eyes in adults.Nearly half of all primary uveal melanoma tumors metastasize;yet,there are currently no effective treatments for metastatic uveal melanoma.At the time of diagnosis,less than 4%of patients with uveal melanoma have detectable metastatic disease.Uveal melanoma disseminates hematogenously,with the most common site of metastasis being liver(93%),followed by lung(24%)and bone(16%).CASE SUMMARY A 57-year-old woman was diagnosed with a dysplastic nevus on her eyelid,which was histologically confirmed as malignant melanoma after resection.The patient had no evidence of metastasis to other organs and received both radiation therapy and chemotherapy.After systemic treatment,a metastatic left neck lymph node was found and another round of chemotherapy was performed after resection.Positron emission tomography-Computed Tomography tracking after completion of chemotherapy revealed two metastatic liver nodules.The patient underwent partial liver resection and showed no signs of recurrence at 1 year after surgery.CONCLUSION Surgery is an effective treatment for metastatic uveal melanoma.In patients with liver metastatic lesions,hepatectomy improves outcome.

Portal vein stenting as a significant risk factor for biliary stricture in adult living donor liver transplantation

BACKGROUND: Although perioperative portal vein (PV) stent implantation is an effective treatment for steno-occlusive disease in adult living donor liver transplantation (LDLT) re-cipients, we experienced high incidence of biliary anastomotic strictures (BAS) after PV stenting. In this study, we sought to clarify the relation between BAS and PV stenting and to suggest the possible mechanism of BAS and measures to reduce its in-cidence. METHODS: We retrospectively analyzed 44 LDLT recipients who underwent PV stent implantation across the line of PV anastomosis regardless of the location of steno-occlusion (stent group) and their matched controls (non-stented LDLT recipients, n=131). RESULTS: The incidence of BAS was higher in patients in the stent group than that in the control group (43.2% vs 17.6%, P=0.001). Cumulative 6-month and 1-, 2- and 5-year BAS rates were 31.8%, 34.1%, 41.4% and 43.2%, respectively, in the stent group and 13.0%, 13.8%, 16.1% and 17.8%, respectively, in the control group (P=0.001). Multivariate analysis revealed that PV stenting was an independent risk factor for BAS. CONCLUSIONS: Although PV stent implantation is a reliable treatment modality for steno-occlusive PV in adult LDLT recipients, innovative methods to prevent the PV stent from crossing the line of PV anastomosis may be necessary to reduce the incidence of postoperative BAS.

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.

Sequential transcatheter arterial chemoembolization and portal vein embolization before right hemihepatectomy in patients with hepatocellular carcinoma

Background:Recent studies showed that sequential selective transcatheter arterial chemoembolization(TACE)and portal vein embolization(PVE)provided better future liver remnant(FLR)regeneration rate and disease-free survival following surgery compared with PVE alone.The present study aimed to clarify whether preoperative sequential TACE and PVE before right hemihepatectomy can reduce postoperative hepatocellular carcinoma(HCC)recurrence and improve long-term disease-free and overall survival.Methods:Recurrence and survival outcomes were retrospectively evaluated in 205 patients with HCC who underwent right hemihepatectomy by a single surgeon from November 1993 to November 2017.Patients were divided into four groups according to the procedure performed before the surgery:sequential TACE and PVE(TACE-PVE),PVE-only,TACE-only,or na?ve control groups.The baseline patient and tumor characteristics,postoperative outcomes,recurrence-free survival and overall survival were analyzed.Results:Baseline patient and tumor characteristics upon diagnosis were similar in all four groups,while sequential TACE and PVE were well tolerated.The TACE-PVE group had a higher mean increase in percentage FLR volume compared with that of the PVE-only group(17.46%±6.63%vs.12.14%±5.93%;P=0.001).The TACE-PVE group had significantly better overall and disease-free survival rates compared with the other groups(both P<0.001).Conclusions:Sequential TACE and PVE prior to surgery can be an effective therapeutic strategy for patients with HCC scheduled for major hepatic resection.The active application of preoperative sequential TACE and PVE for HCC would allow more patients with marginal FLR volume to become candidates for major hepatic resection by promoting compensatory FLR hypertrophy without the deterioration of basal hepatic functional reserve or tumor progression.

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.

Colonic mucormycosis presented with ischemic colitis in a liver transplant recipient

Mucormycosis is an uncommon opportunistic fungal infection with high mortality in liver transplant recipients. Mucormycosis of the gastrointestinal tract can manifest with features similar to ischemic colitis. Typically signs and symptoms of non-gangrenous ischemic colitis resolve spontaneously within 24-48 h. On the other hand, the clinical course of the mucormycosis is commonly fulminant. We encountered a case of invasive fungal colitis presenting with abdominal pain and hematochezia in a liver transplant recipient. Endoscopic examination showed multiple shallow ulcerations and edema with mucosal friabilities on the sigmoid and distal descending colon, which was consistent with ischemic colitis. However, the histological examination obtained from endoscopic biopsies showed fungal hyphae withsurrounding inflammatory cells and mucosal necrosis. The patient was successfully managed with antifungal agent without surgical treatment. Thus, early diagnosis and treatment is essential for improving the prognosis of invasive fungal infection after liver transplantation.

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.

How to reduce and manage the hepatic arterial complications in living and deceased donor liver transplantation?

Hepatic artery(HA)reconstruction in liver transplantation(LT),particularly in living donor liver transplantation(LDLT)is nerve-wracking job due to the smallest and shortest vascular structures.The diameter of donor HA in Asian people is less than 3 mm in more than three quarters of the donors(1).After introduction of microvascular techniques for HA reconstruction in LDLT,the incidence of arterial complications has decreased significantly(2).

Liver transplantation for hepatoblastoma

Liver transplantation is the only potentially curative option for unresectable hepatoblastoma.The introduction of platinum-based chemotherapy drastically improved the survival outcomes of patients with hepatoblastoma.However,the use of neoadjuvant chemotherapy and the optimal number of cycles required in patients listed for liver transplantation,as well as the potential use of adjuvant chemotherapy,remain unclear.Additionally,the shortage of donor liver grafts,along with the lack of clear consensus on the management of metastatic hepatoblastoma,makes the decision on whether to proceed to liver transplantation even more complex and challenging.Technological advances may optimize intraoperative imaging of both the primary tumor and metastatic sites,thus facilitating complete resection.Such improvements,along with the wider use of social media platforms to increase public awareness,could potentially pave the way for more optimal implementation of liver transplantation for the treatment of patients with unresectable hepatoblastoma.

The beneficial impacts of splanchnic vasoactive agents on hepatic functional recovery in massive hepatectomy porcine model

Background:Excessive portal pressure after massive hepatectomy can cause hepatic sinusoidal injury and have deleterious impacts on hepatic functional recovery,contributing to developing post-hepatectomy liver failure.This study aimed to assess the effects of splanchnic vasoactive agents on hepatic functional recovery and regeneration while clarifying the underlying mechanism,using a 70%hepatectomy porcine model.Methods:Eighteen pigs undergoing 70%hepatectomy were involved in this study and divided into three groups:control(n=6),terlipressin(n=6),and octreotide(n=6).Terlipressin(0.5 mg)and octreotide(0.2 mg)were administered 3 times a day for each group with the first dose starting just before surgery until the 7th postoperative day,at which time the surviving pigs were sacrificed.During the period,portal pressure,liver weight,biochemical analysis,histological injury score,and molecular markers were evaluated and compared between groups.Results:The 7-day survival rates in the octreotide,terlipressin,and control groups were 100%,83.3%,and 66.7%,respectively.The portal pressures decreased in both terlipressin and octreotide groups than the control group at 30 minutes,1 hour and 6 hours after hepatectomy.The amount of regeneration measured by liver weight to body weight ratio at the time of sacrifice in the terlipressin group was smaller than that in the control group(117%vs.129%,P=0.03).Serum aspartate aminotransferase(AST)and total bilirubin levels at 1 and 6 hours after hepatectomy and prothrombin time/international normalized ratio(PT/INR)at 6 hours after hepatectomy were significantly improved in the terlipressin and octreotide groups compared to the control group.Serum endothelin-1(ET-1)was significantly lower in the terlipressin group than that in the control group 6 hours after hepatectomy(P<0.01).The histological injury score in the control group was significantly higher than that in the terlipressin group on the 7th postoperative day(P<0.01).Conclusions:Splanchnic vasoactive agents,such as terlipressin and octreotide,could effectively decrease portal pressure and attenuate liver injury after massive hepatectomy.