Intraductal papillary neoplasm of the bile duct:The new frontier of biliary pathology

Intraductal papillary neoplasms of the bile duct(IPNBs)represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen.Since their first description in 2001,several classifications have been proposed,mainly based on histopathological,radiological and clinical features,although no specific guidelines addressing their management have been developed.Bile duct neoplasms generally develop through a multistep process,involving different precursor pathways,ranging from the initial lesion,detectable only microscopically,i.e.biliary intraepithelial neoplasia,to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma.Complex and advanced investigations,mainly relying on magnetic resonance imaging(MRI)and cholangioscopy,are required to reach a correct diagnosis and to define an adequate bile duct mapping,which supports proper treatment.The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB,as well as their natural evolution with a particular focus on prognosis and survival.Aggressive surgical resection,including hepatectomy,pancreaticoduodenectomy or both,represents the treatment of choice,yielding optimal results in terms of survival,although several endoscopic approaches have been described.IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential.The novel subclassification of types 1 and 2 defines the histological and clinical aspects,prognosis and survival.Diagnosis is mainly based on MRI and cholangioscopy.Surgical resection represents the mainstay of treatment,although endoscopic resection is currently applied to nonsurgically fit patients.New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB,to identify targeted therapies.

Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(P<0.0001,for both the parameters).The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in conventionally treated patients(87.4%vs 61.5%,P=0.0493).Other factors affecting recurrence-free survival included viable tumor beyond Milan Criteria on histopathological examination,the percentage of necrosis on CTA≤50%and a pre-transplant serum-fetoprotein level greater than 70 ng/mL.On multivariate analysis,the lack of treatment with DEB-TACE,high levels of-fetoprotein and viable tumor beyond Milan Criteria at histology examination were identified as independent predictors of tumor recurrence.CONCLUSION:DEB-TACE can effectively promote tumor necrosis and improves recurrence-free survival after LT in HCC.

Predictive factors of short term outcome after liver transplantation: A review

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early posttransplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests(platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores(model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1th and the 5th day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.

Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma:Review of the literature

Cholangiocarcinoma(CCA)is a malignant tumor of the biliary system and includes,according to the anatomical classification,intra hepatic CCA(iCCA),hilar CCA(hCCA)and distal CCA(dCCA).Hilar CCA is the most challenging type in terms of diagnosis,treatment and prognosis.Surgery is the only treatment possibly providing long-term survival,but only few patients are considered resectable at the time of diagnosis.In fact,tumor’s extension to segmentary or subsegmentary biliary ducts,along with large lymph node involvement or intrahepatic metastases,precludes the surgical approach.To achieve R0 margins is mandatory for the disease-free survival and overall survival.In case of unresectable locally advanced hCCA,radiochemotherapy(RCT)as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation.Before liver surgery,RCT is believed to enhance the R0 margins rate.For patients meeting the Mayo Clinic criteria,RCT prior to orthotopic liver transplant(OLT)has proved to produce acceptable 5-years survivals.In this review,we analyze the current role of neoadjuvant RCT before resection as well as before OLT.

Radiological response and inflammation scores predict tumour recurrence in patients treated with transarterial chemoembolization before liver transplantation

AIM To investigate the prognostic value of the radiological response after transarterial chemoembolization(TACE)and inflammatory markers in patients affected by hepatocellular carcinoma(HCC)awaiting liver transplantation(LT).METHODS We retrospectively evaluated the preoperative pre dictors of HCC recurrence in 70 patients treated with conventional(n=16)or doxorubicin-eluting bead TACE(n=54)before LT.The patient and tumour characteristics,including the static and dynamic alpha-fetoprotein,neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio( LR)measurements,were recorded.Treatment response was classified according to the modified Response Evaluation Criteria in Solid Tumours(m RECIST)and the European Association for the Study of the Liver(EASL)criteria as complete response(CR),partial response( R),stable disease o progressive disease.After examination of the explanted livers,histological necrosis was classified as complete(100%of the cumulative tumour area),partia(50%-99%)or minimal(<50%)and was correlated with the preoperative radiological findings.RESULTS According to the pre-TACE radiological evaluation,22/70(31.4%)and 12/70(17.1%)patients were beyond Milan and University of San Francisco(UCSF)criteria,respectively.After TACE procedures,the objective response(CR+ R)rates were 71.4%and 70.0%according to m RECIST and EASL criteria,respectively.The agreement between the two guidelines in defining the radiological response was rated as very good both for the overall and target lesion response(weighted k-value:0.98 and 0.93,respectively).Complete and partial histological necrosis were achieved in 14/70(20.0%)and 28/70(40.0%)patients,respectively.Using histopathology as the reference standard,m RECIST criteria correctly classified necrosis in 72.9%(51/70)of patients and EASL criteria in 68.6%(48/70)of cases.The m RECIST non-response to TACE[Exp(b)=9.2, =0.012],exceeding UCSF criteria before TACE[Exp(b)=4.7, =0.033]and a preoperative LR>150[Exp(b)=5.9, =0.046]were independent predictors of tumour recurrence.CONCLUSION The radiological response and inflammatory markers are predictive of tumour recurrence and allow the proper selection of TACE-treated candidates for LT.

Transoesophageal echocardiography during liver transplantation

Liver transplantation(LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver trans-plant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the pro-cedures as a result of both the disease process and the surgery. Transoesophageal echocardiography(TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. More-over, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure.