Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is(limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.

Interventional radiology treatment for pulmonary embolism

Venous thromboembolism(VTE) is an illness that has a potentially life-threatening condition that affects a large percentage of the global population. VTE with pulmonary embolism(PE) is the third leading cause of death after myocardial infarction and stroke. In the first three months after an acute PE, there is an estimated 15% mortality among submassive PE, and 68% mortality in massive PE. Current guidelines suggest fibrinolytic therapy regarding the clinical severity, however some studies suggest a more aggressive treatment approach. This review will summarize the available endovascular treatments and the different techniques with its indications and outcomes.

Non-anatomical liver resection for hepatocellular carcinoma:the SegSubTe classification to overcome the problem of heterogeneity

Background:The superiority of anatomical resection(AR)vs.non-anatomical resection(NAR)in the surgical management of hepatocellular carcinoma(HCC)is debated.ARs are well-defined procedures,whereas the lack of NAR standardization results in heterogeneous outcomes.This study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the tumor.Methods:A single-center retrospective analysis of pre-and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was conducted.The quality of surgery was assessed classifying the type of vascular supply and the level of surgical section(segmental,subsegmental or terminal next to the tumor)of vascular pedicles feeding the HCCs;then,the population was divided in“SegSubTe-IN”or“SegSubTe-OUT”groups,and the tumor recurrence and survival were analyzed.Results:Ninety-seven patients who underwent NAR were included;76%were SegSubTe-IN and 24%were SegSubTe-OUT.Total disease recurrence,local recurrence and cut-edge recurrence in the SegSubTe-IN vs.SegSubTe-OUT groups were 50%vs.83%(P=0.006),20%vs.52%(P=0.003)and 16%vs.39%(P=0.020),respectively.SegSubTe-OUT odds ratio for local recurrence was 4.1 at univariate regression analysis.One-,three-,and five-year disease-free survival rates in the SegSubTe-IN vs.SegSubTe-OUT groups were 81%,58%and 35%vs.46%,21%and 11%,respectively(P<0.001).Conclusions:The SegSubTe classification is a useful tool to stratify and standardize NAR for HCC,aiming at improving long-term oncological outcomes and reducing the heterogeneity of quality of NAR for HCC.

Extravasated contrast volumetric assessment on computed tomography angiography in gastrointestinal bleeding:A useful predictor of positive angiographic findings

BACKGROUND Gastrointestinal bleeding(GIB)is a severe and potentially life-threatening condition,especially in cases of delayed treatment.Computed tomography angiography(CTA)plays a pivotal role in the early identification of upper and lower GIB and in the prompt treatment of the haemorrhage.AIM To determine whether a volumetric estimation of the extravasated contrast at CTA in GIB may be a predictor of subsequent positive angiographic findings.METHODS In this retrospective single-centre study,35 patients(22 men;median age 69 years;range 16-92 years)admitted to our institution for active GIB detected at CTA and further submitted to catheter angiography between January 2018 and February 2022 were enrolled.Twenty-three(65.7%)patients underwent endoscopy before CTA.Bleeding volumetry was evaluated in both arterial and venous phases via a semi-automated dedicated software.Bleeding rate was obtained from volume change between the two phases and standardised for unit time.Patients were divided into two groups,according to the angiographic signs and their concordance with CTA.RESULTS Upper bleeding accounted for 42.9%and lower GIB for 57.1%.Mean haemoglobin value at the admission was 7.7 g/dL.A concordance between positive CTA and direct angiographic bleeding signs was found in 19(54.3%)cases.Despite no significant differences in terms of bleeding volume in the arterial phase(0.55 mL vs 0.33 mL,P=0.35),a statistically significant volume increase in the venous phase was identified in the group of patients with positive angiography(2.06 mL vs 0.9 mL,P=0.02).In the latter patient group,a significant increase in bleeding rate was also detected(2.18 mL/min vs 0.19 mL/min,P=0.02).CONCLUSION In GIB of any origin,extravasated contrast volumetric analysis at CTA could be a predictor of positive angiography and may help in avoiding further unnecessary procedures.

Image-guided locoregional non-intravascular interventional treatments for hepatocellular carcinoma: Current status

Hepatocellular carcinoma(HCC) is one of the most deadly and frequent cancers worldwide,although great advancement in the treatment of this malignancy have been made within the past few decades.It continues to be a major health issue due to an increasing incidence and a poor prognosis.The majority of patients have their HCC diagnosed at an intermediate or advanced stage in theUSA or China.Curative therapy such as surgical resection or liver transplantation is not considered anoption of treatment at these stages.Transarterial chemoembolization(TACE),the most widely used locoregional therapeutic approach,used to be the mainstay of treatment for cases with unresectable cancer entities.However,for those patients with hypovascular tumors or impaired liver function reserve,TACE is a suboptimal treatment option.For example,embolization does not result in complete coverage of a hypovascular tumor,and may rather promotes postoperative tumor recurrence,or leave residual tumor,in these TACE-resistance patients.In addition,TACE carries a higher risk of hepatic decompensation in patients with poor liver function or reserve.Non-vascular interventional locoregional therapies for HCC include radiofrequency ablation(RFA),microwave ablation(MWA),high-intensity focused ultrasound(HIFU),laser-induced thermotherapy(LITT),cryosurgical ablation(CSA),irreversible Electroporation(IRE),percutaneous ethanol injection(PEI),and brachytherapy.Recent advancements in these techniques have significantly improved the treatment efficacy of HCC and expanded the population of patients who qualify for treatment.This review embraces the current status of imaging-guided locoregional non-intravascular interventional treatments for HCCs,with a primary focus on the clinical evaluation and assessment of the efficacy of combined therapies using these interventional techniques.

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.

Mechanisms and therapeutic strategies to combat the recurrence and progression of hepatocellular carcinoma after thermal ablation

Thermal ablation(TA),including radiofrequency ablation(RFA)and microwave ablation(MWA),has become the main treatment for early-stage hepatocellular carcinoma(HCC)due to advantages such as safety and minimal invasiveness.However,HCC is prone to local recurrence,with more aggressive malignancies after TA closely related to TA-induced changes in epithelial-mesenchymal transition(EMT)and remodeling of the tumor microenvironment(TME).According to many studies,various components of the TME undergo complex changes after TA,such as the recruitment of innate and adaptive immune cells,the release of tumor-associated antigens(TAAs)and various cytokines,the formation of a hypoxic microenvironment,and tumor angiogenesis.Changes in the TME after TA can partly enhance the anti-tumor immune response;however,this response is weak to kill the tumor completely.Certain components of the TME can induce an immunosuppressive microenvironment through complex interactions,leading to tumor recurrence and progression.How the TME is remodeled after TA and the mechanism by which the TME promotes HCC recurrence and progression are unclear.Thus,in this review,we focused on these issues to highlight potentially effective strategies for reducing and preventing the recurrence and progression of HCC after TA.

Fracture of inferior vena cava stent after endovascular treatment for Budd-Chiari syndrome:A case series and literature review

Budd-Chiari syndrome(BCS)is a rare condition characterized by hepatic venous outflow obstruction.Balloon angioplasty,with or without stenting,is the recommended first-line treatment modality in Asian countries.As a supplement to balloon angioplasty,expandable metallic Z-stent deployment can effectively improve long-term inferior vena cava(IVC)patency.Although stent placement is a standard and frequently performed treatment,very few IVC stent-related complications,such as stent fractures,have been reported.Here we present a case series and a comprehensive review of IVC stent fractures in patients with BCS.The most common characteristic of IVC stent fractures is a protrusion of the proximal segment of the IVC stent into the right atrium and its systolic and diastolic movements along with heart rhythms.Accurate stent deployment,large-diameter balloon dilation,patient breath-holding training,preferential selection of a triple stent,and the use of an internal jugular vein approach to stent deployment may ensure precise stent localization and avoid postoperative complications.

Liver involvement in patients with COVID-19 infection:A comprehensive overview of diagnostic imaging features

During the first wave of the pandemic,coronavirus disease 2019(COVID-19)infection has been considered mainly as a pulmonary infection.However,different clinical and radiological manifestations were observed over time,including involvement of abdominal organs.Nowadays,the liver is considered one of the main affected abdominal organs.Hepatic involvement may be caused by either a direct damage by the virus or an indirect damage related to COVID-19 induced thrombosis or to the use of different drugs.After clinical assessment,radiology plays a key role in the evaluation of liver involvement.Ultrasonography(US),computed tomography(CT)and magnetic resonance imaging(MRI)may be used to evaluate liver involvement.US is widely available and it is considered the first-line technique to assess liver involvement in COVID-19 infection,in particular liver steatosis and portal-vein thrombosis.CT and MRI are used as second-and third-line techniques,respectively,considering their higher sensitivity and specificity compared to US for assessment of both parenchyma and vascularization.This review aims to the spectrum of COVID-19 liver involvement and the most common imaging features of COVID-19 liver damage.

Combined therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation for small hepatocellular carcinoma

AIM:To assess the efficacy of combined transcatheter arterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)for small hepatocellular carcinoma(HCC). METHODS:Thirty-five patients with a total of 41 HCC nodules(≤3 cm in diameter)were treated with TACE followed by computed tomograghy(CT)-guided percutaneous microwave coagulation therapy(PMCT) within 1-3 wk. RESULTS:By biopsies and enhanced CT scans, complete necrosis of the tumor and 3-5 mm of the surrounding non-cancerous area were observed in 34 foci.In seven foci,incomplete necrosis of the surrounding parenchyma was observed.Serum alpha- fetoprotein(AFP)levels returned to normal 10 d after treatment in 25 patients who originally had high serum AFP levels.The follow-up period was 6-31 mo,and all patients remained alive.One patient had a recurrence in the subsegments of the liver,and another patient had a recurrence near the original lesion. CONCLUSION:Combined therapy with TACE and PMCT is a safe and effective treatment without severe complications for small HCC.

Portal vein thrombosis and arterioportal shunts:Effects on tumor response after chemoembolization of hepatocellular carcinoma

AIM: To evaluate the effect of portal vein thrombosis and arterioportal shunts on local tumor response in advanced cases of unresectable hepatocellular carcinoma treated by transarterial chemoembolization. METHODS: A retrospective study included 39 patients (mean age: 66.4 years, range: 45-79 years, SD: 7) with unresectable hepatocellular carcinoma (HCC) who were treated with repetitive transarterial chemoembolization (TACE) in the period between March 2006 and October 2009. The effect of portal vein thrombosis (PVT) (in 19 out of 39 patients), the presence of arterioportal shunt (APS) (in 7 out of 39), the underlying liver pathology,Child-Pugh score, initial tumor volume, number of tumors and tumor margin definition on imaging were correlated with the local tumor response after TACE. The initial and end therapy local tumor responses were evaluated according to the response evaluation criteria in solid tumors (RECIST) and magnetic resonance imaging volumetric measurements. RESULTS: The treatment protocols were well tolerated by all patients with no major complications. Local tumor response for all patients according to RECIST criteria were partial response in one patient (2.6%), stable disease in 34 patients (87.1%), and progressive disease in 4 patients (10.2%). The MR volumetric measurements showed that the PVT, APS, underlying liver pathology and tumor margin definition were statistically significant prognostic factors for the local tumor response (P = 0.018, P = 0.008, P = 0.034 and P = 0.001, respectively). The overall 6-, 12- and 18-mo survival rates from the initial TACE were 79.5%, 37.5% and 21%, respectively. CONCLUSION: TACE may be exploited safely for palliative tumor control in patients with advanced unresectable HCC; however, tumor response is significantly affected by the presence or absence of PVT and APS.

Locoregional treatments for hepatocellular carcinoma: Current evidence and future directions

Liver cancers are the second most frequent cause of global cancer-related mortality of which 90%are attributable to hepatocellular carcinoma(HCC).Despite the advent of screening programmes for patients with known risk factors,a substantial number of patients are ineligible for curative surgery at presentation with limited outcomes achievable with systemic chemotherapy/external radiotherapy.This has led to the advent of numerous minimally invasive options including but not limited to trans-arterial chemoembolization,radiofrequency/microwave ablation and more recently selective internal radiation therapy many of which are often the first-line treatment for select stages of HCC or serve as a conduit to liver transplant.The authors aim to provide a comprehensive overview of these various image guided minimally invasive therapies with a brief focus on the technical aspects accompanied by a critical analysis of the literature to assess the most up-to-date evidence from comparative systematic reviews and meta-analyses finishing with an assessment of novel combination regimens and future directions of travel.

MR with Gd-EOB-DTPA in assessment of liver nodules in cirrhotic patients

To date the imaging diagnosis of liver lesions is based mainly on the identification of vascular features, which are typical of overt hepatocellular carcinoma(HCC), but the hepatocarcinogenesis is a complex and multistep event during which, a spectrum of nodules develop within the liver parenchyma, including benign small and large regenerative nodule(RN), low-grade dysplastic nodule(LGDN), high-grade dysplastic nodule(HGDN), early HCC, and well differentiated HCC. These nodules may be characterised not only on the basis of their respective different blood supplies, but also on their different hepatocyte function. Recently, in liver imaging the introduction of hepatobiliary magnetic resonance imaging contrast agent offered the clinicians the possibility to obtain, at once, information not only related to the vascular changes of liver nodules but also information on hepatocyte function. For this reasons this new approach becomes the most relevant diagnostic clue for differentiating low-risk nodules(LGDN-RN) from highrisk nodules(HGDN/early HCC or overt HCC) and consequently new diagnostic algorithms for HCC have been proposed. The use of hepatobiliary contrast agents is constantly increasing and gradually changing the standard of diagnosis of HCC. The main purpose of this review is to underline the added value of Gd-EOB-DTPA in early-stage diagnoses of HCC. We also analyse the guidelines for the diagnosis and management of HCC, the key concepts of HCC development, growth and spread and the imaging appearance of precursor nodules that eventually may transform into overt HCC.

Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy

Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management.

Transjugular intrahepatic portosystemic shunt for Budd-Chiari syndrome:A comprehensive review

Budd-Chiari syndrome(BCS)is a relatively rare clinical condition with a wide range of symptomatology,caused by the obstruction of the hepatic venous outflow.If left untreated,it has got an high mortality rate.Its management is based on a step-wise approach,depending on the clinical presentation,and includes different treatment from anticoagulation therapy up to Interventional Radiology techniques,such as transjugular intrahepatic portosystemic shunt(TIPS).TIPS is today considered a safe and highly effective treatment and should be recommended for BCS patients,including those awaiting orthotopic liver transplantation.In this review the pathophysiology,diagnosis and treatment options of BCS are presented,with a special focus on published data regarding the techniques and outcomes of TIPS for the treatment of BCS.Moreover,unresolved issues and future research will be discussed.

Recent advances in non-invasive magnetic resonance imaging assessment of hepatocellular carcinoma

Magnetic resonance(MR) imaging of the liver is an important tool for the detection and characterization of focal liver lesions and for assessment of diffuse liver disease,having several intrinsic characteristics,represented by high soft tissue contrast,avoidance of ionizing radiation or iodinated contrast media,and more recently,by application of several functional imaging techniques(i.e.,diffusion-weighted sequences,hepatobiliary contrast agents,perfusion imaging,magnetic resonance(MR)-elastography,and radiomics analysis). MR functional imaging techniques are extensively used both in routine practice and in the field of clinical and pre-clinical research because,through a qualitative rather than quantitative approach,they can offer valuable information about tumor tissue and tissue architecture,cellular biomarkers related to the hepatocellular functions,or tissue vascularization profiles related to tumor and tissue biology. This kind of approach offers in vivo physiological parameters,capable of evaluating physiological and pathological modifications of tissues,by the analysis of quantitative data that could be used in tumor detection,characterization,treatmentselection,and follow-up,in addition to those obtained from standard morphological imaging. In this review we provide an overview of recent advanced techniques in MR for the diagnosis and staging of hepatocellular carcinoma,and their role in the assessment of response treatment evaluation.

Imaging and radiological interventions in extra-hepatic portal vein obstruction

Extrahepatic portal vein obstruction(EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahepatic branches, splenic or superior mesenteric vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension(PHT) in developing countries. It is a pre-hepatic type of PHT in which liver functions and morphology are preserved till late. Characteristic imaging findings include multiple parabiliary venous collaterals which form to bypass the obstructed portal vein with resultant changes in biliary tree termed portal biliopathy or portal cavernoma cholangiopathy. Ultrasound with Doppler, computed tomography, magnetic resonance cholangiography and magnetic resonance portovenography are non-invasive techniques which can provide a comprehensive analysis of degree and extent of EHPVO, collaterals and bile duct abnormalities. These can also be used to assess in surgical planning as well screening for shunt patency in post-operative patients. The multitude of changes and complications seen in EHPVO can be addressed by various radiological interventional procedures. The myriad of symptoms arising secondary to vascular, biliary, visceral and neurocognitive changes in EHPVO can be managed by various radiological interventions like transjugular intra-hepatic portosystemic shunt, percutaneous transhepatic biliary drainage, partial splenic embolization, balloon occluded retrograde obliteration of portosystemic shunt(PSS) and revision of PSS.

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.

Transjugular intrahepatic portosystemic shunt for pyrrolizidine alkaloid-related hepatic sinusoidal obstruction syndrome

BACKGROUND Treatments for hepatic sinusoidal obstruction syndrome(HSOS)are limited.AIM To evaluate transjugular intrahepatic portosystemic shunting(TIPS)as a treatment for pyrrolidine alkaloid-related HSOS(PA-HSOS).METHODS This retrospective analysis included patients with PA-HSOS admitted to the First Affiliated Hospital of the University of Science and Technology of China(June 2015 to January 2019).Baseline clinical characteristics and follow-up data were extracted from the medical records.All patients included in this study experienced failure of initial therapy.Patients were divided into the TIPS and conservative treatment groups according to the therapy they received.Liver function,maximal ascites depth,imaging characteristics,pathology findings,and survival were compared between groups.RESULTS The TIPS group included 37 patients(28 males),and the conservative treatment group included 17 patients(11 males).Baseline characteristics were similar between groups.There were two deaths in the TIPS group and seven deaths in the conservative treatment group during follow-up(3-48 mo).The 3-,6-,12-and 24-mo survival rates were 94.6%,94.6%,94.6%and 94.6%,respectively,in the TIPS group and 70.6%,57.8%,57.8%and 57.8%,respectively,in the conservative treatment group.Kaplan-Meier analysis revealed significantly longer survival for the TIPS group than for the conservative treatment group(P=0.001).Compared with the pre-treatment value,maximal ascites depth was significantly lower at 1 wk,2 wk,1 mo,and 3 mo for the TIPS group(all P<0.05)but not in the conservative treatment group.Contrast-enhanced computed tomography demonstrated the disappearance of patchy liver enhancement after TIPS.Pathology showed that liver congestion and hepatocyte swelling improved with time after TIPS placement.CONCLUSION TIPS may achieve better outcomes than conventional symptomatic treatment in patients with PA-HSOS.

Post-traumatic hepatic artery pseudoaneurysm treated with endovascular embolization and thrombin injection

Post-traumatic hepatic artery pseudoaneurysm is unc-ommon,appearing in approximately 1%of hepatic trauma cases.Most are extrahepatic(80%)and have a late onset.Although they are usually asymptomatic, they should always be treated becasue of the high risk of complications,especially breakage.Currently the treatment of choice is endovascular embolization with coils or the exclusion of the pseudoaneurysm using other intravascular devices.Recently there have been accounts of a treatment that combines embolization with coils and image-guided percutaneous human thrombin injection.We present a case of post-traumatichepatic artery pseudoaneurysm that was successfully treated using this combined technique.