Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the literature.AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT.METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACE or TAE.Some patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.RESULTS Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC.Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Non-alcoholic fatty liver disease in type 2 diabetes:Emerging evidence of benefit of peroxisome proliferator-activated receptors agonists and incretin-based therapies

Nonalcoholic fatty liver disease(NAFLD)is a global epidemic,affecting more than half of the people living with type 2 diabetes(T2D).The relationship between NAFLD and T2D is bidirectional and the presence of one perpetuates the other,which significantly increases the hepatic as well as extrahepatic complications.Until recently,there was no approved pharmacological treatment for NAFLD/nonalcoholic steatohepatitits(NASH).However,there is evidence that drugs used for diabetes may have beneficial effects on NAFLD.Insulin sensitizers acting through peroxisome proliferator-activated receptor(PPAR)modulation act on multiple levels of NAFLD pathogenesis.Pioglitazone(PPARγ agonist)and saroglitazar(PPARα/γagonist)are particularly beneficial and recommended by several authoritative bodies for treating NAFLD in T2D,although data on biopsyproven NASH are lacking with the latter.Initial data on elafibanor(PPARα/δ agonist)and Lanifibranor(pan PPAR agonist)are promising.On the other hand,incretin therapies based on glucagon-like peptide-1(GLP-1)receptor agonists(GLP-1RA)and dual-and triple-hormone receptor co-agonists reported impressive weight loss and may have anti-inflammatory and antifibrotic properties.GLP-1 RAs have shown beneficial effects on NAFLD/NASH and more studies on potential direct effects on liver function by dual-and triple-agonists are required.Furthermore,the long-term safety of these therapies in NAFLD needs to be established.Collaborative efforts among healthcare providers such as primary care doctors,hepatologists,and endocrinologists are warranted for selecting patients for the best possible management of NAFLD in T2D.

Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms

The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected reactions that occur after exposure to various classes of medication.Even though most cases consist of mild,temporary elevations in liver enzyme markers,DILI can also manifest as acute liver failure in some patients and can be associated with mortality.Herein,we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms:Chronic myeloid leukemia,polycythemia vera,essential thrombocythemia,and myelofibrosis.

Liver-directed therapies for liver metastases from neuroendocrine neoplasms:Can laser ablation play any role?

Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing interest.Catheter-based treatments are used in disseminated disease,whereas ablation techniques are usually indicated when the number of LM is limited.Although radiofrequency ablation(RFA)is by far the most used ablative technique,the goal of this opinion review is to explore the potential role of laser ablation(LA)in the treatment of LM from NEN.LA uses thinner needles than RFA,and this is an advantage when the tumors are in at-risk locations.Moreover,the multi-fiber technique enables the use of one to four laser fibers at once,and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter.Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor,sparing the liver parenchyma more than any other liver-directed therapy,and allowing for repeated treatments with low risk of liver failure.A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA,that can play a useful role in the multimodality approach to LM from NEN.

Conversion therapy in liver transplantation for hepatocellular carcinoma:What's new in the era of molecular and immune therapy?

Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic treatments,fast development of targeted drugs,the success of immunotherapy,as well as the emergence of the therapeutic alliance,conversion therapy has recently become more well developed and an effective therapeutic strategy.This article aimed to review recent developments in conversion therapy in liver transplantation(LT)for HCC.Data sources:We searched for relevant publications on Pub Med before September 2022,using the terms“HCC”,“liver transplantation”,“downstaging”,“bridging treatment”and“conversion therapy.”Results:Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT.Although combining various local and systematic treatments in conversion therapy is still controversial,growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time,which ultimately increases the opportunities for LT.Moreover,the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors.Conclusions:In the era of targeted therapy and immunotherapy,applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients.With the expansion of conversion therapy concepts,further investigation and research is required to realize the full potential of conversion treatment strategies,including accurately selecting candidates,determining the timing of surgery,improving the conversion rate,and guaranteeing the safety and long-term efficacy of treatment.

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions

Clinically,it is highly challenging to promote recovery in patients with acute liver failure(ALF)and acute-on-chronic liver failure(ACLF).Despite recent advances in understanding the underlying mechanisms of ALF and ACLF,standard medical therapy remains the primary therapeutic approach.Liver transplantation(LT)is considered the last option,and in several cases,it is the only intervention that can be lifesaving.Unfortunately,this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant.Another option is to restore impaired liver function with artificial extracorporeal blood purification systems.The first such systems were developed at the end of the 20th century,providing solutions as bridging therapy,either for liver recovery or LT.They enhance the elimination of metabolites and substances that accumulate due to compromised liver function.In addition,they aid in clearance of molecules released during acute liver decompensation,which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy,multiple-organ failure,and other complications of liver failure.As compared to renal replacement therapies,we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems.Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging.The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins.Furthermore,conventional methods such as plasma exchange are being re-evaluated,and novel adsorption filters are increasingly being used for liver indications.These strategies are very promising for the treatment of liver failure.Nevertheless,the best method,system,or device has not been developed yet,and its probability of getting developed in the near future is also low.Furthermore,little is known about the effects of liver support systems on the overall and transplant-free survival of these patients,and further investigation using randomized controlled trials and meta-analyses is needed.This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy.It focuses on general principles of their function,and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF.In addition,we have outlined the basic advantages and disadvantages of each system.

Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature

BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.

Neoplastic disease after liver transplantation: focus on de novo neoplasms

De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma(HCC) recurrence have been reported with the use of m TOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs m TOR-inhibitorfree immunosuppression is more efficacious in reducing HCC recurrence.

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

The AGH score is a predictor of disease-free survival and targeted therapy efficacy after liver transplantation in patients with hepatocellular carcinoma

Background:Liver transplantation(LT)is the“cure”therapy for patients with hepatocellular carcinoma(HCC).However,some patients encounter HCC recurrence after LT.Unfortunately,there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy.The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population,and to evaluate whether these patients are suitable for adjuvant targeted therapy.Methods:Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed.Results:A total of 201 patients were included in the study.The multivariate Cox analysis suggested that preoperative alpha-fetoprotein(AFP)>200μg/L(HR=2.666,95%CI:1.515-4.690;P=0.001),glutamyl transferase(GGT)>96 U/L(HR=1.807,95%CI:1.012-3.224;P=0.045),and exceeding the Hangzhou criteria(HR=2.129,95%CI:1.158-3.914;P=0.015)were independent risk factors for poor disease-free survival(DFS)in patients with HCC who underwent LT.We established an AFP-GGT-Hangzhou(AGH)scoring system based on these factors,and divided cases into high-,moderate-,and low-risk groups.The differences in overall survival(OS)and disease-free survival(DFS)rates among the three groups were significant(P<0.05).The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria,UCSF criteria,Milan criteria,and TNM stage.Only in the high-risk group,we found that lenvatinib significantly improved prognosis compared with that of the control group(P<0.05).Conclusions:The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China.Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Systematic review of ablative therapy for the treatment of renal allograft neoplasms

BACKGROUND To date,there are no guidelines on the treatment of solid neoplasms in the transplanted kidney.Historically,allograft nephrectomy has been considered the only reasonable option.More recently,nephron-sparing surgery (NSS) and ablative therapy (AT) have been proposed as alternative procedures in selected cases.AIM To review outcomes of AT for the treatment of renal allograft tumours.METHODS We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 Checklist.PubMed was searched in March 2019 without time restrictions for all papers reporting on radiofrequency ablation (RFA),cryoablation (CA),microwave ablation (MWA),high-intensity focused ultrasound (HIFU),and irreversible electroporation (IRE) of solid tumours of the kidney allograft.Only original manuscripts describing actual cases and edited in English were considered.All relevant articles were accessed in full text.Additional searches included all pertinent references.Selected studies were also assessed for methodological quality using a tool based on a modification of the Newcastle Ottawa scale.Data on recipient characteristics,transplant characteristics,disease characteristics,treatment protocols,and treatment outcomes were extracted and analysed.Given the nature and the quality of the studies available (mostly retrospective case reports and small retrospective uncontrolled case series),a descriptive summary was provided.RESULTS Twenty-eight relevant studies were selected describing a total of 100 AT procedures in 92 patients.Recipient age at diagnosis ranged from 21 to 71 years whereas time from transplant to diagnosis ranged from 0.1 to 312 mo.Most of the neoplasms were asymptomatic and diagnosed incidentally during imaging carried out for screening purposes or for other clinical reasons.Preferred diagnostic modality was Doppler-ultrasound scan followed by computed tomography scan,and magnetic resonance imaging.Main tumour types were: papillary renal cell carcinoma (RCC) and clear cell RCC.Maximal tumour diameter ranged from 5 to 55 mm.The vast majority of neoplasms were T1a N0 M0 with only 2 lesions staged T1b N0 M0.Neoplasms were managed by RFA (n = 78),CA (n = 15),MWA (n = 3),HIFU (n = 3),and IRE (n = 1).Overall,3 episodes of primary treatment failure were reported.A single case of recurrence was identified.Follow-up ranged from 1 to 81 mo.No cancer-related deaths were observed.Complication rate was extremely low (mostly < 10%).Graft function remained stable in the majority of recipients.Due to the limited sample size,no clear benefit of a single procedure over the other ones could be demonstrated.CONCLUSION AT for renal allograft neoplasms represents a promising alternative to radical nephrectomy and NSS in carefully selected patients.Properly designed clinical trials are needed to validate this therapeutic approach.

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.