Neoadjuvant treatment of pancreatic ductal adenocarcinoma:Whom,when and how

Pancreatic ductal adenocarcinoma(PDAC),which is notorious for its aggressiveness and poor prognosis,remains an area of great unmet medical need,with a 5-year survival rate of 10%-the lowest of all solid tumours.At diagnosis,only 20%of patients have resectable pancreatic cancer(RPC)or borderline RPC(BRPC)disease,while 80%of patients have unresectable tumours that are locally advanced pancreatic cancer(LAPC)or have distant metastases.Nearly 60%of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy(CHT)because of postoperative complications and early cancer recurrence.An important paradigm shift to achieve better outcomes has been the sequence of therapy,with neoadjuvant CHT preceding surgery.Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers:RPC,BRPC,and LAPC.The main goal of neoadjuvant treatment(NAT)is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT,reducing tumour volume before surgery to improve the rate of margin-negative resection(R0 resection,a microscopic margin-negative resection),reducing the rate of positive lymph node occurrence at surgery,providing early treatment of occult micrometastatic disease,and assessing tumour chemosensitivity and tolerance to treatment as potential surgical criteria.In this editorial,we summarize evidence concerning NAT of PDAC,providing insights into future practice and study design.Future research is needed to establish predictive biomarkers,measures of therapeutic response,and multidisciplinary stra tegies to improve patient-centered outcomes.

Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.

Magnetic resonance imaging for diagnosis and neoadjuvant treatment evaluation in locally advanced rectal cancer:A pictorial review

High-resolution pelvic magnetic resonance imaging(MRI) is the primary method for staging rectal cancer.MRI is highly accurate in the primary staging of rectal cancer;however,it has not proven to be effective in restaging,especially in complete response evaluation after neoadjuvant therapy.Neoadjuvant chemoradiotherapy produces many changes in rectal tumors and on adjacent area,as a result,local tumor extent may not be accurately determined.However,adding diffusion-weighted sequences to the standard approach can improve diagnostic accuracy.In this pictorial review,an overview of the situation of MRI in the staging and re-staging of rectal cancer is exhibited as a pictorial assay.An experience-and literature-based discussion of limitations and difficulties in interpretation are also presented.

Neoadjuvant-intensified treatment for rectal cancer:Time to change?

AIM:To investigate whether neoadjuvant-intensified radiochemotherapy improved overall and disease-free survival in patients with locally advanced rectal cancer.METHODS:Between January 2007 and December 2011,80 patients with histologically confirmed rectal adenocarcinoma were enrolled.Tumors were clinically classified as either T3 or T4 and by the N stage based on the presence or absence of positive regional lymph nodes.Patients received intensified combined modality treatment,consisting of neoadjuvant radiation therapy(50.4-54.0 Gy) and infusional chemotherapy(oxaliplatin 50 mg/m 2) on the first day of each week,plus five daily continuous infusions of fluorouracil(200 mg/m 2 per die) from the first day of radiation therapy until radiotherapy completion.Patients received five or six cycles of oxaliplatin based on performance status,clinical lymph node involvement,and potential risk of a non-sphincter-conserving surgical procedure.Surgery was planned 7 to 9 wk after the end of radiochemotherapy treatment;adjuvant chemotherapy treatment was left to the oncologist's discretion and was recommended in patients with positive lymph nodes.After treatment,all patients were monitored every three months for the first year and every six months for the subsequent years.RESULTS:Of the 80 patients enrolled,75 patients completed the programmed neoadjuvant radiochemotherapy treatment.All patients received the radiotherapy prescribed total dose;five patients suspended chemotherapy indefinitely because of chemotherapyrelated toxicity.At least five cycles of oxaliplatin were administered to 73 patients.Treatment was well tolerated with high compliance and a good level of toxicity.Most of the acute toxic effects observed were classified as grades 1-2.Proctitis grade 2 was the most common symptom(63.75%) and the earliest manifestation of acute toxicity.Acute toxicity grades 3-4 was reported in 30% of patients and grade 3 or 4 diarrhoea reported in just three patients(3.75%).Seventy-seven patients underwent surgery;low anterior resection was performed in 52 patients,Miles' surgery in 11 patients and total mesorectal excision in nine patients.Fifty patients showed tumor downsizing ≥ 50% pathological downstaging in 88.00% of tumors.Out of 75 patients surviving surgery,67 patients(89.33%) had some form of downstaging after preoperative treatment.A pathological complete response was achieved in 23.75% of patients and a nearly pathologic complete response(stage ypT1ypN0) in six patients.An involvement of the radial margin was never present.During surgery,intra-abdominal metastases were found in only one patient(1.25%).Initially,45 patients required an abdominoperineal resection due to a tumor distal margin ≤ 5 cm from the anal verge.Of these patients,only seven of them underwent Miles' surgery and sphincter preservation was guaranteed in 84.50% of patients in this subgroup.Fourteen patients received postoperative chemotherapy.In the full analysis of enrolled cohort,eight of the 80 patients died,with seven deaths related to rectal cancer and one to unrelated causes.Local recurrences were observed in seven patients(8.75%) and distant metastases in 17 cases(21.25%).The fiveyear rate of overall survival rate was 90.91%.Using a median follow-up time of 28.5 mo,the cumulative incidence of local recurrences was 8.75%,and the overall survival and disease-free survival rates were 90.00% and 70.00%,respectively.CONCLUSION:The results of this study suggest oxaliplatin chemotherapy has a beneficial effect on overall survival,likely due to an increase in local tumor control.

Acute recurrent pancreatitis:Etiopathogenesis, diagnosis and treatment

Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches.

Impact of treatment modalities on patients with recurrent hepatocellular carcinoma after liver transplantation:Preliminary experience

Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population.Methods:A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study.Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival.Results:Of the 64 patients with recurrent HCC after LT,those who received radical resection followed by nonsurgical therapy had a median overall survival(OS)of 20.9 months after HCC recurrence,significantly superior to patients who received only nonsurgical therapy(9.4 months)or best supportive care(2.4 months).The one-and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy(93.8%,52.6%),poor for patients receiving only nonsurgical therapy(30.8%,10.8%),and dismal for patients receiving best supportive care(0%,0%;overall P<0.001).Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months,far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure(12 months,P<0.001).Compared with tacrolimus-based immunosuppressive therapy,OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence(P=0.035).Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival.Conclusions:Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence.A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.

Risk factors for local recurrence following neoadjuvant chemoradiotherapy for rectal cancers

Local recurrence(LR)has an adverse impact on rectal cancer treatment.Neoadjuvant chemoradiotherapy(nCRT)is increasingly administered to patients with progressive cancers to improve the prognosis.However,LR still remains a problem and its pattern can alter.Correspondingly,new risk factors have emerged in the context of nCRT in addition to the traditional risk factors in patients receiving non-neoadjuvant therapies.These risk factors are decisive when reviewing treatment options.This review aims to elucidate the distinctive risk factors related to LR of rectal cancers in patients receiving nCRT and to clarify their clinical significance.A search was conducted on PubMed to identify original studies investigating patients with rectal cancer receiving nCRT.Outcomes of interest,especially potential risk factors for LR in patients with nCRT,were then analyzed.The clinical importance of these risk factors is discussed.Remnant cancer cells,lymph-nodes and tumor response were found to be major risk factors.Remnant cancer cells decide the status of resection margins.Local excision following nCRT is promising in ypT0-1N0M0 cases.Dissection of lateral lymph nodes should be considered in advanced lowlying cancers.Although better tumor response resulted in a relatively lower recurrence rate,the evidence available is insufficient to justify a non-operative approach in clinical complete responders to nCRT.LR cannot be totally avoided by current multidisciplinary approaches.The related risk factors resulting from nCRT should be considered when making decisions regarding treatment selection.

Neoadjuvant treatment for resectable pancreatic adenocarcinoma

Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound(nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress.

Multiphoton microscopy for tumor regression grading after neoadjuvant treatment for colorectal carcinoma

AIM: To evaluate the feasibility of using multiphoton microscopy(MPM) to assess a tumor regression grading(TRG) system.METHODS: Fresh specimens from seven patients with colorectal carcinoma undergoing neoadjuvant radiochemotherapy at the Fujian Medical University Union Hospital were obtained immediately after proctectomy.Specimens were serially sectioned(10 μm thickness) and used for MPM or stained with hematoxylin and eosin for comparison.Sections were imaged by MPM using 810 nm excitation, and images were collected in two wavelength channels corresponding to second-harmonic generation(SHG) and two-photon excited fluorescence(TPEF) signals.The ratio of these signal intensities was used to distinguish fibrosis from normal mucosal and serosal tissues.RESULTS: TRG of specimens assessed by MPMwere in complete agreement with histologic grading performed by a consulting pathologist.SHG and TPEF images clearly revealed collagen fibers and fragmented elastic fibers in the muscularis propria specimens following neoadjuvant radiochemotherapy.Additionally, blood vessel hyperplasia was observed as thickening and fibrosis of the intima and media, which was accompanied by minimal inflammatory cell infiltration.Furthermore, the SHG/TPEF ratio in stromal fibrosis(4.15 ± 0.58) was significantly higher than those in the normal submucosal(2.31 ± 0.52) and serosal(1.47 ± 0.10) tissues(P < 0.001 for both).Analysis of emission spectra from cancerous tumor cells revealed two peaks corresponding to nicotinamide adenine dinucleotide hydrogen and flavin adenine dinucleotide signals; the ratio of these values was 1.19 ± 0.02, which is close to a normal metabolic state.CONCLUSION: MPM can be used to perform realtime diagnosis of tumor response after neoadjuvant treatment, and can be applied to evaluate TRG.

Sentinel lymph node metastasis after neoadjuvant treatment in breast cancer:Any size matters?

One of the advantages of neoadjuvant chemotherapy(NAC) treatments is its ability to convert patients who need a mastectomy in breast conservative surgery. NAC has also increased the conversion of node positive patients into node negative in around 40% allowing the use of sentinel node biopsy(SLN) in this setting. Timing of SLN biopsy after NAC has been a subject of debate. In patients with clinically node negative before NAC,rates of success and false negative rates of SLN after NAC are similar to those in the adjuvant setting,so SLN after NAC in previous negative axilla has been incorporated in the staging of the axilla. More controversial is its use in patients with positive axillary nodes before NAC who convert to node negative after NAC. Several randomized studies have reported the identification rates and the false negative rates of the SLN after NAC,concordant in the importance of surgical technique. As there is an agreement in the abandon of the immunohistochemistry(IHC) for SLN in the adjuvant setting as SLN IHC detected metastasis appear to have no impact on overall survival,in patients with SLN after NAC the inclusion of isolated tumor cell(ITC) as positive nodes lowers the false negative rates of the technique,suggesting the importance of assessing the SLN by IHC after NAC and considering it as residual disease. Longer follow up is needed to determine the prognostic implications of ITC in the SLN after NAC.

Nonoperative management of gastrointestinal malignancies in era of neoadjuvant treatment

Cancers derived from the gastrointestinal(GI)tract are often treated with radical surgery to achieve a cure.However,recent advances in the management of GI cancers involve the use of a combination of neoadjuvant radiation and chemotherapy followed by surgical intervention to achieve improved local control and cure.Interestingly,a small proportion of patients with highly sensitive tumors achieved a pathological complete response(pCR)(no residual tumor cells in the resected specimen)to neoadjuvant chemoradiation therapy(nCRT).The desire for organ preservation and avoidance of surgical morbidity brings the idea of a nonoperative management(NOM)strategy.Because of the different nature of tumor biology,GI cancers present diverse responses to nCRT,ranging from high sensitivity(anal cancer)to low sensitivity(gastric/esophageal cancer).There is an increasing attention to NOM of localized GI cancers;however,without the use of biomarkers/imaging parameters to select such patients,NOM will remain a challenge.Therefore,this review intends to summarize some of the recent updates from the aspect of current nCRT regimens,criteria for patient selection and active surveillance schedules.We also hope to review significant sequelae of radical surgery and the complications of nCRT to clarify the directions for optimization of nCRT and NOM for oncologic outcomes and quality of life.

Neoadjuvant chemoradiotherapy plus surgery in the treatment of potentially resectable thoracic esophageal squamous cell carcinoma

BACKGROUNDIn recent years, neoadjuvant chemoradiotherapy (NCRT) combined with surgeryhas been gradually applied in patients with locally advanced thoracic esophagealcancer, but its effectiveness and safety remains unclear. In this clinical trial, weprospectively investigated the efficacy and safety of NCRT plus surgery in thetreatment of thoracic esophageal squamous cell carcinoma (TESCC).AIMTo investigate the efficacy and safety of NCRT combined with surgery in thetreatment of potentially resectable TESCC.METHODSThirty patients with advanced TESCC hospitalized in our hospital from July2016 to June 2019 were prospectively studied. All patients received NCRT, whichincluded intensity modulated conformal radiotherapy (40-44 Gy/20-22f, 2 Gy/f)and chemotherapy (paclitaxel 150-175 mg/m2d1, 22 + lobaplatin 25-30 mg/m2d2,23 for two cycles). Surgery was performed after radiotherapy and chemotherapy.The effectiveness and safety of these treatments were observed.RESULTSAmong these 30 patients, complete response was achieved in two cases (6.7%) andpartial response in 26 cases (86.7%), yielding an objective response rate of 100%.All patients underwent radical surgery successfully. The R0 resection rate was100%, and the pathologic complete response rate was 33.3%. The incidence ofgrade III- IV granulocytopenia was 10% during the NCRT, and anastomoticleakage occurred in one patient after surgery.CONCLUSIONFor patients with potentially resectable TESCC, NCRT can effectively reduce thetumor size, increase R0 resection rate, and achieve obvious pathologicaldegradation, with mild adverse reactions. Thus, it is worthy of wider clinicalapplication.

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma

BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy efficacy.AIM To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC patients.METHODS Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included.Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment.Antiallergic efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of nIC.RESULTS From September 2019 to September 2023,142 patients were analyzed.No severe treatment-related adverse events or deaths were observed.Allergy occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,respectively.The long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term efficacy.Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

Role of imaging in evaluating the response after neoadjuvant treatment for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive malignancy.Despite the development of multimodality treatments,including surgical resection,radiotherapy,and chemotherapy,the long-term prognosis of patients with PDAC remains poor.Recently,the introduction of neoadjuvant treatment(NAT)has made more patients amenable to surgery,increasing the possibility of R0 resection,treatment of occult micro-metastasis,and prolongation of overall survival.Imaging plays a vital role in tumor response evaluation after NAT.However,conventional imaging modalities such as multidetector computed tomography have limited roles in the assessment of tumor resectability after NAT for PDAC because of the similar appearance of tissue fibrosis and tumor infiltration.Perfusion computed tomography,using blood perfusion as a biomarker,provides added value in predicting the histopathologic response of PDAC to NAT by reflecting the changes in tumor matrix and fibrosis content.Other imaging technologies,including diffusion-weighted imaging of magnetic resonance imaging and positron emission tomography,can reveal the tumor response by monitoring the structural changes in tumor cells and functional metabolic changes in tumors after NAT.In addition,with the renewed interest in data acquisition and analysis,texture analysis and radiomics have shown potential for the early evaluation of the response to NAT,thus improving patient stratification to achieve accurate and intensive treatment.In this review,we briefly introduce the application and value of NAT in resectable and unresectable PDAC.We also summarize the role of imaging in evaluating the response to NAT for PDAC,as well as the advantages,limitations,and future development directions of current imaging techniques.

Increased CD4/CD8 Lymphocyte ratio predicts favourable neoadjuvant treatment response in gastric cancer:A prospective pilot study

BACKGROUND Despite optimal neoadjuvant chemotherapy only 40%of gastric cancer tumours achieve complete or partial treatment response.In the absence of treatment response,neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone.Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy(5-Fluorouracil,Leucovorin,Oxaliplatin and Docetaxel).Predictive biomarkers detected using immunohistochemistry(IHC)methods may provide useful data regarding treatment response.AIM To investigate the utility of CD4,CD8,Galectin-3 and E-cadherin in predicting neoadjuvant FLOT chemotherapy tumour response in gastric adenocarcinoma.METHODS Forty-three adult patients with gastric adenocarcinoma,of which 18 underwent neoadjuvant chemotherapy,were included in a prospective clinical cohort.Endoscopic biopsies were obtained from gastric cancer and normal adjacent gastric mucosa.Differences in expression of Galectin-3,Ecadherin,CD4^(+)and CD8^(+)molecules between tumours with and without treatment response to neoadjuvant chemotherapy were assessed with IHC.Treatment response was graded by clinical pathologists using the Tumour Regression Score according to the College of American Pathologists criteria.Treatment response was defined as complete or near complete tumour response,whereas partial or poor/no response was defined as incomplete.Digital IHC images were annotated and quantitatively assessed using QuPath 0.3.1.Biomarker expression between responsive and incomplete response tumours was assessed using a two-sided Wilcoxon test.Biomarker expression was also compared between normal and cancer tissue and between 15 paired tumour samples before and after chemotherapy.We performed a preliminary multivariate analysis and power analysis to guide future study.Statistical analyses were completed using R 4.1.2.RESULTS The ratio between CD4^(+)and CD8^(+)lymphocytes was significantly greater in treatment responsive tumours(Wilcoxon,P=0.03).In univariate models,CD4^(+)/CD8^(+)ratio was the only biomarker that significantly predicted favourable treatment response(Accuracy 86%,P<0.001).Using a glmnet multivariate model,high CD4^(+)/CD8^(+)ratio and low Galectin-3 expression were the most influential variables in predicting a favourable treatment response.Analyses of paired samples found that FLOT chemotherapy also results in increased expression of CD4^(+)and CD8^(+)tumour infiltrating lymphocytes(Paired Wilcoxon,P=0.002 and P=0.008,respectively).Our power analysis suggests future study requires at least 35 patients in each treatment response group for CD8 and Galectin-3 molecules,whereas 80 patients in each treatment response group are required to assess CD4 and E-cadherin biomarkers.CONCLUSION We demonstrate that an elevated CD4^(+)/CD8^(+)Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment:A case report

BACKGROUND Lenvatinib has been shown to be noninferior to sorafenib regarding prognosis and recurrence rate in patients with unresectable hepatocellular carcinoma(HCC)who have not received prior systemic chemotherapy.In patients treated with lenvatinib,40%of cases achieved sufficient tumor reduction to make potential surgery possible.However,the outcomes of such surgery are unknown.We report a successful case of hepatic resection for recurrent HCC after lenvatinib treatment.CASE SUMMARY A 69-year-old man underwent right anterior sectionectomy for HCC in segment 8 of the liver.Ten months later,he was found to have an intrahepatic HCC recurrence that grew rapidly to 10 cm in diameter with sternal bone metastases.After confirming partial response to lenvatinib administration for 2 mo,a second hepatectomy was performed.Pathological examination showed that 80%of the tumor was necrotic.The patient did not develop any adverse effects under lenvatinib treatment.He was discharged at 25 d after surgery.Radiation therapy for bone metastases continued to be given under lenvatinib,and the patient has remained alive for 1 year after the second hepatectomy.CONCLUSION The prognosis of patients with recurrent HCC may be improved by liver resection combined with prior lenvatinib therapy.

Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis

BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients.METHODS A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31,2023.The correlation between TIL levels and the NAT pathologic com-plete response(pCR)in TNBC patients was assessed using a systematic review and meta-analysis.Subgroup analysis,sensitivity analysis,and publication bias analysis were also conducted.RESULTS A total of 32 studies were included in this meta-analysis.The overall meta-ana-lysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup(48.0%vs 27.7%)(risk ratio 2.01;95%confidence interval 1.77-2.29;P<0.001,I2=56%).Subgroup analysis revealed that the between-study hetero-geneity originated from differences in study design,TIL level cutoffs,and study populations.Publication bias could have existed in the included studies.The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols(all P≤0.01),and there was no significant between-protocol difference in the statistics among the different NAT protocols(P=0.29).Additionally,sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded.CONCLUSION TILs can serve as a predictor of the response to NAT treatment in TNBC patients.TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs,and this predictive capability is con-sistent across different NAT regimens.

Influence of hyperbaric oxygenation treatment (HBOT) on clinical outcomes (recurrent myocardial infarction and survival rate) during five-year monitoring period after acute myocardial infarction

Surgical treatments of acute myocardial infarction (MI) possess a high clinical effectiveness, but there are fixed limitations, related to the patient’s state, which are limited by medical resources and organizational problems. The development of new medical technologies provides a better and effective non-surgical treatment of acute MI and increases long-term prognosis in this category of patients. The study aims to investigate the influence of hyperbaric oxygenation treatment on clinical outcomes (survival rate and recurrent myocardial infarction (rMI)) during the five-year period of monitoring. The study involved 697 patients who suffered from acute MI, having undergone the standard treatment. The patients were randomly divided into two groups: Group 1 (reference, n = 363);Group 2 (test, n = 334). Patients of Group 2 were given the traditional treatment, accompanied with HBOT (isopression for forty minutes at a working pressure of 0.03 MPa). HBOT was applied first through the fifth day following MI. The treatment course included six cycles, once per day. The clinical assessment was focused on clinical outcome: rMI and mortality related to cardiovascular events. HBOT application that accompanied the acute MI with traditional pharmacotherapy has been proved to reduce rMI within five years following inpatient discharge (rMI rate was 14% in the reference group and 5.4% in the test group, χ2 = 13.3, р < 0.05). The combination of HBOT with traditional methods in treating acute MI makes it possible to raise the five-year survival rate from 84.4% up to 95.9%.

Temozolomide plus rituximab in the treatment of recurrent central nervous system lymphoma:Case report and literature review

Objective： The aim of our study was to investigate the treatment of recurrent central nervous system lymphoma. Methods： A case of recurrent central nervous system lymphoma in a 46-year-old male was treated with temozolomide 150 mg/m2 per day for 5 days; rituximab 750 mg/m2 on dl and d8, injected from Ommaya capsule to lateral ventricle, cycles were repeated every 28 days. Results： The patient achieved complete remission and the side effects was light after the treatment. Conclusion： Using this therapy method had certain curative effect on recurrent central nervous system lymphoma. Further studies should be needed on its indication.