Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

Laparoscopic anatomical liver resection of segment 7 using a sandwich approach to the right hepatic vein (with video)

Full laparoscopic liver resection has been performed widely since it was introduced in the early 1990s.It has been expanded from initial for partial resection of the anterolateral segments to non-restriction of area of the liver[1–3].Anatomical liver resec-tion is considered to have potential superiority than non-anatomic resection in terms of tumor prognosis,thus it is more often rec-ommended in the treatment of hepatocellular carcinoma[4,5].Recently,laparoscopic segmental liver resection according to the Couinaud classification has been widely performed due to its ad-vantages in minimal invasiveness and tumor prognosis.

Action of circulating and infiltrating B cells in the immune microenvironment of colorectal cancer by single-cell sequencing analysis

BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.

Imaging, pathology, and diagnosis of solitary fibrous tumor of the pancreas: A case report and review of literature

BACKGROUND A solitary fibrous tumor(SFT)is often located in the pleura,while SFT of the pancreas is extremely rare.Here,we report a case of SFT of the pancreas and discuss imaging,histopathology,and immunohistochemistry for accurate diagnosis and treatment.CASE SUMMARY A 54-year-old man presented to our hospital with pancreatic occupancy for over a month.There were no previous complaints of discomfort.His blood pressure was normal.Blood glucose,tumor markers,and enhanced computed tomography(CT)suggested a malignant tumor.Because the CT appearance of pancreatic cancer varies,we could not confirm the diagnosis;therefore,we performed endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB).Pathology and immunohistochemistry were consistent with SFT of the pancreas.The posto-perative pathology and immunohistochemistry were consistent with the puncture results.The patient presented for a follow-up examination one month after discharge with no adverse effects.CONCLUSION Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed.CT and pathological histology have diagnostic value for pancreatic tumors.Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively.Surgery is an effective treatment for SFT of the pancreas;however,long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

Clinical review and literature analysis of hepatic epithelioid angiomyolipoma in alcoholic cirrhosis: A case report

BACKGROUND Hepatic epithelioid angiomyolipoma(HEA)has a low incidence and both clinical manifestations and imaging lack specificity.Thus,it is easy to misdiagnose HEA as other tumors of the liver,especially in the presence of liver diseases such as hepatitis cirrhosis.This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis,and analyzed the literature,in order to improve the understanding of this disease.CASE SUMMARY A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver.Based on the patient’s history,laboratory examinations,and imaging examinations,a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed.Postoperative pathology showed HEA.During outpatient follow-up,the patient showed no sign of recurrence.CONCLUSION HEA is difficult to make a definite diagnosis before surgery.HEA has the poten-tial for malignant degeneration.If conditions permit,surgical treatment is recom-mended.

Mutational landscape of TP53 and CDH1 in gastric cancer

In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg.A common gene mutation in gastric cancer(GC)is the TP53 mutation.As a tumor suppressor gene,TP53 is implicated in more than half of all tumor occurrences.TP53 gene mutations in GC tissue may be related with clinical pathological aspects.The TP53 mutation arose late in the progression of GC and aided in the final switch to malignancy.CDH1 encodes E-cadherin,which is involved in cell-to-cell adhesion,epithelial structure maintenance,cell polarity,differentiation,and intracellular signaling pathway modulation.CDH1 mutations and functional loss can result in diffuse GC,and CDH1 mutations can serve as independent prognostic indicators for poor prognosis.GC patients can benefit from genetic counseling and testing for CDH1 mutations.Demethylation therapy may assist to postpone the onset and progression of GC.The investigation of TP53 and CDH1 gene mutations in GC allows for the investigation of the relationship between these two gene mutations,as well as providing some basis for evaluating the prognosis of GC patients.

Percutaneous ultrasound and endoscopic ultrasound-guided biopsy of solid pancreatic lesions: An analysis of 1074 lesions

Backgrounds:Percutaneous ultrasound(US)and endoscopic ultrasound(EUS)-guided pancreatic biopsies are widely accepted in the diagnosis of pancreatic diseases.Studies comparing the diagnostic performance of US-and EUS-guided pancreatic biopsies are lacking.This study aimed to evaluate and compare the diagnostic yields of US-and EUS-guided pancreatic biopsies and identify the risk factors for inconclusive biopsies.Methods:Of the 1074 solid pancreatic lesions diagnosed from January 2017 to February 2021 in our center,275 underwent EUS-guided fine needle aspiration(EUS-FNA),and 799 underwent US-guided core needle biopsy(US-CNB/FNA).The outcomes were inconclusive pathological biopsy,diagnostic accuracy and the need for repeat biopsy.All of the included factors and diagnostic performances of both USCNB/FNA and EUS-FNA were compared,and the independent predictors for the study outcomes were identified.Results:The diagnostic accuracy was 89.8%for EUS-FNA and 95.2%for US-CNB/FNA(P=0.001).Biopsy under EUS guidance[odds ratio(OR)=1.808,95%confidence interval(CI):1.083-3.019;P=0.024],lesion size<2 cm(OR=2.069,95%CI:1.145-3.737;P=0.016),hypoechoic appearance(OR=0.274,95%CI:0.097-0.775;P=0.015)and non-pancreatic ductal adenocarcinoma carcinoma(PDAC)diagnosis(OR=2.637,95%CI:1.563-4.449;P<0.001)were identified as factors associated with inconclusive pathological biopsy.Hypoechoic appearance(OR=0.236,95%CI:0.064-0.869;P=0.030),lesions in the uncinate process of the pancreas(OR=3.506,95%CI:1.831-6.713;P<0.001)and non-PDAC diagnosis(OR=2.622,95%CI:1.278-5.377;P=0.009)were independent predictors for repeat biopsy.Biopsy under EUS guidance(OR=2.024,95%CI:1.195-3.429;P=0.009),lesions in the uncinate process of the pancreas(OR=1.776,95%CI:1.014-3.108;P=0.044)and hypoechoic appearance(OR=0.127,95%CI:0.047-0.347;P<0.001)were associated with diagnostic accuracy.Conclusions:In conclusion,both percutaneous US-and EUS-guided biopsies of solid pancreatic lesions are safe and effective;though the diagnostic accuracy of EUS-FNA is inferior to US-CNB/FNA.A tailored pancreatic biopsy should be considered a part of the management algorithm for the diagnosis of solid pancreatic disease.

Minireview on laparoscopic hepatobiliary and pancreatic surgery

The first laparoscopic cholecystectomy was performed in the mid-1980s. Since then, laparoscopic surgery has continued to gain prominence in numerous fields, and has, in some fields, replaced open surgery as the preferred operative technique. The role of laparoscopy in staging cancer is controversial, with regards to gallbladder carcinoma, pancreatic carcinoma, hepatocellular carcinoma and liver metastasis from colorectal carcinoma, laparoscopy in conjunction with intraoperative ultrasound has prevented nontherapeutic operations, and facilitated therapeutic operations. Laparoscopic cholecystectomy is the preferred option in the management of gallbladder disease. Meta-analyses comparing laparoscopic to open distal pancreatectomy show that laparoscopic pancreatectomy is safe and efficacious in the management of benign and malignant disease, and have better patient outcomes. A pancreaticoduodenectomy is a more complex operation and the laparoscopic technique is not feasible for this operation at this time. Robotic assisted pancreaticoduodenectomy has been tried with limited success at this time, but with continuing advancement in this field, this operation would eventually be feasible. Liver resection remains to be the best management for hepatocellular carcinoma, cholangiocarcinoma and colorectal liver metastases. Systematic reviews and meta-analyses have shown that laparoscopic liver resections result in patients with equal or less blood loss and shorter hospital stays, as compared to open surgery. With improving equipment and technique, and the incorporation of robotic surgery, minimally invasive liver resection operative times will improve and be more efficacious. With the incorporation of robotic surgery into hepatobiliary surgery, donor hepatectomies have also been completed with success. The management of benign and malignant disease with minimally invasive hepatobiliary and pancreatic surgery is safe and efficacious.

Study of wrist-ankle acupuncture therapy for optimizing anaesthesia scheme of painless gastroscopy and improving painless gastroscopy related complications

BACKGROUND Painless gastroscopy is a widely used diagnostic and therapeutic technology in clinical practice.Propofol combined with opioids is a common drug for painless endoscopic sedation and anaesthesia.In clinical work,adverse drug reactions of anaesthesia schemes are often one of the important areas of concern for doctors and patients.With the increase in propofol dosage,the risk of serious adverse drug reactions,such as respiratory depression and hypotension,increases significantly;the use of opioids often causes gastrointestinal reactions in patients after examination,such as nausea,vomiting,delayed recovery of gastrointestinal function and other complications,which seriously affect their quality of life.AIM To observe the effect of wrist-ankle acupuncture therapy on the anaesthesia regimen and anaesthesia-related complications during and after painless gastroscopy examination.METHODS Two hundred patients were selected and randomly divided into a treatment group(n=100)and a control group(n=100).Both groups were routinely anaesthetized with the nalbuphine and propofol regimen,gastroscopy began after the patient lost consciousness,and given supportive treatment and vital sign monitoring.If the patient interrupted the surgery due to intraoperative torsion,intravenous propofol was used to relieve his or her discomfort.The treatment group received wrist-ankle acupuncture on this basis.RESULTS The general data before treatment,American Society of Anesthesiologist(ASA)grade and operation time between the two groups was no significant difference.The Wakeup time,and the Selfambulation time in the treatment group was significantly faster than that in the control group(P<0.05).The total dose of propofol in the treatment group was 109±8.17 mg,significantly lower than that in the control group(P<0.05).The incidence of respiratory depression and hypotension was not significantly different,but the incidence of hiccups was significantly lower than that in the control group(P<0.05).After the examination,the incidence of nausea,vomiting,abdominal distension,and abdominal pain was 11%,8%,6%,and 5%,respectively,which was significantly lower than that in the control group(P<0.05).In addition,both the operators and the patients were more satisfied with this examination,with no significant difference between the groups(P>0.05).CONCLUSION Wrist-ankle acupuncture treatment can optimize the painless gastroscopy and anaesthesia scheme,reduces propofol total dose;shortens patient Wakeup time and Self-ambulation time,improves patient compliance and tolerance,is beneficial to clinical application.

Simultaneous portal and hepatic vein embolization is better than portal embolization or ALPPS for hypertrophy of future liver remnant before major hepatectomy: A systematic review and network meta-analysis

Background:Post-hepatectomy liver failure(PHLF)is the Achilles’heel of hepatic resection for colorectal liver metastases.The most commonly used procedure to generate hypertrophy of the functional liver remnant(FLR)is portal vein embolization(PVE),which does not always lead to successful hypertrophy.Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been proposed to overcome the limitations of PVE.Liver venous deprivation(LVD),a technique that includes simultaneous portal and hepatic vein embolization,has also been proposed as an alternative to ALPPS.The present study aimed to conduct a systematic review as the first network meta-analysis to compare the efficacy,effectiveness,and safety of the three regenerative techniques.Data sources:A systematic search for literature was conducted using the electronic databases Embase,PubMed(MEDLINE),Google Scholar and Cochrane.Results:The time to operation was significantly shorter in the ALPPS cohort than in the PVE and LVD cohorts by 27 and 22 days,respectively.Intraoperative parameters of blood loss and the Pringle maneuver demonstrated non-significant differences between the PVE and LVD cohorts.There was evidence of a significantly higher FLR hypertrophy rate in the ALPPS cohort when compared to the PVE cohort,but non-significant differences were observed when compared to the LVD cohort.Notably,the LVD cohort demonstrated a significantly better FLR/body weight(BW)ratio compared to both the ALPPS and PVE cohorts.Both the PVE and LVD cohorts demonstrated significantly lower major morbidity rates compared to the ALPPS cohort.The LVD cohort also demonstrated a significantly lower 90-day mortality rate compared to both the PVE and ALPPS cohorts.Conclusions:LVD in adequately selected patients may induce adequate and profound FLR hypertrophy before major hepatectomy.Present evidence demonstrated significantly lower major morbidity and mortality rates in the LVD cohort than in the ALPPS and PVE cohorts.

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.

Advancements in understanding mechanisms of hepatocellular carcinoma radiosensitivity:A comprehensive review

Primary liver cancer is a significant health problem worldwide.Hepatocellular carcinoma(HCC)is the main pathological type of primary liver cancer,accounting for 75%-85%of cases.In recent years,radiotherapy has become an emerging treatment for HCC and is effective for various stages of HCC.However,radiosensitivity of liver cancer cells has a significant effect on the efficacy of radiotherapy and is regulated by various factors.How to increase radiosensitivity and improve the therapeutic effects of radiotherapy require further exploration.This review summarizes the recent research progress on the mechanisms affecting sensitivity to radiotherapy,including epigenetics,transportation and metabolism,regulated cell death pathways,the microenvironment,and redox status,as well as the effect of nanoparticles on the radiosensitivity of liver cancer.It is expected to provide more effective strategies and methods for clinical treatment of liver cancer by radiotherapy.

Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically displays mucin-hypersecretion or a papillary growth pattern,and results in cystic dilatation[1].IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts,and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma.IPNBs have similar phenotypic changes in the occurrence and development of all subtypes,and the prognosis is significantly better than that of traditional(nonpapillary)cholangiocarcinoma.AIM To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment.METHODS Invasive IPNB,invasive intraductal papillary mucinous neoplasm of the pancreas(IPMN),and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.Annual percentage changes(APCs)in the incidence and incidence-based(IB)mortality were calculated.We identified the independent predictors of overall survival(OS)and cancer-specific survival(CSS)in indivi duals with invasive IPNB.RESULTS The incidence and IB mortality of invasive IPNB showed sustained decreases,with an APC of-4.5%(95%CI:-5.1%to-3.8%)and-3.3%(95%CI:-4.1%to-2.6%)(P<0.001),respectively.Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma.Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma.A total of 1635 individuals with invasive IPNB were included in our prognosis analysis.The most common tumor sites were the pancreaticobiliary ampulla(47.9%)and perihilar tract(36.7%),but the mucin-related subtype of invasive IPNB was the main type,intrahepatically(approximately 90%).In the univariate and multivariate Cox regression analysis,age,tumor site,grade and stage,subtype,surgery,and chemotherapy were associated with OS and CSS(P<0.05).CONCLUSION Incidence and IB mortality of invasive IPNB trended steadily downward.The heterogeneity of IPNB comprises site and the tumor’s mucin-producing status.

Pathophysiological consequences and treatment strategy of obstructive jaundice

Obstructive jaundice(OJ)is a common problem in daily clinical practice.However,completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management.The effects of OJ are widespread,affecting the biliary tree,hepatic cells,liver function,and causing systemic complications.The lack of bile in the intestine,destruction of the intestinal mucosal barrier,and increased absorption of endotoxins can lead to endotoxemia,production of proinflammatory cytokines,and induce systemic inflammatory response syndrome,ultimately leading to multiple organ dysfunction syndrome.Proper management of OJ includes adequate water supply and electrolyte replacement,nutritional support,preventive antibiotics,pain relief,and itching relief.The surgical treatment of OJ depends on the cause,location,and severity of the obstruction.Biliary drainage,surgery,and endoscopic intervention are potential treatment options depending on the patient's condition.In addition to modern medical treatments,Traditional Chinese medicine may offer therapeutic benefits for OJ.A comprehensive search was conducted on PubMed for relevant articles published up to August 1970.This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.

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.

Insulin-like growth factor 2 mRNA-binding protein 1 promotes cell proliferation via activation of AKT and is directly targeted by microRNA-494 in pancreatic cancer

BACKGROUND Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.METHODS Expression levels of IGF2BP1 and microRNA-494(miR-494)were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot.The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed.The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo.Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the posttranscriptional regulation of IGF2BP1 by miR-494.RESULTS We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients.We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway.Mechanistically,we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer.Furthermore,we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.CONCLUSION Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.

Drainage fluid and serum amylase levels accurately predict development of postoperative pancreatic fistula

AIM To investigate potential biomarkers for predicting postoperative pancreatic fistula( POPF) after pancreaticoduodenectomy(PD).METHODS We prospectively recruited 83 patients to this study. All patients underwent PD(Child's procedure) at the Division of Hepatobiliary and Pancreas Surgery at the First Bethune Hospital of Jilin University between June 2011 and April 2015. Data pertaining to demographic variables, clinical characteristics, texture of pancreas, surgical approach, histopathological results, white blood cell count, amylase and choline levels in the serum, pancreatic/gastric drainage fluid, and choline and amylase levels in abdominal drainage fluid were included in the analysis. Potential correlations between these parameters and postoperative complications such as, POPF, acute pancreatitis, hemorrhage, delayed gastric emptying, and biliary fistula, were assessed. RESULTS Twenty-eight out of the 83(33.7%) patients developed POPF. The severity of POPF was classified as Grade A in 8(28%) patients, grade B in 16(58%), and grade C in4(14%), according to the pancreatic fistula criteria. On univariate and multivariate logistic regression analyses, higher amylase level in the abdominal drainage fluid on postoperative day(POD)1 and higher serum amylase levels on POD4 showed a significant correlation with POPF(P < 0.05). On receiver operating characteristic curve analysis, amylase cut-off level of 2365.5 U/L in the abdominal drainage fluid was associated with a 78.6% sensitivity and 80% specificity [area under the curve(AUC): 0.844; P = 0.009]. A cut-off serum amylase level of 44.2 U/L was associated with a 78.6% sensitivity and 70.9% specificity(AUC: 0.784; P = 0.05).CONCLUSION Amylase level in the abdominal drainage fluid on POD1 and serum amylase level on POD4 represent novel biomarkers associated with POPF development.

Navigated liver surgery:State of the art and future perspectives

Background:In recent years,the development of digital imaging technology has had a significant influence in liver surgery.The ability to obtain a 3-dimensional(3D)visualization of the liver anatomy has provided surgery with virtual reality of simulation 3D computer models,3D printing models and more recently holograms and augmented reality(when virtual reality knowledge is superimposed onto reality).In addition,the utilization of real-time fluorescent imaging techniques based on indocyanine green(ICG)uptake allows clinicians to precisely delineate the liver anatomy and/or tumors within the parenchyma,applying the knowledge obtained preoperatively through digital imaging.The combination of both has transformed the abstract thinking until now based on 2D imaging into a 3D preoperative conception(virtual reality),enhanced with real-time visualization of the fluorescent liver structures,effectively facilitating intraoperative navigated liver surgery(augmented reality).Data sources:A literature search was performed from inception until January 2021 in MEDLINE(Pub Med),Embase,Cochrane library and database for systematic reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases.Results:Fifty-one pertinent articles were retrieved and included.The different types of digital imaging technologies and the real-time navigated liver surgery were estimated and compared.Conclusions:ICG fluorescent imaging techniques can contribute essentially to the real-time definition of liver segments;as a result,precise hepatic resection can be guided by the presence of fluorescence.Furthermore,3D models can help essentially to further advancing of precision in hepatic surgery by permitting estimation of liver volume and functional liver remnant,delineation of resection lines along the liver segments and evaluation of tumor margins.In liver transplantation and especially in living donor liver transplantation(LDLT),3D printed models of the donor’s liver and models of the recipient’s hilar anatomy can contribute further to improving the results.In particular,pediatric LDLT abdominal cavity models can help to manage the largest challenge of this procedure,namely large-for-size syndrome.

Factors associated with failure of enhanced recovery after surgery program in patients undergoing pancreaticoduodenectomy

Background: The enhanced recovery after surgery (ERAS) protocol is an evidence-based perioperative care program aimed at reducing surgical stress response and accelerating recovery. However, a small propor- tion of patients fail to bene t from the ERAS program following pancreaticoduodenectomy. This study aimed to identify the risk factors associated with failure of ERAS program in pancreaticoduodenectomy. Methods: Between May 2014 and December 2017, 176 patients were managed with ERAS program fol-lowing pancreaticoduodenectomy. ERAS failure was indicated by prolonged hospital stay, unplanned read- mission or unplanned reoperation. Demographics, postoperative recovery and compliance were compared of those ERAS failure groups to the ERAS success group. Results: ERAS failure occurred in 59 patients, 33 of whom had prolonged hospital stay, 18 were readmitted to hospital within 30 days after discharge, and 8 accepted reoperation. Preoperative American Society of Anesthesiologists (ASA) score of ≥III (OR = 2.736;95% CI: 1.276 6.939;P=0.028) and albumin (ALB) level of <35g/L (OR=3.589;95% CI: 1.403 9.181;P=0.008) were independent risk factors associated with prolonged hospital stay. Elderly patients (>70 years) were on a high risk of unplanned reoperation (62.5% vs. 23.1%, P=0.026). Patients with prolonged hospital stay and unplanned reoperation had delayed intake and increased intolerance of oral foods. Prolonged stay patients got off bed later than ERAS success patients did (65h vs. 46h, P =0.012). Unplanned reoperation patients tended to experience severer pain than ERAS success patients did (3 score vs. 2 score, P =0.035). Conclusions: Patients with high ASA score, low ALB level or age >70 years were at high risk of ERAS failure in pancreaticoduodenectomy. These preoperative demographic and clinical characteristics are important determinants to obtain successful postoperative recovery in ERAS program.

Personalized pancreatic cancer therapy:from the perspective of mRNA vaccine

Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.