Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the r...Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver re-section and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic pa-tients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.展开更多
The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis w...The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.展开更多
Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to ad...Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to advances in the management of sickle cell disease, patients' life expectancy has increased considerably, exposing them more frequently to neoplasia, including hematological malignancies. The increased risk of leukemogenesis is multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Study Setting: The clinical haematology department of campus teaching hospital and the paediatric onco-haematology unit of Sylvanus Olympio teaching hospital in Lomé were used as study settings. Observations: Four hematologic malignancies were collected in a cohort of 5847 major sickle cell syndromes. The median age of the patients was 31.25 years (extremes: 14 and 58 years) and they were predominantly female (sex ratio M/F = 0.25). Two were on background therapy with hydroxyurea. Among the four patients, there were two cases of acute lymphocytic leukemia, including ALL3 in a 58-year-old SS woman and T-ALL2 in a 12-year-old SC. Then, a case of lymphocytic lymphoma in a 20-year-old SS man was reported and finally a case of chronic myelocytic leukemia in a 33-year-old woman of Sβ+ thalassaemia phenotype. Conclusion: To further report this coexistence, it is therefore essential to systematically consider hematological malignancies during major sickle cell syndromes even if there are similarities in the symptomatology of these two serious pathological situations.展开更多
The incidence of gastrointestinal malignancies has increased over the past decade at an alarming rate.Colorectal and gastric cancers are the third and fifth most commonly diagnosed cancers worldwide but are cited as t...The incidence of gastrointestinal malignancies has increased over the past decade at an alarming rate.Colorectal and gastric cancers are the third and fifth most commonly diagnosed cancers worldwide but are cited as the second and third leading causes of mortality.Early institution of appropriate therapy from timely diagnosis can optimize patient outcomes.Artificial intelligence(AI)-assisted diagnostic,prognostic,and therapeutic tools can assist in expeditious diagnosis,treatment planning/response prediction,and post-surgical prognostication.AI can intercept neoplastic lesions in their primordial stages,accurately flag suspicious and/or inconspicuous lesions with greater accuracy on radiologic,histopathological,and/or endoscopic analyses,and eliminate over-dependence on clinicians.AI-based models have shown to be on par,and sometimes even outperformed experienced gastroenterologists and radiologists.Convolutional neural networks(state-of-the-art deep learning models)are powerful computational models,invaluable to the field of precision oncology.These models not only reliably classify images,but also accurately predict response to chemotherapy,tumor recurrence,metastasis,and survival rates post-treatment.In this systematic review,we analyze the available evidence about the diagnostic,prognostic,and therapeutic utility of artificial intelligence in gastrointestinal oncology.展开更多
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 radia...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.展开更多
BACKGROUND Programmed death protein(PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient(dMMR)/microsatellite instability-high(MSI-H)gastrointestinal malig...BACKGROUND Programmed death protein(PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient(dMMR)/microsatellite instability-high(MSI-H)gastrointestinal malignancies such gastric and colorectal cancer.However,the data on preoperative immunotherapy are limited.AIM To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy.METHODS In this retrospective study,we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies.All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively.PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle.RESULTS Three patients with locally advanced gastric cancer achieved pathological complete response(pCR).Three patients with locally advanced duodenal carcinoma achieved clinical complete response(cCR),followed by watch and wait.Eight of 16 patients with locally advanced colon cancer achieved pCR.All four patients with liver metastasis from colon cancer reached CR,including three with pCR and one with cCR.pCR was achieved in two of five patients with nonliver metastatic colorectal cancer.CR was achieved in four of five patients with low rectal cancer,including three with cCR and one with pCR.cCR was achieved in seven of 36 cases,among which,six were selected for watch and wait strategy.No cCR was observed in gastric or colon cancer.CONCLUSION Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR,especially in patients with duodenal or low rectal cancer,and can achieve high organ function protection.展开更多
Most tumor suppressor and growth-regulating proteins are transported via the plasmic nuclear transporter exportin 1(XPO1).Many malignancies have excessive XPO1 expression,which is associated with disease progression a...Most tumor suppressor and growth-regulating proteins are transported via the plasmic nuclear transporter exportin 1(XPO1).Many malignancies have excessive XPO1 expression,which is associated with disease progression and resistance to therapy.A novel class of anticancer medication called selective inhibitor of nuclear export(SINE)can down-regulate the levels of a number of antigenic proteins in the cytoplasm,activate tumor suppressor and other growth regulating proteins,and promote the nuclear retention and apoptosis of tumor cells.This article discusses the function of XPO1 in drug resistance and tumor development as well as the advancement of XPO1 inhibitor research for the treatment of hematological cancers.展开更多
Co-expression of immune checkpoint(IC)molecules can exacerbate T cell exhaustion in patients with hematological malignancies(HMs)and contribute to the immune escape of tumor cells,which is related to poor clinical out...Co-expression of immune checkpoint(IC)molecules can exacerbate T cell exhaustion in patients with hematological malignancies(HMs)and contribute to the immune escape of tumor cells,which is related to poor clinical outcome.It is worth establishing and optimizing an ideal prediction model based on the co-expression patterns of IC molecules to evaluate the immune status of HM patients and predict their clinical outcome.In this perspective,we summarize the co-expression patterns of IC molecules and their importance as biomarkers that predict the prognosis of patients with different HMs,providing new insights for designing dual IC blockades(ICBs).展开更多
Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely...Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.展开更多
Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabc...Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.展开更多
E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro...E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumorpromoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.展开更多
In this study,we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematolo...In this study,we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies.A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology,Union Hospital,between Apr 2014 and Dec.2014 were enrolled in this study.There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC.The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System,and they were divided into four subgroups [score ≤3 (n=35),score=4 (n=37),score=5 (n=47),and score >6 (n=12)] according to ISTH scores.Using 28-day mortality as the endpoint,the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20).The results showed that the plasma factor V activity was significantly weaker,and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01).The factor V activity,peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01).Among factor V activity,lag time,peak,ETP,and ttPeak,only the factor V activity was significantly decreased in the nonsurvival subgroup compared with the survival subgroup (P<0.01).With the increase in ISTH score,the ETP and peak decreased gradually.The binary logistic regression analysis revealed that PLT,D-dimer,factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System.Using DIC diagnosed by ISTH Integral System as the endpoint,the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT).In conclusion,factor V activity,ETP and peak had diagnostic value for DIC in patients with hematological malignancies,and only factor V activity had limited prognostic value.展开更多
BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with cr...BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.展开更多
BACKGROUND Multiple primary malignancies(MPM)are characterized by two or more primary malignancies in the same patient,excluding relapse or metastasis of prior cancer.We aimed to elucidate the clinical features and su...BACKGROUND Multiple primary malignancies(MPM)are characterized by two or more primary malignancies in the same patient,excluding relapse or metastasis of prior cancer.We aimed to elucidate the clinical features and survival of MPM patients.AIM To elucidate the clinical features and survival of MPM patients.METHODS A retrospective study of MPM patients was conducted in our hospital between June 2016 and June 2019.Overall survival(OS)was calculated using the Kaplan-Meier method.The log-rank test was used to compare the survival of different groups.RESULTS A total of 243 MPM patients were enrolled,including 222 patients with two malignancies and 21 patients with three malignancies.Of patients with two malignancies,51(23.0%)had synchronous MPM,and 171(77.7%)had metachronous MPM.The most common first cancers were breast cancer(33,14.9%)and colorectal cancer(31,14.0%).The most common second cancers were non-small cell lung cancer(NSCLC)(66,29.7%)and gastric cancer(24,10.8%).There was no survival difference between synchronous and metachronous MPM patients(36.4 vs 35.3 mo,P=0.809).Patients aged>65 years at diagnosis of the second cancer had a shorter survival than patients≤65 years(28.4 vs 36.4 mo,P=0.038).Patients with distant metastasis had worse survival than patients without metastasis(20.4 vs 86.9 mo,P=0.000).Following multivariate analyses,age>65 years and distant metastasis were independent adverse prognostic factors for OS.CONCLUSION During follow-up of a first cancer,the occurrence of a second or more cancers should receive greater attention,especially for common concomitant MPM,to ensure early detection and treatment of the subsequent cancer.展开更多
Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group....Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myeloand immunosuppres-sive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.展开更多
BACKGROUND Recurrent acute pancreatitis(RAP)may be a presenting feature of and an indication for resection of pancreatic cysts,including intra-ductal papillary mucinous neoplasm(IPMN).Few data are available regarding ...BACKGROUND Recurrent acute pancreatitis(RAP)may be a presenting feature of and an indication for resection of pancreatic cysts,including intra-ductal papillary mucinous neoplasm(IPMN).Few data are available regarding the prevalence of malignancy and post-operative RAP in this population.AIM To study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy.METHODS This retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016.The prevalence of preoperative high-risk cyst features,and of neoplasia was compared between patients with and without RAP.To identify the cause of pancreatitis,all the patients had a detailed history of alcohol,smoking,medications obtained,and had cross-sectional imaging(contrast-enhanced computed tomography/magnetic resonance imaging)and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis.The incidence of RAP post-resection was the primary outcome.RESULTS IPMN accounted for 101 cases(58.7%){[branch duct(BD)59(34.3%),main duct(MD)42](24.4%)}.Twenty-nine(16.9%)presented with RAP(mean 2.2 episodes):15 had BD-IPMN,8 MD-IPMN,5 mucinous cystic neoplasm and 1 serous cystic neoplasm.Malignancy was similar among those with vs without RAP for all patients[6/29(20.7%)vs 24/143(16.8%)]and IPMN patients[6/23(26.1%)vs 23/78(29.5%)],although tended to be higher with RAP in BD-IPMN,[5/15(33.3%)vs 3/44(6.8%),P=0.04].At mean follow-up of 7.2 years,1(3.4%)RAP patient had post-resection RAP.The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02(P<0.0001).CONCLUSION Malignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP.In addition,specific cyst characteristics were not clearly associated with RAP.The incidence of RAP was markedly decreased in almost all patients following cyst resection.展开更多
Circular RNAs(circ RNAs),a class of endogenous RNA molecules,are produced by alternative splicing of precursor RNA and are covalently linked at the 5′and 3′ends.Recent studies have revealed that dysregulated circ RN...Circular RNAs(circ RNAs),a class of endogenous RNA molecules,are produced by alternative splicing of precursor RNA and are covalently linked at the 5′and 3′ends.Recent studies have revealed that dysregulated circ RNAs are closely related to the occurrence and progression of gastrointestinal malignancies.Accumulating evidence indicates that circ RNAs,including circ PVT1,circ LARP4,circ-SFMBT2,cir-ITCH,circ RNA_100782,circ_100395,circ-DONSON,hsa_circ_0001368,circ NRIP1,circ FAT1(e2),circ CCDC66,circ SMARCA5,circ-ZNF652,and circ_0030235 play important roles in the proliferation,differentiation,invasion,and metastasis of cancer cells through a variety of mechanisms,such as acting as micro RNA sponges,interacting with RNA-binding proteins,regulating gene transcription and alternative splicing,and being translated into proteins.With the characteristics of high abundance,high stability,extensive functions,and certain tissue-,time-and diseasespecific expressions,circ RNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.展开更多
As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malig...As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.展开更多
Malignancies constitute the second cause of death in patients with inflammatory bowel diseases(IBD),after cardiovascular diseases.Although it has been postulated that IBD patients are at greater risk of colorectal can...Malignancies constitute the second cause of death in patients with inflammatory bowel diseases(IBD),after cardiovascular diseases.Although it has been postulated that IBD patients are at greater risk of colorectal cancer compared to the general population,lately there has been evidence supporting that this risk is diminishing over time as a result of better surveillance,while the incidence of extraintestinal cancers(EICs)is increasing.This could be attributed either to systemic inflammation caused by IBD or to long-lasting immunosuppression due to IBD treatments.It seems that the overall risk of EICs is higher for Crohn’s disease patients and it is mainly driven by skin cancers,and liver-biliary cancers in patients with IBD and primary sclerosing cholangitis.The aims of this review were first to evaluate the prevalence,characteristics,and risk factors of EICs in patients with IBD and second to raise awareness regarding a proper surveillance program resulting in early diagnosis,better prognosis and survival,especially in the era of new IBD treatments that are on the way.展开更多
AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV) infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 pa...AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV) infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen(HBs Ag), and antibodies to HBV core(anti-HBc) and surface antigens. Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS HBV DNA was detected in 23(42.6%) of 54 patients with hematological malignancies who were HBsA g negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120 T and S143 L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations. 120 T mutation impairs the detection of HBsA g by CLEIA.展开更多
文摘Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver re-section and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic pa-tients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.
文摘The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.
文摘Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to advances in the management of sickle cell disease, patients' life expectancy has increased considerably, exposing them more frequently to neoplasia, including hematological malignancies. The increased risk of leukemogenesis is multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Study Setting: The clinical haematology department of campus teaching hospital and the paediatric onco-haematology unit of Sylvanus Olympio teaching hospital in Lomé were used as study settings. Observations: Four hematologic malignancies were collected in a cohort of 5847 major sickle cell syndromes. The median age of the patients was 31.25 years (extremes: 14 and 58 years) and they were predominantly female (sex ratio M/F = 0.25). Two were on background therapy with hydroxyurea. Among the four patients, there were two cases of acute lymphocytic leukemia, including ALL3 in a 58-year-old SS woman and T-ALL2 in a 12-year-old SC. Then, a case of lymphocytic lymphoma in a 20-year-old SS man was reported and finally a case of chronic myelocytic leukemia in a 33-year-old woman of Sβ+ thalassaemia phenotype. Conclusion: To further report this coexistence, it is therefore essential to systematically consider hematological malignancies during major sickle cell syndromes even if there are similarities in the symptomatology of these two serious pathological situations.
文摘The incidence of gastrointestinal malignancies has increased over the past decade at an alarming rate.Colorectal and gastric cancers are the third and fifth most commonly diagnosed cancers worldwide but are cited as the second and third leading causes of mortality.Early institution of appropriate therapy from timely diagnosis can optimize patient outcomes.Artificial intelligence(AI)-assisted diagnostic,prognostic,and therapeutic tools can assist in expeditious diagnosis,treatment planning/response prediction,and post-surgical prognostication.AI can intercept neoplastic lesions in their primordial stages,accurately flag suspicious and/or inconspicuous lesions with greater accuracy on radiologic,histopathological,and/or endoscopic analyses,and eliminate over-dependence on clinicians.AI-based models have shown to be on par,and sometimes even outperformed experienced gastroenterologists and radiologists.Convolutional neural networks(state-of-the-art deep learning models)are powerful computational models,invaluable to the field of precision oncology.These models not only reliably classify images,but also accurately predict response to chemotherapy,tumor recurrence,metastasis,and survival rates post-treatment.In this systematic review,we analyze the available evidence about the diagnostic,prognostic,and therapeutic utility of artificial intelligence in gastrointestinal oncology.
基金National Natural Science Foundation(No.81773214)Beijing Municipal Administration of Hospital Medicine Development of Special Funding Support(No.ZYLX202116)+2 种基金Beijing Municipal Administration of Hospitals Incubating Program(No.PZ2020027)Beijing Talent Incubating Funding(No.2019-4)Science Foundation of Peking University Cancer Hospital(No.2023-10)。
文摘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.
基金Supported by the National Natural Science Foundation of China,No.82173156Beijing Hospitals Authority Clinical Medicine Development of Special Funding,No.ZYLX202116.
文摘BACKGROUND Programmed death protein(PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient(dMMR)/microsatellite instability-high(MSI-H)gastrointestinal malignancies such gastric and colorectal cancer.However,the data on preoperative immunotherapy are limited.AIM To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy.METHODS In this retrospective study,we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies.All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively.PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle.RESULTS Three patients with locally advanced gastric cancer achieved pathological complete response(pCR).Three patients with locally advanced duodenal carcinoma achieved clinical complete response(cCR),followed by watch and wait.Eight of 16 patients with locally advanced colon cancer achieved pCR.All four patients with liver metastasis from colon cancer reached CR,including three with pCR and one with cCR.pCR was achieved in two of five patients with nonliver metastatic colorectal cancer.CR was achieved in four of five patients with low rectal cancer,including three with cCR and one with pCR.cCR was achieved in seven of 36 cases,among which,six were selected for watch and wait strategy.No cCR was observed in gastric or colon cancer.CONCLUSION Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR,especially in patients with duodenal or low rectal cancer,and can achieve high organ function protection.
基金National Natural Science Foundation Project(No.81970190)Shaanxi Provincial Social Development Public Relations Key Project(No.2019ZDLSF02-02)National Medical Center Transformation Project(No.2020ZKMC01)。
文摘Most tumor suppressor and growth-regulating proteins are transported via the plasmic nuclear transporter exportin 1(XPO1).Many malignancies have excessive XPO1 expression,which is associated with disease progression and resistance to therapy.A novel class of anticancer medication called selective inhibitor of nuclear export(SINE)can down-regulate the levels of a number of antigenic proteins in the cytoplasm,activate tumor suppressor and other growth regulating proteins,and promote the nuclear retention and apoptosis of tumor cells.This article discusses the function of XPO1 in drug resistance and tumor development as well as the advancement of XPO1 inhibitor research for the treatment of hematological cancers.
基金supported by grants from the National Natural Science Foundation of China(No.82293630,No.82293632 and No.82070152)the Guangdong Natural Science Foundation(No.2023A1515012968)Medical Scientific Research Foundation of Guangdong Province(No.A2023330)。
文摘Co-expression of immune checkpoint(IC)molecules can exacerbate T cell exhaustion in patients with hematological malignancies(HMs)and contribute to the immune escape of tumor cells,which is related to poor clinical outcome.It is worth establishing and optimizing an ideal prediction model based on the co-expression patterns of IC molecules to evaluate the immune status of HM patients and predict their clinical outcome.In this perspective,we summarize the co-expression patterns of IC molecules and their importance as biomarkers that predict the prognosis of patients with different HMs,providing new insights for designing dual IC blockades(ICBs).
文摘Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.
文摘Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
基金Supported by "Kapodistrias" Research Program, Special Accounts Research Fund 70/4/6549, National and Kapodistrian University of Athens, Greece
文摘E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumorpromoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.
文摘In this study,we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies.A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology,Union Hospital,between Apr 2014 and Dec.2014 were enrolled in this study.There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC.The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System,and they were divided into four subgroups [score ≤3 (n=35),score=4 (n=37),score=5 (n=47),and score >6 (n=12)] according to ISTH scores.Using 28-day mortality as the endpoint,the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20).The results showed that the plasma factor V activity was significantly weaker,and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01).The factor V activity,peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01).Among factor V activity,lag time,peak,ETP,and ttPeak,only the factor V activity was significantly decreased in the nonsurvival subgroup compared with the survival subgroup (P<0.01).With the increase in ISTH score,the ETP and peak decreased gradually.The binary logistic regression analysis revealed that PLT,D-dimer,factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System.Using DIC diagnosed by ISTH Integral System as the endpoint,the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT).In conclusion,factor V activity,ETP and peak had diagnostic value for DIC in patients with hematological malignancies,and only factor V activity had limited prognostic value.
文摘BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.
基金the institutional review board of our hospital(2020KY018-KS001).
文摘BACKGROUND Multiple primary malignancies(MPM)are characterized by two or more primary malignancies in the same patient,excluding relapse or metastasis of prior cancer.We aimed to elucidate the clinical features and survival of MPM patients.AIM To elucidate the clinical features and survival of MPM patients.METHODS A retrospective study of MPM patients was conducted in our hospital between June 2016 and June 2019.Overall survival(OS)was calculated using the Kaplan-Meier method.The log-rank test was used to compare the survival of different groups.RESULTS A total of 243 MPM patients were enrolled,including 222 patients with two malignancies and 21 patients with three malignancies.Of patients with two malignancies,51(23.0%)had synchronous MPM,and 171(77.7%)had metachronous MPM.The most common first cancers were breast cancer(33,14.9%)and colorectal cancer(31,14.0%).The most common second cancers were non-small cell lung cancer(NSCLC)(66,29.7%)and gastric cancer(24,10.8%).There was no survival difference between synchronous and metachronous MPM patients(36.4 vs 35.3 mo,P=0.809).Patients aged>65 years at diagnosis of the second cancer had a shorter survival than patients≤65 years(28.4 vs 36.4 mo,P=0.038).Patients with distant metastasis had worse survival than patients without metastasis(20.4 vs 86.9 mo,P=0.000).Following multivariate analyses,age>65 years and distant metastasis were independent adverse prognostic factors for OS.CONCLUSION During follow-up of a first cancer,the occurrence of a second or more cancers should receive greater attention,especially for common concomitant MPM,to ensure early detection and treatment of the subsequent cancer.
文摘Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myeloand immunosuppres-sive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.
文摘BACKGROUND Recurrent acute pancreatitis(RAP)may be a presenting feature of and an indication for resection of pancreatic cysts,including intra-ductal papillary mucinous neoplasm(IPMN).Few data are available regarding the prevalence of malignancy and post-operative RAP in this population.AIM To study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy.METHODS This retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016.The prevalence of preoperative high-risk cyst features,and of neoplasia was compared between patients with and without RAP.To identify the cause of pancreatitis,all the patients had a detailed history of alcohol,smoking,medications obtained,and had cross-sectional imaging(contrast-enhanced computed tomography/magnetic resonance imaging)and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis.The incidence of RAP post-resection was the primary outcome.RESULTS IPMN accounted for 101 cases(58.7%){[branch duct(BD)59(34.3%),main duct(MD)42](24.4%)}.Twenty-nine(16.9%)presented with RAP(mean 2.2 episodes):15 had BD-IPMN,8 MD-IPMN,5 mucinous cystic neoplasm and 1 serous cystic neoplasm.Malignancy was similar among those with vs without RAP for all patients[6/29(20.7%)vs 24/143(16.8%)]and IPMN patients[6/23(26.1%)vs 23/78(29.5%)],although tended to be higher with RAP in BD-IPMN,[5/15(33.3%)vs 3/44(6.8%),P=0.04].At mean follow-up of 7.2 years,1(3.4%)RAP patient had post-resection RAP.The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02(P<0.0001).CONCLUSION Malignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP.In addition,specific cyst characteristics were not clearly associated with RAP.The incidence of RAP was markedly decreased in almost all patients following cyst resection.
基金supported by the National Natural Science Foundation of China(Grant Nos.81702367 and 81772279)the Medical and Health Research Project of Zhejiang Province(Grant No.2018KY159)+1 种基金the Affiliated Hospital of Medical School of Ningbo University Youth Talent Cultivation Program(Grant No.FYQMKY202001)the Scientific Innovation Team Project of Ningbo(Grant No.2017C110019)。
文摘Circular RNAs(circ RNAs),a class of endogenous RNA molecules,are produced by alternative splicing of precursor RNA and are covalently linked at the 5′and 3′ends.Recent studies have revealed that dysregulated circ RNAs are closely related to the occurrence and progression of gastrointestinal malignancies.Accumulating evidence indicates that circ RNAs,including circ PVT1,circ LARP4,circ-SFMBT2,cir-ITCH,circ RNA_100782,circ_100395,circ-DONSON,hsa_circ_0001368,circ NRIP1,circ FAT1(e2),circ CCDC66,circ SMARCA5,circ-ZNF652,and circ_0030235 play important roles in the proliferation,differentiation,invasion,and metastasis of cancer cells through a variety of mechanisms,such as acting as micro RNA sponges,interacting with RNA-binding proteins,regulating gene transcription and alternative splicing,and being translated into proteins.With the characteristics of high abundance,high stability,extensive functions,and certain tissue-,time-and diseasespecific expressions,circ RNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.
基金the Key Program of the National Natural Science Foundation(NNSF)of China(No.81230052 and No.81630006).
文摘As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.
文摘Malignancies constitute the second cause of death in patients with inflammatory bowel diseases(IBD),after cardiovascular diseases.Although it has been postulated that IBD patients are at greater risk of colorectal cancer compared to the general population,lately there has been evidence supporting that this risk is diminishing over time as a result of better surveillance,while the incidence of extraintestinal cancers(EICs)is increasing.This could be attributed either to systemic inflammation caused by IBD or to long-lasting immunosuppression due to IBD treatments.It seems that the overall risk of EICs is higher for Crohn’s disease patients and it is mainly driven by skin cancers,and liver-biliary cancers in patients with IBD and primary sclerosing cholangitis.The aims of this review were first to evaluate the prevalence,characteristics,and risk factors of EICs in patients with IBD and second to raise awareness regarding a proper surveillance program resulting in early diagnosis,better prognosis and survival,especially in the era of new IBD treatments that are on the way.
基金Supported by Japan Society for the Promotion of Science,No.15H05289
文摘AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV) infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen(HBs Ag), and antibodies to HBV core(anti-HBc) and surface antigens. Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS HBV DNA was detected in 23(42.6%) of 54 patients with hematological malignancies who were HBsA g negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120 T and S143 L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations. 120 T mutation impairs the detection of HBsA g by CLEIA.
