Human microbiota constitute a complex and dynamic community that interacts with the innate immunity of the host at various anatomical sites,influencing both physiological and pathological states.In individuals with a ...Human microbiota constitute a complex and dynamic community that interacts with the innate immunity of the host at various anatomical sites,influencing both physiological and pathological states.In individuals with a genetic predisposition,disruptions to the“innate immunity‒microbiota”axis appear to rewire immune responses within the tumor microenvironment(TME),thereby driving cancer pathogenesis.This review summarizes the intricate crosstalk between the microbiota and innate immunity in both healthy and cancerous states,focusing on the modulation of immune recognition and polarization during tumor progression,including immune escape,barrier disruption,chronic inflammatory transformation,and angiogenesis in the initiation phase,as well as the regulation of local invasion,vascular invasion,and pre-metastatic ecological niche formation involved in the metastatic phase.This review also highlights recent advances and challenges in leveraging microbiota for cancer immunotherapy,covering innovations in bacteriophages,genetically engineered probiotics,and bioinformatic applications.Moreover,this review proposes potential approaches to enhance therapeutic efficacy by targeting innate immunity‒microbiota interactions.Further mechanistic insights into these interactions may pave the way for developing innovative microbiota-based cancer immunotherapies.展开更多
The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials...The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials of first-generation inhibitors of mammalian target of rapamycin(m TOR) in OC have demonstrated negative results. The lack of patient selection as well as resistance to selective m TOR complex-1(m TORC1) inhibitors could explain the disappointing results thus far. Nonetheless, a number of novel agents are being investigated, including dual m TORC1/m TORC2, Akt, and PI3 K inhibitors. Although it is likely that inhibition of the PI3K/Akt/m TOR pathway may have little effect in unselected OC patients, certain histological types, such as clear cell or endometrioid OC with frequent phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha(PIK3CA) and/or phosphatase and tensin homolog(PTEN) alterations, may be particularly suited to this approach. Given the complexity and redundancy of the PI3 K signaling network, PI3 K pathway inhibition may be most useful in combination with either chemotherapy or other targeted therapies, such as MEK inhibitors, anti-angiogenic therapy, and hormonal therapy, in appropriately selected OC patients. Here, we discuss the relevance of the PI3 K pathway in OC and provide an up-to-date review of clinical trials of novel PI3 K inhibitors alone or in combination with cytotoxics and novel therapies in OC. In addition, the challenges of drug resistance and predictive biomarkers are addressed.展开更多
Gastric cancer(GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stag...Gastric cancer(GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However,response to chemotherapy varies widely,with some patients presenting no or only minor response to treatment. Hence,chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately,to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment,or that allow modification of chemotherapy resistance. MicroRNAs(miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types,and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in GC.The authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics,and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.展开更多
Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in pati...Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.展开更多
BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial ...BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial issue in the pathogenesis and development of cancer.AIM To evaluate the prognostic value of absolute monocyte count,monocyte to lymphocyte ratio(MLR),the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio(NLR-PLR),and combined platelet and neutrophilto-lymphocyte ratio(PLT-NLR)in peripheral blood samples of patients with colorectal cancer undergoing surgery.METHODS We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery,and 42 healthy controls.The status of absolute monocyte count,MLR,NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery.Haematologic factors were examined in correlation with the type of tumour growth,tumour size,histological type,percentage of mucinous component,grade of malignancy,Tumour-Node-Metastasis stage,venous,lymphatic and perineural invasion of cancer cells,status of lymph node invasion and the presence of cancer cell deposits.The Kaplan-Meier method and the long-rank test were used to compare survival curves.To determine independent prognostic factors,univariate and multivariate Cox proportional hazards regression models were applied.RESULTS The PLT-NLR status was correlated with tumour size and the presence of perineural invasion(P=0.015;P=-0.174,P=0.037).Moreover,high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component(NLR-PLR:P=0.002;P=0.009;PLR-NLR status:P=0.002;P=0.007).The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery[HR=2.903,95%CI:(1.368-6.158),P=0.005]and the status of lymph node metastasis[HR=0.813,95%CI:(0.653-1.013),P=0.050]were independent prognostic factors in colorectal cancer patients.CONCLUSION The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.展开更多
AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorec...AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision （TME）. METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the Amsterdam Cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records. RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）. CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.展开更多
BACKGROUND Despite effective prevention and screening methods,the incidence and mortality rates associated with colorectal cancer(CRC)are still high.Insulin receptor substrate 1(IRS-1),a signaling molecule involved in...BACKGROUND Despite effective prevention and screening methods,the incidence and mortality rates associated with colorectal cancer(CRC)are still high.Insulin receptor substrate 1(IRS-1),a signaling molecule involved in cell proliferation,survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models.However,the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined.AIM To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers,Bax,Bcl-xL and Ki-67 are related to clinicopathological features in human CRC.METHODS The expression of IRS-1,Bax,Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods.The assays were performed using specific antibodies against IRS-1,Bax,Bcl-xL,Ki-67.The associations between the expression of IRS-1,Bax,Bcl-xL,Ki-67 were analyzed in relation to clinicopathological parameters,i.e.,patient age,sex,primary localization of tumor,histopathological type,grading,staging and lymph node spread.Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at P<0.05.RESULTS Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases.IRS-1 expression at any level in primary CRC was associated with tumor grade(69%in moderately differentiated tumors,G2 vs 31%in poorly differentiated tumors,G3)and with histological type(81.9%in adenocarcinoma vs 18.1%in adenocarcinoma with mucosal component cases).Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases(95.1%)and in moderately differentiated tumors(85.2%).We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined.The relationships between studied proteins were related to clinicopathological parameters of CRC.No significant correlation between the expression of IRS-1 and proliferation marker Ki-67,excluding early stage tumors,where the correlation was positive and on a high level(P=0.043,r=0.723).CONCLUSION This study suggests that IRS-1 is co-expressed with both pro-and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC.展开更多
Objective: It is unclear if and to what extent family history of breast/ovarian cancer or BRCA1/2-mutation carriership influences breast cancer treatment strategy. We investigated whether treatment differed between pa...Objective: It is unclear if and to what extent family history of breast/ovarian cancer or BRCA1/2-mutation carriership influences breast cancer treatment strategy. We investigated whether treatment differed between patients from BRCA1/2 families and those unselected for family history. Methods: We included 478 BRCA1/2-related patients referred for genetic testing before or after diagnosis. Two references were used: 13,498 population-based and 6896 hospital-based patients. Surgical treatment and adjuvant chemotherapy use was analyzed using logistic regression models, stratified by tumor size, nodal status, age at and period of diagnosis, and estrogen receptor status (ER). Results: BRCA1/2 cases aged 35 - 52 years at diagnosis and/or with tumors < 2 cm were more likely to have undergone a modified radical mastectomy (Odd Ratios (OR) ranging from 2.8 to 5.1) compared to the references. This effect was most pronounced in patients treated after 1995 (OR 5.7 to 10.3). Compared to the reference groups, chemotherapy was more often administered to BRCA1 and ER-negative BRCA1/2-cases irrespective of age and nodal status (OR 1.9 to 24.3). Conclusion: After 1995 treatment of BRCA1/2-associated patients consisted notably of more mastectomies and adjuvant chemotherapy than their population-based counterparts with the same tumor characteristics. There is a need to be aware of such differences in daily practice and interpretation of survival studies on BRCA1/2 mutation carriers.展开更多
Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast ca...Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic conversion of the mammary epithelial cells. Interestingly, the regulation of some of the shelterin genes is thought to be controlled epigenetically. Methods and Results: In this study, we set out to measure the effect of increased shelterin gene expression on telomere length in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR) using known telomere length assays. We measured telomere lengths using: Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic levels of 5-aza-CdR affect telomere lengths by causing a significant and stable increase in telomere lengths of the breast cancer cell line. The increase in telomere lengths was consistently observed when various telomere length methods were used. Conclusions: Further investigation is required to understand the underlying mechanism involved, and the significance of telomere length elongation in relation to clinical outcome when epigenetic modifying drugs are utilized.展开更多
Background We have developed a tridirectional regimen combining intraperitoneal,intravenous,and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics acc...Background We have developed a tridirectional regimen combining intraperitoneal,intravenous,and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics according to mRNA expression.This multicenter Phase Ⅲ umbrella study compared the efficacy and safety of individualized tridirectional intraperitoneal and systemic chemotherapy with that of standard systemic chemotherapy.Methods BRCA1/TOPO1 mRNA expression was examined in all enrolled patients.The patients were then randomized in a ratio of 3:1 to an individualized arm and a control arm.Patients in the control arm received systemic intravenous/oral chemotherapy,whereas those in the individualized arm received sensitive chemotherapeutics selected from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 according to their BRCA1/TOPO1 mRNA expression and received individualized tridirectional intraperitoneal/intravenous/oral chemotherapy.The primary endpoint was progressionfree survival and the secondary endpoints were response rate,overall survival,and safety.Results Overall,233 of 240 patients enrolled between August 2014 and December 2016 were included in the efficacy analysis.Baseline patient characteristics were balanced between the two arms.The objective response rate was 33.9%in the control arm and 49.1%in the individualized arm(P=0.039).In the control and individualized arms,median progression-free survival was 5.9 months and 8.0 months,respectively(hazard ratio 0.521,95%confidence interval 0.362-0.750,P=0.0005)and median overall survival was 13.5 months and 16.4 months,respectively(hazard ratio 0.684,95%confidence interval 0.474-0.988,P=0.0430).Both regimens were tolerable.Conclusion The primary analysis demonstrated the statistical superiority of this tridirectional individualized regimen and suggests that this regimen has clinical efficacy in patients with advanced gastric cancer.Trial registration Chinese Clinical Trial Registry(chictr.org.cn)Identifier:ChiCTR-IPR-15006201.展开更多
Lung cancer is the leading cause of cancer-related deaths worldwide.Bone is a common metastatic site of lung cancer,about 50%of bone metastatic patients will experience skeletal related events(SREs).SREs not only seri...Lung cancer is the leading cause of cancer-related deaths worldwide.Bone is a common metastatic site of lung cancer,about 50%of bone metastatic patients will experience skeletal related events(SREs).SREs not only seriously impact the quality of life of patients,but also shorten their survival time.The treatment of bone metastasis requires multi-disciplinary therapy(MDT)and development of individualized treatment plan.In order to standardize the diagnosis and treatment of bone metastasis in lung cancer,the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis.展开更多
Although trastuzumab does not bind to human epidermal growth factor receptor 3(HER3),it dephosphorylates HER3 through a previously unknownmechanism.In addition,HER3 is reactivated during prolonged trastuzumab treatmen...Although trastuzumab does not bind to human epidermal growth factor receptor 3(HER3),it dephosphorylates HER3 through a previously unknownmechanism.In addition,HER3 is reactivated during prolonged trastuzumab treatment and upon resistance[1].Previous study showed that tyrosine-protein phosphatase non-receptor type 9(PTPN9)inhibits STAT3/STAT5 signalling by dephosphorylation of epidermal growth factor receptor(EGFR)and human epidermal growth factor receptor 2(HER2)in breast cancer[2],but how this would affect HER3 was not analyzed especially in relation to trastuzumab treatment.We investigated the role of PTPN9 in HER3 signaling in relation to trastuzumab treatment and resistance in HER2 positive breast cancer.The materials and methods applied in this research were described in the supplementary materials.展开更多
Copper,one of the essential nutrients for the human body,acts as an electron relay in multiple pathways due to its redox properties.Both deficiencies and excesses of copper lead to cellular fragility.Therefore,it can ...Copper,one of the essential nutrients for the human body,acts as an electron relay in multiple pathways due to its redox properties.Both deficiencies and excesses of copper lead to cellular fragility.Therefore,it can manifest pro-and anti-cancer properties in tumors.Therefore,it is crucial to clarify the copper activity within the cell.We have thoughtfully summarized the metabolic activi-ties of copper from a macro and micro perspective.Cuproptosis,as well as other forms of cell death,is directly or indirectly interfered with by Cu2+,causing cancer cell death.Meanwhile,we did pan-cancer analysis of cuproptosis-related genes to further clarify the roles of these genes.In addition,copper has been found to be involved in multiple pathways within the metastasis of cancer cells.Given the complexity of copper’s role,we are compelled to ask:is copper a friend or a foe?Up to now,copper has been used in various clinical applications,including protocols for measurement of copper concentration and bioimaging of radioactive 64Cu.But therapeutically it is still a continuation of the old medicine,and new possibilities need to be explored,such as the use of nanomaterials.Some studies have also shown that copper has considerable interventional power in metabolic cancers,which provides the great applications potential of copper therapy in specific cancer types.This paper reviews the dual roles played by cuproptosis in cancer from the new perspectives of oxidative stress,cell death,and tumor metastasis,and points out the value of its application in specific can-cer types,summarizes the value of its testing and imaging from the perspective of clinical application as well as the current feasible options for the new use of the old drugs,and emphasizes the prospects for the application of nano-copper.展开更多
AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcino...AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.展开更多
Background: Non-Hodgkin’s lymphoma is an aggressive malignant disease in children and adolescents. Although it is the fourth most common malignancy in Saudi children as reported in Saudi cancer registry, less informa...Background: Non-Hodgkin’s lymphoma is an aggressive malignant disease in children and adolescents. Although it is the fourth most common malignancy in Saudi children as reported in Saudi cancer registry, less information is available about pediatric Non-Hodgkin lymphoma and its outcome in Saudi Arabia. Study Objectives: To provide demographic data, disease characteristics, treatment protocol, toxicity and outcome of treatment in children & adolescents with Non-Hodgkin’s lymphoma treated at KFMC. This study will form base line for future studies about pediatric Non-Hodgkin’s lymphoma in KFMC, which may help to improve outcome for children with cancer in Saudi Arabia. Study Patients and Method: We retrospectively analyzed 28 children and adolescents diagnosed to have Non-Hodgkin’s lymphoma at KFMC between December 2006 and December 2013, followed-up through June 2014. Results: Of the 28 patients, 10 (35.7%) girls and 18 (64.3%) boys, the male-to-female ratio was 1.8;1. The median age at time of diagnosis was 6.4 years old (range 2.0 to 13.0 years old). The majority of patients (64.3%) were aged between 5 and 12 years old. Burkitt’s lymphoma BL/BLL was the most common pathological subtype (60.7%), and DLBCL was the second most common subtype (21.4%). Abdominal and Retroperitoneal involvement was the most common primary site (78.6%) including the ileocaecal region. Most of the children presented with advanced Stage III and IV (75%), Cytogenetic study which screens specifically for the t (8;14) (q24;q32) a characteristic genetic feature of Burkitt’s Lymphoma was obtained from 21 patients, variant rearrangement was observed in 3/21 samples and complex chromosomes karyotype in addition to IGH/MYC rearrangement was observed in 2/21 samples. Those patients presented with very aggressive lymphoma and combined BM and CNS involvement. We use the French-American-British Mature B-Cell Lymphoma 96 Protocol (FAB LMB 96) for treatment fornewly diagnosed Mature B-Cell type NHL and high risk ALL CCG 1961 Protocol for lymphoblastic lymphoma and international Anaplastic Large Cell Lymphoma 99 Study Protocol for ALCL. The median follow-up in patients not experiencing an adverse event was 53.1 months. The estimated 3-year EFE and OS rates in the entire cohort of patients with newly diagnosed NHL treated in the KFMC were 85.2% and 89.2% respectively;Overall survival (OS) rate of patients with mature B-cell-NHL was 88.9%. Conclusion: The outcomes and survival in our small series appeared to be excellent compared with those reported in other international trials even though most of our patients presented in advanced stage of the disease. We feel that the importance of the current study is to document the relative distribution of various types of pediatric non-Hodgkin’s lymphomas and age-specific distribution in different Histological subtypes.展开更多
The majority of EPID dosimetry literature discusses response linearity and the so-called image lag and ghosting effects despite the lack of a common definition of these quantities. However, the results of these studie...The majority of EPID dosimetry literature discusses response linearity and the so-called image lag and ghosting effects despite the lack of a common definition of these quantities. However, the results of these studies are generally not consistent, and it is often difficult to compare the results from different studies. We present here a detailed study of the acquisition and readout characteristics of a-Si EPID and its dosimetric performance. EPID response was assessed over the range of 1 - 500 MU using different dose rates and integration times. In addition, a computer model was designed to simulate the EPID image formation with different dose, dose rate, and integration time combinations. All aspects of image processing and readout simulation were carried out using custom written MatLab codes. Two distinct signal profiles were observed depending on the delivered dose, dose rate and integration time combination. Total integrated signal (S<sub>T</sub>) is linear with the delivered dose. For dosimetry, image lag and ghosting effects mainly result in the residual signal (S<sub>R</sub>) that appears as delayed signal after the end of irradiation. At its maximum, S<sub>R</sub> is less than 2.5% of S<sub>T</sub>. The readout technique is such that it is impossible to measure S<sub>R</sub> accurately. S<sub>R</sub> is definable only when readout equilibrium occurs. Signal profiles provide a through and reliable description of the EPID response incorporating the dose, dose rate, integration time, and the residual signal. The definition of EPID signals based on this method shall provide an accurate universal EPID dosimetry framework.展开更多
AIM To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs.METHODS We report our 21-year, single-centre cumulative experience of 15 joint arthrop...AIM To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs.METHODS We report our 21-year, single-centre cumulative experience of 15 joint arthroplasties in six inhibitor patients.RESULTS Two low responder inhibitor patients were in the early days treated with FVIII, whereas bypassing agents were used in the rest of the high responder patients. The primary haemostatic outcome was good in 8/15, fair in 4/15 and poor in 3/15 operations. The overall patient outcome, including joint health and patient satisfaction, was good in 10/15, fair 4/15 and poor in 1/15. No deep infections were observed. Cost analysis was most beneficial in low responders and in two immune-tolerized, high responder patients. In all cases, factor replacement comprised the main treatment costs.CONCLUSION Our experience supports the initial use of bypassing agents as well as preoperative immune-tolerance induction when possible. Despite the challenges of haemostasis and severe joint disease, total joint arthroplasty can reach a good outcome, even in inhibitor patients. The risk for deep infection might be smaller than previously reported. Individual planning, intense multidisciplinary teamworkand execution of operations should be centralised in a professional unit.展开更多
基金supported by the Henan Provincial Science and Technology Research Project(grant number 221100310100 to Z.L.and X.H.).
文摘Human microbiota constitute a complex and dynamic community that interacts with the innate immunity of the host at various anatomical sites,influencing both physiological and pathological states.In individuals with a genetic predisposition,disruptions to the“innate immunity‒microbiota”axis appear to rewire immune responses within the tumor microenvironment(TME),thereby driving cancer pathogenesis.This review summarizes the intricate crosstalk between the microbiota and innate immunity in both healthy and cancerous states,focusing on the modulation of immune recognition and polarization during tumor progression,including immune escape,barrier disruption,chronic inflammatory transformation,and angiogenesis in the initiation phase,as well as the regulation of local invasion,vascular invasion,and pre-metastatic ecological niche formation involved in the metastatic phase.This review also highlights recent advances and challenges in leveraging microbiota for cancer immunotherapy,covering innovations in bacteriophages,genetically engineered probiotics,and bioinformatic applications.Moreover,this review proposes potential approaches to enhance therapeutic efficacy by targeting innate immunity‒microbiota interactions.Further mechanistic insights into these interactions may pave the way for developing innovative microbiota-based cancer immunotherapies.
文摘The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials of first-generation inhibitors of mammalian target of rapamycin(m TOR) in OC have demonstrated negative results. The lack of patient selection as well as resistance to selective m TOR complex-1(m TORC1) inhibitors could explain the disappointing results thus far. Nonetheless, a number of novel agents are being investigated, including dual m TORC1/m TORC2, Akt, and PI3 K inhibitors. Although it is likely that inhibition of the PI3K/Akt/m TOR pathway may have little effect in unselected OC patients, certain histological types, such as clear cell or endometrioid OC with frequent phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha(PIK3CA) and/or phosphatase and tensin homolog(PTEN) alterations, may be particularly suited to this approach. Given the complexity and redundancy of the PI3 K signaling network, PI3 K pathway inhibition may be most useful in combination with either chemotherapy or other targeted therapies, such as MEK inhibitors, anti-angiogenic therapy, and hormonal therapy, in appropriately selected OC patients. Here, we discuss the relevance of the PI3 K pathway in OC and provide an up-to-date review of clinical trials of novel PI3 K inhibitors alone or in combination with cytotoxics and novel therapies in OC. In addition, the challenges of drug resistance and predictive biomarkers are addressed.
文摘Gastric cancer(GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However,response to chemotherapy varies widely,with some patients presenting no or only minor response to treatment. Hence,chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately,to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment,or that allow modification of chemotherapy resistance. MicroRNAs(miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types,and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in GC.The authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics,and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.
基金Supported by National Natural Science Foundation of China,No.81220108023,No.81370064 and No.81572329Fundamental Research Funds for the Central Universities,No.20620140729+1 种基金Jiangsu Provincial Program of Medical Sciences,No.BL2012001Distinguished Young Investigator Project of Nanjing,No.JQX12002
文摘Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.
文摘BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial issue in the pathogenesis and development of cancer.AIM To evaluate the prognostic value of absolute monocyte count,monocyte to lymphocyte ratio(MLR),the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio(NLR-PLR),and combined platelet and neutrophilto-lymphocyte ratio(PLT-NLR)in peripheral blood samples of patients with colorectal cancer undergoing surgery.METHODS We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery,and 42 healthy controls.The status of absolute monocyte count,MLR,NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery.Haematologic factors were examined in correlation with the type of tumour growth,tumour size,histological type,percentage of mucinous component,grade of malignancy,Tumour-Node-Metastasis stage,venous,lymphatic and perineural invasion of cancer cells,status of lymph node invasion and the presence of cancer cell deposits.The Kaplan-Meier method and the long-rank test were used to compare survival curves.To determine independent prognostic factors,univariate and multivariate Cox proportional hazards regression models were applied.RESULTS The PLT-NLR status was correlated with tumour size and the presence of perineural invasion(P=0.015;P=-0.174,P=0.037).Moreover,high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component(NLR-PLR:P=0.002;P=0.009;PLR-NLR status:P=0.002;P=0.007).The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery[HR=2.903,95%CI:(1.368-6.158),P=0.005]and the status of lymph node metastasis[HR=0.813,95%CI:(0.653-1.013),P=0.050]were independent prognostic factors in colorectal cancer patients.CONCLUSION The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.
文摘AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision （TME）. METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the Amsterdam Cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records. RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）. CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.
基金Supported by A Research Fellowship of the German Research Foundation(DFG)to Hummel R,No.Hu 1763/1-1Funding was also obtained from a project grant from the National Health and Medical Research Council of Australia No.595964Funding Sources(DFG,National Health and Medical Research Council of Australia)
文摘AIM: To investigate expression of microRNA (miRNA) and potential targets in chemotherapy resistant esophageal cancer cell lines.
文摘BACKGROUND Despite effective prevention and screening methods,the incidence and mortality rates associated with colorectal cancer(CRC)are still high.Insulin receptor substrate 1(IRS-1),a signaling molecule involved in cell proliferation,survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models.However,the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined.AIM To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers,Bax,Bcl-xL and Ki-67 are related to clinicopathological features in human CRC.METHODS The expression of IRS-1,Bax,Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods.The assays were performed using specific antibodies against IRS-1,Bax,Bcl-xL,Ki-67.The associations between the expression of IRS-1,Bax,Bcl-xL,Ki-67 were analyzed in relation to clinicopathological parameters,i.e.,patient age,sex,primary localization of tumor,histopathological type,grading,staging and lymph node spread.Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at P<0.05.RESULTS Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases.IRS-1 expression at any level in primary CRC was associated with tumor grade(69%in moderately differentiated tumors,G2 vs 31%in poorly differentiated tumors,G3)and with histological type(81.9%in adenocarcinoma vs 18.1%in adenocarcinoma with mucosal component cases).Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases(95.1%)and in moderately differentiated tumors(85.2%).We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined.The relationships between studied proteins were related to clinicopathological parameters of CRC.No significant correlation between the expression of IRS-1 and proliferation marker Ki-67,excluding early stage tumors,where the correlation was positive and on a high level(P=0.043,r=0.723).CONCLUSION This study suggests that IRS-1 is co-expressed with both pro-and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC.
文摘Objective: It is unclear if and to what extent family history of breast/ovarian cancer or BRCA1/2-mutation carriership influences breast cancer treatment strategy. We investigated whether treatment differed between patients from BRCA1/2 families and those unselected for family history. Methods: We included 478 BRCA1/2-related patients referred for genetic testing before or after diagnosis. Two references were used: 13,498 population-based and 6896 hospital-based patients. Surgical treatment and adjuvant chemotherapy use was analyzed using logistic regression models, stratified by tumor size, nodal status, age at and period of diagnosis, and estrogen receptor status (ER). Results: BRCA1/2 cases aged 35 - 52 years at diagnosis and/or with tumors < 2 cm were more likely to have undergone a modified radical mastectomy (Odd Ratios (OR) ranging from 2.8 to 5.1) compared to the references. This effect was most pronounced in patients treated after 1995 (OR 5.7 to 10.3). Compared to the reference groups, chemotherapy was more often administered to BRCA1 and ER-negative BRCA1/2-cases irrespective of age and nodal status (OR 1.9 to 24.3). Conclusion: After 1995 treatment of BRCA1/2-associated patients consisted notably of more mastectomies and adjuvant chemotherapy than their population-based counterparts with the same tumor characteristics. There is a need to be aware of such differences in daily practice and interpretation of survival studies on BRCA1/2 mutation carriers.
文摘Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic conversion of the mammary epithelial cells. Interestingly, the regulation of some of the shelterin genes is thought to be controlled epigenetically. Methods and Results: In this study, we set out to measure the effect of increased shelterin gene expression on telomere length in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR) using known telomere length assays. We measured telomere lengths using: Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic levels of 5-aza-CdR affect telomere lengths by causing a significant and stable increase in telomere lengths of the breast cancer cell line. The increase in telomere lengths was consistently observed when various telomere length methods were used. Conclusions: Further investigation is required to understand the underlying mechanism involved, and the significance of telomere length elongation in relation to clinical outcome when epigenetic modifying drugs are utilized.
基金funded by grants from the National Key Research and Development Program of China(grant numbers 2017YFC1308900 and SQ2018ZX090301)the National Natural Science Foundation of China(grant numbers 81370064 and 81672367).
文摘Background We have developed a tridirectional regimen combining intraperitoneal,intravenous,and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics according to mRNA expression.This multicenter Phase Ⅲ umbrella study compared the efficacy and safety of individualized tridirectional intraperitoneal and systemic chemotherapy with that of standard systemic chemotherapy.Methods BRCA1/TOPO1 mRNA expression was examined in all enrolled patients.The patients were then randomized in a ratio of 3:1 to an individualized arm and a control arm.Patients in the control arm received systemic intravenous/oral chemotherapy,whereas those in the individualized arm received sensitive chemotherapeutics selected from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 according to their BRCA1/TOPO1 mRNA expression and received individualized tridirectional intraperitoneal/intravenous/oral chemotherapy.The primary endpoint was progressionfree survival and the secondary endpoints were response rate,overall survival,and safety.Results Overall,233 of 240 patients enrolled between August 2014 and December 2016 were included in the efficacy analysis.Baseline patient characteristics were balanced between the two arms.The objective response rate was 33.9%in the control arm and 49.1%in the individualized arm(P=0.039).In the control and individualized arms,median progression-free survival was 5.9 months and 8.0 months,respectively(hazard ratio 0.521,95%confidence interval 0.362-0.750,P=0.0005)and median overall survival was 13.5 months and 16.4 months,respectively(hazard ratio 0.684,95%confidence interval 0.474-0.988,P=0.0430).Both regimens were tolerable.Conclusion The primary analysis demonstrated the statistical superiority of this tridirectional individualized regimen and suggests that this regimen has clinical efficacy in patients with advanced gastric cancer.Trial registration Chinese Clinical Trial Registry(chictr.org.cn)Identifier:ChiCTR-IPR-15006201.
文摘Lung cancer is the leading cause of cancer-related deaths worldwide.Bone is a common metastatic site of lung cancer,about 50%of bone metastatic patients will experience skeletal related events(SREs).SREs not only seriously impact the quality of life of patients,but also shorten their survival time.The treatment of bone metastasis requires multi-disciplinary therapy(MDT)and development of individualized treatment plan.In order to standardize the diagnosis and treatment of bone metastasis in lung cancer,the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis.
基金supported by Breakthrough Breast cancer(Grant number:CSFKong)through Holbeck Charitable TrustProf A Shaaban is supported by Birmingham CRUK Centre grant.
文摘Although trastuzumab does not bind to human epidermal growth factor receptor 3(HER3),it dephosphorylates HER3 through a previously unknownmechanism.In addition,HER3 is reactivated during prolonged trastuzumab treatment and upon resistance[1].Previous study showed that tyrosine-protein phosphatase non-receptor type 9(PTPN9)inhibits STAT3/STAT5 signalling by dephosphorylation of epidermal growth factor receptor(EGFR)and human epidermal growth factor receptor 2(HER2)in breast cancer[2],but how this would affect HER3 was not analyzed especially in relation to trastuzumab treatment.We investigated the role of PTPN9 in HER3 signaling in relation to trastuzumab treatment and resistance in HER2 positive breast cancer.The materials and methods applied in this research were described in the supplementary materials.
基金Major Science and Technology projects of Henan Province,Grant/Award Number:221100310100。
文摘Copper,one of the essential nutrients for the human body,acts as an electron relay in multiple pathways due to its redox properties.Both deficiencies and excesses of copper lead to cellular fragility.Therefore,it can manifest pro-and anti-cancer properties in tumors.Therefore,it is crucial to clarify the copper activity within the cell.We have thoughtfully summarized the metabolic activi-ties of copper from a macro and micro perspective.Cuproptosis,as well as other forms of cell death,is directly or indirectly interfered with by Cu2+,causing cancer cell death.Meanwhile,we did pan-cancer analysis of cuproptosis-related genes to further clarify the roles of these genes.In addition,copper has been found to be involved in multiple pathways within the metastasis of cancer cells.Given the complexity of copper’s role,we are compelled to ask:is copper a friend or a foe?Up to now,copper has been used in various clinical applications,including protocols for measurement of copper concentration and bioimaging of radioactive 64Cu.But therapeutically it is still a continuation of the old medicine,and new possibilities need to be explored,such as the use of nanomaterials.Some studies have also shown that copper has considerable interventional power in metabolic cancers,which provides the great applications potential of copper therapy in specific cancer types.This paper reviews the dual roles played by cuproptosis in cancer from the new perspectives of oxidative stress,cell death,and tumor metastasis,and points out the value of its application in specific can-cer types,summarizes the value of its testing and imaging from the perspective of clinical application as well as the current feasible options for the new use of the old drugs,and emphasizes the prospects for the application of nano-copper.
基金Supported by National Natural Science Foundation of China,No.81401969Jiangsu Provincial Medical Youth Talent,No.QNRC2016043the Key Medical Science and Technology Development Project of Nanjing,No.ZKX16032
文摘AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.
文摘Background: Non-Hodgkin’s lymphoma is an aggressive malignant disease in children and adolescents. Although it is the fourth most common malignancy in Saudi children as reported in Saudi cancer registry, less information is available about pediatric Non-Hodgkin lymphoma and its outcome in Saudi Arabia. Study Objectives: To provide demographic data, disease characteristics, treatment protocol, toxicity and outcome of treatment in children & adolescents with Non-Hodgkin’s lymphoma treated at KFMC. This study will form base line for future studies about pediatric Non-Hodgkin’s lymphoma in KFMC, which may help to improve outcome for children with cancer in Saudi Arabia. Study Patients and Method: We retrospectively analyzed 28 children and adolescents diagnosed to have Non-Hodgkin’s lymphoma at KFMC between December 2006 and December 2013, followed-up through June 2014. Results: Of the 28 patients, 10 (35.7%) girls and 18 (64.3%) boys, the male-to-female ratio was 1.8;1. The median age at time of diagnosis was 6.4 years old (range 2.0 to 13.0 years old). The majority of patients (64.3%) were aged between 5 and 12 years old. Burkitt’s lymphoma BL/BLL was the most common pathological subtype (60.7%), and DLBCL was the second most common subtype (21.4%). Abdominal and Retroperitoneal involvement was the most common primary site (78.6%) including the ileocaecal region. Most of the children presented with advanced Stage III and IV (75%), Cytogenetic study which screens specifically for the t (8;14) (q24;q32) a characteristic genetic feature of Burkitt’s Lymphoma was obtained from 21 patients, variant rearrangement was observed in 3/21 samples and complex chromosomes karyotype in addition to IGH/MYC rearrangement was observed in 2/21 samples. Those patients presented with very aggressive lymphoma and combined BM and CNS involvement. We use the French-American-British Mature B-Cell Lymphoma 96 Protocol (FAB LMB 96) for treatment fornewly diagnosed Mature B-Cell type NHL and high risk ALL CCG 1961 Protocol for lymphoblastic lymphoma and international Anaplastic Large Cell Lymphoma 99 Study Protocol for ALCL. The median follow-up in patients not experiencing an adverse event was 53.1 months. The estimated 3-year EFE and OS rates in the entire cohort of patients with newly diagnosed NHL treated in the KFMC were 85.2% and 89.2% respectively;Overall survival (OS) rate of patients with mature B-cell-NHL was 88.9%. Conclusion: The outcomes and survival in our small series appeared to be excellent compared with those reported in other international trials even though most of our patients presented in advanced stage of the disease. We feel that the importance of the current study is to document the relative distribution of various types of pediatric non-Hodgkin’s lymphomas and age-specific distribution in different Histological subtypes.
文摘The majority of EPID dosimetry literature discusses response linearity and the so-called image lag and ghosting effects despite the lack of a common definition of these quantities. However, the results of these studies are generally not consistent, and it is often difficult to compare the results from different studies. We present here a detailed study of the acquisition and readout characteristics of a-Si EPID and its dosimetric performance. EPID response was assessed over the range of 1 - 500 MU using different dose rates and integration times. In addition, a computer model was designed to simulate the EPID image formation with different dose, dose rate, and integration time combinations. All aspects of image processing and readout simulation were carried out using custom written MatLab codes. Two distinct signal profiles were observed depending on the delivered dose, dose rate and integration time combination. Total integrated signal (S<sub>T</sub>) is linear with the delivered dose. For dosimetry, image lag and ghosting effects mainly result in the residual signal (S<sub>R</sub>) that appears as delayed signal after the end of irradiation. At its maximum, S<sub>R</sub> is less than 2.5% of S<sub>T</sub>. The readout technique is such that it is impossible to measure S<sub>R</sub> accurately. S<sub>R</sub> is definable only when readout equilibrium occurs. Signal profiles provide a through and reliable description of the EPID response incorporating the dose, dose rate, integration time, and the residual signal. The definition of EPID signals based on this method shall provide an accurate universal EPID dosimetry framework.
文摘AIM To collect data from joint replacement in inhibitor patients, evaluate haemostatic and patient outcomes, and analyse the costs.METHODS We report our 21-year, single-centre cumulative experience of 15 joint arthroplasties in six inhibitor patients.RESULTS Two low responder inhibitor patients were in the early days treated with FVIII, whereas bypassing agents were used in the rest of the high responder patients. The primary haemostatic outcome was good in 8/15, fair in 4/15 and poor in 3/15 operations. The overall patient outcome, including joint health and patient satisfaction, was good in 10/15, fair 4/15 and poor in 1/15. No deep infections were observed. Cost analysis was most beneficial in low responders and in two immune-tolerized, high responder patients. In all cases, factor replacement comprised the main treatment costs.CONCLUSION Our experience supports the initial use of bypassing agents as well as preoperative immune-tolerance induction when possible. Despite the challenges of haemostasis and severe joint disease, total joint arthroplasty can reach a good outcome, even in inhibitor patients. The risk for deep infection might be smaller than previously reported. Individual planning, intense multidisciplinary teamworkand execution of operations should be centralised in a professional unit.
