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Prognostic Analysis Of Salvage Surgery For Hypopharyngeal Squamous Cell Carcinoma And The Role Of Cancer-derived Sialylated-IgG In Hypopharyngeal Squamous Cell Carcinoma

Posted on:2023-06-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:1524306620458834Subject:Oncology
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Background and Objective:Treatment options for recurrent/residual hypopharyngeal squamous cell carcinoma(HPSCC)following radiotherapy are limited,among which salvage surgery is the most preferred and probable one that could achieve radical goals.However,salvage surgery may result in several postoperative complications that significantly impair patients’quality of life.The purpose of this study was to determine the pre-salvage-surgery characteristics that affect the risk of postoperative complications,and provide recommendations for clinicians to predict and intervene preoperatively.Materials and Methods:We conducted a retrospective assessment of patients with recurrent/residual HPSCC who underwent salvage surgery in the Department of Head and Neck Surgery at the Cancer Hospital,Chinese Academy of Medical Sciences,between July 2008 and July 2018.A total of 95 patients were included.Clinicopathological and follow-up data were collected.Univariate and multivariate analyses were performed using a binary logistic regression model to identify potential risk factors for postoperative complications.Results:There was no peri-operative death.38(40%)out of 95 patients developed postoperative complications,12 of whom developed no less than 2 kinds of complications.Pharyngo-cutaneous fistula(PCF)occurred in 27(28.4%)patients.While for 12 patients,the time intervals between salvage surgery and PCF detected were more than 2 weeks.Multivariate analyses showed that salvage surgery for local recurrence/residual was the only independent risk factor for postoperative complication(p=0.032)and PCF(p=0.018).In the subgroup of patients with local disease,time interval from recurrence/residual diagnosis to salvage surgery>90 days(p=0.017)and preoperative hemoglobin<118g/L(p=0.048)were independent risk factors for postoperative complication,while free flap reconstruction(p=0.032)and hemoglobin≥118g/L(p=0.021)were independent protective factors for PCF.Conclusion:Patients with local recurrence/residual experience a high postoperative complication risk.Salvage surgery for local recurrence/residual was the only independent risk factor for postoperative complication.The risk of postoperative complications and PCF may be reduced in this local salvage subgroup by shortening the time interval from recurrence/residual diagnosis to salvage surgery and implying intervention on patients with low hemoglobin.Background and Objective:Patients with hypopharyngeal squamous cell carcinoma(HPSCC)usually has a poor prognosis,especially those with recurrence/residual disease after radical radiotherapy.Salvage surgery is the most preferred and probable curative option for post-radiotherapy recurrence/residual.However,salvage surgery itself and the postoperative complications would affect patients’ respiratory,phonatory and swallowing functions,significantly impairing patients’ quality of life.The purpose of this study was to determine the pre-salvage-surgery characteristics that affect the survival outcomes,and assist clinicians in formulating more reasonable treatment strategies.Materials and Methods:We retrospectively collected the clinical and follow-up data of 76 patients with recurrent/residual HPSCC after radical radiotherapy,who underwent salvage surgery in the Department of Head and Neck Surgery at the Cancer Hospital,Chinese Academy of Medical Sciences between July 2008 and July 2018.The KaplanMeier method was used to draw survival curves and differences among groups were compared by the log-rank test.Multivariate Cox regression analysis was used to identify independent prognostic factors for overall survival.Results:The median overall survival(OS)time was 22 months,with 1-year,2-year,3year,and 5-year OS rates of 64.5%,46.1%,37.9%and 34.5%,respectively.Age at salvage surgery<50(HR:0.348,95%CI 0.182-0.663,p=0.001),radiation dose<70Gy(HR:0.465,95%CI 0.221-0.978,p=0.044),rcT3-4(HR:2.586,95%CI 1.204-5.553,p=0.015)and rcN3(HR:2.838,95%CI 1.346-5.985,p=0.006)were identified as independent risk factors for OS.Patients without any risk factors had a better oncological prognosis with 5-year OS rate of 57.8%,compared to patients with risk factors(with one risk factor:5-year OS rate of 31.3%;with two risk factors:5-year OS rate of 26,6%)(p=0.011).Conclusion:For HPSCC patients with salvage surgery after radical radiotherapy,age at salvage surgery<50,radiation dose<70Gy,rcT3-4 and rcN3 were independent risk factors for OS.Patients without any risk factor could achieve a relatively favorable survival.Background and Objective:Hypopharyngeal squamous cell carcinoma(HPSCC)has one of the worst prognosis among all head and neck malignant tumor.85%of HPSCC patients were diagnosed at advanced stage,with poor 5-year survival rate.The survival of patients with recurrent/residual HPSCC is even worse,with limited treatment options available.Therefore,understanding the molecular mechanisms of the HPSCC and identifying new molecular targets for new therapies to improve treatment outcomes is still needed.Many studies have found that a lot of human carcinomas express cancer-derived sialylated-IgG(SIA-IgG).It has prognosis predictive value and acts as a potential immune checkpoint.However,researches of SIA-IgG in HPSCC are still in relatively blank stage.The aim of this study was to investigate the expression of SIA-IgG and its prognosis predictive value in HPSCC.Meanwhile,exploring its effect on proliferation and migration of HPSCC cells would lay a foundation for further study of the mechanism and its potential value as therapeutic target.Materials and Methods:Paraffin specimens and clinicopathological data of 68 patients with HPSCC who received initial surgery in the Department of Head and Neck Surgery at Cancer Hospital,Chinese Academy of Medical Sciences were retrospectively collected,as well as detailed follow-up data.Immunohistochemical(IHC)staining was used to investigate the expression of SIA-IgG in HPSCC and its relationship with patients’ survival.In vitro studies were performed using Western-blot assay,immunofluorescence assay,CCK-8 proliferation assay,clone formation assay and Transwell assay to investigate the effects of SIA-IgG on the proliferation and migration of HPSCC Fadu cell line.Results:IHC results showed that SIA-IgG was expressed in most of HPSCC tissues and mainly distributed on the cell membrane.Fourteen samples(20.6%)had low expression of SIA-IgG,and 54 samples(79.4%)had high expression of SIA-IgG.Univariate survival analysis suggested that overall survival(OS)of patients with low SIA-IgG expression group was significantly better than that of patients with high SIA-IgG expression group(p<0.05).Multivariate analysis showed that the high expression of SIA-IgG and N2-3 stage were associated with higher risk of death,and both were independent risk factors for OS(p<0.05).In vitro studies showed that human HPSCC Fadu cells could express SIA-IgG,which mainly located on the cell membrane and presented a pseudopod-like structure extending to surrounding cells.Compared with the control group,siRNA knockdown of SIA-IgG significantly inhibited the proliferation and migration of HPSCC F adu cells(p<0.05).Conclusion:SIA-IgG is commonly expressed in HPSCC.High expression of SIA-IgG is associated with poor survival outcomes.The expression of SIA-IgG can be used as a prognostic indicator for HPSCC patients,helping to predict the prognosis of patients and develop more individualized treatment plans.Meanwhile,SIA-IgG can promote cell proliferation and migration capability in HPSCC.SIA-IgG has the potential to become a new immunotherapy target for HPSCC,with further exploring its mechanism in HPSCC development and immune microenvironment,to improve prognosis.
Keywords/Search Tags:hypopharyngeal squamous cell carcinoma, postoperative complication, pharyngo-cutaneous fistula, risk factor, salvage surgery, overall survival, cancer-derived sialylated-IgG, prognosis, tumor marker
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