Long-term Survival Of Patients Research Articles

Torque Teno Virus Loads as a Marker of Immunosuppression in Pediatric Kidney Transplant Recipients.

Long-term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single-stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status. TTV-based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long-term patient and graft survival. Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library. The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High-TTV load and high immunosuppression are associated with a risk of infection, and low-TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner etal. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections. Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV-guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation.

Determinants of long-term survival in patients with IDH-mutant gliomas.

Survival times of patients with IDH-mutant gliomas are variable and can extend to decades. Many studies provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored characteristics of short- and long-term survivors within a cohort of patients with extended follow-up. This single-center, case-control study included 86 patients diagnosed between 1998 and 2023 who either died within 6 years after diagnosis or survived at least 15 years. Patient characteristics and prognostic factors were stratified by short- (< 6 years) versus long-term (≥ 15 years) survival. Forty-seven patients (55%) diagnosed with astrocytoma and 39 patients (45%) with oligodendroglioma were included retrospectively. Median follow-up of the survivors was 16.6 years (range 15-28.9). Thirty-four deaths (40%) had been reported at database closure. Long-term survival was associated with CNS WHO grade 2 (p < 0.01), smaller tumor volumes (p = 0.01), lack of contrast enhancement (p < 0.01), wait-and-scan strategies (p < 0.01) and female sex (p = 0.04). In multivariate analyses for oligodendroglioma, larger T2 tumor volumes were associated with shorter survival (HR 1.02; 95% CI 1.01-1.05; p = 0.04). In patients with astrocytoma, lack of contrast enhancement (HR 0.38; 95% CI 0.15-0.94; p = 0.04) and wait-and-scan strategies (HR 5.75; 95% CI 1.66-26.61; p = 0.01) were associated with longer survival. Large T2 tumor volume and contrast enhancement may be important risk factors for shorter survival, while age might be of lesser importance. Wait-and-scan strategies may yield excellent long-term survival in some patients with astrocytoma.

Identification of prognostic biomarkers in neuroblastoma using WGCNA and multi-omics analysis

BackgroundNeuroblastoma (NB) is one of the most frequent parenchymal tumors among children, with a high degree of heterogeneity and wide variation in clinical presentation. Despite significant therapeutic advances in recent years, long-term survival in high-risk patients remains low, emphasizing the urgent need to find new biomarkers and construct reliable prognostic models.MethodsIn this study, data from neuroblastoma samples in the ArrayExpress database were utilized to identify key gene modules and pivotal genes associated with NB prognosis by weighted gene co-expression network analysis (WGCNA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis was performed using the DAVID database. Based on these hub genes, survival prognosis models were constructed and validated on an independent validation set in the Gene Expression Omnibus (GEO) database. Differences in biological functions and immune microenvironments and the sensitivity to pharmacological and immunotherapeutic treatments of patients in the high- and low-risk groups were examined by gene set enrichment analysis (GSEA) and immune infiltration analysis.ResultsWGCNA identified 14 gene modules and screened the module with the highest relevance to the International Neuroblastoma Staging System (INSS), containing 60 pivotal genes. GO and KEGG analyses demonstrated that these pivotal genes were mainly implicated in biological processes and signaling pathways including DNA replication, cell division, mitotic cell cycle, and cell cycle. Based on Lasso regression and COX regression analysis, a prognostic model containing DHFR, GMPS and E2F3 was constructed, and the RiskScore was significantly correlated with the 1-, 3- and 5-year survival of the patients. GSEA and immune infiltration analyses revealed significant differences in the levels of cell cycle-related pathways and immune cell infiltration between the high and low RiskScore groups. In particular, patients in the high-risk group are less likely to benefit from immunotherapy and may be better suited for treatment with drugs such as Oxaliplatin and Alpelisib.ConclusionThis research systematically identified biomarkers related to NB prognosis and developed a reliable prognostic model applying WGCNA and multiple bioinformatics methods. The model has important application value in predicting patients’ prognosis, evaluating drug sensitivity and immunotherapy effect, and provides new ideas and directions for precise treatment of neuroblastoma.

Long-Term Survival of Patients with Adult T-Cell Leukemia/Lymphoma Treated with Amplified Natural Killer Cell Therapy

Background: Adult T-cell leukemia/lymphoma (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) after a long latent infection. HTLV-1 induces the indolent or aggressive type of leukemia in 5% of HTLV-1 carriers. ATL, especially the aggressive type, is resistant to multi-agent chemotherapy. The indolent type often progresses to the aggressive type. Even in the most indolent-type cases, that is, smoldering ATL, the average survival time is 55.0 months. Case Presentation: Five patients with ATL were followed up for their clinical course after amplified natural killer cell (ANK) therapy. Four patients who received ANK therapy as first-line therapy achieved complete remission and showed long-term survival without aggressive conversion or relapse for more than 5 years. One patient was treated with multiagent chemotherapy due to acute exacerbation but relapsed 2 months later. She was subsequently treated with radiation and ANK therapy and survived for more than 6 years. Furthermore, ANK therapy enhanced the immune function of ATL patients to a level higher than that of normal individuals. Conclusions: ANK therapy has great potential as first-line treatment for ATL.

Smoking cessation assistance among pneumologists and thoracic surgeons in Switzerland: a national survey.

Smoking, with a prevalence of about 25%-30% in Switzerland, is proven to cause major systemic, avoidable diseases including lung cancer, increasing societies morbidity and mortality. Diverse strong quitting smoking recommendations have been made available providing advice facilitating smoking cessation globally. In other European countries like Germany, clinical practice guidelines for smoking cessation services have been implemented. However, in Switzerland, there is still no national consensus on a comprehensive smoking cessation program for lung cancer patients nor on the adequate provider. Our primary aim was to assess the current status of smoking cessation practice among specialists, mainly involved in lung cancer care, in Switzerland in order to uncover potential shortcomings. A self-designed 14-items questionnaire, which was reviewed and approved by our working group consisting of pneumologists and thoracic surgeons, on demographics of the participants, the status of smoking cessation in Switzerland and specialists' opinion on smoking cessation was sent to thoracic surgeons and pneumologists between January 2024 and March 2024 via the commercially available platform www.surveymonkey.com. Data was collected and analysed with descriptive statistics. Survey response rate was 22.25%. Smoking cessation was felt to positively affect long term survival and perioperative outcome in lung cancer surgery. While 33 (37.08%) physicians were offering smoking cessation themselves usually and always (35.96%), only 12 (13.48%) were always referring their patients for smoking cessation. Patient willingness was clearly identified as main factor for failure of cessation programs by 63 respondents (70.79%). Pneumologists were deemed to be the most adequate specialist to offer smoking cessation (49.44%) in a combination of specialist counselling combined with pharmaceutic support (80.90%). The development of Swiss national guidelines for smoking cessation and the implementation of cessation counselling in standardized lung cancer care pathways is warranted in Switzerland to improve long-term survival and perioperative outcome of lung cancer patients.

Clinical Features and Survival Analysis of Lupus Nephritis among Patients with Systemic Lupus Erythematosus: A Three-Decade-Long Retrospective Cohort Study.

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). The aim of our retrospective cohort study was to compare the clinical characteristics, therapy, survival, causes of death, and prognostic factors of LN and non-LN lupus patients. Moreover, we compared a wide spectrum of clinical data of LN patients diagnosed before and since 2005 to determine any changes in disease course and outcomes. Methods: We assessed the clinical and laboratory data of 384 SLE patients, out of whom, 127 patients were diagnosed with LN between 1990 and 2020. Results: Based on our observations, discoid LE, subacute cutaneous LE, antiphospholipid syndrome, Sjögren's syndrome, and rheumatoid arthritis were more common in non-LN patients, while anemia and anti-RNP positivity were more frequent in LN patients. Development of LN did not affect survival rates; male sex and presence of APS were negative prognostic parameters in the non-LN group while achieving remission was a positive prognostic factor in both groups. Death caused by sepsis was more prevalent in the LN group. Serositis and neurological manifestations occurred less frequently in LN patients diagnosed after 2005. The use of mycophenolate mofetil became more common, and the cumulative corticosteroid dose decreased. The SLICC Damage Index score also decreased. Conclusions: Our study demonstrated that the disease course has changed in recent years, and the main therapeutic goal in both SLE and lupus nephritis should be to achieve remission because this significantly improves long-term prognosis and patient survival.

Patient Factors Associated with 10-Year Survival After Arthroplasty for Hip Fracture: A Population-Based Study in Ontario, Canada.

The aim of this study was to describe long-term (10-year) patient survival after arthroplasty for hip fracture and to determine what patient factors are associated with that outcome. We performed a retrospective cohort analysis of patients ≥60 years old who underwent either hemiarthroplasty or total hip arthroplasty for femoral neck fracture between 2002 and 2009. We used routinely collected, validated health-care databases linked through ICES (formerly known as the Institute for Clinical Evaluative Sciences). We estimated the association between baseline variables and survival 10 years post-fracture using Poisson regression. Restricted cubic spline functions modeled the probability of 10-year survival by age and tested whether there was an inflection point after which the probability of 10-year survival decreased more rapidly. We estimated 10-year survival probabilities for different patient groups. There were 19,659 patients in the final cohort. Eighteen percent (3,564) of the patients were alive at 10 years postoperatively. Factors associated with a higher likelihood of 10-year survival included younger age, female sex (risk ratio [RR] = 1.56, 95% confidence interval [CI] = 1.46 to 1.68), lower American Society of Anesthesiologists (ASA) class (ASA I or II versus IV or V: RR = 1.96, 95% CI = 1.76 to 2.19), independent living status (RR = 2.68, 95% CI = 2.23 to 3.22), and fewer specific comorbidities. A threshold age of 73 years was the inflection point after which the probability of 10-year survival decreased more rapidly in females. Estimated 10-year survival probabilities ranged from 79.0% (95% CI = 75.5% to 82.5%) to 0.8% (95% CI = 0.6% to 1.0%). Approximately 1 in 6 patients live at least 10 years following a hip fracture. This study identifies baseline characteristics that predict survival greater than 10 years, including an age of <75 years, an ASA class of I or II, and independent living status prior to the hip fracture. Results can inform discussions around treatment choices, anticipated outcomes, and the natural history of hip fractures. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy.

The European Chronic Thromboembolic Pulmonary Hypertension registry (CTEPH), conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Oof patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes/(s·cm-5). During an observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention (P<0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non-vitamin K oral anticoagulants (P=0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. URL https://clinicaltrials.gov; Unique identifier: NCT02656238.

CBioProfiler: A Web and Standalone Pipeline for Cancer Biomarker and Subtype Characterization.

Cancer is a leading cause of death worldwide, and the identification of biomarkers and subtypes that can predict the long-term survival of cancer patients is essential for their risk stratification, treatment, and prognosis. However, there are currently no standardized tools for exploring cancer biomarkers or subtypes. In this study, we introduced Cancer Biomarker and subtype Profiler (CBioProfiler), a web server and standalone application that includes two pipelines for analyzing cancer biomarkers and subtypes. The cancer biomarker pipeline consists of five modules for identifying and annotating cancer survival-related biomarkers using multiple survival-related machine learning algorithms. The cancer subtype pipeline includes three modules for data preprocessing, subtype identification using multiple unsupervised machine learning methods, and subtype evaluation and validation. CBioProfiler also includes CuratedCancerPrognosisData, a novel R package that integrates reviewed and curated gene expression and clinical data from 268 studies. These studies cover 43 common blood and solid tumors and draw upon 47,686 clinical samples. The web server is available at https://www.cbioprofiler.com/ and https://cbioprofiler.znhospital.cn/CBioProfiler/, and the standalone app and source code can be found at https://github.com/liuxiaoping2020/CBioProfiler.

Perioperative blood transfusions associated with reduced survival in gastroesophageal cancers – A Swedish population-based study

BackgroundBlood transfusion has been associated with decreased long-term survival in cancer patients, possibly due to various immunological factors. We aimed to evaluate if perioperative transfusions decrease survival in patients who undergo resection for esophageal or gastric cancer and to identify factors associated with such events. MethodsA population-based cohort study was conducted based on the Swedish National Registry for Esophageal and Gastric Cancer, which prospectively collects clinical data of patients with these tumors. Almost all patients (96 %) resected for esophageal or gastric cancer in Sweden between 2017 and 2022 were included. Survival data were acquired from the Swedish Cause of Death Registry. Multivariable Cox regression was used to calculate hazard ratios (HR) with 95 % confidence intervals (CI), adjusted for age, fitness, neoadjuvant therapy, surgical access, and pathological TNM stage. ResultsOf all 1365 patients, 227 (17 %) received perioperative transfusions. Transfusion was associated with an increased risk of all-cause mortality within 3 years of surgery (adjusted HR 1.50, 95 % CI 1.17–1.91). To exclude the influence of surgery-related postoperative complications, a sensitivity analysis was performed excluding patients who died within 30 days of resection and the negative impact of transfusions on 3-year mortality remained (adjusted HR 1.30, 95 % CI 1.01–1.68). Increasing age, open surgery, esophagectomy, perioperative bleeding, and nodal tumor involvement were all associated with an increased likelihood of receiving transfusions. ConclusionPerioperative blood transfusions might have a negative impact on 3-year survival in patients who undergo surgery for esophageal or gastric cancer.

Lymphopenia associated with whole-brain radiotherapy and its effects on clinical outcomes of patients with brain metastases

There is increasing awareness of radiotherapy’s potential side effects, such as lymphopenia. Therefore, this study aimed to establish the association between WBRT and the development of lymphopenia in patients with brain metastases undergoing brain radiotherapy (RT), along with evaluating the corresponding clinical outcomes. Including 116 patients with brain metastases undergoing brain radiotherapy, the study collected the absolute lymphocyte counts (ALC) within 2 weeks before brain radiotherapy (pre-radiotherapy, pre-RT), as well as ones at 1 and 2 months after completing RT (post-RT). Univariate and multivariate analyses were performed to identify associations between radiation modality and post-RT ALC. The relationships between post-RT ALC and overall survival were evaluated with Kaplan–Meier analysis and a multivariate Cox regression model. The median ALC definitely decreased at 1 month post-RT, but at 2 months post-RT, gradually rose but not to the pre-RT ALC. The multivariate analysis identified WBRT and lower pre-RT ALC as independent risk factors associated with the decrease in post-RT ALC at 1 month. It also revealed more than 4 brain metastases, G3-4 lymphopenia at 1 month and lower post-RT ALC at 2 months exhibited significantly worse prognosis regardless of the radiation modality. However, there was indeed an independent correlation between radiation modality and the outcome of intracranial progression-free survival (PFS). To approach the feasibility and reasonableness of treatment, clinicians should carefully consider various factors to achieve long-term survival of patients.

Unveiling the mysteries of HER2-low expression in breast cancer: pathological response, prognosis, and expression level alterations

BackgroundThe novel anti-HER2 antibody drug conjugates (ADCs) can effectively improve the long-term survival of patients with HER2-low expression breast cancer. However, pathological responses to neoadjuvant therapy (NAT) within HER2-low expression breast cancer, the relationship between pathological response and prognosis and the transformation of HER2 status are all now poorly understood.MethodsThe patients with HER2-0 and HER2-low expression breast cancer receiving NAT at Harbin Medical University Cancer Hospital between Jan. 2014 and Nov. 2018 were retrospectively explored. HER2 low expression refers to the IHC 1 + or 2 + and FISH negative. The Kappa test was utilized for analyzing the consistency rate of HER2 expression. To evaluate disease-free survival (DFS) and overall survival (OS), this research employed both the Kaplan-Meier analysis and the Cox regression.ResultsIn this study, 178 patients with HER2-0 and 344 patients with HER2-low expression breast cancer were included. In comparison with the HER2-0 group, it is shown that patients in the HER2-low group have more possibility to be younger compared to those 50 years old (P < 0.014), have more premenopausal patients (P < 0.001), a higher proportion of hormone receptor (HR) positive patients (P < 0.001), and less proportion of stage III V patients (P < 0.034). When NAT was finished, the pCR rate became 23.6% in the HER2-0 group while 22.1% in the HER2-low group, and there was also a higher pCR rate in HR- patients in comparison with that in HR + patients (P < 0.01). Considering HER2 expression inconsistency, the overall HER2 inconsistency rate was 30.4% (Kappa = 0.431, P < 0.01). Among patients initially diagnosed as HER2-0, 34% (N = 61) were re-diagnosed as HER2-low after NAT. After stratification by HR expression status, HR+/HER2-0 patients transformed to HER2-low after NAT in 37%, and 32% of HR- patients changed from HER2-0 to HER2-low. In this survival analysis, there were both better DFS rates (P = 0.009) and OS rates (P = 0.026) in the HR-/HER2-low patients in comparison with the HR-/HER2-0 patients, while the HER2-0 and HER2-low patients in the HR + group had no significant survival difference. Additionally, for non-pCR patients, there was better DFS (P = 0.029) and OS (P = 0.038) in the HER2-low group in comparison with that of the HER2-0 group, while no significant survival difference exists between pCR patients.ConclusionAfter HR stratification, there are unique clinical characteristics and prognostic outcomes in HER2-low expression breast cancer, which indicates the potential to become a specific molecular subtype of breast cancer. The significant instability of HER2-low expression status between primary tumor and residual invasive disease suggests that multiple detections of HER2 status should be emphasized in NAT strategies.

Impact of sex on clinical outcomes according to immunologic risk in spousal donor kidney transplantation.

The aim of this study is to investigate the impact of sex on the clinical outcomes of spousal donor kidney transplantation. We analyzed 456 spousal donor kidney transplantation recipients and categorized them into standard or high immunological risk groups according to panel-reactive antibody ≥50% or less. There were 366 recipients in the standard-risk group and 89 recipients in the high-risk group. When comparing biopsy-proven allograft rejection within 1 year from kidney transplantation, husband-to-wife recipients showed significantly higher incidence than wife-to-husband recipients in the high-risk group. By contrast, there was no significant difference between wife-to-husband and husband-to-wife recipients in the standard-risk group. Allograft function recovery was better in husband-to-wife recipients than in wife-to-husband recipients in each group, while husband-to-wife recipients in the high-risk group showed a more rapid decline than other recipients. The long-term patient and allograft survival rates showed no difference between husband-to-wife recipients and wife-to-husband recipients within the same groups. The husband-to-wife recipients with high immunological risk showed a higher risk of biopsy-proven allograft rejection compared to wife-to-husband recipients, so careful monitoring and management may be required.

The Fate of the Aorta after Coarctation Repair: Open Surgical Replacement of Descending Aorta in a High-Volume Unit.

Objectives: Complications after aortic coarctation repair are associated with high mortality and require surgical or endovascular reintervention. For patients unsuitable for endovascular therapies, reoperation remains the only therapeutic option. However, surgical experience and up-to-date follow-up data concerning this overall rare entity in the spectrum of aortic reoperations are still highly limited. Thus, the aim of this study was to analyze the short-term outcomes and long-term survival of patients undergoing surgical descending aorta repair after previous coarctation repair in a high-volume unit. Methods: We present a retrospective single-center analysis of 25 patients who underwent open descending aorta replacement after initial coarctation repair. The surgical history, concomitant cardiovascular malformations, and preoperative characteristics as well as postoperative complications and long-term survival were analyzed. Results: The mean age at operation was 45.4 ± 12.8 years. A proportion of 68% (n = 17) of the patients were male. The most common complication necessitating reoperation after coarctation repair was aneurysm formation (68%) and re-stenosis (16%). The average time between initial repair and reoperation was 26.3 ± 9.9 years. Technical success was achieved in all the operations, while recurrent nerve damage (24%) and bleeding requiring rethoracotomy (20%) were identified as the most common perioperative complications. The one-year mortality was 0% and the overall long-term survival was 88% at 15 years. Conclusions: Open surgical descending aorta replacement can be performed safely and with excellent survival outcomes even in the challenging subgroup of patients after previous coarctation repair. Thus, reoperation should be considered a feasible approach for patients who are unsuitable for endovascular therapies. Nonetheless, concomitant cardiovascular anomalies and frequent preoperations may complicate the redo operation in this patient population.

Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer: reconstructed patient-level meta-analysis of randomized clinical trials.

Neoadjuvant treatment has shown promising results in patients with borderline resectable pancreatic ductal adenocarcinoma. The potential benefits of neoadjuvant treatment on long-term overall survival in patients with resectable pancreatic ductal adenocarcinoma have not yet been established. The aim of this study was to compare long-term overall survival of patients with resectable pancreatic ductal adenocarcinoma based on whether they received neoadjuvant treatment or underwent upfront surgery. A systematic review including randomized clinical trials on the overall survival outcomes between neoadjuvant treatment and upfront surgery in patients with resectable pancreatic ductal adenocarcinoma was conducted up to 1 August 2023 from PubMed, MEDLINE and Web of Science databases. Patient-level survival data was extracted and reconstructed from available Kaplan-Meier curves. A frequentist one-stage meta-analysis was employed, using Cox-based models and a non-parametric method (restricted mean survival time), to assess the difference in overall survival between groups. A Bayesian meta-analysis was also conducted. Five randomized clinical trials comprising 625 patients were included. Among patients with resectable pancreatic ductal adenocarcinoma, neoadjuvant treatment was not significantly associated with a reduction in the hazard of death compared with upfront surgery (shared frailty HR 0.88, 95% c.i. 0.72 to 1.08, P = 0.223); this result was consistent in the non-parametric restricted mean survival time model (+2.41 months, 95% c.i. -1.22 to 6.04, P < 0.194), in the sensitivity analysis that excluded randomized clinical trials with a high risk of bias (shared frailty HR 0.91 (95% c.i. 0.72 to 1.15; P = 0.424)) and in the Bayesian analysis with a posterior shared frailty HR of 0.86 (95% c.i. 0.70 to 1.05). Neoadjuvant treatment does not demonstrate a survival advantage over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma.

Clinical features and surgical strategy of retroperitoneal liposarcoma involving the kidney capsule: a retrospective comparative cohort study.

Valid and generalizable data on the clinical features and surgical strategies for retroperitoneal liposarcoma (LPS) involving the kidney capsule remain scarce. This study aimed to investigate the clinical characteristics, morbidity, mortality, and long-term survival of patients with retroperitoneal LPS involving the kidney capsule. The authors analyzed a prospectively maintained database of patients who underwent surgical resection for retroperitoneal LPS between 2015 and 2020. The patients were categorized into kidney capsule or no kidney capsule groups based on the presence or absence of kidney capsule involvement. A kidney-sparing strategy for retroperitoneal LPS involving the kidney capsule was developed. The primary outcome measure was overall survival (OS). The cumulative event probability curve was estimated using the Kaplan-Meier, and differences between groups using the Log-Rank. The study population consisted of 128 patients-54 with and 74 without kidney capsule involvement. Of these patients, 70 were female (54.7%) and 58 were male (45.3%), with a median age of 55. The median follow-up duration was 35 months. Postoperative morbidity, mortality, length of hospital stay, length of ICU stay, OS, and recurrence-free survival (RFS) did not differ significantly between the groups. Eleven patients developed postoperative acute kidney injury (AKI), and one patient required dialysis during the follow-up period. In multivariable logistic regression analysis, only nephrectomy was independently associated with postoperative AKI. Subgroup analysis of patients with kidney capsule involvement showed that nephrectomy did not improve OS or RFS but significantly decreased postoperative estimated glomerular filtration rate. Nephrectomy was associated with an increased risk of postoperative AKI after retroperitoneal LPS resection. A kidney-sparing strategy for retroperitoneal LPS involving the kidney capsule achieved optimal clinical outcomes.

555. SUPRACLAVICULAR NODE INVOLVEMENT, A NODAL OR METASTATIC DISEASE? - A 10-YEAR EXPERIENCE IN ESOPHAGEAL CARCINOMA AT A TERTIARY REFERRAL CENTRE

Abstract Background Despite the advance in neoadjuvant chemothepray/chemoradiotherapy and favourable outcomes of surgical management in supraclavicular lymph node (SCLN) involvement reported in recent studies, the latest AJCC/UICC TMN classification still regards SCLN metastasis as extra-regional i.e Stage IVB (M1) disease. The role of SCLN dissection and surgical management remain controversial. At National University Hospital of the present study, bilateral supraclavicular lymphadenectomy is routinely performed for resectable thoracic ESCC. The aim of this retrospective cohort study is to investigate the long-term outcome of surgical management in pathological SCLN metastasis and its survival benefit comparing to Stage IIB-IVA diseases. Methods Patients with ESCC who underwent esophagectomy and 3-field lymphadenectomy with curative intent between January 2013 and January 2023 at the single centre were included; cases of salvage esophagectomy post-definitive concurrent chemoradiotherapy, palliative resections, and concurrent head and neck cancers were excluded. Neoadjuvant treatments were considered in cases staged clinically as T2 and/or N1 or greater. Pathological status of lymph nodes was recorded according to JES classification. Demographics and prognostic factors were examined using univariant analysis of overall survival (OS). Patients with SCLN metastases and other LN involvements were compared and OS were analysed using Kaplan-Meier method. Results 544 patients were included. 183 had one or more pathological LN metastasis (pN1:126, pN2 46, and PN3: 11) in which 55 patients had SCLN metastasis. Patients with LN metastasis had poorer prognosis than those without (pN0) with a Hazard Ratio (HR) of 2.68 (95% CI, 1.12-3.40, p&amp;lt;0.01); similar pattern was seen in patients with SCLN metastasis (HR 2.28, p&amp;lt;0.01). The 3-year and 5-year OS of patients with SCLN metastasis was 18.5% and 11.6% respectively whereas those of other LN metastasis was 21.4% and 15.8%; the difference between the groups was not statistically significant (p=0.525) (graph 1). Conclusion Lymph node status (pN) is a well-recognised prognostic factor as reaffirmed, however, within the pN positive cohort, long-term survival of patients with SCLN metastasis, considered as stage IVB (M1), was comparable (p&amp;lt;0.05) to those with other LN metastases. This supports the survival benefit of surgical resection with neoadjuvant therapy in SCLN metastases as following nodal disease treatment algorithm; further evaluation including systemic therapy and lymph node sub-group analysis is being conducted. Whilst randomised controlled trials such as Japanese JCOG2013 provides level I evidence, the present study provides complementary real-world experience for SCLN dissection.

Prognostic value of Glasgow Prognostic Score and its modified scores on 5-year outcome in patients with coronary heart disease undergoing percutaneous coronary intervention

BackgroundGlasgow Prognostic Score (GPS) and its modified counterparts, including the modified GPS (mGPS) and hsCRP-modified GPS (hs-mGPS), are widely used inflammatory indices in clinical settings. Inflammation has gained increased attention in the context of coronary heart disease (CHD); however, its long-term predictive value in patients with CHD remains uncertain. ObjectiveThis study aimed to assess the predictive values of GPS, mGPS, and hs-mGPS for long-term survival in patients following percutaneous coronary intervention (PCI). MethodsConsecutive 10,724 PCI patients were enrolled in 2013. The primary endpoint was 5-year all-cause death. ResultsThis study included 8,909 patients. Individuals with high GPS, mGPS, and hs-mGPS scores exhibited a significantly higher risk of all-cause death compared to those with low scores (all P < 0.05). All three indices (GPS, mGPS, and hs-mGPS) demonstrated predictive values for all-cause death, albeit with relatively low area under the curve values of 0.534, 0.522, and 0.545, respectively. Furthermore, we refined the hs-mGPS using cutoffs (hsCRP at 2 mg/L and albumin at 40 g/L) which are better suited for these patients, to establish the CHD-hs-mGPS. This modification significantly improved the prediction of all-cause death, outperformed the mGPS and demonstrated numerical superiority over both the GPS and hs-mGPS. Notably, only CHD-hs-mGPS exhibited a predictive value for both the ACS and non-ACS subgroups. ConclusionIn patients with CHD who underwent PCI, GPS, mGPS, and hs-mGPS demonstrated significant long-term predictive values for all-cause death. Our parameter-adjusted score, the CHD-hs-mGPS, is applicable to a broad population and moderately enhances the predictive accuracy, facilitating the early identification of patients at high risk of long-term death.

273. PERIOPERATIVE BLOOD TRANSFUSIONS AND SURVIVAL IN GASTROESOPHAGEAL CANCERS – A SWEDISH POPULATION-BASED STUDY

Abstract Background Blood transfusions have been associated with decreased long-term survival in cancer patients, possibly due to immunological factors. This cohort study aimed to investigate associations, if any, between perioperative transfusions and survival in gastroesophageal cancer patients. Methods A population-based cohort study was conducted based on the National Registry for Esophageal and Gastric cancer (NREV), which harbors clinical data including given transfusions. All patients resected for esophageal or gastric cancer in Sweden, between 2017 and 2022, were included and their survival was acquired from the Swedish Cause of Death Registry. Multivariable Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders (age, American Society of Anesthesiologist class, access of surgery and pathological TNM stage) Results Of 1,368 patients, 227 patients (17%) received perioperative transfusions. Transfusion was associated with an increased risk of all-cause mortality within 3 years of surgery (HR 1.48 95% CI 1.17-1.91). Kaplan-Meier curves depicted worse crude survival in patients having received peroperative transfusion (Figure 1). To exclude the effects of surgery-related postoperative complications on short-term mortality, a sensitivity analysis was performed, excluding patients who died within 30 days of resection, and found that the impact of transfusions on survival remained. Conclusion Perioperative blood transfusions might have a negative impact on survival in patients who undergo gastroesophageal cancer surgery.

Exploration of Key Genes Combining with Immune Infiltration Level andTumor Mutational Burden in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a lethal malignancy due to its heterogeneity and aggressive behavior. Recently, somatic mutations and tumor cell interactions with the surrounding tumor immune microenvironment (TIME) have been reported to participate in HCC carcinogenesis and predict HCC progression. In this study, we aimed to investigate the association between tumor mutational burden (TMB) and TIME in HCC. Additionally, we sought to identify differentially expressed genes (DEGs) associated with HCC prognosis and progression. The expression, clinical, and mutational data were downloaded from the cancer genome atlas (TCGA) database. The immune infiltration levels and TMB levels of the HCC samples were estimated and the samples were divided into immune cluster (ICR)-1 and 2 based on immune infiltration score and high and low TMB groups based on TMB score. Thereafter, differential gene expression analysis was conducted to identify the DEGs in the ICR1/2 and high/low TMB groups, and the intersecting DEGs were selected. Thereafter, Cox regression analysis was performed on 89 significant DEGs, among which 19 were associated with prognosis. These 19 DEGs were then used to construct a prognostic model based on their expression levels and regression coefficients. Thereafter, we analyzed the DEGs in mutant and wildtype TP53 HCC samples and identified high BCL10 and TRAF3 expression in the mutant TP53 samples. BCL10 and TRAF3 expression was detected by real-time quantitative reverse transcription PCR and immunohistochemistry, and their clinical correlation, biological function, and immune infiltration levels were analyzed by chi-square analyses, Gene Set Enrichment Analysis (GSEA), and "ssGSEA", respectively. The results of our study revealed that immune infiltration level was correlated with TMB and that they synergistically predicted poor prognosis of HCC patients. DEGs enriched in immune-related pathways could serve as indicators of immunotherapy response in HCC. Among these DEGs, BCL10 and TRAF3 were highly expressed in HCC tissues, especially in the mutant TP53 group, and they co-operatively exhibited immunological function, thereby affecting HCC progression and prognosis. In this study, we identified BCL10 and TRAF3 as potential prognostic indicators in HCC patients. Additionally, we found that BCL10 and TRAF3 influence TMB and TIME in HCC patients and can be used for the development of immune-based therapies for improving the long-term survival of HCC patients.