5-year Patient Survival Research Articles

Circulating Tumor HPV DNA in Patients With Stage I and II HPV-Associated Head and Neck Cancer After Surgery

This cohort study examines the association of posttreatment circulating tumor human papillomavirus DNA (ctHPVDNA) with residual disease and 2-year overall survival and recurrence-free survival in patients with HPV-associated head and neck cancer.

Kidney transplant utilising donors after circulatory death: The first report from the African continent.

At Groote Schuur Hospital in Cape Town, South Africa, the number of deceased organ donors has declined over the past 2 decades, necessitating a more liberal approach to donor selection. In 2007, measures to expand the deceased kidney donor pool were implemented, including an HIV positive-to-positive transplant programme and the utilisation of extended-criteria donors as well as donors after circulatory death (DCDs). To report on our institutional experience with DCD kidney transplants and to encourage this approach among other African centres to improve access to transplantation. An observational cohort study of consecutive DCD kidney transplants at Groote Schuur Hospital over a 17-year period was performed. Primary endpoints were 1-, 2- and 5-year graft and patient survival. Secondary endpoints included the incidence of delayed graft function (DGF), 30-day morbidity, length of stay, and donor and recipient clinical characteristics. Fifteen DCD procurements were performed, with no kidneys discarded. Thirty kidney transplants were performed, with a median (interquartile range) cold ischaemic time of 11.5 (8 - 14) hours. The incidence of DGF was 60.0%, and 30-day morbidity (other than DGF) was 20.0%. Graft survival at 1, 2 and 5 years was 100%, 96.0% and 73.7%, respectively. Patient survival at 1, 2 and 5 years was 93.3%, 93.3% and 88.4%, respectively. Long-term graft and patient survival was comparable with the international literature. DCD may present a unique opportunity to expand deceased donation throughout Africa, particularly in areas affected by a lack of brain death legislation and religious or cultural objections to donation after brain death.

Referrals for proliferative diabetic retinopathy from two UK diabetic retinopathy screening services: a 10-year analysis of visual outcomes, requirement for vitrectomy, and mortality

Background/objectivesTo determine long-term outcomes of patients referred with proliferative diabetic retinopathy (PDR) from diabetic eye screening programmes (DESP) to tertiary care centres in the United Kingdom (UK).MethodsRetrospective multicentre study of patients referred from two DESPs in the UK over a 36-month period (2007–9) and followed-up for 10 years. Critical outcomes included severe vision loss (SVL) and the need for vitrectomy. Other outcomes assessed included moderate vision loss (MVL), and patient survival time. Univariate and multiple variable Cox proportional hazards regressions were used to analyse survival outcomes.Results212 eyes of 150 patients were referred with a diagnosis of PDR. 109 eyes of 72 patients were confirmed to have active PDR and included in the study. 61% of patients had low-risk PDR, while 39% exhibited high-risk features in at least one eye. Eight (7.3%) eyes developed SVL and 16 (14.7%) MVL during follow up. Vitrectomy was required in 24% (95% CI: 15 to 31%) of all PDR eyes and was most commonly performed for vitreous haemorrhage (65%). The 10-year survival in all PDR patients was 76% (95% CI: 63 to 85%) with the mean time to death for all deceased patients being 5.4 ± 3.6 years.On multivariable analysis, only age was found to have a significant association with the survival of patients with PDR.ConclusionsDuring the 10 year follow up SVL was uncommon, but MVL occurred in almost one-fifth of the eyes. Approximately 1 in 4 eyes required vitrectomy, highlighting its significance in patient management.

Results of patient survival after surgical interventions for complicated forms of colon cancer performed in general surgical hospitals

The aim of the study: to evaluate the 1- and 3-year survival of patients operated for complicated forms of colon cancer (СC) in general surgical hospital. Materials and methods. The study group included 71 (100 %) patients with complicated forms of СС. Acute intestinal obstruction was detected in 49 (69.1 %) patients, tumor perforation – in 13 (18.3 %), acute colonic bleeding – in 3 (4.2 %) patients, a combination of acute intestinal obstruction with tumor perforation – in 4 (5.6 %) and intestinal obstruction with bleeding – in 2 (2.8 %) operated patients. Radical operations were performed in 48 (67.6 %) patients, palliative operations – in 18 (25.4 %), symptomatic operations – in 5 (7.0 %) patients. II stage of the disease was diagnosed in 15 (21.1 %), III stage – in 32 (45.1 %), IV stage – in 24 (33.8 %) operated patients. 19 (30.2 %) patients underwent specific chemotherapy after surgery. Results. Among patients with the II stage of the oncological process 1-year survival was 76.9 ± 11.7 %, 3-year – 53.8 ± 13.8 %; with stage III, 1-year survival was 65.6 ± 8.4 %, 3-year – 50.0 ± 8.8 %; in persons with IV stage of СC – 29.2 ± 9.3 % and 8.3 ± 2.6 % respectively (χ2 = 21.8, p = 0.0001). Among male patients, 1-year survival was 51.4 ± 8.5 %, 3-year – 31.4 ± 7.9 %; women – 61.1 ± 8.1 % and 44.4 ± 8.3 %, respectively (χ2 = 2.3, p = 0.1302). Better indicators were found in the case of cancer of the left sections of the large intestine than the right sections – the 1-year survival rate was 60.4 ± 7.1 % and 43.5 ± 10.3 % respectively; 3-year – 39.6 ± 7.1 % and 30.4 ± 9.6 % (χ2 = 0.74, p = 0.3906). Conclusions. The conducted analysis indicates a clear dependence of the survival results on the stage of the disease, gender and localization of the tumor process.

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8months was mandatory for patients with intermediate or high-risk prostate cancer. From 20 institutions, 134 patients enrolled. The median follow-up was 5.16years (range, 1.43-6.47years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

The effectiveness of CA125 and HE4 as clinical prognostic markers in epithelial ovarian cancer patients with BRCA mutation.

To investigate the efficacy of cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting survival outcomes based on breast cancer gene (BRCA) mutational status in epithelial ovarian cancer. Medical records of 448 patients diagnosed with epithelial ovarian cancer at a single tertiary institution in Korea were retrospectively analyzed. Area under the curve, sensitivity, specificity, and accuracy were assessed using the CA125 and HE4 values after surgery and 3 cycles of chemotherapy to predict 1-year survival based on the BRCA mutational status. Kaplan-Meier analysis was used to obtain progression-free and overall survival to evaluate CA125 and HE4 effectiveness in predicting survival outcomes. A total of 423 patients were analyzed, including 180 (42.6%) who underwent interval debulking surgery (IDS) and 243 (57.4%) who underwent primary debulking surgery (PDS). BRCA mutations were observed in 37 (15.2%) and 44 (22.4%) patients in the PDS and IDS groups, respectively. CA125 and HE4 normalization demonstrated the highest specificity in patients with or without BRCA mutations, with specificities of 97.1% and 99.1% in the PDS group and 78.6% and 86.2% in the IDS group, respectively. Normalizing HE4 alone may be an effective prognostic marker, with an area under the curve of 0.774 and specificity of 75.0%, in patients with BRCA mutations. Normalizing both biomarkers emerged as the most effective predictive marker for the 1-year recurrence rate, regardless of BRCA mutational status. A negative HE4 value can be a useful predictor for 1-year recurrence-free survival in patients with BRCA mutations.

Elective Neck Dissection in cT1-4 N0M0 Head and Neck Basaloid Carcinoma.

To investigate the survival benefit of elective neck dissection (END) over neck observation in surgically resected cT1-4 N0M0 head and neck basaloid carcinoma (HNBC). Retrospective cohort study. The 2006 to 2017 hospital-based National Cancer Database. Patients with surgically resected cT1-4 N0M0 HNBC were selected. Linear, binary logistic, Kaplan-Meier, and Cox proportional hazards regression models were implemented. Of 857 patients satisfying inclusion criteria, the majority were male (77.0%) and white (88.1%) with disease of the oral cavity (21.5%) or oropharynx (42.9%) classified as high grade (76.9%) and cT1-2 (72.9%). 389 (45.4%) patients underwent END. END utilization between 2006 and 2017 increased for cT1-2 disease (33.3% vs56.9%, R2 = .699) but remained relatively constant for cT3-4 disease (66.7% vs57.9%, R2 = .062). One-hundred and fifteen(29.6%) ENDs detected occult nodal metastases (ONMs). The 5-year overall survival (OS) of patients undergoing neck observation and END was 65.6% and 66.8%, respectively (P = .652). END was not associated with improved OS in survival analyses stratified by patient demographics, clinicopathologic features, and adjuvant therapy. Compared with surgery alone, adjuvant radiotherapy (adjusted hazard ratio: 0.74, 95% confidence interval [CI]: 0.57-0.97, P = .031) was associated with improved OS. END (hazard ratio [HR]: 0.96, 95% CI: 0.71-1.28, P = .770) and ONM (HR: 1.12, 95% CI: 0.78-1.61, P = .551) were not associated with OS. END is performed in nearly half of patients with HNBC but is not associated with improved OS, even after stratifying survival analyses by patient demographics, clinicopathologic features, and adjuvant therapy. The rate of ONM approaching 30%, however, justifies inclusion of END in the surgical management of HNBC.

Construction and analysis of competitive endogenous RNA networks and prognostic models associated with ovarian cancer based on the exoRBase database.

To construct a competitive endogenous RNA (ceRNA) regulatory network in blood exosomes of patients with ovarian cancer (OC) using bioinformatics and explore its pathogenesis. The exoRbase2.0 database was used to download blood exosome gene sequencing data from patients OC and normal controls and the expression profiles of exosomal mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) were detected independently using R language for differential expression analysis. TargetScan and miRanda databases were combined for the prediction and differential expression of mRNA-binding microRNAs (miRNA). The miRcode and starBase databases were used to predict miRNAs that bind to differentially expressed lncRNAs and circRNAs repectively. The relevant mRNA, circRNA, lncRNA and their corresponding miRNA prediction data were imported into Cytoscape software for visualization of the ceRNA network. The R language and KEGG Orthology-based Annotation System (KOBAS) were used to execute and illustrate the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hub genes were identified using The CytoHubba plugin. Thirty-one differentially expressed mRNAs, 17 differentially expressed lncRNAs, and 24 differentially expressed circRNAs were screened. Cytoscape software was used to construct the ceRNA network with nine mRNA nodes, two lncRNA nodes, eight circRNA nodes, and 51 miRNA nodes. Both GO and KEGG were focused on the Spliceosome pathway, indicating that spliceosomes are closely linked with the development of OC, while heterogenous nuclear ribonucleoprotein K and RNA binding motif protein X-linked genes were the top 10 score Hub genes screened by Cytoscape software, including two lncRNAs, four mRNAs, and four circRNAs. In patients with OC, the expression of eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), SERPINE 1 mRNA binding protein 1 (SERBP1), ribosomal protein L15 (RPL15) and human leukocyte antigen complex P5 (HCP5) was significantly higher whereas that of testis expressed transcript, Y-linked 15 and DEAD-box helicase 3 Y-linked genes was lower compared to normal controls Immunocorrelation scores revealed that SERBP1 was significantly and negatively correlated with endothelial cells and CD4+ T cells and positively correlated with natural killer (NK) cells and macrophages, respectively; RPL15 was significantly positively correlated with macrophages and endothelial cells and negatively correlated with CD8+ T cells and uncharacterized cells, respectively. EIF4G2 was significantly and negatively correlated with endothelial cells and CD4+ T cells, and positively correlated with uncharacterized cells, respectively. Based on the survival data and the significant correlation characteristics derived from the multifactorial Cox analysis (P < 0.05), the survival prediction curves demonstrated that the prognostic factors associated with 3-year survival in patients with OC were The prognostic factors associated with survival were Macrophage, RPL15. This study successfully constructs a ceRNA regulatory network in blood exosomes of OV patients, which provides the specific targets for diagnosis and treatment of OC.

Moderate and Severe Chronic Kidney Disease Predict Greater 5-Year Mortality following Major Lower-Extremity Amputation

Severe Chronic Kidney Disease (CKD) predicts greater mortality after major lower extremity amputation (LEA), but it remains poorly understood whether patients with earlier stages of CKD share similar risk. We assessed long-term postoperative outcomes for patients with CKD in a retrospective chart review of 565 patients who underwent atraumatic major LEA at a large tertiary referral center from 2015 to 2021. We stratified patients by renal function and compared outcomes including survival. Preoperative CKD diagnosis was related to many patient characteristics, co-occurred with many comorbidities, and was associated with less follow-up and survival. Kaplan-Meier and Cox Regression analyses showed significantly worse 5-year survival for major LEA patients with mild, moderate, or severe CKD compared to major LEA patients with no history of CKD at the time of amputation (P < 0.001). Severe CKD independently predicted worse mortality at 1-year (odds ratio [OR] 2.91; P = 0.003) and 5-years (OR 3.08; P < 0.001). Moderate CKD independently predicted worse 5-year mortality (OR 2.66; P = 0.029). This study demonstrates that moderate and severe CKD predict greater long-term mortality following major LEA when controlling for numerous potential confounders. This finding raises questions about the underlying mechanism if causal and highlights an opportunity to improve outcomes with earlier recognition and optimization CKD preoperatively.

Impact of the COVID-19 pandemic on lymphoma incidence and short-term survival - a Swedish Lymphoma Register Study.

The COVID-19 pandemic posed a large challenge for healthcare systems across the world. Comprehensive data on the impact of the COVID-19 pandemic on incidence and mortality in lymphoma are lacking. Using data from the Swedish lymphoma register, we compare incidence and 1-year survival of lymphoma patients in Sweden before (2017-2019) and during the pandemic (2020 and 2021). Fewer patients were diagnosed with lymphomas during March-June 2020, but the annual incidence rates for 2020 and 2021 were similar to those of 2017-2019. A larger proportion of patients presented with stage IV disease during 2021. There were no differences in other base-line characteristics nor application of active treatment in pre-pandemic and pandemic years. One-year overall survival was not inferior among lymphoma patients during the pandemic years compared to pre-pandemic years i.e., 2017-2019. The COVID-19 pandemic had limited impact on the incidence and mortality of lymphoma in Sweden.

HSPA4 upregulation induces immune evasion via ALKBH5/CD58 axis in gastric cancer

IntroductionGastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Recently, targeted therapies including PD1 (programmed cell death 1) antibodies have been used in advanced GC patients. However, identifying new biomarker for immunotherapy is still urgently needed. The objective of this study is to unveil the immune evasion mechanism of GC cells and identify new biomarkers for immune checkpoint blockade therapy in patients with GC.MethodsCoimmunoprecipitation and meRIP were performed to investigate the mechanism of immune evasion of GC cells. Cocuture system was established to evaluate the cytotoxicity of cocultured CD8+ T cells. The clinical significance of HSPA4 upregulation was analyzed by multiplex fluorescent immunohistochemistry staining in GC tumor tissues.ResultsHistone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. The cytotoxicity of CD8+ T cells are impaired and PD1/PDL1 axis is activated when CD8+ T cells are cocultured with HSPA4 overexpressed GC cells. HSPA4 upregulation is associated with worse 5-year overall survival of GC patients receiving only surgery. It is an independent prognosis factor for worse survival of GC patients. In GC patients receiving the combined chemotherapy with anti-PD1 immunotherapy, HSPA4 upregulation is observed in responders compared with non-responders.ConclusionHSPA4 upregulation causes the decrease of CD58 in GC cells via HSPA4/ALKBH5/CD58 axis, followed by PD1/PDL1 activation and impairment of CD8+ T cell’s cytotoxicity, finally induces immune evasion of GC cells. HSPA4 upregulation is associated with worse overall survival of GC patients with only surgery. Meanwhile, HSPA4 upregulation predicts for better response in GC patients receiving the combined immunotherapy.

THE INFLUENCE OF DIABETES-ASSOCIATED FACTORS OF ONCOGENESIS ON THE RISK OF BREAST AND ENDOMETRIAL CANCER AND ON THE SURVIVAL OF WOMEN WITH THIS CANCER

Introduction. Patients with type 2 diabetes mellitus (T2D) have an increased risk of cancer of different localizations. Identification and correction of diabetes-associated factors of oncogenesis can be important in cancer prevention.&#x0D; The aim of the study. To investigate the influence of diabetes-associated factors of oncogenesis on the formation of the risk of breast cancer (BC) and endometrial cancer (EC), as well as on the survival of women with the indicated localization of cancer, and to develop a method of calculating the predicted risk of BC and EC in women with T2D.&#x0D; Materials and methods. The study includes the results of a retrospective epidemiological analysis of cancer cases in patients, residents of Ivano-Frankivsk region with T2D during 2012-2016, with an analysis of 5-year survival of patients. Statistical processing of the results was conducted using STATISTIKA-12 (StatSoft Inc., USA). The impact of the pathogenetic factors of T2D on the development of BC and EC was evaluated through multifactorial analysis and ROC-analysis in the Medcalc v.19.1.6 program. The coefficient of predicted cancer risk was determined using mathematical modelling and a logistic regression equation. Kaplan-Meier cumulative survival analysis and Cox-Mantel Test were used to assess patient survival.&#x0D; Results. BC and EC were most often diagnosed in women of postmenopausal age, with obesity, with a duration of T2D &gt; 5 years, on combined antidiabetic therapy. Among women with BC, who take secretagogues 67% had obesity and 24% were overweight, with EC – 54% and 27% respectively. A new method to calculate the predicted risk of BC and EC (Y) in women with T2D has been introduced. The accuracy of the mathematical model for calculating the Y index is 76.24%. It was proved that coefficient Y increases in women with obesity (p&lt;0.001), duration of T2D &gt; 5 years (p&lt;0.001), on combined therapy with non-secretagogues and secretagogues (p&lt;0.05). It was found that T2D increases the risk of death within 1 year in women with both types of cancer (p&lt;0.05). A worse 5-year survival rate was found in women with EC stage I treated with drugs that increase blood insulin levels (p&lt;0.05), as well as in women with EC stage II with HbA1c &gt; 8.0% (p&lt;0.05).&#x0D; Conclusions. Obesity, duration of diabetes &gt; 5 years, and use of secretagogues in obesity increase the risk of breast and endometrial cancer in women with T2D. The use of antidiabetic drugs that contribute to iatrogenic hyperinsulinemia may negatively affect survival in obese women with breast and endometrial cancer, both by increasing the risk of cardiovascular events and by hyperactivating insulin signaling. Decompensation of diabetes reduces the 5-year survival of patients with breast cancer and endometrial cancer. Detection of a predicted high-grade cancer risk (p = 0.7-1.0) may be an indication for correction of factors of oncogenesis and cancer screening in women with T2D.

Abstract LB042: A potent FGFR4-targeted antibody-drug conjugate therapy for patients with rhabdomyosarcoma and other cancers expressing FGFR4

Abstract Background Rhabdomyosarcoma (RMS) is the most common pediatric sarcoma, representing 3-4% of childhood and adolescent cancers. Although multimodal therapies have significantly improved the overall survival of patients with localized disease, 5-year overall survival for patients with relapsed and metastatic disease has remained dismal. Therefore, new therapies are desperately needed for this deadly disease. Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapy drugs to selectively deliver potent anticancer agents to tumor cells while sparing healthy tissues. FGFR4 is a cell-surface receptor tyrosine kinase highly expressed in RMS and other human cancers such as hepatocellular carcinoma (HCC) and some breast cancers. It is expressed at much lower levels in normal tissues, making it a promising immune target. We hypothesize that an FGFR4-targeted ADC would have potent activity against RMS and other cancers expressing FGFR4 with minimal toxicity toward normal tissues. Methods We developed high-affinity binders to human FGFR4 and determined their internalization ability in RMS cancer cell lines. Our top candidate 3A11, a murine monoclonal antibody, was conjugated to monomethyl auristatin E (MMAE), a potent cytotoxic agent, using a valine-citrulline-p-aminocarbamate linker (VC-PABC), to generate an FGFR4-targeted ADC (3A11-vc-MMAE). We tested the in-vitro efficacy of 3A11-vc-MMAE against multiple cell lines of RMS, triple-negative breast cancer, HCC, and FGFR4 negative controls using a live-cell analysis system Incucyte. Western blots were performed to validate 3A11-vc-MMAE’s mechanism of action. We finally tested the in vivo efficacy of 3A11-vc-MMAE in subcutaneous xenograft models of a fusion-positive RMS (RH4) and a fusion-negative RMS with an FGFR4 V550L activating mutation (RMS559). Results We showed that 3A11 was internalized by FGFR4-expressing cell lines and trafficked to lysosomes. Cell viability assays demonstrated that 3A11-vc-MMAE selectively killed FGFR4-expressing cells with minimal effect on low or non-expression cells. Western blot confirmed that 3A11-vc-MMAE induced apoptosis specifically in FGFR4-expressing RMS cell lines. Mice treated with one cycle of 3A11-vc-MMAE (3mg/kg twice a week for 2 weeks) demonstrated a significantly increased survival rate of 30% for the RH4 model with a median survival of 43 days for 3A11-vc-MMAE and 23 days for control, vehicle-treated mice (p-value = 0.0038), and 70% for the RMS559 model, with a median survival not reached for of 3A11-vc-MMAE treated compared with 23 days for control mice (p-value &amp;lt; 0.0001). Of note, tumors were eradicated in 4 out of 10 mice bearing RMS559 xenografts. Conclusions and Future Directions Our results demonstrate that the ADC 3A11-vc-MMAE provides a potent and specific precision immunotherapy for rhabdomyosarcoma and other cancers with a high expression of FGFR4, which warrants further development for clinical translation. Citation Format: Meijie Tian, Katrina Jia, Jerry T. Wu, Jun S. Wei, Adam T. Cheuk, Zhongmei Zhang, Eleanor G. Pope, Boris Shor, L. Nathan Tumey, Javed Khan. A potent FGFR4-targeted antibody-drug conjugate therapy for patients with rhabdomyosarcoma and other cancers expressing FGFR4 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB042.

Portal-Mesenteric Vein Resection for Borderline / Locally Advanced Pancreatic Cancer: Over 2.5 year survival in patients with good performance status

Background: Pancreatectomy associated with resection of the involved portal-superior mesenteric vein, preceded by neoadjuvant chemotherapy, for locally advanced (LA) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is being performed in major pancreas referral centers globally, but its universal adoption faces challenges, notably in Greece. This study explores our center’s experience with this particular group of patients. Materials and Methods: Data from 43 consecutive patients undergoing pancreatectomy with superior mesenteric (SMV) and/or portal vein (PV) resection (January 2014 – January 2022) were analysed. Clinicopathologic information, perioperative details, complications, and follow-up through December 2023 were recorded. Statistical analyses employed Stata BE version 18.0. Results: Forty-three patients (28 BR, 15 LA) underwent pancreatectomy with superior mesenteric and/or portal vein resection. Neoadjuvant therapy (NAT) was administered to 60.4%, correlating significantly with smaller tumour size (median: 3 cm vs. 5 cm, p = 0.009), but not with overall survival (24 months vs. 26 months, p = 0.95). Venous wall infiltration was present in 55.8%, with a significant correlation with NAT administration (40% vs. 82.3%, p = 0.006). The extent of resection was substantial, with a median of 27 lymph nodes retrieved, 86% R0 resection rate, and a median length of resected vein segments measuring 3 cm, necessitating interposition grafts in 41.8% of cases. Postoperative mortality was 2.3%, with a median overall survival of 25 months. The two-, three-, and five-year overall survival rates were 51.1%, 31%, and 24.1%, respectively, surpassing established benchmark outcomes. Lower Eastern Cooperative Oncology Group (ECOG) status was significantly associated with longer survival (ECOG-0: 32 months, ECOG-1: 24 months, ECOG-2: 12 months, p = 0.018), emphasising its prognostic importance in this context. Conclusions: This series of portomesenteric resection in BR or LA PDAC demonstrated a median survival of two years, extending to 31 months in patients with good performance status, which meet and often exceed established outcome benchmarks.

The effect of antifibrotic agents on acute respiratory failure in COVID-19 patients: a retrospective cohort study from TriNetX US collaborative networks

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure.MethodsData from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated.ResultsThe antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264–0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant.DiscussionThis study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.

Kidney transplant in pediatric gut transplant recipients - Technical challenges and outcomes.

There is limited data in the literature about pediatric kidney transplant (KT) following gut transplant (GT). The purpose of this study is to highlight the technical challenges and outcomes of KT in pediatric gut recipients who developed kidney failure (KF). A retrospective single-center study of pediatric GT recipients from January 2000 to December 2019 was performed. In total, 14 (7%) out of 206 pediatric GT recipients developed KF and were listed for KT. Ten patients underwent kidney after gut transplant (KAGT), three patients underwent simultaneous kidney and re-do gut transplant (SKAGT), and one patient died on the KT waitlist. 1-, 5-, and 10-year kidney graft survival was 100%, 91%, and 78%, respectively. 1-, 5-, and 10-year GT graft survival was 100%, 77%, and 77%, respectively. 1-, 5-, and 10-year patient survival was 100%, 91%, and 91%, respectively. Despite the technical complexity, KAGT and SKAGT for pediatric GT recipients that develop KF can be performed with favorable outcomes.

Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

TRIM11 expression in non-small cell lung cancer is associated with poor prognosis.

Despite promising results of targeted therapy approaches, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death. Tripartite motif containing 11 (TRIM11) is part of the TRIM family of proteins, playing crucial roles in tumor progression. TRIM11 serves as an oncogene in various cancer types and has been reported to be associated with a poor prognosis. In this study, we aimed to investigate the protein expression of TRIM11 in a large NSCLC cohort and to correlate its expression with comprehensive clinico-pathological data. Immunohistochemical staining of TRIM11 was performed on a European cohort of NSCLC patients (n=275) including 224 adenocarcinomas and 51 squamous cell carcinomas. Protein expression was categorized according to staining intensity as absent, low, moderate and high. To dichotomize samples, absent and low expression was defined as weak and moderate and high expression was defined as high. Results were correlated with clinico-pathological data. TRIM11 was significantly more highly expressed in NSCLC than in normal lung tissue and significantly more highly expressed in squamous cell carcinomas than in adenocarcinomas. We found a significantly worse 5-year overall survival for patients who highly expressed TRIM11 in NSCLC. High TRIM11 expression is linked with a poor prognosis and might serve as a promising novel prognostic biomarker for NSCLC. Its assessment could be implemented in future routine diagnostic workup.

DNMT3A promotes glioma growth and malignancy via TNF-α/NF-κB signaling pathway.

DNMT3A is the main molecule responsible for DNA methylation in cells. DNMT3A affects the progression of inflammation, degenerative diseases, and malignant tumors, and exhibits significant aberrantly expression in tumor tissues. Transcriptome data and relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) datasets. Differential expression analysis and prognostic analysis were conducted based on above statistics. We constructed a clinical prognostic model and identified DNMT3A as an independent prognostic factor to accurately predict patient prognosis. Differential gene enrichment analysis revealed that DNMT3A affects the progression of glioma through multiple pathways, among which the tumor necrosis factor-α (TNF-α)/nuclear factor-kappa B (NF-κB) pathway shows a strong correlation. Immunological analysis also revealed a certain correlation between DNMT3A and tumor immunity. We demonstrated through gene editing that DNMT3A can affect the release of TNF-α in cells, thereby affecting the progression of glioma. Functional experiments have also demonstrated that DNMT3A plays a crucial role in tumors. RNA-sequencing and survival analyses of lower-grade glioma (LGG) patients in TCGA, CGGA, and GEO cohorts showed that high DNMT3A expression correlated with poor prognosis of LGG patients. Univariate and multivariate Cox regression analyses showed that DNMT3A expression was an independent prognostic indicator in LGG. The prognosis prediction nomogram with age, World Health Organization (WHO) grading, and DNMT3A expression showed reliable performance in predicting the 1-, 3-, and 5-year overall survival (OS) of LGG patients. Functional enrichment analysis, gene set enrichment analysis (GSEA), and ESTIMATE algorithm analyses showed that DNMT3A expression was associated with the tumor infiltration of immune cells and predicted response to immunotherapy in two immunotherapy cohorts of pan-cancer patients. Furthermore, short hairpin RNA (shRNA)-mediated knockdown of DNMT3A in the LGG cell lines suppressed proliferation, migration, and invasion of LGG cells by downregulating the TNF-α/NF-κB signaling pathway. Our data showed that DNMT3A was a potential prognostic biomarker in glioma. DNMT3A promoted proliferation and malignancy of LGG cells through the TNF-α/NF-κB signaling pathway. DNMT3A is a promising therapeutic target for treating patients with LGG.

Prescribing Trends of Renin-Angiotensin System Inhibitors and Mortality among Acute Coronary Syndrome Patients: Insights from the Malaysian National Cardiovascular Disease Registry.

Despite guideline recommendations, suboptimal prescription rates of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been observed in patients with acute coronary syndrome. This study aimed to examine the temporal trends, variations, and mortality outcomes among acute coronary syndrome patients prescribed ACEIs/ARBs in the multi-ethnic population of Malaysia. This retrospective study utilized data from the Malaysian National Cardiovascular Disease-Acute Coronary Syndrome registry, encompassing consecutive patient records from 2008 to 2017 (N = 60,854). Ten-year temporal trends of on-discharge ACEIs/ARBs prescription were examined. Demographics, clinical characteristics and 1-year all-cause mortality outcomes were compared between patients prescribed and not prescribed ACEIs/ARBs. The 10-year prescription rate of on-discharge ACEIs/ARBs was 52.8% (n = 32,140), with a significant decline over the years [linear trend test, P = 0.008; SD = 0.03; SE = 0.001; 95% CI = 0.55-0.64]. Patients aged ≥65 years (aOR = 0.79; 95% CI = 0.73-0.86) were less likely to be prescribed ACEIs/ARBs than those aged <65 years. In addition, patients with comorbid diabetes mellitus (DM) (aOR = 0.85; 95% CI = 0.79-0.92) and chronic kidney disease (CKD) (aOR = 0.34; 95% CI = 0.30-0.40) were significantly less likely to receive ACEIs/ARBs. IPW-adjusted survival analysis revealed a 38% lower 1-year all-cause mortality rate in patients prescribed on-discharge ACEIs/ARBs (HR = 0.62; 95% CI = 0.56-0.69; P < 0.001). Acute coronary syndrome patients with concomitant DM and CKD were less likely to receive on-discharge ACEIs/ARBs in Malaysia. Suboptimal prescription rates of ACEIs/ARBs persisted over the 10-year period, despite improved 1-year survival in ACS patients prescribed ACEIs/ARBs.