Overall Survival Rate Of Patients Research Articles

Prognostic value of preoperative D-dimer to albumin ratio in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy

BackgroundThe prognostic value of Albumin and D-dimer has been established for multiple tumor types, indicating their potential for predicting tumor development. Nevertheless, the predictive capability of the DDI-to-albumin ratio (DAR) in locally advanced rectal cancer (LARC) remains uncertain.PurposeThe objective of this study was to investigate the prognostic significance of the DAR in LARC.MethodsA total of 513 patients who underwent neoadjuvant chemoradiotherapy (nCRT) prior to total mesorectal excision (TME) between March 2013 to October 2019 were included in this study. Patients were divided into high-level DAR (> 0.016) or low-level DAR (≤ 0.016) groups based on ROC curve analysis optimum cut-off value. The prognostic value of the DAR in LARC was analyzed.ResultsThe study enrolled 513 patients. Patients were stratified into high-level DAR (> 0.016) and low-level DAR (≤ 0.016) cohorts according to the optimal cut-off value determined by ROC curve analysis. The 5-year overall survival (OS) rates for patients in the low DAR group (≤ 0.016) and the high DAR group (> 0.016) were 89.4% and 80.9%, respectively (p = 0.013). The 5-year disease-free survival (DFS) rates were 85.7% and 77.4% (p = 0.027). Multivariate analyses demonstrated that DAR were independent prognostic factors for OS (p = 0.02) and DFS (0.025). Predictive nomograms that included the DAR score group (C-index: OS-0.743, DFS-0.705) were superior to those without DAR scores (C-index: OS-0.721, DFS-0.697).ConclusionThe DAR demonstrates high usability and prognostic value in predicting OS and DFS outcomes among patients diagnosed with LARC who undergo nCRT.

Sorafenib combined with tarexib for first-line treatment of unresectable hepatocellular carcinoma and its predictive role and correlation with PD-L1 CTCs

BackgroundThis study aims to evaluate the safety efficacy of combining the PD-1 antibody Tirelizumab with Sorafenib in the treatment of advanced hepatocellular carcinoma. Additionally we are committed to investigating the relationship between circulating tumor cell (CTC) counts/PD-L1 expression the prognosis of patients with advanced hepatocellular carcinoma.MethodsThis study included 32 patients with unresectable primary liver cancer who received treatment with Tislelizumab in combination with Sorafenib. Tislelizumab was administered via intravenous injection at a dose of 200 mg every 3 weeks, while Sorafenib was given orally at a dose of 400 mg twice daily. Patients were evaluated every 3 cycles (9 weeks) to assess the safety and efficacy of the treatment regimen. Prior to enrollment, all patients underwent CTC counting and assessment of PD-L1 expression in circulating tumor cells. The primary endpoint was the objective response rate (ORR), evaluated by the investigator according to the RECIST v1.1 criteria. Secondary endpoints aimed to assess the relationship between circulating tumor cell (CTC) counts or programmed death ligand 1 (PD-L1) expression and the prognosis of patients with advanced hepatocellular carcinoma.ResultsAs of November 2022, a total of 32 patients have been enrolled in the study and received combination treatment. Among the 32 patients, 31 (96.8%) tested positive for circulating tumor cells (CTCs), with counts ranging from 1 to 45 and a median of 7 (3, 11). PD-L1-positive CTCs were detected in 25 patients (78.1%). All 32 patients were followed up for 2 to 14 months, with a median follow-up time of 6 months. Correlation analysis revealed that distant metastasis, vascular invasion, and the presence of more than 5 CTCs were significantly associated with PD-L1-positive CTCs. The one-year overall survival rates for patients with PD-L1-positive CTCs and those with PD-L1-negative CTCs were 78.5% vs 64.3% (P = 0.309). Additionally, the one-year overall survival rates for the group with rising CTC counts compared to the group with stable or declining counts were 34.3% vs 90% (P = 0.063).ConclusionThe combination of Tislelizumab and Sorafenib demonstrates promising antitumor activity in the first-line treatment of hepatocellular carcinoma, with a relatively high objective response rate (ORR) and acceptable safety profile. Baseline CTC PD-L1 positivity can serve as a predictive marker for selecting hepatocellular carcinoma patients for PD-1/PD-L1 blockade therapy, and dynamic measurement of CTC changes can be used to monitor treatment efficacy.

Extended pelvic evisceration with lateral wall resection in malignant tumors

Patients with tumor involvement of lateral pelvic sidewall represent a peculiar category and were not assessed as the candidates for curative surgery up until recent years. The aim of the current review of literature is to display the working results of the most experienced surgical oncologists in pelvic surgery. We have analyzed issue-related articles, which were published from 1967 till 2023, considering the free margin status as a key prognostic factor. It is elucidated that R0 resection could be achieved in more than a half cases, 5 year overall survival ran up to 50 %, and postoperative mortality was less than 7 %. The majority of authors described high morbidity though (up to 82 %). Exenteration with laterally extended endopelvic resection could improve overall survival rate in patients with locally advanced pelvic malignancies granting sensible patient selection in expert medical care unit.

Survival trends and conditional survival in patients with pulmonary metastases from differentiated thyroid carcinoma.

Patients with pulmonary metastases from differentiated thyroid carcinoma (DTC) have a significantly poorer prognosis compared to DTC patients without metastases. This study aimed to establish a nomogram combined with dynamic survival analysis to predict the survival probability of patients with pulmonary metastases from differentiated thyroid carcinoma and compensate for the underestimation of survival in patients with very poor prognosis. Patient data were collected from the Surveillance, Epidemiological, and End Result (SEER) data resource from 2010 to 2019. Multivariate analysis was carried out by the Cox proportional hazards regression to construct a nomogram. Receiver operating characteristic (ROC) curves along with calibration were employed to assess the effectiveness of the model.The life table was used to estimate the conditional cancer-specific survival (CSS). In the training set, the AUCs for the CSS nomogram were 0.728, 0.741, and 0.779, with a c-index of 0.682, indicating good predictive performance at 3, 5, and 10 years. In the validation set, the AUCs for the CSS nomogram were 0.706, 0.726, and 0.769, with a c-index of 0.696, while the AUCs for the 8th TNM staging system were 0.521, 0.555, and 0.601, with a c-index of 0.579. The overall 5-year conditional survival rate for patients increased slightly from 63.44 to 70.52%. The survival gap was greatest between patients aged <55 years and those aged ≥55 years. We established a nomogram combined with dynamic survival analysis, which serve as promising options for prognosis estimation, to enhance personalized evaluation of survival risks and provide the basis for the development of more clinical treatment approaches.

Role of molecular alterations in transplantation decisions for patients with primary myelofibrosis

AbstractThe aim of our study was to analyze the potential survival benefit associated with hematopoietic stem cell transplantation (HSCT) according to clinicobiological scores, which incorporate molecular data (MIPSS70 and MIPSS70+V2) to facilitate decision-making in this context. One transplant (n = 241) and 1 nontransplant cohort (n = 239) were used to test the hypothesis that patients with primary myelofibrosis with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference. Weighted Cox proportional hazard models and logistic regression analyses were performed. Overall, 105 patients who did not receive transplant could be matched to the 239 patients who did receive transplants. Mean age in matched patients who did and did not undergo transplant was 55.5 and 57.9 years, respectively. Blood cell count and Dynamic International Prognostic Scoring System (DIPSS) score distribution were similar in both groups. HSCT was associated with a higher 6-year overall survival rate in intermediate-2 (60.1% vs 41.5%) and high-risk DIPSS patients (44.4% vs 6.55%), high-risk MIPSS70 (46.5% vs 23.9%), high-risk (73.2% vs 39.7%) or very high-risk MIPSS70+V2 (51.8% vs 24%). Patients with intermediate MIPSS70 scores have an advantage of survival with HSCT only when their myelofibrosis transplant scoring system (MTSS) were low or intermediate. Patients who received transplant had an increased mortality risk the first year, but a significant benefit with HSCT after the 1-year landmark was observed in higher risk patients. This study confirms that, similar to DIPSS, MIPSS70 and MIPSS70+V2 risk score in addition to MTSS can be used to determine which patients with primary myelofibrosis have survival benefit from HSCT over non-HSCT strategies.

Feasibility of robot-assisted surgery for defining circumferential resection margins for rectal cancer: a retrospective study

BackgroundLocal recurrence is a major problem after surgery for rectal cancer. Precision of the circumferential resection margin (CRM) has been shown to be an independent predictor of local recurrence. The purpose of this study is to evaluate the usefulness of robotic surgery for defining the CRM.MethodsA retrospective cohort study of patients with rectal cancer who underwent radical surgery at Tokushima University Hospital from January 2012 to April 2023 was included in this study to evaluate risk factors for CRM involvement. Short-term outcomes, including CRM rates, as well as long-term outcomes, were compared between patients who had undergone robot-assisted versus laparoscopic surgery following propensity score analysis.ResultsA total of 223 patients were analyzed in this study. Multivariate analysis demonstrated that lymph node metastasis was the most significant predictive factor for CRM involvement (p = 0.030), and that robot-assisted surgery tended to lead to less CRM involvement (p = 0.085). The CRM involvement rate for robotic and laparoscopic surgery before propensity score matching was 4.7% and 11.7%, respectively. Following propensity score matching, the CRM involvement rate for robotic surgery was 4.5% versus 11.4% for laparoscopic surgery. Disease-free survival (DFS) and overall survival (OS) rates for patients who had undergone robot-assisted and laparoscopic surgery were not significantly different before or after matching (DFS before matching: p = 0.876, DFS after matching: p = 0.805, OS before matching: p = 0.511, OS after matching: p = 0.458).ConclusionRobot-assisted surgery may be useful in defining the CRM for rectal cancer.

Preoperative D‑dimer level and prognosis in patients diagnosed with gastric cancer and undergoing gastric cancer radical surgery: A retrospective cohort study.

Gastric cancer, one of the most aggressive tumors affecting the digestive tract, has seen a rise in both incidence and mortality rates in recent years, with a lack of clear prognostic indicators. D-dimer, a byproduct of fibrin degradation, is a conventional coagulation biomarker that has been investigated as a potential adverse prognostic factor for postoperative cancer patients. However, conflicting results exist, with some studies suggesting that D-dimer is an independent risk factor for the postoperative prognosis of gastric cancer, and others suggesting that there is no significant association between D-dimer level and gastric cancer prognosis. This controversy underscores the need for further research to determine the true influence of D-dimer level on the prognosis of postoperative cancer patients, including exploring the linear and non-linear associations, and identifying optimal critical values before surgery. The present study aimed to assess the association between preoperative D-dimer levels and 5-year overall survival (OS) rate in patients undergoing radical surgery for gastric cancer. Data was analyzed from patients diagnosed with gastric cancer who underwent a radical gastrectomy at Shanxi Cancer Hospital (Taiyuan, China) in 2017 and were followed up for 5 years until December 2022. Preoperative D-dimer levels and tumor-related indicators were collected as covariates from hospital records, with patient follow-up information obtained from the hospital's tracking system. Utilizing multivariate Cox regression, curve fitting and inflection point analysis, the present study sought to investigate the link between preoperative D-dimer levels and 5-year OS rate following radical surgery for gastric cancer. After strict admission and exclusion procedures, a total of 133 patients were included in the study and were then classified based on D-dimer level. Based on the mean value, the D-dimer levels were segregated into two distinct cohorts: The D-dimer_high group (n=66) and the D-dimer_low group (n=67). Cox multiple regression analysis was conducted using both continuous and binary variables. The results showed no effect in terms of the continuous variables, but higher preoperative D-dimer levels were significantly associated with a higher 5-year overall survival compared with lower preoperative D-dimer levels in the categorical variables. Therefore, curve fitting was performed, which indicated that the association between D-dimer level and 5-year survival rate after radical gastrectomy for cancer showed a U-shaped curve, with P<0.001, high and low D-dimer levels both indicated poorer prognosis. A curvilinear correlation was demonstrated between preoperative D-dimer levels and the 5-year survival rate following radical gastrectomy for cancer. Subsequently, an inflection point analysis found that the inflection point was located at 100-200 ng/ml. In conclusion, in patients undergoing radical gastrectomy for gastric cancer, preoperative D-dimer can be used to indicate the current state of the tumor to some extent through blood coagulation status. Notably, a U-shaped association exists between D-dimer levels and 5-year postoperative survival rate in gastric cancer. This association demonstrates varying effects across different intervals. Specifically, D-dimer levels <100 ng/ml are associated with a worse prognosis, whereas levels >200 ng/ml are associated with a better prognosis.

Tumor-associated macrophages in bladder cancer: roles and targeted therapeutic strategies.

Bladder cancer (BC) is the ninth most common and "expensive" cancer in the world. Despite the availability of various treatment modalities such as chemotherapy, immunotherapy and surgery, the overall survival rate of patients with advanced bladder cancer remains low. As one of the most abundant infiltrating immune cells in bladder cancer, tumor-associated macrophages (TAMs) play an important role in the development of BC and in the standard regimen of intravesical BCG therapy. Targeting TAMs have achieved excellent results in clinical trials for a variety of other cancers, but few studies have been conducted for bladder cancer. Further exploration is still needed to develop TAM-related therapeutic strategies for BC treatment, which are expected to improve the therapeutic efficacy and life quality of patients. This review summarizes the relationship between TAMs in bladder cancer and disease staging, evolution, patient prognosis, and treatment outcome. Several potential TAM targets in BC are also pointed, which may help to inhibit tumor-promoting TAMs and provide new therapeutic approaches for advanced BC.

The impact of adjuvant radiotherapy on overall survival in spinal low-grade gliomas: a propensity score-matched analysis.

Spinal low-grade gliomas (sLGGs) are a group of tumors that arise from glial cells in the spinal cord. Current evidence supporting the use of adjuvant radiotherapy for the management of sLGG is lacking. We hence aimed to compare overall survival rates in patients receiving surgery alone with those receiving surgery with adjuvant radiotherapy. The NCDB, a large, nationwide, US-based cancer registry was used. Relevant cases were identified using the following ICD-O-3 histological codes: 9382, 9384, 9400, 9410, 9411, 9420, 9421, 9424, 9425, and 9450, along with the ICD-O-3 topographical codes for spinal meninges (C70.1) and spinal cord (C72.0), excluding spinal ependymomas. Overall survival was the primary outcome. Propensity score matching 1:1 was used to balance the cohorts prior to Kaplan-Meier survival analysis. A total of 552 patients were included in the study, with 440 in the surgery alone group and 156 in the surgery with adjuvant radiotherapy group. Patients in the surgery with adjuvant radiotherapy group were significantly older (median age 40.0 vs. 24.0 years, p < 0.001), and exhibited higher proportions of WHO grade 2 tumors (p < 0.001). Adjuvant chemotherapy was more frequently administered in the surgery with adjuvant radiotherapy group (23% vs. 7%, p < 0.001). Overall, adjuvant radiotherapy was not associated with improved survival, with a significantly higher mortality in the radiotherapy group before propensity score matching (p < 0.0001). After matching, the difference in overall survival was no longer significant (p = 0.11). This study found no significant overall survival benefit associated with the use of adjuvant radiotherapy for spinal low-grade gliomas (sLGG). Although patients who received adjuvant radiotherapy initially demonstrated higher mortality rates, this difference was largely due to confounding factors such as more advanced disease in this group.

Screening for proline‑rich protein 11 gene expression in cervical cancer: Use as a novel diagnostic biomarker and poor prognostic factor.

Cervical cancer is the fourth most common type of cancer affecting the female population worldwide, and it is associated with a late diagnosis and a poor prognosis. It is thus imperative to improve modern diagnostic methods by searching for novel tumor biomarkers, such as proline-rich protein 11 (PRR11), the expression of which is deregulated in various types of cancer and participates in their cellular progression. However, the involvement of PRR11 in cervical cancer has not yet been fully elucidated. The present study thus aimed to investigate the expression of PRR11 in cervical cancer as a diagnostic and prognostic biomarker, and to characterize the associated clinicopathological features. For this purpose, reverse transcription-quantitative PCR was used to assess the mRNA expression level of PRR11 in 100 cervical cancer and corresponding adjacent normal tissues. Statistical analysis was then performed to determine the association between PRR11 expression and the clinicopathological data of patients, and the overall survival rate of patients. The results revealed that PRR11 gene expression in cervical cancer tissues was significantly higher than that in corresponding normal adjacent tissues. No significant differences were found between PRR11 gene expression, age at diagnosis, FIGO stage, or histological type. Patients with a positive PRR11 expression had a shorter survival rate (P=0.035). As regards the diagnostic value, the results demonstrated that PRR11 expression was able to differentiate cancerous from normal cervical tissue with a sensitivity of 88.75%, a specificity of 100%, an area under the curve of 0.982 and a Youden index of 88.7%. Thus, PRR11 satisfies the standard criteria to be applied in diagnosis. On the whole, the present study demonstrates that PRR11 is well-expressed in cervical cancer tissues, is related to age and a poor prognosis, and may thus serve as a potential novel biomarker for cervical cancer diagnosis.

Efficacy and safety of carmustine wafers, followed by radiation, temozolomide, and bevacizumab therapy, for newly diagnosed glioblastoma with maximal resection.

To improve the outcome in newly diagnosed glioblastoma patients with maximal resection, we aimed to evaluate the efficacy and safety of implantation of carmustine wafers (CWs), radiation concomitant with temozolomide and bevacizumab, and maintenance chemotherapy with six cycles of temozolomide and bevacizumab. This prospective phase II study enrolled glioblastoma patients considered candidates for complete resection (> 90%) of a contrast-enhanced lesion. The CWs were intraoperatively implanted into the resection cavity after achieving maximal resection. Patients without a measurable contrast-enhanced lesion on magnetic resonance imaging within 48h after resection received concomitant radiotherapy and chemotherapy with temozolomide and bevacizumab, followed by maintenance treatment with up to six cycles of temozolomide and bevacizumab. The primary endpoint was the 2-year overall survival rate in glioblastoma patients with protocol treatment. From October 2015 to April 2018, we obtained consent for the first registration from 70 patients across 17 institutions in Japan, and 49 patients were treated according to the protocol. We evaluated the safety in 49 patients who were part of the second registration and the efficacy in 45 glioblastoma patients treated according to the protocol. The profile of hematological and most of the non-hematological adverse effects was similar to that in previous studies, but stroke occurred in 12% of cases (6/49 patients). The estimated 2-year overall survival rate was 51.3%. Implantation of CWs, followed by concomitant radiation, temozolomide, and bevacizumab, and six cycles of temozolomide and bevacizumab may offer some benefit to survival in Japanese glioblastoma patients with maximal resection. jRCTs021180007.

MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway.

This study aims to elucidate the role of minichromosome maintenance protein 4 (MCM4) in malignant melanoma (MM) and explore the underlying mechanism. Initially, data from The Cancer Genome Atlas (TCGA) database and the Molecular Signature Database (MSigDB) were used to investigate the biological impact of MCM4 on MM. Further, a prognostic model using Cox regression analysis was developed to predict the overall survival (OS) rate in the MM patients. The effects of MCM4 on the proliferation, migration, and invasion abilities of MM (B16F0 and A375) cells were demonstrated using the CCK-8, colony formation, EDU, wound scratch, and Transwell assays. In subcutaneous tumor models in C57BL/6 mice invivo, the expression levels of MCM4 in MM cells and tumors were detected using Western blot and immunofluorescence approaches. The bioinformatics analysis indicated that MCM4 was expressed higher in MM tissues than in the normal tissues (p < 0.05). The established OS prediction model could significantly contribute to devising follow-up strategies and treating MM patients. MCM4 knockdown resulted in reduced proliferation, migration, and invasion abilities of MM cells, which were reversed by MCM4 overexpression (p < 0.05). Moreover, MCM4 could activate the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway in MM cells. The PI3K inhibitor (LY294002) could reverse the effects of MCM4 on MM cells. MCM4 could substantially prompt the tumor growth of MM in mice through the PI3K/AKT pathway invivo. In summary, MCM4 prompted the development and metastasis of MM by activating the PI3K/AKT pathway.

Predictive Value of GINI and ALBI Grades in Esophageal Cancer Receiving Chemoradiotherapy.

Objectives: The principal objective of this study was to assess the predictive efficacy of the global immune-nutrition-inflammation index (GINI) and the albumin-bilirubin (ALBI) score among patients receiving chemoradiotherapy for esophageal cancer. Methods: A retrospective analysis was conducted on 46 patients who received definitive or neoadjuvant radiotherapy for esophageal cancer at our institution. Blood samples were collected from these patients prior to the initiation of radiotherapy to measure the biomarkers, including the C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), the global immune-nutrition-inflammation index (GINI), and the albumin-bilirubin (ALBI) grade. The predictive significance of these biomarkers for progression-free survival (PFS) and overall survival (OS) was evaluated using both univariate and multivariate Cox regression analyses. Results: The median follow-up time for this study was 19.5 months (range: 2.6-166.3 months). Univariate analysis revealed that the platelet count (p = 0.003) and monocyte count (p = 0.04) were significant predictors of PFS. In the multivariate analysis, only the platelet count (p = 0.005) remained an independent predictor of PFS. Univariate analysis demonstrated that the neutrophil count (p = 0.04), lymphocyte count (p = 0.01), NLR (p = 0.005), PLR (p = 0.004), CRP (p = 0.02), ALBI grade (p = 0.01), and GINI (p = 0.005) were significant predictors of OS. Multivariate analysis identified the GINI as a predictor of OS, approaching statistical significance (p = 0.08). Conclusion: The results of our study indicate that the pretreatment GINI and ALBI grades are significantly and independently associated with the OS rates in patients with esophageal cancer who are undergoing chemoradiotherapy.

Prediction of Treatment Response Based on Nutritional Status and Tumor Immunity in Oropharyngeal Cancer Patients Treated With Chemoradiotherapy.

Radiotherapy (RT) for advanced oropharyngeal cancer (OPC) is effective, especially when combined with chemotherapy (CRT). However, its success can vary depending on factors, such as tumor stage, HPV infection (p16 status), and the patient's nutritional and immune status. This study examined the controlling nutritional status (CONUT) score and tumor immunity as predictive factors for treatment outcomes in OPC, aiming to develop a personalized risk score. A retrospective analysis was conducted on 84 patients with OPC treated with definitive RT or CRT, and survival outcomes were compared based on various factors, including BMI, CONUT score, CD8 expression, and HLA class II expression. We observed better overall survival (OS) rates in CD8-positive patients and those with higher HLA class II expression. The univariate analysis identified stage, p16 status, BMI, CONUT score, and CD8 expression as significantly associated with OS. In multivariate analysis, stage, BMI, and CONUT score remained significant predictors of OS. A risk scoring system was developed based on stage, p16 status, BMI, CONUT score, and CD8 expression. Patients were categorized into low-risk and high-risk groups, with significantly better survival in the low-risk group. A combined risk score incorporating clinical, nutritional, and immune factors can improve the prediction of treatment outcomes for OPC patients. This risk stratification may enable personalized treatment plans and improve ΟS rates.

Unveiling Tumorigenesis Mechanisms and Drug Therapy in Neuroblastoma by Mass Spectrometry Based Proteomics.

Neuroblastoma (NB) is the most common type of extracranial solid tumors in children. Despite the advancements in treatment strategies over the past years, the overall survival rate in patients within the high-risk NB group remains less than 50%. Therefore, new treatment options are urgently needed for this group of patients. Compared with genomic aberrations, proteomic alterations are more dynamic and complex, as well as more directly related to pathological phenotypes and external perturbations such as environmental changes and drug treatments. This review focuses on specific examples of proteomics application in various fundamental aspects of NB research, including tumorigenesis, drug treatment, drug resistance, and highlights potential protein signatures and related signaling pathways with translational values for clinical practice. Moreover, emerging cutting-edge proteomic techniques, such as single cell and spatial proteomics, as well as mass spectrometry imaging, are discussed for their potentials to probe intratumor heterogeneity of NB.

SERPING1 Reduces Cell Migration via ERK-MMP2-MMP-9 Cascade in Sorafenib- Resistant Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignant tumor, and it ranks 2nd in terms of mortality rate among all malignancies in Taiwan. Sorafenib is a multiple tyrosine kinase inhibitor that suppresses tumor cell proliferation and angiogenesis around tumors via different pathways. However, the survival outcome of advanced HCC patients treated with sorafenib is still unsatisfactory. Unfortunately, there are no clinically applicable biomarkers to predict sorafenib therapeutic efficiency in HCC thus far. We found that serpin peptidase inhibitor, clade G, member 1 (SERPING1) is highly associated with overall and recurrence-free survival rates in HCC patients and is also highly correlated with several clinical parameters. SERPING1 expression was increased with sorafenib in both the HCC cell extract and conditioned medium, which was also observed in sorafenib-resistant HepG2 and Huh7 cells. Sorafenib decreased cell viability and migration, which was similar to the effect of SERPING1 in HCC progression. Moreover, sorafenib inhibited both MMP-2 and MMP-9 activity and enhanced the expression of p-ERK in HCC cells. In summary, sorafenib reduces HCC cancer progression might through the p-ERK-MMP-2-MMP-9 cascade via upregulation of SERPING1. In the present study, the roles and molecular mechanisms of SERPING1 and its value as a marker for predicting sorafenib resistance and progression in HCC patients were examined. The results of the present study provide a deep understanding of the roles of SERPING1 in HCC sorafenib resistance, which can be applied to develop early diagnosis and prognosis evaluation methods and establish novel therapeutic targets for specifically treating HCC.

Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix: Comparison of Its Clinicopathological Characteristics and Programmed Death-ligand 1 Expression Status With Those of Other Endocervical Adenocarcinomas.

Invasive stratified mucin-producing carcinoma (ISMC) is a rare but aggressive variant of endocervical adenocarcinoma (EAC). The aim of this study was to investigate the differences in clinicopathological features, patient outcomes, and programmed death-ligand 1 (PD-L1) expression among ISMC, usual-type EAC (UEA), and gastric-type EAC (GEA). PD-L1 22C3 immunostaining was performed using 20 ISMCs, 20 UEAs, and 20 GEAs. Combined positive score (CPS) method was used to assess PD-L1 immunoreactivity. ISMC was diagnosed at a younger age and showed a more advanced stage and shorter survival than UEA. The disease-free survival (DFS) and overall survival (OS) rates of ISMC patients were lower than those of UEA but comparable to those of GEA. ISMC type was an independent prognostic factor for predicting short DFS [hazard ratio (HR)=2.790, 95% confidence interval (CI)=1.153-6.756] and OS (HR=6.071, 95%CI=1.257-29.327). All ISMCs showed PD-L1 over-expression with a mean CPS of 44.5 (range=10-100), which was higher than those of UEA (mean CPS=8.2) and GEA (mean CPS=6.5). PD-L1 positivity (CPS≥1) was also an independent prognostic factor for worse OS (HR=2.472, 95%CI=1.097-5.570). Despite PD-L1 over-expression, ISMC patients treated with pembrolizumab showed no clinical response. All examined ISMCs over-expressed PD-L1. ISMC showed higher PD-L1 expression than UEA and GEA and worse survival than UEA. PD-L1 over-expression was found to be a significant predictor for worse DFS and OS in patients with ISMC. Our data suggest that PD-L1 over-expression is associated with poor ISMC prognosis.

Treatment Patterns and Clinical Outcomes in Patients with Hodgkin Lymphoma from Saudi Arabia, Türkiye, and South Africa: Subgroup Analysis from the International, Multi-center, Retrospective BHOLISTIC Study.

B-HOLISTIC was a real-world, retrospective study of treatment patterns and clinical outcomes in Hodgkin lymphoma (HL) in regions outside Europe and North America. This subgroup analysis reports findings from Saudi Arabia, Türkiye, and South Africa. Patients aged ≥18 years and diagnosed with stage IIB-IV classical HL receiving frontline chemotherapy (frontline cHL) and/or relapsed/refractory HL (RRHL) from January 2010-December 2013 were assessed. The primary endpoint was progression-free survival (PFS) in patients with RRHL. Overall, 694 patients (RRHL: n=178; frontline cHL: n=653) were enrolled. Among patients with RRHL, >80% received first salvage chemotherapy. The most common first salvage regimens were etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP) in Saudi Arabia (78.3%) and dexamethasone, cytarabine, cisplatin (DHAP) in Türkiye (36.1%) and South Africa (40%). Median PFS (95% confidence interval [CI]) in the RRHL group was 5.1 (3.0-15.9), 19.7 (7.5-not reached), and 5.2 (1.1- 10.1) months in Saudi Arabia, Türkiye, and South Africa, respectively. The 5-year PFS and overall survival (95% CI) rates in patients with RRHL were 33.2% (21.6-45.2) and 78.2% (65.9-86.5) in Saudi Arabia, 42.5% (29.5-54.9) and 79.4% (67.2-87.5) in Türkiye, and 13.1% (4.2-27.0) and 53% (35.5-67.8) in South Africa, respectively. This study showed that the clinical outcomes in Türkiye and Saudi Arabia were generally comparable with Western countries during the study period, although Saudi Arabia had lower PFS rates. Conversely, the clinical outcomes in South Africa were suboptimal, emphasizing the need for novel therapies and improved progression to stem cell transplantation. Additionally, these data may serve as a control group for future studies in these countries and inform clinical decision-making.

Survival penalty in patients undergoing transcatheter versus surgical aortic valve replacement: is it just a question of frailty? Insights from a large cohort with demographic matching

Abstract Background Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are the reference treatments for aortic stenosis. Conflicting data exist on late survival results of these two techniques. While randomised controlled trials (with highly selected patients) assert the non-inferiority of TAVR, real-world data from large registries (with potential uncorrected confounders) suggest the opposite. Comparing the survival rates of SAVR and TAVR with those of a matched reference population could help circumvent potential biases of direct procedural comparisons and quantify the impact of frailty on post-operative survival. Purpose Our study aims to compare the 5-year overall survival rates of SAVR, non-frail TAVR, and frail TAVR patients with the survival of their demographically matched reference population. Methods This study included all consecutive patients undergoing either SAVR or TAVR at a tertiary hospital between January 2010 and December 2021. Each patient underwent a comprehensive geriatric assessment by an experienced geriatric team, from which a Clinical Frailty Scale (CFS) was derived using a validated classification tree. Frailty was defined as a CFS ≥ 6, in accordance with ESC guidelines. The patients were stratified into 3 subgroups: SAVR, non-frail TAVR, and frail TAVR patients. For each subgroup, a corresponding reference population was generated using national actuarial tables to ensure individual-level matching based on age, gender, and year of observation. Survival of each subgroup was then compared to its corresponding reference population over a 5-year period using standardized mortality ratios (SMR) and one-sample logrank tests. Results Our cohort included 1183 SAVR, 254 non-frail TAVR, and 151 frail TAVR patients, with mean ages of 74.1, 85.4, and 85.7 years, and median EuroSCORE II of 2.0%, 4.2%, and 5.4%, respectively. Survival of SAVR patients was equivalent to the reference population (80.1 vs 80.9% survival; SMR = 1.06 [0.89 – 1.25]; p = 0.454; Figure 1A). Similarly, non-frail TAVR patients also achieved survival rates comparable to those of the reference population (50.9 vs 54.0% survival; SMR = 0.94 [0.76 – 1.18]; p = 0.549; Figure 1B). However, frail TAVR patients faced a significantly reduced survival rate (41.7% vs 54.0% survival; SMR = 1.48 [1.15 – 1.90]; p &amp;lt; 0.001; Figure 1C). The frailty of this subgroup could therefore explain a 48% increase in mortality risk compared with their reference population after 5 years. Conclusions Treating non-frail patients with aortic stenosis through TAVR or SAVR restores life expectancy to levels comparable with their reference population, challenging results from other real-world registries. In contrast, TAVR in frail patients is associated with worse survival, raising the question of treatment futility in this specific subgroup. Refining the selection of frail patients who may benefit from TAVR remains an important clinical challenge.

Molecular Targets of Plant-Derived Bioactive Compounds in Oral Squamous Cell Carcinoma.

With a significant increase in both incidence and mortality, oral cancer-particularly oral squamous cell carcinoma (OSCC)-is one of the main causes of death in developing countries. Even though there is evidence of advances in surgery, chemotherapy, and radiotherapy, the overall survival rate for patients with OSCC has improved, but by a small percentage. This may be due, on the one hand, to the fact that the disease is diagnosed when it is at a too-advanced stage, when metastases are already present. This review explores the therapeutic potential of natural herbal products and their use as adjuvant therapies in the treatment of oral cancer from online sources in databases (PubMed, Web of Science, Google Scholar, Research Gate, Scopus, Elsevier). Even if classic therapies are known to be effective, they often produce many serious side effects and can create resistance. Certain natural plant compounds may offer a complementary approach by inducing apoptosis, suppressing tumor growth, and improving chemotherapy effectiveness. The integration of these compounds with conventional treatments to obtain remarkable synergistic effects represents a major point of interest to many authors. This review highlights the study of molecular mechanisms and their efficiency in in vitro and in vivo models, as well as the strategic ways in which drugs can be administered to optimize their use in real contexts. This review may have a significant impact on the oncology community, creating new inspirations for the development of more effective, safer cancer therapies with less toxic potential.