5-year Survival Rate Of Patients Research Articles

A Case Report on Prolonged Response with T-DM1 in Recurrent Advanced Breast Cancer Setting

Breast cancer holds the dubious distinction of being the most prevalent malignant tumour among women worldwide. The 5-year survival rate for patients with advanced or metastatic forms of the disease is estimated at a mere 23%, with approximately 20% of cases exhibiting an amplification of the human epidermal growth factor receptor 2 (HER2). HER2 overexpression was linked to a dismal prognosis prior to the advent of targeted HER2 therapies. The introduction of ado-trastuzumab emtansine (T-DM1) has emerged as one of the standard treatment options for HER2-positive breast cancer patients who experience a recurrence or progression of the disease. This case concerns a patient with recurrent metastatic breast cancer who achieved an unusually extended period of time without the disease progressing while on T-DM1 treatment. After experiencing disease progression on multiple treatment lines involving trastuzumab, the patient achieved a nearly complete clinical remission (cCR) with T-DM1 therapy. The availability of cost-effective biosimilars has expanded access to advanced biologic therapies, which were previously limited to a small segment of the population due to the cost barrier.

Matrine promotes colorectal cancer apoptosis by downregulating shank-associated RH domain interactor expression

BACKGROUND The 5-year survival rate of patients with colorectal cancer (CRC) in China is only 56.9%, highlighting the need for new therapeutic drugs. Previous studies have shown that matrine exhibits antitumor effects by inducing apoptosis. However, the mechanism by which matrine regulates antiapoptotic proteins in CRC remains unclear. AIM To identify apoptotic proteins from proteomics and investigate the role of matrine in impeding CRC apoptosis by regulating these proteins. METHODS Tumor and adjacent normal tissues were collected from 52 patients with CRC who underwent surgery between January and December 2021. Data-independent acquisition quantitative proteomic analysis was performed to identify differentially expressed apoptotic proteins. The selected apoptotic proteins were identified through their association with tumor-node-metastasis (TNM) stage and prognosis, then confirmed by immunohistochemical (IHC) staining in validation cohort. In vitro , the role of matrine or apoptotic proteins on cancer cells were analyzed. RESULTS Compared to normal tissues, 88 anti-apoptotic proteins from proteomic results were selected. Among them, Shank-associated RH domain interactor (SHARPIN) was identified because of its relationship with TNM stage and overall survival in TCGA database. In the IHC-confirmed cohort, SHARPIN was highly expressed in CRC tissues and localized in the cytoplasm. Higher SHARPIN expression was associated with TNM stage, carbohydrate antigen 153 levels, and gross type compared to low expression. SHARPIN knockdown promoted apoptosis, significantly upregulated the expression of Bcl-2 associated agonist of cell death, Bcl-2 associated X protein, caspase 3, and caspase 8, and downregulated B-cell lymphoma-2 (P < 0.05). Importantly, matrine treatment promoted apoptosis and reversed the proliferation, invasion, and migration of CRC cells by repressing SHARPIN. CONCLUSION SHARPIN was identified as an upregulated anti-apoptotic protein in CRC, and matrine exhibited anticancer effects by downregulating its expression. Thus, matrine appears to be a promising drug for CRC.

Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights

BackgroundColorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.MethodsWe utilized single-cell RNA sequencing technology to analyze 13 tissue samples from 4 CRC patients, identifying key cell types within the tumor microenvironment. Intercellular communication was assessed using CellChat, and a risk score model was developed based on eight prognostic genes to enhance patient stratification for immunotherapeutic approaches. Additionally, in vitro experiments were performed on DLX2, a gene strongly associated with poor prognosis, to validate its potential role as a therapeutic target in CRC progression.ResultsEight major cell types were identified across the tissue samples. Within the tumor cell population, seven distinct subtypes were recognized, with the C0 FXYD5+ tumor cells subtype being significantly linked to cancer progression and poor prognosis. CellChat analysis indicated extensive communication among tumor cells, fibroblasts, and immune cells, underscoring the complexity of the tumor microenvironment. The risk score model demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates in CRC patients. Enrichment analysis revealed that the C0 FXYD5+ tumor cell subtype exhibited increased energy metabolism, protein synthesis, and oxidative phosphorylation, contributing to its aggressive behavior. In vitro experiments confirmed DLX2 as a critical gene associated with poor prognosis, suggesting its viability as a target for improving drug sensitivity.ConclusionIn summary, this study advances our understanding of CRC progression by identifying critical tumor subtypes, molecular pathways, and prognostic markers that can inform innovative strategies for predicting and enhancing drug sensitivity. These findings hold promise for optimizing immunotherapeutic approaches and developing new targeted therapies, ultimately aiming to improve patient outcomes in CRC.

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.

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.

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.

Liver Transplant Beyond the Milan Criteria: Distant Metastases of Hepatocellular Carcinoma (Part II)

Liver transplant is one of the most effective ways to treat hepatocellular carcinoma (HCC). Thanks to the implementation of the Milan criteria, developed almost 30 years ago, 5-year survival rates for patients who underwent a transplant for HCC increased and reached the rates for patients with nontumor indications. Despite the emergence of alternative stratification systems, extrahepatic metastases remain a key contraindication to a liver transplant. Nevertheless, there have been reported cases of liver transplants in spite of the contraindication not only in times of diagnostic limitations but also in the 21st century.We have previously reported our own case of a patient who underwent a liver transplant in spite of pulmonary lesions, which postoperatively were found to be HCC metastases. In this part of the review, we discuss similar cases from the literature.If metastatic lesions are successfully treated, a related donor is available, and other modalities are seen as less preferable in terms of the disease prognosis, a liver transplant may be considered an appropriate way to prolong the patient’s life, although such approach should not be recommended for widespread use.

DDDR-16. SORTING TO ENRICH FOR CHEMOTHERAPEUTIC-RESISTANT GLIOMA CELLS BASED ON UNIQUE MEMBRANE PROPERTIES

Abstract Glioblastoma, astrocytoma, and oligodendroglioma comprise a class of aggressive and deadly brain tumors called diffuse gliomas. Around 20,000 glioma cases are diagnosed yearly in the US alone. The current standard chemotherapy treatment, temozolomide (TMZ), is insufficient as the 5-year survival rate of glioblastoma patients is as low as 8%. This is due to the presence of TMZ-resistant cells within tumors that lead to chemoresistance and tumor recurrence. Thus, studying the molecular properties of TMZ-resistant cells would enable more effective means of targeting them and thus improve patient outcomes. We leveraged dielectrophoresis (DEP), a phenomenon by which non-uniform electric fields induce differential movement of cells, as a novel label-free technique to sort glioma cells based on their membrane electrophysiological properties. We were able to successfully use DEP to sort cells from glioblastoma and oligodendroglioma established cell lines, which yielded fractions that differed in membrane capacitance, the membrane’s ability to store charge. Interestingly, the DEP-sorted cell fractions also exhibited significant differences in TMZ resistance, indicating that we were able to use DEP to enrich for TMZ-resistant cells. Further, the differences in TMZ resistance were coupled with their membrane capacitance differences. Because we previously found that changes in membrane capacitance were linked to differences in glycosylation, we utilized lectin analysis to assess glycan expression of DEP-sorted oligodendroglioma cells. Our data show that TMZ-resistant oligodendroglioma cells enriched from DEP sorting had reduced levels of mannose glycans compared to less TMZ-resistant fractions. Collectively, our novel findings demonstrate (a) TMZ-resistant glioma cells can be enriched by DEP, and (b) TMZ resistance is correlated with membrane capacitance and cell surface glycosylation. These findings could enable further characterization of TMZ-resistant cells to better understand molecular mechanisms of TMZ resistance and the development of more effective treatment strategies for gliomas through targeting membrane properties such as glycosylation.

Impact of ascites grading and non-selective β-blockers on 1-year prognosis of Acute-on-chronic liver failure

Objective: To investigate the influence of ascites grading and non-selective β- blockers (NSBBs) on the 1-year prognosis of patients with acute-on-chronic liver failure (ACLF). Methods: A total of 1 386 patients with ACLF were graded for ascites and followed up for one year. Kaplan-Meier Log-rank test and Cox regression were used for multivariate regression to analyze the effects of ascites grading and NSBBs on the 1-year prognosis of ACLF. Results: The incidence of ascites in 1 836 patients with ACLF was 77.56% on admission. Ascites grade was related to the 1-year prognosis of ACLF [log rank (Mantel-Cox) χ2=21.384, p=0.000]. Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin time activity(PTA), urea, MELD-Na score, and application of NSBBs were closely related to the 1-year prognosis of ACLF. The result of Kaplan-Meier Log-rank test for patients treated with NSBBs in the grade 2/3 ascites group suggest that NSBBs can improve the 1-year survival rate of ACLF patients with grade 2 and grade 3 ascites ( log rank (Mantel-Cox) χ2=6.113, p=0.013). Conclusions: Ascites grading and application of NSBBs can affect the 1-year prognosis of ACLF. NSBBs may be beneficial to the long-term prognosis of ACLF. Patients treated with NSBBs before the onset of ACLF should continue NSBBs treatment.

The Ongoing Development of Watch and Wait

AbstractThe nonoperative management of rectal cancer, known as watch and wait (W&amp;W), has gained increasing acceptance in recent years. This approach is based on using complete clinical response (cCR) as a marker for complete pathological response (pCR) following neoadjuvant chemoradiation (nCRT). Advances in nCRT regimens have resulted in higher tumor regression rates, making W&amp;W a viable option for selected patients. This study presents the historical evolution and efficacy of the W&amp;W strategy and offers modern recommendations based on recent clinical findings. Key findings include an 85 to 92% 5-year disease-free survival rate in patients achieving cCR, highlighting the potential for improved quality of life and reduced morbidity without compromising survival outcomes.

Treatment Patterns and Clinical Outcomes in Patients with Hodgkin Lymphoma from Saudi Arabia, Türkiye, and South Africa: Subgroup Analysis from the International Multicenter Retrospective B-HOLISTIC 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 with relapsed/refractory HL (RRHL) from January 2010 to 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, and cisplatin in Saudi Arabia (78.3%) and dexamethasone, cytarabine, and cisplatin 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 those of 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. These data may serve as a control group for future studies in these countries and inform clinical decision-making.

Clinicopathological characteristics of mucinous breast cancer: a retrospective analysis of a 6-years study from national cancer center in Vietnam.

To evaluate clinicopathological features in women with mucinous breast cancer (MBC), distinguishing between pure (PMC) and mixed (MMC) subtype. A retrospective analysis of all 358 women with MBC treated at Vietnam National Cancer hospital from June 2015 to December 2020. PMC was defined by ≥ 90% mucinous components. We identified 358 women with MBC (245 PMC and 113 MMC) representing 2.7% of all 13,254 BC patients. The proportions of stage I, II, III and IV were 34.9%, 50.8%, 10.4% and 3.9% respectively. The rate of HER2 overexpression was 12%, and only 1.4% of patients was treated with anti-HER2. 193 patients (53.9%) had chemotherapy, including 55 patients (15.4%) treated in the neoadjuvant setting. Only 3 patients (5.5%) achieved pCR. PMC patients were older (54.4 ± 13.3 vs 51.1 ± 13.1years), had lower Ki67 expression, lower incidence of nodal metastasis (N +) (p values < 0.05). At a median follow-up of 58months, the 5-year overall survival rate of non-metastatic patients was 86.6%. Multivariate analysis showed N + to be the most significant prognostic factor (HR = 3.3; 95%CI 1.5-7.1), followed by T-stage (HR = 2.9; 95%CI 1.4-6.3), HER2 + (HR = 2.5; 95%CI 1.2-5.3) and MMC subtype (HR = 1.9; 95%CI 1.0-3.9). Poor prognostic factors of MBC include high T-stage, N-positivity, HER2 overexpression and MMC subtype. Given the low response rate to neoadjuvant CT, upfront surgery is appropriate for MBC patients.

The 5-year relative survival rate among cancer patients in Henan province of China, 2015-2019

Objective: To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data. Methods: Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019. Results: During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P＜0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P＜0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion: The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.

GINS1 Enhances Glycolysis, Proliferation and Metastasis in Lung Adenocarcinoma Cells by Activating the Notch/PI3K/AKT/mTORC1 Signaling Pathway

Lung cancer is the most common type of cancer, accounting for more than half of all cancer cases, with lung adenocarcinoma (LUAD) representing over half of lung cancer patients. Currently, the 5-year survival rate for metastatic LUAD patients remains low and there is an urgent need for new biomarkers as targets for targeted therapy. Go-Ichi-Ni-San 1 (GINS1), an important member of the GINS family, is closely related to the occurrence and development of human malignant tumors. This study aims to explore the role of GINS1 in glycolysis, proliferation, and metastasis of LUAD cells and the related molecular mechanisms. The expression of GINS1 was analysed using bioinformatics between LUAD patients and healthy controls. The expression levels of GINS1 in LUAD and adjacent tissues were detected by immunohistochemistry and Western blot. Western blot and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) were used to detect the expression of GINS1 in LUAD cell lines A549, SK-LU-1, Calu-3, H1299 and BEAS-2B. Stably knockdown GINS1 in A549 cells and its negative control cell line, as well as stably overexpress GINS1 in H1299 cells and its negative control cell line, were constructed by lentiviral transduction. Colony formation test was used to detect cell proliferation. Scratch test was used to detect cell migration. Transwell test was used to detect cell invasion, and the test kits were used to detect glucose consumption and lactate production. The expression levels of glycolysis-related proteins, Notch signaling pathway proteins and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway proteins were detected by Western blot. The Notch receptor agonist Jagged1 was added to cells from the shGINS1-A549 group and the Notch receptor inhibitor LY3039478 was added to cells from the GINS1-OE-H1299 group for the regression assay. The expression of GINS1 was up-regulated in LUAD patients, tissues and cell lines, and correlated with overall survival (P<0.05). Knockdown of GINS1 significantly inhibited the proliferation, migration and invasion of A549 cells (P<0.05), while overexpression of GINS1 significantly enhanced the proliferation, migration and invasion of H1299 cells (P<0.05). Furthermore, knockdown of GINS1 resulted in reduced glucose consumption, reduced lactate production, and reduced expression levels of glycolytic-related proteins in A549 cells (P<0.05); overexpression of GINS1 enhanced glycolytic level in H1299 cells (P<0.05). The expression levels of Notch1, Notch3, phosphorylated-PI3K (p-PI3K), phosphorylated-AKT (p-AKT) and phosphorylated-mTORC1 (Ser2448)[p-mTORC1 (Ser2448)] in A549 cells were significantly decreased by GINS1 knockdown (P<0.05), while the expression levels of PI3K, AKT, mTOR and p-mTORC2 (Ser2481) were not significantly changed (P>0.05). Overexpression of GINS1 increased the levels of Notch1, Notch3 and PI3K/AKT/mTORC1 pathway phosphorylated proteins in H1299 cells (P<0.05). Jagged1 significantly reversed the inhibition of glycolysis, proliferation and metastasis induced by GINS1 knockdown in A549 cells (P<0.05), and LY3039478 significantly inhibited the enhancement of glycolysis, proliferation and metastasis induced by GINS1 overexpression in H1299 cells (P<0.05). The expression of GINS1 enhances the expression of Notch1 and Notch3 receptors, and then phosphorylates and activates the downstream PI3K/AKT/mTORC1 signaling pathway to enhance the glycolysis, proliferation and metastasis of LUAD cells.

Clinical study on conversion therapy of hepatocellular carcinoma - summary and comparison of clinical data from a single center of consecutive four years

AimThe purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy.MethodsA retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed.ResultsA total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively.ConclusionsWith conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery.Trial registrationThis was a retrospective study and it did not interfere with treatment decisions.

SURGICAL TREATMENT OF RECTAL CANCER WITH PRESERVATION OF THE LEFT COLIC ARTERY AND ICG NAVIGATION

Goal. To analyze the peculiarities of surgical diagnosis of lymphogenic metastasis in patients with colorectal cancer. Generalization of data from Ukrainian and foreign literature, results of randomized studies and meta-analyses. The study is based on the results of observation of 88 patients with colorectal cancer (CRC) of the prospective study group. To analyze the features of surgical diagnostics of lymphogenic metastasis in patients with colorectal cancer. Materials and methods. The results of surgical treatment of 88 patients with rectal cancer were analyzed and systematized. These patients underwent examination and treatment in 2023-2024 at the "Prykarpattian Clinical Oncology Center of the Ivano-Frankivsk Regional Council." The study included patients with stage II-III colorectal cancer (T2-3N0-2M0) without complicated courses. All patients received treatment based on NCCN recommendations. Surgical treatment was performed in standard volume with the removal of all regional lymph node groups and preservation of the left colic artery using real-time lymph node mapping with indocyanine green. All patients were divided into two study groups: Group I included 45 patients who underwent anterior or low anterior resection of the rectum with preservation of the left colic artery. This group was subdivided into two subgroups: Ia – 13 patients who underwent intraoperative indocyanine green injection for real-time lymph node visualization. Ib – 32 patients who did not receive this drug but underwent the same volume of surgery. Group II consisted of 43 patients who underwent anterior or low anterior resection of the rectum with high ligation of the inferior mesenteric artery. This group served as the control group. Results. The main mechanisms of lymphogenic metastasis in colorectal cancer patients in Ivano-Frankivsk were characterized. Literature data on the features of surgical diagnostics of colorectal cancer metastasis were summarized. A review of literature shows the social significance of these studies, as this pathology often leads to patient disability, requiring surgical interventions and further palliative treatment due to the widespread metastasis associated with this disease. The priority task for researchers remains the search for the most effective treatment methods for this pathology, based on randomized studies of colorectal cancer treatment and international protocols. According to the literature, surgical treatment of colorectal cancer remains insufficiently effective at the current stage of oncology. Modern methods offer low 5-year survival rates, emphasizing the need to study factors for individualized treatment. The overall 5-year survival rate for colorectal cancer patients from 2018-2022 was (45.8±2.3)%. The effectiveness of using real-time ICG navigation for lymph node mapping and preservation of the left colic artery in stage II-III (T2-4N1-2M0) rectal cancer patients has been proven. This technique allows for optimal lymphadenectomy, reducing the frequency of surgical complications by 14.7% (p&lt;0.05). Conclusion. Ensuring radical resection of rectal cancer while maximizing blood supply preservation to the anastomosis is the main goal of colorectal surgeons. Over the past two decades, surgical techniques have significantly improved due to advancements in surgical equipment. It is anticipated that surgical technologies will further evolve towards enhancement and individualization in the future. Our procedure serves as an example of modern and personalized rectal cancer surgery.

Optimal transplant strategy of pediatric liver transplantation for fibropolycystic liver disease: Multicenter retrospective study in Japan.

To assess the preoperative disease characteristics and indications for living donor liver transplantation (LDLT), complications, patient survival, and prognosis after LDLT for fibropolycystic liver disease (FLD) in children. We undertook a cross-sectional survey of patients who underwent LDLT for FLD between January 2002 and December 2020. A total of 35 patients (22 male and 13 female individuals) with FLD were included in this study, of whom 19 (54.3%) had isolated congenital hepatic fibrosis and 16 (45.6%) had Caroli syndrome. Refractory gastrointestinal bleeding was the most frequent symptom related to the indication for LDLT, being found in 48.6% of our patients, followed by uncontrollable cholangitis and ascites. The median age at the time of LDLT was 8.1years old. Of the 27 patients presenting with renal involvement, 13 patients required kidney transplantation (KT). Overall, the renal function after LDLT decreased regardless of renal involvement; however, patients with renal involvement had a significantly lower estimated glomerular filtration rate than those without renal involvement throughout the course of this study (p<0.01). The 5-year overall patient survival rate was 97.1%. Two patients died with a median follow-up of 8.9years after LDLT; one died due to sepsis 2weeks after simultaneous liver-kidney transplantation and the other committed suicide 10years after LDLT. The prognosis of the pediatric patients who underwent LDLT for FLD was excellent. However, an individualized treatment approach based on the status of the renal function and liver disease is important, as a certain proportion of patients require KT.

High BMI Is Associated with Changes in Peritumor Breast Adipose Tissue That Increase the Invasive Activity of Triple-Negative Breast Cancer Cells

Breast cancer is the most common cancer in women with multiple risk factors including smoking, genetics, environmental factors, and obesity. Smoking and obesity are the top two risk factors for the development of breast cancer. The effect of obesity on adipose tissue mediates the pathogenesis of breast cancer in the context of obesity. Triple-negative breast cancer (TNBC) is a breast cancer subtype within which the cells lack estrogen, progesterone, and HER2 receptors. TNBC is the deadliest breast cancer subtype. The 5-year survival rates for patients with TNBC are 8–16% lower than the 5-year survival rates for patients with estrogen-receptor-positive breast tumors. In addition, TNBC patients have early relapse rates (3–5 years after diagnosis). Obesity is associated with an increased risk for TNBC, larger TNBC tumors, and increased breast cancer metastasis compared with lean women. Thus, novel therapeutic approaches are warranted to treat TNBC in the context of obesity. In this paper, we show that peritumor breast adipose-derived secretome (ADS) from patients with a high (&gt;30) BMI is a stronger inducer of TNBC cell invasiveness and JAG1 expression than peritumor breast ADS from patients with low (&lt;30) BMI. These findings indicate that patient BMI-associated changes in peritumor AT induce changes in peritumor ADS, which in turn acts on TNBC cells to stimulate JAG1 expression and cancer cell invasiveness.

Tailoring Escalation Adjuvant Therapy for Early-Stage Triple-Negative Breast Cancer in the CBCSG010 Clinical Trial Biomarker Analysis.

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. The CBCSG010 trial is a prospective and multicenter phase III clinical trial confirming that adding adjuvant capecitabine significantly improved the 5-year disease-free survival (DFS) rate in patients with TNBC by 5.9%. In this study, we attempted to identify the specific population that benefited from adjuvant therapy. In this retrospective exploratory analysis, we performed RNA sequencing of tumor tissues from patients with TNBC in the CBCSG010 clinical trial. A single-sample gene set enrichment analysis algorithm and survival analysis were performed to characterize the intrinsic molecular features of the TNBC microenvironment and assess the associations between immune-related gene expression levels or immune cell counts with capecitabine treatment efficacy. Additionally, we performed immunohistochemical staining of 2 markers, PD-L1 and CD8, and hematoxylin-eosin staining of stromal tumor-infiltrating lymphocytes (sTILs) on formalin-fixed, paraffin-embedded specimens to validate findings from bioinformatics analyses. We found that patients with TNBC with high immune-infiltration treated with capecitabine were more likely to have a better prognosis. We used a cutoff of ≥25 combined positive score (CPS) of PD-L1, ≥10% positive sTILs, and ≥10% positive cells of CD8 to define the "immune-hot" patients. Among immune-hot patients, Kaplan-Meier curves showed that 5-year DFS rates were 96.9% and 79.4% in the capecitabine and control groups, respectively (hazard ratio, 0.13; 95% CI, 0.03-0.52; P=.049 in favor of capecitabine). In the capecitabine group, the 5-year DFS rate was higher for immune-hot patients than for immune-cold patients (96.9% vs 76.4%; hazard ratio, 0.11; 95% CI, 0.04-0.29; P=.028). Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine, and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients.

Pediatric Kidney Transplantation in an Under-resourced Country: A Single-Center Experience.

Kidney transplant is the optimal method for managing children with end-stage kidney disease. This study aimed to present the experience and results of the pediatric kidney transplant program at our center. A single-center observational study was conducted at Children's University Hospital in Damascus, Syria. We reviewed the medical records of all kidney transplants performed between April 2018 and December 2022. All patients were under 14 years old when they underwent kidney transplant. All donors were living, as an effective deceased donor program is currently not an option in Syria. From April 2018 to December 2022, 33 pediatric kidney transplants were performed at our center. Most recipients were boys (n = 24; 72.7%), and 9 were girls (27.3%). Median age was 10 years (range, 4.5-14 y). The most frequent underlying diseases for kidney failure were renal dysplasia-hypoplasia (42.5%), reflux nephropathy (18.2%), and neurogenic bladder with posterior urethral valves (12%). In 10 patients, kidney transplant was performed preemptively (30.3%). Initial graft function was observed in all grafts (100%). During observation time (5 years), 28 patients (85%) retained adequate graft function. The 1-year graft and patient survival rates were 91%. Syria is still suffering from the consequences of the war, affecting organ transplantation in many ways. The good 1-year graft and patient survival in our center was encouraging. However, we admit that the number of patients was small and the follow-up duration was also not long enough; future research is needed to improve long-term outcomes.