Number Of Tumors Research Articles

Development and validation of an early recurrence predictive model for intrahepatic cholangiocarcinoma based on a systematic review and meta-analysis of 17 cohorts

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor with a high incidence of recurrence after surgery. This study aims to identify the early recurrence (ER) risk factors in ICC and develop an ER predictive model for ICC. MethodA computerized search was performed in Embase, Web of Science, Cochrane Library, and PubMed to identify studies focusing on the risk factors associated with ER in ICC. Based on the results of the meta-analysis, an ER predictive model was developed and validated using an external cohort of patients diagnosed with ICC through postoperative pathological examinations who received curative-intent surgery at West China Hospital of Sichuan University. ResultsA total of 4,534 ICC patients from 17 studies were included in the meta-analysis. The results indicated that gender, preoperative serum level of CA199, CEA, tumor size, tumor number, differentiation, macrovascular invasion, microvascular invasion, perineural invasion, lymph node metastasis, and AJCC T stage were ER risk factors for ICC. All risk factors were scored according to their weightings, and a risk predictive model was established. The area under the curve of the validation cohort was 0.902, indicating high predictive accuracy. Additionally, the calibration curve demonstrated that the predicted ER rate aligned well with the actual ER rate in the validation cohort. ConclusionThe predictive model accurately assesses the risk of ER in ICC patients undergoing surgical resection, providing valuable prognostic insights and guiding the tailoring of individualized treatment strategies to improve patient outcomes.

Shikonin induces ferroptosis in osteosarcomas through the mitochondrial ROS-regulated HIF-1α/HO-1 axis

BackgroundThe most common malignant bone tumour is osteosarcoma, which has an unsatisfactory prognosis and unsatisfactory treatment. Ferroptosis shows promise as an effective OS therapy. A substance extracted from the Lithospermum erythrorhizon, Shikonin (SHK), inhibits a number of tumours, including ovarian, gastric, and lung cancers. However, whether SHK induces OS ferroptosis and its mechanisms are not clear. PurposeOur study is aimed at investigating whether SHK causes ferroptosis and elucidating its molecular mechanism. MethodsCell counting Kit-8, cell cycle and cell apoptosis assay were utilised to assess therapeutic effect of SHK against OS. Normal cells, including H9C2, AML-12 and HK-2, haematoxylin and eosin staining and mice serum biomarker tests were used to assess SHK biosafety. Malondialdehyde (MDA) levels, the glutathione (GSH)/oxidized glutathione (GSSG) ratio, reactive oxygen species (ROS), lipid peroxide (LPO), and intracellular Fe2+ detection, quantitative reverse transcription PCR (qRT-PCR), Western blotting (WB) and rescue experiments were employed to confirm whether SHK induced ferroptosis in OS cells. Molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay were used to evaluate the direct binding between SHK and hypoxia-inducible factor-1α (HIF-1α). Protein stability and degradation analysis, small RNA interference, flow cytometry, qRT-PCR, and WB were used to investigate the molecular mechanism of ferroptosis. In vivo xenografts of nude mouse was used to study the anti-OS effect of SHK. ResultsSHK significantly reduced OS cell viability and induced apoptosis and G2/M arrest. SHK increased intracellular levels of MDA, ROS, LPO, and Fe2+ while simultaneously reducing the GSH/GSSG ratio and GPX4 and SLC7A11 expression. CETSA and DARTS results demonstrated that SHK did not bind targetly to HIF-1α. Instead, mitochondrial ROS (MitoROS) promoted HIF-1α expression, resulting in HO-1 overexpression, excess Fe2+ production, ROS accumulation and GPX depletion, and ferroptosis. Furthermore, inhibition of MitoROS using Mito-TEMPO downregulated HIF-1α/HO-1 axis and mitigated the SHK-induced ferroptosis. In vivo, SHK effectively suppressed OS growth with favourable biosafety, confirming the molecular mechanism underlying SHK-induced ferroptosis in OS. ConclusionWe observe that HIF-1α/HO-1 axis is the crucial factor in SHK-induced OS ferroptosis. Importantly, we demonstrate that HIF-1α is indirectly regulated by MitoROS rather than SHK bound directly to HIF-1α. Our research suggest that SHK is a potential drug candidate for OS treatment and may help in identifying novel therapeutic targets for OS.

Surgical microwave ablation of 397 neuroendocrine liver metastases: a retrospective cohort analysis of 16 years of experience.

Neuroendocrine tumors (NET) constitute a heterogeneous group of malignancies whose incidence has been on the rise over the past two decades, currently documented at 5.25 per 100,000. Liver metastasis develops in over 60% of NET patients. Even after resection recurrence rates are high, underscoring the importance of parenchymal-sparing interventions. In this study, we conducted 105 surgical microwave ablations and examined outcomes related to survival and local recurrence. Retrospective review of patients who underwent a surgical microwave ablation (MWA) at a single-center, high-volume institution from September 2007 through December 2022 using a prospective database. Primary outcome was overall survival. A total of 105 operations were performed on 94 patients, with 397 tumors undergoing MWA. Median tumor size was 1.3cm (range 0.3-8.0), and the median number of tumors ablated was 2 (range 1-12). Laparoscopic approach was utilized 69.5% of the time. The most common concomitant procedure performed was hepatectomy (33.3%) and cholecystectomy (23.8%). Clavien-Dindo grade III or IV complications occurred in 9 patients (9.6%). Mortality within 30days occurred in 1 patient (1.1%). The rate of incomplete ablation was 0.3% per tumor. Local recurrence occurred in 2.8% of tumors. Median OS was 9.43years [95% CI 4.23-14.63years], with a 5- and 10-year survival probability of 70.2% and 48.2%, respectively. Surgical MWA offers an efficacious, parenchymal-sparing treatment of hepatic metastasis of NET, with low rates of incomplete ablation and local recurrence per tumor.

The characteristics of pediatric primary retroperitoneal teratoma and the influencing factors of perioperative complications

To explore the characteristics of pediatric primary retroperitoneal teratoma and the influencing factors of perioperative complications. The clinical data, imaging data, pathology results, perioperative complications, etc of patients with primary retroperitoneal teratoma admitted and treated at Shanxi Children's Hospital from March 2013 to September 2023 were retrospectively analyzed. The patients were divided into no complication group and complication group according to whether there were perioperative complications. The differences between the two groups were compared, and the influencing factors of complications were analyzed by multivariate logistic regression model. A total of 33 patients were included in this study, including 7 males and 26 females, with an age of [M (Q1, Q3), 9.0 (4.0, 24.0)] months. Nineteen cases had tumors located in the left upper abdomen and 14 cases in the right upper abdomen, among which 17 cases grew across the midline, with the maximum tumor diameter of (12.9±4.5) cm. All patients had anatomical displacement of retroperitoneal vessels and organs: the number of anatomical displaced arteries was 3 (3, 4), the number of anatomical displaced veins was 4 (3, 5), the number of anatomical displaced organs was 5 (4, 6). Pathologic examination revealed 28 mature teratomas (Grade 0 and Grade 1) and 5 immature teratomas (Grade 2 and Grade 3). There were 18 cases in no complication group and 15 cases in the complication group. The incidence of perioperative complications was 45.5% (15/33). The number of tumors crossing the midline (6/18 vs 11/15, P=0.037), the number of tumors adhering closely to the surrounding tissues (7/18 vs 12/15, P=0.033), the number of anatomical displaced veins [4 (3, 4) vs 5 (4, 5), P=0.001], and the number of anatomical displaced organs [4 (3, 5) vs 6 (5, 6), P=0.001] were significantly different between the two groups. Multivariate logistic regression model analysis showed that the number of anatomical displaced organs (OR=8.781, 95%CI: 2.155-35.784, P=0.002) was the influencing factor for perioperative complications of pediatric primary retroperitoneal teratoma.

Multiparametric MRI based deep learning model for prediction of early recurrence of hepatocellular carcinoma after SR following TACE.

Surgical resection (SR) following transarterial chemoembolization (TACE) is a promising treatment for unresectable hepatocellular carcinoma (uHCC). However, biomarkers for the prediction of postoperative recurrence are needed. To develop and validate a model combining deep learning (DL) and clinical data for early recurrence (ER) in uHCC patients after TACE. A total of 511 patients who received SR following TACE were assigned to derivation (n = 413) and validation (n = 98) cohorts. Deep learning features were taken from the largest tumor area in liver MRI. A nomogram using DL signatures and clinical data was made to forecast early recurrence risk in uHCC patients. Model performance was evaluated using area under the curve (AUC). A total of 2278 subsequences and 31,346 slices multiparametric MRI including contrast-enhanced T1WI, T2WI and DWI were input in the DL model simultaneously. Multivariable analysis identified three independent predictors for the development of the nomogram: tumor number (hazard ratio [HR]:3.42, 95% confidence interval [CI]: 2.75-4.31, P = 0.003), microvascular invasion (HR: 9.21, 6.24-32.14; P < 0.001), and DL scores (HR: 17.46, 95% CI: 12.94-23.57, P < 0.001). The AUC of the nomogram was 0.872 and 0.862 in two cohorts, significantly outperforming single-subsequence-based DL mode and clinical model (all, P < 0.001). The nomogram provided two risk strata for cumulative overall survival in two cohorts, showing significant statistical results (P < 0.001). The DL-based nomogram is essential to identify patients with uHCC suitable for treatment with SR following TACE and may potentially benefit personalized decision-making.

8080 Factors Affecting Survival of Lymph Node Positive Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program

Abstract Disclosure: M. Mortagy: None. A. Abdelhameed: None. M. Hegazy: None. Introduction: 50-70% of patients with MTC have positive lymph nodes. The Aim is to identify factors affecting survival of the lymph node positive MTC sub-population. Understanding these factors is important in treating these patients. Methods 1359 patients with lymph node positive MTC who were diagnosed with positive histology or cytology from 1975 to 2020 were extracted from SEER after removing duplicates. Survival analysis was performed, and Kaplan-Meier graph was produced. Univariate and multivariable Cox regression were performed, and respective hazard ratios (HR) were generated. Results: The cohort were 54% males with a median age of 55 years. Median survival: for the cohort was 163 months with survival of 91%, 80% and 74% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.04), female sex (HR 0.64), T4 stage (HR 2.48), M1 stage (HR 5.43), bone metastasis (HR 4.74), brain metastasis (HR 17.1), liver metastasis (HR 5.41), lung metastasis (HR 5.97), distant lymph node metastasis (HR 6.00), number of positive lymph nodes (HR 1.008), lymph node ratio (HR 4.50), tumor size (HR 1.02), multifocal tumor (HR 0.69), total number of malignant tumors (HR 1.21), not performing total thyroidectomy (HR 6.35), chemotherapy (HR 3.85), radiotherapy after surgery (HR 1.67), beam radiotherapy (HR 2.20), systemic therapy after surgery (HR 0.67). Univariate Cox regression was not statistically significant for grade, treatment delay, total number of benign tumors, race/ethnicity, income, and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for number of positive lymph nodes (HR 1.03), bone metastasis (HR 0.18), liver metastasis (HR 14.57), multifocal tumor (HR 3.49), total number of malignant tumors (HR 2.66), T4 stage (HR 3.57), M1 stage (HR 3.65), not performing total thyroidectomy (HR 352.43), tumor size (HR 1.03). Conclusion: Number of positive lymph nodes, T4 stage, M1 stage, presence of liver metastasis, presence of multifocal tumor, not performing total thyroidectomy and large tumor size lead to worse prognosis. Age, gender, chemotherapy, and lymph node ratio don’t affect survival. Future research is required to study this group of patients. Presentation: 6/2/2024

8061 Factors Affecting Survival of Metastatic Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program

Abstract Disclosure: A. Abdelhameed: None. H. Ibrahim: None. M. Mortagy: None. Introduction: Medullary thyroid cancer (MTC) arises from parafollicular cells of the thyroid. 43% of patients with MTC have metastasis. It was shown that the overall 5-year survival of patients with MTC is 40.4%. The clinical course of MTC is highly variable. The Aim is to identify factors affecting survival of the metastatic MTC sub-population. Understanding these factors is important in treating these patients. Methods 340 patients: with metastatic MTC who were diagnosed from 1975 to 2020 were extracted from SEER after removing duplicates and those not diagnosed by positive histology or cytology. Survival analysis was conducted, and Kaplan-Meier graph was generated. Univariate Cox regression was performed for all variables and respective hazard ratios (HR) were produced. Multivariable cox regression was performed for statistically significant variables. Results: The cohort were 59% males with a median age of 60 years. Median survival for the cohort was 20 months with survival of 63%, 41% and 31% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.02), brain metastasis (HR 2.70), liver metastasis (1.65), lung metastasis (1.42), not performing total thyroidectomy (HR 2.77), lymph node ratio (HR 2.45), and systemic therapy after surgery (HR 0.34). Univariate Cox regression was not statistically significant for sex, grade, radiotherapy, chemotherapy, treatment delay, bone metastasis, distant lymph node metastasis, multifocal cancer, total number of benign and malignant tumors, race/ethnicity, income, tumor size and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for age (HR 1.04), presence of lung metastasis (HR 1.91), and systemic therapy before surgery (HR 14.41). Conclusion: Increasing age, presence of lung metastasis and systemic therapy before surgery lead to worse prognosis in metastatic MTC. Gender, grade, radiotherapy, chemotherapy, treatment delay, bone or brain or liver metastasis, presence of multifocal cancer, race, tumor size and surgery don't affect survival according to multivariable cox regression. Future research is needed to study this group of patients. Presentation: 6/2/2024

Establishment of a clinical model based on vessels encapsulating tumour clusters that could efficiently predict recurrence of patients with hepatocellular carcinoma after curative hepatectomy

According to previous studies, vessels encapsulating tumor clusters (VETC) could promote metastasis of hepatocellular carcinoma (HCC) in a manner independent from epithelial-mesenchymal transition (EMT). However, the prognostic significance of VETC among patients undergoing curative hepatectomy has not been fully explored. This study was performed to assess the prognostic significance of VETC among patients undergoing curative hepatectomy.81 patients undergoing curative hepatectomy were included in this study. A predictive model based on VETC was established. Then this predictive model based on VETC was compared with American Joint Committee on Cancer Tumor Nodal Metastasis (AJCC TNM) and Barcelona Clinic Liver Cancer (BCLC) system.It was revealed by multivariate Cox regression analysis that high neutrophil lymphocyte ratio (NLR) (P=0.013, HR=6.175, 95%CI: 1.468-25.977), number of tumors (P＜0.001, HR=4.119, 95%CI 1.886-8.995) and VETC positivity (P=0.010, HR=2.440, 95%CI 1.235-4.821) were independent predictive factors for disease-free survival (DFS). Additionally, by Kaplan-Meier analysis, we revealed that VETC positivity was associated with worse DFS (P=0.018). Then the clinical predictive model combining NLR, number of tumors, and VETC was compared with AJCC TNM stage and BCLC classification system by performing time-dependent receiver operating curve (td-ROC) analysis, revealing that the clinical predictive model was superior to AJCC TNM stage and BCLC system at different time points. Additionally, we demonstrated that the clinical model could well predict DFS by plotting calibration curves.VETC could be utilized as an efficient prognostic factor for HCC and the clinical predictive model combining NLR, number of tumors, and VETC was superior to AJCC TNM stage and BCLC system in predicting cancer recurrence.

Living donor liver transplantation for hepatocellular carcinoma using expanded criteria and alpha-fetoprotein threshold of 1000 ng/mL

BackgroundNew guidelines propose a minimum 5-year survival of 60% for hepatocellular carcinoma (HCC) with living donor liver transplantation (LDLT). This study aimed to evaluate the 5- and 10-year survival rates after transplantation for the expanded criteria for HCC. MethodsThis single-center retrospective cohort study included 208 patients who underwent LDLT for the expanded criteria (the largest tumor diameter of ≤10 cm, any tumor number, and alpha-fetoprotein [AFP] level of <1000 ng/mL) and analyzed 5- and 10-year overall survival (OS) and recurrence risk (RR) rates. ResultsWith a median follow-up of 65.1 months (IQR, 19.1–80.2), the 5- and 10-year OS and RR rates were 67.0% and 61.0% and 20.5% and 22.5%, respectively. The largest tumor diameter of >6 cm (hazard ratio [HR], 3.7; 95% CI, 1.7–8.2; P = .001) and AFP level of >400 ng/mL (HR, 4.0; 95% CI, 1.8–9.0; P = .001) were predictors of recurrence. Patients outside the Milan criteria (MC) were grouped into low- and high-risk HCC based on tumor size and AFP level. For low-risk HCC (tumor size of <6 cm, any tumor number, and AFP level of <400 ng/mL), the 5-year RR was comparable to the MC and increased the transplant pool by 35.7% (P > .5). The median number of tumors and the rate of microvascular invasion in the high-risk group, low-risk group, and MC were 2.0 (1.0–3.2), 4.0 (2.0–5.0), and 1.0 (1.0–2.0) (P < .001) and 72.2% (13/18), 44.0% (22/50), and 22.8% (32/140) (P < .001), respectively. ConclusionThe expanded criteria met the benchmark for 5-year survival. LDLT for the low-risk HCC in the expanded criteria was associated with an acceptable RR.

Machine Learning Model Based on Prognostic Nutritional Index for Predicting Long-Term Outcomes in Patients With HCC Undergoing Ablation.

To develop multiple machine learning (ML) models based on the prognostic nutritional index (PNI) and determine the optimal model for predicting long-term survival outcomes in hepatocellular carcinoma (HCC) patients after local ablation. From January 2009 to December 2019, we analyzed data from 848 primary HCC patients who underwent local ablation. ML models were constructed and evaluated using the concordance index (C-index), concordance-discordance area under curve (C/D AUC), and Brier scores. The optimal ML model was interpreted using the partial dependence plot (PDP) and SHapley Additive exPlanations (SHAP) framework. Additionally, the prognostic performance of our model was compared with other models. Alkaline phosphatase, preoperation alpha-fetoprotein level, PNI, tumor number, and tumor size were identified as independent prognostic factors for ML model construction. Among the 19 ML algorithms tested, the Aorsf model showed superior performance in both the training cohort (C/D AUC: 0.733; C-index: 0.736; Brier score: 0.133) and validation cohort (C/D AUC: 0.713; C-index: 0.793; Brier score: 0.117). The time-dependent AUC of the Aorsf model for predicting overall survival was as follows: 1-, 3-, 5-, 7-, and 9-year were 0.828, 0.765, 0.781, 0.817, and 0.812 in the training cohort, 0.846, 0.859, 0.824, 0.845, and 0.874 in the validation cohort, respectively. The PDP and SHAP algorithms were employed for visual interpretation. Furthermore, time-AUC and decision curve analysis demonstrated that the Aorsf model provided superior clinical benefits compared to other models. The PNI-based Aorsf model effectively predicts long-term survival outcomes after ablation therapy, making a significant contribution to HCC research by improving surveillance, prevention, and treatment strategies.

Helicobacter Pylori Infection as the Predominant High-Risk Factor for Gastric Cancer Recurrence Post-Gastrectomy: An 8-Year Multicenter Retrospective Study.

The reappearance of gastric cancer, a frequent postoperative complication following radical gastric cancer surgery, substantially impacts the near-term and far-reaching medical outlook of patients. The objective of this research was to create a machine learning algorithm that could recognize high-risk factors for gastric cancer recurrence and anticipate the correlation between gastric cancer recurrence and Helicobacter pylori (H. pylori) infection. This investigation comprised 1234 patients diagnosed with gastric cancer, and 37 characteristic variables were obtained. Four machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), k-nearest neighbor algorithm (KNN), and multilayer perceptron (MLP), were implemented to develop the models. The k-fold cross-validation technique was utilized to perform internal validation of the four models, while independent datasets were employed for external validation of the models. In contrast to the other machine learning models, the XGBoost algorithm demonstrated superior predictive ability regarding high-risk factors for gastric cancer recurrence. The outcomes of Shapley additive explanation (SHAP) analysis revealed that tumor invasion depth, tumor lymph node metastasis, H. pylori infection, postoperative carcinoembryonic antigen (CEA), tumor size, and tumor number were risk elements for gastric cancer recurrence in patients, with H. pylori infection being the primary high-risk factor. Out of the four machine learning models, the XGBoost algorithm exhibited superior performance in predicting the recurrence of gastric cancer. In addition, machine learning models can help clinicians identify key prognostic factors that are clinically meaningful for the application of personalized patient monitoring and immunotherapy.

The Efficacy and Safety of Bevacizumab Plus Anti-PD-1/PD-L1 Inhibitors in Combination with Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma.

To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC). In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0-13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, P = 0.69) or OS (HR, 0.71, P = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS. Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.

The clinical prognostic risk stratification system for HIV infected hepatocellular carcinoma

BackgroundPatients with human immunodeficiency virus (HIV) are more susceptible to liver cancer because of their compromised immune system. There is no specific prognostic model for HIV-infected hepatocellular carcinoma (HCC) patients. MethodsClinical data of 85 patients with HIV-infected HCC was divided into a 7:3 ratio for training and internal validation sets, while the data of 23 patients with HIV-infected HCC was served as the external validation set. Data of 275 HIV-negative HCC patients was considered as external HIV-negative validation set. Variables associated with overall survival (OS) in the training set were used to develop the HIV-infected HCC prognosis (HIHP) model. The model was tested in the internal and external validation sets. The predictive accuracy of the model was assessed with conventional HIV-negative HCC prognostic scoring systems. ResultsIn the training set, variables independently associated with OS in multivariable analysis were organ involvement and tumor number. The HIHP model demonstrated a significant association with OS in the training set, with a median OS of 13 months for low risk, 7 months for medium risk, and 3 months for high risk (p < 0.001). The HIHP model showed a significant association with OS, and exhibited greater discriminative abilities compared to conventional HIV-negative HCC prognostic models both in the internal and external validation sets. In the external HIV-negative validation set, the HIHP model did not show better discrimination than conventional HIV-negative HCC scores. ConclusionThe new model presented in the work provided a more accurate prognostic prediction of OS in HIV-infected HCC patients. However, the model is not applicable to patients with HIV-negative HCC.

Transarterial chemoembolization combined with lenvatinib plus tislelizumab for unresectable hepatocellular carcinoma: a multicenter cohort study.

Comparing the efficacy of transarterial chemoembolization (TACE) combined with lenvatinib plus tislelizumab (TLT) with TACE combined with lenvatinib (TL) for unresectable hepatocellular carcinoma, particularly in determining which patients can benefit more from the TLT treatment. From March 2021 to September 2023, a total of 169 patients from three centers were included in this study, with 103 patients receiving TLT and 66 patients receiving TL. The Kaplan-Meier method was utilized to evaluate the cumulative overall survival (OS) and progression-free survival (PFS) between the two groups and were assessed using the log-rank test. Subgroup analysis on tumor number, maximum tumor diameter, presence of portal vein thrombosis, AFP level, and Child-Pugh class were conducted. The median OS was 26 months in the TLT group, and 20 months in the TL group. The median PFS was 14 months in the TLT group and 9 months in the TL group. The Kaplan-Meier curve demonstrated a significantly superior OS and PFS in the TLT group compared to the TL group. Subgroup analysis showed that for patients with a maximum tumor diameter greater than 7 cm, AFP > 400 ng/ml and accompanied by portal vein tumor thrombus, and Child-Pugh class A, there was a statistically significant difference in OS between TLT and TL groups. OS and PFS were significantly improved in patients who received TLT compared to those who received TL, patients with a largest tumor diameter greater than 7 cm, AFP > 400 ng/ml, Child-Pugh class A and PVTT appeared to derive more benefit.

Hexokinase 2 as an independent risk factor for worse patient survival in esophageal adenocarcinoma and as a potential therapeutic target protein: A retrospective, single‑center cohort study.

Cancer cells exhibit a distinct metabolic profile that features an upregulation of less efficient glycolysis accompanied by lactate production for energy generation, in contract to the characteristic metabolism of normal cells. Consequently, cancer research has focused on the enzymes that participate in these cancer metabolic pathways. Among them, hexokinase 2 (HK2) has an important position as the initial enzyme in the glycolytic pathway. Increased expression levels of HK2 have been correlated with an increased risk of poor patient outcomes and advanced tumor stages in a number of malignant tumors, such as gastric carcinoma. The present study aimed to investigate the specific role of HK2 in patients diagnosed with esophageal adenocarcinoma. A total of 643 patients with esophageal adenocarcinoma were included. Immunohistochemical staining and HK2 mRNA in situ probes were used to investigate the association of HK2 expression levels with clinical and molecular tumor characteristics. Patients who exhibited high HK2 expression levels demonstrated significantly reduced overall survival (OS) times compared with patients who exhibited low HK2 expression levels (29.6 vs. 39.9 months, respectively; P=0.027). Furthermore, high HK2 expression levels were demonstrated to be an independent risk factor for reduced patient survival (hazard ratio, 1.65; 95% CI, 1.09-2.50; P=0.018). Significantly reduced patient survival was also demonstrated in the subgroups of male patients, patients with primarily resected tumors, patients with HER2-negative tumors and patients with tumors exhibiting Y chromosome loss. Elevated expression of HK2 was identified as a risk factor for unfavorable patient survival in esophageal adenocarcinoma. This revelation suggests the potential for future diagnostic and therapeutic avenues tailored to this specific patient subset. Identifying patients with high HK2 expression may pinpoint a higher-risk cohort, paving the way for comprehensive prospective studies that could advocate for intensified monitoring and more aggressive therapeutic regimens. Furthermore, the targeted inhibition of HK2 could hold promise as a strategy to potentially enhance patient outcomes.

Rationale of restaging transurethral resection of bladder tumor in patients with nonmuscle invasive bladder cancer in the current era

Background: We present retrospective data of patients with nonmuscle invasive bladder cancer (NMIBC) who underwent restaging transurethral resection of bladder tumor (Re-TURBT) at a tertiary care center. Materials and Methods: Records of all NMIBC patients undergoing Re-TURBT between March 2021 and September 2023 were retrospectively analyzed. Patients were risk stratified based on TURBT pathology. Re-TURBT was performed between 4 and 6 weeks. Adverse features such as number, size, and appearance were noted. Patients with persistent disease at Re-TURBT were counseled for early cystectomy with urinary diversion or intravesical Bacillus Calmette–Guerin (BCG). In case of disease upstaging, patients were counseled for radical cystectomy. Results: Thirty-eight NMIBC patients (30 males and 8 females) underwent Re-TURBT. Six patients had residual/persistent disease at 6 weeks, all high risk and high grade (HG, P value not significant, P = 0.31). There was no association with number and appearance of tumors with residual/persistence at 6 weeks. The mean lesion size on imaging in cases with and without residual disease was 3.32 ± 0.86 versus 3.39 ± 0.92 cm, respectively, P value not significant (0.868). There was no residual disease in the low-grade (LG) pT1 group, but HG pTa and pT1 (n = 3) had residual disease. Four HG pT1 patients opted for early cystectomy. Two patients each had pT0 and two pT2. At 3 months of follow-up, urethral strictures were seen both in high risk and intermediate risk. Among four patients who had stricture, meatal stenosis was common (50%, n = 2). Two patients had long-segment stricture requiring perineal urethrostomy with stage I Johannsen repair. All HG pT1 lesion patients eventually underwent cystectomy (3 were under staged and two treated completely with TURBT, one with TURBT + BCG and one patient progressed to metastasis). Conclusion: Re-TURBT is essential for the management of HG pTa and HG pT1 lesions for accurate staging and treatment of residual disease. However, LG pT1 patients can safely be excluded from Re-TURBT.

Sinonasal Tumors: What the Multidisciplinary Cancer Care Board Wants to Know.

Sinonasal neoplasms are a remarkably heterogeneous group, reflecting the numerous tissue types present in the nasal cavity and paranasal sinuses. These entities can be relatively benign (ie, respiratory epithelial adenomatoid hamartoma) or can be exceedingly aggressive (ie, NUT carcinoma). Certain sinonasal tumors have a propensity to spread through local invasion and destruction, while others have a high likelihood of perineural spread. The genetic and molecular mechanisms underlying sinonasal tumor behavior have recently become better understood, and new tumor types have been described using these genetic and molecular data. This has prompted an expansion in the number of tumors included in the World Health Organization fifth edition classification system for head and neck tumors, along with a new classification structure. Radiologists' familiarity with this classification structure is crucial to understanding the expected behavior of these tumors and to collaboration with the multidisciplinary cancer care board in making decisions for optimal patient care. ©RSNA, 2024.

Treatment strategies with electrochemotherapy for limb in-transit melanoma: Real-world outcomes from a European, retrospective, cohort study

BackgroundThis study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM). MethodsWe audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006–2020) within the International Network for Sharing Practices of ECT (InspECT). Results452 patients were included, 58 % pre-treated (93 % had lower limb ITM, 44 % had ≤10 metastases [median size 1.5 cm]. Treatment strategies included first-line ECT (n = 145, 32 %), ECT with concurrent locoregional/systemic treatment (n = 163, 36 %), and salvage ECT (n = 144, 32 %). The objective response rate was 63 % (complete response [CR], 24 %), increasing to 74 % (CR, 39 %) following retreatment (median two ECT, range 1–8). CR rate in treatment-naïve and pre-treated patients was 50 % vs 32 % (p < 0.001). Bleomycin de-escalation was associated with lower CR (p = 0.004). Small tumour number and size, hexagonal electrode, retreatment, and post-ECT skin ulceration predicted response in multivariable analysis. At a median follow-up of 61 months, local and locoregional recurrence occurred in 55 % and 81 % of patients. Median local progression-free, new lesions-free, and regional recurrence-free survival were 32.9, 6.9, and 7.7 months. Grade-3 toxicity was 15 %. Concurrent treatment and CR correlated with improved regional control and survival. Concomitant checkpoint inhibition did not impact toxicity or survival outcomes. The median overall survival was 5.7 years. ConclusionsAmong patients with low-burden limb-only ITM, standard-dose bleomycin ECT results in durable local response. Treatment naivety, low tumour volume, hexagonal electrode application, retreatment, and post-ECT ulceration predict response. CR and concurrent treatment correlate with improved regional control and survival outcomes. Combination with checkpoint inhibitors is safe but lacks conclusive support.

Triiodothyronine (T3) suppresses hepatic tumorigenesis and development by inhibiting the phosphorylation of ERK.

The effect of triiodothyronine (T3) on the phosphorylation of ERK and the occurrence and development of hepatocellular carcinoma (HCC) is controversial and remains to be clarified. In the present study, both in vitro (hepatoma cell lines) and in vivo (wild-type mice [WT] and mouse models of HCC [HrasG12Vand KrasG12Dtransgenic mice (Hras-Tg and Kras-Tg)]) systems were used to investigate the effect of T3 on p-ERK and hepatocarcinogenesis. The results showed that, in vitro, T3 treatment elevated the levels of p-ERK in hepatoma cells within 30 min. However, p-ERK levels returned to normal after 1 h with no significant effects on cellular proliferation or apoptosis. Interestingly, in vivo, T3 induced early rapid and transient activation of ERK and later persistent downregulation of p-ERK in liver tissues of WT. In Hras-Tg, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes were significantly reduced withT3treatment compared with the untreated group. Furthermore, the levels of albumin, HrasG12V, and p-ERK in hepatic precancerous and tumor tissues were all significantly downregulated with T3 treatment; however, the levels of endogenous Hras were not affected. In WT, T3 also induced downregulation of Albumin in liver tissues, but without influence on the expression of endogenous Hras and p-MEK. Especially, the inhibitory effect of T3 on p-ERK and hepatic tumorigenesis and development without influence on the levels of KrasG12D and p-MEK was further confirmed in Kras-Tg. In conclusion, T3 suppresses hepatic tumorigenesis and development by independently and substantially inhibiting the phosphorylation of ERK in vivo.

Yes-associated protein indispensably mediates hirsutine-induced inhibition on cell growth and Wnt/β-catenin signaling in colorectal cancer

Background and purpose: Targeting Wnt/β-catenin signaling emerges as one of the promising strategies for colorectal cancer (CRC) treatment, as this signaling is highly activated in CRC progression. Despite reports on the cytotoxic effects of hirsutine (HT), an indole alkaloid found in herbal medicines from the genus Uncaria, its therapeutic potential for CRC and the involved mechanisms are poorly understood. This study investigates the anticancer efficacy and the probable mechanisms of HT against CRC. Methods: To evaluate in vitro anticancer activity of HT, cell growth examined by MTT and colony formation assay, and apoptosis examined by flow cytometry were performed. To explore the mechanisms, RNA-sequencing, western blotting, dual-luciferase reporter assays, immunofluorescence, and co-immunoprecipitation were performed. Mouse model of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colon cancer was utilized to assess HT's in vivo anticancer efficacy. Results: HT significantly inhibited CRC cell proliferation with IC50 values of 22.25 ± 3.27 μM for SW620 cells and 22.24 ± 2.36 μM for HCT116 cells, and induced apoptosis. HT decreased protein levels of Wnt3a and β-catenin dose- and time-dependently, and inhibited TOP/FOP FLASH reporter activity, nuclear travel of β-catenin, and downstream targets like c-Myc, Cyclin D1, VEGF. HT reduced β-catenin protein half-life, and the reversal of this effect by MG132 indicated that HT facilitated proteasome-dependent degradation of β-catenin in these two cell lines. HT also increased β-catenin ubiquitination without affecting Axin and β-TrCP levels. HT treatment for 24 h induced YAP cytoplasmic retention, enhanced YAP interacting with β-catenin and β-TrCP, triggering destruction complex formation and β-catenin ubiquitination and degradation, while YAP siRNA impaired these effects. Additionally, β-catenin overexpression and LiCl treatment counteracted HT-induced inhibition on cell growth and Wnt/β-catenin cascade. In model of AOM/DSS-induced mouse colon cancer, compared with AOM/DSS treatment group, HT recovered colon length, reduced tumor numbers and radius, and downregulated β-catenin and Ki-67, while upregulated cleaved PARP in the colorectal tissue with tumors. Conclusion: HT exhibits anticancer activity against CRC probably by inhibiting Wnt/β-catenin signaling, with YAP playing an indispensible role during the process, highlighting HT as a potential novel candidate drug for CRC therapy.