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BackgroundThe association of the p53 rs1042522 and rs17878362 polymorphisms with cervical cancer risk has been reported in several published original studies and meta-analyses. However, the conclusions of these studies were contradictory. Consequently, we conducted an updated meta-analysis to further validate these debates.ObjectiveTo evaluate the association between the p53 rs1042522 and rs17878362 polymorphisms and cervical cancer risk.Materials and MethodsPubMed, Medline, Ovid, Embase, CNKI, and China Wanfang databases were searched. Association was assessed using odds ratio (OR) with 95% confidence interval (CI). Moreover, the false-positive reporting probability (FPRP), Bayesian false-finding probability (BFDP), and Venice criteria were used to assess the credibility of statistically significant association.ResultsA significantly decreased cervical cancer risk was revealed for the p53 rs1042522 polymorphism (Pro/Pro +Arg/Pro vs. Arg/Arg: OR = 0.79, 95% CI = 0.71-0.87; Pro/Pro vs. Arg/Arg: OR = 0.80, 95% CI = 0.70-0.91; Arg/Pro vs. Arg/Arg: OR = 0.78, 95% CI = 0.71-0.86; Pro vs. Arg: OR = 0.87, 95% CI = 0.81-0.93) in overall analysis and several subgroup analyses, such as in Caucasians, Asians, Indians, and so on. However, no significant association was found between the p53 rs17878362 polymorphism and cervical cancer risk. Despite these statistically significant results, reliability analysis using FPRP, BFDP, and Venice criteria deemed all associations “unreliable”.ConclusionsAfter considering the reliability of the results, this study indicates that the p53 rs1042522 polymorphism is not associated with the cervical cancer risk.

ObjectivesTo assess the diagnostic accuracy of multimodal ultrasound in differentiating anaplastic thyroid carcinoma (ATC) from papillary thyroid carcinoma (PTC) and to evaluate its capability in detecting thyroid carcinoma (TC) aggressiveness.MethodsSixty nude mice were randomly assigned to ATC and PTC groups and injected subcutaneously with KHM-5M and TPC-1 cell lines, respectively. Tumors were analyzed using B-mode ultrasound (B-US), Color Doppler flow imaging (CDFI), elastography, and contrast-enhanced ultrasound (CEUS). A logistic model integrating multimodal ultrasound data was constructed, and Ki-67 and CD31 expressions in tumor tissues were analyzed immunohistochemically. Correlations between ultrasound features and aggressiveness markers were investigated.ResultsThe ATC group exhibited significantly higher strain-elastography scores (p=0.009) and Adler grades in CDFI (p=0.045). CEUS revealed a higher frequency of heterogeneous enhancement (95.2% vs. 48.1%, p

BackgroundSystemic inflammation (SI) and insulin resistance (IR) are correlated to the progression of gastrointestinal (GI) cancer. Therefore, this study aimed to analyze the potential clinical value of the C-reactive protein-triglyceride-glucose index (CTI) in relation to SI and IR in patients with GI cancer.MethodsThis prospective cohort study included patients with GI cancer. Patient data were collected from Fujian Cancer Hospital as an external validation cohort. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses were used to predict the efficacy and accuracy of CTI survival prediction. Multivariate survival analysis was performed to evaluate the potential prognostic value of the CTI. Multiple logistic regression was performed to evaluate the relationship between the CTI and 90-day and 180-day mortalities.ResultsWe divided 1520 patients with GI cancer (mean age, 60.39 ± 11.3 years; male sex, 67%) into a training cohort and internal validation cohort; the external validation cohort included 476 patients. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses of all cohorts indicated that the CTI could reliably and accurately predict the short- and long-term survival outcomes of patients with GI cancer. Multivariate survival analysis showed that for each standard deviation increase in the CTI, the risk of death increased by 32%, 21%, and 40% in the training, internal validation, and external validation cohorts, respectively. A high CTI was correlated to worse survival in patients with GI cancer (training cohort, hazard ratio [HR]=1.67, 95% confidence interval [CI]=1.35–2.08; internal validation cohort, HR=1.51, 95% CI=1.07–2.14, and external validation cohort, HR=1.59, 95% CI=1.18–2.13). In different tumor subgroups, a high CTI predicted worse survival outcomes for upper GI cancer (HR=1.54, 95% CI=1.18–2.01) and lower GI cancer (HR=1.98, 95% CI=1.36–2.86). Multivariate logistic regression analysis showed that a high CTI was positively correlated with 90-day (odds ratio [OR]=3.25, 95% CI=1.75–6.23) and 180-day mortalities (OR=2.66, 95% CI=1.72–4.15).ConclusionsThe CTI is related to SI and IR and can predict the short- and long-term prognosis of patients with GI cancer. Evaluation of the CTI could provide clinicians with an effective tool for predicting the prognosis of patients with GI cancer.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=31813, identifier ChiCTR1800020329.

BackgroundFerroptosis is a cell death mode caused by excessive accumulation of lipid peroxides caused by disturbance of intracellular metabolic pathway, which is closely related to iron and cholesterol metabolism homeostasis. Its regulation within the hypoxic metabolic tumor microenvironment (TME) has the potential to improve the effectiveness of tumor immunotherapy. The predictive role of ferroptosis in gastric cancer (GC) hypoxia TME, particularly in relation to TME immune cell infiltration, has not been fully explained.MethodsBy analyzing the mRNA expression data of ferroptosis and hypoxia-related genes, a prediction model was constructed to evaluate further the predictive value of immune cell infiltration, clinical characteristics, and immunotherapy efficacy of gastric cancer, and the essential genes were validated.ResultsTwo distinct molecular states of ferroptosis-hypoxia were identified in GC. Notably, patients with high ferroptosis-hypoxia risk scores (FHRS) displayed significant levels of hypoxia and epithelial-mesenchymal transition (EMT), which were associated with unfavorable prognosis, increased chemoresistance, and heightened immunosuppression.ConclusionsThis study demonstrates that ferroptosis under hypoxic conditions significantly affects the modulation of the tumor immune microenvironment. The FHRS can independently predict prognosis in gastric cancer. Assessing the molecular status of ferroptosis-hypoxia in individual patients will help in selecting more suitable immunotherapy regimens by providing a better understanding of TME characteristics and predicting immunotherapeutic outcomes.

IntroductionBreast cancer is currently the most prevalent cancer globally; however, it generally has a favorable prognosis and is linked to a high survival rate. While effective treatments can extend survival and mitigate associated side effects, not all survivors are exempt from complications. Notably, a significant proportion of survivors experience sleep disorders following surgery, which can severely impact their quality of life. Exercise is frequently recommended as a non-pharmacological intervention to enhance sleep quality among breast cancer survivors and may also play a role in reducing recurrence rates. Recognizing that various forms of exercise may yield different outcomes in addressing sleep disorders in this population, we conducted a network review meta-analysis to assess the effectiveness of diverse exercise modalities for breast cancer survivors suffering from sleep disturbances.MethodsWe searched four electronic databases for randomized controlled trials of individuals diagnosed breast cancer with sleep disorders by different exercise therapy. The primary outcomes included Yoga, Pilates, Qigong, Tai Chi, Walking, Dance, Resistance training, Football, Virtual reality therapy, Activity change exercise, Software-guided exercises. The methodological quality of the included studies was assessed using the Cochrane Bias risk Assessment tool, and network meta-analysis was performed using Stata15 software. The review was pre-registered (PROSPERO ID: CRD42023442892).ResultsData on 3083 breast cancer survivors with sleep disturbances from 34 eligible randomized controlled trials were analyzed, with 23 classified as medium risk and 2 as high risk. Network meta-analysis showed that walking exercise [Standard Median Different (SMD) =3.06, 95% Confidence Interval (95%CI)=(-5.89,-0.23)] significantly improved sleep disorder (Surface Under the Cumulative Ranking curve, SUCRA: 84.5%) and reduced Pittsburgh sleep quality index (PSQI) score.DiscussionBased on the network ranking table, we can conclude that walking exercise offers greater benefits compared to other exercise interventions for improving sleep quality in breast cancer patients. This finding presents a novel perspective on exercise interventions for breast cancer survivors experiencing sleep disorders.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=442892, identifier CRD42023442892.

BackgroundApatinib is a small molecule anti-angiogenesis targeted drug that has demonstrated significant efficacy as a late-line treatment in advanced gastric cancer in phase 3 clinical trials. This study amid to evaluate the correlation between dose exposure intensity and efficacy and safety of apatinib in the treatment of advanced gastric cancer.MethodsWe conducted an observational, retrospective cohort study of patients with advanced gastric cancer who received apatinib targeted therapy in Beijing Friendship Hospital affiliated to Capital Medical University between June 1, 2018, and June 30, 2021. Dose exposure intensity (DEI) was defined as the product of dose and continuous medication time. Patients were assigned to high-dose exposure intensity (HDEI) and low-dose exposure intensity (LDEI) cohorts. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and safety. The relationship between HDEI and LDEI and clinical outcomes was analyzed by using the Kaplan-Meier curve and χ2 test.Results61 patients were enrolled and assigned into two retrospective cohorts. The median PFS (mPFS) were 6.50 months (95% confidence interval (CI) [4.80-9.20]) and 4.10 months (95% CI [3.70-5.20]), and the median OS (mOS) were 10.70 months (95% CI [9.20-18.50]) and 7.50 months (95% CI [6.80-9.30]) for the HDEI and LDEI cohorts, respectively. The mPFS were 5.85 months (95% CI [5.00-7.00]) and 4.60 months (95% CI [4.10-5.90]), and mOS were 9.60 months (95% CI [9.10-12.40]) and 7.60 months (95% CI [7.20-10.20]) the for the 250 mg cohort and 500 mg cohorts. The mPFS were 6.65 months (95% CI [5.90-9.20]) and 4.10 months (95% CI [3.90-5.20]), and the mOS were 11.20 months (95% CI [9.20-18.50]) and 7.60 months (95% CI [7.20-9.60])for the long medication time and short medication time cohorts, respectively. The most common TRAEs of any grade were hypertension, proteinuria, and neutrophil count decreased. The incidence of grade 3-4 adverse reactions in the 500 mg cohort was higher than the 250 mg cohort (P=0.0016).ConclusionThe efficacy of apatinib in advanced gastric cancer was significantly positively correlated with dose exposure intensity, and HDEI can prolong PFS and OS. Early application of low-dose apatinib (250 mg/d) can improve patients’ tolerability, and the adverse reactions are controllable.

Metformin (MET) is a commonly used drug for the treatment of type 2 diabetes in the department of endocrinology. In recent years, due to the few clinically effective treatment options including glioma, some scholars have proposed the possibility of metformin in the treatment of glioma, and studies have shown that metformin has a certain inhibitory effect on this tumor. This review explores the multiple mechanisms through which metformin exerts its antitumor effects, focusing on signaling pathways such as AMPK/mTOR, ferroptosis, autophagy, apoptosis and chloride ion channels (CLIC1). Metformin’s inhibition of glioma proliferation involves complex cellular processes, including mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and modulation of immune responses. Additionally, metformin affects glioma stem cells by inhibiting key pathways, including STAT3, mTOR, and AKT, and altering the tumor microenvironment. While preclinical studies suggest that metformin enhances radiosensitivity and reduces tumor recurrence, its clinical application remains in early stages, with further studies needed to optimize dosing regimens and understand its full therapeutic potential. This review provides a comprehensive analysis of metformin’s molecular mechanisms in glioma treatment and highlights its potential as a novel therapeutic strategy, especially for treatment-resistant gliomas.

ObjectivesTo develop a novel automatic delineation model, the Multi-Scale Channel Attention U-Net (MCAU-Net) model, for gallbladder segmentation on CT images of patients with liver cancer.MethodsWe retrospectively collected the CT images from 120 patients with liver cancer, based on which ground truth was manually delineated by physicians. The images and ground truth constitute a dataset, which was proportionally divided into a training set (54%), a validation set (6%), and a test set (40%). Data augmentation was performed on the training set. Our proposed MCAU-Net model was employed for gallbladder segmentation and its performance was evaluated using Dice Similarity Coefficient (DSC), Jaccard Similarity Coefficient (JSC), Positive Predictive Value (PPV), Sensitivity (SE), Hausdorff Distance (HD), Relative Volume Difference (RVD), and Volumetric Overlap Error (VOE) metrics.ResultsOn the test set, MCAU-Net achieved DSC, JSC, PPV, SE, HD, RVD, and VOE values of 0.85 ± 0.22, 0.79 ± 0.23, 0.92 ± 0.14, 0.84 ± 0.23, 2.75 ± 0.98, 0.18 ± 0.48, and 0.22 ± 0.42, respectively. Compared to the control models, U-Net, SEU-Net and TransUNet, the MCAU-Net improved DSC 0.06, 0.04 and 0.06, JSC by 0.09, 0.06 and 0.09, PPV by 0.08, 0.08 and 0.05, SE by 0.05,0.05 and 0.07, and reduced HD by 0.45, 0.28 and 0.41, RVD by 0.07, 0.03 and 0.07, VOE by 0.04, 0.02 and 0.08 respectively. Qualitative results revealed that MCAU-Net produced smoother and more accurate boundaries, closer to the expert delineation, with less over-segmentation and under-segmentation and improved robustness.ConclusionsThe MCAU-Net model significantly improves gallbladder segmentation on CT images. It satisfies clinical requirements and enhances the efficiency of physicians, particularly in segmenting complex anatomical structures.

BackgroundIt is uncommon to come across instances of aplastic anemia in individuals suffering from papillary thyroid carcinoma complicated by Hashimoto’s thyroiditis. Here, a unique case is presented.Case presentationA 23-year-old male was admitted to the hospital for “a lump in his right neck”. Laboratory tests revealed a decrease in white blood cells (WBC), red blood cells (RBC), and platelet count (PLT). Bone marrow aspiration revealed an extremely low degree of hyperplasia of hematopoietic cells. Simultaneously, the levels of thyroglobulin antibodies and thyroid peroxidase antibodies were significantly elevated. Neck ultrasound findings revealed nodules in both lobes of the thyroid. Moreover, fine-needle aspiration biopsy indicated the atypical presence of proliferative thyroid epithelial cells. Even after implementing various treatments hematopoietic function could not be restored. However, following a surgery, the patient’s WBC, RBC, and platelet counts gradually returned to normal.ConclusionsHere, we present a case that thyroid cancer complicated with Hashimoto’s thyroiditis may affect hematopoietic function.

BackgroundTo estimate the global burden of pancreatic cancer in 2019 and 2021 including incidence, mortality, and disability-adjusted-life-years (DALYs).MethodsData on pancreatic cancer incidence, mortality and DALYs were downloaded from the Global Health Data Exchange. The 95% uncertainty intervals (UIs) were reported for annual numbers and rates (per 100,000 populations).ResultsIn 2021, there were 508,532 (95% UI: 462,09 to 547,208) incident cases of pancreatic cancer globally, of which 273,617 (250,808 to 299,347; 53.8%) were in males. The age-standardized incidence rate was 6.0 (5.5 to 6.5) per 100,000 people in 2019 and decreased to 5.9 (5.4 to 6.4) per 100,000 people in 2021. There was a 3.9% increase in the number of deaths from pancreatic cancer from 486,869 (446,272 to 517,185) in 2019 to 505,752 (461,224 to 543,899) in 2021. There was a 3.5% increase in DALYs due to pancreatic cancer, increasing from 10.9 million (10.1 to 11.7) in 2019 to 11.3 million (10.5 to 12.2) in 2021. In 2021, the highest age-standardized death rates were observed in Greenland and Monaco, and the highest age-standardized DALY rates were observed in Greenland and Uruguay. The numbers of incident cases and deaths peaked at the ages of 70 to 74 years. The pancreatic cancer burden increased as the socio-demographic index increased. To 2044, the number of incident cases and deaths will be more than 875 thousand and 879 thousand, respectively.ConclusionThe disease burden of pancreatic cancer remains high, especially in high-income regions. More cancer prevention measures are needed in the future to reduce the burden of pancreatic cancer.

lncRNAs (long non-coding RNAs) are heterogeneous RNA molecules that modulate various cellular processes, such as proliferation, differentiation, migration, invasion, and apoptosis, via different mechanisms. An increasing amount of research indicates that abnormal expression of lncRNA influences the development of drug resistance as well as the genesis and advancement of cancer, including melanoma. Furthermore, they are attractive biomarkers for non-invasive cancer diagnostics due to their strongly modulated expression and improved tissue and disease specificity. This review offers a succinct overview of the present understanding concerning the potential diagnostic biomarker potential of lncRNAs in melanoma. Cell death occurs frequently during growth and throughout life and is an active, organized, and genetically determined process. It is essential for the regulation of homeostasis. Controlled cell death and non-programmed cell death are both forms of cell death. The most prevalent forms of regulatory cell death are pyroptosis, ferroptosis, autophagy, necroptosis, necrosis, and apoptosis. Ferroptosis, pyroptosis, and autophagy are less common forms of cell death compared to necrosis, apoptosis, and necroptosis. ncRNAs are regulatory RNA molecules that are not involved in encoding proteins. They primarily consist of circular RNAs (circ RNAs), lncRNAs, and microRNAs (miRNAs). Moreover, non-coding RNAs have the ability to modulate tumor cell autophagy, pyroptosis, and ferroptosis at the transcriptional or post-transcriptional stage, as well as function as oncogenes and tumor suppressor genes, which can have considerable effects on the incidence and growth of tumors. This review concentrated on the recent advancements in the research of the diagnostic and therapeutic functions of ncRNAs in the regulation of programmed cell death in melanoma.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated both efficacy and safety in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients infected with hepatitis B virus (HBV). However, its applicability in individuals with liver cirrhosis remains largely unexplored due to the potential for unpredictable complications. Here, we report three cases (P1, P2, and P3) of relapsed/refractory DLBCL with HBV-related cirrhosis treated with CAR-T cell infusion. P1 and P2 received CAR-T cell infusion following a conditioning regimen of fludarabine and cyclophosphamide (FC) for lymphodepletion, while P3 received the SEAM (semustine, etoposide, cytarabine, and melphalan) regimen and autologous stem cell transplantation bridging CAR-T cell infusion. P1 and P2 achieved rapid complete remission (CR), whereas P3 initially exhibited stable disease a month after CAR-T infusion and subsequently achieved CR after local radiation salvage therapy and lenalidomide maintenance. With a median follow-up of 42 months after CAR-T, the progression-free survival rate was 100%. Notably, during follow-up, these patients experienced complications associated with cirrhosis, including endoscopic variceal bleeding, HBV reactivation, or the diagnosis of hepatic malignancy. Our findings suggest that CAR-T therapy is applicable and effective for the treatment of DLBCL patients with HBV-related cirrhosis, albeit necessitating monitoring for potential hepatic complications.

PurposesOsimertinib, one of the third-generation EGFR-tyrosine kinase inhibitors (TKIs) designed to target EGFR T790M mutation, significantly improves the prognosis of lung cancer. However, drug resistance still happens and MET amplification is responsible for one of the main causes. Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection, but fundamentally limited by observer subjectivity. Herein, we assessed the value of next-generation sequencing (NGS) method in MET amplification detection in non-small cell lung cancer (NSCLC), as well as revealed the mutation profiling of NSCLC patients with osimertinib resistance to provide some valuable clues to the mechanisms of resistance.MethodsA total of 317 cancer tissue samples from 317 NSCLC patients at time of progression following osimertinib were submitted to NGS and only 96 tissues were tested by FISH simultaneously. With FISH results as gold standard, enumeration algorithm was applied to establish the optimal model for identifying MET amplification using gene copy number (GCN) data.ResultsThe optimal model for identifying MET amplification was constructed based on the GCN of MET, BRAF, CDK6 and CYP3A4, which achieved a 74.0% overall agreement with FISH and performed well in identifying MET amplification except polysomy with a sensitivity of 85.7% and a specificity of 93.9%. The inconsistency between NGS and FISH occurred mainly in polysomy subtype, while MET GCN ≥ 5 could be reliably recognized by NGS. Moreover, the most frequently mutated genes in NSCLC patients with osimertinib resistance were EGFR (59.94%), followed by TP53 (43.85%), NRG1 (9.46%), PIK3CA (6.31%), and ATM (5.36%). The known resistance mechanisms, including MET amplification, EGFR (C797S, L718Q/R), TP53, CDK4, CDK6, CDKN2A, BRAF, KRAS, NRAS and PIK3CA mutations were also disclosed in our cohort.ConclusionsNGS assay can achieve a high concordance with FISH in MET amplification detection and has advantages in portraying various genetic alterations, which is of worthy in clinical promotion.

IntroductionCircular RNA CDR1as/ciRS-7 has been reported to function as an oncogenic regulator in various cancers. However, the prognostic value of CDR1as/ciRS-7 expression in solid tumors remains unclear. Herein, we conducted an updated meta-analysis to investigate the association between CDR1as/ciRS-7 expression and clinical outcomes in solid tumors.MethodsA systematic search was performed through the PubMed, EMBASE, Web of Science, and Ovid databases for eligible studies on clinical values of CDR1as/ciRS-7 in solid tumors. The pooled hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the correlation between CDR1as/ciRS-7 and clinical outcomes.ResultsA total of 2424 patients from 17 studies between 2017 and 2023 were included. The results suggested that elevated CDR1as/ciRS-7 expression predicted a poor overall survival (OS) for 12 types of solid tumors (HR=1.93, 95% CI: 1.43-2.60, P

ObjectiveTo assess the efficacy and safety of anlotinib combined with immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC).MethodsClinical data on patients with advanced NSCLC were collected from June 2019 to October 2022 at Hebei General Hospital, China. The efficacy and safety of anlotinib combined with ICIs and platinum-containing chemotherapy were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoint was the disease control rate (DCR) and overall survival (OS). Survival curves were created using the Kaplan–Meier method. The efficacy and adverse reactions were evaluated according to the RECIST 1.1 and CTCAE 5.0 standards.ResultsA total of 54 patients were enrolled in this study after propensity score matching (PSM), including 27 men and 17 women, with a median age of 59. A total of 26 patients received anlotinib + ICIs + platinum-containing chemotherapy (AIC), 15 patients received anlotinib + platinum-containing chemotherapy (AC), and 13 patients received ICIs + platinum-containing chemotherapy (IC). The PFS of the AIC group was 7.76 months (95% CI: 3.71–NC). The DCR was 65.38%. The OS endpoint had not been reached, The AIC combination regimen group had a significantly longer PFS than the IC group (mPFS, 7.76 vs. 2.33 months, p=0.012, HR=0.23, 95% CI: 0.06–0.8). There was no significant difference in the DCR between the two groups (65.38% vs. 53.85%, p=0.326). There was a statistically significant difference in PFS between the AC group and the IC group (mPFS, 9.2 vs. 2.33 months, p=0.02, HR=0.14, 95% CI: 0.03–0.65). There was no significant difference in the DCR between the two groups (40% vs. 53.85%, p=0.445). The common adverse reactions of the combination of anti-angiogenic agents, ICIs, and platinum-containing chemotherapy were anemia (34.62%), allergic reactions (19.23%), thrombocytopenia (11.54%), gastrointestinal reactions (15.38%), and hepatobiliary disorders (11.54%). Most of them were manageable.ConclusionsAnlotinib combined with immune checkpoint inhibitors and platinum-containing chemotherapy regimens offers a good survival benefit for patients with advanced non-small-cell lung cancer who fail to respond to standard therapy. When both efficacy and safety are considered, a combination of anti-angiogenic agents, ICIs, and platinum-containing chemotherapy can be used as a choice for the treatment of advanced NSCLC.

ObjectivesTo evaluate the effectiveness of high-intensity focused ultrasound (HIFU) therapy for treating uterine fibroids by utilizing multi-sequence magnetic resonance imaging radiomic models.MethodsOne hundred and fifty patients in our hospital were randomly divided into a training cohort (n=120) and an internal test cohort (n=30), and forty-five patients from another hospital serving as an external test cohort. Radiomics features of uterine fibroids were extracted and selected based on preoperative T2-weighted imaging fat suppression(T2WI-FS)and contrast-enhanced T1WI(CE-T1WI)images, and logistic regression was used to develop the T2WI-FS, CE-T1WI, and combined T2WI-FS + CE-T1WI models, along with the radiomics–clinical model integrating radiomics features with imaging characteristics. The performance and clinical applicability of each model were assessed through receiver operating characteristic (ROC) curve, decision curve analysis (DCA), as well as Network Readiness Index (NRI) and Integrated Discrimination Index (IDI).ResultsThe AUC values of the radiomics–clinical model and the T2WI-FS + CE-T1WI model were the highest. In the training cohort, the radiomics–clinical model showed higher AUC values than the T2WI-FS + CE-T1WI model, while in the internal and external testing cohorts, the AUC values of the T2WI-FS + CE-T1WI model were higher than that of the radiomics–clinical model. DCA further demonstrated that these two models achieved the greatest net benefit. NRI and IDI analyses suggested that the T2WI-FS + CE-T1WI model had higher clinical utility.ConclusionsBoth the T2WI-FS + CE-T1WI model and the radiomics–clinical model demonstrate higher predictive value and larger net benefit compared to other models.

Pralsetinib and selpercatinib have been approved as specific tyrosine kinase inhibitors (TKIs) for the treatment of patients with non-small cell lung cancer (NSCLC) harboring rearranged during transfection (RET) fusion and mutation. However, adverse events associated with pralsetinib and selpercatinib are not fully understood, especially in the real world. In this case, invasive aspergillosis that appeared concurrent with RET-TKI targeted therapy is proposed to be an additional adverse drug reaction (ADR) that was not mentioned in previous reports. Here, we describe the process of clinical diagnosis and treatment of invasive aspergillosis and attempt to explore its possible pathogenesis in association with RET-TKI targeted therapy, with the aim of providing clinicians a more in-depth understanding of the ADR associated with RET-TKIs, as well as to prevent serious outcomes caused by reduction or discontinuation of antitumor therapy.

BackgroundPancreatic metastasis from renal cell carcinoma (PMRCC) is unusual and there is no consensus on its treatment. The present study aims to evaluate the clinical outcomes of surgical resection for PMRCC.MethodsPubMed and Web of Science were searched for Eligible studies from January 1980 to January 2024. Individual-patient data were pooled.ResultsA total of 436 participants were identified. The morbidity and 90-day mortality were 38.1% and 3.4%, respectively. Post-pancreatectomy recurrence occurred in 44.1% of the patients. The overall median survival was 116 months, with a 3-, 5- and 10-year survival rate of 85.3%, 76.6%, and 46.5% respectively. On univariate analysis, repeat metastasectomy was associated with a significantly better prognosis (P =0.003).ConclusionThese data suggest that surgical resection is a safe and effective therapeutic option for PMRCC. Repeat metastasectomy is positively suggested for recurrent disease provided all metastases can be removed curatively. Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024525218.

PurposeTo assess the dosimetric effectiveness of image-guided radiation treatment (IGRT) and online adaptive radiation therapy (oART) for cervical cancer. As well as survival follow-up was conducted to validated the safety and efficacy of oART.MethodsA total of 15 cervical cancer patients were enrolled. oART was performed on a CT-integrated linear accelerator. The initial plan was revised to include the distribution of IGRT dose using daily fan-beam CT (FBCT) images, after which the distinctions between ART and IGRT in terms of target coverage and organs at risk (OARs) sparing were analyzed. Survival follow-up was conducted to validated the safety and efficacy of oART in this group.ResultsPTV Dmax value decreased by 1.23 Gy in the ART plan when compared to that in the IGRT plan; PTV D95 increased by 1.34 Gy; PTV V50 coverage increased by 4.86%; CTV coverage increased by 3.02%; PTV D2cc of the colon, rectum, and small intestine decreased by 1.24 Gy, 1.29 Gy, and 1.12 Gy, respectively. The V10 and V30 of the pelvis increased by 1.27% and 0.56%, respectively, while the V30 of the left and right femoral heads dropped by 2.82% and 3.41%, respectively. Except for the pelvic changes, all other differences were statistically significant (p < 0.01). The average time for the ART procedure was 21.22 min (range: 18.72–24.90 min). The median follow-up time is 28.0 months. Median event-free survival and overall survival were not reached. EFS rate and OS rate at 3 years were 79.4% and 92.9%.ConclusionOnline ART for cervical cancer can minimize the dose of OARs and enhance the target volume coverage significantly when compared to IGRT with satisfied survival time.

ObjectiveThe primary objective of this study was to provide valuable evidence for the management of patients diagnosed with uterine smooth muscle tumors of uncertain malignant potential (STUMP), with a focus on those with reproductive aspirations.MethodsWe conducted a retrospective analysis of clinical and pathological data from the medical records and slides of STUMP patients treated at Drum Tower Hospital, affiliated with Nanjing University Medical School, from January 2009 to December 2021.ResultsThirty-four patients were included in the study, with a median follow-up duration of 76 months (range: 13-157 months). After slide review, the diagnosis agreement rate was 77.3% (34/44 among initially considered cases). The consistency rate between our hospital’s diagnosis and those of other institutions was 75% (15/20). The accuracy rate of intraoperative frozen section diagnosis was low, at 21.4% (3/14). Half of the patients (17) underwent myomectomy, while the other half (17) received hysterectomy, including one subtotal hysterectomy. Two recurrences were observed (5.9%), one as STUMP and the other as leiomyosarcoma, with one recurrence in each surgical group. Notably, 4 of 9 patients with reproductive aspirations successfully underwent cesarean deliveries. Patients with single lesions appeared to exhibit potentially favorable fertility outcomes compared to those with multiple lesions.ConclusionThe diagnosis of STUMP was difficult. Myomectomy potentially could serve as an alternative for patients with reproductive needs. In selected cases with single lesions, it may indicate potentially favorable fertility outcomes.

Bladder cancer (BC) is a serious and common malignant tumor of the urinary system. Accurate and convenient diagnosis and treatment of BC is a major challenge for the medical community. Due to the limited medical resources, the existing diagnosis and treatment protocols for BC without the assistance of artificial intelligence (AI) still have certain shortcomings. In recent years, with the development of AI technologies such as deep learning and machine learning, the maturity of AI has made it more and more applied to the medical field, including improving the speed and accuracy of BC diagnosis and providing more powerful treatment options and recommendations related to prognosis. Advances in medical imaging technology and molecular-level research have also contributed to the further development of such AI applications. However, due to differences in the sources of training information and algorithm design issues, there is still room for improvement in terms of accuracy and transparency for the broader use of AI in clinical practice. With the popularization of digitization of clinical information and the proposal of new algorithms, artificial intelligence is expected to learn more effectively and analyze similar cases more accurately and reliably, promoting the development of precision medicine, reducing resource consumption, and speeding up diagnosis and treatment. This review focuses on the application of artificial intelligence in the diagnosis and treatment of BC, points out some of the challenges it faces, and looks forward to its future development.

BackgroundConformal proctectomy with sphincter preservation (CPSP) is designed to preserve the rectal wall as much as possible in very low rectal cancer patients. Evaluations of anal function and quality of life outcomes are lacking.MethodsThis study included male patients with very low (≤ 5 cm from the anal verge) rectal adenocarcinoma between January 1, 2020, and January 1, 2022. A LARS score questionnaire survey and EORTC-QLQ-CR38 questionnaire survey were administered.ResultsA total of 21 very low rectal cancer patients were enrolled in follow-up. The average age of the patients was 56.7 years, the tumors were 1.9 ± 0.6 cm in size, and the distance from the anal verge was 4.8 ± 0.5 cm. All patients were followed up, and the mean follow-up period was 2.7 ± 0.5 years. The LARS score increased significantly from 4.1 ± 2.8 before surgery to 19.1 ± 6.0 at the 1st year after surgery (P < 0.001) and then decreased to 13.1 ± 4.2 (P < 0.001) at the 2nd year. The quality of life of patients was also lower at the 1st year after surgery (61.1 ± 9.6 vs. 74.2 ± 11.2, P < 0.001) and was restored at the 2nd year after surgery (80.6 ± 11.9 vs. 74.2 ± 11.2, P = 0.029). During standard follow-up at the outpatient department, no rectal tumor relapse was confirmed in these patients, although 2 patients were found to have suspected recurrence of local lymph node metastasis.ConclusionsThese results suggest that the CPSP technique preserves acceptable defecation function and is a safe and feasible option for male patients with very low rectal cancer.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2100052094.

BackgroundBreast cancer, particularly triple-negative (TNBC), is a leading malignancy with aggressive traits and high metastasis rates. Clinical trial is an important tool for optimizing therapeutic strategies in the evaluation of the safety and efficacy for TNBC. Our bibliometric study of TNBC clinical trials aims to assess therapeutic strategies, identify trends, and explore advancements in treatment. We focus on mapping knowledge development, including key research entities and topics, and analyzing research trends and emerging methods. This analysis intends to inform future research, especially in personalized and precision medicine for TNBC.MethodsWe selected publications on clinical trials for the treatment of TNBC from 1997 to 2024 in the Web of Science Core Collection (WoSCC). After an initial screening, we downloaded key data including titles, publication years, authors, countries, institutional affiliations, journals, keywords, and abstracts, and saved them in BibTex format. We then conducted a bibliometric analysis using Bibliometrix in R and VOSviewer to illustrate the prospects, highlights, and trends of TNBC treatment options. Furthermore, to emphasize the hot topics in TNBC treatment strategies, we performed a bibliometric analysis of immunotherapy using the same approach.Results1907 publications were included, most of which were from China, Italy, and the United States. The number of annual publications has increased dramatically since 2010. The focus of TNBC clinical trial research has shifted from understanding the biology, such as breast cancer subtyping and genotyping, to novel therapeutic approaches. The major advancement in clinical trials is the switch from late-stage palliative treatment to early preoperative neoadjuvant therapy, as more TNBC cases are discovered at an early stage. Immunotherapy is also highlighted with additional alternatives for advanced or metastasized TNBC, such as targeted inhibitors with unusual mutation rates and antibody drug conjugates (ADC).ConclusionsThis investigation made it apparent how immunotherapy has recently made major advancements in TNBC treatment plans and how ADCs, or targeted therapies, are currently popular for TNBC. By identifying significant papers, comprehending trending topics, and collaborating across multiple disciplines, this study may accelerate research on TNBC therapy options.

ObjectiveSorafenib, a multikinase inhibitor, is currently the standard treatment for advanced liver cancer. However, its application has become limited by the development of drug resistance. We intended to explore the mechanisms underlying the development of sorafenib resistance, therefore identifying an effective strategy to overcome sorafenib resistance remain challenges.MethodsHere, the follow-up of liver cancer patients undergoing sorafenib therapy, as well as animal tumor challenge and treatment were performed. The sorafenib-resistant liver cancer cell lines Huh7/SOR and HepG2/SOR were also established. miRNA and mRNA microarray analyses, TargetScan prediction, dual luciferase reporter assay, RNA pull-down assay, co-mmunoprecipitation (Co-IP) and pull-down assays, a transcription factor-specific NRF2 assay, an iron detection assay, a lipid peroxidation quantification assay, a ROS measurement assay, and GSH/GSSG and GSH-px standard quantitative assays were used.ResultsWe showed that upregulation of the provirus-integrating site for Moloney murine leukemia virus 3 (Pim-3) predicted poor response and unsatisfactory prognosis in sorafenib-treated liver cancer patients. Similarly, Pim-3 expression was positively associated with sorafenib resistance in liver cancer cells. Furthermore, microRNA-936 (miR-936) targeted the 3’-noncoding region (3'-UTR) of Pim-3 but exhibited lower expression in sorafenib-resistant liver cancer cells than in their parental cells. The high expression of Pim-3 mediated by miR-936 insufficiency activated the ANKRD18A/Src/NRF2 pathway which rearranged the expression of the indicated markers involved in iron distribution and lipid peroxidation homeostasis. MiR-936 overexpression and GV102-Pim-3-shRNA significantly attenuated the activity of the ANKRD18A/Src/NRF2 pathway to decrease the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A), Src, and Nuclear factor (erythroid-derived 2)-like 2 (NRF2), especially decreasing NRF2 nuclear retention and transcriptional activity. The transcriptional activity of NRF2 prompted cell ferroptosis because the transfection of miR-936 mimics, GV102-Pim-3-shRNA and GV102-NRF2-shRNA plasmid increased the expression of transferrin receptor 1 (TFR1) and divalent metal transporter 1 (DMT1) but decreased the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), thus facilitating the accumulation of intracellular Fe2+, lipid peroxides, and reactive oxygen species (ROS) but reducing the glutathione (GSH) level. Moreover, the elevated expression of Pim-3, resulting from the absence of miR-936 enhances sorafenib resistance in liver cancer by inhibiting cell ferroptosis.ConclusionPim-3 can be regarded as a target in the treatment of sorafenib-resistant liver cancer.

BackgroundDifficulty in achieving complete resection leads to a poor prognosis for retroperitoneal soft tissue sarcoma, hence emphasizing the significance of adjuvant treatment. The benefit of preoperative radiotherapy for retroperitoneal liposarcoma was initially demonstrated by the STRASS trial. However, the impact of intraoperative radiotherapy (IORT) on retroperitoneal liposarcoma remains unexplored.MethodPatients with retroperitoneal liposarcoma were identified in the Surveillance, Epidemiology, and End Results (SEER) database, treated between 2000 and 2019. Subsequently, a 1:1 propensity score-matched (PSM) analysis was conducted based on variables identified from a multivariate analysis. T-tests were used to assess differences in normally distributed continuous variables, while the rank-sum test was applied to variables that did not follow a normal distribution. The chi-squared test was utilized to evaluate differences in categorical variables. Ultimately, survival analysis was performed using SPSS to evaluate patient prognosis.ResultA total of 2129 patients with retroperitoneal liposarcoma were included in our study. Age, sex, histology, grading, chemotherapy, and tumor size as independent prognostic risk factors for these patients through multivariate Cox regression analysis. Subsequently, 66 patients were included in the survival analysis through PSM, with 33 patients receiving IORT. Finally, the survival analysis revealed that there was no difference in overall survival among patients with retroperitoneal liposarcoma, regardless of whether they received IORT or not (p= 0.711).ConclusionAs an exploratory study, our findings suggest that patients may not derive benefit from intraoperative radiotherapy. These observations are intended to lay the groundwork for future prospective clinical studies.

PurposeThis study aimed to compare postoperative gastrointestinal symptoms between patients who underwent laparoscopic distal gastrectomy with Roux-en-Y (R-Y) and Billroth-II with Braun (B-II B) reconstruction.MethodsThis observational study retrospectively analyzed 151 patients (110 in R-Y group and 41 in B-II B group) who underwent laparoscopic distal gastrectomy from January 2020 to December 2021. A comparison was made regarding surgical outcomes, perioperative nutritional and inflammatory markers, postoperative dietary patterns, and gastrointestinal symptoms between the two groups.ResultsThe operation time was longer in the R-Y group than the B-II B group (261.00 ± 56.17 min versus 239.88 ± 57.78 min, p = 0.046). However, there were no significant differences in the length of hospital stay, ASA classification, complications, nutritional and inflammatory indexes, or recovery of postoperative diet between the two groups. Additionally, there were no significant differences in the occurrence of postoperative gastrointestinal symptoms in the post-discharge week (PDW) 1 and postoperative month (POM) 1 between the B-II B and R-Y groups.ConclusionsAbdominal distention emerged as the main gastrointestinal symptom burden in patients with gastric cancer undergoing laparoscopic distal gastrectomy. Both Billroth-II with Braun and R-Y reconstructions exhibited a high and similar incidence of gastrointestinal symptoms in the short term. Therefore, medical staff should pay attention to the management of gastrointestinal symptoms in these patients postoperatively.

Renal cell carcinoma is a urological malignancy with a high metastatic rate, while targeted therapy for renal cell carcinoma still has much room for improvement. Some cutting-edge researches have focused on exosome in cancer treatment and there are some breakthroughs in breast cancer, lung cancer, and pancreatic cancer. Up to now, exosome in renal cell carcinoma progression and implications for targeted therapy has been under research by scientists. In this review, we have summarized the structure, formation, uptake, functions, and detection of exosomes, classified the mechanisms of exosomes that cause renal cell carcinoma progression, and listed the promising utilization of exosomes in targeted therapy for renal cell carcinoma. In all, based on the mechanisms of exosomes causing renal cell carcinoma progression and borrowing the successful experience from renal cell carcinoma models and other cancers, exosomes will possibly be a promising target for therapy in renal cell carcinoma in the foreseeable future.

Since the onset of the COVID-19 pandemic, the SARS-CoV-2 virus has caused over 600 million confirmed infections and more than 6.8 million deaths worldwide, with ongoing implications for human health. COVID-19 has been extensively documented to have extrapulmonary manifestations due to the widespread expression of necessary ACE2 receptors in the human body. Nevertheless, the association between COVID-19 and cancer risk remains inadequately explored. This study employs Mendelian randomization (MR) methods to examine the causal relationship between genetic variations associated with COVID-19 and the risk of developing cancer. The findings indicate that COVID-19 has negligible impact on most cancer risks. Interestingly, a higher COVID-19 impact is associated with a decreased risk of thyroid cancer. In summary, our findings demonstrate a genetic correlation between COVID-19 and thyroid cancer, contributing to our understanding of the interplay between COVID-19 and cancer risk.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally, trailing only behind lung cancer, and stands as the third most prevalent malignant tumor, following lung and breast cancers. The primary cause of mortality in colorectal cancer (CRC) stems from distant metastasis. Among the various routes of metastasis in CRC, lymph node metastasis predominates, serving as a pivotal factor in both prognostication and treatment decisions for patients. This intricate cascade of events involves multifaceted molecular mechanisms, highlighting the complexity underlying lymph node metastasis in CRC. The cytokines or proteins involved in lymph node metastasis may represent the most promising lymph node metastasis markers for clinical use. In this review, we aim to consolidate the current understanding of the mechanisms and pathophysiology underlying lymph node metastasis in colorectal cancer (CRC), drawing upon insights from the most recent literatures. We also provide an overview of the latest advancements in comprehending the molecular underpinnings of lymph node metastasis in CRC, along with the potential of innovative targeted therapies. These advancements hold promise for enhancing the prognosis of CRC patients by addressing the challenges posed by lymph node metastasis.

A 33-year-old young woman with a rare female appendage tumor of suspected Wolffian origin was initially diagnosed with a benign lesion after the resection of a tubal lesion due to the benign cytomorphology of the tumor tissue. However, 1 year after surgery, she was diagnosed with stage IV fallopian tube cancer due to a recurrence, which presented with substantial ascites and invasion of multiple organs, including the bilateral ovaries, intestines, pelvic peritoneum, greater omentum, and appendix. After tumor cytoreduction, the patient responded well to treatment, which included a regimen of platinum-based drugs combined with docetaxel, aromatase inhibitors such as letrozole, antihormonal therapy, and targeted therapy with bevacizumab.

PurposeAccurate preoperative identification of Human epidermal growth factor receptor 2 (HER2) low expression breast cancer (BC) is critical for clinical decision-making. Our aim was to use machine learning methods to develop and validate an ultrasound-based radiomics nomogram for predicting HER2-low expression in BC.MethodsIn this retrospective study, 222 patients (108 HER2-0 expression and 114 HER2-low expression) with BC were included. The enrolled patients were randomly divided into a training cohort and a test cohort with a ratio of 8:2. The tumor region of interest was manually delineated from ultrasound image, and radiomics features were subsequently extracted. The features underwent dimension reduction using the least absolute shrinkage and selection operator (LASSO) algorithm, and rad-score were calculated. Five machine learning algorithms were applied for training, and the algorithm demonstrating the best performance was selected to construct a radiomics (USR) model. Clinical risk factors were integrated with rad-score to construct the prediction model, and a nomogram was plotted. The performance of the nomogram was assessed using receiver operating characteristic curve and decision curve analysis.ResultsA total of 480 radiomics features were extracted, out of which 11 were screened out. The majority of the extracted features were wavelet features. Subsequently, the USR model was established, and rad-scores were computed. The nomogram, incorporating rad-score, tumor shape, border, and microcalcification, achieved the best performance in both the training cohort (AUC 0.89; 95%CI 0.836-0.936) and the test cohort (AUC 0.84; 95%CI 0.722-0.958), outperforming both the USR model and clinical model. The calibration curves showed satisfactory consistency, and DCA confirmed the clinical utility of the nomogram.ConclusionThe nomogram model based on ultrasound radiomics exhibited high prediction value for HER2-low BC.

RET fusions were discovered in non-small cell lung cancer (NSCLC), and the efficacy of RET-targeted treatment in these patients has been previously established. However, patients with required resistance to RET-TKIs have limited treatment options. Herein, we describe a case of critical and advanced lung adenocarcinoma harboring RET fusion. Despite a significant response to Prasetinib previously, the patient developed refractory malignant pleural effusion after 24 months of treatment. He was treated simultaneously with intrapleural plus systemic Tislelizumab injection combined chemotherapy, thereby achieving an excellent clinical benefit maintaining control of pleural effusion for over 6 months. Hence, we would like to discuss intrapleural immunotherapy as an additional treatment method in refractory malignant pleural effusion while demonstrating good treatment tolerance.

BackgroundHigh BMI (Body Mass Index) is a significant factor impacting health, with a clear link to an increased risk of leukemia. Research on this topic is limited. Understanding the epidemiological trends of leukemia attributable to high BMI risk is crucial for disease prevention and patient support.MethodsWe obtained the data from the Global Burden of Disease Study, analyzing the ASR (age-standardized rates), including ASDR (age-standardized death rate) and age-standardized disability-adjusted life years (DALYs) rate, and estimated annual percentage change (EAPC) by gender, age, country, and region from 1990 to 2019.ResultsIn 2019, deaths and DALYs have significantly increased to 21.73 thousand and 584.09 thousand. The global age-standardized death and DALYs rates have slightly increased over the past 30 years (EAPCs: 0.34 and 0.29). Among four common leukemia subtypes, only CML (Chronic Myeloid Leukemia) exhibited a significant decrease in ASDR and age-standardized DALYs rate, with EAPC of -1.74 and -1.52. AML (Acute Myeloid Leukemia) showed the most pronounced upward trend in ASDR, with an EAPC of 1.34. These trends vary by gender, age, region, and national economic status. Older people have been at a significantly greater risk. Females globally have borne a higher burden. While males have shown an increasing trend. The regions experiencing the greatest growth in ASR were South Asia. The countries with the largest increases were Equatorial Guinea. However, It is worth noting that there may be variations among specific subtypes of leukemia. Regions with high Socio-demographic Index (SDI) have had the highest ASR, while low-middle SDI regions have shown the greatest increase in these rates. All ASRs values have been positively correlated with SDI, but there has been a turning point in medium to high SDI regions.ConclusionsLeukemia attributable to high BMI risk is gradually becoming a heavier burden globally. Different subtypes of leukemia have distinct temporal and regional patterns. This study’s findings will provide information for analyzing the worldwide disease burden patterns and serve as a basis for disease prevention, developing suitable strategies for the modifiable risk factor.

BackgroundProlonged postoperative hospital stay following gastric cancer (GC) surgery is an important risk factor affecting patients’ mood and increasing complications. We aimed to develop a nomogram to predict risk factors associated with prolonged postoperative length of stay (PLOS) in patients undergoing gastric cancer resection.MethodsData were collected from 404 patients. The least absolute shrinkage and selection operator (LASSO) was used for variable screening, and a nomogram was designed. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC). The consistency between the predicted and actual values was evaluated via a calibration map, and the clinical application value was evaluated via decision curve analysis (DCA) and clinical impact curve analysis (CICA).ResultsA total of 404 patients were included in this study. Among these patients, 287 were assigned to the training cohort, and 117 were assigned to the validation cohort. According to the PLOS quartile distance, 103 patients were defined as having prolonged PLOS. LASSO regression and logistic multivariate analysis revealed that 4 clinical characteristics, the neutrophil–lymphocyte ratio (NLR) on postoperative day one, the NLR on postoperative day three, the preoperative prognostic nutrition index and the first time anal exhaust was performed, were associated with the PLOS and were included in the construction of the nomogram. The AUC of the nomogram prediction model was 0.990 for the training set and 0.983 for the validation set. The calibration curve indicated good correlation between the predicted results and the actual results. The Hosmer-Lemeshow test revealed that the P values for the training and validation sets were 0.444 and 0.607, respectively, indicating that the model had good goodness of fit. The decision curve analysis and clinical impact curve of this model showed good clinical practicability for both cohorts.ConclusionWe explored the risk factors for prolonged PLOS in GC patients via the enhanced recovery after surgery (ERAS) program and developed a predictive model. The designed nomogram is expected to be an accurate and personalized tool for predicting the risk and prognosis of PLOS in GC patients via ERAS measures.

Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.

BackgroudHuman epithelial growth factor receptor 2 (HER2) amplification is an important mechanism of acquired resistance to anti-epidermal growth factor receptor (EGFR) therapy in non-small cell lung cancer (NSCLC) patients. For patients with both EGFR mutation and HER2 amplification, there is currently no unified standard treatment, and further exploration is needed on how to choose the therapy.Methods and resultsA female NSCLC patient developed bone and brain metastases 14 and 42 months after radical surgery, respectively. The second genetic sequencing detected EGFR L858R mutation and HER2 amplification, and therefore initiated treatment with almonertinib and pyrotinib. The patient achieved partial remission and did not show any further progression during the follow-up period.ConclusionFor NSCLC patients with both EGFR mutation and HER2 amplification, the combination of almonertinib and pyrotinib is a valuable therapy that can continuously reduce tumor burden and achieve long-term survival.

MET exon 14 (METex14) skipping is the most reported MET mutation in non-small cell lung cancer (NSCLC) and has been confirmed to respond to MET tyrosine kinase inhibitors (TKI) in clinical trials. While MET TKI tepotinib was recently approved for METex14 skipping NSCLC in China, real-world evidence is limited. We report our experience treating NSCLC patients referred from oncology sites across China with tepotinib in the Boao Lecheng Pilot Zone. Four patients have been prescribed the drug with a median age of 67 years (range, 61–71 years). One patient has concomitant BRAF V600E mutation, and another patient had savolitinib as first line of therapy but discontinued due to hepatotoxicity. Till the end of follow-up, four patients were all on tepotinib therapy, with a median duration of therapy of 19 months. One patient achieved partial response and three achieved stable disease. Three patients had peripheral edema, but all were mild. Our experience showed in real clinical setting, tepotinib had robust and durable clinical activity and a favorable toxicity profile in Chinese patients with METex14 skipping NSCLC. It is the first report on the effectiveness of tepotinib in a patient with both METex14 skipping and BRAF V600E mutations and successful MET inhibitor switch after MET inhibitor-induced liver injury.

BackgroundCuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing’s sarcoma (ES).MethodsThe GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration.ResultsUsing Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram’s performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES.ConclusionThe findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.

ObjectiveThis study aims to establish a prediction model for neoadjuvant immunochemotherapy (NICT) in lung squamous cell carcinoma to guide clinical treatment.MethodsThis retrospective study included 50 patients diagnosed with lung squamous cell carcinoma who received NICT. The patients were divided into the pathological complete response (PCR) group and the non-PCR group. HE staining and multiple immunofluorescence (mIF) techniques were utilized to analyze the differences in the immune microenvironment between these groups. LASSO regression and optimal subset regression were employed to identify the most significant variables and construct a prediction model.ResultsThe PCR group showed higher densities of lymphocyte nuclei and karyorrhexis based on HE staining. Furthermore, based on mIF analysis, the PCR group showed higher cell densities of CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region, while showing lower cell densities of CD3+Foxp3+, Foxp3+, and CD163+. Logistic univariate analysis revealed CD8+PD-L1+, PD-L1+, CD8+, CD4+LAG-3+, lymphocyte nuclei, and karyorrhexis as significant factors influencing PCR. By using diverse screening methods, the three most relevant variables (CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region) were selected to establish the prediction model. The model exhibited excellent performance in both the training set (AUC=0.965) and the validation set (AUC=0.786). In the validation set, In comparison to the conventional TPS scoring criteria, the model attained superior accuracy (0.85), specificity(0.67), and sensitivity (0.92).ConclusionNICT treatment might induce anti-tumor effects by enriching immune cells and reactivating exhausted T cells. CD8+, PD-L1+, and CD8+PD-L1+ cell abundances within the tumor region have been closely associated with therapeutic efficacy. Incorporating these three variables into a predictive model allows accurate forecasting of treatment outcomes and provides a reliable basis for selecting NICT treatment strategies.

ObjectiveTo develop a CT-based nomogram to predict the response of advanced esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemotherapy plus immunotherapy.MethodsIn this retrospective study, 158 consecutive patients with advanced ESCC receiving contrast-enhanced CT before neoadjuvant chemotherapy plus immunotherapy were randomized to a training cohort (TC, n = 121) and a validation cohort (VC, n = 37). Response to treatment was assessed with response evaluation criteria in solid tumors. Patients in the TC were divided into the responder (n = 69) and non-responder (n = 52) groups. For the TC, univariate analyses were performed to confirm factors associated with response prediction, and binary analyses were performed to identify independent variables to develop a nomogram. In both the TC and VC, the nomogram performance was assessed by area under the receiver operating characteristic curve (AUC), calibration slope, and decision curve analysis (DCA).ResultsIn the TC, univariate analysis showed that cT stage, cN stage, gross tumor volume, gross volume of all enlarged lymph nodes, and tumor length were associated with the response (all P < 0.05). Binary analysis demonstrated that cT stage, cN stage, and tumor length were independent predictors. The independent factors were imported into the R software to construct a nomogram, showing the discriminatory ability with an AUC of 0.813 (95% confidence interval: 0.735–0.890), and the calibration curve and DCA showed that the predictive ability of the nomogram was in good agreement with the actual observation.ConclusionThis study provides an accurate nomogram to predict the response of advanced ESCC to neoadjuvant chemotherapy plus immunotherapy.

BackgroundBreast cancer (BC) in adolescents and young adults (AYAs, aged 15–39 years), remains inadequately understood. The incidence of BC in AYAs has been steadily increasing, making it the second leading cause of cancer-related mortality among females aged 0–39 globally. This study aimed to elucidate the clinical characteristics and long-term outcomes of AYAs and older adults (OAs, aged > 39 years) with BC who underwent surgery.MethodsFrom January 2011 to June 2017, BC patients who underwent surgery were enrolled in this study and divided into AYA group and OA group. Clinical characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between these two groups, both before and after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard regression analyses were performed to assess the influence of age on OS and RFS.ResultsCompared to the OA group, the AYA group exhibited a younger age at menarche (p < 0.001), a lower prevalence of menopausal status (p < 0.001), a reduced occurrence of comorbid conditions (p < 0.001), fewer instances of undergoing mastectomy (p = 0.031), a higher incidence of Triple-Negative Breast Cancer (TNBC) (p = 0.046), and elevated Ki-67 levels (p = 0.036). In terms of prognostic outcomes, within the study cohort, AYAs had a higher mortality rate and poorer long-term survival compared to OAs, both before and after PSM. In the PSM cohort, AYAs experienced a significantly shorter mean OS (p < 0.001) and RFS (p < 0.001). Young age (15–39 years) emerged as an independent risk factor for OS (HR 2.659, 95% CI 1.385–5.106, p = 0.003) and RFS (HR 3.235, 95% CI 2.085–5.022, p < 0.001) in BC patients following surgery.ConclusionSignificant differences were identified in the clinicopathological characteristics between AYA and OA patients with BC. In comparison to OA patients, AYA patients exhibited a less favorable long-term prognosis, with young age emerging as an independent prognostic risk factor for both OS and RFS in BC patients following surgery. Further investigations are warranted to develop age-specific therapeutic approaches for AYA BC patients.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%–26.1%), 22.8% (95% CI 14.2%–31.4%) and 32.8% (95% CI 24.1%–41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%–84.9%), 72.7% (95% CI 63.7%–81.7%), and 62.3% (95% CI 53.5%–71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Neuroendocrine prostate neoplasms, encompassing small cell carcinoma, carcinoid, and large cell carcinoma, are infrequently observed in malignant prostate tumors. The occurrence of large cell neuroendocrine prostate cancer (LCNEPC) is exceedingly rare. In this study, the patient initially presented with a persistent dysuria for a duration of one year, accompanied by a serum prostate-specific antigen (PSA) level of 17.83ng/mL. Prostate magnetic resonance imaging (MRI) and chest computed tomography (CT) scan showed that a neoplastic lesion was considered, and prostate biopsy confirmed prostate adenocarcinoma with a Gleason score of 7 (4 + 3). Then, thoracoscopic lung tumor resection was performed, and the pathological examination revealed the presence of primary moderately differentiated invasive adenocarcinoma of the lung and metastatic prostate adenocarcinoma, the Gleason score was 8 (4 + 4). After 1 year of endocrine therapy with goserelin acetate and bicalutamide, he underwent a laparoscopic radical prostatectomy (LRP), the pathological report indicated the presence of adenocarcinoma mixed with NE carcinoma. Two months after the LRP, the patient experienced gross hematuria and sacral tail pain. Further examination revealed multiple metastatic lesions throughout the body. He also underwent transurethral resection of bladder tumor (TURBT) for bladder tumor and received etoposide+ cisplatin chemotherapy three weeks post-surgery. The patient eventually died of multi-organ failure due to myelosuppression after chemotherapy. This case report presents an uncommon instance of LCNEPC with widespread systemic metastases, while also providing a comprehensive review of existing literature to facilitate improved management and treatment strategies for similar patients in subsequent cases.

BackgroundThe progress in Colorectal cancer (CRC) screening and management has resulted in an unprecedented caseload for histopathological diagnosis. While artificial intelligence (AI) presents a potential solution, the predominant emphasis on slide-level aggregation performance without thorough verification of cancer in each location, impedes both explainability and transparency. Effectively addressing these challenges is crucial to ensuring the reliability and efficacy of AI in histology applications.MethodIn this study, we created an innovative AI algorithm using transfer learning from a polyp segmentation model in endoscopy. The algorithm precisely localized CRC targets within 0.25 mm² grids from whole slide imaging (WSI). We assessed the CRC detection capabilities at this fine granularity and examined the influence of AI on the diagnostic behavior of pathologists. The evaluation utilized an extensive dataset comprising 858 consecutive patient cases with 1418 WSIs obtained from an external center.ResultsOur results underscore a notable sensitivity of 90.25% and specificity of 96.60% at the grid level, accompanied by a commendable area under the curve (AUC) of 0.962. This translates to an impressive 99.39% sensitivity at the slide level, coupled with a negative likelihood ratio of

ObjectivesTo investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa).MethodsWe performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance.ResultsPPAT and normalized PPAT were associated with BM (P

Radiotherapy stands as a cornerstone in the treatment of numerous malignant tumors, including non-small cell lung cancer. However, the critical challenge of amplifying the tumoricidal effectiveness of radiotherapy while minimizing collateral damage to healthy tissues remains an area of significant research interest. Radiosensitizers, by methods such as amplifying DNA damage and fostering the creation of free radicals, play a pivotal role in enhancing the destructive impact of radiotherapy on tumors. Over recent decades, nano-dimensional radiosensitizers have emerged as a notable advancement. Their mechanisms include cell cycle arrest in the G2/M phase, combating tumor hypoxia, and others, thereby enhancing the efficacy of radiotherapy. This review delves into the evolving landscape of nanomaterials used for radiosensitization in non-small cell lung cancer. It provides insights into the current research progress and critically examines the challenges and future prospects within this burgeoning field.