Radioisotope-labeled prostate-specific membrane antigen (PSMA) PET tracers have gained popularity in diagnosing prostate cancer (PCa). Recently, a novel biphenyl-containing tracer [68Ga]Ga-PSMA-D5 targeting PSMA has been developed for PET imaging of PCa. The advantages of [68Ga]Ga-PSMA-D5 include high tumor uptake, simple synthesis, and convenient labeling, making it a promising PSMA PET tracer. In order to facilitate the routine production and clinical application of [68Ga]Ga-PSMA-D5, a straightforward and efficient automated synthesis is described. The optimum labeling parameters were determined at laboratory scale, and subsequently incorporated into an automated production process. Further studies have demonstrated that clinical doses of [68Ga]Ga-PSMA-D5 can be prepared within 25 min, with excellent radio chemical purity (>99 %) and activity yield (70.8 % ± 2.3 %, non-decay corrected). All the quality control results satisfy the required criteria for release. PET/CT imaging has shown that [68Ga]Ga-PSMA-D5 can safely and effectively target prostate cancer-associated lesions with excellent tumor-to-background contrast. This methodology facilitates efficient synthesis of [68Ga]Ga-PSMA-D5 in a commercially available synthesis module and shows diagnostic value for PCa in further clinical application.

Sex and gender have emerged as central modifiers of disease biology, phenotype, and clinical outcomes in myeloproliferative neoplasms (MPNs). This review will uniquely highlight issues affecting women with MPN and articulate their relevant determinants.

A higher overall prevalence of MPN has been established in women. The incidence of essential thrombocythemia (ET) predominates, while, conversely, polycythemia vera (PV) and myelofibrosis (MF) are seen in lower frequencies as compared to men. Diagnostic criteria are dictated by sex-driven physiological variances in hemoglobin and hematocrit levels in PV, mandating separate diagnostic thresholds, respectively: > 16.0 g/dL and > 48% in women vs. > 16.5 and > 49% in men.

Women with MPN harbor fewer acquired somatic mutations and a lower frequency of high-risk mutations than their male counterparts; lower JAK2V617F driver variant allele frequency and attenuated allele burden kinetics have also been reported. Women with MPN are younger at diagnosis than men and, contingent on subtype, display more indolent disease features. Importantly, validated symptom burden assessments consistently disclose higher scores in women vs. men.

Women with MPN have a unique thrombotic diathesis with respect to men, more frequently involving the splanchnic venous system in those ultimately diagnosed with PV. Outcomes data depict female sex as a variable associated with more favorable clinical trajectories, including lower rates of MF/leukemic transformation and secondary cancers, as well as improved overall survival rates vis-à-vis men.

Potential challenges at each significant life stage will be addressed: puberty, preconception and fertility, and perimenopause; these include issues surrounding oral contraceptives and hormone use. Prospective studies suggest overall favorable maternal and fetal outcomes with pregnancy in women with MPN. Full details on risks and reported outcomes will be discussed, as well as a risk-adapted approach to management informed by obstetric and thrombosis history. Recommendations include aspirin 81 mg daily in all patients and cytoreduction with interferon-α in those with antecedent thrombosis, as well as in low-risk cases with higher-risk features (e.g., poorly controlled hematocrit and recurrent fetal loss). Antepartum anticoagulation with low molecular weight heparin (LMWH) is recommended in cases with previous venous thromboembolism.

This review highlights female sex and gender as critical drivers of MPN incidence, presentation, and natural history. It further outlines the impact and management of MPN as related to unique female reproductive phases. A sex-informed lens will be required in order to recalibrate current prognostic tools, a requisite to refining patient counselling and clinical decision-making in line with precision medicine. Moreover, while several mechanisms underpinning sex-defined discrepancies have been defined, these mandate further prospective study. Finally, sex and gender-based differences must be weighted in clinical trials with systematized procedures to correct participation imbalances in favor of sex and gender equity.

Endometrial cancer (EC) is a malignancy of the endometrial epithelium. The prevalence and mortality rates associated with the disease are on the rise globally. A total of 20 cases of type I EC tissues were collected for transcriptomic sequencing, our findings indicate that PAX2 is highly expressed in EC tissues and is closely related to the pathogenesis of EC. PAX2 is a member of the paired homeobox domain family and has been linked to the development of a number of different tumours. In normal endometrial tissue, PAX2 is methylated; however, in EC, it is demethylated. Nevertheless, few studies have focused on its role in EC. A protein-protein interaction (PPI) analysis revealed a regulatory relationship between PAX2 and CD133, which in turn affects the activity of AKT1. CD133 is a well-known marker of tumor stem cells and is involved in tumor initiation, metastasis, recurrence, and drug resistance; AKT1 promotes cell survival by inhibiting apoptosis and is considered a major promoter of many types of cancer. Nevertheless, further investigation is required to ascertain whether PAX2 affects the progression of EC by regulating the CD133-AKT1 pathway. The present study demonstrated that PAX2 promoted cell proliferation, migration, invasion and adhesion, and inhibited apoptosis. Its mechanism of action was found to be the inhibition of mitochondrial oxidative phosphorylation, promotion of glycolysis, increase in mitochondrial copy number, and increase in the levels of reactive oxygen species (ROS) and hexokinase, as well as the concentration of mitochondrial calcium ions. This was achieved through the promotion of CD133 expression and the phosphorylation of AKT1. In conjunction with the aforementioned regulatory pathways, the progression of EC is facilitated.

Underweight women and those with obesity, defined as having a body mass index (BMI) ≥ 30 kg/m2, diagnosed with breast cancer (BC) are known to have worse prognosis. Whether BMI impacts BC stage at diagnosis and BC specific survival (BCSS) is not understood. We aim to better understand the relationship between BMI with stage at BC diagnosis and BCSS.

Women age ≥ 15 years old diagnosed with BC between 2014 and 2019 were identified from the California Cancer Registry. BMI at diagnosis was classified as underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity class 1-2 (30-39.9 kg/m2), and obesity class 3 (≥ 40 kg/m2). BC late stage of diagnosis was defined as American Joint Committee on Cancer stage 3 and 4. Multivariate logistic regression was performed to compare sociodemographic and clinical factors associated with late stage. Multivariable cox proportional hazards regression models assessed association of BMI and BCSS.

Of 159,248 patients: 2.2% were underweight, 34.6% normal weight, 30.5% overweight, 26.7% obesity class 1-2, and 6.0% obesity class 3. Compared to normal weight, patients who were underweight [Hazard Ratio (HR) 1.54, 95% Confidence Interval (CI) 1.51-1.57], obesity class 1-2 [HR 1.06, 1.05-1.07], and obesity class 3 [HR 1.14, 1.12-1.16] were more likely to be diagnosed with late-stage BC. In models stratified by age, patients ≥ 40 years who were underweight had worse BCSS, while patients ≥ 51 years with obesity class 1-2 had better BCSS.

Patients with obesity class 1-2 were more likely to be diagnosed with a later stage, but had improved BCSS, supporting an "obesity paradox" in BC and suggesting that other measures are needed to better assess body composition, adipose distribution, and metabolic health of patients. Patients who were underweight had worse survival, suggesting this high-risk group may benefit from being assessed and treated for possible sarcopenia and malnourishment.

The stage at which Colorectal cancer (CRC) diagnosed is a crucial prognostic factor. Our study proposed a novel approach to aid in the diagnosis of stage IV CRC by utilizing supervised machine learning, analyzing clinical history, and laboratory values, comparing them with those of stage I CRC.

We conducted a respective study using patients diagnosed with stage I (n = 433) and stage IV CRC (n = 457). We employed supervised machine learning using random forest. The decision tree is used to visualize the model to identify key clinical and laboratory factors that differentiate between stage IV and stage I CRC.

The decision tree classifier revealed that symptoms combined with laboratory values were critical predictors of stage IV CRC. Change in bowel habits was predictive for stage IV CRC among 14 of 22 patients (63 %). Weight loss, constipation, and abdominal pain in combination with different levels of carcinoembryonic antigen (CEA) were predictors for stage IV CRC. A CEA level higher than 260 was indicative for stage IV CRC in all observed patients (61 out of 61 patients). Additionally, a lower CEA level, in combination with hemoglobin, white blood cell count, and platelet count, also predicted stage IV CRC.

By applying a machine learning based approach, we identified symptoms and laboratory values (CEA, hemoglobin, white blood cell count, and platelet count), as crucial predictors for stage IV CRC diagnosis. This method holds potential for facilitating the diagnosis of stage IV CRC in clinical practice, even before imaging tests are conducted.

The pachysandra alkaloids found in Sarcococca ruscifolia demonstrate notable anti-hepatocellular carcinoma activity. Despite their efficacy, the structural diversity of these compounds remains limited, and their precise antitumor mechanism is still unclear. In pursuit of identifying novel lead compounds with high efficacy and low toxicity for combating hepatocellular carcinoma, twenty-three compounds of C20-ketone pachysandra alkaloid derivatives were designed and synthesized by using 3-dimethylamine pachysandra alkaloids as scaffolds. Subsequent in vitro anticancer activity experiments showed that synthetic pachysandra alkaloids had a stronger effect on HepG2 cells than did their natural counterparts, with low toxicity and high selectivity. The most potent derivative, 6k, had an IC50 value of 0.75 μM, demonstrating 25.7-fold greater anticancer activity than sarcovagine D against HepG2 cells. Through network pharmacology and molecular docking analysis, it was revealed that synthetic pachysandra alkaloids may exert their effects by inhibiting the JAK2/STAT3 pathway, thereby preventing the proliferation of liver cancer cells. Further research through scratch tests, immunofluorescence experiments, and Western blot analysis revealed that compound 6k effectively inhibited the migration of HepG2 cells and induced mitochondria-mediated intrinsic apoptosis of HepG2 cells by regulating the JAK2/STAT3 signaling pathway. The aforementioned results indicate that compound 6k could be developed as a potential candidate for the treatment of hepatocellular carcinoma.

Targeting more than one in nine men before age 70, prostate cancer is the most common type of cancer in men. The increased levels of cyclins, leading to activation of cyclin-dependent kinases (CDKs), play a critical role in the increased proliferation of prostate cancer cells. In this study, the regulation of the cyclin D1 (CCND1) promoter activity by activator protein-1 (AP-1) and SRY-related HMG-box (SOX) transcription factors has been characterized in PC3 prostate cancer cells. The SOX and AP-1 transcription factors can cooperate to activate the CCND1 promoter in PC3 prostate cancer cells and such cooperation can be enhanced by protein kinase A (PKA) and/or mitogen-activated protein kinase kinase 1 (ERK kinase 1, MAP2K1) signaling pathways. Moreover, anacardic acid analogs have been assessed for their potential in reducing cell viability and CCND1 promoter activity. The anacardic acid analog 8b, obtained from γ-resorcylic acid, reduces the viability and proliferation of PC3 cells by decreasing CCND1 promoter activity. The effect of analog 8b, which perfectly mimics the structure of anacardic acid, can be attributed to the inhibition of the activities of the transcription factors SOX and AP-1, which are important regulators of CCND1 promoter activity in prostate cancer cells.

With the increase in life expectancy, age-related conditions and diseases have become a widespread and relevant social burden. Among these, immunosenescence and cancer cachexia play a significant often intertwined role. Immunosenescence is the progressive aging decline of both the innate and adaptive immune systems leading to increased infection susceptibility, poor vaccination efficacy, autoimmune disease, and malignancies. Cancer cachexia affects elderly patients with cancer causing severe weight loss, muscle wasting, inflammation, and reduced response to therapies. Whereas the connections between immunosenescence and cancer cachexia have been raising attention, the molecular mechanisms still need to be completely elucidated. This review aims at providing the current knowledge about the interplay between immunosenescence, skeletal muscle, and cancer cachexia, analyzing the molecular pathways known so far to be involved. Finally, we highlight potential therapeutic strategies suited for elderly population aimed to block immunosenescence and to preserve muscle mass in cachexia, also presenting the analysis of the current state-of-the-art of related clinical trials.

Bladder cancer (BCa) is a leading malignancy in the urinary tract system, often resulting in poor prognosis due to rapid relapse and metastasis, with a low 5-year survival rate. Although the role of N6-methyladenosine (m6A) methylation and long noncoding RNAs (lncRNAs) is implicated in BCa progression, research on how lncRNAs influence BCa prognosis and potential therapeutic interventions remains scarce.

RNA expression profiles and gene mutations for 406 BCa patients were retrieved from the The Cancer Genome Atlas (TCGA) database. A comprehensive dataset was established to correlate lncRNAs with 21 identified m6A-associated genes, categorized into writers, erasers, and readers. Pearson correlation analysis between these m6A genes and lncRNAs was performed and a prognostic model derived from m6A-associated lncRNAs was developed. Immune infiltration was analyzed using multiple evaluative methods and the correlation between single nucleotide variant (SNV) mutations and drug sensitivity was assessed for the correlative relationship with the m6A-associated lncRNA-derived risk scores.

We identified 3,462 m6A-associated lncRNAslinked to BCa prognosis, of which 238 lncRNAs showed significant associations with overall survival in BCa patients. A m6A-associated lncRNA-derived risk model comprising 26 selected lncRNAs was developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, where BCa patients with higher m6A-associated lncRNA-derived risk scores had poorer outcomes. The prognostic significance and reliability was validated, with an area under the curve (AUC) value exceeding 0.7 at multiple time points. Additionally, a nomogram integrating clinical features and m6A-associated lncRNA-derived risk scores had enhanced prognostic accuracy over other clinical indicators, with promise for clinical decision-making. A negative correlation was observed between m6A-associated lncRNA-derived risk scores and tumor mutational burden (TMB). Moreover, patients with high m6A-associated lncRNA-derived risk score group showed significant enrichment of regulatory T cells (Tregs), M2 macrophages, and fibroblasts, highlighting the potential involvement of immune and stromal cells in these BCa patients.

These findings highlight the prognostic value and clinical relevance of m6A-associated lncRNAs in BCa for future patient stratification and personalized therapy approaches.

Diffuse large B-cell lymphoma (DLBCL) presents a substantial clinical challenge due to its aggressive nature and resistance to conventional therapies, thereby developing novel treatment strategies is critical. In this work, we take advantage of the insensitivity of heat shock protein (HSP) expression in senescent tumor cells to combine mild photothermal therapy (MPTT) for efficient DLBCL treatment. Insensitivity to HSPs implies that cells are less capable of activating their usual stress protection mechanisms during MPTT, which reduces their tolerance to heat damage. Consequently, the treatment can more effectively destroy target cells at lower temperatures while minimizing the risk of thermal injury to surrounding healthy tissues. Abemaciclib can inhibit CDK4/6 activity, thereby inhibiting Rb phosphorylation to suppress the activity of the E2F transcription factor and prevent the transition from G1 to S phase, leading to cell cycle arrest and ultimately cellular senescence. The experimental results indicated that abemaciclib effectively promoted the senescence of DLBCL cells, accompanied by a significant reduction in HSP70 expression. Subsequently, a novel near-infrared (NIR) absorbing organic polymer photothermal agent (PYIT-OD) with excellent optical properties and photostability was used for MPTT. The integration of pro-senescence strategies with MPTT, as evidenced by both in vitro and in vivo experimental outcomes, markedly enhanced treatment efficacy, effectively reducing damage to normal tissues at mild temperatures and enhancing antitumor effects. This work not only reveals potential biological mechanisms but also provides theoretical foundations and practical guidance for developing more precise and less toxic DLBCL treatment regimens in clinical practice.

Osteosarcoma (OS) is a prevalent form of bone cancer among younger people, particularly children and adolescents. Ferroptosis is a non-apoptotic cell death identified by increased levels of iron-dependent lipid peroxidation. This study was designed to develop a prognostic model based on differentially expressed genes (DEGs) associated with ferroptosis and examined the functions of ferroptosis-related genes (FRGs) in OS cells. Gene expression profiles in OS were retrieved from TARGET and GEO databases, while GTEx provided data for healthy tissues. Prognostic genes were identified through bioinformatics analysis and data integration. In vitro experiments, cell cultures, qRT-PCR, immunohistochemistry (IHC), cell transfection, Edu assays, DHE assays, migration, and invasion assays validated the prognostic model and explored the functional role of FRGs in OS cells. Univariate Cox regression analysis demonstrated that 12 DEGs were differentially expressed. Based on four FRGs in OS constructed a risk-scoring model. The high-risk (HR) group showed a considerably lower OS rate than the low-risk (LR) group (p < 0.001 in the TARGET and p < 0.05 in the GSE21257 cohorts). A risk score was validated as an independent predictive factor for OS via multivariate Cox regression. Functional analysis shows that these FRGs affect the occurrence of ferroptosis by influencing the intracellular ROS levels and play a regulatory role in the proliferation, migration, and infiltration of OS cells. The findings suggested that four FRGs demonstrate significant prognostic value in OS, offering potential insights into novel therapeutic targets for OS treatment.

Endometrial cancer (EC) is the 6th most common cancer among women worldwide. No effective non-invasive screening methods or approved blood biomarkers for EC exist. Previous research explored Attenuated Total Reflection-Fourier Transform Infrared (ATR-FtIR) and Raman spectroscopies, using dried blood plasma. Fresh, 'wet', blood samples, that might provide faster results, have not been investigated. This study compared ATR-FtIR and Raman spectroscopies on 'wet' and dry blood plasma samples for EC detection. It also conducted a preliminary exploration into their diagnostic potential for EC in high-risk individuals with polycystic ovary syndrome (PCOS).

'Wet' and dry blood plasma samples from participants with EC, PCOS and healthy controls were analysed using ATR-FtIR and Raman spectroscopies. Machine learning algorithms and multivariate statistical analyses assessed spectral variance across datasets to evaluate the techniques' diagnostic performance.

Raman analysis of 'wet' plasma achieved 82% accuracy in detecting EC, while ATR-FtIR spectroscopy reached 78%. When combined, diagnostic accuracy reached 86%. In comparison, dry plasma analysis with ATR-FtIR detected EC with 83% accuracy. Spectral similarities were found between EC and PCOS.

Our study suggests that ATR-FtIR and Raman spectroscopies could revolutionise early diagnosis of EC. More research is required to validate these promising findings.

Young-onset colorectal cancer (YOCRC) refers to colorectal cancer diagnosed in individuals under the age of 50. Whilst the overall incidence of colorectal cancer is decreasing, YOCRC cases are increasing and now accounts for up to 10% of all colorectal cancers. YOCRC more frequently presents with acute symptoms, where radiologists play an important role in identifying malignancy and distinguishing it from benign colonic pathologies. Risk factors associated with YOCRC, such as inflammatory bowel disease and hereditary syndromes, may exhibit specific imaging manifestations. In addition, YOCRC is frequently associated with a mucinous histopathological subtype which may be identifiable based on the presence of specific imaging features. Given their younger age, these patients are more likely to undergo aggressive treatment and complex surgical interventions. Specific considerations such as fertility preserving surgical techniques must be factored in when managing these patients. As the incidence of YOCRC increases, guidance for colonoscopy screening protocols may need revision. This includes evaluating the role of ionising imaging techniques in both diagnosing and follow-up to balance early detection and minimising radiation exposure in this younger patient population.

Low-density lipoprotein receptor-related protein 8 (LRP8) is a crucial regulator of lipid metabolism and is implicated in the development and treatment of various cancers. However, its role in bladder cancer (BCa) remains unknown. We analyzed LRP8 expression in BCa using the TCGA database and clinical samples. We manipulated LRP8 expression in tumor cell lines using siRNA or overexpression plasmid transfection. Cell proliferation, migration, invasion, apoptosis, and drug resistance were assessed through CCK-8, transwell, flow cytometry, and IC50 assays. Additionally, a rescue experiment confirmed the association between LRP8 and lipid metabolism. LRP8 was significantly upregulated in BCa tissues and cells. Knockdown of LRP8 reduced tumor cell proliferation, migration, invasion, and increased apoptosis while enhancing cisplatin sensitivity. Overexpression of LRP8 boosted malignant progression and cisplatin resistance in tumor cells. The expression level of LRP8 is positively linked with the expression of lipid metabolism-related genes, phospholipid accumulation, and triglyceride accumulation. Notably, inhibiting lipid metabolism reversed the malignant progression and cisplatin resistance induced by LRP8 overexpression. LRP8 could promote BCa malignant progression and cisplatin resistance through lipid metabolism regulation.

Pancreatic metastases from renal cell carcinoma (RCC) are usually managed surgically but with significant morbidity. As an alternative, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has shown promising results in treatment of pancreatic neuroendocrine tumors. The aim of our study was to assess technical success, effectiveness, and safety of EUS-RFA in patients with pancreatic metastases of RCC.

This retrospective, observational study included consecutive patients referred for EUS-RFA of pancreatic RCC metastases. EUS-RFA was performed through 18G or 19G dedicated RFA needles. Effectiveness of EUS-RFA treatment was defined by necrosis with no contrast enhancement or lesion disappearance, determined by contrast-enhanced computed tomography (CT) scan, at 2 to 5 months post procedure, 1 year, and at the end of follow-up. Safety was assessed per and post procedure.

Between January 2015 and January 2021, eight patients with 11 lesions were treated and median time from RCC diagnosis to pancreatic metastases RFA was 8.5 years (1-15). Mean lesion size was 13.9 mm (± 3.9). Technical success assessed by immediate post procedure contrast-enhanced CT or Doppler was 100%. At the first CT scan follow-up, complete response was 45.4% and partial response was 27.3%. At 1 year, complete response was 45.4% and partial response was 27.3%. Three patients had multiple EUS-RFAs. Adverse events occurred in 3 patients (mild acute pancreatitis, abdominal pain, and pancreatic fistula with retro-gastric pseudocyst).

Our study demonstrated the feasibility and safety of EUS-RFA for patients with pancreatic metastases of RCC.

Endometrial cancer (EC) is a common gynecological malignancy with increasing incidence, especially in developed nations. Understanding genetic variations, particularly single nucleotide polymorphisms (SNPs), is crucial for uncovering the disease's pathogenesis, progression, and treatment responses. This study explores the global research landscape of SNPs in EC, focusing on field evolution, key contributors, and emerging trends.

A systematic search of the Web of Science Core Collection (WoSCC) retrieved 838 publications on SNPs in EC from 1991 to 2024. Bibliometric indicators, including publication volume, citation counts, and keyword occurrences, were analyzed using VOSviewer, CiteSpace, and the R package "bibliometrix" for visual mapping and trend analysis.

The United States (230 publications) and China (182 publications) were leaders in research output. Harvard University and the National Cancer Institute were prominent contributors. Key themes included "microsatellite instability" (a hallmark of DNA mismatch repair deficiency) and "genome-wide association studies" (GWAS), identifying susceptibility loci like HNF1B and CYP19A1. Recent trends, such as "Mendelian randomization," have enhanced causal inference in risk factor studies. SNP research has advanced risk prediction models and personalized therapeutic strategies, such as hormone therapy tailored to genetic profiles.

SNP research has deepened our understanding of EC's genetic basis, with a growing emphasis on Mendelian randomization and GWAS. These advancements have refined risk prediction and opened new avenues for personalized medicine. Integrating SNP data with environmental and hormonal factors remains crucial for advancing prevention, diagnosis, and treatment strategies in EC.

This study explored the relationship between cognitive function and brain structure in lung cancer (LCs) patients without brain metastases and healthy controls (HCs). A cohort of 75 chemotherapy-naive LCs without brain metastases and 29 age-, sex-, and education-matched HCs underwent cognitive assessments and structural MRI. The MRI focused on cortical thickness, surface area, and volume of subcortical structures. We examined the relationships among these parameters. The volume of twelve subcortical structures was significantly reduced in patients with advanced-stage lung cancer (aLCs) compared to HCs (p < 0.05). In aLCs, cortical thickness decreased in one brain region and surface area in five regions (p < 0.05). Patients with early-stage lung cancer (eLCs) exhibited increased cortical thickness in three regions. When comparing eLCs to aLCs, there was a notable decrease in cortical thickness and surface area (p < 0.05). Visuospatial/executive and delayed memory functions were impaired in aLCs and worsened with disease progression. These impairments correlated positively with the thickness of several cerebral cortices and the surface area and volume of subcortical structures (p < 0.05). Structural brain changes and cognitive dysfunction are evident in aLC patients, independent of metastasis. Since none of the patients received chemotherapy, the observed abnormalities in aLCs, absent in eLCs, are likely attributable to the disease itself rather than chemotherapy effects.

Systemic therapies that have shown a benefit in advanced prostate cancer are being evaluated in earlier disease stages. We sought to determine the prevalence of transcriptomic changes in signatures related to treatment susceptibilities in patients with nonmetastatic prostate cancer.

Patients with nonmetastatic prostate cancer with Decipher genomic classifier and whole-transcriptome profiling data for biopsy specimens from October 2016 to February 2024 were included (n = 140 548). Predefined treatment-related signatures of androgen receptor activity (AR-A), PTEN loss, homologous recombination deficiency (HRD), RB loss, immune activity, and prostate-specific membrane antigen (PSMA; FOLH1) expression, along with Decipher scores and prostate cancer subtypes, were assessed.

The prevalence of low AR-A scores and the basal subtype, which are associated with lower responsiveness to androgen deprivation therapy (ADT), increased with American Joint Committee on Cancer (AJCC) stage and Decipher genomic risk. The prevalence of cancers with a potential response to PI3K inhibitors, according to PTEN loss, and a response to PARP inhibitors, according to HRD status, also increased with AJCC stage and Decipher genomic risk score (all p < 0.001). The prevalence of high PSMA expression was greater in AJCC grade IIC-IIIC disease, so these patients would be potential candidates for PSMA radioligand therapies. More than 60% of patients with AJCC grade IIC-IIIC disease and very high Decipher scores (>0.85) are potential candidates for targeted therapies.

Treatment-related signature scores vary by AJCC stage and Decipher score and may be useful in guiding trials and selecting targeted therapies for nonmetastatic prostate cancer. Higher-stage prostate cancers appear to be more basal and androgen-independent, and thus may be more susceptible to intensified ADT + androgen receptor pathway inhibitors or therapies targeting PARP or PSMA.

Lung cancer is a complex disease with varying subtypes. The genetic architectures and risk factors that are similar or distinct among these subtypes remain unclear. In this work, Genome-wide association studies (GWAS) conducted by the International Lung Cancer Consortium and transdisciplinary Research in Cancer of the Lung were utilized to illustrate the genetic landscapes of different subtypes of lung cancer. GWAS of 942 phenotypes from UK Biobank and 902 phenotypes from FinnGen Biobank were analyzed to identify the genetic risk factors specific or common to each subtype of lung cancer through two sample Mendelian randomization inverse variance weighting method. Multivariable Mendelian randomization was employed to assess the true causals of lung cancer. We found that lung cancer, small cell lung carcinoma, squamous cell lung cancer and lung adenocarcinoma shared similar, yet varied genetic architectures. Genetic risk loci at 15q25 were identified in all types of lung cancer. Yet, genetic risk loci at 5p15 were observed in squamous cell lung cancer and lung adenocarcinoma, but not in small cell lung carcinoma. Out of 942 phenotypes from UK Biobank, smoking, time spent watching television, age first had sexual intercourse, alcohol usually taken with meal and age at first live birth were common risk factors for all types of lung cancer. Moreover, out of 902 traits in FinnGen Biobank, chronic obstructive pulmonary disease (COPD) was positively associated with small cell lung carcinoma, squamous cell lung cancer and lung adenocarcinoma. Angina pectoris and myocardial infarction were negatively associated with lung cancer, squamous cell lung cancer and lung adenocarcinoma. And Alzheimer's disease was negatively associated with lung cancer, small cell lung carcinoma and squamous cell lung cancer. In further weighted median and weighted mode methods, myocardial infarction, angina pectoris and Alzheimer's disease also had genetical associations with lung cancer or its subtypes. Even, considering factors such as smoking, COPD, and other risk factors together, myocardial infarction, angina pectoris and Alzheimer's disease retained the genetical associations with lung cancer and its subtypes. Overall, in a phenome-wide Mendelian randomization analysis, our results have highlighted both similar and distinct risk factors among different subtypes of lung cancer. Additionally, our findings have provided genetic associations linking myocardial infarction, angina pectoris and Alzheimer's disease with lung cancer or its various subtypes.

Melanoma, known for its aggressive behavior and tendency to metastasize to the brain and lungs, is a formidable challenge in oncology. Radiotherapy is a potent treatment for localized solid tumors, effective against both intracranial and extracranial metastases. Yet, some melanoma patients exhibit substantial resistance to radiotherapy, with the underlying mechanisms of this resistance remaining elusive. While radiotherapy can stimulate the infiltration of immune cells, thereby triggering a range of immunostimulatory effects, it can also suppress the tumor microenvironment (TME), limiting its effectiveness. In physiological conditions, cytokines inhibit the activity of immunosuppressive cells through paracrine and autocrine signaling, while also activating immune cells to boost antitumor responses. Here, we found that Interleukin (IL)-21 expression was higher in the mice with good radiotherapy response to melanoma than in the mice with poor radiotherapy response. Interestingly, we also observed the higher infiltration of M2 TAMs and lower CD8+ T cells in the group with poor radiotherapy response. To tackle this issue, we explored the therapeutic potential of a plasmid encoding IL-21, delivered via attenuated Salmonella, in mice bearing melanomas. Our findings revealed that IL-21 administration significantly reduced M2 TAMs infiltration and enhanced CD8+ T cells infiltration and granzyme B (GZMB) expression within melanoma tumors. Most importantly, the combination of IL-21 with radiotherapy led to markedly tumor reduction compared to either treatment alone. This research highlights the potential of IL-21 as a valuable adjunct to radiotherapy in the treatment of melanoma, presenting a promising strategy for enhancing antitumor immune responses and optimizing patient outcomes.

The utility of the immune prognostic index (IPI) for esophageal squamous cell carcinoma (ESCC) has yet to be established after minimally invasive esophagectomy (MIE). The purpose of this study was to investigate the value of IPI in predicting the prognosis and postoperative adjuvant chemotherapy (AC) benefits of ESCC patients.

Between January 2011 and December 2018, 613 ESCC patients underwent MIE at our center and were divided into two groups: low IPI and high IPI.Log-rank tests were used to compare the overall survival (OS) and disease-free survival (DFS) of patients in different groups based on Kaplan-Meier survival analysis. Differences in clinical characteristics between groups were eliminated by propensity score matching (PSM) analysis. To identify independent risk factors influencing OS and DFS, the Cox proportional risk model was used.

In comparison to the high IPI group, the low IPI group had a better 5-year OS and DFS in both the entire and matched cohorts (P < 0.05). IPI was found to be an independent prognostic factor for OS and DFS in a multivariate analysis of the entire cohort and the matched cohort (P < 0.05). In subgroup analyses of most clinicopathological factors, high IPI was associated with a higher risk of death or recurrence in the matched cohorts. When combined with 8th TNM staging, the 5-year OS and DFS of stage II or III patients with low IPI in the AC group were not different from those in the non-AC group (P > 0.05), and AC of stage III patients with high IPI significantly prolonged 5-year OS and DFS (OS: 37.4% vs 26.2%, P = 0.018; DFS: 33.6% vs 19.8%, P = 0.042).

Preoperative IPI is a promising predictor of ESCC after MIE. For stage III ESCC patients with high IPI, AC can significantly reduce the risk of death or recurrence.

In recent years, magnolol (MG), a natural active compound of polyphenolic nature, has garnered significant interest for its anti-cancer effects. Numerous studies conducted on cell lines and animal models have indicated a positive impact of administering drugs or semi-synthesized products derived from MG, including a decreased incidence of various cancers. This review aims to illustrate the underlying cellular and molecular basis of its actions. The article includes in-depth explanations of phytochemistry, semi-synthetic derivatives, bioavailability, pharmacokinetics, preclinical research, anti-tumor mechanisms, human clinical studies, toxicity, side effects, and safety. It also demonstrates that, in contrast to the wealth of synthetic medications, MG is highly effective against bladder, colon, gastric, skin, liver, lung, gallbladder, and prostate cancers. The findings of this review indicate that MG is a promising candidate as an anti-tumor agent, and future research should focus on developing new semi-synthetic derivative compounds with potential anti-tumor properties.

Predicting cancer incidence has long been a challenge for clinicians and researchers. Accurate predictions are essential for health planning to ensure adequate resources for diagnosis, treatment, and rehabilitation. Current prediction methods rely on historical data, assuming persistent patterns of cancer incidence.

In this study, the Google Trends tool was used to obtain the relative search volume index (RSVI) for the topic "cancer" each year from 2017 to 2023 in the United States and worldwide. The proposed model incorporated actual cancer incidence rates and yearly changes in RSVI.

The model was applied to predict the rates of new cancer cases in fifty American states over four consecutive years (2017, 2018, 2019, 2020). The selection of years was restricted with data availability. In most states, the percentage error did not exceed 6%. The high degree of similarity between the actual and predicted cancer incidence rates was notable. Similar results were obtained when predicting cancer incidence rates in the countries studied.

The model has successfully provided accurate short-term predictions of cancer incidence rates across all 50 American states and 54 countries since 2017.

The role of the number of negative lymph nodes (NLNs) removed on survival and tumor recurrence after surgery in patients with non-small-cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the effect of the number of NLNs on overall survival (OS), recurrence-free survival (RFS), and recurrence rate of patients with NSCLC after surgery. This multicenter retrospective cohort study examined the medical profile of 1002 patients with a definite diagnosis of NSCLC who underwent surgery between 2021 and 2023 at one of our medical centers. Patients with NSCLC were classified into 4 groups based on the number of NLNs removed during surgery as follows. I: <10 (196 patients); II: 10 to 19 (341 patients); III: 20 to 30 (267 patients); and IV: >30 NLN (198 patients). The patients' demographics, tumor characteristics, and pathological findings were obtained by reviewing their medical records. The 5-year survival rate was 36.1%. The OS rate in groups I, II, III, and IV patients was 14%, 25%, 33%, and 43%, respectively (log-rank = 161.2, P = .001). Also, the RFS rate in patients of groups V/III was significantly higher than in groups I/II (P < .05). Multivariate analysis showed that the OS rate in group V and II patients was significantly higher than the other 2 groups (I and II). In addition, age > 65 years, comorbidity, tumor size > 3, advanced tumor stage, presence of metastasis, lymph node ratio > 0.3, total lobectomy, central tumor, and no adjuvant chemotherapy are significantly associated with decreased OS rate of patients with NSCLC. The increase in the number of NLNs removed during surgery was associated with an increase in the OS and RFS rates. Attention to this number can be a key factor in improving the survival prediction of patients with NSCLC.

For centuries, a competitive evolutionary race between prokaryotes and related phages or other mobile genetic elements has led to the diversification of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR‑associated sequence (Cas) genome‑editing systems. Among the different CRISPR/Cas systems, the CRISPR/Cas9 system has been widely studied for its precise DNA manipulation; however, due to certain limitations of direct DNA targeting, off‑target effects and delivery challenges, researchers are looking to perform transient knockdown of gene expression by targeting RNA. In this context, the more recently discovered type VI CRISPR/Cas13 system, a programmable single‑subunit RNA‑guided endonuclease system that has the capacity to target and edit any RNA sequence of interest, has emerged as a powerful platform to modulate gene expression outcomes. All the Cas13 effectors known so far possess two distinct ribonuclease activities. Pre‑CRISPR RNA processing is performed by one RNase activity, whereas the two higher eukaryotes and prokaryotes nucleotide‑binding domains provide the other RNase activity required for target RNA degradation. Recent innovative applications of the type VI CRISPR/Cas13 system in nucleic acid detection, viral interference, transcriptome engineering and RNA imaging hold great promise for disease management. This genome editing system can also be employed by the Specific High Sensitivity Enzymatic Reporter Unlocking platform to identify any tumor DNA. The discovery of this system has added a new dimension to targeting, tracking and editing circulating microRNA/RNA/DNA/cancer proteins for the management of cancer. However, there is still a lack of thorough understanding of the mechanisms underlying some of their functions. The present review summarizes the recent updates on the type VI CRISPR/Cas system in terms of its structural and mechanistic properties and some novel applications of this genome‑editing tool in cancer management. However, some issues, such as collateral degradation of bystander RNA, impose major limitations on its in vivo application. Furthermore, additional challenges and future prospects for this genome editing system are described in the present review.

The aim of this study is to evaluate the use of indocyanine green (ICG) as a detection modality in sentinel lymph node (SLN) procedures for vulvar cancer.

A retrospective cohort study was performed from January 2008-August 2022 including all patients who underwent a SLN procedure for ≤4 cm vulvar cancer tumors with clinically/radiological normal inguinal nodes. SLN procedures with Tc99 +/- blue dye were compared to those with ICG +/- Tc99. Patient and tumor characteristics were collected as well as short-term and long-term complications. A subset analysis of SLN procedures with ICG alone was described.

A total of 229 patients were included, representing 365 groins. Detection modality was Tc99 +/-blue dye in 189 patients (304 groins) and ICG +/-Tc99 in 40 patients (60 groins). The SLN detection rate for Tc99 +/- blue dye was 93.4 % and for ICG +/- Tc99 90.3 % (p = 0.4). The SLN was positive in 17.3 % of the Tc99 +/- blue dye group vs 23.2 % in the ICG +/- Tc99 group (p = 0.3). There was no significant difference in short- or long-term complications. The detection rate among 15 patients (22 groins) where ICG was used as a single modality was 90.9 %. There were no specific patient or tumor characteristics related to SLN mapping failure.

The use of ICG +/- Tc99 as detection modality shows promising results with a success rate comparable to Tc99 +/- blue dye, supporting the use of ICG. Future studies are needed to confirm the efficacy and long-term safety of ICG alone.

The present study aimed to investigate the role of 6‑phosphofructo‑2‑kinase/fructose‑2,6‑biphosphatase 4 (PFKFB4) in endometrial cancer cells and to explore its potential molecular mechanisms. PFKFB4 expression in endometrial cancer tissues was detected by immunohistochemistry. Cell Counting Kit‑8, Transwell assays and flow cytometry were used to detect cell proliferation, invasion and apoptosis in endometrial cancer cells after PFKFB4 knockdown. An enzyme‑linked immunosorbent assay was used to detect the glucose and lactic acid contents. Western blotting was performed to detect the levels of glycolysis‑related enzymes, steroid receptor coactivator‑3 (SRC‑3), and phosphorylated SRC‑3. In vivo experiments were performed to investigate the tumorigenic potential of PFKFB4. PFKFB4 expression was upregulated in endometrial cancer tissues compared with that in normal controls, and its upregulation was positively correlated with the depth of myometrial invasion, lymph node metastasis, surgical pathological stage and vascular invasion. PFKFB4 knockdown significantly inhibited proliferation and invasion, increased apoptosis, and decreased oxygen consumption and lactic acid production in endometrial cancer cells. PFKFB4 knockdown decreased SRC‑3 phosphorylation. After simultaneous PFKFB4 knockdown and SRC‑3 overexpression in cancer cells, oxygen consumption, lactic acid production, and glycolysis‑related protein expression were increased compared with those in control cells. PFKFB4 knockdown inhibited tumor proliferation, apoptosis and the expression of Ki‑67. PFKFB4 may regulate glycolysis in endometrial cancer cells by targeting SRC‑3, thus promoting endometrial cancer progression.

Clinical trials in oncology initially recruit heterogeneous populations, without catering for all types of variability. The target cohort is often not representative, leading to variability in pharmacokinetics (PK). To address enrollment challenges in clinical trials, physiologically based pharmacokinetic models (PBPK) models can be used as a guide in the absence of large clinical studies. These models require patient-specific systems data relevant to the handling of drugs in the body for each type of cancer, which are scarce.

This review explores system parameters affecting PK in cancer and highlights important gaps in data. Changes in drug-metabolizing enzymes (DMEs) and transporters have not been fully investigated in cancer. Their impaired expression can significantly affect capacity for drug elimination. Finally, the use of PBPK modeling for precision dosing in oncology is highlighted. Google Scholar and PubMed were mainly used for literature search, without date restriction.

Model-informed precision dosing is useful for dosing in sub-groups of cancer patients, which might not have been included in clinical trials. Systems parameters are not fully characterized in cancer cohorts, which are required in PBPK models. Generation of such data and application of cancer models in clinical practice should be encouraged.

This study aimed to elucidate the clinical outcomes of patients with pathologic T3 (pT3) and pathologic T4 (pT4) tumors who underwent radical resection with multivisceral resection (MVR) and to assess the prognostic significance of MVR in locally advanced colorectal cancers (CRCs) in pT3 and pT4 tumors.

This multicenter retrospective analysis evaluated the characteristics, clinicopathologic stages, perioperative factors, and clinical outcomes of patients who underwent primary colorectal resection. Patients were divided into 4 groups: those with a pT3 tumor who did not undergo MVR (pT3 - MVR; n = 1108), those with a pT3 tumor who underwent MVR (pT3 + MVR; n = 56), those with a pT4 tumor who did not undergo MVR (pT4 - MVR; n = 306), and those with a pT4 tumor who did underwent MVR (pT4 + MVR; n = 123). Univariate and multivariate regression analyses were performed to identify risk factors for recurrence.

The pT3 + MVR group exhibited a higher 5-year recurrence rate than the pT3 - MVR group, with recurrence rates similar to those of the pT4 - MVR or pT4 + MVR groups (pT3 - MVR, 17.4%; pT3 + MVR, 31.6%; pT4 - MVR, 33.4%; pT4 + MVR, 35.1%). Multivariate analysis identified MVR as an independent risk factor for recurrence, particularly peritoneal dissemination, in pT3 tumors, whereas MVR had less effect on recurrence in pT4 tumors.

pT3 tumors requiring MVR had a higher recurrence rate than pT4 tumors. The surgeon's clinical assessment of potential T4 tumors requiring MVR at the time of surgery was an important prognostic indicator in advanced CRC.

The incidence of secondary cardiac malignancies is on the rise due to the aging population. A 63-year-old male presented with recurrent chest pain and anterior ST elevations on ECG, leading to primary PCI, but continued to experience chest pain and persistent ST elevation. Cardiac imaging revealed a cardio-invasive lung malignancy.

The initiation and progression of clear cell renal cell carcinoma (ccRCC) are closely linked to significant metabolic alterations. Specifically, lipid metabolism alterations and their association with the high invasiveness in ccRCC require further investigation. After conducting RNA-sequencing (RNA-seq), we discovered that Hydroxyacyl-CoA Dehydrogenase Trifunctional Multienzyme Complex Subunit Beta (HADHB) was significantly downregulated in the highly invasive ccRCC cell line. It was found that the expression of HADHB in ccRCC tumor tissues was lower than that in paracancer tissues, which is associated with poor patient prognosis. Subsequently, we confirmed that highly invasive ccRCC exhibited an increased lipid accumulation due to the suppression of mitochondrial fatty acid transport and enhanced conversion of fatty acids to triglycerides within cancer cells. Specifically, the downregulation of HADHB inhibited mitochondrial fatty acid β-oxidation (FAO) in cancer cells, leading to partial impairment of mitochondrial function and decreased ATP production. However, this trade-off involving the reduction of a high-yield ATP production conferred an advantage by reducing reactive oxygen species (ROS) generation within cancer cells, thereby protecting them from oxidative stress and enhancing their invasive potential. Furthermore, the downregulation of HADHB promoted epithelial-mesenchymal transition (EMT) and angiogenesis in cancer cells, accelerating the progression of ccRCC and endowing ccRCC cells with metastatic capabilities.

The neutrophil-to-lymphocyte ratio (NLR) not only indicates the inflammatory response within the tumor microenvironment but may also correlate with tumor biological behavior (such as aggressiveness). The present study aimed to systematically review and conduct a meta-analysis on the impact of the NLR on the prognosis of patients with renal cell carcinoma (RCC). To this aim, a comprehensive search of multiple relevant databases, including PubMed, Embase and the Cochrane Library, was conducted to identify literature related to NLR and RCC prognosis. Following rigorous literature screening and quality assessment, a systematic quantitative analysis was ultimately performed on several studies that met the inclusion criteria. The results indicated a significant association between elevated NLR levels and poor prognosis in patients with RCC, suggesting that high NLR levels may serve as an independent predictor of unfavorable outcomes. Therefore, the present study provides important evidence for clinical decision-making, further demonstrating that NLR can serve as an independent prognostic indicator for patients with RCC, aiding healthcare professionals in making more precise judgments in patient management and treatment strategy formulation.

Acute myeloid leukemia (AML) is characterized by the uncontrolled proliferation of myeloid leukemia cells in the bone marrow and other hematopoietic tissues and is highly heterogeneous. While with the progress of sequencing technology, understanding of the AML-related biomarkers is still incomplete. The purpose of this study is to identify potential biomarkers for prognosis of AML. Based on WGCNA analysis of gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases were employed for investigating potential biomarkers for the prognosis of AML. This study screened a total of 6153 genes by analyzing various changes in 103 acute myeloid leukemia (AML) samples, including gene mutation expression, methylation level distribution, mRNA expression, and AML-related genes in public databases. Moreover, seven AML-related co-expression modules were mined by WGCNA analysis, and twelve biomarkers associated with the AML prognosis were identified from each top 10 genes of the seven co-expression modules. The AML samples were then classified into two subgroups, the prognosis of which is significantly different, based on the expression of these twelve genes. The differentially expressed 7 genes of two subgroups (HOXB-AS3, HOXB3, SLC9C2, CPNE8, MEG8, S1PR5, MIR196B) are mainly involved in glucose metabolism, glutathione biosynthesis, small G protein-mediated signal transduction, and the Rap1 signaling pathway. With the utilization of WGCNA mining, seven gene co-expression modules were identified from the TCGA database, and there are unreported genes that may be potential driver genes of AML and may be the direction to identify the possible molecular signatures to predict survival of AML patients and help guide experiments for potential clinical drug targets.

The uterine carcinoma is the most commonly diagnosed malignancy in the female pelvis. Accurate identification of tumour origin is crucial for determining appropriate treatment approaches. This study aims to develop a prediction model using multiple MRI parameters to accurately diagnose uterine cancer with an indistinctive origin and those involving both the endometrium and cervix prior to treatment.

This prospective cohort study included patients who were newly diagnosed with uterine carcinoma who underwent MRI and were considered for hysterectomy within 6 months after MRI.

A total of 78 patients with uterine carcinoma were enrolled. Certain imaging features were found to be consistent with cervical carcinoma, included parametrial, vaginal, stromal invasion, and peripheral rim enhancement. Cervical cancer appeared hyperintense compared to the myometrium unlike endometrial cancer.

The study found that certain morphologic features were reliable indicators for detecting cervical carcinoma.

Liver cancer is prevalent with the third highest mortality rate globally. The biomechanical properties of cancer cells play a crucial role in their proliferation and differentiation. Studying the morphological and mechanical properties of individual living cells can be helpful for early diagnosis of cancers. Herein, atomic force microscopy (AFM) was used to investigate the effects of Phellinus linteus on hepatocyte cells (HL-7702) and hepatocellular carcinoma cells (SMCC-7721) in terms of morphological and mechanical changes at the nanoscale. The water extract of Phellinus linteus (PLWE) resulted in increased height and surface roughness of SMCC-7721 cells. Also, the PLWE-treated showed that the average adhesion decreased by 1.69 nN and the average Young's modulus increased by 0.379 kPa. Additionally, the SMCC-7721 cells treated with PLWE showed clearly reduced activity compared with HL-7702 cells. This study suggested that Phellinus Linteus could be a potential candidate for selective anti-cancer therapy, providing a new avenue for the treatment of hepatocellular carcinoma.

Bis(indolyl)methanes (BIMs) are a class of compounds known for their diverse biological activities, including potential anticancer properties. Modern synthetic chemistry techniques are examined in this work to develop and manufacture novel anticancer medications with increased effectiveness and fewer side effects. The cytotoxic efficacy of a moderate and very effective method for creating pharmacologically active BIMs 3a-j using ZrO2 nanoparticles as a catalyst was assessed against the MCF-7 breast cancer cell line. Remarkably, compounds 3a and 3b exhibited exceptional potency, with IC50 values of 0.17 and 0.13 μM, respectively, surpassing the activity of standard anticancer agents sorafenib (IC50: 1.23 μM). Another compound 3j demonstrated moderate inhibition effect with an IC50 value of 8.6 μM. These results highlight the potential of BIMs as promising anticancer agents and warrant further investigation into their mechanism of action and therapeutic applications.

To identify the predictors of local recurrence and distant metastasis after radical surgery for stage I-III colorectal cancer.

Patient and tumor characteristics, clinicopathological stages, perioperative factors, and postoperative outcomes, including local and distant recurrence, of patients who underwent primary colorectal resection were evaluated in this multicenter retrospective analysis. Univariate and multivariate regression analyses were performed to identify the risk factors for local and distant recurrences, with a focus on the intraoperative blood loss (IBL) ratio [IBL (mL)/total blood volume (mL)] and postoperative complications.

The risk factors for local and distant recurrence pattern differed. The predictors for local recurrence included perioperative factors, such as the IBL ratio and anastomotic leakage, as well as tumor factors, including pT4, rectal cancer, and poorly differentiated histology, in the multivariate analysis. On the other hand, the predictors for distant recurrence included perioperative factors, such as Clavien-Dindo score ≥ 3, and absence of adjuvant chemotherapy as well as tumor factors including pT stage, pN stage, and rectal cancer. The area under the receiver operating characteristic curve (AUC) for local recurrence in the IBL ratio was 0.745, which was higher than the AUCs for other recurrence patterns in the IBL ratio. Patients with a higher IBL ratio had a higher rate of early local recurrence within 2 years postoperatively (Wilcoxon test and p = 0.028).

Reducing IBL and formulating perioperative strategies to prevent anastomotic leakage may help decrease the local recurrence rate and improve prognosis.