Screening programs for colorectal cancer (CRC) reduce CRC incidence and mortality, while balancing benefits and harms of the population. However, benefits vary widely among individuals. Low-risk individuals may face unnecessary burdens, while high-risk individuals could benefit from more intensive screening. Risk-based screening addresses these issues by tailoring screening strategies using risk factors such as age, sex, race, ethnicity, lifestyle factors, genetic predisposition, and previous screening results. Potential benefits of risk-based screening include improved cost-effectiveness, efficient resource use and reduced unnecessary procedures. Challenges include a lack of validated risk stratification tools, data availability, healthcare capacity, and ethical considerations. Several countries started to evaluate risk-based screening programs with optimistic results. While promising, further research is necessary to address the remaining challenges. Nevertheless, risk-based screening has the potential to enhance patient experiences, optimize the balance of individual-level benefits and harms, and positively impact the overall burden and costs associated with CRC screening.

To assess the levels of knowledge, attitudes and practices (KAP) toward skin cancer prevention among Malaysian adults and to examine differences in KAP across socio-demographic groups.

Cross-sectional online survey.

Community-based study conducted in Malaysia using social media recruitment.

A total of 386 adults aged ≥18 years residing in Malaysia. Most participants were young adults (86.3%), female (55.4%) and of Chinese ethnicity (65.5%). Healthcare professionals were excluded.

Primary outcomes were levels of knowledge, attitude and preventive practices toward skin cancer, measured using the validated KAP-SC-Q (Knowledge, Attitude and Practice of Skin Cancer Questionnaire) and categorised as poor, moderate or good. Secondary outcomes included differences in KAP across socio-demographic and clinical characteristics, analysed using independent t-tests and χ² tests.

Over half of participants demonstrated poor knowledge of skin cancer (56.0%) and the vast majority showed inadequate preventive practices (84.2%), while attitudes toward skin cancer were predominantly positive (62.4%). Significant differences in mean KAP scores and categorical levels were observed across several socio-demographic variables. Participants with tertiary education had higher knowledge (14.32 vs 12.61) and attitude scores (20.01 vs 15.95; p<0.001) than those with lower education. Individuals with a diagnosis of skin disease had significantly higher knowledge (14.95 vs 13.03; p=0.001), attitude (20.03 vs 18.21; p=0.007) and practice scores (12.10 vs 9.72; p<0.001). Personal history of skin cancer and severe sunburn was associated with better preventive practices but poorer attitudes (p<0.001), and light-skinned participants were more likely to have poor knowledge and attitudes (p<0.05).

Malaysian adults exhibited limited knowledge and very poor preventive practices toward skin cancer despite generally positive attitudes. These findings highlight substantial gaps between awareness and behaviour and support the need for targeted public health interventions to correct misconceptions, improve risk perception especially in high-risk groups and promote effective ultraviolet protection behaviours.

A 79-year-old Japanese man developed a low abdominal mass. Contrast-enhanced computed tomography revealed a left-sided pelvic kidney measuring 60 mm, suggestive of renal cell carcinoma. Abnormal vascular anatomy was also noted, including three renal arteries arising from the abdominal aorta, umbilical artery, and inferior mesenteric artery, respectively. On the basis of these findings, we performed robot-assisted radical nephrectomy with placement of fluorescent ureteral stents to facilitate intraoperative identification of both ureters. The patient was positioned in steep Trendelenburg, and the pelvic kidney was removed safely. The console time was 156 min, and the estimated blood loss was 20 mL. To our knowledge, this is the first case of robot-assisted radical nephrectomy for renal cell carcinoma arising in a pelvic kidney. Steep Trendelenburg positioning and placement of fluorescent ureteral stents were key to achieving a favorable surgical outcome.

Colon adenocarcinoma (COAD), although the third-most common type of gastrointestinal tumors, still lacks specific biomarkers for early diagnosis, treatment, and prognosis.

This study aimed to evaluate the CD276 in tumorigenesis, prognosis and immunity for colon adenocarcinoma.

The CD276 expression in colon adenocarcinoma was established by using RNA-sequencing transcriptomic data of The Cancer Genome Atlas (TCGA) databases. The biological functions of CD276 were evaluated using the Metascape database and Gene Set Enrichment Analysis (GSEA). The association between CD276 and immune cell infiltration was investigated by TIMER website. Correlation analysis was performed between CD276 expression and clinicopathological characteristics. CD276 expression was significantly elevated in colon adenocarcinoma tumor (p < 0.0001). High CD276 was associated with microsatellite instability (MSI) status, patients' survival, and disease progression. Cox regression analysis revealed that CD276 was a risk factor for overall survival [hazard ratio (HR): 1.848, p = 2.64E-03], disease-specific survival (HR: 2.406, p = 5.35E-04), and progression-free interval (HR: 1.772, p = 2.04E-03). Moreover, CD276 level was significantly associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression.

Our analyses indicated that increased CD276 may contribute to colon adenocarcinoma development by activating tumor-promoting signal pathways and altering the immune microenvironment.

Feline oral squamous cell carcinoma (FOSCC) and human head and neck squamous cell carcinoma (HNSCC) are the 4th most common malignant neoplasms in cats and humans. Most cats are not treated due to the poor prognosis and die of their disease within a few months of diagnosis. In humans, despite surgery, radiation therapy, and chemotherapy, 1/3 of patients develop loco-regional recurrence within 5 years. FOSCC has commonly been proposed as a model for HNSCC since FOSCC is a spontaneous model and exhibits similar biologic behaviour, treatment course, and outcome to the human disease. The objective of this study was to identify genetic similarities and differences with HNSCC, therapeutic targets, and possible causes of FOSCC through whole exome sequencing. Thirty-six matched normal FOSCC tumours and three matched normal chronic gingivostomatitis lesions were sequenced with a previously validated custom Roche Nimblegen exome reagent, based on the Felis_catus_9.0 genome assembly, covering 35.7 Mb. The exome libraries were pooled and sequenced on the Illumina Novaseq6000 as 2 × 150 bp reads. The data was analysed with the McDonnell Genome Institute's (MGI) cancer informatics pipelines, namely the Genome Modelling System (GMS), which was adapted to the feline genome. TP53 harboured consequential variants in 71% of the FOSCC tumours and was the most commonly mutated gene. Consequential variants in TTN were seen in 18% tumours and consequential variants in FSIP2, LRP1B, RYR2 were seen 9% of tumours. Genes with highly recurrent copy number variants (CNVs) included CKDN2A, PTEN, and MYC. TMB was very low, 0-1.6 (mean 0.66). Six cats had a history of chronic gingivostomatitis for years before the diagnosis of FOSCC. Despite the low TMB, the genomic landscape of FOSCC parallels HPV-negative HNSCC. Aside from TP53, recurrent small-scale mutations in FOSCC were uncommon, but recurrent CNVs were common. FOSCC is a genetically and clinically heterogenous cancer. A multifactorial cause is suspected. Chronic gingivostomatitis, immunosuppression, and/or viral infection may be associated with FOSCC in young cats.

INBRX-105, a tetravalent, PD-L1-targeted TNFRSF9 (4-1BB) agonist, demonstrated preclinical antitumor activity. This first-in-human study evaluated INBRX-105 in solid tumors.

This open-label, 4-part, phase 1 study evaluated INBRX-105 alone or with pembrolizumab in adults with locally advanced/metastatic, unresectable solid tumors (NCT03809624). INBRX-105 was administered intravenously once every 2 weeks or 4 weeks in parts 1 (single-agent dose escalation; 0.001-3 mg/kg) and 2 (single-agent expansion) or once every 3 weeks in parts 3 (combination dose escalation; INBRX-105 0.03-1.0 mg/kg) and 4 (combination expansion). Part 2 enrolled patients with checkpoint inhibitor-relapsed/refractory (CPI-R/R) tumors. Part 4 enrolled patients with CPI-R/R or CPI-naïve disease. The primary endpoint was safety and tolerability of INBRX-105. Preliminary clinical response was a secondary endpoint.

Of 160 patients assessed, 81 received monotherapy (median age, 65 years; female, 50.6%), and 79 combination therapy (median age, 64 years; female, 38%). The INBRX-105 maximum tolerated dose was 0.3 mg/kg once every 3 weeks. Head and neck squamous cell carcinoma (n = 61) and non-small cell lung cancer (n = 25) were the most common tumor types. The most common any-grade INBRX-105-related adverse events (AE) were fatigue (monotherapy, 35.8%; combination, 17.7%), increased aspartate aminotransferase (25.9%; 15.2%), and nausea (19.8%; 17.7%). INBRX-105-related hepatic AEs occurred in 41 patients [monotherapy, n = 25 (grade ≥3, n = 11); combination, n = 16 (grade ≥3, n = 6)]. In all patients, the objective response rate was 8.8% [monotherapy, 3.7%; combination, 13.9% (CPI-naïve, 30%; CPI-R/R, 8.6%)]; the disease control rate was 43.1%.

The low response rates and hepatic safety signals observed do not support further clinical development of INBRX-105.

Tumor resistance to CPIs often develops, underscoring an unmet need. This first-in-human phase 1 trial evaluated INBRX-105-a tetravalent, PD-L1-targeted 4-1BB agonist-alone or with pembrolizumab. Unfortunately, clinical development of INBRX-105 was ended because of hepatotoxicity and limited efficacy. Novel treatment combinations with nonredundant, complementary immunotherapies are needed.

To compare outcomes of cutaneous ureterostomy (CU) and ileal conduit (IC) after radical cystectomy (RC), evaluating whether CU may expand surgical eligibility for frail patients with bladder cancer.

This longitudinal study, incorporating both prospective and retrospective data, included patients with urothelial carcinoma of the bladder who underwent radical cystectomy (RC) between January 2013 and June 2020. The clinical characteristics, surgical outcomes, complication rates, and mortality at 90 days and 365 days were analyzed and compared according to the type of urinary diversion.

A total of 127 patients were included: 70 (55%) underwent IC and 57 (45%) CU, all with a single stoma. CU patients were significantly older (P < 0.01), had higher ASA scores (P = 0.008), and showed a trend toward more advanced tumor staging (P = 0.051). Despite their poorer clinical status, CU patients demonstrated complication and mortality rates at 90 and 365 days, which were comparable to those of the IC group (P = 0.12, 0.28, and 0.62, respectively). CU was also associated with a shorter length of hospital stay (P < 0.01), earlier diet resumption (P < 0.01), and more days out of hospital within the first 90 days (P = 0.04).

A standardized CU technique represents a viable option for frail patients undergoing cystectomy, offering morbidity and mortality outcomes comparable to those of IC and potentially expanding surgical eligibility in high-risk populations.

Breast cancer remains one of the most prevalent and deadly malignancies in women. Metastasis remains an unmet clinical need specially in some subtypes such as triple negative breast cancer. Among non-metastatic patients, more than 40 % fail to achieve a complete pathological response during the course of treatment, facing high rates of local failure post-resection and distant metastases. Recent studies suggest an association between the presence of circulating tumor cells (CTCs) and the aggressiveness of the disease. Herein, we describe an orthotopic syngeneic mouse model in which tumor cells are directly inoculated into the exposed mammary gland. This model allows mechanistic studies on tumor progression and the evaluation of novel therapeutic strategies. Furthermore, the inclusion of surgical resection of established tumor closely mimics current clinical approaches in breast cancer treatment and enables the investigation of mechanisms underlying tumor relapse and metastasis. This chapter outlines the complete protocol, including all necessary steps and materials, for establishing a metastatic breast cancer model in mice. The model is based on CTCs that persist in the bloodstream and subsequently colonize distant organs (primarily the lungs) following surgical resection of the primary tumor.

Lung cancer is the leading cause of cancer-related mortality globally, primarily due to the high rate of diagnoses at advanced stages when metastasis has already occurred. The metastatic process is complex, making its study challenging. Experimental models that replicate metastasis are crucial for understanding the underlying biological mechanisms. Among these, intracardiac injection in mice is a valuable method for studying metastasis, as it releases tumor cells directly into the systemic circulation, promoting the colonization of secondary organs like the brain, bones, liver, and adrenal glands. This model is particularly significant in lung cancer research, as it enables the evaluation of tumor cell's ability to survive in circulation, adapt to distant microenvironments and grow there. This chapter outlines the protocol for intracardiac tumor cell injection in mice, focusing on technical considerations providing an essential tool for studying metastatic lung cancer.

The tumour microenvironment (TME) represents a heterogenous and dynamic niche, comprising cancer cells, extracellular matrix, stromal cells, vasculature and immune cells. The composition of the immune infiltrate varies between patient and tumour type, with the overall number, spatial localisation and functional status constituting the immune contexture. The presence of certain immune cells, including specific subsets of CD8 and CD4 T cells, natural killer cells, B cells and dendritic cells has been linked with favourable prognosis and response to treatment, including immunotherapy. In contrast, subsets of immune cells including macrophages, myeloid cells and neutrophils are frequently associated with poor prognosis, treatment resistance and tumour growth. Therefore, assessment of the immune contexture can be used to evaluate prognostic and predictive immune biomarkers, with CD8 cytolytic and memory T cells emerging as key immune effectors associated with clinical benefit across multiple solid malignancies. Here, we illustrate a straightforward automated immunohistochemistry (IHC) protocol for the detection and characterization of different subtypes of T-cells within the microenvironment of murine tumours. We also briefly illustrate the downstream process of visualization of these specific lymphocytic populations, ultimately providing both qualitative and quantitative analysis. The general protocol can readily be adapted to study a wide range of murine tumours and normal tissue (including secondary lymphoid organs), as well as profiling of other immune cell populations.