The unreasonable effectiveness of AI CADe polyp detectors to generalize to new countries

$\textbf{Background and aims}$: Artificial Intelligence (AI) Computer-Aided Detection (CADe) is commonly used for polyp detection, but data seen in clinical settings can differ from model training. Few studies evaluate how well CADe detectors perform on colonoscopies from countries not seen during training, and none are able to evaluate performance without collecting expensive and time-intensive labels. $\textbf{Methods}$: We trained a CADe polyp detector on Israeli colonoscopy videos (5004 videos, 1106 hours) and evaluated on Japanese videos (354 videos, 128 hours) by measuring the True Positive Rate (TPR) versus false alarms per minute (FAPM). We introduce a colonoscopy dissimilarity measure called "MAsked mediCal Embedding Distance" (MACE) to quantify differences between colonoscopies, without labels. We evaluated CADe on all Japan videos and on those with the highest MACE. $\textbf{Results}$: MACE correctly quantifies that narrow-band imaging (NBI) and chromoendoscopy (CE) frames are less similar to Israel data than Japan whitelight (bootstrapped z-test, |z| > 690, p < $10^{-8}$ for both). Despite differences in the data, CADe performance on Japan colonoscopies was non-inferior to Israel ones without additional training (TPR at 0.5 FAPM: 0.957 and 0.972 for Israel and Japan; TPR at 1.0 FAPM: 0.972 and 0.989 for Israel and Japan; superiority test t > 45.2, p < $10^{-8}$). Despite not being trained on NBI or CE, TPR on those subsets were non-inferior to Japan overall (non-inferiority test t > 47.3, p < $10^{-8}$, $\delta$ = 1.5% for both). $\textbf{Conclusion}$: Differences that prevent CADe detectors from performing well in non-medical settings do not degrade the performance of our AI CADe polyp detector when applied to data from a new country. MACE can help medical AI models internationalize by identifying the most "dissimilar" data on which to evaluate models

Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations

金沢大学医薬保健学総合研究科先進的地域医療研究講座 = Department of Advanced Research in Community MedicineTo clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we assessed the DNA methylation of cancer-associated genes in a cohort of BRAF-mutant precancerous lesions from 94 individuals. We then compared those results with the lesions’ clinicopathological features, especially colorectal subsites. The lesions included hyperplastic polyps (n = 16), traditional serrated adenomas (TSAs) (n = 15), TSAs with sessile serrated adenomas (SSAs) (n = 6), SSAs (n = 49) and SSAs with dysplasia (n = 16). The prevalence of lesions exhibiting the CpG island methylator phenotype (CIMP) was lower in the sigmoid colon and rectum than in other bowel subsites, including the cecum, ascending, transverse and descending colon. In addition, several cancer-associated genes showed higher methylation levels within lesions in the proximal to sigmoid colon than in the sigmoid colon and rectum. These results indicate that the methylation status of lesions with BRAF mutation is strongly associated with their location, histological findings and neoplastic pathways. By contrast, no difference in aberrant DNA methylation was observed in normal-appearing background colonic mucosa along the bowel subsites, which may indicate the absence of an epigenetic field defect

Activated macrophages promote invasion by early colorectal cancer via an IL-1β-SAA1 axis

本研究は，低分化成分に着目して早期大腸がんの分子解析を行った．T1 大腸がんの臨床検体を用いたRNA-seqを行い，低分化成分でのserum amyloid A1（SAA1）の高発現を同定した．大腸がん細胞を用いた機能解析，マクロファージとの共培養実験，臨床検体の免疫染色解析の結果，T1大腸がんの浸潤先進部では，マクロファージとがん細胞がIL-1βとSAA1を介して相互作用することで浸潤を促進すると考えられ，SAA1が早期大腸がんの治療層別化マーカーおよび治療標的となる可能性が示唆された

Insulin-like Growth Factor-1, Insulin-like Growth Factor Binding Protein-3 and the Incidence of Malignant Neoplasms in a Nested Case-Control Study

Insulin-like growth factor (IGF)-1 is a potent mitogen, but IGF binding protein (IGFBP)-3 inhibits IGF1. To elucidate the relationship between both IGF1 and IGFBP and the risk of tumorigenesis, the association between IGF1 and IGFBP3 serum levels and of malignant tumor incidence was investigated in a prospective case-control study nested in the Japan Collaborative Cohort Study. A baseline survey was started in 1988-1990, 110,585 subjects were enrolled, and 35% of participants donated blood samples. Those who had been diagnosed with malignant tumors by 1997 were considered cases. The analysis involved 1,349 cases and 4,012 controls. Conditional logistic regression was used to estimate ORs for cancer incidence associated with IGF-related molecules. After controlling for alcohol intake, body mass index (BMI), and smoking, participants with high total-IGFBP3 and free-IGFBP3, which is estimated by the molar difference of (IGFBP3 - IGF1), had a risk of future neoplasms (P-trend 0.014 and 0.009, respectively), but those with IGF1 did not. People in the second to fifth quintiles had a lower risk than those in the first quintile (ORs 0.676-0.736 and 0.6570.870, respectively). Limiting subjects to those followed for 3 years weakened the negative associations of total- and free-IGFBP3, whereas a positive relationship of free-IGF1, which was estimated by the molar ratio of IGF1/IGFBP3, was seen (P-trend = 0.004, 0.002, and 0.013, respectively). After controlling for alcohol intake, smoking, BMI, and diabetes mellitus, the results were confirmed. These findings suggest that serum IGF1 and IGFBP3 are related to future risk of malignant neoplasms

Insulin-like growth factor-1, IGF binding protein-3, and the risk of esophageal cancer in a nested case-control study

AIM: To assess the relationship between serum levels of insulin-like growth factor-1 (IGF1)/IGF-binding protein-3 (IGFBP3) and the risk of esophageal carcinoma. METHODS: We assessed the relationship between the serum levels of these molecules and the risk of esophageal cancer in a prospective, nested case-control study of participants from the Japan Collaborative Cohort Study. A baseline survey was conducted from 1988 to 1990. Of the 110585 enrolled participants, 35% donated blood samples. Those who had been diagnosed with esophageal cancer were considered cases for nested case-control studies. A conditional logistic model was used to estimate odds ratios for the incidence of esophageal cancer associated with serum IGF1 and IGFBP3 levels. RESULTS: Thirty-one cases and 86 controls were eligible for the present assessment. The molar ratio of IGF1/IGFBP3, which represents the free and active form of IGF1, was not correlated with the risk of esophageal carcinoma. A higher molar difference between IGFBP3 and IGF1, which estimates the free form of IGFBP3, was associated with a decreased risk of esophageal carcinoma (P = 0.0146), and people in the highest tertile had the lowest risk (OR = 0.107, 95% CI: 0.017-0.669). After adjustment for body mass index, tobacco use, and alcohol intake, the molar difference of IGFBP3-IGF1 was inversely correlated with the risk of esophageal carcinoma (P = 0.0150). CONCLUSION: The free form of IGFBP3, which is estimated by this molar difference, may be inversely associated with esophageal cancer incidence