Artificial Intelligence Program to Predict p53 Mutations in Ulcerative Colitis-Associated Cancer or Dysplasia.

BACKGROUND: The diagnosis of colitis-associated cancer or dysplasia is important in the treatment of ulcerative colitis. Immunohistochemistry of p53 along with hematoxylin and eosin (H&E) staining is conventionally used to accurately diagnose the pathological conditions. However, evaluation of p53 immunohistochemistry in all biopsied specimens is expensive and time-consuming for pathologists. In this study, we aimed to develop an artificial intelligence program using a deep learning algorithm to investigate and predict p53 immunohistochemical staining from H&E-stained slides. METHODS: We cropped 25 849 patches from whole-slide images of H&E-stained slides with the corresponding p53-stained slides. These slides were prepared from samples of 12 patients with colitis-associated neoplasia who underwent total colectomy. We annotated all glands in the whole-slide images of the H&E-stained slides and grouped them into 3 classes: p53 positive, p53 negative, and p53 null. We used 80% of the patches for training a convolutional neural network (CNN), 10% for validation, and 10% for final testing. RESULTS: The trained CNN glands were classified into 2 or 3 classes according to p53 positivity, with a mean average precision of 0.731 to 0.754. The accuracy, sensitivity (recall), specificity, positive predictive value (precision), and F-measure of the prediction of p53 immunohistochemical staining of the glands detected by the trained CNN were 0.86 to 0.91, 0.73 to 0.83, 0.91 to 0.92, 0.82 to 0.89, and 0.77 to 0.86, respectively. CONCLUSIONS: Our trained CNN can be used as a reasonable alternative to conventional p53 immunohistochemical staining in the pathological diagnosis of colitis-associated neoplasia, which is accurate, saves time, and is cost-effective.

We developed a diagnostic tool for determining the pathology of ulcerative colitis­associated neoplasia using artificial intelligence, which precisely predicted p53 immunohistochemical positivity of intestinal glands in the colon from the hematoxylin and eosin­stained slides.

Clinical significance of CD8+ and FoxP3+ tumor-infiltrating lymphocytes and MFG-E8 expression in lower rectal cancer with preoperative chemoradiotherapy.

Preoperative chemoradiotherapy (CRT) for rectal cancer contributes to tumor down-staging and decreases locoregional recurrence. However, each patient shows a significantly different response to CRT. Therefore, the identification of predictive factors to CRT response would be beneficial to avoid unnecessary treatment. Cancer immunity in patients has been suggested to play an important role in the eradication of the tumor by CRT. In the present study, the utility of CD8+ and forkhead box P3 (FoxP3)+ tumor-infiltrating lymphocytes (TILs) and the expression of a novel immuno-regulatory factor, lactadherin (MFG-E8), in predicting CRT effectiveness in patients with rectal cancer was examined. A total of 61 patients with rectal cancer, who underwent curative resection following CRT were included in the study. The numbers of CD8+ and FoxP3+ TILs in a biopsy taken before CRT and MFG-E8 expression level in the specimens obtained at the time of the surgery after CRT were examined using immunohistochemical staining, and their association with clinicopathological characteristics, including patient survival, was determined. The tumors with more CD8+ TILs in the biopsy samples before CRT showed a significantly more favorable CRT response. The patients with tumors and a higher number of CD8+ TILs before CRT also exhibited significantly longer disease-free and overall survival times. Higher MFG-E8 expression level in post-CRT specimens was significantly associated with favorable CRT response; however, no significant association was found with any other clinicopathological characteristics, including survival time. The number of CD8+ TILs before CRT was a valuable predictor for CRT response and was associated with favorable prognosis in patients with lower rectal cancer and who were treated with CRT. High MFG-E8 expression level after CRT was also associated with a favorable CRT response.

Occurrence of IgG4-related hypophysitis lacking IgG4-bearing plasma cell infiltration during steroid therapy.

Eight years after an episode of multiple IgG4-related disease, a pituitary mass with panhypopituitarism and a visual disturbance developed in a 70-year-old man under low-dose steroid therapy. A pituitary biopsy revealed findings of lymphocytic hypophysitis with the absence of IgG4-positive plasma cell infiltration. The serum IgG4 level was unremarkable. Although performing a pituitary biopsy and measuring the serum IgG4 level is crucial for making a diagnosis of IgG4-related hypophysitis, it is occasionally difficult to diagnose the disease in patients treated with steroid therapy, as observed in the present case. Based on a review of the diagnosis, conducting a careful assessment is required, especially in men and elderly patients thought to have solitary hypophysitis.