Out-of-distribution (OOD) generalization is a critical challenge in deep learning. It is specifically important when the test samples are drawn from a different distribution than the training data. We develop a novel real-time deep learning based architecture, TransRUPNet that is based on a Transformer and residual upsampling network for colorectal polyp segmentation to improve OOD generalization. The proposed architecture, TransRUPNet, is an encoder-decoder network that consists of three encoder blocks, three decoder blocks, and some additional upsampling blocks at the end of the network. With the image size of $256\times256$, the proposed method achieves an excellent real-time operation speed of \textbf{47.07} frames per second with an average mean dice coefficient score of 0.7786 and mean Intersection over Union of 0.7210 on the out-of-distribution polyp datasets. The results on the publicly available PolypGen dataset (OOD dataset in our case) suggest that TransRUPNet can give real-time feedback while retaining high accuracy for in-distribution dataset. Furthermore, we demonstrate the generalizability of the proposed method by showing that it significantly improves performance on OOD datasets compared to the existing methods.

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