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Two different ways have been developed to perform endoscopic surgery. The standard way is multiport laparoscopic surgery. When entering through a natural orifice, we use single-port surgery for transanal work (transanal endoscopic microsurgery). In clinical routine, we moved from intralumenal surgery toward surgery in the perirectal area and finally the free abdomen. In the context of natural orifice translumenal endoscopic surgery, we have modified the length and diameter of optics and tube and developed new mechanisms for steering long curved instruments. This technology is then used for transvaginal cholecystectomy and transanal rectosigmoid resection. Global clinical application of transanal endoscopic microsurgery has proven superiority in preciseness and clinical results for adenomas and early cancer. The initial clinical study for transvaginal cholecystectomy is successfully performed in 6 female patients with an average operation time of 80 minutes and without major complication. Feasibility of transanal rectosigmoid resection is demonstrated in an ex vivo experimental model.