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Surgical resection is considered a crucial treatment in patients with primary colonic lymphoma, but combining surgery with chemotherapy has provided additional therapeutic benefits in some studies. To further explore the optimal therapeutic approach in different clinical scenarios, we reviewed cases with localized large-cell lymphoma and analyzed the factors related to the outcomes. The 74 cases diagnosed between February 1979 and October 2010 were retrospectively reviewed for clinical features, laboratory findings, and pathological diagnosis. The outcomes were correlated with their demographics and different treatment modalities. Of the 74 cases, only the patients who had complete tumor resection had significantly improved progression-free survival (PFS). The patients treated with resection and chemotherapy had better overall survival (OS) and PFS than those treated with resection alone. The OS and PFS of the patients who were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy without surgery were similar to those of patients treated with CHOP and resection, but the patients treated with resection followed by cyclophosphamide, vincristine, and prednisone (COP) chemotherapy had significantly better OS and PFS than the patients treated with COP chemotherapy alone. For patients with diffuse large B-cell lymphoma (DLBCL), rituximab-based chemotherapy with or without resection had similar OS and PFS. We conclude that chemotherapy alone provides similar therapeutic effect compared with surgery and chemotherapy and that surgical resection can be spared if an endoscopic diagnosis could be made. [ABSTRACT FROM AUTHOR]