BackgroundPerianal/perineal rhabdomyosarcoma (PRMS) is rare, easy to be misdiagnosed and has poor prognosis. This study was designed to analyze the clinical, diagnostic, pathological and prognostic features of PRMS, and to explore its therapeutic modality.MethodsClinical data of PRMS patients in the Sixth Affiliated Hospital and the Cancer Center of Sun Yat-sen University and related Chinese literatures published between 1987 and 2018 were described and analyzed. Chi-square test was used to test the differences between groups. The Kaplan-Meier methods were used to estimate and compare survival rates.Results35 patients, 20 identified in the Chinese literatures and 15 of our center from 1997 to 2019, were included in this study. 34 cases presented as perianal mass and one presented as inguinal mass. 20 patients complained about pain and 16 cases were misdiagnosed as perianal abscess, in which pain was found related to misdiagnosis (p＜0.05). The average time from symptoms to pathological diagnosis was 3.1 months. 13 cases were categorized into IRS group III/IV and 20 cases into stages 3/4. 14 Cases were diagnosed as embryonal rhabdomyosarcoma pathologically and 9 as alveolar rhabdomyosarcoma. Five patients survived for more than two years, three of them survived for more than five years. The overall survival rates of two years and five years were 32% and 24% respectively, in which misdiagnosis contributes to poor prognosis (p＜0.05). MRI showed that PRMS was closely related to external anal sphincter in 10 cases. ConclusionPRMS is easy to be misdiagnosed, which could lead to worse outcome. Patients with painful perianal mass should be evaluated to exclude PRMS. MRI shows PRMS is closely related to external anal sphincter. Comprehensive therapy including radical operation and chemotherapy is recommended.

Purpose: Perianal/perineal rhabdomyosarcoma (PRMS) is rare, easy to be misdiagnosed and has poor prognosis. This study was designed to analyze the clinical, diagnostic, pathological and prognostic features of PRMS, and to explore its therapeutic modality.Methods: Clinical data of PRMS patients in the Sixth Affiliated Hospital and the Cancer Center of Sun Yat-sen University and related Chinese literatures published between 1987 and 2018 were described and analyzed. Chi-square test was used to test the differences between groups. The Kaplan-Meier methods were used to estimate and compare survival rates.Results: 35 patients, 20 identified in the Chinese literatures and 15 of our center from 1997 to 2019, were included in this study. 34 cases presented as perianal mass and one presented as inguinal mass. 20 patients complained about pain and 16 cases were misdiagnosed as perianal abscess, in which pain was found related to misdiagnosis (p＜0.05). The average time from symptoms to pathological diagnosis was 3.1 months. 13 cases were categorized into IRS group III/IV and 20 cases into stages 3/4. 14 Cases were diagnosed as embryonal rhabdomyosarcoma pathologically and 9 as alveolar rhabdomyosarcoma. Five patients survived for more than two years, three of them survived for more than five years. The overall survival rates of two years and five years were 32% and 24% respectively, in which misdiagnosis contributes to poor prognosis (p＜0.05). MRI showed that PRMS was closely related to external anal sphincter in 10 cases. Conclusion: PRMS is easy to be misdiagnosed, which could lead to worse outcome. Patients with painful perianal mass should be evaluated to exclude PRMS. MRI shows PRMS is closely related to external anal sphincter. Comprehensive therapy including radical operation and chemotherapy is recommended.

Colorectal cancer (CRC) with KRAS mutation is prone to develop metachronous metastasis. However, effective measures for prediction and prevention of such clinical issue are currently unavailable. In this study, we confirmed that KRAS mutation is a risk factor for CRC metachronous metastasis through meta-analysis and public database analysis. Based on the ICGC-AGRO database, we have constructed a risk scoring model for predicting metachronous metastasis in KRAS-mutant CRC using machine learning, which was validated in public datasets. Furthermore, we discovered that KRAS inhibitors can effectively suppress the migration and invasion capabilities of high risk CRC cells by wound healing assay and transwell experiment, which was validated ex vivo and in vivo using organoids and splenic liver metastatic mouse model. Finally, RNA sequencing, RT-qPCR, and western blots have proven that KRAS inhibitors can suppress the epithelial-mesenchymal transition (EMT) and transforming growth factor beta (TGF-beta) signaling pathway in CRC. Collectively, our study suggests that KRAS inhibitors may inhibit the metastatic ability of CRC by suppressing EMT and the TGF-beta pathway, suggesting their potential for the prevention of metachronous metastasis in CRC with KRAS mutation.