Patients with anorectal malignant melanoma (AMM) generally have an unfavorable prognosis, and surgical managements are still in controversy. The purpose of this study was to evaluate the surgical treatment for AMM in China and to compare the survival of abdominoperineal resection (APR) and local excision (LE) in patients with AMM. Between 1995 and 2007, 54 patients managed with curative surgical resection for AMM were reviewed, 39 patients underwent APR, and 15 patients underwent LE. Life table was carried out and Kaplan-Meier test was used to compare the effects of these two different surgical procedures in survival. The overall 1-year, 2-year, 3-year, and 5-year survival rates after curative operation were 80, 54, 43, and 26%, respectively; LE group were 67, 48, 48, and 16%, and APR group were 84, 57, 42, and 30%, respectively. The median survival for all LE and APR were 25 months, 13 months, and 25 months, respectively. Kaplan-Meier test showed that there was no significant difference between APR and LE in survival (P=0.281); however, a 5-year survival advantage for the patients who underwent APR was found, despite the severity of tumor. Local recurrence after LE was more popular than APR (P=0.020). The prognosis of AMM after curative surgery is poor now, and patients undergoing APR have no significant survival advantage than those underwent LE. Local recurrence after LE was more popular than APR.

Oxaliplatin, a third generation platinum compound, is a component of the FOLFOX regimen (oxaliplatin + 5-fluorouracil + leucovorin), which has been considered a standard adjuvant treatment for colorectal cancer (CRC).¹ x 1 de Gramont, A., Figer, A., Seymour, M. et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000; 18: 2938–2947 Crossref | PubMed | Scopus (3075) | Google Scholar See all References Recently a phase III European trial, MOSAIC (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer), has confirmed that FOLFOX regimen improves the adjuvant treatment of colon cancer.² x 2 Andre, T., Boni, C., Mounedji-Boudiaf, L. et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004; 350: 2343–2351 Crossref | PubMed | Scopus (2273) | Google Scholar See all References Unfortunately, this platinum-containing regimen frequently induces peripheral sensory neurotoxicity, which often prevents patients from receiving oxaliplatin chemotherapy. Neurotoxicity associated with oxaliplatin often produces two clinically distinct syndromes: a transient, acute syndrome that appears during, or shortly after, administration of oxaliplatin and usually disappears within 7 days and a dose-limiting, cumulative sensory neuropathy.³ x 3 Lehky, T.J., Leonard, G.D., Wilson, R.H., Grem, J.L., and Floeter, M.K. Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy. Muscle Nerve. 2004; 29: 387–392 Crossref | PubMed | Scopus (190) | Google Scholar See all References

Background: Lysine methyltransferase 2 (KMT2) family proteins methylate lysine 4 on histone H3 (H3K4) to promote genome accessibility and transcription. Dysregulation or mutation of KMT2 family have been observed frequently in various types of human cancers. Colorectal cancer is the third most common cancer worldwide. However, few studies have evaluated the role of KMT2 family mutations in colorectal cancer. The present study aimed to explore the impact of KMT2 family mutations on clinicopathological, molecular characteristics and prognosis in colorectal cancer. Methods: A total of 316 colorectal cancer patients were enrolled; tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of clinical pathological features and molecular characteristics in patients were then analyzed. The cBioPortal dataset was used for investigating the KMT2 family mutations data and their correlation with clinical outcomes. Results: The overall mutation frequencies of KMT2A-D were 9.5%, 0.5%, 13%, and 13%, respectively, which were more often present at right-sided primary and earlier stage tumors. KMT2A-D mutations are associated with enhanced genomic instability, including a higher level of microsatellite instability (MSI-H) and tumor mutational burden (TMB-H). In addition, our results highlight the co-occurring gene mutations within the Wnt signaling, ERBB2/4, TGF-β superfamily pathway, and PI-3-kinase pathway in KMT2-mutant colorectal cancer. KMT2 family mutations were predictive biomarker for better overall survival in metastatic colorectal cancer. Conclusions: Collectively, we identified that KMT2 family mutations were correlated with higher-TMB and higher-MSI, thus resulting in a better outcome for colorectal cancer patients.