Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The de...Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, “new” RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into question because of the inferior prognosis in the COIN trial and the NORDIC-VII trial. Also, bevacizumab plus oxaliplatin-based chemotherapy was questioned because of the NO16966 trial. By the update and further analysis of the COIN trial and the NORDIC-VII trial, cetuximab plus FOLFOX was reported to be reliable again. But bevacizumab plus oxaliplatin-based chemotherapy was still controversial. In addition, some trials have reported that bevacizumab is not suitable for conversion therapy. The results of the FIRE-III trial showed that cetuximab led to a significant advantage over bevacizumab in response rate (72% vs 63%, P = 0.017) for evaluable population. With the balanced allocation of second-line treatment, the FIRE-III trial was expected to provide evidence for selecting following regimens after first-line progression. There is still no strong evidence for the efficacy of targeted therapy as a preoperative treatment for resectable CLM or postoperative treatment for resected CLM, although the combined regimen is often administered based on experience. Combination therapy with more than one targeted agent has been proven to provide no benefit, and even was reported to be harmful as first-line treatment by four large clinical trials. However, recent studies reported positive results of erlotinib plus bevacizumab for maintenance treatment. The mechanism of antagonism between different targeted agents deserves further study, and may also provide greater understanding of the development of resistance to targeted agents.展开更多
Primary malignant melanoma originating in the colon is an extremely rare disease.Herein,we report a case of primary melanoma of the ascending colon.The patient was a 57-year-old male who was admitted to our hospital f...Primary malignant melanoma originating in the colon is an extremely rare disease.Herein,we report a case of primary melanoma of the ascending colon.The patient was a 57-year-old male who was admitted to our hospital for persistent abdominal pain and episodes of bloody stool,nausea and vomiting.A computed tomography scan revealed lower intestinal intussusception and enlarged lymph nodes in the abdominal cavity and retroperitoneum.During laparoscopic operation,multiple enlarged lymph nodes were found.Several segments of the proximal small intestine were incarcerated into the distal small intestine,forming an internal hernia and obstruction.The necrotic terminal ileum was invaginated into the ascending cecum.Subsequently,adhesive internal hernia reduction and palliative right hemicolectomy were performed.Pathologic examination of the excised specimen revealed a polypoid mass in the ascending colon.Histological examination showed epithelioid and spindle tumor cells with obvious cytoplasmic melanin deposition.Immunohistochemical staining revealed that the tumor cells were positive for S-100,HmB-45 and vimentin,confirming the diagnosis of melanoma.The patient history and a thorough postoperative investigation excluded the preexistence or coexistence of a primary lesion elsewhere in the skin,anus or oculus or at other sites.Thus,we consider our case to represent an aggressive primary colon melanoma presenting as ileocecal intussusception and intestinal obstruction.展开更多
文摘Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, “new” RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into question because of the inferior prognosis in the COIN trial and the NORDIC-VII trial. Also, bevacizumab plus oxaliplatin-based chemotherapy was questioned because of the NO16966 trial. By the update and further analysis of the COIN trial and the NORDIC-VII trial, cetuximab plus FOLFOX was reported to be reliable again. But bevacizumab plus oxaliplatin-based chemotherapy was still controversial. In addition, some trials have reported that bevacizumab is not suitable for conversion therapy. The results of the FIRE-III trial showed that cetuximab led to a significant advantage over bevacizumab in response rate (72% vs 63%, P = 0.017) for evaluable population. With the balanced allocation of second-line treatment, the FIRE-III trial was expected to provide evidence for selecting following regimens after first-line progression. There is still no strong evidence for the efficacy of targeted therapy as a preoperative treatment for resectable CLM or postoperative treatment for resected CLM, although the combined regimen is often administered based on experience. Combination therapy with more than one targeted agent has been proven to provide no benefit, and even was reported to be harmful as first-line treatment by four large clinical trials. However, recent studies reported positive results of erlotinib plus bevacizumab for maintenance treatment. The mechanism of antagonism between different targeted agents deserves further study, and may also provide greater understanding of the development of resistance to targeted agents.
文摘Primary malignant melanoma originating in the colon is an extremely rare disease.Herein,we report a case of primary melanoma of the ascending colon.The patient was a 57-year-old male who was admitted to our hospital for persistent abdominal pain and episodes of bloody stool,nausea and vomiting.A computed tomography scan revealed lower intestinal intussusception and enlarged lymph nodes in the abdominal cavity and retroperitoneum.During laparoscopic operation,multiple enlarged lymph nodes were found.Several segments of the proximal small intestine were incarcerated into the distal small intestine,forming an internal hernia and obstruction.The necrotic terminal ileum was invaginated into the ascending cecum.Subsequently,adhesive internal hernia reduction and palliative right hemicolectomy were performed.Pathologic examination of the excised specimen revealed a polypoid mass in the ascending colon.Histological examination showed epithelioid and spindle tumor cells with obvious cytoplasmic melanin deposition.Immunohistochemical staining revealed that the tumor cells were positive for S-100,HmB-45 and vimentin,confirming the diagnosis of melanoma.The patient history and a thorough postoperative investigation excluded the preexistence or coexistence of a primary lesion elsewhere in the skin,anus or oculus or at other sites.Thus,we consider our case to represent an aggressive primary colon melanoma presenting as ileocecal intussusception and intestinal obstruction.
