Abstract. to test the safety and immune responses of a novel peptide vaccine derived from RNF43 (ring finger protein 43) and tOmm34 (34-kda translocase of the outer mitochondrial membrane) administered in combination with chemotherapy in patients with metastatic colorectal cancer, a phase I clinical trial with 21 HLA-A2402-positive metastatic colorectal cancer patients was conducted. Patients received a weekly peptide vaccine (1 mg of each peptide in incomplete Freund's adjuvant) in combination with oral UFT (300 mg/m 2 /day) and UZEL (75 mg/day) for 4 weeks, followed by 1 week of rest. The protocol consisted of at least two cycles of this regimen. After the 2nd cycle, vaccinations were given biweekly or monthly, depending on the condition of the patient. Clinical responses were judged 10 weeks after the 2nd cycle by performing computed tomography (CT) scans and assessing the cytotoxic T lymphocyte (CTL) responses against RNF43 and TOMM34 in peripheral lymphocytes. The vaccinations were well tolerated without any serious adverse events. CTL responses were induced against both antigens in 8 patients and against one antigen in 12 patients, while 1 patient had no CTL response. The rate of stable disease was 83%. The group with CTL responses against both antigens had the most long-term survivors, followed by the group showing CTL responses against one antigen (p=0.0079). The patients with no CTL responses had the lowest survival. The safety and immunological responsiveness of the present combination therapy suggests that it is clinically beneficial for metastatic colorectal cancer. Further clinical trials are warranted.
In T1 tumors, central node dissection is not required, but resection with proximal and distal 3-cm margins are required; in T2, central node dissection that includes the intermediate node should be performed in addition to resection with proximal and distal 5-cm margins. In T3 and T4, central node dissection that includes the main node should be performed in addition to resection with proximal and distal 7-cm margins. However, for T2 more than 5 cm from the primary feeding artery, and for T3 more than 7 cm from the primary feeding artery, proximal and distal resection alone may be adequate.
Although the five-year survival rate in patients with inferior mesenteric artery root nodal metastases was lower than in those without metastases, inferior mesenteric artery root nodal dissection should be performed after high ligation of the inferior mesenteric artery for patients with pT3 and pT4 cancers.
J-pouch reconstruction increased reservoir function and provided better functional outcome than straight anastomosis, even five years after surgery, especially in patients whose anastomosis is less than 4 cm from the anal verge.
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