Feasibility of restorative proctocolectomy in patients with ulcerative colitis-associated lower rectal cancer: A retrospective study.

BACKGROUND/OBJECTIVE: Restorative proctocolectomy (RP) may improve quality of life in patients with ulcerative colitis (UC)-associated lower rectal cancer to a greater extent than total proctocolectomy. However, patients with UC-associated cancer often have flat mucosal lesions that make it extremely difficult to endoscopically delineate the tumor margins. Therefore, there is a potential risk of residual tumor and local recurrence after RP in patients with UC-associated lower rectal cancer. The aim of this study was to assess the feasibility of RP in patients with UC-associated cancer of the lower rectum. METHODS: We retrospectively identified nine patients who had undergone RP for UC-associated lower rectal cancer at the Niigata University Medical and Dental Hospital between January 2000 and December 2016. The incidence of flat mucosal cancer, distal margin status, and oncologic outcomes were evaluated in the nine patients. RESULTS: Eight (89%) of the nine patients had flat mucosal cancer in the lower rectum. The median length of the distal margin was 22 mm (range 0-55 mm). No patient developed local or distant recurrence during follow-up. One patient had a positive distal margin. This patient underwent annual pouchoscopy, but had no local recurrence and died of pancreatic cancer 81 months after RP. The remaining eight patients were alive at the final observation. Five-year and 10-year overall survival rates in the nine patients were 100% and 66.7%, respectively. CONCLUSION: Patients with UC-associated lower rectal cancer often have lesions of the flat mucosal type. However, RP is feasible and not necessarily contraindicated in such patients.

Development of PEGylated aspartic acid-modified liposome as a bone-targeting carrier for the delivery of paclitaxel and treatment of bone metastasis.

To prevent bone metastasis, we developed polyethylene glycol (PEG)-conjugated aspartic acid (Asp)-modified liposomes (PEG-Asp-Lipo) as a bone-targeting carrier of paclitaxel (PTX) by using Asp-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-Asp). The affinity of Asp-modified liposomes to hydroxyapatite increased as the concentration of DPPE-Asp increased. The bone accumulation of [3H]-labeled PEG(2)-Asp(33)-Lipo was approximately 24.6% 360 min after intravenous injection in mice, in contrast to 5.4% and 6.7% of [3H]-labeled normal Lipo and PEG(2)-Lipo, respectively. Similarly, [14C]-labeled PTX encapsulated into PEG(2)-Asp(33)-Lipo predominantly accumulated in the bone. Furthermore, using an in situ imaging experiment, we observed that near-infrared fluorescence-labeled PEG(2)-Asp(33)-Lipo selectively accumulated in the bone near the joint after intravenous injection in mice. We also found that FITC-labeled PEG(2)-Asp(33)-Lipo predominantly accumulated on eroded and quiescent bone surfaces. In a bone metastatic tumor mouse model, in which B16-BL6/Luc cells were injected into the left ventricle of female C57BL/6 mice, metastatic bone tumor growth was significantly inhibited by an intravenous injection of PEG(2)-Asp(33)-liposomal PTX. In contrast, PEGylated liposomal PTX hardly affected the growth of metastatic bone tumors. These findings indicate that PEG(2)-Asp(33)-Lipo is a promising bone-targeting carrier for the delivery of PTX and treatment of bone metastasis.