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The therapeutic efficacy of gemcitabine is severely compromised due to its rapid plasma metabolism. Moreover, its hydrophilicity poses a challenge for its efficient entrapment in nanosized delivery systems and to provide a sustained release profile. In this study, gemcitabine was covalently conjugated to poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate) (PEG-PCC) which could self-assemble into micelles of 23.6 nm. These micelles afforded protection to gemcitabine from plasma metabolism as evident by negligible amount of gemcitabine and its metabolite dFdU detected in the plasma after 24 h. A controlled release of gemcitabine from the micelles was observed with 53.89% drug release in 10 days in the presence of protease enzyme Cathepsin B. Gemcitabine conjugated micelles were cytotoxic, showed internalization, and induced cell apoptosis in MIA PaCa-2 and L3.6pl pancreatic cancer cell lines. These micelles efficiently inhibited tumor growth when injected intravenously into MIA PaCa-2 cell derived xenograft tumor bearing NSG mice at a dose of 40 mg/kg in terms of reduced tumor volume and tumor weight (0.38 g vs 0.58 g). TUNEL assay revealed that gemcitabine conjugated micelles induced a much higher extent of apoptosis in the tumor tissues compared to free gemcitabine. In conclusion, gemcitabine conjugated micelles were able to enhance the drug payload, protect it from rapid plasma metabolism, and provide a sustained release and showed enhanced antitumor activity, and thus have the potential to provide a better therapeutic alternative for treating pancreatic cancer.

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selection, perioperative procedures and outcomes reporting. The aim of this study is to present our 10-year, singlecenter experience of minimally-invasive and open MWA for NLM. Methods: A retrospective review of patients who underwent surgical MWA from 2008-2018 at our tertiary institution was performed and only patients treated with surgical MWA for NLM were included. Patient demographics (age, sex, race) and outcomes (treatment modality, tumor characteristics, presence of symptoms/symptom improvement, regional and metastatic recurrence) were entered into a custom REDCapÒ database. Patients were broadly divided as to whether MWA was performed for curative intent [CI] (no evidence of disease after ablation of all detectable liver tumors and no extrahepatic disease at conclusion of planned procedures) or cytoreduction [CR] (intentionally untreated intrahepatic or known extrahepatic disease). Results: Of the 50 patients who underwent surgical MWA for NLM, 78% (39/50) were able to be treated with a minimally-invasive approach. Overall, 68% (34/50) underwent ablation for curative intent, and of these patients 38% (13/34) underwent concurrent hepatectomy. Of the 40% (20/50) of patients experiencing carcinoid symptoms refractory to medical therapy preoperatively, treatment improved symptoms in 92.3% (12/13) of patients treated with curative intent and 100% (7/7) for patients treated for cytoreduction. Postoperative imaging within 12 months of surgical MWA revealed incomplete ablation/local recurrence in 20.6% (7/34) of CI patients. Median follow-up for patients treated with curative intent was 27.3 months (10.4-39.1 IQR) with overall recurrence in 50% (17/34). Median recurrence for curative intent was similar between minimally-invasive (n = 27) and open (n = 7) MWA operations (14.9 versus 12.7 months). Conclusion:Microwave ablation with and without concurrent liver resection for neuroendocrine liver metastases is an effective alternative for select patients. Microwave ablation provides excellent symptom control for patients treated with curative or cytoreductive intent. A minimallyinvasive approach is oncologically comparable to open microwave ablation.