Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l -glutamic acid and l -lysine within an amphiphilic polymer of poly( l -glutamic acid-co- l -lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate in the periphery and core of tumors without any signs of serum biochemical or hematological alterations, normal organ histopathological abnormalities, or overt deterioration in animal health. Furthermore, P(Glu-co-Lys)-GNRs penetrated the tumor microenvironment to accumulate in the hypoxic cores of tumors to potently radiosensitize heterotopic and orthotopic pancreatic cancers in vivo.

Localized hepatocellular carcinoma (HCC) that is unresectable and non-transplantable can be treated by several liver-directed therapies. External beam radiation therapy (EBRT) is an increasingly accepted and widely utilized treatment modality in this setting. Accelerated charged particles such as proton beam therapy (PBT) and carbon ion radiation therapy (CIRT) offer technological advancements over conventional photon radiotherapy. In this review, we summarize the distinct advantages of CIRT use for HCC treatment, focusing on physical and biological attributes, and outline dosimetric and treatment planning caveats. Based on these considerations, we posit that HCC may be among the best indications for use of CIRT, as it allows for maximizing tumoricidal doses to the target volume while minimizing the dose to the organs at risk.

Background: Extended pancreatectomy (EP) is the only potential cure for patients with borderline resectable and locally advanced pancreatic cancer.Methods: In the period 2011-2018, 618 resections were performed in patients with pancreatic adenocarcinoma. Standard resections were performed in 476 (77%) patients. EP was performed in 142 (23%) patients. Extended pancreaticoduodenectomy was performed in 79 (55.6%), extended distal resections in 52 (36.6%), extended total pancreatectomy in 11 (7.8%). EP with arterial resections was performed in 14 (2.3%) patients, with venous resections in 91 (14.7%) patients.Results: One or more postoperative complications occurred in 182 patients (38.2%) in the standard resection group and in 63 (44.3%) in the EP group. Mortality was 13.2% (15 patients): 6 (4.2%) patients died after EP and 9 (1.9%) after standard pancreatectomy. Median survival and 5-year overall survival rates were reduced in patients having EP compared with those undergoing a standard resection (15 months, 18% and 25 months, 33%, respectively; c 2 ¼ 2.83, P¼ 0.09, c 2 ¼ 0.16, P¼0.69).Conclusions: These results suggest that morbidity and mortality after EP are comparable with standard pancreatectomy. However, long term results of EP are worse compared with standard pancreatectomy. Extended resections are possible and can increase the number of radically operated patients.

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