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The present study was designed to elucidate the effectiveness of portal decompression and FK506 (FK) pretreatment in extended hepatectomy in dogs. In the first set of experiment the effect of portal decompression was evaluated in two groups of dogs which underwent extended hepatectomies (80%) with or without (control) a side-to-side portacaval shunt. The presence of the shunt significantly (p < 0.05) improved the 7-day survival of the animals (57.1%) when compared with those of the control group (28.6%) and eventually the portal pressure was significantly lower and mean arterial pressure was significantly higher in the shunt group (p < 0.05). Moreover, the animals with lower portal pressure (≤220 mm of saline) had a significantly improved 7-day survival rate than those with higher portal pressure (p < 0.001). To evaluate the role of FK pretreatment in extended hepatectomy, a more severe model of 90% hepatectomy was used in four different groups: portacaval shunt, shunt and FK pretreatment, FK pretreatment, and hepatectomy only (control). Although the shunt improved the survival rate in the 80% hepatectomy model, neither shunt (8.3%) nor FK pretreatment (0%) independently improved the survival of the animals when the hepatectomy was extended to 90%. FK pretreatment significantly improved the survival (33.3%, p < 0.05) and hepatic functions of the animals only in the presence of a shunt. Also hepatic microcirculation measured with a laser Doppler flowmeter was significantly better in the remnant liver of all treated groups than in the control group (p < 0.01). In conclusion, extended hepatectomy (90%) could be performed in otherwise normal liver after FK pretreatment and a side-to-side portacaval shunt, which improve the regenerative response in a stable hemodynamic animal.

Osteosarcoma (OS) is one of the most common primary malignant tumors originating in bones. Its high malignancy typically manifests in lung metastasis leading to high mortality. Although remarkable advances in surgical resection and neoadjuvant chemotherapy have lengthened life expectancy and greatly improved the survival rate among OS patients, no further breakthroughs have been achieved. It is challenging to treat patients with chemoresistant tumors and distant metastases. Recent studies have identified a compelling set of links between hypoxia and chemotherapy failure. Here, we review the evidence supporting the positive effects of hypoxia in the tumor microenvironment (TME). In addition, certain anticancer effects of immune checkpoint inhibitors have been demonstrated in OS preclinical models. Continued long-term observation in clinical trials is required. In the present review, we discuss the mutualistic effects of the TME in OS treatment and summarize the mechanisms of immunotherapy and their interaction with TME when used to treat OS. We also suggest that immunotherapy, a new comprehensive and potential antitumor approach that stimulates an immune response to eliminate tumor cells, may represent an innovative approach for the development of a novel treatment regimen for OS patients.