ABSTRACT
We have recently witnessed substantial progress with immunotherapy for selected diseases. Checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cells are among the most promising agents. Whereas much of the early success with CAR-T cells has been demonstrated with hematological malignancies, important barriers remain for the application of CAR-T cell therapies for the management of metastatic solid tumors. The challenges are particularly apparent when considering primary and metastatic tumors in the liver. At baseline, the intrahepatic space is immunosuppressive and this feature is exploited by malignant cells. Fortunately, our evolving understanding of liver immune cell biology is allowing the development of novel immunotherapeutic strategies for the treatment of liver tumors. Furthermore, the unique anatomic features of the liver make possible highly selective immunotherapeutic delivery approaches that may maximize antitumor efficacy while limiting off-target damage to healthy tissues. This review summarizes the immunobiology of the intrahepatic space and how this knowledge enables identification of hurdles and potential solutions to the barriers facing immunotherapy for liver tumors.
Subject(s)
Immune Tolerance , Immunotherapy , Liver Neoplasms/immunology , Liver Neoplasms/therapy , Animals , Dendritic Cells/immunology , Dendritic Cells/metabolism , Endothelial Cells/immunology , Endothelial Cells/metabolism , Hepatic Stellate Cells/immunology , Hepatic Stellate Cells/metabolism , Humans , Immunomodulation/drug effects , Immunomodulation/genetics , Immunomodulation/immunology , Kupffer Cells/immunology , Kupffer Cells/metabolism , Liver/immunology , Liver/metabolism , Liver/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Lymphocyte Subsets/pathology , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Molecular Targeted Therapy , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/metabolism , Signal Transduction/drug effectsABSTRACT
BACKGROUND: The current study sought to determine predictive risk factors and inpatient resource utilization associated with discharge to skilled nursing facility (SNF) in hospitalized elderly patients with colon cancer. MATERIALS AND METHODS: Inpatient data from U.S. community hospital discharges from 2003 to 2011 was analyzed in a retrospective cohort study using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS). Subjects included hospitalized postoperative colon cancer patients over age of 65 (N = 98,797). RESULTS: The proportion of elderly colon cancer patients discharged to a SNF increased by 16.67% from 2003 to 2011 (18-21%). Elderly patients discharged to a SNF had increased hospitalization costs (+$10,293.70, p < 0.01) compared to elderly colon cancer patients discharged home. Hospitalization predictive risk factors associated with SNF placement include age above 75 (OR, 4.07; 95% CI, 3.90, 4.25; p < 0.01), paralysis (OR, 3.60; 95% CI, 3.06-4.23; p < 0.01), length of stay (LOS) 10 days or more (OR, 3.00; 95% CI, 2.88-3.13; p < 0.01), psychoses (OR, 2.91; 95% CI, 2.56-3.32; p < 0.01), and neurological disorders (OR, 2.34; 95% CI, 2.17-2.52; p < 0.01). CONCLUSIONS: Despite increased costs and worse clinical outcomes associated with SNF placement, over 40% increase of hospital discharge to SNF should be anticipated from this population over the next 20 years. Neurologic and psychiatric comorbidities have significantly negative clinical impacts and increase the likelihood of colon cancer patients' discharge to a SNF.
Subject(s)
Colonic Neoplasms/surgery , Skilled Nursing Facilities , Aged , Aged, 80 and over , Female , Hospitalization/economics , Humans , Length of Stay , Male , Retrospective Studies , Risk FactorsABSTRACT
The results of the colorectal carcinoma screening project in the region of Frýdek-Místek for the period of 1999 - 2001 are presented here. Of the 225 patiens diagnosed with carcinoma, 9 of the cases (4 %) were detected using the fecal occult bleeding test. Of 1000 people tested, a factor of 2.9 patients with carcinoma and 12.5 patients with adenomatous polyps were diagnosed, with 7.3 % test positivity. A statistically significant shift has been noted to detection in earlier stages of the disease (p = 0.05). From 49 - 53 % of the patients operated on in the period of 1999 - 2001 had their tumors in the stage A or B according to Dukes, a 13 - 17 % increase over the year of 1998. This shift was due above all to educating the local population.
