We hypothesized that general surgeons are more likely to use a robotic surgical platform at hospitals where more urologic and gynecologic robotic operations are performed, suggesting that ...hospital-related factors are important for choice of usage of minimally invasive platforms.
We queried the National Inpatient Sample from 2010 to 2014 for patients who underwent stomach, gallbladder, pancreas, spleen, colon and rectum, or hernia (general surgery), prostate or kidney (urologic surgery), and ovarian or uterine surgery (gynecologic surgery). Hospitals were grouped into quartiles according to percent volume of robotic urologic or gynecologic operations. Multivariable logistic regression modeling determined independent variables associated with robotics.
Survey-weighted results represented 482,227 open, 240,360 laparoscopic, and 42,177 robotic general surgical operations at 3,933 hospitals. Robotics use increased with each year studied and was more likely to be performed on younger men with private insurance. The odds of a general surgery patient receiving a robotic operation increased with urologic and gynecologic use at the hospital. Patients at top quartile hospitals for robotic urologic surgery had 1.34 times greater odds of receiving robotic general surgery operations (confidence interval 1.15–1.57, P < .001) and 1.53 times greater odds (confidence interval 1.32–1.79, P < .001) at top quartile robotic gynecologic hospitals. These findings were independent of study year, surgical site, insurance type, and hospital type and persisted when only comparing laparoscopic to robotic procedures.
Use of robotics in general surgery is independently associated with use in urologic and gynecologic surgery at a hospital, suggesting that institutional factors are important drivers of use when considering laparoscopy versus robotics in general surgery.
A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer ...(GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2
,
;
;
;
;
;
;
;
;
;
) and M1 (M1
,
;
;
;
;
;
;
) macrophages, and cytolytic T-lymphocytes (CTL
,
;
;
;
;
). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2
expression was associated with histological types and later stages. Low M2
expression was associated with significantly better 5-year OS and DFI. We validated M2
in prospectively collected peritoneal fluid of a GC patient cohort (
= 28). Single-cell RNA sequencing was used for signature expression in
cells and the log-rank test compared OS. GC patients with high M2
in
cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2
was significantly and independently associated with survival. As an independent predictor of poor survival, M2
may be prognostic in primary tumors and peritoneal fluid of GC patients.
The translation of laboratory science into effective clinical cancer therapy is gaining momentum more rapidly than any other time in history. Understanding cancer cell-surface receptors, cancer cell ...growth, and cancer metabolic pathways has led to many promising molecular-targeted therapies and cancer gene therapies. These same targets may also be exploited for optical imaging of cancer. Theoretically, any antibody or small molecule targeting cancer can be labeled with bioluminescent or fluorescent agents. In the laboratory setting, fluorescence imaging (FI) and bioluminescence imaging (BLI) have long been used in preclinical research for quantification of tumor bulk, assessment of targeting of tumors by experimental agents, and discrimination between primary and secondary effects of cancer treatments. Many of these laboratory techniques are now moving to clinical trials. Imageable engineered fluorescent probes that are highly specific for cancer are being advanced. This will allow for the identification of tumors for staging, tracking novel therapeutic agents, assisting in adequate surgical resection, and allowing image-guided biopsies. The critical components of FI include (1) a fluorescent protein that is biologically safe, stable, and distinctly visible with a high target to background ratio and (2) highly sensitive optical detectors. This review will summarize the most promising optical imaging agents and detection devices for cancer clinical research and clinical care.
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Imageable engineered fluorescent probes are being deployed for clinical visualization of cancer. These will allow identification of tumors for staging, tracking novel therapeutic agents including viruses and immune cells. This review summarizes use of these promising optical imaging agents and detection devices for cancer trials and clinical care.
There exists no coherent national strategy for the early detection or prevention of gastric cancer in the United States (US), even among identified high-risk groups such as Asian Americans, African ...Americans, Hispanic Americans, and Alaska Native/American Indian peoples. As a result, patients with gastric cancer in the US are diagnosed at later stages and demonstrate worse overall survival compared to nations of East Asia with established screening programs (
Table 1
). The under-recognition of gastric cancer risk within minority communities is a significant unaddressed healthcare disparity.
To address this disparity, the Division of Gastroenterology and Hepatology and the Center for Asian Health Research and Education at Stanford University hosted the inaugural Gastric Cancer Summit on March 5–6, 2020. This Summit brought together academic physicians, researchers, policy leaders, and patient advocates to identify strategies to combat gastric cancer in high-risk US populations through prevention and early detection. The first day of the Summit consisted of health policy- and advocacy-oriented presentations, and the second day consisted of scientific presentations on advances in early detection and prevention.
Triple-negative breast cancer is the most aggressive subtype of breast cancer and is difficult to treat. Breast cancer is considered to be poorly immunogenic and hence is less responsive to ...immunotherapies. We tested whether the oncolytic poxvirus CF33-hNIS-ΔF14.5 could modulate tumor immune microenvironment and make the tumors responsive to the immune checkpoint inhibitor anti-PD-L1. We found that virus infection causes the upregulation of PD-L1 levels on triple-negative breast cancer cells in vitro as well as in vivo in mice. In a mouse model of orthotopic triple-negative breast cancer, the virus was found to increase tumor infiltration by CD8+ T cells. Likewise, in mice treated with CF33-hNIS-ΔF14.5 high levels of proinflammatory cytokines IFNγ and IL-6 were found in the tumors but not in the serum. The levels of immune modulation were even higher in mice that were treated with a combination of the virus and anti-PD-L1 antibody. While CF33-hNIS-ΔF14.5 and anti-PD-L1 antibody failed to exert significant anti-tumor effect as a single agent, a combination of the two agents resulted in significant anti-tumor effect with 50% mice experiencing complete tumor regression when both agents were injected intra-tumorally. Furthermore, the 'cured' mice did not develop tumor after re-challenge with the same cancer cells suggesting that they developed immunity against those cancer cells. Taken together, our study shows that CF33-hNIS-ΔF14.5 favorably modulates tumor immune microenvironment in triple-negative breast cancer model making them responsive to the immune checkpoint inhibitor anti-PD-L1, and hence warrants further studies to determine the clinical applicability of this combination therapy.
Background
The rise in the incidence of gastric cancer (GC) and colorectal cancer (CRC) in young adults (YA) remains unexplained. We aim to identify differences in these malignancies between YA and ...older patients.
Patients and Methods
We retrospectively analyzed the California Cancer Registry for all GC and CRC cases from 2000 to 2012. Pearson’s Chi square analysis and stepwise regression model with backward elimination were used to analyze differences in demographic, clinical, and histopathologic features, and log-rank test to compare survival between young (≤ 40 years) and older adults (41–90 years) with GC or CRC, separately.
Results
We analyzed 19,368 cases of GC and 117,415 cases of CRC. YA accounted for 4.6% of GC (
n
= 883) and 2.8% of CRC (
n
= 3273) patients. Compared with older patients, YA were more likely to be Hispanic (
P
< 0.0001) and have poorly differentiated (
P
< 0.0001), higher histologic grade (
P
< 0.0001), and signet ring features (
P
< 0.0001). Synchronous peritoneal metastases were more common in YA patients (32.1% vs. 14.1% GC, 8.8% vs. 5.4% CRC,
P
< 0.0001). The 5-year overall survival (OS) of YA with CRC or GC was longer than that of older patients with the same stage of malignancy; except YA with stage I GC, who demonstrated poor OS and disease-specific survival (DSS) (65.1% and 67.9%, respectively) which were significantly worse than those of adults aged 41–49 years (70.7% and 76.2%, respectively) and 50–64 years (69.1% and 78.1%, respectively).
Conclusions
YA with GC or CRC have distinctly worse clinical and histopathologic features compared with older patients and are disproportionately of Hispanic ethnicity. These results contribute to improving understanding of younger versus older GI cancer patients.
Drug resistance is the major challenge facing cancer chemotherapy and nanoscale delivery systems based on natural materials, such as sericin, are a promising means of overcoming drug resistance. Yet, ...no attempt of introducing synthetic poly(γ-benzyl-L-glutamate) (PBLG) onto sericin polypeptide to fabricate a facile biocompatible and biodegradable micelle has been tried. Here, we prepared a polypeptide-based amphiphilic polymer containing hydrophilic sericin polypeptide backbone and PBLG side chains via ring-opening polymerization (ROP) strategy. The introduction of PBLG side chains remarkably enhances the stability of sericin micelles in water. Meanwhile, the micelles exhibited a high loading capacity and pH-responsive release ability for antitumor drug doxorubicin (DOX), called sericin-PBLG-DOX. Owing to the excellent cell membrane penetration of sericin-PBLG, the cellular uptake of DOX when loaded into micelles was improved. Subsequently, sericin-PBLG-DOX was transferred into perinuclear lysosomes, where the release rate of DOX was accelerated. Compared to the same dose of DOX, sericin-PBLG-DOX could induce a more efficient anti-tumor effect both in vitro and in vivo, and these micelles have promise for future clinical applications in overcoming cancer drug resistance with good biosafety, enhanced cellular uptake, pH-triggered drug release, efficient anti-tumor effects, and minimized systemic toxicity.
Pancreatic ductal adenocarcinoma (PDAC) has been increasing by 0.5% per year in the United States. PDAC portends a dismal prognosis and novel therapies are needed. This study describes the generation ...and characterization of a novel oncolytic chimeric orthopoxvirus for the treatment of pancreatic cancer.
After chimerization and high-throughput screening, CF33 was chosen from 100 new chimeric orthopoxvirus isolates for its ability to kill pancreatic cancer cells. In vitro cytotoxicity was assayed in six pancreatic cancer cell lines. In vivo efficacy and toxicity were evaluated in PANC-1 and MIA PaCa-2 xenograft models.
CF33 caused rapid killing of six pancreatic cancer cells lines in vitro, releasing damage-associated molecular patterns, and regression of PANC-1 injected and non-injected distant xenografts in vivo after a single low intratumoral dose of 10
plaque-forming units. Using luciferase imaging, CF33 was noted to preferentially replicate in tumors which corresponds to the low viral titers found in solid organs.
The low dose of CF33 required to treat pancreatic cancer in this preclinical study may ease the manufacturing and dosing challenges currently facing oncolytic viral therapy.
Oncolytic viroimmunotherapy is an exciting modality that can offer lasting anti-tumor immunity for aggressive malignancies like colon cancer. The impact of oncolytic viruses may be extended by ...combining them with agents to prime a tumor for viral susceptibility. This study investigates vitamin D analogue as an adjunct to oncolytic viral therapy for colon cancer. While vitamin D (VD) has historically been viewed as anti-viral, our in vitro investigations using human colon cancer cell lines showed that VD does not directly inhibit replication of recombinant chimeric poxvirus CF33. VD did restrict growth in HT29 but not HCT116 human colon cancer cells. In vivo investigations using HCT116 and HT29 xenograft models of colon cancer demonstrated that a VD analogue, calcipotriol, was additive with CF33-based viral therapy in VD-responsive HT29 but not in HCT116 tumors. Analyses of RNA-sequencing and gene expression data demonstrated a downregulation in the Jak-STAT signaling pathway with the addition of VD to viral therapy in HT29 models suggesting that the anti-inflammatory properties of VD may enhance the effects of viral therapy in some models. In conclusion, VD may prime oncolytic viral therapy in certain colon cancers.
Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for ...gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer.
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