Pancreatic cancer is marked by complement-high blood monocytes and tumor-associated macrophages

Pancreatic ductal adenocarcinoma (PDA) is accompanied by reprogramming of the local microenvironment, but changes at distal sites are poorly understood. We implanted biomaterial scaffolds, which act as an artificial premetastatic niche, into immunocompetent tumor-bearing and control mice, and identified a unique tumor-specific gene expression signature that includes high expression of C1qa, C1qb, Trem2, and Chil3 Single-cell RNA sequencing mapped these genes to two distinct macrophage populations in the scaffolds, one marked by elevated C1qa, C1qb, and Trem2, the other with high Chil3, Ly6c2 and Plac8 In mice, expression of these genes in the corresponding populations was elevated in tumor-associated macrophages compared with macrophages in the normal pancreas. We then analyzed single-cell RNA sequencing from patient samples, and determined expression of C1QA, C1QB, and TREM2 is elevated in human macrophages in primary tumors and liver metastases. Single-cell sequencing analysis of patient blood revealed a substantial enrichment of the same gene signature in monocytes. Taken together, our study identifies two distinct tumor-associated macrophage and monocyte populations that reflects systemic immune changes in pancreatic ductal adenocarcinoma patients

Synergistic Analysis of Circulating Tumor Cells Reveals Prognostic Signatures in Pilot Study of Treatment-Naïve Metastatic Pancreatic Cancer Patients

Pancreatic ductal adenocarcinoma is typically diagnosed at late stages and has one of the lowest five-year survival rates of all malignancies. In this pilot study, we identify signatures related to survival and treatment response found in circulating tumor cells (CTCs). Patients with poor survival had increased mutant KRAS expression and deregulation of connected pathways such as PI3K-AKT and MAPK signaling. Further, in a subset of these patients, expression patterns of gemcitabine resistance mechanisms were observed, even prior to initiating treatment. This work highlights the need for identifying patients with these resistance profiles and designing treatment regimens to circumvent these mechanisms

Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers

Ninety-eight patients were included of which 74 (75%) had metastatic and 24 (25%) had locally advanced disease at the time of treatment with FOLFIRI. The median age was 60 (range, 22-86) years. The number of patients with extrahepatic cholangiocarcinoma, gall bladder cancer and intrahepatic cholangiocarcinoma were 10, 17 and 71, respectively. FOLFIRI was used as 1st, 2nd, 3rd or 4th - Nth lines in 8, 50, 36 and 4 patients, respectively. Median duration on FOLFIRI in the entire cohort was 2.2 (range, 0.5-8.4) mo. The median PFS and overall survival were 2.4 (95% confidence interval (CI): 1.7-3.1) and 6.6 (95%CI: 4.7-8.4) mo, respectively. Median PFS for patients treated with FOLFIRI in 1st, 2nd, 3rd or 4th - Nth lines were 3.1, 2.5, 2.3 and 1.5 mo, respectively. Eighteen patients received concurrent bevacizumab (n = 13) or EGFR-targeted therapy (n = 5) with FOLFIRI, with a median PFS of 2.7 mo (95%CI: 1.7-5.1).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Role of pelvic CT during surveillance of patients with resected biliary tract cancer

Abstract Background The aim of the study was to identify the frequency of isolated pelvic metastasis with the goal of determining the utility of pelvic CT as a surveillance strategy in patients with resected biliary tract cancer (BTC). Methods Study eligibility criteria included patients 18 years or older with BTC who underwent R0 or R1 surgical resection at University of Michigan between 2004 and 2018, with a minimum 6-month disease-free surveillance period. CT and MRI reports were independently graded by two radiologists as positive (organ metastasis, peritoneal carcinomatosis, or enlarged lymph nodes), equivocal (borderline lymph nodes or non-nodular ascites), or negative (absence of or benign findings) in the abdomen and pelvis separately. A 3rd blinded radiologist reviewed all positive and equivocal scans. Clinic notes were reviewed to identify new or worsening signs and symptoms that would warrant an earlier pelvic surveillance scan. A 95% binomial proportion confidence interval was used to find the probability of isolated pelvic metastasis. Results BTC were anatomically classified as extra-hepatic (distal and hilar) cholangiocarcinoma (38; 25%), intra-hepatic cholangiocarcinoma (57; 38%), and gallbladder cancer (56; 37%). 151 patients met eligibility criteria, of which 123 (81%) had no pelvic metastasis, 51 (34%) had localized upper abdominal metastasis, and 23 (15%) had concomitant abdominal and pelvic metastasis. Median follow-up time was 19.2 months. One (0%) subject with resected BTC (intra-hepatic) developed isolated osseous pelvic metastasis during surveillance (95% CI 0.004–0.1; p = 0.0003). 3 (2%) subjects developed isolated simple ascites (equivocal grade) without concurrent upper abdominal metastasis. Conclusion Isolated pelvic metastasis is a rare occurrence during surveillance in patients with resected BTCs, and therefore, follow-up pelvic CT in absence of specific symptoms may be unnecessary