The role of procalcitonin in identifying community-associated bacterial infections among patients with coronavirus disease 2019 is not yet established. In 2,443 patients with 148 bacterial coinfections, mean procalcitonin levels were significantly higher with any bacterial infection (13.16 ± 51.19 ng/ml; P = 0.0091) and with bacteremia (34.25 ± 85.01 ng/ml; P = 0.0125) than without infection (2.00 ± 15.26 ng/ml).

KRAS G12C mutations are critical in the pathogenesis of multiple cancer types, including non-small cell lung (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal (CRC) cancers. As such, they have increasingly become a target of novel therapies in the management of these malignancies. However, the therapeutic success of KRAS G12C inhibitors to date has been far more limited in CRC and PDAC than NSCLC. In this review, we briefly summarize the biochemistry of KRAS targeting and treatment resistance, highlight differences in the epidemiology of various G12C-mutated cancers, and provide an overview of the published data on KRAS G12C inhibitors for various indications. We conclude with a summary of ongoing clinical trials in G12C-mutant CRC and a discussion of future directions in the management of this disease. KRAS G12C mutation, targeted therapies, colorectal cancer, non-small cell lung cancer, pancreatic cancer, drug development.

Pancreatic cancer is a highly aggressive malignancy with a climbing incidence. The majority of cases are detected late, with incurable locally advanced or metastatic disease. Even in individuals who undergo resection, recurrence is unfortunately very common. There is no universally accepted screening modality for the general population and diagnosis, evaluation of treatment response, and detection of recurrence relies primarily on the use of imaging. Identification of minimally invasive techniques to help diagnose, prognosticate, predict response or resistance to therapy, and detect recurrence are desperately needed. Liquid biopsies represent an emerging group of technologies which allow for non-invasive serial sampling of tumor material. Although not yet approved for routine use in pancreatic cancer, the increasing sensitivity and specificity of contemporary liquid biopsy platforms will likely change clinical practice in the near future. In this review, we discuss the recent technological advances in liquid biopsy, focusing on circulating tumor DNA, exosomes, microRNAs, and circulating tumor cells.

The gut microbiome plays an important role in the carcinogenesis of luminal gastrointestinal malignancies and response to antineoplastic therapy. Preclinical studies have suggested a role of intratumoral gammaproteobacteria in mediating response to gemcitabine-based chemotherapy in pancreatic ductal adenocarcinoma (PDAC). To our knowledge, this is the first study to evaluate the impact of the PDAC microbiome on chemotherapy response using samples from human pancreatic tumor resections. We performed 16S rRNA gene amplification and sequencing on both formalin-fixed paraffin-embedded (FFPE) and fresh frozen human PDAC resection samples. We analyzed frozen samples from 26 patients with resected PDAC and examined tumor and tumor-adjacent normal tissue. These patients represented nine long-term survivors (LTS) and nine short-term survivors (STS) after neoadjuvant gemcitabine therapy and eight control patients who did not receive any neoadjuvant therapy prior to resection. We also included FFPE samples from five patients, including tumor samples (3 samples per patient), tumor-adjacent normal tissue (2 per patient) and tumor-adjacent paraffin (1 per patient). Within frozen tissue, total DNA yields were high, but bacterial DNA was generally low, comparable to those seen in negative controls. In FFPE tissue, DNA yields were low and bacterial abundances were comparable in paraffin, tumor and normal PDAC samples. Gammaproteobacteria concentrations did not correlate with outcomes in patients treated with neoadjuvant gemcitabine-based chemotherapy. Our study found low microbial biomass in pancreatic tumor tissue, with no detectable association between bacterial taxa and chemotherapy outcomes. These results suggest a limited role of the microbiome in gemcitabine-based chemotherapy response in PDAC. Preclinical studies have implicated the pancreatic tumor microbiome in driving response to therapy. Cytidine deaminase, an enzyme produced by gammaproteobacteria, can metabolize gemcitabine and has been hypothesized to inhibit pancreatic tumor response to chemotherapy. Several clinical trials have evaluated the role of the tumor microbiome in pancreatic cancer treatment. We evaluated the impact of the pancreatic tumor microbiome on chemotherapy response using samples from human pancreatic tumor resections. We found a low microbial load that is partially attributable to contaminants and that gammaproteobacteria levels did not correlate with outcomes in patients with pancreatic cancer treated with gemcitabine-based chemotherapy.

HER2 amplification, which results in overexpression of the receptor tyrosine kinase HER2, has been described in a wide variety of malignancies. HER2-targeting agents have been incorporated into the treatment paradigms for HER2-overexpressing breast and gastric cancer. More recently, these agents have shown promise in other gastrointestinal malignancies, such as colon cancer and biliary tract tumors. This study discusses two patients with gallbladder carcinoma and a third with ampullary carcinoma who were able to achieve marked responses to HER2-directed therapy. These cases underscore the importance of molecular analysis for HER2 amplification/HER2 overexpression, irrespective of tumor histology, and highlight a need for further investigation of HER2-directed therapy beyond breast and gastroesophageal cancers. Key Points: