An update on pharmacotherapies for colorectal cancer: 2023 and beyond.

INTRODUCTION: Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide. The treatment of metastatic colorectal cancer (mCRC) is difficult, and mCRC has a survival rate of only 13-17% compared with 70-90% in locoregional CRC. There is ongoing research effort on pharmacotherapy for CRC to improve the treatment outcome. AREAS COVERED: We reviewed the current literature and ongoing clinical trials on CRC pharmacotherapy, with a focus on targeted therapy based on the results of genetic testing. The pharmacotherapies covered in this article include novel agents targeting EGFR and EGFR-related pathways, agents targeting the VEGF pathway, immunotherapy options depending on the MMR/MSI status, and new therapies targeting genetic fusions such as NTRK. We also briefly discuss the value of next-generation sequencing (NGS) in treatment selection and response monitoring. EXPERT OPINION: We advocate for the early and routine use of NGS to genetically characterize CRC to assist with pharmacotherapy selection. Targeted therapy is a promising field of ongoing research and improves CRC treatment outcome.

Successful surgical treatment of Stanford type A aortic dissection due to Salmonella aortitis.

BACKGROUND: Salmonella spp. cause infectious aortitis through the hematogenous spread of an intestinal Salmonella infection. Salmonella aortitis can result in extensive tissue damage in the aorta leading to complications including dissection, abscess formation, pseudoaneurysms, and rupture, which require early diagnosis and treatment with both surgery and antibiotic therapy. CASE PRESENTATION: We report a case of Salmonella aortitis complicated by Stanford type A aortic dissection. A 62-year-old man with a history of heroin use presented with chest pain, epigastric pain and vomiting. The computed tomography scan showed Stanford type A aortic dissection without malperfusion. At the time of surgery, an aortic dissection with purulent fluid and contained rupture was noted in the ascending aorta. Fluid culture was consistent with Salmonella. A composite valve-graft conduit aortic root replacement with ascending aorta and hemiarch replacement was performed. The patient recovered well and was discharged on long-term antibiotics. CONCLUSIONS: This rare case of a Stanford type A aortic dissection with contained rupture due to Salmonella aortitis was successfully treated with emergent surgery and antibiotic therapy.

Sports Team Participation and Vaping Among High School Students: 2015-2019.

BACKGROUND AND OBJECTIVES: Electronic vapor products (EVPs) have gained popularity among adolescents despite the health risks. This study aimed to evaluate whether sports team participation, a well-established protective factor against cigarette use, is similarly associated with decreased EVP use. METHODS: This cross-sectional study analyzed the 2015-2019 Youth Risk Behavior Survey cohorts. Survey-weighted logistic regressions investigated associations between sports team participation and past 30-day exclusive cigarette use, exclusive EVP use, and dual cigarette/EVP use among US high school students, adjusting for sex, grade, and survey year. RESULTS: The analytic cohort included 16 790 sports team participants (1.7% exclusive cigarette users, 18.3% exclusive EVP users, 5.5% dual users) and 13 972 nonparticipants (3.1% exclusive cigarette users, 13.4% exclusive EVP users, 7.6% dual users). Sports team participation was associated with lower odds of cigarette use (adjusted odds ratio [aOR], 0.58; 95% confidence interval [CI], 0.48-0.71) and dual use (aOR, 0.74; 95% CI, 0.63-0.88) and higher odds of EVP use (aOR, 1.39; 95% CI, 1.25-1.54). Among exclusive cigarette users and exclusive EVP users, sports team participation was associated with lower odds of frequent (≥20 days in the past month) than intermittent (1-19 days in the past month) cigarette use (aOR, 0.30; 95% CI, 0.19-0.49) and EVP use (aOR, 0.74; 95% CI, 0.61-0.91), respectively. CONCLUSIONS: Our findings suggest that risk profiles for cigarette and EVP use differ with respect to sports team participation. Given the health risks associated with EVP use, aggressive efforts must be taken to educate student athletes about the health risks of EVP use.

Age restriction warning label efficacy and high school student consumption of highly-caffeinated products.

Age restriction warning labels (ARLs) are placed on highly-caffeinated food and drinks, such as Red Bull, to deter consumption by minors who are especially vulnerable to the risks of excessive caffeine consumption. Previous studies have shown that ARLs on media like TV programs and video games fail to discourage minors. However, it is unclear how ARLs on food and drink packages affect minors' purchasing behavior. High school students aged 14 to 17 years (n = 150, Mage = 15.2, 51% male) were asked to choose between seven novel product dyads (three food/drink dyads, two movie dyads, and two video game dyads); each dyad contained one product with an ARL and one without. Participants were then asked how ARLs and parental permissiveness of ARL products influenced their decision. Roughly half of the participants selected food and drink products with ARLs. Over two-thirds (69%) of the students reported that they were not discouraged by ARLs on highly caffeinated food and drinks. Participants reported their parents as significantly less permissive of age-restricted food and drink products than of age-restricted media merchandise (p < .01). Perceived parental permissiveness was not correlated with minors' perception of ARL or simulated product choice. Current ARLs on highly caffeinated food and drink items may be ineffective for adolescents and may actually increase product appeal. Pediatricians should educate patients and parents regarding the health risks of excessive caffeine consumption.

Long non-coding RNAs: novel prognostic biomarkers for liver metastases in patients with early stage colorectal cancer.

Liver metastasis is the primary cause of death for colorectal cancer (CRC) patients. To investigate the prognostic value of long non-coding RNAs (lncRNAs) on colorectal liver metastases, quantitative reverse-transcriptase PCR (quantitative RT-PCR) was performed on 15 lncRNAs in 51 stage IV CRC with liver metastases and 57 stage I/II CRC specimens. The expression levels of four lncRNAs (GAS5, H19, MEG3 and Yiya) were significantly different between liver metastases and primary tumors of stage IV CRC patients. Furthermore, the high expression levels of GAS5 and Yiya were significantly associated with future occurrence of liver metastases in early stage CRC patients. Kaplan-Meier analysis showed that the high expression levels of GAS5 or Yiya were correlated with poor prognosis of early stage CRC patients (p = 0.0206 and 0.0005 for GAS5 and Yiya, respectively). Yiya expression was proved to be an independent prognostic indicator of colorectal liver metastases in a multivariate analysis (relative risk = 10.7; p < 0.0001). Our study revealed that GAS5 and Yiya were promising prognostic biomarkers of liver metastases for early stage CRC patients.

Quantitative assessment of short amplicons in FFPE-derived long-chain RNA.

Formalin-fixed paraffin-embedded (FFPE) tissues are important resources for molecular medical research. However, long-chain RNA analysis is restricted in FFPE tissues due to high levels of degradation. To explore the possibility of long RNA quantification in FFPE tissues, we selected 14 target RNAs (8 mRNAs and 6 long noncoding RNAs) from literatures, and designed short (~60 bp) and long (~200 bp) amplicons for each of them. Colorectal carcinomas with adjacent normal tissues were subjected to quantitative reverse-transcription PCR (quantitative RT-PCR) in 3 cohorts, including 18 snap-frozen and 83 FFPE tissues. We found that short amplicons were amplified more efficiently than long amplicons both in snap-frozen (P = 0.0006) and FFPE (P = 0.0152) tissues. Nonetheless, comparison of colorectal carcinomas with their adjacent normal tissues demonstrated that the consistency of fold-change trends in a single short amplicon between snap-frozen and FFPE tissues was only 36%. Therefore, we innovatively performed quantitative RT-PCR with 3 non-overlapping short amplicons for 14 target RNAs in FFPE tissues. All target RNAs showed a concordance of 100% of fold-change trends in at least two short amplicons, which offers sufficient information for accurate quantification of target RNAs. Our findings demonstrated the possibility of long-chain RNA analysis with 3 non-overlapping short amplicons in standardized-preserved FFPE tissues.