Microsatellite Instability Analysis and Its Prognostic Value in Invasive Nonampullary Duodenal Adenocarcinoma.

PURPOSE: Nonampullary duodenal adenocarcinoma (NADA) is a rare disease. Although several prognostic factors have been reported for this disease, they remain controversial due to their rarity. In this study, we retrospectively analyzed 54 cases of invasive NADA, focusing on the microsatellite instability (MSI) phenotype, programmed cell death-ligand 1 (PD-L1) expression, and prognostic factors. METHODS: Expression of the PD-L1 protein and cell differentiation markers in tumors was detected by immunohistochemistry. Microsatellite markers (NR-21, NR-22, NR-24, BAT-25, and BAT-26) were amplified for MSI assessment by PCR. RESULTS: The incidence of MSI in invasive NADA was 35.2%. No significant correlation between the MSI phenotype and clinicopathological factors was observed. Positive expression of PD-L1 by immune cells was common in advanced-stage disease (p = 0.054), and positive expression of PD-L1 in cancer cells correlated significantly with the histologically undifferentiated type (p = 0.016). Kaplan-Meier survival analysis demonstrated a significantly better overall survival (OS) in patients with MSI (p = 0.013) and at early-stage disease (p = 0.000) than in those with microsatellite-stable or at late tumor stages. Univariate and multivariate analyses showed that MSI (hazard ratio [HR]: 0.282, 95% confidence interval [CI]: 0.106-0.751, p = 0.011) and early tumor stage (stage I-II) (HR: 8.81, 95% CI: 2.545-30.500, p = 0.001) were independent better prognostic factors of OS. CONCLUSIONS: MSI and early tumor stage (stage I-II) were independent better prognostic factors of OS. A high proportion of MSI phenotypes and positive PD-L1 expression may be helpful for identifying immune checkpoint inhibitors as a novel therapeutic strategy.

Gastric adenocarcinoma of the fundic gland: A review of clinicopathological characteristics, treatment and prognosis.

Gastric adenocarcinoma of the fundic gland is a rare, well-differentiated gastric cancer entity, and very few patients transition to poorly differentiated tubular adenocarcinoma during progression. Gastric adenocarcinoma of the fundic gland originates from the mucosa of the gastric fundic gland, usually without chronic gastritis or intestinal metaplasia. Histologically, the tumor cells are closely arranged to form anastomosing tubular glands, and more than 95% of tumor cells differentiate towards chief cells. Most gastric adenocarcinoma of the fundic gland cases are characterized by submucosal involvement, but the tumor volume is usually small, with lymphatic and vascular invasion rarely observed. Therefore, endoscopic submucosal dissection can be an ideal treatment, leading to a favorable prognosis, and recurrence and metastasis of the disease are uncommon.

Clinical characteristics and responses to chemotherapy and immune checkpoint inhibitor treatment for microsatellite instability gastric cancer.

During the process of DNA replication, insertions or deletions of repeat sequences easily occur in microsatellites due to DNA polymerase slippage in instances of defective mismatch repair; this phenomenon is known as microsatellite instability. Based on genetic profiling, microsatellite instability gastric cancer is regarded as a separate subtype of gastric cancer that is associated with old age, the female sex, a distal gastric location, and a lower number of lymph node metastases. According to numerous retrospective studies, microsatellite instability is a favourable predictive marker for prognosis. However, during the perioperative period, gastric cancer patients with microsatellite instability after chemotherapy often exhibit a poor and unfavourable prognosis. This result still remains controversial. The efficacy of adjuvant chemotherapy in microsatellite instability-high tumours ranges from detrimental to beneficial effects. Due to the widespread expression of immune checkpoint molecules (such as programmed death-1 and programmed death-ligand 1) in tumours with microsatellite instability, immune checkpoint inhibitors have been utilized to treat microsatellite instability gastric cancer and tremendously improve the efficacy of treatment and survival of microsatellite instability patients. In this review, we attempt to outline the definitions of microsatellites and microsatellite instability, the methods used to screen for microsatellite instability, the clinical characteristics of microsatellite instability gastric cancer, and its responses to chemotherapy and immune checkpoint inhibitor treatment. Overall, determining the status of microsatellites is essential before developing a tailored treatment strategy for patients with microsatellite instability gastric cancer.

Correlations between microsatellite instability and the biological behaviour of tumours.

PURPOSE: Microsatellites are widely distributed repetitive DNA motifs, accounting for approximately 3% of the genome. Due to mismatch repair system deficiency, insertion or deletion of repetitive units often occurs, leading to microsatellite instability. In this review, we aimed to explore the relationship between MSI and biological behaviour of colorectal carcinoma, gastric carcinoma, lymphoma/leukaemia and endometrial carcinoma, as well as the application of frameshift peptide vaccines in cancer therapy. METHODS: The relevant literature from PubMed and Baidu Xueshu were reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS: Microsatellite instability is divided into three subtypes: high-level, low-level microsatellite instability, and stable microsatellites. The majority of tumour patients with high-level microsatellite instability often show a better efficacy and prognosis than those with low-level microsatellite instability or stable microsatellites. In coding regions, especially for genes involved in tumourigenesis, microsatellite instability often results in inactivation of proteins and contributes to tumourigenesis. Moreover, the occurrence of microsatellite instability in coding regions can also cause the generation of frameshift peptides that are thought to be unknown and novel to the individual immune system. Thus, these frameshift peptides have the potential to be biomarkers to raise tumour-specific immune responses. CONCLUSION: MSI has the potential to become a key predictor for evaluating the degree of malignancy, efficacy and prognosis of tumours. Clinically, MSI patterns will provide more valuable information for clinicians to create optimal individualized treatment strategies based on frameshift peptides vaccines.

Using polyethylene plastic bag to prevent moderate hypothermia during transport in very low birth weight infants: a randomized trial.

OBJECTIVE: Hypothermia remains a significant problem among very low birth weight (VLBW) infants. The use of occlusive polyethylene plastic bags immediately after birth has been proven to be effective for preterm infants to reduce hypothermia. This study aims to determine whether placing VLBW infants in plastic bags during transport reduces hypothermia. STUDY DESIGN: Study infants were randomly assigned to a standard thermoregulation protocol or to a standard thermoregulation protocol with placement of the torso and lower extremities inside a polyethylene plastic bag during transport. The primary outcome measures were axillary temperature before and after transport and the occurrence of moderate hypothermia upon neonatal intensive care unit admission. RESULT: The 108 VLBW infants recruited into the study were randomized to the plastic bag (n = 54) group or to standard group (n = 54) and had similar baseline characteristics. VLBW infants in the plastic bag group had a lower rate of moderate hypothermia (3.7 vs 27.8%; risk ratio 0.10; confidence interval 0.02-0.46; P < 0.001) and higher axillary temperatures (36.4 ± 0.4 °C vs 35.9 ± 0.9 °C; P = 0.001) upon NICU admission compared to infants receiving standard care. CONCLUSION: Placing VLBW infants in polyethylene plastic bags during transport reduces the occurrence of hypothermia, especially moderate hypothermia.