Identification of a prognostic DNA repair gene signature in esophageal cancer.

Background: DNA repair plays a crucial role in the development and progression of different types of cancers. Nevertheless, little is known about the role of DNA repair-related genes (DRRGs) in esophageal cancer (EC). The present study aimed to identify a novel DRRGs prognostic signature in EC. Methods: Gene set enrichment analysis (GSEA) was performed to screen 150 genes related to DNA repair, which is the most important enrichment gene set in EC. Univariate and multivariate Cox regression analyses were used to screen DRRGs closely associated with prognosis. The difference in the expression of hub DRRGs between tumor and normal tissues was analyzed. Combined with clinical indicators (including age, gender, and tumor stage), we evaluated whether the 4-DRRGs signature was an independent prognostic factor. In addition, we evaluated the prediction accuracy using a receiver operating characteristic (ROC) curve and visualized the model's performance via a nomogram. Results: Four-DRRGs (NT5C3A, TAF9, BCAP31, and NUDT21) were selected by Cox regression analysis to establish a prognostic signature to effectively classify patients into high- and low-risk groups. The area under the curve (AUC) of the time-dependent ROC of the prognostic signature for 1- and 3-year was 0.769 and 0.720, respectively. Compared with other clinical characteristics, the risk score showed a robust ability to predict the prognosis in EC, especially in the early stage of EC. Furthermore, we constructed a nomogram to interpret the clinical application of the 4-DRRGs signature. Conclusions: In conclusion, we identified a prognostic signature based on the DRRGs for patients with EC, which can contribute independent value in identifying clinical outcomes that complement the TNM system in EC.

Risk of hepatitis B virus reactivation in cancer patients undergoing treatment with tyrosine kinase-inhibitors.

This editorial commented on an article in the World Journal of Gastroenterology titled "Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors: Case Report and Literature Analysis" by Colapietro et al. In this editorial, we focused on providing a more comprehensive exploration of hepatitis B virus reactivation (HBVr) associated with the usage of tyrosine kinase inhibitors (TKIs). It includes insights into the mechanisms underlying HBV reactivation, the temporal relationship between TKIs and HBV reactivation, and preventive measures. The aim is to understand the need for nucleos(t)ide analogs (NAT) and serial blood tests for early recognition of reactivation and acute liver injury, along with management strategies. TKIs are considered to be an intermediate (1%-10%) of HBVr. Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen, anti-hepatitis B core antigen (HBc), and anti-hepatitis B surface antibody. Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV. Nucleoside or nucleotide analogs (NAs) like entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) form the basis of HBV reactivation prophylaxis and treatment during immunosuppression. Conversely, lamivudine, telbivudine, and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains. However, these less effective NAs may still be utilized in cases where ETV, TDF, and TAF are not feasible treatment options.

Disparities in time to treatment initiation for rectal cancer patients: an analysis of demographic and socioeconomic factors.

Background: This study investigated demographic and socioeconomic factors contributing to disparities in the time to treatment for rectal cancer. Subgroup analysis based on age < 50 and ≥ 50 was performed to identify differences in time to treatment among young adults (age < 50) compared to older adults with rectal cancer. Methods: An analysis was performed using data from the National Cancer Database, spanning from 2004 to 2019. The study encompassed 281,849 patients diagnosed with rectal cancer. We compared time intervals from diagnosis to surgery, radiation, and chemotherapy, considering age, sex, race, and socioeconomic variables. Analyses were performed for the entire cohort and for two subgroups based on age (< 50 and ≥ 50). Results: Overall, Hispanic patients experienced longer times to surgery, radiation, and chemotherapy compared to non-Hispanic patients (surgery: 94.2 vs. 79.1 days, radiation: 65.0 vs. 55.6 days, chemotherapy: 56.4 vs. 47.8 days, all p < 0.001). Patients with private insurance had shorter times to any treatment (32.5 days) compared to those with government insurance or no insurance (30.6 and 32.5 days, respectively, p < 0.001). Black patients experienced longer wait times for both radiation (63.4 days) and chemotherapy (55.2 days) compared to White patients (54.9 days for radiation and 47.3 days for chemotherapy, both p < 0.001). Interestingly, patients treated at academic facilities had longer times to treatment in surgery, radiation, and chemotherapy compared to those treated at comprehensive and community facilities. When analyzed by age, many of the overall differences persisted despite the age stratification, suggesting that these disparities were driven more by demographic and socioeconomic variables rather than by age. Conclusion: Significant differences in the time to treatment for rectal cancer have been identified. Hispanic patients, individuals lacking private insurance, Black patients, and patients receiving care at academic facilities had the longest times to treatment. However, these differences were largely unaffected by the age (< 50 and ≥ 50) subgroup analysis. Further investigation into the causes of these disparities is warranted to develop effective strategies for reducing treatment gaps and enhancing overall care for rectal cancer patients.

Early Stage Breast Cancer: Does Histologic Subtype (Ductal vs. Lobular) Impact 5 Year Overall Survival?

Histology is an important predictor of the behavior of breast cancer. We aim to study the impact of histology on the overall survival (OS) of breast cancer patients. We studied 11,085 breast cancer patients diagnosed with T1-T2 tumors, clinically node-negative and non-metastatic, from 2004 to 2019 included in the National Cancer Database. Kaplan-Meier curves, log-rank tests and Cox regression models were used to study the impact of histology and other variables on OS. In our patient population, 8678 (78.28%) had ductal cancer (IDC), while 2407 (21.71%) had lobular cancer (ILC). ILC patients were significantly more likely to be older, Caucasian, have a lower grade at diagnosis and be hormone receptor-positive compared to IDC patients. There was no statistically significant difference in the 5-year OS of early stage ductal (16.8%) and lobular cancer patients (16.7%) (p = 0.200). Patients of Hispanic and African American origin had worse OS rates compared to non-Hispanic and Caucasian patients, respectively. For node-positive disease, HER2+ tumors and triple-negative tumors, chemotherapy had a positive influence on OS (HR 0.85, 95% CI 0.77-0.93, p = 0.0012). Histology did not have a significant impact on the 5-year OS of early stage breast cancer patients.

Expression of c-erb-B2 oncoprotein as a neoantigen strategy to repurpose anti-neu antibody therapy in a model of melanoma.

In this study, we tested a novel approach of "repurposing" a biomarker typically associated with breast cancer for use in melanoma. HER2/neu is a well characterized biomarker in breast cancer for which effective anti-HER2/neu therapies are readily available. We constructed a lentivirus encoding c-erb-B2 (the animal homolog to HER2/neu). This was used to transfect B16 melanoma in vitro for use in an orthotopic preclinical mouse model, which resulted in expression of c-erb-B2 as a neoantigen target for anti-c-erb-B2 monoclonal antibody (7.16.4). The c-erb-B2-expressing melanoma was designated B16/neu. 7.16.4 produced statistically significant in vivo anti-tumor responses against B16/neu. This effect was mediated by NK-cell antibody-dependent cell-mediated cytotoxicity. To further model human melanoma (which expresses <5% HER2/neu), our c-erb-B2 encoding lentivirus was used to inoculate naïve (wild-type) B16 tumors in vivo, resulting in successful c-erb-B2 expression. When combined with 7.16.4, anti-tumor responses were again demonstrated where approximately 40% of mice treated with c-erb-B2 lentivirus and 7.16.4 achieved complete clinical response and long-term survival. For the first time, we demonstrated a novel strategy to repurpose c-erb-B2 as a neoantigen target for melanoma. Our findings are particularly significant in the contemporary setting where newer anti-HER2/neu antibody-drug candidates have shown increased efficacy.

Liposomal Phenylephrine Nanoparticles Enhance the Antitumor Activity of Intratumoral Chemotherapy in a Preclinical Model of Melanoma.

Intratumoral injection of anticancer agents has limited efficacy and is not routinely used for most cancers. In this study, we aimed to improve the efficacy of intratumoral chemotherapy using a novel approach comprising peri-tumoral injection of sustained-release liposomal nanoparticles containing phenylephrine, which is a potent vasoconstrictor. Using a preclinical model of melanoma, we have previously shown that systemically administered (intravenous) phenylephrine could transiently shunt blood flow to the tumor at the time of drug delivery, which in turn improved antitumor responses. This approach was called dynamic control of tumor-associated vessels. Herein, we used liposomal phenylephrine nanoparticles as a "local" dynamic control strategy for the B16 melanoma. Local dynamic control was shown to increase the retention and exposure time of tumors to intratumorally injected chemotherapy (melphalan). C57BL/6 mice bearing B16 tumors were treated with intratumoral melphalan and peri-tumoral injection of sustained-release liposomal phenylephrine nanoparticles (i.e., the local dynamic control protocol). These mice had statistically significantly improved antitumor responses compared to melphalan alone (p = 0.0011), whereby 58.3% obtained long-term complete clinical response. Our novel approach of local dynamic control demonstrated significantly enhanced antitumor efficacy and is the subject of future clinical trials being designed by our group.

Role of Surgery in Metastatic Melanoma and Review of Melanoma Molecular Characteristics.

We aimed to review the molecular characteristics of metastatic melanoma and the role of surgery in metastasectomy for metastatic melanoma. We performed a systematic literature search on PubMed to identify relevant studies focusing on several mutations, including NRAS, BRAF, NF1, MITF, PTEN, TP53, CDKN2A, TERT, TMB, EGFR, and c-KIT. This was performed in the context of metastatic melanoma and the role of metastasectomy in the metastatic melanoma population. A comprehensive review of these molecular characteristics is presented with a focus on their prognosis and role in surgical metastasectomy.

Time to treatment disparities in gastric cancer patients in the United States of America: a comprehensive retrospective analysis.

Introduction: Gastric cancer ranks as the 5th most prevalent cancer and the 4th leading cause of cancer-related deaths worldwide. Various treatment modalities, including surgical resection, chemotherapy, and radiotherapy, are available for gastric cancer patients. However, disparities related to age, sex, race, socioeconomic factors, insurance status, and demographic factors often lead to delayed time to treatment. Methods: In this retrospective study, conducted between 2004 and 2019, we utilized data from the National Cancer Database (NCDB) to investigate the factors contributing to disparities in the time to first treatment, surgery, chemotherapy, and radiotherapy among gastric cancer patients. Our analysis incorporated several variables, and statistical analysis was conducted to provide valuable insights into these disparities. Results: We observed notable disparities in the timing of treatment for various demographic groups, including age, sex, race, insurance status, geographic location, and facility type. These disparities include longer time to treatment in males (32.67 vs 30.75), Native Americans (35.10 vs 31.09 in Asians), low-income patients (32 vs 31.15), patients getting treatment in an academic setting (36.11 vs 29.61 in community setting), significantly longer time to chemotherapy in 70+ age group (51.13 vs 40.38 in <40 y age group), black race (55.81 vs 47.05 in whites), low income people (49.64 vs 46.74), significantly longer time to radiotherapy in females (101.61 vs 79.75), blacks and Asians (109.68 and 113.96 respectively vs 92.68 in Native Americans) etc. There are various other disparities in time to surgery, chemotherapy, and radiotherapy. Conclusions: Understanding these disparities is crucial in developing targeted strategies to improve timely access to appropriate treatments and enhance outcomes for gastric cancer patients. Future research with updated data and prospective study designs can provide a more comprehensive understanding of the factors influencing patient outcomes in gastric cancer.

Disparities in Time-to-treatment for Patients With Melanoma.

BACKGROUND/AIM: This study aimed to investigate the demographic and socioeconomic factors associated with disparities in the time-to-treatment for melanoma. PATIENTS AND METHODS: We conducted an analysis of patients with melanoma from 2004 to 2019 using the National Cancer Database. Time intervals from diagnosis to surgery, radiation, and chemotherapy were compared based on age, sex, race, and socioeconomic status. RESULTS: A total of 647,273 patients with melanoma were included. Overall, Hispanic patients had the longest times to surgery, radiation, and chemotherapy compared to non-Hispanic patients (surgery 38.52 vs. 31.90 days, radiation 130.12 vs. 99.67 days, chemotherapy 93.66 vs. 83.72 days, all p<0.01). Similarly, black patients and those who were uninsured had the longest times-to-treatment. CONCLUSION: We identified significant disparities in time-to-treatment, related to both race and socioeconomic factors. It is increasingly imperative to conduct further investigations into the root causes of these disparities to effectively address and rectify the inequities present in breast cancer care.

Clinical manifestations and expression of CD18 to guide the diagnosis of leukocyte adhesion deficiency type 1

Background: Leukocyte adhesion deficiency type 1 (LAD-1) is an inborn error of immunity characterized by a defect in leukocyte trafficking. Methods: Patients with clinical suspicion of LAD-1 were referred to our institution. Complete blood count and flow cytometric analysis, to identify the expression of CD18, CD11b, and the lymphocyte population phenotyping, were performed, and statistical analysis was completed. Results: We report clinical manifestations and immunological findings of six Mexican patients diagnosed with LAD-1. The diagnosis was based on typical clinical presentation, combined with laboratory demonstration of leukocytosis, and significant reduction or near absence of CD18 and its associated molecules CD11a, CD11b, and CD11c on leukocytes. We found atypical manifestations, not described in other countries, such as early-onset autoimmunity or infections caused by certain microorganisms. Conclusions: Patients with LAD-1 may present with atypical manifestations, making flow cytometry an indispensable tool to confirm the diagnosis. We present the first report of LAD-1 patients in a Latin American country (AU)

Effect of low-level creatinine clearance on short-term postoperative complications in patients with colorectal cancer.

Background: Renal function is closely related to cancer prognosis. Since preoperative renal insufficiency has been identified as a risk factor for postoperative complications, this study aimed to investigate the effect of preoperative creatinine clearance rate (CrCl) on short-term prognosis of patients undergoing colorectal surgery. Methods: A retrospective analysis was conducted of the electronic health records of 526 adult patients who underwent elective colorectal cancer (CRC) surgery from September 2014 to February 2019 at the First Affiliated Hospital of Wenzhou Medical University. Cases were divided into two groups according to CrCl level and clinical variables were compared. Risk factors associated with postoperative complications were evaluated through univariate and multivariate logistic regression analyses. Results: A total of 526 patients met the inclusion criteria. The overall rate of postoperative complications was 28.14%. Overall, the incidence of postoperative complications was significantly higher in the low CrCl patients. A low-level CrCl, multi-organ combined resection, and Charlson comorbidity index (CCI) were independent risk factors for short-term complications in patients with CRC. However, a low CrCl was identified as an independent risk factor for short-term postoperative complications in elderly, but not young patients in a subgroup analysis. Conclusions: Preoperative low-level CrCl, multi-organ combined resection, and CCI were significant risk factors of postoperative complications in CRC patients. Preoperative low-level CrCl and multi-organ combined resection has a poor prognostic impact for elderly patients with CRC. These findings should have important implications for health care decision-making among patients with CRC who are at higher risk for post-operative complications.