Background and Aim
Knowledge of lymph node metastasis (LNM) status is crucial to determine whether patients with superficial esophageal squamous cell carcinoma (ESCC) can be cured with endoscopic ...resection alone, without the need for additional esophagectomy. The present study aimed to identify predictive factors and develop a prediction model for LNM in patients with superficial ESCC.
Methods
Clinicopathologic data from 501 patients with superficial ESCC treated with radical esophagectomy were reviewed. Stepwise logistic regression analysis determined the predictors of LNM. Using these predictors, a nomogram for predicting the risk of LNM was constructed and internally validated using a bootstrap resampling method.
Results
LNM rates of tumors invading the lamina propria, muscularis mucosa, and SM1 layers were 3.7%, 15.5%, and 40.7%, respectively. Deep tumor invasion depth, moderately or poorly differentiated histology, and lymphovascular invasion were independent predictors of LNM. ESCC with muscularis mucosa and SM1 invasion had odds ratios of 3.635 and 11.834, respectively, compared with that for ESCC confined to the lamina propria. Large tumor size (>2.0 cm) and presence of tumor budding showed borderline significance for LNM prediction. These five variables were incorporated into a nomogram. A constructed nomogram showed good calibration and good discrimination with an area under the receiver‐operating characteristic curve (area under the curve AUC) of 0.812. After bootstrapping, AUC was 0.811.
Conclusions
We developed a nomogram that can facilitate individualized prediction of risk of LNM in patients with superficial ESCC. This model can aid in decision‐making for the need for additional esophagectomy after endoscopic resection for superficial ESCC.
Abstract
Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to ...evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using
Sac
II enzyme digestion. A total of 191 patients with stage I–IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I–IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I–IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis.
Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT 04253509) for lung cancer on 5 February 2020,
https://clinicaltrials.gov/ct2/show/NCT04253509
. Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022,
https://cris.nih.go.kr
,
https://who.init/ictrp
. Healthy control samples were retrospectively registered.
To compare pneumonic-type invasive mucinous adenocarcinoma (pIMA) confined to a single lobe with clinical T2, T3, and T4 stage lung cancer without pathological node metastasis regarding survival ...after curative surgery and to identify prognostic factors for pIMA.
From January 2010 to December 2017, 41 patients (15 male; mean age ± standard deviation, 66.0 ± 9.9 years) who had pIMA confined to a single lobe on computed tomography (CT) and underwent curative surgery were identified in two tertiary hospitals. Three hundred and thirteen patients (222 male; 66.3 ± 9.4 years) who had non-small cell lung cancer (NSCLC) without pathological node metastasis and underwent curative surgery in one participating institution formed a reference group. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox proportional hazard regression analysis was performed to identify factors associated with the survival of patients with pIMA.
The 5-year RFS and OS rates in patients with pIMA were 33.1% and 56.0%, respectively, compared with 74.3% and 91%, 64.3% and 71.8%, and 46.9% and 49.5% for patients with clinical stage T2, T3, and T4 NSCLC in the reference group, respectively. The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 NSCLC and significantly worse than that of patients with clinical stage T3 NSCLC (
= 0.012). The differences in OS between patients with pIMA and those with clinical stage T3 or T4 NSCLC were not significant (
= 0.11 and
= 0.37, respectively). In patients with pIMA, the presence of separate nodules was a significant factor associated with poor RFS and OS {unadjusted hazard ratio (HR), 4.66 (95% confidence interval CI, 1.95-11.11),
< 0.001 for RFS; adjusted HR, 4.53 (95% CI, 1.59-12.89),
= 0.005 for OS}.
The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 lung cancer. Separate nodules on CT were associated with poor RFS and OS in patients with pIMA.
Summary
Numerous staple crops exhibit polyploidy and are difficult to genetically modify. However, recent advances in genome sequencing and editing have enabled polyploid genome engineering. The ...hexaploid black nightshade species Solanum nigrum has immense potential as a beneficial food supplement. We assembled its genome at the scaffold level. After functional annotations, we identified homoeologous gene sets, with similar sequence and expression profiles, based on comparative analyses of orthologous genes with close diploid relatives Solanum americanum and S. lycopersicum. Using CRISPR‐Cas9‐mediated mutagenesis, we generated various mutation combinations in homoeologous genes. Multiple mutants showed quantitative phenotypic changes based on the genotype, resulting in a broad‐spectrum effect on the quantitative traits of hexaploid S. nigrum. Furthermore, we successfully improved the fruit productivity of Boranong, an orphan cultivar of S. nigrum suggesting that engineering homoeologous genes could be useful for agricultural improvement of polyploid crops.
The low response rate of current cancer immunotherapy suggests the presence of few antigen-specific T cells and a high number of immunosuppressive factors in tumor microenvironment (TME). Here, we ...develop a syringeable immunomodulatory multidomain nanogel (iGel) that overcomes the limitation by reprogramming of the pro-tumoral TME to antitumoral immune niches. Local and extended release of immunomodulatory drugs from iGel deplete immunosuppressive cells, while inducing immunogenic cell death and increased immunogenicity. When iGel is applied as a local postsurgical treatment, both systemic antitumor immunity and a memory T cell response are generated, and the recurrence and metastasis of tumors to lungs and other organs are significantly inhibited. Reshaping of the TME using iGel also reverts non-responding groups to checkpoint blockade therapies into responding groups. The iGel is expected as an immunotherapeutic platform that can reshape immunosuppressive TMEs and synergize cancer immunotherapy with checkpoint therapies, with minimized systemic toxicity.
As the majority of incidentally detected lesions in the anterior mediastinum is small nodules with soft tissue appearance, the differential diagnosis has typically included thymic neoplasm and ...prevascular lymph node, with benign cyst. Overestimation or misinterpretation of these lesions can lead to unnecessary surgery for ultimately benign conditions. Diagnosing mediastinal cysts using MRI serves as a problem-solving modality in distinguishing between surgical and nonsurgical anterior mediastinal lesions. The pitfalls of MRI evaluation for anterior mediastinal cystic lesions are as follows: first, we acknowledge the limitation of T2-weighted images for evaluating benign cystic lesions. Due to variable contents within benign cystic lesions, such as hemorrhage, T2 signal intensity may be variable. Second, owing to extensive necrosis and cystic changes, the T2 shine-through effect may be seen on diffusion-weighted images (DWI), and small solid portions might be missed on enhanced images. Therefore, both enhancement and DWI with apparent diffusion coefficient values should be considered. An algorithm will be suggested for the diagnostic evaluation of anterior mediastinal cystic lesions, and finally, a management strategy based on MRI features will be suggested.
Programmed cell death ligand 1 (PD-L1) expression is an important biomarker for predicting response to immunotherapy in clinical practice. Hence, identification and characterization of factors that ...predict high expression of PD-L1 in patients is critical. Various studies have reported the association of PD-L1 expression with driver genetic status in non-small cell cancer; however, the results have been conflicting and inconclusive. We analyzed the relationship between PD-L1 expression and clinicopathological factors including driver genetic alterations in 1000 resected lung cancers using a clinically validated PD-L1 immunohistochemical assay. PD-L1 expression was significantly higher in squamous cell carcinoma (SCC) compared to adenocarcinomas. PD-L1 expression in adenocarcinoma was associated with higher N-stage, solid histologic pattern,
wild type, and
positive, but no significant association with the clinicopathological factors in SCC.
mutant adenocarcinomas with distinctive clinicopathologic features, especially solid histologic pattern and higher stage showed higher PD-L1 expression. To the best of our knowledge, this study is the largest to evaluate the association between PD-L1 expression and clinicopathological and molecular features in lung cancer with a highly prevalent
mutation. Therefore, our results are useful to guide the selection of lung cancer, even
-mutated adenocarcinoma patients with PD-L1 expression, for further immunotherapy.
Abstract Background There is controversy regarding palliative chemotherapy for large cell neuroendocrine carcinoma (LCNEC). We evaluated whether advanced LCNEC should be treated similarly to small ...cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Patients and methods The clinical reports and tumor specimens of 45 consecutive patients who were diagnosed with advanced LCNEC were reviewed. They were divided into SCLC ( n = 11) and NSCLC regimen groups ( n = 34) according to first-line chemotherapeutic regimens. Results Most patients were male (96%) and smokers (93%) with a median age of 64 years. Neuroendocrine differentiation was established in 42 (93%) tumors by immunohistochemical analyses. Regarding the efficacy of first-line chemotherapy in the SCLC and NSCLC regimen groups, the response rates were 73% and 50% ( P = 0.19), and the median progression-free survival times were 6.1 and 4.9 months ( P = 0.41), respectively. The difference in overall survival between the two treatment groups was 7.3 months (16.5 vs. 9.2 months, P = 0.10). There was also a considerable difference in the type and efficacy of salvage chemotherapeutic regimens between the two groups: salvage regimens with irinotecan, platinum, or taxanes were commonly used with relatively high objective responses in the SCLC regimen group, whereas frequently used agents in the NSCLC regimen group such as pemetrexed, gefitinib, or erlotinib were associated with no objective response. Conclusion Regarding palliative chemotherapy for advanced LCNEC, treatment similar to SCLC is more appropriate than NSCLC.
Background
Excessive muscle loss is an important prognostic factor in esophageal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT), as reported in our previous research.
Objective
In ...this pilot study, we prospectively tested the feasibility of a health coaching mobile app for preventing malnutrition and muscle loss in this patient population.
Methods
Between July 2019 and May 2020, we enrolled 38 male patients with esophageal cancer scheduled for NACRT. For 8 weeks from the start of radiotherapy (RT), the patients used Noom, a health coaching mobile app that interactively provided online advice about food intake, exercise, and weight changes. The skeletal muscle index (SMI) measured based on computed tomography and nutrition-related laboratory markers were assessed before and after RT. We evaluated the changes in the SMI, nutrition, and inflammatory factors between the patient group that used the mobile app (mHealth group) and our previous study cohort (usual care group). Additionally, we analyzed the factors associated with walk steps recorded in the app.
Results
Two patients dropped out of the study (no app usage; treatment changed to a definitive aim). The use (or activation) of the app was noted in approximately 70% (25/36) of the patients until the end of the trial. Compared to the 1:2 matched usual care group by propensity scores balanced with their age, primary tumor location, tumor stage, pre-RT BMI, and pre-RT SMI level, 30 operable patients showed less aggravation of the prognostic nutritional index (PNI) (–6.7 vs –9.8; P=.04). However, there was no significant difference in the SMI change or the number of patients with excessive muscle loss (∆SMI/50 days >10%). In patients with excessive muscle loss, the walk steps significantly decreased in the last 4 weeks compared to those in the first 4 weeks. Age affected the absolute number of walk steps (P=.01), whereas pre-RT sarcopenia was related to the recovery of the reduced walk steps (P=.03).
Conclusions
For esophageal cancer patients receiving NACRT, a health care mobile app helped nutritional self-care with less decrease in the PNI, although it did not prevent excessive muscle loss. An individualized care model with proper exercise as well as nutritional support may be required to reduce muscle loss and malnutrition.
PDF
