Differences In Clinicopathological Characteristics Research Articles

Risk factors and prognostic analysis of microscopic positive esophageal margins after radical surgery for proximal gastric cancer.

Proximal gastric cancer has been on the rise worldwide in recent years. A positive surgical margin may result in incomplete tumor and affect the prognosis of patients. This study aims to analyse the risk factors for and prognosis associated with microscopic positive esophageal margins (R1 resection) after radical surgery for proximal gastric cancer patients. This was a retrospective analysis of 316 patients with proximal gastric cancer who underwent surgical resection at the Department of Gastrointestinal Surgery of Hengshui People's Hospital from January 2013 to June 2018. Patients were divided into the R1 group (n = 24) and R0 group (n = 292) according to the esophageal margin status. Differences in clinicopathological characteristics and prognosis between the two groups were compared. Tumor location at the esophagogastric junction, Borrmann type 3/4, Lauren diffuse/mixed type, margin distance < 3cm, pT4 stage, and vascular invasion were identified as independent risk factors for positive esophageal margins in proximal gastric cancer patients (all P < 0.05). The 5-year overall survival rate was significantly lower in the R1 group than in the R0 group (45.8% vs. 64.2%, P < 0.05). Subgroup analysis revealed that the 5-year overall survival rate was significantly lower in the R1 group in the pT2-3 and pN0 stages (P < 0.05), while there was no significant difference in the pT4 and pN(+) stages (P > 0.05). Multivariate Cox regression analysis revealed that Borrmann type, Lauren type, pT stage, pN stage, and lymphovascular invasion were independent risk factors affecting the prognosis of patients with proximal gastric cancer (all P < 0.05), while esophageal margin status was not an independent risk factor affecting prognosis (P > 0.05). Positive esophageal margins in proximal gastric cancer are associated with various clinicopathological factors and lead to a worse prognosis in patients with pT2-3 and pN0 stages but do not affect the prognosis of patients with pT4 and pN(+) stages.

Diagnosis of TP53-mutated myeloid disease by the ICC and WHO fifth edition classifications

AbstractThe International Consensus (ICC) and World Health Organization fifth edition (WHO5) classifications introduced new, but differing, categories of myeloid disease defined by TP53 mutations. We reviewed a cohort of 188 cases of TP53-mutated myeloid disease to determine how diagnoses and outcomes differ between the 2 classifications. Overall, 120 (64%) cases were classified differently by the ICC and WHO5, including 24 of 80 (30%) cases with <20% blasts. These cases were discrepantly categorized primarily because of inclusion of complex karyotype (CK) as a surrogate for biallelic TP53 inactivation only in the ICC. However, there were no significant differences in clinicopathologic characteristics or overall survival between cases categorized as TP53-mutated disease by both classifications and those with a single TP53 mutation and CK, suggesting that CK reliably identifies TP53-mutated cases with biallelic TP53 inactivation. Most of cases of acute myeloid leukemia (AML; 96/102 [94%]) were discrepantly diagnosed between the ICC and WHO5 because of the introduction of AML with mutated TP53 as a distinct category only in the ICC. Nearly all of these were instead diagnosed as AML, myelodysplasia related (AML-MR) by WHO5. However, when compared with a separate cohort of patients with AML-MR without TP53 mutations, patients with TP53-mutated AML showed a distinct genetic profile and significantly worse overall survival, supporting the inclusion of AML with mutated TP53 as a distinct disease category. Overall, our results show that a significant percentage of TP53-mutated myeloid disease is classified differently by the ICC and WHO5 and highlight areas to address in future classification systems.

Increased risk of breast cancer among premenopausal women with pituitary gland disorders in Taiwan: a population-based matched-cohort study.

An association between pituitary gland disorders and breast cancer remains controversial. We examined the prevalence and risk of breast cancer over a 15-year follow-up period or until diagnosed as breast cancer among premenopausal women (12-49 years old) with pituitary gland disorders in Taiwan. This retrospective matched-cohort study included 52,265 individuals each in the study group (women with pituitary gland disorders) and the matched control group from 2000 to 2004 identified using Taiwan's National Health Insurance Research Database. We compared sociodemographic characteristics and medical disorders between the two groups and examined the differences in clinicopathological characteristics of breast cancer. We also estimated the risk of breast cancer over 15 years of follow-up (median follow-up time = 11.2 years). Overall, 924 (1.8%) and 734 (1.4%) patients in the study and control groups, respectively, were diagnosed as having breast cancer (p < 0.001). Over the 15-year follow-up period, the study group had a 1.16-fold (95% confidence interval [CI] = 1.04-1.29, p < 0.05) increased risk of breast cancer compared with the control group. This risk was particularly pronounced in the 20-29 and 30-39 age groups (adjusted hazard ratio = 1.46 and 1.25, respectively; 95% CI = 1.15-1.86 and 1.07-1.44, p value < 0.01, respectively). Our findings reveal a relationship between pituitary gland disorders and breast cancer among premenopausal women in an Asian country. Physicians should check for signs of breast cancer in premenopausal women with pituitary gland disorders for early detection and treatment. Future studies should confirm our findings and clarify the causal relationship.

Identification of novel markers for neuroblastoma immunoclustering using machine learning.

Due to the unique heterogeneity of neuroblastoma, its treatment and prognosis are closely related to the biological behavior of the tumor. However, the effect of the tumor immune microenvironment on neuroblastoma needs to be investigated, and there is a lack of biomarkers to reflect the condition of the tumor immune microenvironment. The GEO Database was used to download transcriptome data (both training dataset and test dataset) on neuroblastoma. Immunity scores were calculated for each sample using ssGSEA, and hierarchical clustering was used to categorize the samples into high and low immunity groups. Subsequently, the differences in clinicopathological characteristics and treatment between the different groups were examined. Three machine learning algorithms (LASSO, SVM-RFE, and Random Forest) were used to screen biomarkers and synthesize their function in neuroblastoma. In the training set, there were 362 samples in the immunity_L group and 136 samples in the immunity_H group, with differences in age, MYCN status, etc. Additionally, the tumor microenvironment can also affect the therapeutic response of neuroblastoma. Six characteristic genes (BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM) were identified by machine learning, and these genes are associated with multiple immune-related pathways and immune cells in neuroblastoma. BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM may serve as biomarkers that reflect the conditions of the immune microenvironment of neuroblastoma and hold promise in guiding neuroblastoma treatment.

Predictive Value of Immune Activity Changes in Breast Cancer Patients Treated With Dose-dense Neoadjuvant Chemotherapy: A Retrospective Study.

Dose-dense chemotherapy is recommended for patients with breast cancer who have a high recurrence risk. However, whether dose-dense neoadjuvant chemotherapy (ddNAC) improves patient prognoses compared to the normal-dose regimen remains controversial. In this study, we evaluated the predictive value of immune activities on short-term outcomes for patients treated with ddNAC. We classified 82 patients with human epidermal growth factor receptor 2-negative breast cancer treated with NAC into a normal dose group (62 patients) and ddNAC group (20 patients) and examined the differences in clinicopathological features. The ddNAC group was further divided according to patient responses to NAC and the predictive factors for pathological complete response (pCR) were evaluated. There were no differences in the clinicopathological features before NAC between the normal dose and ddNAC groups. Although the pCR rates tended to be higher in the ddNAC group compared than those in the normal dose group (35.0% vs. 25.8%), there was not significant difference (p=0.264). Among all patients treated with ddNAC, the absolute lymphocyte count decreased and the neutrophil-to-lymphocyte ratio increased during dose-dense doxorubicin plus cyclophosphamide treatment. There was no significant correlation between the pCR and any of the clinicopathological parameters tested including systemic peripheral markers and tumor-infiltrating lymphocyte levels. ddNAC affected the levels of systemic peripheral immune markers. However, monitoring these markers may not be useful for predicting responses to ddNAC.

Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix: Comparison of Its Clinicopathological Characteristics and Programmed Death-ligand 1 Expression Status With Those of Other Endocervical Adenocarcinomas.

Invasive stratified mucin-producing carcinoma (ISMC) is a rare but aggressive variant of endocervical adenocarcinoma (EAC). The aim of this study was to investigate the differences in clinicopathological features, patient outcomes, and programmed death-ligand 1 (PD-L1) expression among ISMC, usual-type EAC (UEA), and gastric-type EAC (GEA). PD-L1 22C3 immunostaining was performed using 20 ISMCs, 20 UEAs, and 20 GEAs. Combined positive score (CPS) method was used to assess PD-L1 immunoreactivity. ISMC was diagnosed at a younger age and showed a more advanced stage and shorter survival than UEA. The disease-free survival (DFS) and overall survival (OS) rates of ISMC patients were lower than those of UEA but comparable to those of GEA. ISMC type was an independent prognostic factor for predicting short DFS [hazard ratio (HR)=2.790, 95% confidence interval (CI)=1.153-6.756] and OS (HR=6.071, 95%CI=1.257-29.327). All ISMCs showed PD-L1 over-expression with a mean CPS of 44.5 (range=10-100), which was higher than those of UEA (mean CPS=8.2) and GEA (mean CPS=6.5). PD-L1 positivity (CPS≥1) was also an independent prognostic factor for worse OS (HR=2.472, 95%CI=1.097-5.570). Despite PD-L1 over-expression, ISMC patients treated with pembrolizumab showed no clinical response. All examined ISMCs over-expressed PD-L1. ISMC showed higher PD-L1 expression than UEA and GEA and worse survival than UEA. PD-L1 over-expression was found to be a significant predictor for worse DFS and OS in patients with ISMC. Our data suggest that PD-L1 over-expression is associated with poor ISMC prognosis.

A real-world retrospective study to assess efficacy and safety of alectinib as adjuvant therapy in IB-IIIB NSCLC patients harboring ALK rearrangement.

Alectinib has demonstrated promising disease-free survival (DFS) benefit for early-stage non-small cell lung cancer (NSCLC) patients with ALK rearrangement positive in phase 3 ALINA trial. However, real-world evidence for the efficacy and safety of alectinib in early-stage ALK-positive NSCLC is limited. We retrospectively reviewed 68 patients with stage IB-IIIB ALK-positive NSCLC who underwent complete pulmonary resections from April 2010 to July 2023 at a single institution. 38 (55.9%) enrolled patients had N2 lymph node metastasis, and 17 (24.9%) patients had multi-station N2 metastasis. Patients were stratified into two groups according to the adjuvant treatment regimen, with 19 patients in the alectinib group and 49 patients in the chemotherapy group. There were no significant differences in clinicopathological characteristics between the two groups. After curative resection surgery, patients in alectinib group received oral alectinib at a dose of 600 mg twice daily and patients in chemotherapy group received platinum-based doublet chemotherapy regimen every 3 weeks for 4 cycles. The primary endpoint was 3-year DFS. The Kaplan-Meier method was used to estimate DFS and overall survival (OS). Safety analyses were conducted by comparing the incidence of adverse events between the two groups. At the last follow-up date (January 22th, 2024), A total of 1 (5.3%) and 28 (57.1%) DFS events were observed in alectinib group and chemotherapy group respectively. The 3-year DFS showed significant improvement in the alectinib group compared with chemotherapy group (91.7% vs 60.7%, P=0.051). In the IIIAN2 subgroup, the 3-year DFS rate in the alectinib group reached a satisfactory 87.5%. In both groups, the majority of AEs were graded as level 1 or 2, No grade 3-4 AEs were observed in alectinib group. Alectinib, as adjuvant therapy, demonstrated favorable efficacy and manageable safety in patients with completely resected ALK-positive stage I B-IIIB non-small cell lung cancer. A limitation of this study is the small sample size, and a larger-scale real-world sample study is needed to further evaluate the efficacy and safety of alectinib as adjuvant therapy.

MRI-based radiomics for stratifying recurrence risk of early-onset rectal cancer: a multicenter study

Early-onset rectal cancer (EORC) is characterized by a unique disease process with different clinicopathological features compared with late-onset rectal cancer (LORC). Research on the risk of recurrence in EORC patients, however, is limited. We aim to develop a predictive model to accurately predict EORC recurrence risk. Rectal cancer patients who underwent radical surgery and T2-weighted imaging and diffusion-weighted imaging magnetic resonance imaging (MRI) were retrospectively enrolled from three medical institutions from November 2012 to November 2018. Differences in clinicopathological characteristics between EORC and LORC were compared. Five prediction models for disease-free survival were constructed based on clinicopathological variables and five radiomic features from pretreatment MRI of the EORC. A fixed cut-off value calculated in the training set was used to stratify EORC patients into high-risk and low-risk groups of post-operative recurrence. Model performance was evaluated by concordance index (C-index) and receiver operating characteristic curve. A total of 264 EORC patients (median age, 43 years, 163 males) and 778 LORC patients (median age, 62 years, 520 males) were enrolled. Pretreatment positive carcinoembryonic antigen [hazard ratio (HR)= 2.84, P= 0.006], pathological positive lymph node status (pN positive) [HR= 2.86, P= 0.011] and MRI-based radiomics score [HR= 2.72, P < 0.001] are independent risk factors for disease-free survival in EORC patients. The EORC-ClinPathRadiom model, constructed by integrating the clinicopathological characteristics and MRI-based radiomics features of EORC, showed C-index of 0.82, 0.82, and 0.81 in the training, internal, and external test sets, respectively. This model effectively stratified EORC patients into high risk and low risk of recurrence (HRs for the training, internal, and external test sets were 8.96, 6.81, and 7.46, respectively). The EORC-ClinPathRadiom model can effectively predict and stratify the risk of post-operative recurrence in EORC patients.

560. ANALYSIS OF CLINICOPATHOLOGICAL CHARACTERISTICS AND PROGNOSIS OF SYNCHRONOUS MULTIPLE PRIMARY ESOPHAGEAL SQUAMOUS CELL CARCINOMAS (SMP-ESCC) AFTER RECEIVING NEOADJUVANT THERAPY

Abstract Background SMP-ESCC is a rare subtype of esophageal cancer. Esophagectomy after neoadjuvant therapy became the standard treatment. However, there are still no studies comparing SMP-ESCC and single lesion esophageal squamous cell carcinomas (SL-ESCC) after neoadjuvant therapy. Our study aimed to analyze the differences of clinicopathological features and prognosis between SMP-ESCC and SL-ESCC. Methods All patients who received neoadjuvant therapy (Platinum-based chemotherapy regimen with or without radiotherapy at a total dose of 41.4-50.4 Gy/23-28 times) and plan esophagectomy were consecutively collected from January 2019 to March 2023. SMP-ESCC was defined as multiple lesions in the esophagus found at the time of diagnosis by endoscopy, with lesions more than 1 cm apart by normal mucosa, and diagnosed by pathology as squamous carcinoma or Tis. The cohort was divided into two groups (SMP-ESCC vs. SL-ESCC) with a 1:1 ratio through propensity score matching, and the differences in clinicopathological features and prognosis were compared. Results A total of 926 patients were enrolled, 58 (6.4%) patients had the type of SMP-ESCC. SMP-ESCC had higher pN stages (p&amp;lt;0.001), and a lower rate of pathological complete response (13.8% vs. 29.4%, p=0.016). SMP-ESCC had a poorer OS (49.8% vs. 65.0%, p=0.020) and DFS (21.1% vs. 61.0%, p&amp;lt;0.001) (Figure A-B). After matching, SMP-ESCC had a poorer 3-year DFS (33.5% vs. 60.9%, p=0.020) and a trend of poorer OS (51.0% vs. 71.7%, p=0.086) (Figure 1 C-D). Multivariate Cox regression analysis indicated that SMP-ESCC was an independent risk factor for OS (HR: 2.258, 95%CI: 1.006-5.068, p=0.048) and DFS (HR: 2.175, 95%CI: 1.157-4.092, p=0.016). Conclusion SMP-ESCC had a poorer response to neoadjuvant therapy compared to patients with SL-ESCC. And SMP-ESCC was an independent risk factor for OS and DFS, leading to a poorer prognosis. Therefore, SMP-ESCC need more rational and effective treatment in the perioperative period.

231. DESCRIBING THE LANDSCAPE OF ESOPHAGECTOMY BETWEEN EASTERN AND WESTERN ESOPHAGEAL SOCIETIES: COMPARATIVE STUDIES FROM THE JAPANESE NCD AND DUTCH DUCA

Abstract Objective Differences in clinicopathological characteristics of patients with esophageal cancer between countries may exist and impact on perioperative and surgical treatment as well as outcomes. Identification of these discrepancies may help the interpretation of present and future studies. Methods Data on patient demographics, comorbidity, pathology, surgical procedure, and short-term outcomes were retrieved, and compared between countries. Furthermore, we conducted a risk factor analysis focused on the major postoperative complications after esophagectomy to reveal the similarities and differences in risk factors. Results The mean annual number of resections for oesophageal cancer was 6673 in NCD (5.3 cases per 100,000 population) and 551 (3.1 cases per 100,000 population) in DUCA. Patients from the NCD were older and had a lower BMI. Complete minimally invasive esophagectomy was performed in 52.7% in NCD and 85% in DUCA. A cervical anastomosis was performed in 83.5% of patients in the NCD and in 33.8% in the DUCA likely reflecting differences in the location of primary tumors. Mortality within 30 days after surgery in the NCD and DUCA was 0.8% and 2.7%, respectively. Risk factors for postoperative major complications were similar between countries. Conclusions Although there were differences in patient variables, no significant differences were observed in short-term outcomes and risk factors of postoperative complications. The current results provide insight into contemporary demographics and outcomes of esophageal cancer resections from two an Asian and Western perspective.

Breast-conserving surgery versus modified radical mastectomy in T1-2N3M0 stage breast cancer: a propensity score matching analysis.

Breast-conserving surgery (BCS) plus radiotherapy and mastectomy exhibit highly comparable prognoses for early-stage breast cancer; however, the safety of BCS for T1-2N3M0 breast cancer remains unclear. This study compared long-term survival for BCS versus (vs.) modified radical mastectomy (MRM) among patients with T1-2N3M0 breast cancer. Data of patients with T1-2N3M0 breast cancer were extracted from the Surveillance, Epidemiology, and End Results database. Eligible patients were divided into 2 groups, BCS and MRM; Pearson's chi-squared test was used to estimate differences in clinicopathological features. Propensity score matching (PSM) was used to balance baseline characteristics. Univariate and multivariate analyses were performed to investigate the effects of surgical methods and other factors on breast cancer-specific survival (BCSS) and overall survival (OS). In total, 2124 patients were included; after PSM, 596 patients were allocated to each group. BCS exhibited the same 5-year BCSS (77.9% vs. 77.7%; P = 0.814) and OS (76.1% vs. 74.6%; P = 0.862) as MRM in the matched cohorts. Multivariate survival analysis revealed that BCS had the same BCSS and OS as MRM (hazard ratios [HR] 0.899 [95% confidence intervals (CI) 0.697-1.160], P = 0.413 and HR 0.858 [95% CI 0.675-1.089], P = 0.208, respectively); this was also seen in most subgroups. BCS demonstrated better BCSS (HR 0.558 [95% CI 0.335-0.929]; P = 0.025) and OS (HR 0.605 [95% CI 0.377-0.972]; P = 0.038) than MRM in those with the triple-negative subtype. BCS has the same long-term survival as MRM in T1-2N3M0 breast cancer and may be a better choice for triple-negative breast cancer.

Differential neuropsychiatric associations of plasma biomarkers in older adults with major depression and subjective cognitive decline

Older adults with major depressive disorder (MDD) or early cognitive decline during the subjective cognitive decline (SCD) stage may exhibit neuropsychiatric symptoms such as anxiety, depression, and subtle cognitive impairment. The clinicopathological features and biological mechanisms of MDD differ from those of SCD among older adults; these conditions thus require different treatment strategies. This study enrolled 82 participants above 50 years old with normal cognitive levels from the communities to examine biomarker–behavior correlations between MDD (n = 23) and SCD (n = 23) relative to a normal control (NC) group (n = 36). Multidomain assessments were performed for all participants, including immunomagnetic reduction tests to detect plasma beta-amyloid (Aβ), total tau (Tau), phosphorylated tau-181 (p-Tau181), neurofilament light chain, and glial fibrillary acidic protein (GFAP). This study observed that depressive symptoms in MDD were associated with amyloid pathology (plasma Aβ40 vs. HADS-D: R = 0.45, p = 0.031; Aβ42/Aβ40 vs. HADS-D: R = −0.47, p = 0.024), which was not observed in the NC (group difference p < 0.05). Moreover, cognitive decline in MDD was distinguished by a mixed neurodegenerative process involving amyloid (plasma Aβ42 vs. facial memory test: R = 0.48, p = 0.025), tau (Tau/Aβ42 vs. digit symbol substitution test (DSST): R = −0.53, p = 0.01), and astrocytic injury (plasma GFAP vs. Montreal cognitive assessment score: R = −0.44, p = 0.038; plasma GFAP vs. DSST: R = −0.52, p = 0.014), findings that did not apply to the NC (group difference p < 0.05). Moreover, this study revealed different biomarker–behavior correlations between individuals with SCD and the NC. Compared with the NC, cognitive decline in the SCD group might be unrelated to amyloid pathology and instead might be early manifestations of tau pathology. This study underscores the difference in clinicopathological features between MDD and SCD among older adults, which differ from those of the NC. These findings enhance our understanding of the mechanisms underlying MDD and SCD in older individuals.

Expression profiles of cadherin 17 and claudin 18.2 in comparison with peptide hormonal expression in pancreatic neuroendocrine tumours: Implications for targeted immunotherapy

Cadherin 17 (CDH17) and claudin 18.2 (CLDN18.2) are highly selective markers of intestinal and gastric lineages and are expressed in adenocarcinomas of various organs. They have also been identified as potential targets for immunotherapy. Expression of CDH17 and CLDN18.2 has been observed in a subset of pancreatic neuroendocrine tumours (PanNETs). This study investigates the immunohistochemical expression of CDH17 and CLDN18 in PanNETs in comparison with hormonal expression profiles to provide baseline data for determining candidate indications for targeted therapy with CDH17 and CLDN18.2 in PanNETs, including insulinomas (n = 22), glucagonomas (n = 13), gastrinomas (n = 3), serotoninomas (n = 2) and PanNETs not otherwise specified (NOS) (n = 17). In the normal pancreas, CDH17 was expressed in the lateral membrane of ducts and some islet cells, whereas CLDN18 was occasionally expressed in the intercalated ducts and centroacinar cells. In PanNETs, CDH17 and CLDN18 was detected by membranous staining. CDH17 expression was observed in 10 of 17 (58.8 %) PanNETs NOS, 3 of 13 (23.1 %) glucagonomas, 1 of 3 (33.3 %,) gastrinomas, 1 of 2 (50 %) serotoninomas, and none of the insulinomas. According to predefined criteria, 7 of 17 (41.2 %) PanNETs NOS, 1 of 3 (33.3 %) gastrinomas, and 1 of 2 (50 %) serotoninomas were classified as CDH17-positive. There were no significant differences in clinicopathological features between CDH17-positive and CDH17-negative PanNETs, except for a higher tumour grade in the former (p<0.05). For CLDN18, expression was noted in 2 out of 3 (66.7 %) gastrinomas, one with focal staining and the other with diffuse staining. One of three (33.3 %) gastrinomas was classified as CLDN18-positive using predefined criteria. These findings suggest that a particular subset of PanNETs, including PanNET NOS, gastrinoma, and serotoninoma, may be potential candidates for CDH17-targeted immunotherapy. Additionally, gastrinoma may be a potential candidate for immunotherapy targeting CLDN18.2.

Select black men are potential candidates for prostate hemi-ablation based on radical prostatectomy histopathology for intermediate-risk prostate cancer-a multicenter SEARCH cohort study.

Partial gland ablation (PGA) is increasingly popular as a treatment for men with intermediate-risk prostate cancer (IR-PCa) to preserve functional outcomes while controlling their cancer. We aimed to determine the impact of race and clinical characteristics on the risk of upstaging (≥pT2c) and having adverse pathological outcomes including seminal vesicle invasion (SVI), extra prostatic extension (EPE) and lymph node invasion (LNI) at radical prostatectomy (RP) among men with IR disease eligible for PGA with hemi-ablation (HA). Retrospective analysis. Multicenter. We studied patients diagnosed with unilateral IR-PCa treated with RP between 1988 and 2020 at 9 different Veterans Affairs hospitals within the SEARCH cohort. We analyzed differences in clinicopathological characteristics and outcome variables (odds of ≥pT2c and SVI, EPE and LNI) by race using multivariable logistic regression after adjusting for covariates. Among 3127 patients, 33% were African American (AA) men with unilateral IR-PCa undergoing RP. Compared to non-AA men, AA individuals were younger (61 vs. 65 years, p < 0.001), presented with a higher prostate specific antigen (PSA) category (≥10 ng/ml; 34 vs. 26%, p < 0.001), and had a lower clinical stage (p < 0.001). Among the 2,798 (89.5%) with ≥pT2c stage, AA men exhibited higher ≥ pT2c rates (93 vs. 89%, p < 0.001), primarily due to increased pT2c staging (64 vs. 57%), where upstaging beyond pT2 was lower than non-AA men (29 vs. 32%). On multivariable analysis, AA men were found to have higher odds of ≥pT2c (odds ratio [OR]: 1.39 CI, 1.02-1.88, p = 0.04), lower odds of EPE (OR: 0.73 CI, 0.58-0.91, p < 0.01) and no statistically significant associations with LNI (OR: 0.79 CI, 0.42-1.46, p = 0.45) and SVI (OR: 1 CI, 0.74-1.35, p = 0.99) compared to non-AA men. On multivariable analysis, clinical features associated with higher odds of ≥pT2c were pre-operative PSA ≥ 15 (OR = 2.07, P = 0.01) and higher number of positive cores (HPC) on biopsy (OR = 1.36, P < 0.001). Similarly, PSA ≥ 15, Gleason grade ≥3 and HPC on biopsy were associated with higher odds of SVI, EPE and LNI, respectively. In men with IR-PCa undergoing RP, AA men demonstrated an overall higher likelihood of ≥pT2c with lower upstaging beyond pT2, lower likelihood of EPE and no significant difference in likelihood of SVI and LNI compared to non-AA men. These findings support select AA men to be potential candidates for PGA, such as HA. Clinical factors are predictive of higher pathological stage and adverse pathological outcomes at RP and could be considered when selecting candidates for PGA.

Integrated single-cell and bulk RNA sequencing analyses identify an immunotherapy nonresponse-related fibroblast signature in gastric cancer.

Factors that determine nonresponse to immune checkpoint inhibitor (ICI) remain unclear. The protumor activities of cancer-associated fibroblasts (CAFs) suggest that they are potential therapeutic targets for cancer treatment. There is, however, a lack of CAF-related signature in predicting response to immunotherapy in gastric cancer (GC). Single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data of GC immunotherapy were downloaded from the Gene Expression Omnibus database. Bulk RNA-seq data were obtained from The Cancer Genome Atlas. The R package 'Seurat' was used for scRNA-seq data processing. Cellular infiltration, receptor-ligand interactions, and evolutionary trajectory analysis were further explored. Differentially expressed genes affecting overall survival were obtained using the limma package. Weighted Gene Correlation Network Analysis was used to identify key modules of immunotherapy nonresponder. Prognostic model was constructed by univariate Cox and least absolute contraction and selection operator analysis using the intersection of activated fibroblast genes (AFGs) with key module genes. The differences in clinicopathological features, immune microenvironment, immunotherapy prediction, and sensitivity to small molecule agents between the high- and low-risk groups were further investigated. Based on scRNA-seq, we finally identified 20 AFGs associations with the prognosis of GC patients. AFGs' high expression levels were correlated with both poor prognosis and tumor progression. Three genes ( FRZB , SPARC , and FKBP10 ) were identified as immunotherapy nonresponse-related fibroblast genes and used to construct the prognostic signature. This signature is an independent significant risk factor affecting the clinical outcomes of GC patients. Remarkably, there were more CD4 memory T cells, resting mast cells, and M2 macrophages infiltrating in the high-risk group, which was characterized by higher tumor immune exclusion. Moreover, patients with higher risk scores were more prone to not respond to immunotherapy but were more sensitive to various small molecule agents, such as memantine. In conclusion, this study constructed a fibroblast-associated ICI nonresponse gene signature, which could predict the response to immunotherapy. This study potentially revealed a novel way to overcome immune resistance in GC.

Clinical Implications of the Degree of Pancreatic Invasion in Ampulla of Vater Carcinoma.

Ampulla of Vater carcinoma (AVC) stage T3 was subdivided according to the degree of pancreatic invasion into T3a (≤ 0.5cm) and T3b (> 0.5cm) by the 8th edition of the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) cancer staging system. However, the differences in clinicopathological features and survival outcomes between the two categories have not been well discussed. We retrospectively analyzed 133 consecutive patients who underwent pancreatoduodenectomy for AVC at our institution between 2002 and 2020. Clinicopathological features and survival outcomes of patients with AVC were analyzed, with a focus on the depth of pancreatic invasion. In addition, the survival outcomes of patients with T3 AVC were compared with those of patients with resectable pancreatic head carcinoma (R-PhC) who underwent pancreatoduodenectomy during the same period. The overall survival (OS) in patients with T3b AVC (n = 12) was significantly worse than that in patients with T3a AVC (n = 39) [median survival time (MST) 9.2 vs. 74.5 months, p < 0.001). A multivariate analysis identified T3b tumor (hazard ratio 5.64, p = 0.009) as an independent prognostic factor. The OS of patients with T3a AVC was significantly better than that of patients with R-PhC who received adjuvant chemotherapy (n = 276, MST 35.0 months, p = 0.007). In contrast, the OS of patients with T3b AVC tended to be worse than that of patients with R-PhC managed without adjuvant chemotherapy, although this difference was not statistically significant (n = 163; MST, 17.5; p = 0.140). AVC with > 0.5cm invasion into the pancreas was associated with poor survival and represented advanced tumor progression to systemic disease.

The Clinicopathological Features and Prognoses of Lower Uterine Segment Cancer: A Retrospective, Single-Center Cohort Study.

This study used single-center data to analyze the clinicopathological features of site-specific endometrial cancer. Patients with endometrial carcinoma who had undergone surgery at Peking Union Medical College Hospital, China, between March 2016 and January 2022 were enrolled. Clinical information and pathological characteristics were summarized, and microsatellite status was analyzed using the immunohistochemical method. Patient prognoses were measured in terms of the rates of overall survival and progression-free survival. The mean patient age was 49 years (ranging: from 25 to 76 years old), and there was no difference in clinicopathological features between endometrioid and type II endometrial carcinoma in LUSC. The ER and PR expression ratios were 80.4% and 64.3%, respectively, in this LUSC cohort, and the MMR deficiency ratio was 33.9%, including 39.6% in endometrioid carcinoma and 15.4% in type II endometrial carcinoma. Combined MSH2&MSH6 loss was more common than combined MLH1&PMS2 being unexpressed (16.1% vs 12.5%), and dMMR patients differed significantly from the pMMR group in terms of vascular invasion (P=0.003). The combination of chemotherapy and radiotherapy did not provide a statistically significant improvement in prognosis compared to chemotherapy alone. The results of this study showed that LUSC patients tended to be younger and their tumors had less expression of hormone markers. The biological behavior of both endometrioid cancer and type II EC may be similar when EC occurs in this area. Furthermore, this type of tumor also showed a higher incidence of vascular invasion, and the combination of chemotherapy and radiotherapy did not provide significant improvement. Thus, successful treatment of LUSC tumors requires aggressive surgical intervention and a more effective postoperative treatment approach.

Integrating single-cell RNA-seq to identify fibroblast-based molecular subtypes for predicting prognosis and therapeutic response in bladder cancer.

Bladder cancer (BLCA) is a highly aggressive and heterogeneous disease, posing challenges for diagnosis and treatment. Cancer immunotherapy has recently emerged as a promising option for patients with advanced and drug-resistant cancers. Fibroblasts, a significant component of the tumor microenvironment, play a crucial role in tumor progression, but their precise function in BLCA remains uncertain. Single-cell RNA sequencing (scRNA-seq) data for BLCA were obtained from the Gene Expression Omnibus database. The R package "Seurat" was used for processing scRNA-seq data, with uniform manifold approximation and projection (UMAP) for downscaling and cluster identification. The FindAllMarkers function identified marker genes for each cluster. Differentially expressed genes influencing overall survival (OS) of BLCA patients were identified using the limma package. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, and chemotherapeutic drug sensitivity between high- and low-risk groups were investigated. RT-qPCR and immunohistochemistry validated the expression of prognostic genes. Fibroblast marker genes identified three molecular subtypes in the testing set. A prognostic signature comprising ten genes stratified BLCA patients into high- and low-score groups. This signature was validated in one internal and two external validation sets. High-score patients exhibited increased immune cell infiltration, elevated chemokine expression, and enhanced immune checkpoint expression but had poorer OS and a reduced response to immunotherapy. Six sensitive anti-tumor drugs were identified for the high-score group. RT-qPCR and immunohistochemistry showed that CERCAM, TM4SF1, FN1, ANXA1, and LOX were highly expressed, while EMP1, HEYL, FBN1, and SLC2A3 were downregulated in BLCA. A novel fibroblast marker gene-based signature was established, providing robust predictions of survival and immunotherapeutic response in BLCA patients.

HER2-negative or low expression as an unfavorable prognostic factor in patients with stage I/II uterine carcinosarcoma.

Uterine carcinosarcoma (UCS) is uncommon high-grade endometrial cancer with limited treatment options. We evaluated the prognostic significance of human epidermal growth factor receptor 2 (HER2) expression and HER2 gene amplification within large cohorts of UCS, and clarify clinicopathologic characteristics of HER2-low UCS. We examined HER2 protein expression in 148 patients of UCS using in vivo diagnostic HER2 immunohistochemistry (IHC) kits and HER2 gene amplification using fluorescence in situ hybridization (FISH) in 72 patients. HER2 IHC score was evaluated according to the latest American Society of Clinical Oncology/College of American Pathologists criteria for gastric cancer, which was negative in 41 patients, low expression of 1+ was observed in 57 patients, and HER2 high expression was observed in 50 patients (2+ in 38 and 3+ in 12 patients). There was no significant statistical difference in clinicopathological characteristics based on HER2 protein expression status. HER2 negative and low expression compared to high expression revealed poor overall survival in stage I/ II. The concordance between IHC and FISH results were relatively low compared to other cancer types (HER2 IHC score 1+, 2+, and 3+ were 5%, 15%, and 50%), and combining these results was not efficient as a prognostic factor in UCS. In contrast, the HER2 IHC score alone was a prognostic factor in stage I/II UCS. HER2 low group did not show specific clinicopathologic features. Since the HER2 IHC score low in advanced UCS is a predictive factor, stratification of UCS using HER2 IHC score for HER2 IHC score low group and developing adjuvant therapy may be proposed in the near future.

Identification of a basement membrane-related gene signature for predicting prognosis, immune infiltration, and drug sensitivity in colorectal cancer.

Colorectal cancer (CRC) is the most common malignancy affecting the gastrointestinal tract. Extensive research indicates that basement membranes (BMs) may play a crucial role in the initiation and progression of the disease. Data on the RNA expression patterns and clinicopathological information of patients with CRC were sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. A BM-linked risk signature for the prediction of overall survival (OS) was formulated using univariate Cox regression and combined machine learning techniques. Survival outcomes, functional pathways, the tumor microenvironment (TME), and responses to both immunotherapy and chemotherapy within varying risk classifications were also investigated. The expression trends of the model genes were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and the Human Protein Atlas (HPA) database. A nine-gene risk signature containing UNC5C, TINAG, TIMP1, SPOCK3, MMP1, AGRN, UNC5A, ADAMTS4, and ITGA7 was constructed for the prediction of outcomes in patients with CRC. The expression profiles of these candidate genes were verified using RT-PCR and the HPA database and were found to be consistent with the findings on differential gene expression in the TCGA dataset. The validity of the signature was confirmed using the GEO cohort. The patients were stratified into different risk groups according to differences in clinicopathological characteristics, TME features, enrichment functions, and drug sensitivities. Lastly, the prognostic nomogram model based on the risk score was found to be effective in identifying high-risk patients and predicting OS. A basement membrane-related risk signature was constructed and found to be effective for predicting the prognosis of patients with CRC.