Pathological TNM Stage Research Articles

The effect of anti-spasmodic administration on the accuracy of magnetic resonance imaging staging of rectal cancer.

Magnetic resonance imaging is the primary method for local staging in rectal cancer patients. Administration of intravenous (IV) hyoscine butylbromide is thought to improve accuracy, but there are contraindications and potential adverse effects. The aim was to assess the efficacy of IV hyoscine butylbromide on the accuracy of MRI rectal cancer staging of T2 and T3 rectal cancers. A retrospective cohort study was carried out on patients prospectively recorded on the Cabrini Monash colorectal neoplasia database. A total of 74 patients (53 males, 21 females) MRI pelvis and rectums with antispasmodics were performed at multiple centres in the pre-operative setting between 2010 and 2016. Each patient underwent total mesorectal excision of rectal cancer. The excision specimens were assessed and given a pathological TNM stage, which was considered the reference standard. There was no statistically significant impact on the overall accuracy of MRI rectal cancer staging between patient groups who received IV hyoscine butylbromide and groups who did not receive IV hyoscine butylbromide. The accuracy of T2 and T3 staged rectal cancers was more likely to be correct (compared with T1 cancers) with the administration of IV hyoscine butylbromide. Still, there was no improvement in the accuracy of N-staging. Given the potential side effects and adverse outcomes of IV anti-spasmodic agents, department protocols may need to be re-assessed regarding the prescription of these medications for MRI rectal cancer staging.

DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation.

DPY30, a core subunit of the SET1/MLL histone H3K4 methyltransferase complexes, plays an important role in diverse biological functions through the epigenetic regulation of gene transcription, especially in cancer development. However, its involvement in human colorectal carcinoma (CRC) has not been elucidated yet. Here we demonstrated that DPY30 was overexpressed in CRC tissues, and significantly associated with pathological grading, tumor size, TNM stage, and tumor location. Furthermore, DPY30 knockdown remarkably suppressed the CRC cell proliferation through downregulation of PCNA and Ki67 in vitro and in vivo, simultaneously induced cell cycle arrest at S phase by downregulating Cyclin A2. In the mechanistic study, RNA-Seq analysis revealed that enriched gene ontology of cell proliferation and cell growth was significantly affected. And ChIP result indicated that DPY30 knockdown inhibited H3 lysine 4 trimethylation (H3K4me3) and attenuated interactions between H3K4me3 with PCNA, Ki67 and cyclin A2 respectively, which led to the decrease of H3K4me3 establishment on their promoter regions. Taken together, our results demonstrate overexpression of DPY30 promotes CRC cell proliferation and cell cycle progression by facilitating the transcription of PCNA, Ki67 and cyclin A2 via mediating H3K4me3. It suggests that DPY30 may serve as a potential therapeutic molecular target for CRC.

Prognostic value of postoperative ctDNA detection in patients with early non-small cell lung cancer: a systematic review and meta-analysis.

Circulating tumor DNA (ctDNA) has emerged as a potential biomarker for monitoring early non-small cell lung cancer (ENSCLC), particularly after radical surgery. However, the prognostic value of postoperative ctDNA is still being investigated due to the small sample size and heterogeneity of patients with ENSCLC in current trials. Moreover, the potential clinical utility of ctDNA assessment for administering adjuvant therapy (AT) in patients with ENSCLC is also an important area of active research. We aimed to identify the prognostic value of postoperative ctDNA detection in ENSCLC patients with stages I-III. This study type is a systematic review and meta-analysis. We conducted a search in the Cochrane Library, Embase, PubMed, and ScienceDirect for prospective or retrospective investigations involving patients with ENSCLC, gathering outcomes based on predefined end points. The literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the Newcastle-Ottawa scale was employed to carry out a quality evaluation of the included studies. The primary end point of the study was to evaluate the association of ctDNA status in two time points (within 1 month after surgery and long-term postoperative monitoring with more than 3 months) with relapse-free survival (RFS) and overall survival (OS). In addition, the study investigated the role of ctDNA in predicting the response to AT. The secondary end points of the study were to determine the impact of ctDNA on RFS and OS in different subgroups of ENSCLC patients based on pathological subtypes and TNM staging. In total, 2149 studies were screened, and 11 studies met the inclusion criteria for the analysis. The presence of ctDNA within 1 month after surgery as well as long-term postoperative ctDNA were both associated with poorer RFS [hazard ratio (HR) = 4.43; 95% CI: 3.23-6.07 and HR = 7.99; 95% CI: 3.28-19.44, respectively] and worse OS (HR = 5.07; 95% CI: 2.80-9.19 and HR = 7.49; 95% CI: 3.42-16.43, respectively). Most subgroup analyses yielded similar results. Moreover, ctDNA-positive patients could acquire survival benefits from AT (HR = 0.30; 95% CI: 0.16-0.54), while ctDNA-negative patients that received AT did not show significant improvement in RFS (HR = 1.18; 95% CI: 0.67-2.09). The postoperative ctDNA assessment is a promising approach to stratify the risk of relapse and death in ENSCLC patients. Our data suggest that patients with negative ctDNA in the postoperative setting may not benefit from AT, which warrants further investigation. This finding, if validated in prospective trials with a larger sample size, could aid in better-individualized treatment for patients and avoid potential side effects of AT. This study was designed in accordance with PRISMA and registered with PROSPERO (CRD42022311615).

Development and Validation of a New Staging System for Esophageal Squamous Cell Carcinoma Patients Based on Combined Pathological TNM, Radiomics, and Proteomics.

This study aimed to construct a new staging system for patients with esophageal squamous cell carcinoma (ESCC) based on combined pathological TNM (pTNM) stage, radiomics, and proteomics. This study collected patients with radiomics and pTNM stage (Cohort 1, n=786), among whom 103 patients also had proteomic data (Cohort 2, n=103). The Cox regression model with the least absolute shrinkage and selection operator, and the Cox proportional hazards model were used to construct a nomogram and predictive models. Concordance index (C-index) and the integrated area under the time-dependent receiver operating characteristic (ROC) curve (IAUC) were used to evaluate the predictive models. The corresponding staging systems were further assessed using Kaplan-Meier survival curves. For Cohort 1, the RadpTNM4c staging systems, constructed based on combined pTNM stage and radiomic features, outperformed the pTNM4c stage in both the training dataset 1 (Train1; IAUC 0.711 vs. 0.706, p<0.001) and the validation dataset 1 (Valid1; IAUC 0.695 vs. 0.659, p<0.001; C-index 0.703 vs. 0.674, p=0.029). For Cohort 2, the ProtRadpTNM2c staging system, constructed based on combined pTNM stage, radiomics, and proteomics, outperformed the pTNM2c stage in both the Train2 (IAUC 0.777 vs. 0.610, p<0.001; C-index 0.898 vs. 0.608, p<0.001) and Valid2 (IAUC 0.746 vs. 0.608, p<0.001; C-index 0.889 vs. 0.641, p=0.009) datasets. The ProtRadpTNM2c staging system, based on combined pTNM stage, radiomic, and proteomic features, improves the predictive performance of the classical pTNM staging system.

Elective Neck Dissection Improves Regional Control in cN0 Minor Salivary Gland Carcinoma in the Oral Cavity

Consensus regarding whether elective neck dissection (END) provides better outcomes than observation in clinically node negative minor salivary gland (MSG) carcinoma is lacking. Therefore, this study aimed to compare the impact of END with that of observation on regional control (RC) and overall survival (OS) and to detect the predictors for lymph-node metastasis in oral MSG carcinoma. A single-institution, retrospective cohort study was designed; it included patients with clinically node negative oral MSG carcinoma treated at a tertiary teaching hospital between January 2002 and January 2022. The primary predictor variable was END and primary outcome variables were RC and OS. The secondary outcome variable was lymph-node metastasis. Other covariates included demographic and pathologic features, TNM stage, and adjuvant treatment. The Kaplan-Meier method and Cox proportional hazards model were used to determine the effect of END on RC and OS. The chi-squared test and logistic regression models were used to identify independent predictors for lymph-node metastasis. A total of 268 patients (107 men and 161 women) with a mean age of 46.4±15.5years were included. The 5-year RC rate was statistically different between the observation and END groups (75%; 95% confidence interval [CI], 67%-83; 95% CI, 81%-93%, respectively; P=.014). Cox regression analysis confirmed that END (hazard ratio [HR] 2.395; 95% CI: 1.433-8.275; P=.034) was independently associated with a decreased risk of regional recurrence. The 5-year OS rates for the observation and END groups were 66% (95% CI, 56-76%) and 76% (95% CI, 66-86%), respectively, and the difference was not statistical (P=.057). Occult metastasis occurred in 24.6% of patients. Primary tumor location on the tongue/floor of the mouth (odds ratio [OR], 4.287; 95% CI, 1.773-9.125; P=.011), T3/4 stage (OR, 3.286; 95% CI, 1.228-8.253; P=.021), and high-grade disease (OR, 6.674; 95% CI, 2.199-14.326; P<.001) were independently associated with an increased risk of occult metastasis. RC was better with END than with observation, but OS was comparable with the two approaches. Primary tumor location on tongue/floor of the mouth, T3/4 stage, and high-grade disease were associated with an increased risk of lymph-node metastasis.

DNA repair/recombination protein 54L promotes the progression of lung adenocarcinoma by activating mTORC1 pathway.

Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer and has a poor prognosis. RAD54L is a DNA repair protein upregulated in several cancer types, but its role in LUAD progression remains unclear. The objective of this study was to characterise the molecular pathways that oncogenic RAD54L modulates to drive LUAD progression. The Cancer Genome Atlas (TCGA)‒LUAD dataset was analysed to compare the RAD54L mRNA expression in LUAD tumours to that in normal lung tissue. RAD54L and E2F7 mRNA expression was confirmed in human cancer cell lines using RT-qPCR. Bioinformatics tools were used to predict the target genes and downstream signalling pathways of RAD54L. Proteins related to RAD54L, apoptosis, migration, and the mTORC1 pathway were assessed by Western blotting. Using the TCGA‒LUAD dataset, we found that RAD54L was higher in LUAD tumours compared to that in non-cancerous lung tissue, and RAD54L levels were significantly correlated with pathological TNM stage and unfavourable prognosis in patients with LUAD. RAD54L was ubiquitously upregulated in LUAD cells (NCI-H1975, H1299, H23 and A549). Furthermore, RAD54L silencing decreased cell proliferation, invasion, and migration, and induced cell apoptosis and G1 cell cycle phase arrest in H1299 and H23 human lung cancer cell lines. E2F7 was predicted as a target gene of RAD54L. E2F7 overexpression restored malignant cell behaviour in si-RAD54L-treated H1299 cells. Bioinformatic analysis suggested that the mTORC1 signalling pathway is downstream of RAD54L. Rapamycin treatment impaired RAD54L-mediated malignant cell behaviour in H1299 cells. Additionally, RAD54L promoted the progression of xenograft tumours and metastasis in vivo. In conclusion, the E2F7-RAD54L axis promotes the progression of LUAD through the mTORC1 signalling pathway.

Comparison of histopathological turnaround times for mandibulectomies, glossectomies, and incisional biopsies of the tongue

Diagnostic histopathology plays a key role in the management of oral cancer and timely reports are essential. The aim of this study was to retrospectively compare the time interval between receipt of the specimen and issue of the histopathology report (the ‘turnaround time’, TT) of two types of oral cancer resections (mandibulectomies and glossectomies) and incisional biopsies from the tongue (n = 100 of each). The information documented included the number of days from receipt of the specimen until the sample was ready for reporting, and the number of subsequent days until the report was authorised by the pathologist. The number of days mandibulectomies required decalcification, the number of blocks processed per sample, and pathological TNM stage were also recorded. Results showed that mandibulectomies had statistically significantly longer TT than glossectomies. Incisional biopsies had the shortest TT with 87% reported in seven days and 95% in ten. There were also statistically significantly longer TT for pT3/pT4 than for pT1/pT2 glossectomies, and between the number of blocks processed for the three main groups. Decalcification and the interval whilst the slides awaited the pathologists’ attention were identified as ‘bottlenecks’. Dentate mandibulectomies had the longest TT of all; extraction of teeth at operation and detachment of the lower border of the mandible at macroscopic sampling are thus potential means by which the decalcification delay might be reduced. Expectations of the multidisciplinary team managing the patient should be realistic when scheduling postoperative discussion.

Prognostic Analysis of Patients with TRG1 after Neoadjuvant Chemoradiotherapy in Rectal Cancer: Tumor Regression Pattern Will Affect Survival

<h3>Purpose/Objective(s)</h3> Tumor regression grade (TRG) is an evaluation method to reflect tumor response to neoadjuvant chemoradiotherapy (NCRT) in patients with rectal cancer. Tumor shrinks dramatically in the case of TRG1 and shows high sensitivity to NCRT. However, the prognosis of patients who had TRG1 was different from each other. Additionally, there may be two different ways of tumor response to NCRT: shrinkage or fragmentation, and whether the patterns of tumor regression would affect prognosis is still not clear. The purpose of this study is to assess which factors would affect the survival of TRG1 patients. <h3>Materials/Methods</h3> This is a retrospectively analysis of patients with locally advanced rectal cancer (LARC) and received NCRT at our institution. TRG scores were evaluated according to the guideline of National Comprehensive Cancer Network (NCCN). We analyzed several clinicopathological factors and their relationship with survival outcome including overall survival (OS) and disease-free survival (DFS). <h3>Results</h3> A total of 73 patients were enrolled in this study including 46 males (63.0%) and 27 females (37.0%). The median age was 59 years (range,26-84). Among them, 33 showed tumor shrinkage, while 40 (54.8%) showed tumor fragmentation. Fifteen (20.5%) patients were diagnosed as stage I, twenty-two (30.1%) as stage II, and thirty-six patient (49.3%) as stage III after surgery. There were 19.2%, 47.9%, and 32.9% of patients with high, intermediate, and low NAR score respectively. In univariate analysis, tumor regression pattern (<i>p</i>=0.004), pathologic TNM stage (<i>p</i>=0.026) and neoadjuvant rectal cancer (NAR) score (<i>p</i>=0.041) was associated with DFS. Only tumor regression pattern showed prognostic significance for DFS in multivariate analysis (HR=10.659, 95%CI 1.384-82.118, <i>p</i>=0.023). All deaths were observed in fragmentation group. <h3>Conclusion</h3> Tumor regression pattern was an independent factor affecting DFS in LARC patients with TRG1. Patients with tumor shrinkage response had more favorable prognosis compared to fragmented response.

Calreticulin as a prognostic biomarker and correlated with immune infiltrate in kidney renal clear cell carcinoma.

Background: Calreticulin (CALR) has been investigated in several malignant diseases and is associated with immune-cell infiltration. However, the prognostic value of CALR in kidney renal clear cell carcinoma (KIRC) is still unknown. Methods: Based on the computational analysis, data from 530 KIRC cases and 72 normal kidney samples from The Cancer Genome Atlas (TGCA-KIRC) database were analyzed in this study. The expression of CALR mRNA in pan-cancer and immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER) database. The CALR protein expression was obtained from the UALCAN and Human Protein Atlas (HPA) databases. Survival, functional, and statistical analyses were conducted using R software. Results: The CALR expression was higher in KIRC cases than in normal kidneys. A high CALR expression was correlated with TNM stage, pathological stage, and histological grade. Kaplan-Meier survival analysis showed that a high CALR expression was associated with poor overall survival, disease-specific survival, and progression-free interval. Gene set enrichment analysis (GSEA) indicated that CALR was enriched in IL-6 and IL-2 signaling, interferon signaling, TNF signaling, inflammatory response, apoptosis, and the p53 pathway. CALR is correlated with immune-infiltrating cells. A significant correlation was observed between CALR expression and immunomodulators. Conclusion: We identified CALR as a prognostic biomarker of KIRC. Meanwhile, the CALR expression associated with immune infiltration indicated that CALR might be a potential immunotherapy target for patients with KIRC.

ISPARTA BURDUR YÖRESİNDEKİ KOLON KANSERİ HASTALARININ DEMOGRAFİK VE KLİNİK ÖZELLİKLERİ

Objective&#x0D; To define the demographic and clinicopathological&#x0D; characteristics of colon cancer patients followed up&#x0D; at Suleyman Demirel University, Medical Oncology&#x0D; Outpatient Clinic.&#x0D; Material and Method&#x0D; Outpatient archive files of 582 patients who applied&#x0D; to Suleyman Demirel University Faculty of Medicine,&#x0D; Medical Oncology Clinic and received a diagnosis of&#x0D; colon cancer between 2010-2021 were examined and&#x0D; patients’ age, gender, tumor location, family history&#x0D; of cancer, and pathological TNM stage at the time of&#x0D; diagnosis were recorded.&#x0D; Results&#x0D; Median age was 63.5 years. Of the 582 patients, 375&#x0D; (64.4%) were male and 207 (35.6%) were female.&#x0D; Thirty-four (5.8%) of the patients had family history&#x0D; of colon cancer. The origin of the tumor was the right&#x0D; colon in 147 (25.3%) patients, the left colon in 168&#x0D; (28.9%), and the rectum in 265 (45.5%). At the time&#x0D; of diagnosis, T stage was T1 in 35 (6%) patients,&#x0D; T2 in 61 (10.5%), T3 in 418 (71.8%), and T4 in 67&#x0D; (11.5%). Pathological N stage was N0 in 246 (42.3%)&#x0D; patients, N1 in 168 (28.9%), and N2 in 168 (28.9%).&#x0D; When staging was made according to TNM grades,&#x0D; 82 (14.1%) patients were diagnosed with Stage 1&#x0D; disease, 153 (26.3%) with Stage 2 disease, 242&#x0D; (41.6%) with Stage 3, and 105 (18%) patients were&#x0D; diagnosed with Stage 4 disease. Metastasis was&#x0D; detected at the time of diagnosis in 106 (18.2%) of&#x0D; the patients.&#x0D; Conclusion&#x0D; Most of the patients who apply to Suleyman Demirel&#x0D; University Faculty of Medicine, Medical Oncology&#x0D; Outpatient Clinic from the Isparta-Burdur region are&#x0D; patients diagnosed at an advanced stage. It is of&#x0D; vital importance to raise awareness of colon cancer&#x0D; screenings and increase awareness of colon cancer&#x0D; in the community of this region.

High CENPA expression in papillary renal cell carcinoma tissues is associated with poor prognosis.

ObjectiveThis work focused on investigating the relation of centromeric protein A (CENPA) gene expression with prognosis of papillary renal cell carcinoma (PRCC).MethodsWe obtained data from PRCC cases in TCGA. Thereafter, CENPA levels between the paired PRCC and matched non-carcinoma samples were analyzed by Wilcoxon rank-sum test, while the relations of clinicopathological characteristics with CENPA level were examined by logistic regression and Wilcoxon rank-sum test. The prognostic value of CENPA was assessed by plotting the receiver operating feature curve (ROC) and calculating the value of area under curve (AUC). In addition, relations between clinicopathological characteristics and PRCC survival were analyzed through Kaplan–Meier (KM) and Cox regression analyses. After dividing the total number of patients into the trial cohort and the validation cohort in a ratio of 7:3, we constructed a nomogram in trial cohort according to multivariate Cox regression results for predicting how CENPA affected patient survival and used the calibration curve to verify its accuracy in both cohorts. We also determined CENPA levels within cancer and matched non-carcinoma samples through immunohistochemistry (IHC). Finally, we utilized functional enrichment for identifying key pathways related to differentially expressed genes (DEGs) between PRCC cases with CENPA up-regulation and down-regulation.ResultsCENPA expression enhanced in PRCC tissues compared with healthy counterparts (P < 0.001). CENPA up-regulation was related to pathological TNM stage and clinical stage (P < 0.05). Meanwhile, the ROC curves indicated that CENPA had a remarkable diagnostic capacity for PRCC, and the expression of CENPA can significantly improve the predictive accuracy of pathological TNM stage and clinical stage for PRCC. As revealed by KM curves, PRCC cases with CENPA up-regulation were associated with poor survival compared with those with CENPA down-regulation (Risk ratio, RR = 3.07, 95% CI: 1.58–5.97, P = 0.001). In the meantime, univariate as well as multivariate analysis showed an independent association of CENPA with overall survival (OS, P < 0.05) and the nomogram demonstrated superior predictive ability in both cohorts. IHC analysis indicated that PRCC cases showed an increased CENPA positive rate compared with controls. As revealed by functional annotations, CENPA was enriched into pathways associated with neuroactive ligand receptor interactions, cytokine receptor interactions, extracellular matrix regulators, extracellular matrix glycoproteins and nuclear matrisome.ConclusionCENPA expression increases within PRCC samples, which predicts dismal PRCC survival. CENPA may become a molecular prognostic marker and therapeutic target for PRCC patients.

P1.12-05 Prediction of Clinically Significant Pathological Upstaging in Resected Lung Cancer: Insight from COVID-19 Pandemic (1st wave)

IntroductionWe aim to investigate clinicopathological characteristics of our surgical lung cancer population presenting during the 1st wave of pandemic, describe the key service parameters, and to identify pathological upstaging compared to a pre-pandemic cohort.MethodsThis is part of an ongoing observational study including all primary lung cancer patients who underwent resection at our centre. Data were collected as part of an institutional lung cancer database. COVID vulnerability status was derived from Department of Health (UK) guidelines. Clinically significant pathological upstaging was defined as migration between clinical and pathological final TNM stage, either major (between stages) or minor (between substages except IA). Logistic regression was employed to identify independent predictors of upstaging, and a 3-tier risk stratification system was developed.ResultsWe included 242 cases from 1st wave and 456 cases from a 2019 cohort. Radiological lesion size, nodal status, Maximum Standard Unit Value (SUVmax) and histological risk group were independent predictors of upstaging. The 3-tier system stratified such risk into low (8.3%), intermediate (26.1%) and high (48.4%), with AUC of 0.683. There was 20.4% reduction in caseload, and significant drop in all-purpose frozen section usage. No significant difference was seen regarding patients classified as clinically extremely vulnerable (CEV), clinically vulnerable (CV) as well as multimorbidity. No significant changes were observed for surgical waiting time, histological subtypes, final pathological stage, R0 resection or clinically significant upstaging (30.1% vs 30.2%), but there was minor impact on pathology reporting times.ConclusionsView Large Image Figure ViewerDownload Hi-res image Download (PPT)KeywordsLung cancer, Pathological upstaging, COVID-19 IntroductionWe aim to investigate clinicopathological characteristics of our surgical lung cancer population presenting during the 1st wave of pandemic, describe the key service parameters, and to identify pathological upstaging compared to a pre-pandemic cohort. We aim to investigate clinicopathological characteristics of our surgical lung cancer population presenting during the 1st wave of pandemic, describe the key service parameters, and to identify pathological upstaging compared to a pre-pandemic cohort. MethodsThis is part of an ongoing observational study including all primary lung cancer patients who underwent resection at our centre. Data were collected as part of an institutional lung cancer database. COVID vulnerability status was derived from Department of Health (UK) guidelines. Clinically significant pathological upstaging was defined as migration between clinical and pathological final TNM stage, either major (between stages) or minor (between substages except IA). Logistic regression was employed to identify independent predictors of upstaging, and a 3-tier risk stratification system was developed. This is part of an ongoing observational study including all primary lung cancer patients who underwent resection at our centre. Data were collected as part of an institutional lung cancer database. COVID vulnerability status was derived from Department of Health (UK) guidelines. Clinically significant pathological upstaging was defined as migration between clinical and pathological final TNM stage, either major (between stages) or minor (between substages except IA). Logistic regression was employed to identify independent predictors of upstaging, and a 3-tier risk stratification system was developed. ResultsWe included 242 cases from 1st wave and 456 cases from a 2019 cohort. Radiological lesion size, nodal status, Maximum Standard Unit Value (SUVmax) and histological risk group were independent predictors of upstaging. The 3-tier system stratified such risk into low (8.3%), intermediate (26.1%) and high (48.4%), with AUC of 0.683. There was 20.4% reduction in caseload, and significant drop in all-purpose frozen section usage. No significant difference was seen regarding patients classified as clinically extremely vulnerable (CEV), clinically vulnerable (CV) as well as multimorbidity. No significant changes were observed for surgical waiting time, histological subtypes, final pathological stage, R0 resection or clinically significant upstaging (30.1% vs 30.2%), but there was minor impact on pathology reporting times. We included 242 cases from 1st wave and 456 cases from a 2019 cohort. Radiological lesion size, nodal status, Maximum Standard Unit Value (SUVmax) and histological risk group were independent predictors of upstaging. The 3-tier system stratified such risk into low (8.3%), intermediate (26.1%) and high (48.4%), with AUC of 0.683. There was 20.4% reduction in caseload, and significant drop in all-purpose frozen section usage. No significant difference was seen regarding patients classified as clinically extremely vulnerable (CEV), clinically vulnerable (CV) as well as multimorbidity. No significant changes were observed for surgical waiting time, histological subtypes, final pathological stage, R0 resection or clinically significant upstaging (30.1% vs 30.2%), but there was minor impact on pathology reporting times. Conclusions KeywordsLung cancer, Pathological upstaging, COVID-19 Lung cancer, Pathological upstaging, COVID-19

LBA4 Adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy: Results from the randomized, phase III CheckMate 914 trial

CheckMate 914 (NCT03138512) is a phase III, randomized, double-blind, multicenter, 2-part trial evaluating NIVO+IPI vs PBO (part A) or NIVO monotherapy vs NIVO+IPI vs PBO (part B) in mutually exclusive patients (pts) with localized RCC at high risk of post-nephrectomy relapse. We report the primary analysis for part A of this trial. CheckMate 914 key inclusion criteria: radical or partial nephrectomy with negative surgical margins > 4 and ≤ 12 weeks before randomization; predominant clear cell histology; pathological TNM stage T2a (grade [G] 3 or 4) N0M0, T2b (any G) N0M0, T3 (any G) N0M0, T4 (any G) N0M0, or any T (any G) N1M0; and no clinical/radiological evidence of residual disease or distant metastases. Pts were randomized 1:1 to NIVO 240 mg Q2W (× 12 doses) + IPI 1 mg/kg Q6W (× 4 doses) or equivalent PBO for 24 weeks or until disease recurrence/unacceptable toxicity. Stratification factors: TNM stage and type of nephrectomy. Primary endpoint: disease-free survival (DFS) per blinded independent central review; secondary endpoints include overall survival and safety. 816 pts were randomized to NIVO+IPI (n = 405) vs PBO (n = 411). With 37.0 months of median follow-up (range, 15.4–58.0), the primary efficacy endpoint of DFS was not met (HR, 0.92; 95% CI, 0.71–1.19; P = 0.5347). Median DFS was not reached with NIVO+IPI and 50.7 months with PBO; DFS probabilities at 24 months were 76.4% and 74.0%, respectively. Median (Q1, Q3) treatment duration was 5.1 (2.8, 5.3) months and 5.1 (5.1, 5.3) months, respectively. Any-grade treatment-related adverse events (AEs) were reported in 88.9% vs 56.8% of pts treated with NIVO+IPI vs PBO; grade ≥ 3 treatment-related AEs were reported in 28.5% vs 2.0%, respectively. Treatment-related AEs led to discontinuation of NIVO+IPI in 29.0% of pts and of PBO in 1.0% of pts. The CheckMate 914 trial of NIVO+IPI vs PBO in pts with localized RCC at high risk of relapse after nephrectomy did not meet the primary endpoint of DFS. Safety of NIVO+IPI was consistent with its known profile in advanced RCC, although the rate of discontinuation due to treatment-related AEs was higher with adjuvant NIVO+IPI vs PBO in this trial.

Bioinformatics analysis on differentially expressed genes between colorectal adenoma and colorectal adenocarcinoma

Colorectal adenoma (CRA) is the main cause of the progression of Colorectal adenocarcinoma (COAD). Therefore, it is very important to accurately reveal its developmental mechanism. Differential expression genes (DEGs) in three microarray datasets were screened using GEO and GEO2R. R packages were used for gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) path enrichment analysis. Hub genes screened by STRING, Cytoscape and CytoHubba were used. R was used for DEGs of hub genes, and Gene Expression Profiling Interactive Analysis (GEPIA2) database was used for prognostic Analysis. R-packet were used to analyze tumor pathology, tumour, lymph-nodes, and metastases (TNM) staging, enrichment, immune invasion and prognosis. Among the 66 genes, including 36 up-regulated and 30 down-regulated genes. Survival analysis showed that COL1A1, COL5A2, COL5A1 and secreted protein acidic and rich in cysteine (SPARC) were associated with disease-free survival in patients. The four genes were related to tumor pathological stage, TNM stage and immune invasion. COL1A1 and COL5A2 were highly expressed in chromatin modification and cellular senescence. Low expression of COL5A1 and SPARC was significantly enriched in neutrophil degranulation and Wp VegfavegFR2 signaling pathways. Obviously, these four key genes can serve as important targets for early diagnosis, treatment, immunity and prognosis of CRA to COAD.

Nonbilharzial Squamous Cell Bladder Cancer: An Indian Experience.

Anand RajaBackground Squamous cell carcinoma represents the second most common histological type of bladder cancer. Nonbilharzial squamous cell carcinomas of bladder are rare histological variant with limited experience. Objective We aimed to review our experience to determine various treatment patterns and survival outcomes for this malignancy. Methods Data from patients treated at our center from 1995 to 2016 was collected from patient records and analyzed. Clinicopathological variables, treatment patterns, and follow-up data were extracted. Results A total of 32 patients were included in the study with a median age of 55.5 years. Hematuria was the most common presentation. Overall, 16 patients underwent radical cystectomy, 8 underwent definitive radiotherapy (RT), 4 received palliative RT, and 4 patients defaulted for any treatment. Surgery conferred better survival rates as compared with RT (31.9 vs. 7.45 months). In the surgical group, only pathological TNM staging was a significant prognostic factor. Conclusion In localized nonbilharzial squamous cell bladder cancer, radical cystectomy with bilateral pelvic node dissection appears to be treatment modality of choice. Larger series are needed to validate the role of other perioperative modalities.

To CT or not to CT: Questioning the Cost-Effectiveness of CT Thorax in Head and Neck Cancers

Computed tomography (CT) scan has been an integral part of the diagnostic workup for patients with head and neck squamous cell carcinoma. Our study was designed to find out the incidence of distant metastasis and second primary tumor and to correlate the cost-effectiveness of CT thorax in detecting the same. This study was conducted among 326 cancer patients who visited our center with curative intent in the year 2021, with lesions in various head and neck subsites. Data were collected based on their pathological TNM staging and the presence of distant metastasis as evident on their CT thorax imaging with various variables related to the disease. Incremental cost-effectiveness ratio (ICER) was calculated for detecting a single metastatic deposit and second primary tumor in terms of Indian currency and was correlated to each subsite and stage of disease at presentation. Out of these 326 patients, 281 patients were included in our study after considering the inclusion criteria, and among these 281 patients, 235 of them underwent CT thorax for metastatic workup. No patient was found to have a second primary. Metastases were found in 12 patients. The site of primary lesion and clinical tumor (cT) staging were found to be significantly influencing the incidence of metastasis on CT thorax. ICER was least for larynx, pharynx, and paranasal sinuses and was highest for oral cavity primaries and early-stage disease. As per our observations and results of ICER, CT thorax is indeed a valuable modality but should be used judiciously when it comes to initial diagnostic workup.

Prostate cancer grade downgrading at time of prostatectomy provides risk-stratification insight into future tumor behavior after prostatectomy.

Prostate biopsy (Bx) sampling-based diagnosis of prostate cancer (PCa) has well-described inaccuracy when compared against whole gland analysis upon prostatectomy. Although upgrading of PCa Grade Group (GG) is often described, the occurrence and prognostic implications of downgrading PCa GG at the time of radical prostatectomy (RP) is less understood. Our objective was to evaluate whether downgrading PCa GG at the time of RP was associated with future tumor behavior. The SEER database was searched from 2010 to 2017 and patients were included if they were assigned pathological grades on both Bx and RP specimen. Patients were stratified into Bx GG > RP GG and Bx GG ≤ RP GG groups, and tumor behavior after treatment was examined. Cox regression was used for the survival analysis. Here, 99,835 patients were included in this study. A total of 18,516 (18.5%) patients encountered downgrading from Bx GG to RP GG. A downgrading of 1 grade occurred in 13,969 (75.4%) of these patients and of 2 or more grades occurred in 4547 (24.6%) patients. A history of higher Bx GG compared with RP GG increased the risk of cancer-specific mortality (CSM) for each given RP GG controlling for age, race, preop prostate-specific antigen level, percentage of positive biopsy cores, and pathologic TNM stages. Specifically, a history of high Bx GG conferred a 45% increased risk of CSM for any given RP GG (hazard ratio = 1.45 95% confidence interval = 1.16-1.82, p < 0.001). A history of higher Bx GG, and hence downgrading at the time of RP, demonstrates some value as a risk-stratification tool for future cancer outcomes after prostatectomy.

A Very rare case report of male invasive micropapillary breast carcinoma in China and review of literature.

IntroductionTo report a rare case of male breast micropapillary carcinoma (MBMC) with early metastasis of axillary lymph nodes, the molecular characteristics were further studied in both primary and metastatic foci. In addition, we have reviewed similar published cases in the literature and tried to outline the molecular characteristics of this disease.Presentation of caseA 63-year-old male patient presented with a painless mass on the medial side of left breast and was pathologically diagnosed with MBMC. Postoperative examination revealed 80 % invasive ductal carcinoma (IDC) and 20 % invasive micropapillary carcinoma (IMPC) in the mass, with a histological grade WHO III. There were 25 axillary lymph nodes, 11 of which were metastatic, including 5 macrometastasis and 1 micrometastasis, with a lymph node metastasis rate of 44 % (11/25). Pathological TNM stage: pT2N2M0. Immunohistochemical results in primary foci: AR (90 %, +), HER- 2 (1 +) and ER (90 %, +), PR (60 %, +), E - cadherin (+), EGFR (−), GATA - 3 (90 %, 3 +), Ki - 67 (50 %). Lymph node metastasis: AR (40 %, strong +), HER-2 (2+), ER (90 %, strong +), PR (40 %, strong +), Ki-67 (50 %). AR and Ki-67 were obviously expressed in both primary and metastatic foci. A mixture of IDC and IMPC was found in lymph node metastases, both of which expressed varying degrees of AR and Ki-67.Clinical discussionMBMC is easy to early metastasized to lymph node. In this case, there was no significant difference between primary and metastatic cancer in molecular results. It is positive for ER and PR, but negative for HER-2 in this patient. There is few data on male HER-2 expression, HER-2 expression is deficient in this case. AR is found to be positive in 50 % of MBMC cases, although their clinical relevance has not been established yet. The significance of EGFR in the prognosis of MBMC remains unclear, however, EGFR positive expression is not found in this patient.ConclusionsMBMC is a rare disease characterized by early lymph node metastasis, high histological grade, positive ER and PR, and generally negative HER-2. The molecular biological characteristics and prognostic significance of MBMC need to be further studied in order to develop the optimal treatment strategy.

Combining Single-Cell and Transcriptomic Data Revealed the Prognostic Significance of Glycolysis in Pancreatic Cancer.

Background: Pancreatic cancer (PC), the most common fatal solid malignancy, has a very dismal prognosis. Clinical computerized tomography (CT) and pathological TNM staging are no longer sufficient for determining a patient’s prognosis. Although numerous studies have suggested that glycolysis is important in the onset and progression of cancer, there are few publications on its impact on PC. Methods: To begin, the single-sample gene set enrichment analysis (ssGSEA) approach was used to quantify the glycolysis pathway enrichment fraction in PC patients and establish its prognostic significance. The genes most related to the glycolytic pathway were then identified using weighted gene co-expression network analysis (WGCNA). The glycolysis-associated prognostic signature in PC patients was then constructed using univariate Cox regression and lasso regression methods, which were validated in numerous external validation cohorts. Furthermore, we investigated the activation of the glycolysis pathway in PC cell subtypes at the single-cell level, performed a quasi-time series analysis on the activated cell subtypes and then detected gene changes in the signature during cell development. Finally, we constructed a decision tree and a nomogram that could divide the patients into different risk subtypes, according to the signature score and their different clinical characteristics and assessed the prognosis of PC patients. Results: Glycolysis plays a risky role in PC patients. Our glycolysis-related signature could effectively discriminate the high-risk and low-risk patients in both the trained cohort and the independent externally validated cohort. The survival analysis and multivariate Cox analysis indicated this gene signature to be an independent prognostic factor in PC. The prognostic ROC curve analysis suggested a high accuracy of this gene signature in predicting the patient prognosis in PC. The single-cell analysis suggested that the glycolytic pathway may be more activated in epithelial cells and that the genes in the signature were also mainly expressed in epithelial cells. The decision tree analysis could effectively identify patients in different risk subgroups, and the nomograms clearly show the prognostic assessment of PC patients. Conclusion: Our study developed a glycolysis-related signature, which contributes to the risk subtype assessment of patients with PC and to the individualized management of patients in the clinical setting.

Influencing factors of lung cancer patients' participation in shared decision-making: a cross-sectional study

The purpose of this study was to investigate and analyze the level of actual participation and perceived importance of shared decision-making on treatment and care of lung cancer patients, to compare their differences and to explore their influencing factors. A total of 290 lung cancer patients were collected from oncology and thoracic surgery departments of a comprehensive medical center in Qingdao from October 2018 to December 2019. Participants completed a cross-sectional questionnaire to assess their actual participation and perceived importance in shared decision-making on treatment and care. Descriptive analysis and non-parametric tests were carried out to assess the status quo of patients' shared decision-making on treatment and care. Binary logistic regression analysis with a stepwise back-wards was applied to predict factors that affected patients' participation in shared decision-making. The results showed that patients with lung cancer had a low degree of participation in shared decision-making. There were significant differences between actual participation and perceived importance of shared decision-making on treatment and care. Education level, age, gender, income, marital status, personality, the course of the disease (> 6months), and the pathological TNM staging (III) affected patient's level of participation in shared decision-making. Actual participation in shared decision-making on the treatment and care of lung cancer patients was low and considered unimportant. We could train oncology nurses to use patient decision aids to help patients and families participate in shared decision-making on patients' value, preferences and needs.