Tumor Clinical Stage Research Articles

A comparison of real-world outcomes by mismatch repair status in patients with stage II/III rectal cancer in the Netherlands.

260 Background: A subset of rectal tumours (~3–5%) have mismatch repair deficiency (dMMR); the remaining are classified as MMR proficient (pMMR). A recent trial for stage II/III dMMR rectal cancer (RC) showed that 6 months of neoadjuvant treatment with dostarlimab, a programmed cell death protein 1 inhibitor, induced a 100% clinical complete response rate and allowed for organ preservation. Using real-world data from the Netherlands, a dMMR patient cohort was compared to a matched pMMR cohort to assess if clinical outcomes differed, even after matching for baseline characteristics. Methods: Utilizing data from the Netherlands Cancer Registry, this retrospective analysis assessed patients with stage II/III RC treated from 2015–2022 with known MMR status. The dMMR cohort was matched 1:2 to a cohort of pMMR patients on age, year of diagnosis, tumour clinical (cT) stage, and node clinical (cN) stage. Event-free survival (EFS; defined as first occurrence of locoregional failure, distant metastasis, a new primary colorectal tumour, or death from any cause) and overall survival (OS) were compared using Kaplan-Meier methodology and a univariable Cox model. Results: Among the 7939 patients included, 184 (2.3%) had dMMR tumours. After matching and a loss of 8 dMMR patients due to ineligibility, 176 dMMR patients were compared to 363 pMMR patients. Matching successfully removed differences in age, cT, and cN stage; however, dMMR patients continued to have more BRAF mutants (p=0.014), more poorly differentiated tumours (p<0.001) and more variation in histology (p=0.01). dMMR patients had a statistically significant lower risk of experiencing an event (hazard ratio [HR] 0.54 [95% confidence interval (CI) 0.38–0.77], p<0.001), with a 3-year EFS of 79.6% (95% CI 73.7–86.1) compared to pMMR patients (64.7% [95% CI 59.8–70.1]). For OS, there was no significant difference between the dMMR and pMMR cohorts (HR 0.73 [95% CI 0.47–1.16], p=0.181); however, within the small group of patients with an event, OS at 1 year for dMMR patients was 68.4% (95% CI 55.1–84.9) compared to 93.5% (95% CI 89.5–97.7) for pMMR patients (p=0.001). Conclusions: dMMR RC is rare, and tumour characteristics differ from those of patients with pMMR tumours (1). After controlling for clinical stage and age, this study suggests dMMR patients have improved EFS compared to pMMR patients. There is no significant difference in OS between groups but dMMR patients with an event have worse OS than pMMR patients, highlighting an additional need to prevent recurrence of disease within dMMR patients.1. Lunenberg, R et al. Poster presented at ESMO Congress (Presentation 569P), 13-17 Sept 2024, Barcelona, Spain.

Comparison between neoadjuvant chemotherapy followed by surgery and definitive chemoradiotherapy for survival in patients with resectable esophageal squamous cell carcinoma (JCOG2305A).

417 Background: Neoadjuvant triplet chemotherapy followed by surgery (Neo-S) has become the standard treatment for resectable esophageal squamous cell carcinoma (ESCC) based on the results of JCOG1109. However, definitive chemoradiotherapy (CRT) remains an option for organ preservation with curative intent. This analysis aimed to explore subgroups of patients undergoing CRT, including salvage treatment, to identify those with survival outcomes potentially equivalent to Neo-S. Methods: Pooled data from two clinical trials of patients with resectable (T1N1-3M0 and T2-3NanyM0) ESCC. JCOG0909 was a single-arm trial that evaluated upfront CRT consisting of 5-FU (1000 mg/m 2 on day1-4, 29-32) and cisplatin (80 mg/m 2 on day1, 29) combined with radiotherapy at a dose of 50.4 Gy, including salvage treatment. If there was no progression at the time of salvage treatment, it was not regarded as an event for progression-free survival (PFS) in JCOG0909. JCOG1109 compared neoadjuvant treatment with doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy with radiotherapy followed by surgery. The patients were enrolled in JCOG0909 between 2010 and 2014 and in JCOG1109 between 2012 and 2018. Subgroup analyses of clinical data, including tumor location, cT, cN, and clinical stage, were conducted on overall survival (OS) and PFS using Cox proportional hazards regression models for patients with JCOG0909 and JCOG1109. When a subgroup with a multivariable hazard ratio (HR) of more than 0.91 was detected, CRT including salvage treatment was considered not to be inferior to Neo-S in that subgroup. Results: Ninety-three patients in the CRT group from JCOG0909 and 196 patients in the Neo-S group from the triplet chemotherapy arm of JCOG1109 were included in this analysis. Although there were no significant differences, PFS and OS tend to be better in the Neo-S group than in the CRT group (PFS, HR 0.72, 95% confidence interval [CI] 0.50-1.03; OS, HR 0.89, 95% CI 0.59-1.36). For patients with Ut/Mt or cT1-2 disease, OS in the Neo-S group had a HR of 0.91 or more compared with those in the CRT group (Table). Conclusions: Subgroups in which OS after CRT including salvage treatment was not inferior to that of Neo-S were identified. Hazard ratios of Neo-S to CRT by subgroups in multivariable Cox regression. Progression-free survival Overall survival Subgroups Hazard ratio 95% confidence interval Hazard ratio 95% confidence interval Ut/Mt 0.85 0.56-1.28 1.13 0.70-1.83 Lt 0.45 0.21-0.97 0.44 0.19-1.00 cT1-2 0.88 0.46-1.68 1.45 0.65-3.24 cT3 0.66 0.42-1.02 0.72 0.44-1.16 cStage IB+II 0.79 0.45-1.36 1.06 0.56-2.00 cStage III 0.75 0.45-1.23 0.92 0.52-1.62 Overall 0.72 0.50-1.03 0.89 0.59-1.36 Ut upper thoracic esophagus, Mt middle thoracic esophagus, Lt lower thoracic esophagus.

Utility of computed tomography (CT) –based staging of mismatch repair deficient (dMMR) colon cancer.

45 Background: dMMR tumors are characterized by rapid primary tumor growth with reduced likelihood for nodal and distant metastases compared to MMR proficient (pMMR) tumors. Neoadjuvant immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy for localized colon cancer with high pathologic complete response rates and low relapse rates. This raises the question if surgical treatment could be avoided with accurate radiographic staging while avoiding overtreatment of early stage tumors. This study assesses the utility of radiographic staging by CT for dMMR tumors compared to pathologic staging. Methods: Patients with stage I-III colon cancer treated with upfront surgical resection were retrospectively reviewed from a single institution from 2012 to 2023 in two cohorts: 1) dMMR colon cancer and 2) pMMR colon cancer limited to similar sample size as matched controls. Clinical stage was determined based on CT scans prior to surgical resection by 2 independent radiologists blinded to pathologic stage, and the results were correlated to pathologic stage. Clinical characteristics were extracted from the electronic medical record. Statistical analysis was performed using SPSS. Results: We identified 80 patients with dMMR colon cancer and 66 with pMMR tumors. CT clinical tumor staging was discordant from pathologic staging for 68% of dMMR tumors and 61% for pMMR tumors. For T4 dMMR tumors, CT had a 74% sensitivity and 44% specificity. T4 tumors were understaged by radiology to less than T4 for 56% of cases. For dMMR nodal staging, CT had 89% sensitivity and 50% specificity (Table 1). For pathologic node positive tumors, 14% were understaged by radiologist CT read to node negative. For pathologic node negative tumors, 50% of tumors were overstaged to node positive by radiologist CT read. There was poor inter-rater reliability for both T stage and N stage for dMMR and pMMR tumors. The weakest agreement between radiologists was for T stage (dMMR kappa = 0.246, mMMR kappa = 0.145). Conclusions: Radiologic clinical staging of dMMR and pMMR colon cancer does not correlate well with pathologic staging. There were high rates of understaging by CT evaluation for patients who may be candidates for neoadjuvant treatment (T4, N+). Furthermore, there was poor inter-rater reliability between radiologists, indicating that CT staging alone may not be sufficient. Additional diagnostic modalities for nodal detection may be necessary to accurately clinically stage patients before neoadjuvant ICIs in patients with locally advanced disease. Comparing utility of pMMR versus dMMR tumors for T4 and node positive disease. pMMR (n = 66) dMMR (n = 80) T4 versus T3 or less Sensitivity (%) 92 74 Specificity (%) 51 47 PPV (%) 80 77 NPV (%) 82 63 Node positive versus node negative Sensitivity (%) 60 50 Specificity (%) 75 89 PPV (%) 81 89 NPV (%) 53 50 Abbreviations: PPV = positive predictive value; NPV = negative predictive value.

MYBL2 promotes proliferation of clear cell renal cell carcinoma by regulating TOP2A and activating AKT/mTOR signaling pathway.

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system, and clear cell renal cell carcinoma (ccRCC) is the most common subtype. MYBL2 has been reported to be overexpressed in various tumors and associated with poor prognosis in patients, but its biological role in ccRCC remains unclear. In this study, we investigated the mRNA and protein expression levels of MYBL2 in ccRCC samples and evaluated the prognostic value of MYBL2 using TCGA dataset. Invitro functional assays were performed using CCK-8, EdU, colony formation, cell scratch, and transwell assays, as well as invivo tumorigenesis assays to investigate the biological functions of MYBL2 in ccRCC. Additionally, gene set enrichment analysis (GSEA) was used to explore the downstream pathways of MYBL2, which were further validated. Finally, we predicted the target genes of MYBL2 using bioinformatics and validated them using ChIP and dual-luciferase reporter gene assays. MYBL2 expression was significantly higher in ccRCC than in adjacent normal tissues and was associated with poor prognosis. MYBL2 expression was positively correlated with the pathological tumor grade and clinical TNM stage of ccRCC patients. Knockdown of MYBL2 significantly inhibited the proliferation of renal cancer cells invitro and invivo, and knockdown of MYBL2 could inhibit cell invasion and migration, while overexpression of MYBL2 had the opposite effect. GSEA revealed that MYBL2 was associated with the mTOR signaling pathway and cell cycle pathway, which was confirmed by our study. Finally, we found that TOP2A was a target gene of MYBL2, and MYBL2 could bind to the TOP2A promoter to regulate its transcriptional activity, promoting the proliferation of clear cell renal cell carcinoma cells. MYBL2 emerges as a highly expressed factor that significantly correlates with adverse patient prognosis in ccRCC. Mechanistically, MYBL2 transcriptionally upregulates TOP2A, thereby modulating the proliferation of ccRCC cells. Furthermore, MYBL2 activates the mTOR signaling pathway, a critical node in the progression of ccRCC. Collectively, these findings position MYBL2 as a promising candidate for both a biological marker and a therapeutic target in the management of ccRCC.

Dissecting Tumor Size Underestimation in Pancreatic Cancer: A Comparative Analysis of Preoperative Treatments.

Tumor size (TS) in pancreatic ductal adenocarcinoma (PDAC) is one of the most important prognostic factors. However, discrepancies between TS on preoperative images (TSi) and pathological specimens (TSp) have been reported. This study aims to evaluate the factors associated with the differences between TSi and TSp. We retrospectively analyzed patients with PDAC who underwent surgery at our institution between January 2010 and November 2023. TS discrepancy (TSD[%]) was defined as ([TSp - TSi]/TSp) × 100. Using logistic regression, we generated a receiver operating characteristic (ROC) curve to define the cutoff for TSi underestimation predicting clinical tumor (T) stage migration. Univariate and multivariate analyses were performed to evaluate predictors of TSi underestimation. Of the 231 patients, 99 (42%) patients received preoperative chemotherapy. The ROC curve determined a TSD underestimation cutoff of 25.9%. The number of TSp > TSi cases was 185 (80%), and TSi underestimation was present in 117 (51%) patients. T stage migration rates were 76%, 26%, and 50% in clinical stage (c) T1, cT2, cT3, respectively, among the patients with chemotherapy, and 93%, 33%, and 14%, respectively, in those without chemotherapy. Multivariate analyses revealed that independent predictors of TSi underestimation were posterior surface invasion in the patients with preoperative chemotherapy and anterior surface invasion in those without chemotherapy. TS was more commonly underestimated than overestimated, and cT1 rarely corresponded to pathological (p)T1. The factors contributing to TSi underestimation differed between patients with and without preoperative chemotherapy. Therefore, these two groups should be considered separately for accurate TSi evaluation.

VPS45 Contributes to the Progression of Hepatocellular Carcinoma by Triggering the Wnt/β-Catenin Signaling Pathway.

Vacuolar protein sorting 45 (VPS45) has recently been implicated in the development of ovarian cancer and non-small cell lung cancer. However, its role in the onset and progression of hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of VPS45 in HCC. Bioassays were conducted to assess the prognostic significance of VPS45 in HCC. Techniques such as western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) were used to confirm the expression levels of VPS45 in HCC tissues and cell lines, as well as to evaluate the expression of downstream effectors in its potential tumorigenic pathways. The impact of VPS45 on HCC cell invasion, proliferation, and migration was assessed using the Cell Counting Kit-8 (CCK-8), wound healing, and transwell assays. Furthermore, the effect of VPS45 on HCC tumorigenesis in vivo was evaluated through subcutaneous tumor formation assays in BALB/c nude mice. VPS45 is markedly overexpressed in both HCC tissues and cell lines. Its expression escalates with advancing tumor grade and clinical stage, and high VPS45 levels are indicative of poor prognosis. In vitro experiments revealed that VPS45 overexpression significantly boosts HCC cell proliferation, migration, and invasion. Conversely, VPS45 knockdown hindered HCC progression in vivo. Investigation into pathway protein expression suggests that VPS45 facilitates HCC progression through its involvement in the Wnt/β-catenin signaling pathway. The overexpression of VPS45 contributes to the development of malignant phenotypes in HCC cells, resulting in a poor prognosis. Targeting VPS45 may offer a viable therapeutic strategy for managing HCC.

Comprehensive Pan-Cancer Analysis and Functional Studies Reveal SLC2A6 as a Ferroptosis Modulator in Hepatocellular carcinoma

Soluble vector family member 6 (SLC2A6) has been implicated in the aggressiveness and poor prognosis of various cancers, yet its specific role in hepatocellular carcinoma (HCC) remains to be fully elucidated. This study utilized multiple databases to investigate the relationship between SLC2A6 expression and clinical stage, methylation status, drug sensitivity, immune infiltration, and immune checkpoint regulation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Furthermore, in vitro and in vivo experiments were performed to assess the impact of SLC2A6 knockout on the proliferation, migration, invasion, and underlying mechanisms in hepatocellular carcinoma (LIHC) cells. SLC2A6 expression was significantly correlated with tumor prognosis, clinical stage, and methylation levels, and was found to influence immune cell infiltration and immune checkpoint gene expression. In LIHC, SLC2A6 was associated with key biological processes, including the cell cycle, P53 signaling, and ferroptosis. Knockdown of SLC2A6 markedly suppressed the proliferation, migration, and invasion of HCC cells, with this inhibition being closely tied to the ferroptosis pathway. SLC2A6 plays a pivotal role in the regulation of pan-cancer processes, particularly in tumor prognosis and immune-related mechanisms. In LIHC, it emerges as a potential prognostic biomarker and therapeutic target for the regulation of ferroptosis, offering new insights for targeted cancer therapies.

Risk scoring system for evaluating pathological upstaging after radical nephroureterectomy for upper tract urothelial carcinoma: A multicenter study in Japan.

Accurate preoperative staging of upper tract urothelial carcinoma is often difficult. Therefore, we aimed to investigate the preoperative factors associated with pathological upstaging in patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy and to develop a risk-scoring system to assess pathological upstaging. This retrospective study enrolled 386 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy at Tottori University Hospital and affiliated hospitals between January 2015 and December 2021. Patients with clinical tumor stage 4, clinical node +, and those who received neoadjuvant chemotherapy were excluded from the study. The association between preoperative patient factors and pathological upstaging was analyzed. Statistical analyses included the t-test, chi-squared test, and logistic regression analysis. Of the 386 patients, 32 were excluded. Finally, 354 patients were included in this study, of whom 87 (24.6%) were pathologically upstaged. Hydronephrosis, positive urine cytology result, and maximum tumor diameter <30 mm were associated with upstaging. We developed a risk scoring system in which the score was the sum of the number of applicable items for three factors: hydronephrosis, positive urine cytology result, and maximum tumor size <30 mm. The probabilities of ureteral cancer upstaging were 0%, 8.3%, 29.5%, and 50.0% for scores of 0, 1, 2, and 3, respectively. Hydronephrosis, urine cytology, and maximum tumor diameter were associated with pathological upstaging. Our risk-scoring system may be useful in predicting pathological upstaging, especially in patients with ureteral cancer.

Immunonutrition to improve the quality of life of upper gastrointestinal cancer patients undergoing neoadjuvant treatment prior to surgery (NEOIMMUNE): double-blind randomized controlled multicenter clinical trial.

Malnutrition is common with esophagogastric cancers and is associated with negative outcomes. We aimed to evaluate if immunonutrition during neoadjuvant treatment improves patient's health-related quality of life (HRQOL) and reduces postoperative morbidity and toxicities during neoadjuvant treatment. A multicenter double-blind randomized controlled trial (RCT) was undertaken. Included patients had untreated nonmetastatic esophagogastric tumor, aged 18 ≥ years with a life expectancy of >3months. The study was powered for 80% power to detect a clinically relevant difference in EORTC-QLQC30 with standard deviation of 15 between groups. Primary end point was the quality of life as measured by the global health status at 30days after surgery. An intention-to-treat analysis was employed. The study was terminated at the interim analysis stage. About 300 patients were randomized: 149 to the IMPACT group and 151 to the control-formula group. Patient groups were well-balanced in terms of age, sex, body mass index, WHO performance status, and clinical tumor stage. Analysis of the primary end point for the study of global health status at 30-day postoperatively failed to show any significant differences between the groups (55.4 ± 18.6 [IMPACT] vs. 55.9 ± 19.8 [control]; P = 0.345). No significant differences between the groups were detected in the majority of domains from EORTC QLQC30 and OG25 tools after neoadjuvant therapy and 30 days postoperatively. Finally, no significant differences were seen between groups in neoadjuvant therapy or postoperative complications, or tumor response. The results of this multicenter double-blind RCT fail to demonstrate any HRQOL benefits to the utilization of immunonutrition during neoadjuvant therapy in patients with esophagogastric cancer.

Quality of life and functional outcomes in patients with locally advanced rectal cancer receiving total neoadjuvant therapy versus concurrent chemoradiotherapy: An analysis of the XXX trial.

To explore differences in the effects of total neoadjuvant therapy (TNT) and preoperative concurrent chemoradiotherapy (CRT) on quality of life and functional outcomes in patients with locally advanced rectal cancer. In the study, 591 patients with distal or middle-third, clinical primary tumor stage cT3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to receive short-term radiotherapy (25 Gy in five fractions) followed by 4 cycles of CAPOX (TNT group, n=297) or standard concurrent chemoradiotherapy (50 Gy in 25 fractions concurrently with oral capecitabine) (CRT group, n=294) before surgery. After a 6-year follow-up, the surviving patients were sent surveys, including the EORTC QLQ-C30, EORTC QLQ-CR29, and Wexner incontinence score questionnaires. Differences between the two groups were compared, and baseline data from the general population who completed the EORTC QLQ-C30 were also compared. The median follow-up was 77.38 (59.07-103.20) months, with 196 out of 414 surviving patients (47.3%) completing the questionnaire. Patients in the TNT group had better emotional function (94.16±10.19 vs. 90.17±14.63, P=0.031) but more severe diarrhea (12.46±21.73 vs. 6.74±16.03, P=0.036) than did those in the CRT group. However, the mean differences between the two groups were less than 5 points, which is not clinically significant, and there were no significant differences in other quality of life items. The Wexner incontinence scores were 5 (0-6) and 3 (0-6) for the TNT and CRT groups, respectively, with no significant difference between the groups (P=0.357). Compared to the general population data from the completed EORTC QLQ-C30 assessment, the patients did not exhibit differences greater than 5 points in terms of worse function or more severe symptoms. There were no significant differences in quality of life or anal function between patients receiving TNT and those receiving CRT. After 6 years, patients were able to maintain stability.

The Immune Contexture in Canine Anal Sac Adenocarcinoma: Immunohistochemical Quantification of Tumor-Infiltrating Lymphocytes and Tumor-Associated Macrophages with Image Analysis.

Canine anal sac gland adenocarcinomas (ASACs) are locally aggressive and highly metastatic to regional lymph nodes. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) can be effective prognostic and predictive markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine ASACs and their relationship with tumor size, histologic metastatic status, and tumor clinical stage. Thirty ASACs with known tumor size, metastatic status, and clinical stage were immunolabeled for Iba1 (macrophages), CD20 (B cells), CD3 (T cells), and Foxp3 (regulatory T cells). With image analysis, two areas of 1 mm2 were analyzed for each case at the tumor core (TC) and invasive margin (IM) and immune cells were counted. Eighteen patients had metastasis at the time of diagnosis, of which fifteen were nodal only, and three were both distant and nodal. The median tumor size was 32.5 mm (range 11-70). The clinical stage was I in five cases, II in seven cases, III in fifteen cases, and IV in three cases. T cells and macrophages were the most abundant immune cells in all tumors. Tumor size did not influence the number or type of infiltrating immune cells. By contrast, significantly higher numbers of TC T lymphocytes were found in patients without metastasis, while significantly higher numbers of TC macrophages were found in dogs with metastasis. Immune cell infiltrate did not differ according to clinical stage. The results indicate that the tumor immune microenvironment, specifically TILs and TAMs, contribute to tumor behavior and may influence metastatic potential; in particular, high CD3 infiltration may prevent tumor progression, while increased macrophage infiltration could promote it.

Predictors of delayed hospital discharge after robot-assisted partial nephrectomy: the impact of single-port robotic surgery.

To evaluate the predictors of delayed discharge for patients undergoing robot-assisted partial nephrectomy (RAPN) at our Institution since the introduction of the single port (SP) robotic system. We performed a retrospective review of our prospectively maintained database of patients undergoing RAPN from September 2020 to August 2024. Patients were categorized by the postoperative day of their discharge: POD1 (single overnight stay) or POD > 1 (more than one night stay). Multivariable logistic regression analysis was used to test the probability of prolonged hospital stay (defined as more than one night stay) adjusting for age at surgery, surgical approach, Charlson comorbidity index, baseline hemoglobin, antiplatelet or anticoagulant medications, clinical tumor stage, and intraoperative blood transfusion. Overall, 255 patients were identified for the analysis. Patients discharged on POD1 were younger (p = 0.004), reported a lower Charlson Comorbidity Index (p = 0.002), higher preoperative hemoglobin levels (p = 0.005), and smaller tumor size (p < 0.001). Higher rates of discharge on POD1 were recorded for both multiport transperitoneal (59.5 vs. 40.5%, p = 0.02) and SP retroperitoneal (81.5 vs. 18.5%, p = 0.004). Clinical tumor stage (p = 0.02) and intraoperative blood transfusion (p = 0.05) emerged as independent risk factors for POD > 1. Baseline hemoglobin emerged as a protective factor (p = 0.05) as well as SP approach (p = 0.03). SP-RAPN holds potential to shorten hospitalization without hampering surgical outcomes. By maximizing the adoption of a RP approach and minimizing surgical invasiveness, SP robotic surgery allows to significantly expand the pool of RAPN patients that can be discharged after a single overnight stay.

Predictive values of body mass index, prognostic nutritional index and C-reactive protein to prealbumin ratio for prognosis of patients receiving radical gastrectomy.

we aimed to analyze the predictive values of body mass index (BMI), prognostic nutritional index (PNI) and C-reactive protein to prealbumin ratio (CRP/PA) for the prognosis of patients receiving radical gastrectomy. one hundred patients subjected to radical gastrectomy from August 2015 to January 2018 were enrolled. The cut-off values of BMI, PNI and CRP/PA on the receiver operating characteristic (ROC) curves were obtained and applied to establish a low BMI group (n = 46) and a high BMI group (n = 54), a low PNI group (n = 48) and a high PNI group (n = 52), as well as a low CRP/PA group (n = 57) and a high CRP/PA group (n = 43). through comparing the low BMI group with the high BMI group, there were differences in the tumor diameter, invasion depth, clinical stage, and lymph node metastasis status (p < 0.05). Differences were found in the invasion depth, tumor diameter, lymph node metastasis status, clinical stage, and postoperative adjuvant therapy in the low CRP/PA group compared with the high CRP/PA group (p < 0.05). The survival rate of all patients was 45.00 % (45/100) during the 5 years of follow-up. According to the Kaplan-Meier survival analysis, the low BMI group, low PNI group and high CRP/PA group had significantly reduced overall survival rates in comparison to those of the high BMI group, high PNI group and low CRP/PA group, respectively (p < 0.05). BMI, PNI and CRP/PA have important predictive values for the prognosis of patients undergoing radical gastrectomy.

Primary retroperitoneal lymph node dissection in clinical stage 2a/b non-seminomatous germ cell tumour.

To reassess the role of primary retroperitoneal lymph node dissection (RPLND) in patients with marker-negative non-seminomatous germ cell tumour (NSGCT) clinical stage (CS) 2a, to explore results in patients with CS 2b and to evaluate surgical methods, recurrence, and adjuvant chemotherapy indications. Data from 17 institutions were collected, comprising 305 men who underwent primary RPLND for CS 2 NSGCT. Regression analyses were conducted to predict histology in the RPLND specimen and disease-free survival (DFS). A larger retroperitoneal lymph node diameter was associated with pure teratoma in the RPLND specimen (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.07; P = 0.03), but no association was observed with DFS. The 5-year DFS rates in marker negative CS 2a and 2b were 79% and 76%. In men with non-teratomatous viable cancer in the RPLND specimen, the 5-year DFS rates for CS 2a and 2b were 95% and 87% with adjuvant chemotherapy, and 67% and 74% without adjuvant chemotherapy. We did not identify an association between the number of adjuvant chemotherapy cycles and DFS. Our study suggests considering primary RPLND not only in marker-negative CS 2a but also in CS 2b. Further research should determine the efficacy of primary RPLND in men with CS 2c and marker-positive CS 2, as well as which patients may benefit from adjuvant chemotherapy and the optimal cycle number.

Predictive model for PSA persistence after radical prostatectomy using machine learning algorithms.

To evaluate the efficacy of a machine learning model for predicting prostate-specific antigen (PSA) persistence after radical prostatectomy (RP). Data from 470 patients who underwent RP at the Affiliated Hospital of Qingdao University from January 2018 to June 2021 were retrospectively analyzed. Ten risk factors, including age, body mass index (BMI), preoperative PSA, biopsy Gleason score, total prostate specific antigen density (PSAD), clinical tumor stage, clinical lymph node status, seminal vesicle invasion, capsular invasion and positive surgical margin, were included in the analysis. The data were randomly divided into a training set and a test set at a ratio of 7:3, and seven different machine learning algorithms were compared. The confusion matrix, receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic performance of the model, and the random forest algorithm found to be the optimal prediction model. In the entire cohort, 142 (30.21%) patients developed PSA persistence. Based on all included risk factors, the random forest model had the best effect among the seven models, with an AUC of 0.8607 in the training set and 0.8011 in the test set. The feature importance results showed that capsular invasion, positive surgical margin, preoperative PSA and biopsy Gleason score were the four most important risk factors for PSA persistence after RP. The Random Forest algorithm performed excellently in this study and can be used to construct a predictive model for PSA persistence. By incorporating clinical data from the Asian region and exploring the risk factors for PSA persistence, this study contributes to the existing research and aids clinicians in assessing the risk of PSA persistence occurrence, enabling timely treatment planning and improving patient prognosis.

Unlocking the diagnostic potential of vascular endothelial growth factor and interleukin-17: Advancing early detection strategies for hepatocellular carcinoma.

Tian et al investigated the diagnostic value of serum vascular endothelial growth factor (VEGF) and interleukin-17 (IL-17) in primary hepatocellular carcinoma (PHC). Their retrospective study, published in the World Journal of Gastrointestinal Surgery, revealed that the serum levels of VEGF and IL-17 are significantly elevated in PHC patients compared with healthy controls. These biomarkers are closely associated with pathological features such as tumor metastasis and clinical tumor node metastasis stage. A receiver operating characteristic analysis further confirmed the diagnostic efficacy thereof, suggesting that VEGF and IL-17 could serve as valuable tools for early detection and treatment guidance. This study underscores the potential of integrating these biomarkers into clinical practice to increase diagnostic accuracy and improve patient management in PHC.

Significant Effect of Carbon-Ion Radiation Therapy Combined With Androgen Deprivation on Biochemical Recurrence Rates in High-Risk Prostate Cancer Patients: A Two-Center Controlled Trial Compare With X-Ray External Beam Radiation Therapy.

To compare the effects of carbon-ion radiation therapy (CIRT) and external beam radiotherapy (EBRT) on the prognosis of patients with prostate cancer. The effects of initial prostate-specific antigen (iPSA), clinical Tumor (cT) stage, radiotherapy method, and other clinical factors on the prognosis of 577 patients with radiotherapy were analyzed. Cox regression analysis showed that CIRT (RR: 0.49, p = 0.0215), cT stage ≥ 3 (RR: 2.72, p = 0.0003), and iPSA ≥ 16 ng/mL (RR: 1.74, p = 0.0347) were independent predictors of biochemical recurrence (BCR). After propensity score matching (PSM), CIRT (RR: 0.42, p = 0.0147), cT stage ≥ 3 (RR: 2.55, p = 0.0092), and iPSA ≥ 16 ng/mL (RR: 2.12, p = 0.0366) were still the predictors of univariate analysis. In multivariate analysis, CIRT (RR: 0.42, p = 0.015) and cT stage≥ 3 (RR:2.21, p = 0.0332) were independent predictors of BCR. Among them, we used iPSA and cT stages to establish a new radiotherapy selection model based on BCR risk. Patients who met more than one factor (score ≥ 1) and underwent CIRT had significantly better BCR progression-free survival (PFS) than those who received EBRT (p ≤ 0.01). This was also confirmed by Kaplan-Meier analysis after PSM. CIRT patients exhibited lower 5-year BCR rates compared to the EBRT group. Patients with a risk score of our model ≥ 1 undergoing CIRT were more likely to experience BCR benefits compared to those receiving EBRT.

Highly specific multiplex DNA methylation detection for liquid biopsy of colorectal cancer

BackgroundCirculating tumor DNA (ctDNA) has emerged as a useful biomarker for cancer detection and prognosis. In this study, we developed a strategy for developing a highly specific multiplex qPCR assay to detect methylated ctDNA in the blood of colorectal cancer (CRC) patients and investigated the potential use for the detection and prognosis of CRC. MethodsBisulfite conversion and amplicon sequencing were used to confirm potential CRC-specific DNA methylation markers. The selected DNA methylation candidates were validated by qMSP. The six best-performing markers were used to develop a new single-tube multiplex quantitative methylation-specific PCR assay (mqMSP). The mqMSP assay was applied to analyze plasma samples from 114 CRC patients, 47 patients with advanced adenoma, 45 patients with benign polyps, and 57 healthy controls. The clinical performance of the assay and associations with clinical outcomes were assessed. ResultsSix DNA methylation biomarkers were confirmed to be specifically hypermethylated in CRC tumor tissues. The newly developed mqMSP assay detected CRC with extremely high specificity (specificity of 98.2 %, with sensitivity of 67.5 %). The detection rate of ctDNA was significantly correlated with tumor size and clinical stage, with ctDNA methylation levels in the blood markedly increased with larger tumor size, poor differentiation, and advanced stage. Moreover, high preoperative methylated ctDNA level was associated with worse recurrence-free survival and overall survival. ConclusionWe provided a strategy for identification of multiple highly-specific DNA methylation markers for designing multiplex DNA methylation assays for liquid biopsies of CRC. The newly developed assay has potential for CRC early detection, and prognosis.

A 3-arm randomized control trial to compare the efficacy of re-circulant hyperthermic intravesical chemotherapy versus conventional intravesical mitomycin C and BCG therapy for intermediate-risk non-muscle invasive bladder cancer.

To evaluate the efficacy and side effects of re-circulant hyperthermic intravesical chemotherapy versus conventional treatments for intermediate risk non-muscle invasive bladder cancer (NMIBC). A randomized 3-arm, parallel group trial was conducted at a single tertiary care centre. 135 patients with low-grade intermediate-risk cancer, having undergone complete resection of bladder tumor were included. Patients were assigned 1:1:1, to receive intra-vesical chemo-hyperthermia (C-HT), mitomycin-C (MMC) or BCG therapy. There was no treatment crossover. Patients were followed up with check cystoscopy every 3 months for histopathological recurrence. The three arms were comparable in terms of age, gender, tumor size, number of tumors and clinical stage or grade of tumors. Mean tumor size was 2.58 (± 0.88) cm and the mean number of tumors resected was 2.04 (± 1.02) (Range 1-5). There was no significant difference between the various groups for tumor recurrence (χ2 = 1.96, p = 0.375) or time to recurrence (13.6 vs. 10.8 vs. 9.8 months, p = 0.844)though incidence of non-healing necrotic area was higher with C-HT (22.2% vs. 11.1% and 4.8%, χ2 = 6.093, p = 0.048). Median (IQR) follow up period was 26 (12-52) months. Treatment discontinuation or drug intolerance was significantly higher in BCG arm (p = 0.03). Intravesical C-HT with MMC, conventional MMC and BCG are equally effective and comparable alternatives for intravesical therapy in low-grade intermediate-risk NMIBC. Higher incidence of non-healing resection site with C-HT and higher local symptoms with BCG are a concern.

Can Ki-67 serve as a suitable marker to indicate the necessity of staging diagnostics in cases of low-risk breast cancer?

For many years, staging tests have not been routinely employed for low-risk early breast cancer (EBC). However, the role of Ki-67 in determining the need for staging tests in low-risk EBC remains unclear. Our study aimed to assess the number and types of staging diagnostics, additional imaging, false-positive results, and rate of distant metastases in low-risk EBC with low and high Ki-67 (< / ≥ 25%). This is a retrospective, single institution cohort study. All patients with newly diagnosed low-risk breast cancer at the University Medical Center in Freiburg in 2017 and 2021 were included. Low-risk was defined as clinical tumor stage T1/2, node negative (N0), hormone receptor positive, HER2 negative, asymptomatic EBC. Information on demographics, clinical and pathological characteristics, as well as number and type of performed staging diagnostics was obtained. Rate and type of additional imaging or follow-up diagnostics due to suspicious findings was analyzed. The patients were divided into two groups (Ki-67 < and ≥ 25%) and rates of distant metastases, performed staging diagnostics and false positive rates were compared. A total of 189 patients with low-risk EBC were identified, with 54% (n = 102) having Ki-67 < 25% and 46% (n = 87) having Ki-67 ≥ 25%. Risk for distant metastases was 0% in Ki-67 < 25% and 1.1% in patients with Ki-67 ≥ 25% (p = 0.46). Due to suspicious findings in the initial staging diagnostic, additional imaging was required for 11.8% (n = 12) of patients with Ki-67 < 25% compared to 19.5% (n = 17) of patients with Ki-67 ≥ 25% (p = 0.16). False positive rates did not differ significantly between the two groups (7.6% in Ki-67 < 25% vs. 9.8% in Ki-67 ≥ 25%; p = 0.55). Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.