Early Recurrence Research Articles

The impact of time to postoperative recurrence on the prognosis of patients with esophageal cancer post recurrence: exploratory analysis of OGSG 1003.

The association between recurrence timing and prognosis in patients with locally advanced resectable esophageal cancer undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy remains unclear. This study aimed to clarify this association using multicenter prospective clinical trial data. Among 162 patients enrolled in a NAC phase II study comparing the efficacy of cisplatin and fluorouracil plus docetaxel with cisplatin and fluorouracil plus adriamycin, 64 patients with recurrence after R0 resection were included in this study. We evaluated the association between recurrence timing and overall survival after recurrence (OSr), along with clinicopathological factors associated with recurrence timing and OSr. Among 64 patients, 46 (71.9%) and 59 (92.2%) experienced recurrence within 1 and 2years after surgery, respectively. Groups based on recurrence timing, including ≤ 6, 6-12, and > 12 months, had median OSr of 3.6, 13.9, and 13.4 months, respectively. The prognosis was significantly poorer for patients with recurrence ≤ 6 months after surgery than for other patients (P < 0.001). Multivariate analysis revealed pathological lymph node staging as an independent factor associated with early recurrence (odds ratio: 3.46, 95% confidence interval: 1.47-8.02, P = 0.0045). On the other hand, multivariate analysis for factors associated with OSr revealed pT (hazard ratio [HR]: 1.91, 95%CI 1.26-2.88, P = 0.0022), early recurrence (HR: 6.88, 95%CI 2.68-17.6, P < 0.001), and treatment after recurrence, with both local treatment (HR: 0.47, 95%CI 0.22-0.98, P = 0.043) and chemotherapy (HR: 0.25, 95%CI 0.11-0.58, P = 0.0011) as independent prognostic factors. Patients with advanced esophageal cancer experiencing recurrence within 6 months after esophagectomy following NAC have an extremely poor prognosis, suggesting that an advanced pN stage is associated with early recurrence.

Impact of Diabetes Mellitus and Obesity Comorbidities on Survival Outcomes after Hepatocellular Carcinoma Resection: A Multicenter Retrospective Study

Introduction: This study aimed to evaluate the association of obesity and diabetes mellitus (DM) comorbidity with hepatocellular carcinoma (HCC) recurrence and survival. Methods: We investigated 1,644 patients who underwent hepatic resection for solitary HCC without vascular invasion using computed tomography. Patients were categorized into four groups according to the combination of obesity and DM comorbidities: OB (+) or (−) and DM (+) or (−). Postoperative cumulative recurrence rates within and beyond 2 years and beyond 5 years were assessed. Results: Multivariate Cox proportional hazard regression analysis revealed that the adjusted hazard ratios (HRs) of reduced recurrence-free survival was 1.10 (95% confidence interval [CI]: 0.91–1.33; p = 0.31), 0.94 (95% CI: 0.78–1.12; p = 0.48), and 1.24 (95% CI: 1.01–1.54; p = 0.045) in the OB(+)DM(−), OB(−)DM(+), and OB(+)DM(+) groups compared with the OB(−)DM(−) group, respectively. Additionally, the corresponding adjusted HRs of reduced overall survival were 0.93 (p = 0.57), 0.97 (p = 0.76), and 1.38 (p = 0.013) for OB(+)DM(−), OB(−)DM(+), and OB(+)DM(+) groups, respectively. No significant difference in the early recurrence rate was determined among the four groups. The OB(+)DM(+) group demonstrated an increased risk for late recurrence beyond 2 years and 5 years postoperatively compared with the OB(−)DM(−) group (HR: 1.51; p = 0.024 and HR: 2.53; p = 0.046, respectively). The OB(+)DM(−) and OB(−)DM(+) groups demonstrated an increased risk for late recurrence beyond 5 years postoperatively (HR: 3.83; p < 0.001 and HR: 1.95; p = 0.037, respectively). Conclusions: Obesity and DM coexistence increased late recurrence and worsened prognosis in patients with HCC undergoing hepatic resection. The results help surgeons develop possible different surveillance protocol and need to focus on diabetes/obesity control during life-long surveillance for patients with HCC.

Molecular Subtype of Small Cell Lung Cancer: Challenge for Transforming into Clinical Practice

Small cell lung cancer (SCLC), one of the histological subtypes of lung cancer, is characterized by high proliferation, early metastasis, susceptibility to drug resistance and recurrence. For several years, SCLC has always been regarded as a homogeneous disease, treated with a unified radiotherapy and chemotherapy strategy. Despite significant early therapeutic effects, drug resistance and recurrence occur quickly, and there is a lack of satisfactory treatment results, which may be due to insufficient understanding of the tumor heterogeneity of SCLC at present. Recently, the concept of SCLC molecular subtype based on the definition of relatively high expression of lineage transcription factors has been proposed in preclinical studies. This article mainly elaborates on the current status and latest findings of SCLC molecular subtype, emphasizing the potential problems that molecular typing may encounter in clinical practice, aiming to promote understanding of the research progress of molecular subtype in SCLC. .

A Clinical Study of Anterior Abdominal Wall Hernias and Its Management: A Medical College Experience.

Objective We aim to evaluate the various risk factors contributing to the occurrence of anterior abdominal wall hernias and assess the various surgical modalities. Materials and methods This prospective observational research was conducted between 2022 and 2024 at a tertiary care health center, involving 100 participants with an anterior abdominal wall hernia diagnosis aged over 14 years. The study excluded patients under 14 years with bleeding diathesis, inherited coagulopathies, inguinal or femoral hernias, or recurrent ventral hernias. Participants underwent detailed clinical examinations and biochemical evaluationsand underwent a primary ultrasonography (USG)/contrast-enhanced computed tomography (CECT) to determine defect size. Risk factors were documented, including age, gender, occupation, body mass index (BMI), comorbidities, previous surgery history, multiparity, smoking, chronic straining due to constipation or benign prostatic hyperplasia (BPH), malnutrition, chronic steroid use, chronic renal failure, and chronic liver disease. The surgical procedure was determined by the same surgical team for all cases. Standard antibiotic prophylaxis and preoperative painting/draping protocols were followed in all cases. Intraoperatively, intraoperative time (in hours) was documented. Postoperative parameters included pain, hematoma formation, seroma formation, surgical site infections (SSIs), and early recurrence. These intra- and postoperative findingsconstituted the primary outcome parameters. Secondary outcome parameters included hospital stayduration and time taken to return to work. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 16 (IBM SPSS Statistics, Armonk, NY) software. Results The study analyzed the occurrence of ventral hernias in 100 patients, with the fourth decade having the highest occurrence (n=42 (42%)). The majority of the participants were male (female: n=47 (47%), male: n=53 (53%)). The majority of the participants were laborers, and 24% (n=24) were office workers. The study found that hypertension, diabetes mellitus, and chronic obstructive pulmonary disease were risk factors for hernias. Other risk factors included obesity, previous history of surgery, multiparity, smoking, chronic straining, malnutrition, and chronic steroid use. The most common type of ventral hernia was umbilical hernia (n=33 (33%)), followed by paraumbilical hernias (n=30 (30%)), and incisional hernias (n=20 (20%)). Of the 100 patients, 74% underwent open hernia repair, with the mean operation time being minimal in cases managed with laparoscopic repair (2.5±0.67 hours). Postoperative painwas highest with the Rives-Stoppa (RS) repair with component separation group. The incidence of surgical site infection was the maximum among cases of open anatomical repair (41.7%), followed by RS repair (31.3%), while it was the minimum in laparoscopic repair (3.7%). Early recurrence was lower in the laparoscopic group (n=1 (3.7%)). Conclusion The study highlights risk factors for abdominal wall hernia and management approaches. Understanding these is crucial for identifying and preventing recurrence. Surgeons must choose the right surgical approach based on patient health and symptoms to achieve desired outcomes and minimize complications. In addition, surgical expertise, availability of resources, and knowledge of what works best for the surgeon constitute important determinants of surgical outcomes.

A CT-based radiomics tumor quality and quantity model to predict early recurrence after radical surgery for colorectal liver metastases.

This study aimed to develop a tumor radiomics quality and quantity model (RQQM) based on preoperative enhanced CT to predict early recurrence after radical surgery for colorectal liver metastases (CRLM). A retrospective analysis was conducted on 282 cases from 3 centers. Clinical risk factors were examined using univariate and multivariate logistic regression (LR) to construct the clinical model. Radiomics features were extracted using the least absolute shrinkage and selection operator (LASSO) for dimensionality reduction. The LR learning algorithm was employed to construct the radiomics model, RQQM (radiomics-TBS), combined model (radiomics-clinical), clinical risk score (CRS) model and tumor burden score (TBS) model. Inter-model comparisons were made using area under the curve (AUC), decision curve analysis (DCA) and calibration curve. Log-rank tests assessed differences in disease-free survival (DFS) and overall survival (OS). Clinical features screening identified CRS, KRAS/NRAS/BRAF and liver lobe distribution as risk factors. Radiomics model, RQQM, combined model demonstrated higher AUC values compared to CRS and TBS model in training, internal and external validation cohorts (Delong-test P < 0.05). RQQM outperformed the radiomics model, but was slightly inferior to the combined model. Survival curves revealed statistically significant differences in 1-year DFS and 3-year OS for the RQQM (P < 0.001). RQQM integrates both "quality" (radiomics) and "quantity" (TBS). The radiomics model is superior to the TBS model and has a greater impact on patient prognosis. In the absence of clinical data, RQQM, relying solely on imaging data, shows an advantage in predicting early recurrence after radical surgery for CRLM.

General Anesthesia Improves Efficiency of High-Power Short-Duration Catheter Ablation for Atrial Fibrillation: Comparison with Mild Conscious Sedation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia globally. High-power, short-duration radiofrequency (RF) catheter ablation (CA) for AF has recently emerged, reducing ablation times and enhancing patient tolerability with comparable efficacy and safety. While the benefits of general anesthesia (GA) for standard-power, standard-duration CA are well-established, data comparing GA to mild conscious sedation (MCS) for high-power, short-duration CA are limited. We included patients undergoing high-power, short-duration CA for AF under GA (group 1) or MCS (group 2). Procedural characteristics, success rates, and mid-term outcomes were compared. In total, 131 patients, 47 in the GA group and 84 in the MCS group, were included. CA was performed for paroxysmal AF in 34 patients in group 1 (72.3%) and 68 patients in group 2 (80.9%). We found lower a mean total procedure time (100 [90-120] vs. 160 [130-180] min, p < 0.0001), lower radiation exposure (932.5 [625-1716] vs. 2445 [1228-4791] μGy, p < 0.0001 and 4.5 [3-7.1] 7.3 [4.2-13.5] min, p = 0.0003) and fewer RF applications (71 [54.8-83.8] vs. 103 [88.5-120.5], p < 0.0001) in the GA group. No major complications occurred. The 6-month AF recurrence rate was comparable between the groups (21.2% vs. 33.3%, p = 0.15). In patients undergoing high-power, short-duration RFCA for AF, the use of GA is associated with better procedural efficiency while simultaneously associated with an early recurrence rate comparable to MCS.

Prediction of non-muscle invasive bladder cancer recurrence using deep learning of pathology image

We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752–0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer–Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Lecithin-cholesterol acyltransferase is a potential tumor suppressor and predictive marker for hepatocellular carcinoma metastasis

BACKGROUND Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, and metastasis is the main cause of early recurrence and poor prognosis. However, the mechanism of metastasis remains poorly understood. AIM To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment. METHODS The candidate molecule lecithin-cholesterol acyltransferase (LCAT) was screened by gene microarray and bioinformatics analysis. The expression levels of LCAT in clinical cohort samples was detected by quantitative real-time polymerase chain reaction and western blotting. The proliferation, migration, invasion and tumor-forming ability were measured by Cell Counting Kit-8, Transwell cell migration, invasion, and clonal formation assays, respectively. Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression. The immunohistochemistry for Ki67, E-cadherin, N-cadherin, matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC. Gene set enrichment analysis (GSEA) on various gene signatures were analyzed with GSEA version 3.0. Three machine-learning algorithms (random forest, support vector machine, and logistic regression) were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases. RESULTS LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues. LCAT was significantly downregulated in HCC tissues, which is correlated with recurrence, metastasis and poor outcome of HCC patients. Functional analysis indicated that LCAT inhibited HCC cell proliferation, migration and invasion both in vitro and in vivo . Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis (HCC size ≤ 3 cm vs 3-9 cm, P &lt; 0.001; 3-9 cm vs &gt; 9 cm, P &lt; 0.01; metastatic-free HCC vs extrahepatic metastatic HCC, P &lt; 0.05). LCAT suppressed the growth, migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling. Our results indicated that the logistic regression model based on LCAT, TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients. CONCLUSION LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling. LCAT is a prognostic marker and potential therapeutic target for HCC.

Preoperative CT features for characterization of vessels that encapsulate tumor clusters in hepatocellular carcinoma

PurposeTo explore the capability of preoperative CT imaging features, in combination with clinical indicators, for predicting vessels that encapsulate tumor clusters (VETC) pattern and prognosis in hepatocellular carcinoma (HCC). Materials and methodsFrom January 2015 to May 2022, patients with HCC who underwent curative resection and preoperative enhanced CT were retrospectively included. Clinical indicators and imaging featuresassociated with the VETC pattern were determined by logistic regression analyses. The early recurrence (ER) rate was determined using the Kaplan-Meier survival curve. Factors associated with ER after surgical resection were identified by Cox regression analyses. ResultA total of 243 patients with HCCwere evaluated. The total bilirubin > 17.1 μmol/L (odds ratio [OR] 3.43, 95 % Confidence Interval [CI] 1.70, 6.91, p = 0.001), serum α-fetoprotein > 100 ng/mL (OR 2.41, 95 % CI 1.25, 4.67, p = 0.009), intratumor artery (IA) (OR 2.00, 95 % CI 1.04, 3.86,p = 0.039) and arterial peritumoral enhancement (OR 2.60, 95 % CI 1.13, 5.96, p = 0.025) were independent risk factors for VETC+–HCC. The VETC+status andCT feature ofIA were associated with an increased risk of recurrence, with a shorter median RFS, compared to those without these factors (p < 0.001 and p = 0.019, respectively). In multivariable Cox regression analysis, the VETC+(hazard ratio [HR] 2.60, 95 % CI 1.66, 4.09, p < 0.001), morphological patterns of confluent multinodular growth (HR 1.79, 95 % CI 1.10, 2.91,p = 0.019), the number of the tumors (≥2) (HR 2.69, 95 % CI 1.56, 4.65, p < 0.001), and the IA (HR 1.73, 95 % CI 1.12, 2.66, p = 0.013) were independent predictors of ER in patients with HCC after surgical resection. ConclusionPreoperative CT features combined with clinical indicators could predict VETC pattern, and the CT features, along with VETC status, were of prognostic significance for early postoperative recurrence in patients with HCC. Clinical Relevance StatementPreoperative CT features combined with clinical indicators could predict VETC pattern, and the CT features, along with VETC status, were of prognostic significance for early recurrence in patients with HCC after surgical resection.

Prostate-specific membrane antigen-radioguided surgery salvage lymph node dissection: experience with fifty oligorecurrent prostate cancer patients

PurposeThe higher detection efficacy of PSMA PET for oligometastatic recurrence of prostate cancer has promoted new loco-regional treatment options. PSMA-targeted radioguided surgery (PSMA-RGS) was introduced to facilitate salvage surgery of small tumor deposits. The objectives of this retrospective analysis are to describe an independent single-center consecutive cohort of patients undergoing PSMA-RGS and to evaluate its clinical and oncological outcomes.MethodBetween 2018 and 2022, 53 patients were treated with PSMA-RGS and 50 patients were available for final analyses. All patients were initially treated with radical prostatectomy (RP) and presented with biochemical recurrence (BCR) with at least one positive lesion on PSMA-PET imaging. After preparation of 99mTc-PSMA-I&S and intravenous injection, surgery was performed by using a gamma-probe intraoperatively.ResultsMedian age was 70 years (IQR 65–73) and the median PSA at salvage surgery was 1.2 ng/mL (IQR 0.6-3.0). In all patients pathologically positive lesions could be removed during PSMA-RGS. 29 (58%) patients had one pathologically positive lesion, 14 (28%) had two and 7 (14%) had three or more, respectively. The overall complication rate was 26% with 4 (8%), 1 (2%), and 8 (16%) having Clavien-Dindo (CD) type I, II, and IIIb complications, respectively. During the follow-up period 31 (62%) patients experienced BCR and 29 (58%) received further therapy.ConclusionsPSMA-RGS is a promising treatment option to enhance salvage surgery in early biochemical recurrence. However, only 42% of the patients treated with PSMA RGS remain without a biochemical recurrence. Further research is mandatory to identify patients, who profit from PSMA-RGS.

Nanochannel-confined platinum nanostructure for enhancement of luminol-dissolved oxygen electrochemiluminescence coupled with gated aptasensor for sensitive detection of carcinoembryonic antigen

Rapid and precise detection of tumor biomarkers in serum is of great significance for early diagnosis, treatment assessment, and recurrence monitoring of cancers. The fabrication of user-friendly electrochemiluminescence (ECL) aptasensors with effective signal amplification is highly desirable. In this study, an ECL aptasensor was developed with luminol-based ternary ECL platform using dissolved oxygen as endogenous co-reactant and nanochannel-confined platinum nanoparticles (PtNPs) as co-reactant promoter, which can realize highly sensitive detection of the tumor biomarker, carcinoembryonic antigen (CEA). On the cost-effective indium tin oxide (ITO) electrode, amino-modified vertically-ordered mesoporous silica film (NH2-VMSF) was easily grown to form high-density nanochannel array with ultrasmall nanochannels. PtNPs were then in-situ synthesized within the nanochannels via electrodeposition. Ternary ECL system was successfully fabricated as confined PtNPs can catalyze the electroreduction of dissolved oxygen at negative potentials as well as electrochemical oxidation of luminol, enhancing the ECL signal of luminol. The recognitive aptamer (Apt) was covalently immobilized on the outer surface of NH2-VMSF, resulting in the fabrication of an aptasensor. In presence of CEA, a decreased ECL signal was obtained as the formed complex on the recognition interface hindered the diffusion of ECL emitter to the supporting electrode. Based on this signal turn-off mode, sensitive detection of CEA was achieved ranged from 10 fg mL−1 to 100 ng mL−1, with a low detection limit (DL, 0.4 fg mL−1). The aptasensor displayed high selectivity and good reproducibility. The nanochannel-based aptasensor and ternary ECL system demonstrates great potential in convenient and sensitive detection of cancer biomarker.

Characteristics of Abdominal Fat Based on CT Measurements to Predict Early Recurrence After Initial Surgery of NMIBC in Stage Ta/T1

IntroductionThis study aimed to assess the predictive value of abdominal fat characteristics measured by computed tomography (CT) in identifying early recurrence within one year post-initial transurethral resection of bladder tumor (TURBT) in patients with nonmuscle-invasive bladder cancer (NMIBC). A predictive model integrating fat features and clinical factors was developed to guide individualized treatment. Materials and MethodsA retrospective analysis of 203 NMIBC patients from two medical centers was conducted. Abdominal CT images were analyzed using 3D Slicer software. Spearman correlation, logistic regression, and the Lasso algorithm were employed for data analysis. Predictive efficacy was assessed using the area under the curve (AUC) of receiver operating characteristic (ROC) and decision curve analysis (DCA). Calibration was evaluated using the Hosmer-Lemeshow test. ResultsSignificant differences in abdominal fat characteristics were found between the recurrence and nonrecurrence groups. All fat features positively correlated with body mass index (BMI), with bilateral perirenal fat thickness (PrFT) showing superior predictive performance. Multivariate logistic regression identified independent predictors of early recurrence, including tumor number, early perfusion chemotherapy, left and right PrFT, and visceral fat area (VFA) at umbilical and renal hilum levels. The Lasso-based model achieved an AUC of 0.904, outperforming existing models. ConclusionAbdominal fat characteristics, especially bilateral PrFT, strongly correlate with early recurrence in NMIBC. The Lasso-based model, integrating fat and clinical factors, offers superior predictive efficacy and could improve individualized treatment strategies.

Intraindividual comparison of prognostic imaging features of HCCs between MRIs with extracellular and hepatobiliary contrast agents.

Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (HBA-MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs. The present study included 102 prospectively enrolled at-risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA-MRI and HBA-MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs. The frequencies of prognostic imaging features were not significantly different between the two MRIs (p = .07 to >.99). Non-smooth tumour margin (ECA-MRI, odds ratio [OR] = 5.30; HBA-MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA-MRI, OR = 4.26; HBA-MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two-trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA-MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA-MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA-MRI vs 51.3% on HBA-MRI, p = .75) were not significantly different between the two MRIs. Prognostic imaging features of HCC may be comparable between ECA-MRI and HBA-MRI.

Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238.

In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy. Patients 15 years or older with resected stage IIIB-C/IV melanoma were stratified by stage and tumor PD-L1 status and randomly assigned to receive nivolumab 3 mg/kg every 2 weeks, or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks for 1 year or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Patients with recurrence in each group were assessed for PFS and OS from subsequent systemic therapy (SST) initiation per recurrence timing (≤12 months [early] v >12 months [late] from initial therapy). Recurrences occurred in 198 (44%) of 453 nivolumab-treated patients (122 early, 76 late) and 232 (51%) of 453 ipilimumab-treated patients (160 early, 72 late). Median PFS on next-line systemic therapy for nivolumab-treated patients recurring early versus late was 4.7 versus 12.4 months (24-month rates, 16% v 31%); median OS was 19.8 versus 42.8 months (24-month rates: 37% v 73%). In response to subsequent therapy, patients on nivolumab with late versus early recurrence were more likely to benefit from anti-PD-1 monotherapy. Nivolumab-treated patients with either an early or late recurrence benefitted from an ipilimumab-based therapy or targeted therapy, each with similar OS. Postrecurrence survival was longer for patients who recurred >12 months. Patients on nivolumab who recurred early benefitted from SST but had better survival with ipilimumab-based regimens or targeted therapy compared with anti-PD-1 monotherapy.

New Biomarkers to Define A Biological Borderline Situation for Pancreatic Adenocarcinoma - Results of An Ancillary Study of the PANACHE01-PRODIGE48 Trial.

To investigate in patients treated for a resectable pancreatic ductal adenocarcinoma (PA), the prognostic value of baseline CA19-9 and circulating tumour DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial. Biological borderline situation that was first used by the MD Anderson, became a standard practice following the international consensus conference in 2016 to manage PA. Regarding the risk of systemic disease especially in the setting of "markedly elevated" CA19-9, neoadjuvant therapy is advised to avoid unnecessary surgery, with risk of early recurrence. To best define biological borderline situations, new biomarkers are needed. Characteristics at diagnosis and OS were compared between patients with or without ctDNA status available. OS was estimated with Kaplan Meier method and compared with log-rank test. Restricted cubic spline approach was used to identify optimal threshold for biological parameters for death risk stratification. Univariate and multivariate Cox proportional hazard models were estimated to assess the association of ctDNA status and other parameters with OS. Among the 132 patients from the primary population for analysis in the PANACHE01 -PRODIGE 48 trial, 92(71%) were available for ctDNA status at diagnosis. No selection bias was identified between patients with or without ctDNA status. 14 patients (15%) were ctDNA+ and exhibited a higher risk for death (P=0,0188; HR95% CI: 2.28 (1.12-4.63). In the 92 patients with ctDNA status available among the others parameter analysed only CA19-9 was statically associated with OS in univariate analysis. Patients with log of CA19-9 equal or superior to 4.4 that corresponds to a CA19-9 of 80 UI/mL were identified at higher risk for death (P=0,0143; HR95% CI: 2.2 (1.15-4.19). In multivariate analysis CA19-19 remained independently associated with OS (p-value=0.0323). When combining the two biomarkers, median OS was of 19.4 (IC 95% 3.8-Not reached) months, 30.2 (IC 95% 17.1-NR) months and not reached (IC 95% 39.3-NR) for "CA19-9 high and ctDNA+ group", "CA19-9 high or ctDNA+ group", and "CA19-9 low and ctDNA- group", respectively (logrank P=0,0069). Progress in the management of potentially operable PA remains limited, relying solely on strategies to optimize the sequence of complete treatment, based on modern multidrug chemotherapy (FOLFIRINOX, GemNabPaclitaxel) and surgical resection. The identification of risk criteria, such as the existence of systemic disease, is an important issue, currently referred to as "biologic borderline disease". Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. Combining ctDNA to CA19-9 could be of interest to best define biological borderline situations in PA.

Hybrid approach for Recurrence of Cardiovascular Disease Prediction Using Machine Learning Techniques

Cardiovascular disease remains a global health concern, being a leading cause of mortality. In response to the critical nature of heart-related conditions, this research focuses on the development of smart systems leveraging machine learning algorithms for accurate and timely diagnosis. The study explores various machine learning approaches to predict recurrence of heart diseases based on patient data encompassing key health factors. With heart disease being a prevalent cause of death worldwide, real-time forecasting methods from medical data sources have become crucial. The implementation of machine learning in healthcare demonstrates its potential for early and precise recurrence of disease detection. Despite the abundance of health information generated by medical institutions, there is an underutilization of this data, leading to a healthcare system that is "data rich" but "knowledge poor." This work aims to address this gap by presenting a reliable recurrence heart disease prediction system. The research highlights the necessity for effective analysis methods to uncover connections and patterns within healthcare data. The proposed prediction system utilizes a diverse set of health factors, contributing to a comprehensive understanding of heart disease. By leveraging machine learning algorithms, the system aims to enhance the accuracy and efficiency of diagnosis. The findings of this research not only contribute to the advancement of predictive healthcare but also underscore the significance of unlocking valuable insights from the vast pool of medical data. Ultimately, the implementation of such intelligent systems holds promise for improving patient outcomes and reducing the burden of cardiovascular diseases on global healthcare systems. The paper demonstrated Hybrid methods: Support Vector Machine (SVM), Random Forest (RF), and Naïve Bayes (NB), to build the prediction models. Data preprocessing and feature selection steps were done before building the models. The models were evaluated based on the accuracy, precision, recall, and F1-score. The Random Forest model performed best with 94.27% accuracy.

Ten-year outcomes of a randomized clinical trial of endothermal ablation versus conventional surgery for great saphenous varicose veins.

Surgical ligation and stripping (surgery) and endothermal ablation are both effective treatments for varicose veins, improving quality of life (QoL) up to 5 years. Few data are available on long-term outcomes. The aim of this study was to evaluate the outcomes 10 years after interventions in an RCT. Previously this RCT demonstrated that endothermal ablation is associated with superior postprocedural QoL, more rapid recovery, and lower rates of early clinical recurrence. This analysis reports outcomes at 10 years. Patients with symptomatic varicose veins owing to unilateral great saphenous vein reflux were randomized to either surgery or endovenous laser ablation (EVLA). Outcomes at 10 years included clinical recurrence and QoL. Data were obtained for 206 of 280 patients (73.6%) at 10 years. Both groups retained significant QoL improvement compared with pretreatment levels (Aberdeen Varicose Vein Questionnaire (AVVQ), Short Form 36 (SF-36®), and EQ-5D™; P < 0.001). Clinical disease progression from baseline was observed in only 10.7% of patients. The clinical recurrence rate was lower in the EVLA group (37 versus 59%; P = 0.005). The number needed to treat with EVLA to avoid one clinical recurrence within 10 years was five. This was associated with significantly higher (better) generic QoL scores with EVLA in several SF-36® domains, including bodily pain (median 84 (i.q.r. 51-100) versus 62 (41-84); P = 0.009) and general health (77 (62-87) versus 67 (52-82); P = 0.017). AVVQ scores in the EVLA group were also lower (better) (3.1 (0-7.7) versus 6.3 (0.7-13.3); P = 0.029). Both surgery and endothermal ablation are effective treatments for varicose veins at 10 years, with durable improvement in QoL and a very low rate of disease progression. However, endothermal ablation was associated with superior clinical and QoL outcomes. Registration number: NCT00759434 (http://www.clinicaltrials.gov).

Intratumoral Heterogeneity Assessment of the Extracellular Bone Matrix and Immune Microenvironment in Osteosarcoma Using Digital Imaging to Predict Therapeutic Response

The assessment of chemotherapy response in osteosarcoma (OS) based on the average percentage of viable cells is limited, as it overlooks the spatial heterogeneity of tumor cell response (foci of resistant cells), immune microenvironment, and bone microarchitecture. Despite the resulting positive classification for response to chemotherapy, some patients experience early metastatic recurrence, demonstrating that our conventional tools for evaluating treatment response are insufficient. We studied the interactions between tumor cells, immune cells (lymphocytes, histiocytes, and osteoclasts), and bone extracellular matrix (ECM) in 18 surgical resection samples of OS using multiplex and conventional immunohistochemistry (IHC: CD8, CD163, CD68, and SATB2), combined with multiscale characterization approaches in territories of good and poor response (GRT/PRT) to treatment. GRT and PRT were defined as subregions with <10% and ≥10% of viable tumor cells, respectively. Local correlations between bone ECM porosity and density of immune cells were assessed in these territories. Immune cell density was then correlated to overall patient survival. Two patterns were identified for histiocytes and osteoclasts. In poor responder patients, CD68 osteoclast density exceeded that of CD163 histiocytes but was not related to bone ECM load. Conversely, in good responder patients, CD163 histiocytes were more numerous than CD68 osteoclasts. For both of them, a significant negative local correlation with bone ECM porosity was found (P < .01). Moreover, in PRT, multinucleated osteoclasts were rounded and intermingled with tumor cells, whereas in GRT, they were elongated and found in close contact with bone trabeculae. CD8 levels were always low in metastatic patients, and those initially considered good responders rapidly died from their disease. The specific recruitment of histiocytes and osteoclasts within the bone ECM, and the level of CD8 represent new features of OS response to treatment. The associated prognostic signatures should be integrated into the therapeutic stratification algorithm of patients after surgery.

Recurrence pattern and its risk factors in patients with resected pancreatic ductal adenocarcinoma – A retrospective analysis of 272 patients

BackgroundThe aim of this study was to investigate the patterns of recurrence and their associated risk factors in patients who underwent resection for pancreatic carcinoma. MethodsThis retrospective study included 272 patients, who underwent Ro/R1-resection of PDAC from 2005 to 2020 at the University Hospital Erlangen. Risk factors for different recurrence patterns and the prognostic value of recurrence pattern on the overall survival after recurrence were evaluated. Results61 % of the patients experienced recurrence, mostly within the first 12 postoperative months (62 %) and in the form of metastases (87 %). The median overall survival from recurrence was 9.2 months. The preoperative absence of diabetes and the presence of lymph node metastasis were independent risk factors for recurrence and a preoperative CA19-9 exceeding 97 U/ml for early recurrence. Additionally, lymph node metastases were associated with a higher risk of metastatic recurrence. Early recurrence, but not the site of recurrence, was identified as an independent prognostic factor for worse overall survival from recurrence. ConclusionThe occurrence of recurrence and especially of early and metastatic recurrence are associated with a worse overall survival. Patients lacking preoperative diabetes, having high preoperative CA19-9 values and lymph node metastases are particularly at risk for (early) recurrence.

Development of an artificial intelligence–based model to predict early recurrence of neuroendocrine liver metastasis after resection

PurposeWe sought to develop an artificial intelligence (AI)–based model to predict early recurrence (ER) after curative-intent resection of neuroendocrine liver metastases (NELMs). MethodsPatients with NELM who underwent resection were identified from a multi-institutional database. ER was defined as recurrence within 12 months of surgery. Different AI-based models were developed to predict ER using 10 clinicopathologic factors. ResultsOverall, 473 patients with NELM were included. Among 284 patients with recurrence (60.0%), 118 patients (41.5%) developed an ER. An ensemble AI model demonstrated the highest area under receiver operating characteristic curves of 0.763 and 0.716 in the training and testing cohorts, respectively. Maximum diameter of the primary neuroendocrine tumor, NELM radiologic tumor burden score, and bilateral liver involvement were the factors most strongly associated with risk of NELM ER. Patients predicted to develop ER had worse 5-year recurrence-free survival and overall survival (21.4% vs 37.1% [P = .002] and 61.6% vs 90.3% [P = .03], respectively) than patients not predicted to recur. An easy-to-use tool was made available online: (https://altaf-pawlik-nelm-earlyrecurrence-calculator.streamlit.app/). ConclusionAn AI-based model demonstrated excellent discrimination to predict ER of NELM after resection. The model may help identify patients who can benefit the most from curative-intent resection, risk stratify patients according to prognosis, as well as guide tailored surveillance and treatment decisions including consideration of nonsurgical treatment options.