Early Recurrence Research Articles

ABCD2-I Score Predicts Unplanned Emergency Department Revisits within 72 Hours Due to Recurrent Acute Ischemic Stroke.

the ABCD2 score is valuable for predicting early stroke recurrence after a transient ischemic attack (TIA), and Doppler ultrasound can aid in expediting stroke triage. The study aimed to investigate whether combining the ABCD2 score with carotid duplex results can enhance the identification of early acute ischemic stroke after TIA. we employed a retrospective cohort design for this study, enrolling patients diagnosed with TIA who were discharged from the emergency department (ED). The modified ABCD2-I (c50) score, which incorporates a Doppler ultrasound assessment of internal carotid artery stenosis > 50%, was used to evaluate the risk of acute ischemic stroke within 72 h. Patients were categorized into three risk groups: low risk (with ABCD2 and ABCD2-I scores = 0-4), moderate risk (ABCD2 score = 4-5 and ABCD2-I score = 5-7), and high risk (ABCD2 score = 6-7 and ABCD2-I score = 8-9). between 1 January 2014, and 31 December 2019, 1124 patients with new neurological deficits were screened, with 151 TIA patients discharged from the ED and included in the analysis. Cox proportional hazards analysis showed that patients in the high-risk group, as per the ABCD2-I (c50) score, were significantly associated with revisiting the ED within 72 h due to acute ischemic stroke (HR: 3.12, 95% CI: 1.31-7.41, p = 0.0102), while the ABCD2 alone did not show significant association (HR: 1.12, 95% CI: 0.57-2.22, p = 0.7427). ABCD2-I (c50) scores effectively predict early acute ischemic stroke presentations to the ED within 72 h after TIA.

Impact of anatomical liver resection for hepatocellular carcinoma in preventing early-phase local recurrence after surgery.

The superiority of anatomical liver resection (AR) for localized hepatocellular carcinoma (HCC) over nonanatomical liver resection (NR) remains controversial. This study aimed to investigate the impact of AR in preventing local and early HCC recurrence. A total of 280 patients who underwent initial liver resection for solitary HCC ≤5 cm in diameter were categorized into the AR and NR groups and compared using propensity score matching analysis. Between the matched pairs (n = 87 in each group), the incidence rates of local and early (recurrence within 2 years after surgery) recurrences in the AR group were significantly lower than those in the NR group (13.8% vs. 28.7%, p = .025; 20.7% vs. 35.6%, p = .028, respectively). The overall survival in the AR group was better than that in the NR group (median: 13.4 vs. 7.6 years, p = .003). NR was among independent risk factors for early recurrence (odds ratio: 1.98, 95% CI: 1.1-3.6, p = .023) and prognostic factors for local recurrence (hazard ratio: 2.44, 95% CI: 1.4-4.4, p = .003). AR is superior in controlling local and early recurrence postoperatively for solitary HCC ≤5 cm in diameter compared with NR.

COMPARISON OF TOTAL EXTRAPERITONEAL (TEP) AND EXPANDED VIEW TOTAL EXTRAPERITONEAL (eTEP) METHODS AT INGUINAL HERNIA REPAIR

Abstract Background Laparoscopic hernia repair has been accepted as first-line treatment for inguinal hernia by major surgical institutions today, with low complication and recurrence rates. The aim of this prospective clinical study, we compared two different laparoscopic approaches in terms of technical ease, patients' early postoperative quality of life, pain management, complication and early recurrence rates. Method Patients with inguinal hernia who were planned to undergo laparoscopic hernia repair were randomized and operated with total extraperitoneal repair (TEP) and extended view total extraperitoneal repair (eTEP) methods in July and August 2023. During the postoperative follow-up, 24th-hour pain scores and 24th-hour quality of life scores were noted with a visual analogue scale (VAS) and quality of recovery test (QoR T15). At the 1st week outpatient clinic follow-up, their pain scores were questioned with VAS. They were checked by physical examination for complications or early recurrence. Patients were called for follow-up at the 1st and 3rd months after the surgery. Results The number of fixative staples was significantly higher in TEP group (p < 0.001). The operation time was significantly shorter in eTEP group (p: 0.031). Time to return to work was significantly longer in TEP group (p: 0.024). VAS scores on the 1st postoperative day were found to be significantly lower in eTEP group (p < 0.001), no significant difference was detected in the 1st week scores. The QoR test scores on the first postoperative day were significantly higher in eTEP group (p:0.006). The difference between number of patients with seroma, ecchymosis or hematoma was not significant in two groups. Conclusions Both methods we used did not make a significant difference in the incidence of complications. On the other hand, we revealed that eTEP method may be more advantageous in terms of ease of surgery, patients' quality of life in the early period.

PHASIX™ ST MESH FOR CRURAL REINFORCEMENT DURING GIANT HIATAL HERNIA REPAIR: PRESENTATION OF SURGICAL TECHNIQUE

Abstract Aim Crural mesh reinforcement during large hiatal hernia repair has been advocated to defend against early recurrences. However, the optimal mesh material and configuration remain in question. This study presents the rationale and surgical technique for crural repair augmentation using Phasix™ ST Mesh. Methods We present a case of a giant hiatal hernia and outline the rationale and surgical technique for using Phasix™ ST Mesh in the repair. Results A 72-year-old man presented with a giant type IV hiatal hernia. A massive mediastinal protrusion of intra-abdominal fat and viscera, and an associated crucial cardiorespiratory compromise were noted. A preoperative CT scan revealed a widened hiatus measuring 9.2 × 7.6 cm. The patient underwent laparoscopic hiatal hernia repair and Nissen fundoplication. During the procedure, following visceral reduction and hernia sac dissection and excision, a widened round hiatus and significantly thinned crura were found. To reinforce the primary crural suturing, two strips of Phasix™ ST Mesh, each measuring 1.5 × 4 cm, were used, and a U-shaped mesh was placed onlay to augment the repair. The procedure lasted 214 minutes, and the patient was discharged on the 3rd postoperative day without complications. Conclusions The application of Phasix™ ST Mesh in the repair of giant hiatal hernias offers the dual benefits of reconstructing the original anatomy and reinforcing the hiatus, while avoiding the implantation of permanent foreign material around the esophagus.

Cavutilide (Refralon) for pharmacological cardioversion of early recurrence atrial fibrillation and flutter in blanking period after pulmonary veins isolation

Objective. Evaluate efficacy and safety of cavutilide (Refralon) for pharmacological cardioversion in patients with recurrent atrial fibrillation and flutter (AF/AFL), in 90days blanking period of catheter ablation.Materials and methods. included 56 patients: 46 patients with recurrent paroxysmal AF/AFL and 10 patients with recurrent persistent AF/AFL. In 45 patients (80.3%), sinus rhythm (SR) restoration was performed within 7 days from the moment of catheter ablation. Intraoperative confirmation of pulmonary vein (PV) isolation was noted in 85.7% cases (n=48). After excluding contraindications, cavutilide was administrated in the intensive care unit according to a 4-stage protocol (5 µg/kg – 5 µg/kg-10 µg/ kg – 10 µg/kg). Effectiveness of pharmacological cardioversion was assessed as the fact of restoring SR and the fact of preservation of SR 24 hours after cavutilide administration. Safety points – QT prolongation, ventricular arrhythmogenic effects, pauses and bradyarrhythmias.Results. The overall effectiveness of cavutilide among all included patients reached 98.2% (n=55), and preservation of SR 24 hours after cavutilide administration was observed in 94.5% (n=53) patients. All the patients with recurrent persistent AF/AFL successfully restored and maintained SR 24 hours after cavutilide administration 100% (n=10). In patients with recurrent paroxysmal AF/AFL restoration of SR observed in 97.8% (n=45) and preservation of SR after 24 hours – in 93.4% (n=43), respectively. The effectiveness of cavutilide did not depend on the results of the catheter ablation. Recurrences of AF/AFL after SR restoration were more common in patients without successful PV isolation. QT prolongation >500ms observed in 8.9% (n=5) of cases, including 1 case of self-terminating torsade de pointes, managed by MgSO4 infusion. Bradyarrhythmias that did not require urgent therapy were noted in 10.7% (n=6) of cases.Conclusion. Pharmacological cardioversion with Cavutilide (Refralon) is highly effective and safe method of SR restoration in patients with recurrent AF/AFL in 90days blanking period after catheter ablation.

Progress of circulating tumor DNA methylation for gastric cancer screening and management

Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.

Impact of the timing of early recurrences during the blanking period in patients after cryoballoon ablation: insights from the COMPARE CRYO study using continuous rhythm monitoring

Abstract Background Early recurrences (ER) during the blanking period after pulmonary vein isolation (PVI) are common. While many of those correlate to late recurrences (LR) after the blanking period, some do not. The impact of the timing of ER is difficult to assess with non-invasive Holter monitoring due to under sampling. Purpose To evaluate the impact of the timing of ER after cryoballoon ablation using continuous rhythm monitoring by means of an implantable cardiac monitor (ICM). Methods This is a prespecified sub study of the COMPARE-CRYO study. The trial enrolled patients with paroxysmal atrial fibrillation and compared PVI with the PolarX cryoballoon and the ArcticFront cryoballoon. All patients underwent ICM implantation at the end of the PVI. ER was defined as recurrence of any atrial arrhythmia > 30 seconds between days 0-90 after PVI. LR was defined as recurrence of any atrial arrhythmia > 30 seconds between days 91-365. Results ER occurred in 116 of 201 patients (58%). A total of 5330 episodes occurred, 4210 in patients with LR and 1120 in patients without LR (Figure 1A). Median time to the latest episode of ER in the blanking period was 18 days (IQR 8.5-36.5) in patients with no LR and 80 days (IQR 27-89) in patients with LR (p<0.001). The latest episode of ER occurred between days 0-30, 31-60 and 61-90 in 41%, 13% and 46% of patients respectively. Freedom from recurrence of atrial arrhythmias 1 year after the PVI was 81% in patients without ER and 37% in patients with ER (p<0.001, Figure 1B). When patients were classified according to their latest episode of ER occurring between days 0-30, 31-60 and 61-90, freedom from any atrial arrhythmia at 1 year was 60%, 53% and 11% (p<0.001, Figure 1C) respectively. ROC analyses revealed a strong correlation of LR with the timing of the latest episode of ER in the blanking period (AUC=0.81, p<0.001) with an optimal cutoff value at 61 days (SN 64%, SP 88%). Median AF burden in the blanking period was 0% (IQR 0-0) in patients with ER but no LR and 0.2% (IQR 0-2) in patients with ER and LR (p<0.001). This was similarly true for all individual months (0-30 days: 0% vs. 1.8%, p<0.001, 31-60 days: 0% vs. 0.1%, p<0.001, 61-90 days: 0% vs. 0.1%, p p<0.001). There were no differences in the duration of ER episodes or in clinical characteristics between patients with and without LR Conclusion ER after cryoballoon PVI is common. While ER during the first and second month after PVI disappear in the majority of patients, presence of ER in the third month after PVI are highly predictive for ablation failure.

Impact of early recurrences on late recurrences after pulmonary vein isolation with pulsed field ablation. A subanalysis from the EU-PORIA multicenter international registry

Abstract Background Early recurrences of atrial tachyarrhythmia (ERAT) are commonly observed after pulmonary vein isolation (PVI) with thermal energies. ERAT during the 90-day blanking period (BP) should not be considered therapy failure as the cardiac tissue is still healing and the long-term benefit of PVI may not be immediately apparent. With the introduction of pulsed field ablation (PFA), a non thermal, myocardial-specific ablation technology for atrial fibrillation (AF), the significance of ERAT following PVI is unclear. Methods EU-PORIA (EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation), a multicentre international registry, collected data from 1233 patients treated with the pentaspline PFA catheter. For the current analysis, patients with a previous AF ablation procedure, patients treated with lesions beyond PVI, and patients without complete follow up data (during and following the BP) were excluded. The rate and significance of ERAT following PFA PVI were analysed. Results This subanalysis included 1011 patients (38% female, 66±11 years old, 64% paroxysmal atrial fibrillation [PAF]). ERATs were recorded in 178/1011 (18%) of patients (16% in PAF and 21% in persAF, p=0,021). Notably, ERAT patients were older (67,1±11,4 Vs 65,4±10,9, p=0,015) and had a higher median CHA2DS2-VASc Score (2,5 [IQR:1-4] Vs 2 [IQR:1-3]; p=0,019). The 35-mm catheter was more often used in ERAT patients (48/178(27%) Vs 148/833(18%) – p=0,005). At a median follow-up of 365 days (IQR 347-390), 100/178(56%) of patients with ERAT had documented late recurrence (LR), compared to only 147/833(18%) of patients in sinus rhythm throughout BP (p<0,001). Kaplan Meier estimates for overall freedom from AF/AT outside of the BP was 77% at one year for all patients. Patients with ERAT had a significantly lower freedom from AF/AT compared to patients with no ERAT (42% vs 84%, log-rank p<0,001). The absence of ERAT was associated with long-term success independent of the type of AF (41% Vs 88% in PAF, 43% vs 74% in persistent AF; p<0,001 for both). Among ERAT patients, no additional predictors for LR were identified. Conclusions In this large multicentre international registry, early recurrence of atrial tachyarrhythmia following PFA PVI were recorded in 18% of patients. ERAT was associated with late recurrences in the majority of cases, independent of AF type. The need for a blanking period following non thermal energy ablation for atrial fibrillation should be further questioned.

The new "olive strategy" for pulsed field ablation of atrial fibrillation: procedural data and early follow-up

Abstract Background Pulsed field ablation (PFA) is a new myocardial-specific ablation technology for atrial fibrillation (AF). Direct current electric energy is applied to cells and disrupts cell membranes by creating pores. Purpose The aim of this single-center study was to report procedural data and early recurrence of atrial tachyarrhythmia (ERAT) following a new PFA-based ablation strategy for pulmonary vein isolation (PVI). Methods Consecutive patients with symptomatic AF were enrolled to undergo PFA-PVI using the pentaspline catheter. A new ablation strategy was performed: In total 10 applications per pulmonary vein (PV) were delivered. In addition to the conventional four applications in flower- and four applications in basket-configuration, two applications were delivered in a smaller "olive"-configuration. ERAT was defined as any documented AF/atrial tachycardia (AT) lasting more than 30 seconds during a 90-days blanking period. Procedural and demographic data were analysed. Results 60 patients (37% female, age 67±12, 43% paroxysmal atrial fibrillation [PAF]) were included in this preliminary analysis. 239 PVs were identified, and all PVs could be isolated using solely the PFA device. All PVs were isolated with the first application. 40 applications per patient were delivered. No complications occurred. Procedure time was 30±11 min, fluoroscopy time was 6±3 min. Median follow-up time was 100 days. 20% of patients experienced an early recurrence after a median of 2 days (IQR 1-7.25; 92% AF, 8% AT). Kaplan Meier estimated freedom of AF/AT was 83.3 % at 3 months, 92.3% for PAF and 76.5% for persistent atrial fibrillation (p=0.11). Conclusions Our data show feasibility of a new ablation strategy with the pentaspline PFA-catheter. This study indicates high acute efficacy and safety. 83.3% of patients are free of AF/AT at 3 months. Longer follow-up times are needed to assess the clinical outcome and will be available at the time of presentation.

Reconsidering S100B: Why it is time to abandon its use in detecting disease recurrence in stage III melanoma patients

BackgroundEspecially in the era of successful systemic therapy, there is an urgent need to detect early disease recurrence in stage III melanoma patients. This study investigates if serum S100 calcium-binding protein B (S100B) can detect disease recurrence in stage III melanoma patients. MethodsA retrospective cohort study was conducted at the University Medical Center Groningen (UMCG). Adult AJCC 8th stage III melanoma patients in whom serum S100B was measured as part of follow-up from January 2010 until April 2023 were included. The association between serum S100B and disease recurrence was evaluated using standard definitions for sensitivity and positive predictive value (PPV). ResultsOverall, 147 patients were included (mean age was 60.4 years, 53.1 % were female). Most patients were classified as stage IIIB (39, 26.5 %) and IIIC (73, 49.7 %). During median follow-up of 56 months, 69 (46.9 %) patients experienced disease recurrence. Seventeen out of 18 patients with elevated serum S100B (≥0.15 μg/L) experienced disease recurrence (PPV of 94.4 %). However, 52 out of 69 patients with disease recurrence had normal serum S100B (sensitivity of 24.6 %). Eight out of 17 (47.1 %) patients were asymptomatic (P = 0.608), twelve (70.6 %) patients had at least four distant metastases (P < 0.001). ConclusionThe clinical value of serum S100B to detect disease recurrence in stage III melanoma patients is negligible since only one out of four patients with disease recurrence have elevated serum S100B. Furthermore, half of stage III melanoma patients with elevated S100B experienced symptoms, and most patients already have multiple distant metastases.

Impact of early atrial arrhythmia recurrence on long-term CryoPVI success

Abstract Background According to current guidelines, the occurrence of atrial fibrillation (AF) recurrence within the first 90 days after pulmonary vein isolation (PVI) should not indicate re-do procedures. Accordingly, a 90-day blanking period is usually accepted. However, data suggests that early atrial arrhythmia relapses during the blanking period have an impact on the efficacy. The optimal period for indicating a re-ablation therefore remains unclear. Methods We prospectively analyzed consecutive AF patients who underwent cryoballoon PVI (CryoPVI) in a single-center cohort between 2018 and 2023. We divided patients into four groups according to arrhythmia recurrence (recurrence between 0-30 days, recurrence between 30-60 days, recurrence between 60-90 days and no recurrence within the first 90 days). CryoPVI was performed in a standardized procedure. At 3, 6, 12, 18, 24 and 36 months after CryoPVI follow up was performed. Efficacy endpoint was the occurrence of symptomatic atrial arrhythmia relapse. Results During the study period 1179 patients underwent a first CryoPVI. Of these, 84 patients (7.1%) had atrial arrhythmia relapse between 0-30 days, 38 patients (3.2%) had atrial arrhythmia relapse between 30-60 days, and 38 patients (3.2%) had a relapse between 60-90 days. Overall, 1019 (86.4%) patients didn’t have an atrial arrhythmia relapse between 0-90 days after CryoPVI. Primary efficacy endpoint incidence after 36 months was significantly higher in patients who experienced atrial arrhythmia relapse within the first 90 days (between 0-30 days 62.5% vs. between 30-60 days 70.1% vs. between 60-90 days 77.9% vs. no recurrence ≤ 90 days 41.6%, p&amp;lt;0.0001). Conclusion Atrial arrhythmia relapse within the first 90 days is associated with a reduced long-term efficacy of CryoPVI. Re-ablation should be indicated regardless of the time of recurrence.

Radiofrequency balloon ablation: 1-year outcomes of the AURORA registry

Abstract Background and Objectives A novel irrigated radiofrequency balloon (RFB) for pulmonary vein isolation (PVI) integrated into 3D mapping system was recently launched. Methods Patients ablated for paroxysmal atrial fibrillation (PAF) or persistent atrial fibrillation (persAF) at two German high-volume electrophysiology centers were included into the prospective AURORA registry. All patients underwent clinical follow-up (FU) at 90, 180 and 360 days following ablation including 24h Holter ECGs. Results A total of 101 patients were enrolled (50 from centre A, 51 from centre B) and 86 patients (48% male, 65 ± 11 years, 55% PAF, 59 ± 7% left ventricular ejection fraction (LVEF)) completed the follow-up. Mean ablation and procedure times were 26 ± 13 min and 71 ± 20 min, respectively. Dose area product was 1501 ± 1634 mGycm2. Acute PVI was achieved in 100%. Atrial fibrillation (AF) free survival after a mean FU of 361 (219-375) days was 78.4% for PAF and 75.4% for persAF. (p= 0.828). A multiple regression analysis did not reveal any clinical or procedural predictors of AF recurrence among sex, age, BMI, left atrial diameter, LVEF, ablation time, procedure time and single shot PVI. However, early recurrence of atrial tachyarrhythmia (ERAT) was an independent predictor for AF recurrence at 1-year (Hazard Ratio [HR]: 3.198; 95% confidence interval [95% CI]: 1.036 - 10.32, p value = 0.0433). Primary adverse events occurred in 3.5% of patients (1 postprocedural pharyngeal bleeding, 1 myocardial infarction, 1 non-cardiovascular death); no pericardial effusion, stroke or phrenic nerve paralysis were observed. Conclusions RFB-based PVI is clinically effective and safe. ERAT at the first follow-up visit is an independent predictor of late AF recurrence.

Improved procedural workflow for catheter ablation of paroxysmal AF with high density mapping system and advanced technology: insights from a multicenter, international study

Abstract Background A high incidence of pulmonary vein (PV) reconnection has been reported in patients with clinical recurrences of AF. Low-voltage activity beyond PVs (e.g. antral activity potentials, RAP) likely represent vulnerabilities in antral lesion sets and they may contribute to ablation failures. Purpose The aim of this study is to validate a structured application of an approach that includes the complete abolition of any antral potential achieving electrical quiescence in antral regions. Methods DELETE AF is a prospective, single-arm, international post-market cohort study. Consecutive patients from 10 centers who were undergoing radiofrequency ablation of paroxysmal AF were included. The Lumipoint map-analysis tool was used sequentially on each PV component. Post-ablation, all patients were monitored with ambulatory event monitoring, starting within 30 days post-ablation to proactively detect and manage any recurrences within the 90-day blanking period, as well as Holter monitoring at 3, 6, 9, and 12 months post-ablation. Additional ECG monitoring were performed as indicated by patient symptoms. The ablation endpoint was PV isolation (PVI). Long-term outcome was the recurrence of AF over follow-up. Data are reported as median [IQ range]. Results One-hundred ten cases of AF ablation were analyzed: 28 (25.5%) females, age=63[56-69] years, 24 (21.8%) patients with a history of AT/AFL. The procedure duration was 58[24-76] min (RF delivery time=18[12-28] min, number of ablation spots=77[44-101]) and the fluoroscopy time was 13[9-19] min. Thirty-eight (34.5%) were repeat ablation: in these patients after initial mapping a total of 114 PV gaps (PVGs) in 29 (76.3%) patients and 69 RAPs in 15 patients (39.5%) were found. After ablation, a total of 5 early PVGs in 2 (1.8%) patients (all in de novo procedures) and a total of 10 RAPs in 7 (6.3%) patients (3 out 38 -7.9%- of repeat ablations vs 4 out 72 -5.6%- of de novo cases, p=0.690) were detected after first remapping. Each residual PVG was first targeted and additional focal ablations were performed at any low-voltage propagation suspected within the region of previous antral ablation. Acute procedural success was 100%, with all PVs successfully isolated and RAPs completely abolished in all study patients except for one that still exhibited a residual low-voltage antral signal after adenosine infusion with no PV conduction. Eighty-six (78.2%) patients had complete follow-up information. During the 90-day blanking period, 8 (9.2%) patients experienced an early recurrence. After the blanking period, over a follow-up of 357[190-380] days, 13 patients (15.1%) suffered an AF recurrence (time to recurrence: 207[144-300] days). No major complications or adverse events occurred. Conclusion A structured ablation workflow for catheter ablation, with consistent high-density mapping and improved diagnostic tools to guide the ablation, proved to be safe and effective in paroxysmal AF.

Impact of pulmonary vein variant anatomy during cryo-ablation in paroxysmal and persistent AF patients: 1-year outcome from a nationwide multicenter clinical setting

Abstract Background Complete electrical pulmonary vein isolation (PVI) by cryo-balloon approach is a well-established ablation strategy of atrial fibrillation (AF). While contrast findings exist regarding the influence of variant pulmonary vein (PV) anatomy on predicting AF recurrence, limited data are currently available specifically for cases involving the POLARx cryoablation system during PVI. Purpose We report the real-world experience of POLARx in the context of de novo AF ablation in a multicenter Italian registry. Methods Consecutive patients undergoing AF ablation from the CHARISMA registry at 10 Italian centres were included. Protocol-directed cryoablation was delivered for 180 sec or 240 sec according to operator’s preference for isolation achieved in ≤60 sec, or 240 sec if isolation occurred &amp;gt;60 sec or when time to isolation was not available. The ablation endpoint was PVI as assessed by entrance and exit block. All patients were followed-up for at least 12 months after the procedure. Results Four-hundred twenty-nine patients were included (n=358, 83.4% paroxysmal AF, n=71, 16.6% persistent AF, mean age 60.7±10 years, 28.3% female, mean LVEF 58±8%). PVI was achieved in all pts using only cryoablation. Twenty-eight (6.6%) patients exhibited an anatomical variant: 17 (4.0%) a common ostium and 11 (2.6%) an adjunctive PV. The mean number of freeze applications per patient was 5.1 (1.2 for LSPV, 1.3 for LIPV, 1.2 for RSPV and 1.3 for RIPV). Over a median of 398[370-461] days of follow-up, 14 (3.2%) patients experienced an early recurrence of AF during the 90-day blanking period. Overall, 63 patients (14.7%) suffered an AF recurrence after the 90-day blanking period (median time to recurrence 342[171-381] days). The proportion of patients exhibiting AF/AT recurrences was higher in the persistent AF group (17 out 71, 23.9%) than in the paroxysmal AF group (46 out 358, 12.8%, p=0.026), with a hazard ratio of 2.02 (95%CI: 1.2 to 3.5, p=0.0137) whereas patients with anatomy variant showed a similar AF/AT recurrence rate (5 out 28, 17.9%) than in the standard anatomy group (58 out of 401, 14.5%) with a hazard ratio of 1.43 (0.6 to 3.6, p=0.441). Four (0.9%) transient phrenic nerve palsy were observed, both with full recovery in the 48-h post procedure; no major procedure-related adverse events were reported. Conclusion In this multicenter study, the cryo-balloon system demonstrated safety and efficacy in treating both paroxysmal and persistent AF patients, yielding a low incidence of AF/AT recurrence during follow-up, regardless of the presence of variant PV anatomy.

#2811 Factor B inhibition with iptacopan in C3 glomerulopathy recurrence after transplantation: a case presentation

Abstract Background and Aims C3 glomerulopathy (C3G) is a clinical-pathological entity resulting from dysregulation of the alternative pathway of the complement system (APC) in the fluid phase. The recurrence risk of C3G after kidney transplantation is about 70% with high risk of graft loss. Standard treatment relies on nephroprotection and unspecific immunosuppression but there are currently new molecules that target specifically APC under development. A novel factor B inhibitor, iptacopan, has shown promising results both in native kidney and transplant recurrence cases in a phase II trial. Method We present a real-world clinical case of early C3G recurrence after kidney transplantation treated with iptacopan (Novartis MAPs program). Patient was vaccinated for encapsulated bacteria. Iptacopan was initiated 200 mg BID. We also present histological response. Results 38-year-old male with chronic kidney disease secondary to C3G initially presented with nephrotic syndrome and hematuria at the age of 31y following a respiratory infection. Blood test showed low serum C3 levels and the presence of C3 nephritic factor without pathological genetic alterations. Kidney biopsy confirmed membranoproliferative glomerulonephritis (MPGN) with predominant C3 deposition. He progressed to CKD stage G5 requiring hemodialysis instead of nephroprotection and immunosuppression with corticosteroids and mycophenolate; and addition with cyclophosphamide and rituximab after 19 months from onset. Five years later, the patient was admitted as first kidney transplant recipient from deceases donor Maastricht-III. Induction therapy included thymoglobulin, and tacrolimus, mycophenolate, and corticosteroids. He experienced delayed graft function requiring hemodialysis. An early biopsy proved C3G recurrence with endocapillary proliferation without C4d deposit and absence of donor specific antibodies. Despite conventional immunosuppression and addition of rituximab and plasma exchange; hemodialysis requirement still be present. So, because C3G pathophysiological base, iptacopan was begun with successful clinical response as he reached hemodialysis discontinuation; and kidney function stabilized after one year of treatment with an estimated glomerular filtration rate about 30 mL/min/1.73 m2. In the follow-up biopsy 5 months later, deposit of C3 in the glomerulus disappeared compared to the post-transplant recurrence but with persistence of endocapillary and mesangial proliferation (see Fig. 1). However, interestingly, he experienced a clinical recurrence with acute kidney injury and hematuria after unintentional iptacopan discontinuation, which was resolver after reinitiating and recovering its previous graft function. No infectious complications were observed after one year of treatment with factor B inhibitor. Conclusion New molecules under development that specifically target APC (fluid phase) may change the treatment scenario of C3G and its recurrence in kidney transplantation. We expose a real-practice early C3G recurrence after kidney transplantation successfully treated with iptacopan. The patient reached kidney function stabilization and disappearance of C3 deposits on immunofluorescence of the follow-up biopsy, identical results as the phase II clinical trial of iptacopan in C3G. So, we might conclude that iptacopan is an effective and safe option for C3G recurrence after kidney transplantation. But, data from randomized studies are needed in order to confirm the efficacy and safety of new inhibitors of the APC as iptacopan.

The role of adjuvant transcatheter arterial chemoembolization following repeated curative resection/ablation for hepatocellular carcinoma with early recurrence: a propensity score matching analysis

BackgroundThe role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC.MethodsInformation for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM).ResultsOf the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6–16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn’t. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC.ConclusionAdjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort.

Can early post-operative MRI describe a predictor model for the likelihood of early breast cancer recurrence after conservative surgery?

Can early post-operative MRI describe a predictor model for the likelihood of early breast cancer recurrence after conservative surgery?

Interleukin-41: a novel serum marker for the diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma.

For the lack of effective serum markers for hepatocellular carcinoma(HCC) diagnosis, it is difficult to detect liver cancer and identify its recurrence early. Databases were used to analyze the genes potentially associated with alpha-fetoprotein(AFP). ELISA assay was used to detect the serum IL-41 in HCC, liver metastases, hepatitis, and healthy people. Immunohistochemical staining was used to analyze the relative quantification of IL-41 in HCC and paracancer tissues. Various survival curves were plotted according to clinical pathological data and helped us draw the ROC curve of IL-41 diagnosis of HCC. The serum expression of IL-41 was highest in AFP negative HCC patients and significantly higher than that in AFP positive HCC and metastatic cancer patients. There was a significant negative correlation between elevated serum IL-41 and AFP(<1500ng/ml). The clinicopathological features suggested that the serum IL-41 level was significantly correlated with capsule invasion, low differentiation and AFP. High serum expression of IL-41 suggests poorer survival and earlier recurrence after resection, and IL-41 upregulated in patients with early recurrence and death. The expression of IL-41 was higher in HCC tissues of patients with multiple tumors or microvascular invasion. The ROC curve showed that serum IL-41 had a sensitivity of 90.17 for HCC and a sensitivity of 96.63 for AFP-negative HCC, while the specificity was higher than 61%. IL-41 in serum and tissue suggests poor prognosis and postoperative recurrence in HCC patients and could be a new serum diagnostic marker for AFP negative patients.

MRI radiomics based on deep learning automated segmentation to predict early recurrence of hepatocellular carcinoma.

To investigate the utility of deep learning (DL) automated segmentation-based MRI radiomic features and clinical-radiological characteristics in predicting early recurrence after curative resection of single hepatocellular carcinoma (HCC). This single-center, retrospective study included consecutive patients with surgically proven HCC who underwent contrast-enhanced MRI before curative hepatectomy from December 2009 to December 2021. Using 3D U-net-based DL algorithms, automated segmentation of the liver and HCC was performed on six MRI sequences. Radiomic features were extracted from the tumor, tumor border extensions (5 mm, 10 mm, and 20 mm), and the liver. A hybrid model incorporating the optimal radiomic signature and preoperative clinical-radiological characteristics was constructed via Cox regression analyses for early recurrence. Model discrimination was characterized with C-index and time-dependent area under the receiver operating curve (tdAUC) and compared with the widely-adopted BCLC and CNLC staging systems. Four hundred and thirty-four patients (median age, 52.0 years; 376 men) were included. Among all radiomic signatures, HCC with 5 mm tumor border extension and liver showed the optimal predictive performance (training set C-index, 0.696). By incorporating this radiomic signature, rim arterial phase hyperenhancement (APHE), and incomplete tumor "capsule," a hybrid model demonstrated a validation set C-index of 0.706 and superior 2-year tdAUC (0.743) than both the BCLC (0.550; p < 0.001) and CNLC (0.635; p = 0.032) systems. This model stratified patients into two prognostically distinct risk strata (both datasets p < 0.001). A preoperative imaging model incorporating the DL automated segmentation-based radiomic signature with rim APHE and incomplete tumor "capsule" accurately predicted early postsurgical recurrence of a single HCC. The DL automated segmentation-based MRI radiomic model with rim APHE and incomplete tumor "capsule" hold the potential to facilitate individualized risk estimation of postsurgical early recurrence in a single HCC. A hybrid model integrating MRI radiomic signature was constructed for early recurrence prediction of HCC. The hybrid model demonstrated superior 2-year AUC than the BCLC and CNLC systems. The model categorized the low-risk HCC group carried longer RFS.

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.