Association of ZFHX3 Genetic Polymorphisms and Extra-Pulmonary Vein Triggers in Patients With Atrial Fibrillation Who Underwent Catheter Ablation

Background: The ZFHX3 gene (16q22) is the second most highly associated gene with atrial fibrillation (AF) and is related to inflammation and fibrosis. We hypothesized that ZFHX3 is associated with extra-pulmonary vein (PV) triggers, left atrial (LA) structural remodeling, and poor rhythm outcomes of AF catheter ablation (AFCA).Methods: We included 1,782 patients who underwent a de novo AFCA (73.5% male, 59.4 ± 10.8 years old, 65.9% paroxysmal AF) and genome-wide association study and divided them into discovery (n = 891) and replication cohorts (n = 891). All included patients underwent isoproterenol provocation tests and LA voltage mapping. We analyzed the ZFHX3, extra-PV trigger-related factors, and rhythm outcomes.Result: Among 14 single-nucleotide polymorphisms (SNPs) of ZFHX3, rs13336412, rs61208973, rs2106259, rs12927436, and rs1858801 were associated with extra-PV triggers. In the overall patient group, extra-PV triggers were independently associated with the ZFHX3 polygenic risk score (PRS) (OR 1.65 [1.22–2.22], p = 0.001, model 1) and a low LA voltage (OR 0.74 [0.56–0.97], p = 0.029, model 2). During 49.9 ± 40.3 months of follow-up, clinical recurrence of AF was significantly higher in patients with extra-PV triggers (Log-rank p < 0.001, HR 1.89 [1.49–2.39], p < 0.001, model 1), large LA dimensions (Log-rank p < 0.001, HR 1.03 [1.01–1.05], p = 0.002, model 2), and low LA voltages (Log-rank p < 0.001, HR 0.73 [0.61–0.86], p < 0.001, model 2) but not the ZFHX3 PRS (Log-rank p = 0.819).Conclusion: The extra-PV triggers had significant associations with both ZFHX3 genetic polymorphisms and acquired LA remodeling. Although extra-PV triggers were an independent predictor of AF recurrence after AFCA, the studied AF risk SNPs intronic in ZFHX3 were not associated with AF recurrence.

Calcitonin level in the postoperative period as a risk factor for persistence of medular thyroid cancer

Aim — to evaluate the possibility of using basal calcitonin levels in the postoperative period to assess the effectiveness of surgical treatment of medullary thyroid cancer and the likelihood of its persistence (recurrence). Materials and methods. A single-site retrospective study was conducted to assess results of surgical treatment of 194 patients (74.2 % women and 25.8 % men), from them148 (76.3 %) patients had primary forms of the disease (group 1) and 46 (23.8 %) the recurrent form (group 2). Primary surgery included thyroidectomy, supplemented with thecentral and lateral dissection of the neck. Patients in group 1 were divided into two subgroups depending on the postoperative calcitoninlevels: group 1A with normal calcitonin levels (≤ 18 pg/ml)and group 1B with hypercalcitoninemia (> 18 pg/ml). The quantitative­determination of blood serum calcitonin levels was performed using automatic immunochemiluminescent analyzer «MAGLUMI» («Snibe Diagnostic», China) in 1 week and 1 year after surgery. Accumulation and primary data processing were performed in MS Excel 2013, statistical processing was performed using StatPlus programs with descriptive statistics, parametric and nonparametric methods for testing statistical hypotheses (Student’s criteria, Mann-Whitney, Fisher angular transformation), analysis of conjugation tables, ROC-analysis. The results were considered statistically significantat p < 0.05. Results. The average duration of follow-up was 67.5 months. The results of surgery were analyzed in terms of absence or presence of clinical recurrence, calcitoninlevels in the early postoperative period (5 days) were used as a predictor. After 2 years of follow-up,normocalcitoninemiawas accompanied by recurrence in almost 2 % of cases, while hyper­calcitoninemia — in 61 % to 74 %, depending on the stage and frequency of the disease. The correlationsbetween postoperative calcitonin levels and presence of recurrence (persistence) of medullary thyroid cancer has been established: AUC = 0.928 (0.867; 0.989, Juden index (J) = 0.429, threshold (cut-off point) ≥ 28.1 pg/ml, sensitivity = 0.938 (0.854; 1,000), specificity = 0.855 (0.789; 0.920), predictive value of positive result(PPV) = 0.699, predictive value of negative resultPNV = 0.991. Moreover, countersensitivity scores and incidence of negative test results in patients with relapse depending on the level of postoperative calcitonin were calculated. Conclusions. Postoperative calcitonin levels in 5 days after surgery can be used for assessment of efficacy of the surgical treatment (AUC — 0,928 (0,867; 0,989), Juden index — 0,429)). The prognosis of recurrence-free disease does not depend on the disease stage. At calcitonin levels < 18 pg/ml, clinical signs of the disease persistence (recurrence) were detected in 1.5 % of cases (PNV = 0.991). The reliability of predicting the disease recurrence depended on the stage and frequency of surgery: PRV = 0.612 in primary forms without metasta­­ses, PRV = 0.825 in recurrent forms. Calcitonin values < 28.1 pg/ml can be considered a relatively «safe» level.

Clinical Outcomes of Computational Virtual Mapping-Guided Catheter Ablation in Patients With Persistent Atrial Fibrillation: A Multicenter Prospective Randomized Clinical Trial

Background: Clinical recurrence after atrial fibrillation catheter ablation (AFCA) still remains high in patients with persistent AF (PeAF). We investigated whether an extra-pulmonary vein (PV) ablation targeting the dominant frequency (DF) extracted from electroanatomical map–integrated AF computational modeling improves the AFCA rhythm outcome in patients with PeAF.Methods: In this open-label, randomized, multi-center, controlled trial, 170 patients with PeAF were randomized at a 1:1 ratio to the computational modeling-guided virtual DF (V-DF) ablation and empirical PV isolation (E-PVI) groups. We generated a virtual dominant frequency (DF) map based on the atrial substrate map obtained during the clinical AF ablation procedure using computational modeling. This simulation was possible within the time of the PVI procedure. V-DF group underwent extra-PV V-DF ablation in addition to PVI, but DF information was not notified to the operators from the core lab in the E-PVI group.Results: After a mean follow-up period of 16.3 ± 5.3 months, the clinical recurrence rate was significantly lower in the V-DF than with E-PVI group (P = 0.018, log-rank). Recurrences appearing as atrial tachycardias (P = 0.145) and the cardioversion rates (P = 0.362) did not significantly differ between the groups. At the final follow-up, sinus rhythm was maintained without any AADs in 74.7% in the V-DF group and 48.2% in the E-PVI group (P &lt; 0.001). No significant difference was found in the major complication rates (P = 0.489) or total procedure time (P = 0.513) between the groups. The V-DF ablation was independently associated with a reduced AF recurrence after AFCA [hazard ratio: 0.51 (95% confidence interval: 0.30–0.88); P = 0.016].Conclusions: The computational modeling-guided V-DF ablation improved the rhythm outcome of AFCA in patients with PeAF.Clinical Trial Registration: Clinical Research Information Service, CRIS identifier: KCT0003613.

P-BN15 Outcomes following surgical repair of giant para-oesophageal hernia of over 200 cases with long-term follow up: a 20-year experience

Background Symptomatic giant para-oesophageal hernia (PEH) can often be troublesome and may require surgical intervention. It commonly presents with dyspnoea, post-prandial pain, vomiting and dysphagia but rarely strangulation. In a good proportion of patients, iron deficiency anaemia may also be present. Patients are often elderly and may have co-morbidities and hence there may be a reluctance to refer and to offer surgery. This long-term study offers an insight to the outcomes following this complex surgery in a relatively elderly cohort of patients. Methods A retrospective analysis of prospectively collected data of patients who underwent surgery for symptomatic PEH from January 2001- June 2021 was performed. Clinical presentation, management, post-operative clinical outcomes, radiographic evaluation, pre and post-operative haemoglobin levels, respiratory function {Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1)} as well as quality-of-life (QoL) with SF-36 questioners (including general health, physical, emotional and social components) were assessed. Results 202 patients (122-females) with median age 68 years (36-88) underwent PEH-surgery. The commonest symptomEighty-one presented with dyspnoea(41%). Ninety-five(47%) were ASA III, 119(59%) had microcytic-anaemia. 142(70%) had a fundoplication during PEHR. Hospital-stay was significantly lower in laparoscopic group Mortality:1.8%(2/112). Median follow-up:10 years. Symptoms improved in 166(82%) with respiratory function and anaemia. 42(21%) had radiological recurrences but only nine (4.5%) clinical recurrence requiring surgery. Conclusions Laparoscopic repair of giant para-oesophageal hernia is safe with good outcomes in all age groups with improvement in symptoms, quality of life, respiratory function and associated anaemia.

STUDY OF RECURRENCE AND SITE OF RECURRENCE IN PATIENTS WITH ADVANCED EPITHELIAL OVARIAN CANCER - A SINGLE CENTER EXPERIENCE

OBJECTIVE– Study of recurrence and pattern of recurrence in Stage III epithelial ovarian cancer. METHODOLOGY – A prospective observational, study was conducted at a tertiary hospital in Bangalore, India from April 2017 to April 2019. Informed and written consent was taken before including the patient in the study. All patients diagnosed with stage III epithelial ovarian with no residual disease following cytoreductive surgery (primary, interval and secondary) with or without Hyperthermic Intraperitoneal Chemotherapy (HIPEC) were included in the study. Patients were followed every 3-6 months up to maximum period of 24 months from the date of surgery. Last date of follow up was on 30/04/19. During follow up patient symptoms, physical examination and serum CA-125 were recorded to detect recurrence. If patient symptoms, physical examination and rising serum CA-125 are suggestive of recurrence, imaging in form of CECTabdomen/ PETCT was done for detection of recurrence. Patients were monitored for two types of recurrence. Biochemical recurrence dened as rising CA125 in absence of clinical evidence of recurrence either by physical examination or by imaging. Clinical recurrence dened as recurrence in any part of body noted on physical examination or imaging and then proving it by biopsy with or without rise in serum CA-125.Site of rst recurrence was recorded. RESULTS- A total of 84 patients were included in the study. 45 patients underwent interval, 25 patients underwent primary and 14 patients underwent secondary cytoreductive surgery. Mean duration of follow up was 18.25 months. 4 patients lost follow up. 2 patients died following surgery. Recurrence was noted in 14 patients (16.66%). Clinical recurrence was noted in 13 patients (15.47%) and biochemical recurrence was noted in 1 patient (1.19%). 8 patients had recurrence in peritoneal cavity (57.14%). 1 patient each had recurrence right inguinal lymph node, paraaortic lymph node+ peritoneum, left iliac lymph node, left supraclavicular lymph node and left inguinal lymph node. CONCLUSION – In this study clinical recurrence was more common than biochemical recurrence. Peritoneal cavity was most common site for recurrence. This study shows importance of optimal cytoreductive reductive surgery in preventing recurrence in carcinoma ovary as peritoneal cavity is most common site of recurrence

The relationship between endoscopic and clinical recurrence in postoperative Crohn’s disease: a systematic review and meta-analysis

Background and Aims We aimed to quantify the magnitude of the association between endoscopic recurrence and clinical recurrence [symptom relapse] in patients with postoperative Crohn’s disease. Methods Databases were searched to October 2, 2020 for randomised controlled trials [RCTs] and cohort studies of adult patients with Crohn’s disease with ileocolonic resection and anastomosis. Summary effect estimates for the association between clinical recurrence and endoscopic recurrence were quantified by risk ratios [RR] and 95% confidence intervals [95% CI]. Mixed-effects meta-regression evaluated the role of confounders. Spearman correlation coefficients were calculated to assess the relationship between these outcomes as endpoints in RCTs. An exploratory mixed-effects meta-regression model with the logit of the rate of clinical recurrence as the outcome and the rate of endoscopic recurrence as a predictor was also evaluated. Results Thirty-seven studies [N=4053] were included. For 8 RCTs with available data, the RR for clinical recurrence for patients who experienced endoscopic recurrence was 10.77 [95% CI 4.08-28.40; GRADE moderate certainty evidence]; the corresponding estimate from 11 cohort studies was 21.33 [95% CI 9.55-47.66; GRADE low certainty evidence]. A single cohort study showed a linear relationship between Rutgeerts score and clinical recurrence risk. There was a strong correlation between endoscopic recurrence and clinical recurrence treatment effect estimates as trial outcomes [weighted Spearman correlation coefficient 0.51]. Conclusions The associations between endoscopic recurrence and subsequent clinical recurrence lend support to the choice of endoscopic recurrence to monitor postoperative disease activity and as a primary endpoint in clinical trials of postoperative Crohn’s disease.

677 ROBOTIC-ASSISTED HIATAL HERNIA AND GASTROESOPHAGEAL REFLUX DISEASE RE-DO SURGERY: A SINGLE INSTITUTION EXPERIENCE

Hiatal hernia recurrence (HHR) after surgical repair associated with dysphagia, gastroesophageal reflux disease or other symptoms represents a non-negligible disease that frequently needs a reoperative solution. The repair of a relapsed hiatal hernia represents a surgical challenge due to anatomic changes and fibrosis, and the robotic approach seems to provide benefits because offers enhanced visualization and dexterity. Methods Between June 2019 and February 2021, 7 patients (1 male, 6 female) underwent redo robotic approach surgery for hiatal hernia recurrence after being pre operative diagnosed. All surgeries were elective and all patients had both clinical and radiologic recurrence. Biosynthetic tissue absorbable mesh was applied in one patient with double time recurrence hernia. Four patients underwent total fundoplication (Nissen), 2 patients had Toupet fundoplication, and one patient had hiatus repair without fundoplication. Results The mean age of the patients was 62.7 years and the main expressed symptom for the patient was dysphagia. Time to clinical recurrence was 13 months. Biosynthetic mesh was used in one patient. The mean operative time was 143 minutes (80–240) and no intraoperative complications were described. There were no conversions to open or laparoscopic procedures. The early and 30 day mortality rate was 0% and mean hospital stay was 2.7 days. Conclusion Robotic support, when available, can be beneficial in redo surgery for GERD and hiatal hernia recurrence. Despite our short experience, we believe the robotic approach for redo hiatal surgery is safe and effective with low complication rates even in high-risk patients.