Long-term Recurrence Research Articles

Long-term follow up of ALA 10% gel and red-light photodynamic therapy for the treatment of squamous cell carcinoma in situ.

Photodynamic Therapy (PDT) with 10% aminolevulinic acid (ALA) gel and narrow-band red light has been previously shown to be safe and effective for the treatment of squamous cell carcinoma in situ (SCCis) on the trunk and extremities. However, there is a paucity of data in the literature evaluating long-term disease recurrence after PDT. Hence, we performed a follow-up study in which nine of the original twelve patients from our pilot study returned 29-40 months after their last PDT treatment. All patients were clinically clear of disease and only one of seven patients biopsied had residual disease, indicating a long-term clearance rate of 88%. Cosmetic outcomes and patient satisfaction were favorable. Our data supports that red-light PDT with 10% ALA gel can achieve long-term clinical and histopathologic disease clearance and is a viable alternative to surgery for select SCCis.

Research on the wound healing effect of Shengji Huayu Formula ethanol extract-derived fractions in streptozotocin-induced diabetic ulcer rats

BackgroundDiabetic ulcer is a common complication of diabetes. It is characterized by a long-term disease course and high recurrence rate. Shengji Huayu Formula (SHF) is an effective formula for treating diabetic ulcers. However, the specific effective parts of SHF remain unclear. Clarifying the active polar site of SHF would be helpful to refine research on the components in SHF that promote wound healing. This research aims to focus on evaluating the activity of polar fractions.MethodsA diabetic rat model was established by intraperitoneally injecting streptozotocin (STZ) and was adopted to confirm the therapeutic effect of SHF. Four different polarity parts were extracted from SHF and prepared into a cream to evaluate the activity. High-performance liquid chromatography (HPLC) was used to detect chemical constituents in chloroform extracts.ResultsIt was discovered that dracorhodin, aloe-emodin, rhein, imperatorin, emodin, isoimperatorin, chrysophanol, physcion, and tanshinone IIA were the main components of the chloroform extract from SHF. The results revealed that chloroform extract could effectively accelerate diabetic wound healing by promoting collagen regeneration and epidermal repair. Chloroform extract of SHF could stimulate the generation of vascular endothelial growth factor (VEGF). The results are also indicated that the effective active fraction was the chloroform part, and the method of detecting the main chemical constituents in the active part was successfully established.ConclusionSHF could improve diabetic ulcers by promoting granulation tissue synthesis. In this study, four polar parts (petroleum ether, chloroform, ethylacetate, n-butanol) were extracted from a 95% ethanol extract. In contrast, chloroform polar parts showed a higher wound closure rate, stimulated more collagen regeneration and promoted more production of vascular endothelial cells. In conclusion, the chloroform extract of SHF was the effective polar part in ameliorating diabetic wound healing.

Risk factors of common bile duct stones recurrence and nomogram for predicting recurrence after endoscopic retrograde cholangiopancreatography: a dual-center retrospective cohort study.

Common bile duct stone (CBDS) is one of the common diseases in the digestive system, for which endoscopic retrograde cholangiopancreatography (ERCP) is a treatment procedure. However, the risk factors for CBDS recurrence after ERCP remains unclear. This study aims to compare the risk factors of CBDS recurrence after ERCP, and to set up a nomogram model to predict the long-term risk. A retrospective analysis of 355 patients was reviewed. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. The R packages were used for the model building. The validation set contained 100 patients. The patients were divided into three subgroups: treated by cholecystectomy after ERCP (11.76% recurrence rate), treated without surgery after ERCP (19.70%), and with a prior history of cholecystectomy (43.64%). Each of them has different independent risk factors, and high body mass index (BMI) is correlated with an increased risk among all the subgroups. A prior history of cholecystectomy is a candidate factor that increases the risk of CBDS recurrence in patients older than 60 years, with a greater BMI, or receiving ERCP combined with EPBD. We built a nomogram model to predict the risk of long-term CBDS recurrence based on the risk factors including age, BMI, CBD diameter, the number of CBDS, and the gallbladder- or biliary tract-related events. CBDS recurrence is related to congenital and anatomical factors. Cholecystectomy would not be helpful to prevent CBDS recurrence, and a prior history of cholecystectomy may indicate a high risk of recurrence.

Ileoanal pouch-related fistulae: A systematic review with meta-analysis on incidence, treatment options and outcomes.

Ileoanal pouch related fistulae (PRF) are a complication of restorative proctocolectomy often requiring repeated surgical interventions and with a high risk of long-term recurrence and pouch failure. To assess the incidence of PRF and to report on the outcomes of available surgical treatments. A PRISMA-compliant systematic literature search for articles reporting on PRF in patients with inflammatory bowel diseases (IBD) or familial adenomatous polyposis (FAP) from 1985 to 2020. 34 studies comprising 770 patients with PRF after ileal-pouch anal anastomosis (IPAA) were included. Incidence of PRF was 1.5-12%. In IBD patients Crohn's Disease (CD) was responsible for one every four pouch-vaginal fistulae (PVF) (OR 24.7; p=0.001). The overall fistula recurrence was 49.4%; procedure-specific recurrence was: repeat IPAA (OR 42.1; GRADE +); transvaginal repair (OR 52.3; GRADE ++) and transanal ileal pouch advancement flap (OR 56.9; GRADE ++). The overall failure rate was 19%: pouch excision (OR 0.20; GRADE ++); persistence of diverting stoma (OR 0.13; GRADE +) and persistent fistula (OR 0.18; GRADE +). PVFs are more frequent compared to other types of PRF and are often associated to CD; surgical treatment has a risk of 50% recurrence. Repeat IPAA is the best surgical approach with a 42.1% recurrence rate.

Abstract P6-14-11: Exosome-mediated Circ-CRSP1 promotes tumor proliferation and metastasis through stabilizing ELAVL1 protein and suppresses anti-tumor immune response in regulating the progression of Triple-Negative Breast Cancer

Abstract Background: Triple-negative breast cancer (TNBC) is one of the most malignant subtype of breast cancer. Lacking targetable molecular drivers, chemotherapy is almost the only effective systematic treatment for TNBC. Compared with other types of breast cancer, TNBC shows a higher long-term recurrence rate and worse prognostic outcome, and its main cause of death is tumor metastasis. Therefore, there is an urgent clinical need to explore underlying molecular mechanisms and find novel targets for therapeutic intervention, as well as biomarkers for early clinical diagnosis. Materials & Methods: To explore the signal pathways and target molecules related to tumor immunity by bioinformatics analysis of tissue samples [TNBC (n = 55), Her2 (n = 39), Luminal B (n = 30), Luminal A (n = 29), healthy (n = 11)]. Co-culture experiment was conducted to study the effect of TNBC-derived exosome-mediated molecules on the proliferation and migration of breast cancer. qRT-PCR assay was used to confirm the expression level of Circ-CRSP1 in tumor tissues, breast cancer cells, exosomes of breast cancer cells and serum exosomes of breast cancer patients. Overexpression and knockout experiments investigated the role of Circ-CRSP1 in promoting the proliferation and migration of TNBC cells. Protein molecular docking technique was used to predict the possible targeting binding protein ELAVL1, and molecular experiments and nude mice model were used to study the mechanism of Circ-CRSP1-ELAVL1 complex in tumor immunity. Results: TNBC-derived exosome-mediated molecular transmission promotes the proliferation and migration of breast cancer, and may promote distant metastasis of breast cancer by changing the tumor microenvironment (TME) before metastasis. Bioinformatics analysis of TNBC tumor samples confirmed that TNBC is strongly associated with tumor immune-related biological processes and signal pathways. Circ-CRSP1 is highly expressed in TNBC tumor tissues, TNBC cells, exosome derived from TNBC cells and serum exosomes of TNBC patients, and is related to the poor clinical prognosis of TNBC patients. Overexpression of Circ-CRSP1 enhanced the proliferation and migration ability of TNBC cells, and the expression levels of EMT and cell-cycle related genes altered. Circ-CRSP1 binds to protein ELAVL1 at the physical level. The target gene of Circ-CRSP1-ELAVL1 complex is involved in the immune response, and the overexpression of Circ-CRSP1 significantly down-regulates the expression level of immune-related genes. Conclusion: Exosome-mediated Circ-CRSP1 promotes the transport of ELAVL1 from nucleus to cytoplasm through targeted binding with ELAVL1, and then regulates cytoplasmic proliferation and metastasis and inhibits the stability and translation of anti-tumor immune-related gene mRNA, thus finally promotes the proliferation, invasion and metastasis of TNBC. This study can further understand the mechanism of circRNA in the growth and metastasis of TNBC from the theoretical level, further explore the feasibility of Circ-CRSP1 as a molecular target for gene therapy, and provide theoretical basis and pre-clinical data for Circ-CRSP1 in serum exosomes as a high risk screening index and prognostic marker for TNBC patients. Citation Format: Sujin Yang, Jinhai Tang. Exosome-mediated Circ-CRSP1 promotes tumor proliferation and metastasis through stabilizing ELAVL1 protein and suppresses anti-tumor immune response in regulating the progression of Triple-Negative Breast Cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-14-11.

Long-Term Outcome of Adrenocorticotropic Hormone Therapy in Children With New-Onset Infantile Spasms

BackgroundTo investigate for pretreatment clinical variables to predict the outcome of new-onset epileptic spasms after adrenocorticotropic hormone (ACTH) therapy and to identify risk factors for poor long-term outcome. MethodsWe retrospectively studied 129 consecutive patients with infantile spasms syndrome (ISS). These patients received ACTH with antiseizure medication therapy for the first time and were regularly followed up for more than six months at our hospital. The response to treatment was assessed after two weeks of ACTH injection. Kaplan-Meier survival analysis and the multivariate Cox proportional hazard regression model were used. ResultsAmong the 129 patients, 61 (47.3%) had a good response after two weeks of ACTH treatment. At the time of the latest follow-up, 71 (55%) patients were seizure-free (International League Against Epilepsy class1). The univariate analysis revealed that normal neurodevelopment (P = 0.018), time lag of less than one month (P = 0.026), no hypsarrhythmia on EEG (P = 0.004), and serum calcium level ≥2.50 mmol/L (P = 0.035) were significantly associated with a good response. Only a good response to ACTH therapy was significantly associated with a positive long-term outcome. The Kaplan-Meier survival analysis showed that serum calcium level ≧2.50 mmol/L was significantly associated with a positive long-term outcome (P = 0.030). Multivariate analysis confirmed that no response to ACTH therapy was an independent variable that predicted long-term seizure recurrence (P < 0.001, hazard ratio = 4.602, confidence interval = 2.252 to 9.406). ConclusionsA good response to ACTH therapy had a significant predictive value for long-term seizure outcomes. Calcium may play an important role in the treatment of ISS with ACTH.

Risk Factors for Long-Term Contracture Recurrence after Collagenase Injection for Dupuytren Disease: A Prospective Cohort Study

In Dupuytren disease, little is known about the long-term outcomes of collagenase injection or risk factors for contracture recurrence. In this prospective study, 159 patients (242 fingers) with Dupuytren disease and active extension deficit (AED) ≥20° in a metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joint were treated with collagenase injection during a 14-month period. At 5 years, 18 patients were deceased, 2 could not be contacted, and 13 had undergone fasciectomy. The remaining 126 patients (199 treated fingers) participated in a follow-up evaluation at 52-96 (mean 65) months after injection, with physical examination (114 patients) or telephone interview (12 patients). Recurrence was defined as subsequent treatment (surgery or repeat injection) or ≥20° AED worsening in a treated joint between the 6-week and 5-year measurements. The mean AED at baseline was 42° (SD 24) for MCP joints and 31° (SD 29) for PIP joints and at 5 years 11° (SD 17) and 17° (SD 23), respectively. Recurrence occurred in 17% of MCP joints and 25% of PIP joints. Statistically significant risk factors for PIP joint contracture recurrence were greater baseline AED (odds ratio 1.04, 95% CI 1.02-1.06) and small finger treatment (OR 4.6, 95% CI 1.5-14.3), with no significant risk factors found for MCP contracture recurrence.

Cell-free urinary tumor DNA to detect minimal residual disease prior to repeat-transurethral resection of bladder tumor in non–muscle-invasive bladder cancer: A prospective study.

LBA445 Background: Cell-free urinary tumor DNA (utDNA) generated from tumor genomic sequencing is an emerging biomarker showing tremendous potential for detecting minimal residual disease (MRD) in muscle-invasive and metastatic bladder cancer. We performed a prospective study to assess utDNA’s ability to measure MRD at the time of standard-of-care repeat transurethral resection of bladder tumor (rTURBT) in non-muscle invasive bladder cancer (NMIBC). Methods: Patients with high-risk NMIBC were enrolled prior to rTURBT. Index tumor and rTURBT mutational profile was performed via PredicineWES whole exome sequencing across 20,000 genes. Genes with non-synonymous (NS) mutations observed in index and rTURBT specimens identified in a minimum of two samples are reported. Urine samples were taken immediately prior to r-TURBT. utDNA detection was performed by ultra-deep sequencing of urinary cfDNA using a custom panel of up to 50-baseline mutations per patient together with a fixed core panel covering hotspot regions and actionable variants via PredicineBEACON. Urinary tumor fraction was used to call utDNA positivity. The primary endpoint was the detection of utDNA to predict MRD at the time of repeat-TURBT. Results: Eleven patients underwent rTURBT for high-risk NMIBC. Residual tumor was detected at rTURBT in 8/11 (73%) patients. Fifty genes with NS mutations found in at least two samples were identified including TP53, PIK3CA, RB1, MYC, CDKN1A and ARID1A. A median of 146 (range 39-418) and 91 NS (range 2-312) mutations were identified in the index and re-TUR specimens, respectively. Concordance rates were 83% on average between index and rTURBT, highest for patients upstaged to T2 disease, and lowest for patients harboring CIS. New somatic variants not observed in the index tissue were detected in rTURBT for 4/6 patients and 7/14 were also detected in the pre-operative urine. Overall, 50% of utDNA mutations were concordant with index tumor tissue, 39% were concordant with rTURBT tissue, and 33% were concordant with both. The tumor fraction of utDNA was higher in patients with residual disease (mean 2.5% vs. 0.2%, p=0.10). Using tumor-fraction to predict MRD, the area under the receiver-operator curve was 0.85. Using an optimal threshold of ≥3.3% tumor-fraction to define utDNA positivity, the test had a sensitivity of 75% at 100% specificity. Conclusions: Urinary tumor DNA shows promise as a surrogate for minimal residual disease and may predict TURBT pathology for NMIBC. Genomic alterations between index and rTURBT tumors are highly concordant in papillary tumors even in the setting of upstaging, which may aid in targeted intravesical or systemic therapy selection. Larger cohorts and long-term follow up is needed to determine if utDNA can risk-stratify patients prior to rTURBT and predict long-term recurrence.

Stenting as a bridge to surgery in obstructing colon cancer: Long-term recurrence pattern and competing risk of mortality.

Stenting as a bridge to curative surgery (SBTS) for obstructing colon cancer (OCC) has been associated with possibly worse oncological outcomes. To evaluate the recurrence patterns, survival outcomes, and colorectal cancer (CRC)-specific death in patients undergoing SBTS for OCC. Data from 62 patients undergoing SBTS at a single tertiary centre over ten years between 2007 and 2016 were retrospectively examined. Primary outcomes were recurrence patterns, overall survival (OS), cancer-specific survival (CSS), and CRC-specific death. OS and CSS were estimated using the Kaplan-Meier curves. Competing risk analysis with cumulative incidence function (CIF) was used to estimate CRC-specific mortality with other cause-specific death as a competing event. Fine-Gray regressions were performed to determine prognostic factors of CRC-specific death. Univariate and multivariate subdistribution hazard ratios and their corresponding Wald test P values were calculated. 28 patients (45.2%) developed metastases after a median period of 16 mo. Among the 18 patients with single-site metastases: Four had lung-only metastases (14.3%), four had liver-only metastases (14.3%), and 10 had peritoneum-only metastases (35.7%), while 10 patients had two or more sites of metastatic disease (35.7%). The peritoneum was the most prevalent (60.7%) site of metastatic involvement (17/28). The median follow-up duration was 46 mo. 26 (41.9%) of the 62 patients died, of which 16 (61.5%) were CRC-specific deaths and 10 (38.5%) were deaths owing to other causes. The 1-, 3-, and 5-year OS probabilities were 88%, 74%, and 59%; 1-, 3-, and 5-year CSS probabilities were 97%, 83%, and 67%. The highest CIF for CRC-specific death at 60 mo was liver-only recurrence (0.69). Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictive of CRC-specific death. The peritoneum was the most common metastatic site among patients undergoing SBTS. Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictors of CRC-specific death.

Surgical Outcomes, Long-Term Recurrence Rate, and Resource Utilization in a Prospective Cohort of 165 Patients Treated by Transanal Total Mesorectal Excision for Distal Rectal Cancer

A transanal total mesorectal excision (taTME) is a smart alternative to a conventional TME. However, worrisome reports of a high recurrence and complications triggered a moratorium in a few countries. This study assessed the outcomes and resource utilization of a taTME. Consecutive patients with distal rectal cancer treated by a taTME were prospectively included. Outcomes were reported as the median and interquartile range (IQR). One hundred sixty-five patients (67% male and 33% female) with a tumor 7 cm (IQR 5-10) from the anal verge were followed for 50 months (IQR 32-79). The resection margins were threatened in 25% of the patients, while 75% of the patients received neoadjuvant radiochemotherapy. A good mesorectal dissection and clear margins were achieved in 96% of the specimens, and 27 lymph nodes (IQR 20-38) were harvested. Ninety-day major morbidity affected 36 patients (21.8%), including 12 with anastomotic leakages (7.2%). A recurrence occurred locally in 9 patients (5.4%), and 44 patients had a distant metastasis (26.7%). The five-year disease-free survival and overall survival were 67% and 90%, respectively. A multivariate analysis found a long operation and frailty predicted an anastomotic leak, while a positive distal margin and lymph nodes predicted a local recurrence and distant metastasis. A two-team taTME saved 102 min of operative time and EUR 1385 when compared to a one-team approach. Transanal total mesorectal excision produced sound surgical quality and excellent oncologic outcomes.

Hiatal hernia recurrences after laparoscopic surgery: exploring the optimal technique.

The recurrence rate of hiatal hernia (HH) after laparoscopic surgery with crural repair and Nissen or Toupet fundoplication is high (< 25-42%). HH repair can be reinforced with additional anterior sutures, vertical mesh strips (VMS) or mesh placement but the effect in the long-term (> 1year) is still unclear. We determined the recurrence rate of HH after surgery and established whether the use of reinforcement techniques could reduce long-term recurrence rates. In this retrospective cohort study patients were included if they underwent a laparoscopic fundoplication in this hospital between 2012 and 2019. HH was measured with computed tomography and baseline patient characteristics and surgical details were collected. Primary outcomes were recurrence of symptoms and re-intervention, secondary outcome was effect of surgical reinforcement techniques. Statistical analyses comprised chi-square tests, Mann-Whitney U tests and uni- and multivariable logistic regression analyses. In total, 307 patients were included, 206 women and 101 men. During primary surgery, 208 patients underwent a Toupet fundoplication and 97 patients underwent a Nissen fundoplication. Reinforcements consisted of anterior sutures in 132 patients, VMS in 89 patients and mesh in 17 patients. After primary surgery, recurrence of HH was diagnostically confirmed in 64 patients (20.8%). Use of VMS during primary surgery was significantly associated with fewer recurrences (OR = 0.34, p = 0.048), corrected for confounding factors. Secondary surgery was performed in 54 patients (17.6%) and tertiary surgery in five patients (1.6%). Mesh and VMS were used more during secondary and tertiary surgery. The recurrence rate among HH patients in this cohort study was 20.8% with a mean follow-up time of 6years. Secondary surgery was performed in 17.6% of the patients. In future, the use of VMS might lead to fewer recurrences after primary laparoscopic repair of HH.

Circulating tumor DNA (ctDNA) for response assessment in patients with anal cancer treated with definitive chemoradiation.

1 Background: We hypothesized that circulating tumor DNA (ctDNA) clearance could provide an early signal for clinical complete response (cCR) and/ or long-term recurrence compared to standard clinical exam modalities in patients with anal squamous cell carcinoma (ASCC) undergoing definitive chemoradiation (CRT). Methods: Since early 2021 patients with ASCC undergoing CRT at 2 institutions were offered ctDNA monitoring with a commercially available tumor-bespoke multiplex PCR assay. All patients provided written informed consent for ctDNA testing. Patients were clinically restaged, 3-4 months post-CRT, by clinical exam, endoscopy, and/ or MRI and annually with CT chest, abdomen, and pelvis. cCR was defined as no tumor by digital exam, endoscopy and/or MRI. Molecular ctDNA response is described according to cCR, tumor recurrence, and survival. Results: From January 2021 to September 2022, 31 patients with ASCC treated with definitive CRT underwent ctDNA response assessment. The majority (68%) of patients had stage III disease. Patients were treated to a median radiation dose of 54Gy in 27 fractions with combinatorial mitomycin and fluoropyrimidine-based chemotherapy in 94%, and fluoropyrimidine-based chemotherapy alone in 6%. The median follow up was 22 weeks. ctDNA testing was performed in 25 of these patients at baseline, 26 patients during CRT, and 20 patients 30-days post-CRT. At baseline 88% of patients had detectable ctDNA. Patients with stage III, as compared to stage I-II, disease had numerically higher baseline ctDNA levels (26 vs 4 mean tumor molecules per milliliter (MTM/mL), p=0.08). ctDNA levels decreased with treatment (19 vs 0.9 MTM/mL, p=0.05) among the 18 patients with detectable ctDNA and ctDNA tested during CRT, with 50% of patients entering molecular remission. Similarly, ctDNA levels decreased (21 vs 0.2 MTM/mL, p=0.05) among the 16 patients with detectable ctDNA and ctDNA tested post-CRT, with 94% entering molecular remission. All patients in molecular remission were confirmed to have a cCR. Time to molecular ctDNA remission was significantly shorter than time to cCR (median 30 vs 135 days, p &lt;0.01). There were no molecular recurrences among the 16, 14, and 7 patients with ctDNA testing at 2-4 months, 4-8 months, and 8-12 months post-CRT. All patients are alive and without clinical/ radiographic evidence of disease. Conclusions: Surveillance ctDNA monitoring may provide an earlier response assessment for patients with ASCC undergoing CRT compared to standard clinical measures. Longer term follow-up is required to determine if ctDNA response correlates with long term recurrence free survival. Larger trials are needed to assess the clinical utility of integrating molecular ctDNA response in therapeutic response surveillance.

The long-term locoregional recurrence rate of transanal total mesorectal excision in rectal cancer patients: a systematic review

The long-term locoregional recurrence rate of transanal total mesorectal excision in rectal cancer patients: a systematic review

Abstract WMP88: Endovascular Versus Medical Treatment For Chronic Occlusion Of The Internal Carotid Artery: Systematic Review And Meta-analysis

Introduction: Chronic occlusion of the ICA (COICA) is an important cause of ischemic strokes. Evidence has showed that medical management (MM) alone is not sufficient for prevention of ischemic events. Carotid occlusion endovascular revascularization &amp; stenting (COERS) is a promising technique, yet its safety and superiority to MM remain unclear. Objective: To pool and compare rates of safety and efficacy outcomes of COERS versus MM of COICA. Methods: We conducted a systematic search in Embase, Medline, and Web of Science for studies reporting short and long-term outcomes of symptomatic COICA patients who received MM and/or COERS. Main efficacy outcomes were successful recanalization and long-term recurrence of ischemic events. Safety outcomes for COERS were periprocedural (&amp;lt;30 days) events. We performed a meta-analysis of proportions for MM and COERS groups, using GLMM transformation and a random-effects model. Results: 11 studies contained data of COICA patients undergoing COERS, 3 studies of patients who received only MM, and 2 studies compared both arms; they provided data for 513 and 313 patients in the COERS and MM groups, respectively. The pooled recanalization rate after treatment with COERS was 75% (95% CI 0.67-0.82, PI 0.49-0.94, I 2 64%). Recurrence rates of ischemic events at long-term follow-up were 19% (95% CI 0.15-0.25, PI 0.11-0.32, I 2 25%) with MM, and 11% (95% CI 0.07-0.19, PI 0.02-0.42, I 2 2%) after COERS; comparison meta-analysis showed a similar non-significant trend (MM:24% vs. COERS:13%, OR 0.52, 95% CI 0.17-1.59, I 2 0%). The rate of periprocedural events in the COERS group were 2.3% (95% CI 0.012-0.045, I 2 0%) for stroke/TIA, and 2.1% (95% CI 0.011-0.038, I 2 0%) for any ICH. Conclusion: COERS is a feasible technique and a safe strategy for maximizing secondary stroke prevention for the treatment of symptomatic COICA. Still, further prospective trials to better define safety and efficacy boundaries are needed before starting a RCT.

Hemorrhoid laser dearterialization: systematic review and meta-analysis.

Hemorrhoidal disease is a common and troublesome condition. Excisional hemorrhoidectomy can assure the best chance of cure but it is hampered by postoperative pain and potential long-term morbidity therefore minimally invasive techniques have been developed. Since 2009 a doppler-guided hemorrhoidal dearterialization with laser (the hemorrhoidal laser procedure; HeLP) has been proposed to control symptoms without significant sequelae. The aim of this systematic review is to analyze the benefits and disadvantages of HeLP for symptomatic hemorrhoids. The Medline/PubMed, Embase, and Cochrane library databases were searched from January 2010 to March 2022, language was restricted to English and documents to the full text. Randomized and non-randomized, prospective and retrospective cohort studies were included. Risk of bias assessment was performed using the Risk of bias for non-randomized studies (ROBINS-I) and the RoB2 Tool for randomized clinical trial. Primary outcome was to assess the efficacy of HeLP on symptoms' resolution. Secondary objectives were postoperative pain and complications, comparison with other interventional techniques, and evaluation of long-term recurrence. Whenever possible, a meta-analysis was conducted. The GRADE approach was employed to assess the certainty of evidence. We included six non-randomized and one randomized study. HeLP improved or resolved preoperative symptoms in 83.6 to 100% of patients during follow-up. In the randomized study symptoms resolved in 90% of patients after HeLP and 53.3% after rubber band ligation as comparator. Published data indicate that HeLP is effective, relatively safe, with limited recurrence rate, after a short to medium follow-up. The quality of evidence was however low. There is a paucity of studies assessing the benefits or harms of laser dearterialization for the treatment of hemorrhoids and randomized trials are furthermore rare, therefore trials with adequate power and proper design, assessing the advantages and disadvantages of HeLP versus other minimally invasive techniques, are needed. Furthermore, studies evaluating long-term follow-up are wanted.

Prognosis of adults and children following a first unprovoked seizure.

Prognosis of adults and children following a first unprovoked seizure.

Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials

Neoadjuvant ipilimumab plus nivolumab has yielded high response rates in patients with macroscopic stage III melanoma. These response rates translated to high short-term survival rates. However, data on long-term survival and disease recurrence are lacking. In OpACIN, 20 patients with macroscopic stage III melanoma were randomized to ipilimumab 3mg/kg plus nivolumab 1 mg/kg q3w four cycles of adjuvant or split two cycles of neoadjuvant and two adjuvant. In OpACIN-neo, 86 patients with macroscopic stage III melanoma were randomized to arm A (2×ipilimumab 3 mg/kg plus nivolumab 1 mg/kg q3w; n= 30), arm B (2× ipilimumab 1 mg/kg plus nivolumab 3mg/kg q3w; n= 30), or arm C (2× ipilimumab 3 mg/kg q3w plus 2× nivolumab 3 mg/kg q2w; n= 26) followed by surgery. The median recurrence-free survival (RFS) and overall survival (OS) were not reached in either trial. After a median follow-up of 69 months for OpACIN, 1/7 patients with a pathologic response to neoadjuvant therapy had disease recurrence. The estimated 5-year RFS and OS rates for the neoadjuvant arm were 70% and 90% versus 60% and 70% for the adjuvant arm. After a median follow-up of 47 months for OpACIN-neo, the estimated 3-year RFS and OS rates were 82% and 92%, respectively. The estimated 3-year RFS rate for OpACIN-neo was 95% for patients with a pathologic response versus 37% for patients without a pathologic response (P < 0.001). In multiple regression analyses, pathologic response was the strongest predictor of disease recurrence. Of the 12 patients with distant disease recurrence after neoadjuvant therapy, 5 responded to subsequent anti-PD-1 and 8 to targeted therapy, although 7 patients showed progression after the initial response. Updated data confirm the high survival rates after neoadjuvant combination checkpoint inhibition in macroscopic stage III melanoma, especially for patients with a pathologic response. Pathologic response is the strongest surrogate marker for long-term outcome.

Management of lentiginous melanoma with imiquimod assessed by reflectance confocal microscopy.

Management of lentiginous melanoma with imiquimod assessed by reflectance confocal microscopy.

Long-term prognostic impact of beta-blockers in patients with Takotsubo syndrome: Results from the RETAKO Registry

BackgroundNo evidence-based therapy has yet been established for Takotsubo syndrome (TTS). Given the putative harmful effects of catecholamines in patients with TTS, beta-blockers may potentially decrease the intensity of the detrimental cardiac effects in those patients. ObjectiveThe purpose of this study was to assess the impact of beta-blocker therapy on long-term mortality and TTS recurrence. MethodsThe cohort study used the national Spanish Registry on TakoTsubo Syndrome (RETAKO). A total of 970 TTS post-discharge survivors, without pheochromocytoma, left ventricular outflow tract obstruction, sustained ventricular arrhythmias, and significant bradyarrhythmias, between January 1, 2003, and July 31, 2018, were assessed. Cox regression analysis and inverse probability weighting (IPW) propensity score analysis were used to evaluate the association between beta-blocker therapy and survival free of TTS recurrence. ResultsFrom 970 TTS patients, 582 (60.0%) received beta-blockers. During a mean follow-up of 2.5±3.3 years, there were 87 deaths (3.6 per 100 patients/year) and 29 TTS recurrences (1.2 per 100 patient/year). There was no significant difference in follow-up mortality or TTS recurrence in unadjusted and adjusted Cox analysis (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.59–1.27, and 0.95, 95% CI 0.57–1.13, respectively). After weighting and adjusting by IPW, differences in one-year survival free of TTS recurrence between patients treated and untreated with beta-blockers were not found (average treatment effect −0.01, 95% CI −0.07 to 0.04; p=0.621). ConclusionsIn this observational nationwide study from Spain, there was no significant association between beta-blocker therapy and follow-up survival free of TTS recurrence.

Comparative analysis of mid-term outcomes of Rigid and NeoRing support rings in mitral regurgitation surgery: a prospective randomized trial

Highlights. For the first time, as part of a prospective randomized study, a comparative assessment of the mid-term results of mitral valve annuloplasty using a new biological NeoRing ring (CJSC NeoKor, Kemerovo) and a RIGID ring (CJSC NPP MedInzh, Penza) in patients with connective tissue dysplasia was carried out. Predictors of the conversion of sinus rhythm to atrial fibrillation and residual mitral insufficiency in the medium-term follow-up period were determined.Aim. To analysis and compare mid-term results of mitral valve annuloplasty conducted using NeoRing и RIGID rings.Methods. From November 2019 to March 2022, 62 patients with mitral valve (MV) dysplasia underwent MV annuloplasty using NeoRing semi-rigid rings (CJSC NeoKor, Kemerovo, n = 31) and rigid RIGID rings (CJSC NPP MedInzh, Penza, n = 31). There were no differences between the groups at baseline.Results. Two deaths were registered during inpatient treatment in the RIGID group. Both devices showed a satisfactory outcome during inpatient treatment in the form of restoration of MV function (p&lt;0.001) and the frequency of detected maximum residual mitral regurgitation (MR) up to grade 1 in the NeoRing group 9.7% and in the RIGID group 29%, respectively, no statistically significant intergroup differences were noted (p = 0.292). After 12 months, freedom from ≥2 grade MR in the NeoRing group was 93.5% and 77.4% in the RIGID group (p = 0.147). In the RIGID group, patients had higher values of the transvalvular mitral diastolic gradient – PAV 3.70 [3.00–4.40] mm Hg vs. NeoRing group 2.3 [2.05–2.85] mmHg (p&lt;0.001), as well as a higher transvalvular flow rate – VAV 79 [71–94] cm/sec vs. 70 [64–79] cm/sec (p = 0.017). The analysis of the achievement of composite primary endpoint (recurrence of ≥2 grade MR, MACCE, new onset arrhythmias, reoperations) by the device was carried out. The composite endpoint rate in the RIGID group was 3.067 times higher compared to the NeoRing group, odds differences were statistically significant (p = 0.037, 95% CI: 1.053–8.934).Conclusion. The outcome of MV annuloplasty conducted using rigid and semi-rigid rings revealed no significant differences in long-term survival and recurrence of MR between groups. Given the statistically significant difference in achieving the combined endpoint, lower inpatient and long-term indicators of transmitral pressure gradient, and a positive effect on cardiac chambers reverse remodeling, it was concluded that the use of semi-rigid NeoRing rings for MV annuloplasty when performing valvepreserving operations for connective tissue dysplasia is preferable.