Clinical Significance and Risk Factors of Local Recurrence in Synovial Sarcoma: A Retrospective Analysis of 171 Cases

Objective: To investigate risk factors of local recurrence of synovial sarcoma and the impact of local recurrence on survival.Methods: We retrospectively reviewed clinical data of patients with II to IIIB (AJCC8) synovial sarcoma who underwent surgery at our center between March 2005 and December 2016. Data relating clinicopathological factors, treatment and prognosis were collected. The impact of local recurrence on overall survival (OS), local recurrence-free survival (LRFS), and distant relapse-free survival (DRFS) were analyzed. The prognostic factors associated with local recurrence were also analyzed using Kaplan-Meier Curves and Cox regression analysis.Results: A total of 171 patients were included in this analysis. After a median follow-up of 48 months, 66 patients (38.6%) experienced local recurrence. The 5-year OS, LRFS, and DRFS rates of patients with local recurrence were 37.6, 6.1, and 24.1%, respectively. Multivariate analysis showed that larger initial tumors, multiple recurrences, positive resection margins, marginal resection, and lack of adjuvant therapy were associated with higher local recurrence.Conclusion: Local recurrence of synovial sarcoma is associated with distant metastasis and poor survival. Chemoradiation improves the prognosis of patients with local recurrence, in particular those for which recurrence occurs shortly after initial treatment.

«Վահագնի երգը» և հայկական էպոսը Նոր տեսակետ հայկական էպոսի ծագման և ձևավորման վերաբերյալ

Multiple recurrences of the sound combination erk- in the ancient Armenian hymn on the birth of Vahagn, the god of thunder and war, can be considered an anagram of the word erku (two) with an allusion to twins. Moreover, in the expression cov cirani (purple sea) one can see an anagram of Covinar, the name of the mother of the epic twins Sanasar and Baghdasar, first heroes of the epic "Daredevils of Sassoun". In this context it becomes obvious that the image of Sanasar, the elder of the twins, founder of the dynasty of heroes, directly goes back to Vahagn. The same picture of the birth of mythological twins occurs in the ancient epic “Vipasank”.

Molecular subtyping of ependymoma and prognostic impact of Ki-67

Although ependymomas (EPNs) have similar histopathology, they are heterogeneous tumors with diverse immunophenotypes, genetics, epigenetics, and different clinical behavior according to anatomical locations. We reclassified 141 primary EPNs from a single institute with immunohistochemistry (IHC) and next-generation sequencing (NGS). Supratentorial (ST), posterior fossa (PF), and spinal (SP) EPNs comprised 12%, 41%, and 47% of our cohort, respectively. Fusion genes were found only in ST-EPNs except for one SP-EPN with ZFTA-YAP1 fusion, NF2 gene alterations were found in SP-EPNs, but no driver gene was present in PF-EPNs. Surrogate IHC markers revealed high concordance rates between L1CAM and ZFTA-fusion and H3K27me3 loss or EZHIP overexpression was used for PFA-EPNs. The 7% cut-off of Ki-67 was sufficient to classify EPNs into two-tiered grades at all anatomical locations. Multivariate analysis also delineated that a Ki-67 index was the only independent prognostic factor in both overall and progression-free survivals. The gain of chromosome 1q and CDKN2A/2B deletion were associated with poor outcomes, such as multiple recurrences or extracranial metastases. In this study, we propose a cost-effective schematic diagnostic flow of EPNs by the anatomical location, three biomarkers (L1CAM, H3K27me3, and EZHIP), and a cut-off of a 7% Ki-67 labeling index.

Small but Challenging Conjunctival Melanoma: New Insights, Paradigms and Future Perspectives

Although its incidence has increased over the last decades, conjunctival melanoma (CM) remains a rare but challenging periocular malignancy. While there is currently no recognized standard of care, “no-touch” surgical excision followed by adjuvant treatments is usually recommended. Despite its small size, managing CM is challenging for clinicians. The first challenge is the high risk of tumour local recurrence that occurs in about one third of the patients. The management of locally advanced CM (≥T2) or multiple recurrences may require mutilating surgeries such as orbital exenteration (OE). The second challenge is the metastatic spread of CM that occurs in about one quarter of patients, regardless of whether complete surgical excision is performed or not. This highlights the infiltrative and highly aggressive behaviour of CM. Recently, attention has been directed towards the use of eye-sparing strategies to avoid OE. Initially, wide conservative surgeries followed by customized brachytherapy or radiotherapy have appeared as viable strategies. Nowadays, new biological insights into CM have revealed similarities with cutaneous melanoma. These new findings have allowed clinicians to reconsider the management of locally advanced CM with “medical” eye-sparing treatment as well as the management of metastatic spread. The aim of this review was to summarize the current and future perspectives of treatment for CM based on recent biological findings.

Cardiac and non-cardiac characteristics of Jervell-Lange-Nielsen syndrome

We aimed to analyze the management of children with Jervell-Lange-Nielsen syndrome based on their clinical and genetic characteristics and to assess the effectiveness of their therapy.Methods. We analyzed medical data from 12 Jervell and Lange-Nielsen syndrome patients. Mean follow-up was 8.3±5.1 years. Comprehensive cardiological examination include the standard 12-lead electrocardiography (ECG), echocardiography, stress-test, 24-hour Holter recordings, blood tests, thyroid ultrasound, and assessment of thyroid hormone levels, and if necessary, consultation with a neurologist.Results. At the first visit, the mean age was 3.0±2 years old, girls prevailed (67%). All patients are alive now. The mean QTc was 578.9±57.3 ms. Cardiac events had 10 patients (83%), mean age at the first event was 1.9±1.6 years. In 67% of children, syncope was initially regarded as epileptic. All patients received beta-blockers, which were prescribed at mean age 3.0±2.3 years (from 1 month to 7 years). In 8 patients cardiac events recurred despite regular and adequate beta-blocker therapy, all of them were implanted with implanted cardioverter-defibrillator. It was found that patients with the first syncope under the age of 1.5 and delayed initiation of therapy (at the mean age 4.3±1.7 years) had multiple recurrences of syncope despite therapy. Non-cardiac symptoms include sensorineural hearing loss in 100% of cases and hypochromic anemia in 75% of cases.Conclusion. In Jervell-Lange-Nielsen patients who are characterized by resistant ventricular tachyarrhythmia aggressive antiarrhythmic therapy at a very early age is essential for increasing the risk of life-threatening cardiac events. Consequently, diagnosis of the disease in the first days of life is extremely relevant. ECG screening is crucial in solving the problem of early diagnosis of the disease. Extracardiac pathology in patients with Jervell-Lange-Nielsen syndrome necessitates the interaction of doctors of different specialties together when managing a patient.

US Database Study of Clinical Burden and Unmet Need in Recurrent Pericarditis

Background Patients with recurrent pericarditis (RP) may develop complications, multiple recurrences, or inadequate treatment response. This study aimed to characterize disease burden and unmet needs in RP. Methods and Results This retrospective US database analysis included newly diagnosed patients with RP with ≥24 months of continuous history following their first pericarditis episode. RP was defined as ≥2 pericarditis episodes ≥28 days apart. Some patients had ≥2 recurrences, while others had a single recurrence with a serious complication, ie, constrictive pericarditis, cardiac tamponade, or a large pericardial effusion with pericardiocentesis/pericardial window. Among these patients with multiple recurrences and/or complications, some had features relating to treatment history, including long‐term corticosteroid use (corticosteroids started within 30 days of flare, continuing ≥90 consecutive days) or inadequate treatment response (pericarditis recurring despite corticosteroids and/or colchicine, or other drugs [excluding NSAIDs] within 30 days of flare, or prior pericardiectomy). Patients (N=2096) had hypertension (60%), cardiomegaly (9%), congestive heart failure (17%), atrial fibrillation (16%), autoimmune diseases (18%), diabetes mellitus (21%), renal disease (20%), anxiety (21%), and depression (14%). Complications included pericardial effusion (50%), cardiac tamponade (9%), and constrictive pericarditis (4%). Pharmacotherapy included colchicine (51%), NSAIDs (40%), and corticosteroids (30%), often in combination. This study estimates 37 000 US patients with RP; incidence was 6.0/100 000/year (95% CI, 5.6‒6.3), and prevalence was 11.2/100 000 (95% CI, 10.6‒11.7). Conclusions Patients with RP may have multiple recurrences and/or complications, often because of inadequate treatment response and persistent underlying disease. Corticosteroid use is frequent despite known side‐effect risks, potentially exacerbated by prevalent comorbidities. Substantial clinical burden and lack of effective treatments underscore the high unmet need.

Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma

Objective To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD). Methods The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized. Results High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer. Conclusions The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.