A rare case of papillary fibroelastoma involving the tricuspid valve. A single center experience over a period of 22 years (1999-2021).

BACKGROUND AND AIM: Papillary fibroelastoma (PFE) represents only 16% of the benign cardiac tumor and approximately 15% of these are located on the tricuspid valve. MATERIALS AND METHODS: Over a period of 22 years (1999-2021) we observed 75 pts with cardiac tumors at our Center over 9650 pts operated on but only one case of a tricuspid valve PFE in a 69-year-old patient. Trans-thoracic echocardiography demonstrated a mobile mass (20 × 10 mm), adhering to the atrial side of the septal leaflet of the tricuspid valve of unknown origin. In consideration of the mobility of the mass and the consequent high embolic risk, surgical removal was made. The patient underwent surgery through a median sternotomy on CPBP. A 'gelatinous' mass adhering to the tricuspid leaflet was found and completely removed. The postoperative course was uneventful. The pathological diagnosis was PFE. CONCLUSIONS: PFEs of the tricuspid valve are rare entities being in most cases found incidentally. In our experience, the incidence of this tumor in this location is 1/10,000 cases of cardiac surgery. Although most patients are asymptomatic, surgical treatment is nevertheless recommended in consideration of the high embolic risk.

Impact of COVID-19 Infection on Liver Transplant Recipients: Does It Make Any Difference?

The first case of coronavirus disease 2019 (COVID-19) was diagnosed in December 2019 in Wuhan, China. Since then, this novel infectious disease, caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has grown into a pandemic with over 330 million infected individuals worldwide, many of them with innate or acquired immunosuppression. Liver transplantation (LT) is offered as a curative therapy for end-stage liver disease as well as for acute liver failure cases. Advances in immunosuppressive therapy decreased the rates of acute and chronic graft rejection, significantly improving the quality of life. Liver transplant recipients are considered at particularly high risk for developing critical COVID-19 infection because of their chronic immunosuppressed state. Available data are heterogeneous, and the mortality rate is variably reported in the literature. There is controversy regarding whether their immunosuppressive status is a risk or a protective factor for developing severe respiratory disease. Moreover, the mechanism of action is still unclear. We report the clinical outcome of three liver transplant recipients who had COVID-19 pneumonia at different moments following liver transplantation. All patients received a standard immunosuppression regimen and specific antiviral therapy, requiring no invasive mechanical ventilation. They were discharged from the hospital with no long-term COVID-19 complications.

Thyroid Microcarcinoma in Pediatric Population in Romania.

Thyroid microcarcinoma in pediatric population in Romania Non-medullary thyroid cancer (TC) is the most common endocrine malignancy, with an increasing incidence in the recent years, due to the increase of the thyroid microcarcinoma. Thyroid microcarcinoma (mTC) is defined, according to WHO criteria, as ≤1 cm dimension thyroid carcinoma, being a rare disease in children population. In adults, the current guidelines recommend a limited surgical approach. In children, however, there are no specific guidelines for mTC. Due to the scarcity of these tumors, mTC in children have largely been understudied, to our knowledge with only one previous publication reporting on the outcomes of a large historic series of patients with mTC from the USA. In Romania, the incidence of TC is rising, one of the reason may be the effect of Chernobyl nuclear accident in the past and the iodine deficiency. The purpose of this study was to describe the characteristics and outcome of children diagnosed with mTC in Romania diagnosed from 1 January 2000 to 31 December 2018. During the study period we identified 77 cases of differentiated TC (papillary and follicular) and of these 20 cases (19.4%) were mTC. The mTC represented roughly one fifth of our nationwide pediatric population diagnosed in the last 20 years, the majority of cases being recorded in adolescents aged between 15-18 years. Although patients with apparently more unfavorable local phenotype were identified, this was not reflected in the outcome of the patients in terms of remission of the disease and survival. Our study illustrates the heterogeneity of the real-life practice with respect to the pediatric mTC, and underscores the need for carefully designed multicenter international studies, including larger cohorts of patients in order to provide the data required for establishing evidence based uniform protocols. The European Reference Networks (ERN), such as the ERN for Rare Endocrine Diseases (Endo-ERN) provides an ideal platform to initiate such collaborative studies.

Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas.

PURPOSE: To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). PATIENTS AND METHODS: Patients, predominantly men, with their CSSCs' immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort's objective response rate at week 15 (ORRW15). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORRW15 difference between PD-L1+ and PD-L1- patients, was assessed for ORR, disease control rate, and safety, but not survival. RESULTS: Median age of all patients was 79 years. The primary cohort's ORRW15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORRW15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1- patients (17%; P = .02). Responders' W15 total FACT-G score had improved (P = .025) compared with nonresponders. CONCLUSION: First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.

Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis.

BACKGROUND: The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized. AIM: To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting. METHODS: We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data. RESULTS: MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58-7.07), peripheral oedema (OR 2.87 95% CI 1.93-4.27) and syncope (OR 6.71, 95% CI 3.00-14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03-10.09), peripheral oedema (arOR 1.39, 95% CI 1.17-1.66), syncope (arOR 1.56, 95% CI 1.22-1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04-7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21-1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach. CONCLUSIONS: In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors.

Post-Treatment Thyroid Diseases in Children with Brain Tumors: A Single-Center Experience at "Prof. Dr. Ion Chiricuța" Institute of Oncology, Cluj-Napoca.

AIM OF STUDY: The purpose of the study was to evaluate the association of thyroid dysfunction occurring in pediatric patients treated for brain tumors. PATIENTS AND METHODS: A total of 255 patients with brain tumors were treated between 2001 and 2018 at the "Prof. Dr. Ion Chiricuța" Institute of Oncology, Cluj-Napoca. Due to a minimum follow-up of 4 years, we studied 184 out of the 255 patients. The cohort included 69 girls (37.5%) and 109 boys (62.5%), with a median age of 8.4 years. The evaluated tumors included medulloblastomas (47 patients), astrocytomas (44 patients), ependymomas (22 patients), gliomas (20 patients), germ cell tumors (12 patients), primitive neuroectodermal tumors (4 patients), as well as other types of tumors (15 patients); in 20 of the cases, biopsy could not be performed. RESULTS: There was a 60% overall survival rate; among the 120 surviving patients, 11 (9.1%) were diagnosed with iatrogenic thyroid disease. We observed an important number of iatrogenic thyroid disease cases in this group of patients, thus revealing the importance of long-term thyroid function evaluation in all children who finalized their treatment for brain tumors. Through this study, we aimed to provide an accurate image of the methodology of monitoring for thyroid dysfunction in childhood brain tumor survivors. CONCLUSION: Given the fact that the probability of developing thyroid dysfunction in the pediatric population treated for brain tumors is not rare, we recommend that childhood brain tumor survivors be monitored for iatrogenic thyroid disease, in order to provide early diagnosis and treatment.

Pediatric Thyroid Cancer in Europe: An Overdiagnosed Condition? A Literature Review.

Thyroid neoplastic pathology is the most common form of cancer associated with radiation exposure. The most common histopathological type of thyroid carcinoma is the differentiated thyroid cancer (these include papillary and follicular type), which represents over 90% of all cases, especially affecting girls rather than boys. Although patients are diagnosed in advanced stages as compared to adults, the prognosis of the disease is very good, with a 30-year survival rate of over 95% but post-therapeutic morbidity remains quite high. The treatment is based in particular on the therapeutic guidelines for adults, but as children have some histopathological and genetic characteristics of thyroid cancer, as well as different initial clinical presentations, we decided to review the literature on this pathology among the pediatric population, focusing on cases in Europe. The major interest is the impact of the Chernobyl accident.

Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma.

BACKGROUND: The objective was to assess the response rate and survival of patients with metastatic mucosal melanoma (MM) and uveal melanoma (UM) treated with anti-CTLA-4 or anti-PD-1 monoclonal antibodies (mAbs). METHODS: A multicenter retrospective study was performed in 25 dermatology departments in France. All patients with stage III-C to IV MM or UM who were treated with anti-CTLA-4 or anti-PD-1 mAbs between 2008 and 2016 were included and compared after adjustment for main prognostic factors with a second cohort of patients treated with chemotherapy. Tumor response was evaluated according to RECIST v. 1.1 criteria at Week 12. RESULTS: Four-hundred-and-thirty-nine patients were included, 229 MM (151 immunotherapy, 78 chemotherapy) and 210 UM (100 immunotherapy, 110 chemotherapy). Response rates of MM patients treated with immunotherapy were 18/151 (11.9%; 95% CI:7.2%-18.2%), versus 11/78 (14.1%, 95% CI:7.3%-23.8%) in patients treated with chemotherapy (p=0.87). No tumor response was observed in UM patients treated with immunotherapy, versus 4/110 responses (3.6%, 95% CI:1.0-9.0%) in patients treated with chemotherapy (p=0.15). The adjusted overall survival (OS) of MM patients treated with immunotherapy was longer than that of patients treated with chemotherapy HR=0.62 (95% CI: 0.43-0.91), p=0.014, with an unadjusted median OS of 15.97 months [interquartile range (IQR)=6.89-27.11] and 8.82 months [IQR=5.02-14.92], respectively. The adjusted OS of UM patients treated with immunotherapy was not significantly different from that of patients treated with chemotherapy (HR=0.98, 95% CI: 0.66-1.44) p=0.92, with an unadjusted median OS of 13.38 months [IQR=6.03-29.57] and 11.02 months [IQR=6.13-23.93], respectively. CONCLUSION: Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor.

Vemurafenib and concomitant stereotactic radiation for the treatment of melanoma with spinal metastases: A case report.

A 56-year-old man with BRAFV600E melanoma and spinal metastases treated with vemurafenib and stereotactic radiation showed a partial response without neurological, skin or mucosal toxicity, 8 months after completion of this combination. This case suggests that stereotactic radiation spares normal tissues and might be safer than conventional fractionated radiation with vemurafenib.

Defining and recognising locally advanced basal cell carcinoma.

BACKGROUND: Rarely, basal cell carcinomas (BCCs) have the potential to become extensively invasive and destructive, a phenomenon that has led to the term "locally advanced BCC" (laBCC). We identified and described the diverse settings that could be considered "locally advanced". METHODS: The panel of experts included oncodermatologists, dermatological and maxillofacial surgeons, pathologists, radiotherapists and geriatricians. During a 1-day workshop session, an interactive flow/sequence of questions and inputs was debated. RESULTS: Discussion of nine cases permitted us to approach consensus concerning what constitutes laBCC. The expert panel retained three major components for the complete assessment of laBCC cases: factors of complexity related to the tumour itself, factors related to the operability and the technical procedure, and factors related to the patient. Competing risks of death should be precisely identified. To ensure homogeneous multidisciplinary team (MDT) decisions in different clinical settings, the panel aimed to develop a practical tool based on the three components. CONCLUSION: The grid presented is not a definitive tool, but rather, it is a method for analysing the complexity of laBCC.