Neo-adjuvant chemotherapy in non-small cell lung cancer (NSCLC).
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
A Terzi
Publications and source records attributed to A Terzi.
Surgical treatment of complicated pilonidal disease: limited separate elliptical excision with primary closure.
OBJECTIVE: We aimed at treating complicated pilonidal sinus (PS) patients by a simple and effective surgical procedure. METHOD: Between 2000 and 2004, 24 selected complicated PS patients were treated with 'limited separate elliptical excision and primary closure'. Patients with extensive or bilateral gluteal involvement, having more lateral, caudal or cephalic sinuses, multiple recurrences and unhealed chronic wounds after pilonidal surgery were included. Asymmetric excision and primary closure was performed to main diseased tissue in the midline. Additionally, small separate elliptical excisions with primary closure were performed in other involved tissues. The fistula tract or granulation tissue were excised subcutaneously if present. All patients were operated under local anaesthesia. The fascial attachments between the skin and coccyx were released at the deep point in the midline and at one side of wound. Suction drains and prophylactic antibiotics were used; subcutaneous tissues were closed with running polyglactin sutures and skin with polypropylene subcutaneously. RESULTS: The mean age of patients was 28.4 years (range 18-38). The mean follow-up time was 2.8 years. One recurrence, one seroma, one wound infection and one wound breakdown were recorded. Healing was always by first intention except in patients with wound infection and breakdown. CONCLUSION: Most of the complicated PS patients can be operated with acceptable rates of recurrences and complications by using 'limited separate elliptical excisions with primary closure'.
Adult↗
Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD.
Identifying pre-clinical Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI) is a major issue in clinical diagnosis. Establishing a combination of predictive markers from different fields of research might help in increasing the diagnostic accuracy. Aim of this study was to evaluate the potential role of 99mTc-ECD single photon emission computed tomography (SPECT) and memory scores in predicting conversion to AD in MCI subjects. Thirty-one MCI subjects underwent a clinical and neuropsychological examination, and a regional cerebral blood flow (rCBF) SPECT scan at baseline. Subjects had been followed periodically through 2 years in order to monitor the progression of cognitive symptoms. Canonical variate analysis of principal components was able to separate all subjects who converted to AD from those who remained stable, the former being characterized by a specific hypometabolic pattern, involving the parietal and temporal lobes, precuneus, and posterior cingulate cortex. Canonical correlation analysis of combined baseline memory deficits and rCBF SPECT images identified pre-clinical AD with a sensitivity and specificity of 77.8%. The pattern of hypoperfusion 99mTc-ECD SPECT and the severity of memory deficits predict the risk of progression to probable AD dementia in MCI subjects.
Alzheimer Disease↗
The use of flexible spiral drains after non-cardiac thoracic surgery. A clinical study.
OBJECTIVE: After an observational study on 50 patients determined the efficacy and safety of a small calibre (19F), flexible, fluted spiral drains with round cross-section after non-cardiac thoracic surgery we undertook a prospective study to compare these drains to standard chest drains also in terms of pain using a Visual Analog Score. METHODS: One hundred consecutive patients who had to undergo non-cardiac chest surgery either by thoracotomy or by VATS were randomly assigned to receive small calibre drains with round cross-section (group A) or the standard chest drains (group B) to drain the pleural space. Drains were connected to a unitized chest drainage system. Pain was assessed using a Visual Analog Scale (VAS) 0-100. RESULTS: The amount of fluid evacuated daily in patients who received the spiral drains was as much as 1150 ml, that of patients who received standard drains was as much as 950 ml. In no case did spiral drains have to be replaced with standard tubes. In group A first drain was removed after a mean of 3.4 days and the second after a mean of 5.9 days; in group B after a mean of 4.1 and 6.1 days, respectively. Patients were discharged after a mean of 8.5 days in group A (SD 4.04) and 8.1 days in group B (SD 4.76). There were no drains-related complications in both groups. The drains-related pain for the patient was significantly less for patients with spiral drains compared to standard drains at rest, during cough induced by respiratory therapists and at the time of removal. CONCLUSIONS: Spiral drains proved to be at least as safe and effective as conventional tubes after lung surgery; they allowed for evacuation of large amounts of blood/fluid as well as air, and were associated with minimal discomfort.
Chest Tubes↗
Isolated metastasis of malignant melanoma into follicular carcinoma of the thyroid gland.
A 38-yr-old woman with a history of malignant melanoma (MM) presented with a thyroidal nodule. Fine needle aspiration biopsy of the thyroid was consistent with metastatic MM. The patient underwent thyroidectomy: microscopic examination revealed a follicular carcinoma nodule harboring a focus of metastatic melanoma. On review of the fine needle aspiration biopsy specimen, the population of cells with more uniform nuclei with focal follicle formation, which initially was interpreted as cells originating from normal thyroid tissue, was seen to actually represent the follicular carcinoma component. Tumor-to-tumor metastasis is an interesting phenomenon and there are only few cases of MM metastasis to other tumors. MM metastasis into a neoplastic thyroid nodule is a very rare combination and may be explained because the nodule in question represents the most highly vascularized component of the thyroid.
Adenocarcinoma, Follicular↗
Lung resection for bronchogenic carcinoma after pneumonectomy: a safe and worthwhile procedure.
OBJECTIVES: Patients treated surgically for lung cancer can develop either a metachronous cancer or a recurrence. The appearance of a new cancer on the remaining lung after a pneumonectomy poses unique treatment problems, and surgery is often considered contraindicated. We report on the outcome of resections for lung cancer after pneumonectomy performed for lung cancer. METHODS: We reviewed the records of patients who underwent a resection of bronchogenic carcinoma on the remaining lung from 1990 to 2002. RESULTS: There were 14 patients (13 males and 1 female) with a median age of 64 years (range 51-74). Median preoperative Fev1 was 1.45 (range 1.35-2.23), corresponding to 59% of predicted Fev1 (range 46-80%). Resection was performed between 11 and 264 months after pneumonectomy (median 35.5). The resections performed were: one wedge resection in 11 patients, two wedge resections in two patients and two segmentectomies in two other patients; one patient underwent a third resection. Diagnosis was metachronous cancer in 12 patients and metastasis in two patients. Complications occurred in three patients (21%), while operative mortality was nil. Mean hospital stay was 10.5 days (6-25). Two patients received chemotherapy (one after local recurrence, one after the third resection). Overall 1, 3 and 5 year survivals were 57, 46 and 30%, respectively (median 21 months). For patients with a metachronous cancer they were 69, 55 and 37% (median 57 months), respectively, while neither patient with a metastatic tumor survived 1 year (P=0.03). CONCLUSIONS: Limited lung resection on a single lung is a safe procedure associated with acceptable morbidity and mortality rates. In patients with a metachronous lung cancer, long-term survival with a good quality of life can be obtained with limited resection on the residual lung.
Aged↗
Persistent excess mortality from lung cancer in patients with stage I non-small-cell lung cancer, disease-free after 5 years.
Among patients with non-small-cell lung cancer (NSCLC), those with pathological stage I have the best expectation of survival; however, survival is reduced to less than 50% in the long term. At present, it is unclear when patients can be reasonably defined as cured, and if they experience a higher incidence of malignant/nonmalignant diseases and a lower expectation of survival than the general population. A total of 134 stage I NSCLC patients, who had undergone resection at the Thoracic Surgery Unit of the General Hospital of Verona (north-eastern Italy) from October 1987 to December 1993, were still disease-free at 5 years. These subjects were further followed up, and morbidity and mortality rates were compared with those recorded in the general population of the same geographical area. The standardised incidence ratios (SIRs) for all malignancies and for lung cancer were higher than expected (2.39, 95% CI=1.6-3.5, P<0.001; 10.1, 95% CI=6.2-15.6, P<0.0001, respectively). The standardised mortality ratio (SMR) was also significantly increased (1.73, 95% CI=1.1-2.6, P=0.013). The excess mortality could be entirely explained by an increase in mortality from lung cancer (5.7, 95% CI=2.8-10.1, P<0.0001). This study shows that patients, resected for pathological stage I NSCLC and tumour-free after 5 years, have a higher incidence of new lung cancer compared with the general population, which in turn determines an excess in all-cause mortality in the following years.
Adult↗
Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer.
Fascin-1, the most expressed form of fascin in vertebrate tissues, is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this protein in nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for fascin expression. Overall, variable fascin immunoreactivity was detected in 98% of 116 squamous cell carcinomas, in 78% of 96 adenocarcinomas, in 83% of six large cell carcinomas, and in the two adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (P<0.001), also when the surrounding invasive carcinoma was unreactive. Fascin immunoreactivity correlated with high tumour grade (P=0.017) and, in adenocarcinomas, with high Ki-67 labelling index (P=0.021). Adenocarcinomas with a prevalent bronchiolo-alveolar in situ component were less commonly immunoreactive for fascin than invasive tumours (P=0.005). Contralateral thoracic or distant metastases were associated significantly with diffuse (>60% immunoreactive tumour cells) fascin expression in adenocarcinomas (P=0.043), and marginally with strong fascin immunostaining in squamous cell carcinomas (P=0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (>60% immunoreactive neoplastic cells) and/or strong immunoreactivity for fascin had a shorter survival (P=0.006 for adenocarcinomas and P=0.026 for squamous cell carcinomas), even after multivariate analysis (P=0.014 and 0.050, respectively). The current study documents for the first time that fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable clinical course of the disease. Targetting the fascin pathway could be a novel therapeutic strategy of NSCLC.
Adult↗
Sleeve lobectomy for non-small cell lung cancer and carcinoids: results in 160 cases.
OBJECTIVE: To assess operative mortality (OM), morbidity and long-term results of sleeve lobectomies performed for non-small cell lung cancer (NSCLC) and carcinoids during a 35-year period. METHODS: A retrospective review of patients who underwent a sleeve lobectomy for NSCLC and carcinoids was undertaken, univariate and multivariate analyses of factors influencing early mortality in NSCLC were performed and for this purpose the series was split into an early and a contemporary phase, the Kaplan-Meier method was used to calculate the cumulative survival rate, and statistical significance was calculated with the log-rank test. Causes of death were evaluated in relation to the stage of the disease. RESULTS: OM for NSCLC was 14.6% in the early phase and 6% in the contemporary one; late stenosis occurred in 7.7% of NSCLC patients in the early phase and in 2% in the contemporary one. No OM or late stenosis occurred in carcinoid patients. Three, 5 and 10-year survival rates excluding carcinoids were 77, 62 and 31% for stage I(A-B), 45, 34 and 27% for stage II(A-B), 33, 22 and 0% for stage III(A-B). The 10-year survival rate for carcinoids was 100%. There was no significant difference in long-term survival between stages II and III, while the difference between stage I and stages II and III was significant (P<0.001). When survival was analyzed in relation to nodal status, 3, 5 and 10-year survival rates were 71, 57 and 33% for N0 disease, 42, 33 and 22% for N1 disease, and 34 and 19% with the last observation at 82 months of 19% for N2 disease; there was no significant difference in survival between N1 and N2 disease. A second primary lung cancer occurred in six patients (3.7%) who underwent resection. Late mortality was not related to cancer in most stage I patients while in stages II and III patients it was related to local and distant recurrences. CONCLUSIONS: Sleeve lobectomy is a valid alternative to pneumonectomy: careful patient selection and surgical technique make it possible to achieve a mortality rate comparable to or lower than that for pneumonectomy along with a better quality of life. In addition, it allows further lung resection, if necessary.
Carcinoid Tumor↗
Completion pneumonectomy for non-small cell lung cancer: experience with 59 cases.
OBJECTIVE: The objective of this study was to assess the results of completion pneumonectomy performed for non-small cell lung cancer, classified as second primary or recurrence/metastasis. METHODS: From 1982 to 2000, 59 patients underwent completion pneumonectomy for lung cancer, classified second primary or recurrence/metastasis according to a modified form of Martini's criteria, after a mean interval from first resection of 60 months for second primary lung cancers and 19 months for recurrences/metastases. RESULTS: Operative mortality was 3.4% and complications occurred in 30% of patients. Five-year survival rate for completely resected patients was 25% (median 20 months). No significant difference in long-term survival was detected between second primary and recurrent tumors; survival was not adversely affected by a resection interval of less than 2 years or less than 12 months. CONCLUSIONS: Completion pneumonectomy for non-small cell lung cancer is a safe surgical procedure in experienced hands; long-term survival is acceptable and the best results are obtained for stage I lung cancer. Distinction between second primary lung cancer and recurrence failed to demonstrate a prognostic value.
Adult↗
A phase II study of induction chemotherapy with gemcitabine (G) and cisplatin (P) in locally advanced non-small cell lung cancer: interim analysis.
BACKGROUND: Gemcitabine-cisplatin (GP) combination is one of the most active and well tolerated regimens in advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the activity and toxicity of the GP regimen as a 21-day schedule in patients (pts) with stage IIIAN2-IIIB NSCLC. PATIENTS AND METHODS: From October 1997 to July 2000, 47 pts entered the study: 43 were eligible (40 men and three women); median age was 61 years (range 45-73); ECOG PS 0-1; histology was squamous (20 pts), adenocarcinoma (12 pts), large cell (five pts), and undifferentiated (six pts); stage was IIIAN2 (14 pts, 32.56%), and IIIB (29 pts, 67.44%). Malignant pleural effusion or superior vena cava syndrome was criteria of exclusion. Induction treatment consisted of three cycles of GP (G 1250 mg/m(2) i.v. on days 1 and 8, and P 100 mg/m(2) on day 8 every 3 weeks). Responding and stable pts underwent surgery (S) and/or radiotherapy (RT). RESULTS: Following a minimum of two cycles, 39 pts were evaluable for response and 42 for toxicity. Two pts had complete responses (CR; 5.2%), 24 had partial response (PR; 61.5%), eight had stable disease (SD; 20.5%), and five had progressive disease (PRO; 12.8%). WHO grades 3 and 4 anaemia, neutropenia and thrombocytopenia were observed in two, four and two pts, respectively; non-haematological toxicity was moderate. After induction, stable and responding pts received either RT (18 pts) or S+RT (13 pts). Among the 16 resected pts, a radical complete resection was possible in 13 cases (81.3%), whereas tumour down-staging was observed in nine pts (56.2%). CONCLUSION: GP, as a 3-week neoadjuvant schedule, appears a safe and active regimen.
Aged↗
The acquisition of control crosslinguistically: structural and lexical factors in learning to licence PRO.
Rules for interpreting empty category (EC) subjects of complement clauses vary crosslinguistically across structural and lexical dimensions. In adult Greek, a distinction is made between the verbs meaning WANT and TRY, the former but not the latter permitting the EC subject of its subjunctive complement to refer outside the sentence. The EC is pro for WANT and PRO for TRY. In adult Spanish, both the verbs meaning WANT and TRY require the EC subject (pro) to refer outside when the complement is in the subjunctive, and require the EC subject (PRO) to refer to the main clause subject when the complement is in the infinitive. Twenty-three Greek-speaking four- to five-year-olds and 10 adults, 29 Spanish-speaking four- to five-year-olds, 18 six- to seven-year-olds and eight adults took part in act-out experiments. The results indicate an awareness of language-particular distinctions governing the interpretation of EC complement subjects. However, child speakers of both languages experience difficulty in giving sentence external reference, leading to error in the case of subjunctive sentences for Spanish-speaking children. We argue that the data overall is most compatible with children having access to the empty category PRO by age four, and that failure to give external reference of an EC when required can plausibly be treated as performance error. A picture verification task produced less clear results, but points to the need for data from younger children to establish whether there is an early stage in which lexical semantics dominates children's interpretation of ECs.
Adult↗
Immunoreactivity for thyroid transcription factor-1 in stage I non-small cell carcinomas of the lung.
Thyroid transcription factor-1 (TTF-1) is a nuclear protein regulating the transcriptional activity of lung-specific genes in the normal and neoplastic bronchioloalveolar cells. It has been implicated in the normal growth and development of the lung, and the disruption of the TTF-1 locus leads to neonatal death with pulmonary hypoplasia. We evaluated retrospectively the prevalence and clinical significance of TTF-1 immunoreactivity in 222 patients with stage I non-small cell lung carcinoma (NSCLC) with a follow-up time of at least 5 years, and we investigated its relationship with other markers of tumor growth, namely cell proliferation and angiogenesis. TTF-1 immunoreactivity was documented by using the commercially available monoclonal antibody 8G7G3/1 in 72% of 97 adenocarcinomas, 5% of 119 squamous cell carcinomas, and in the glandular component of two adenosquamous carcinomas. Four large cell carcinomas were completely unreactive. In adenocarcinomas, but not squamous cell carcinomas, TTF-1 immunoreactivity correlated significantly with microvessel density (p = 0.04) and inversely with the tumor proliferation fraction assessed by Ki-67 immunostaining (p = 0.03). Also, TTF-1-immunoreactive adenocarcinomas showed a trend for a size less than 3 cm (p = 0.08). TTF-1 expression was not related to specific growth patterns, tumor grade, or tumor cell typing. TTF-1 immunoreactivity did not significantly affect patient survival, although patients with more than 75% immunoreactive neoplastic cells showed a trend for longer overall and disease-free survival. Our findings suggest that TTF-1 could be involved in the development of small pulmonary adenocarcinomas, but it has not prognostic implications in patients with stage I NSCLC.
Adenocarcinoma↗
Gated blood pool tomography for the evaluation of global and regional left ventricular function in comparison to planar techniques and echocardiography.
BACKGROUND: Multigated radionuclide ventriculography (MUGA) is a simple and reliable tool for the assessment of global systolic and diastolic function and in several studies it is still considered a standard for the assessment of left ventricular ejection fraction. However the evaluation of regional wall motion by MUGA is critical due to two-dimensional imaging and its clinical use is progressively declining in favor of echocardiography. Tomographic MUGA (T-MUGA) is not widely adopted in clinical practice. The aim of this study was to compare T-MUGA to planar MUGA (P-MUGA) for the assessment of global ejection fraction and to transthoracic echocardiography for the evaluation of regional wall motion. METHODS: A 16-segment model was adopted for the comparison with echo regional wall motion. For each one of the 16 segments the normal range of T-MUGA ejection fraction was quantified and a normal data file was defined; the average value -2.5 SD was used as the lower threshold to identify abnormal segments. In addition, amplitude images from Fourier analysis were quantified and considered abnormal according to three different thresholds (25, 50 and 75% of the maximum). RESULTS: In a study group of 33 consecutive patients the ejection fraction values of T-MUGA highly correlated with those of P-MUGA (r = 0.93). The regional ejection fraction (according to the normal database) and the amplitude analysis (50% threshold) allowed for the correct identification of 203/226 and 167/226 asynergic segments by echocardiography, and of 269/302 and 244/302 normal segments, respectively. Therefore sensitivity, specificity and overall accuracy to detect regional wall motion abnormalities were 90, 89, 89% and 74, 81, 79% for regional ejection fraction and amplitude analysis, respectively. CONCLUSIONS: T-MUGA is a reliable tool for regional wall motion evaluation, well correlated with echocardiography, less subjective and able to provide quantitative data.
Echocardiography↗
Early hilar lung cancer--clinical aspects and long term survival. Identification of a subgroup of stage IA patients with more favorable prognosis.
Twenty-nine patients out of 2018 operated on for a non-small-cell lung cancer from 1987 to February 1998 met the criteria proposed by the Japan Lung Cancer Society (JLCS) for the definition of early hilar lung cancer (EHLC). Twenty-six patients were symptomatic and 20 had a radiologically visible lesion. All cancers were located and diagnosed by bronchoscopy and all patients were resected. At histology, all tumors were squamous in nature. The five-year cumulative survival rate was 96%--a second primary lung cancer (2nd Pr.) developed in 4 patients (13.8%). The definition of EHLC proposed by the JLCS allows the selection of a subgroup of stage I patients with a very good prognosis. Nevertheless, a close follow-up is mandatory because more than 10% of these patients develop a 2nd Pr.
Adult↗
Late esophagopleural fistula after left pneumonectomy: report on one case.
Esophagopleural fistula is an uncommon complication of pneumonectomy. Late nonmalignant esophagopleural fistula after left pneumonectomy for lung cancer is exceedingly uncommon. We report on one patient who developed such a fistula 33 months after the operation. Signs and symptoms were first attributed to infection of the thoracotomy incision and diagnosis was made only after detection of some food coming from the pleural space. Thoracostomy, enteral feeding by a percutaneously placed gastrostomy tube and myoplasty allowed both closure of the fistula and obliteration of the pleural space.
Esophageal Fistula↗
[Traumatic rupture of the aortic isthmus. Our experience with 23 cases].
BACKGROUND: Traumatic rupture of the aortic isthmus is a highly lethal lesion. Controversy currently exists regarding the best management of the lower body circulation system during repair of an acute aortic transsection. The aim of this study was to evaluate our results using different methods of distal aorta perfusion in order to prevent ischemia of the spinal cord. METHODS: Between October 1987 and October 1999, 23 patients (20 males, 3 females, mean age 28 years) with rupture of the thoracic aorta underwent surgical repair; 18 of these were acute ruptures and 5 post-traumatic pseudoaneurysms. RESULTS: All cases of rupture were associated with violent, sudden deceleration and in all but one subject it was due to a traffic accident. Twenty patients had severe associated lesions involving the cranium, abdomen, thorax or leg fractures. The operation was performed with a left postero-lateral thoracotomy in all but one case which underwent sternotomy (the patient with an associated lesion of the distal part of the arch). In 1 patient repair was accomplished using simple aortic cross-clamping, in another with total cardiopulmonary bypass, deep hypothermia and cardiac arrest and in 4 cases with partial cardiopulmonary bypass (1 left atrium-femoral artery and 3 femoro-femoral bypass). Seventeen patients were treated using the centrifugal pump (Bio-Medicus) for left atrium-femoral artery bypass. The perioperative mortality was 8.6%, including 2 patients operated in cardiogenic shock. In the 21 surviving patients the postoperative period was free from any cardiovascular complications, with no cases of paraplegia. There were no late deaths (mean follow-up 4 years) and all patients are in good clinical conditions. CONCLUSIONS: These results indicate that the outcome mainly depends on preoperative clinical conditions, associated lesions and the timing of the operation. We conclude that the Bio-Medicus centrifugal pump is a simple and safe means of perfusing the lower body, kidney, and spinal cord without heparinization in a patient with multiple injuries.
Adolescent↗
[Left atrial myxoma. Clinical and surgical features in 26 surgically treated cases].
BACKGROUND: Left atrial myxomas are the most common benign intracardiac tumors. The aim of this study was to compare our experience with the data reported in the literature. METHODS: Between May 1985 and August 1999, 26 patients (8 males, 18 females) with left atrial myxomas underwent surgical resection of these tumors at the Department of Cardiac Surgery, Ospedali Riuniti of Bergamo (Italy). Symptoms included congestive heart failure, dyspnea, arrhythmias, chest pain and syncope. Diagnosis was established preoperatively in all patients by echocardiography and angiocardiography was performed in 8 cases. All tumors were excised with a wide margin of uninvolved atrial septum. Two patients underwent concomitant coronary artery bypass. RESULTS: There was 1 early death due to irreversible ventricular fibrillation. Follow-up was completed for the 25 late survivals. Three patients died, years after operation, due to extracardiac causes. One patients had recurrence of the tumor, which was successfully removed 4 years after initial operation. All other patients are asymptomatic and free from disease. CONCLUSIONS: Operation for left atrial myxoma can be undertaken solely on the basis of echocardiographic findings, but coronary angiography should be performed in older patients who are at risk for coronary artery disease. Surgical excision of left atrial myxomas must be performed as soon as possible after diagnosis is established because of the high risk of valvular obstruction or systemic embolization. Biatrial approach allows for the inspection of the four cardiac chambers, limits manipulation of the mass, and facilitates the complete excision of the tumor. Thus, surgical intervention can be curative for patients with left atrial myxomas and most of these can expect an excellent outcome. Since late recurrence, although rare, has been reported, especially in familial myxomas, long-term clinical and echocardiographic follow-up is recommended.
Adult↗