Pheochromocytoma: 25 years of experience. Report of 199 cases

The methods for diagnosing pheochromocytoma have progressed in 25 years, so changing the clinical, biological and tumoral presentations. The authors compare the features of 199 patients with pheochromocytoma operated between 1975 and 2001 by quartiles. The frequency and known duration of hypertension, plasma adrenaline, the tumour size and proportion of cases which were malignant from the outset, have decreased over the observation period (p < 0.01). The average age and proportion of familial cases or associated with diabetes or those of asymptomatic patients (with incidentaloma), has not changed significantly. The pheochromocytoma were adrenal (104 right, 60 left, 12 bilateral) or ectopic (23) and 13 were malignant from the outset. Over a median 5 year follow-up, 35 pheochromocytomas recurred either in the benign or malignant forms. Recurrences of tumours of the right adrenal were more common than those of the left adrenal gland (p = 0.03). In conclusion, pheochromocytomas are diagnosed earlier, at a stage when the tumours are smaller and less secreting. The higher incidence and recurrence rate of right adrenal pheochromocytoma remain unexplained.     

Value of the study of electrocardiographic P wave in pheochromocytoma]

The diagnostic value of electrocardiographic P wave analysis in the frontal plane was assessed with respect to previously reported abnormalities: right atrial hypertrophy-dilatation; an enlarged, crenalleted summit without criteria of right atrial hypertrophy. Two observers studied the ECG recordings of 20 hypertensive patients with pheochromocytomas: 10 men and 10 women, aged 45.5 +/- 16 years, and in 30 patients with essential hypertension, 15 men and 15 women, aged 48.9 +/- 9 years (NS). The duration of hypertension was 2.6 +/- 2 years versus 4.7 +/- 4 years (p = 0.02). Right atrial hypertrophy-dilatation was observed in 5 patients in the pheochromocytoma group and in none of the essential hypertensive patients: an isolated abnormality of the summit of the P wave was observed in 5 other cases of pheochromocytoma and by 1 observer in 1 of the essential hypertension. These abnormalities disappeared after ablation of the tumour. These changes were not recorded in 3 patients who had predominant noradrenaline hypersecretion; nevertheless, comparison of the urinary adrenaline, noradrenaline, normeta- and metanephrine levels were inconclusive. No relationship was established between these concentrations, global urinary catecholamines and meta block, the duration of hypertension, the frequency and level of hypertensive crises, or the presence of "ischaemic" ST-T wave changes. P wave changes are thought to be related to high plasma catecholamine levels irrespective of the clinical impact; the sensitivity of these changes is modest (10/20) but the specificity is better within a group of hypertensive patients. An experienced observer can orient the diagnostic investigations to the search for a pheochromocytoma or to a secondary recurrence of the tumour from the surface ECG. The role of marker of a very high noradrenaline or adrenaline secretion cannot be confirmed from a series limited in separated plasma concentration measurements.     

Pulmonary haemodynamics at rest and during exercise in patients with significant pulmonary vein stenosis after radiofrequency catheter ablation for drug resistant atrial fibrillation.

AIMS: Iatrogenic pulmonary vein (PV) stenosis after radiofrequency catheter ablation for atrial fibrillation (AF) is a new pathology in cardiology. The effects of PV stenosis on the pulmonary circulation are not yet known. We provide long-term follow-up data in patients with significant PV stenosis including magnetic resonance imaging (MRI) and Swan Ganz (SG) right heart catheterization. METHODS AND RESULTS: One hundred and seventeen patients had MRI 12-24 months after the AF ablation procedure. Eleven patients (58+/-7 years, nine males) with significant stenosis (n=9) or occlusion of the proximal PV (n=5) at this follow-up were re-examined using MRI and SG right heart catheterization at rest and during exercise (follow-up time since PV ablation 50+/-15 months). None of these underwent previous PV angioplasty. When compared with prior MRI studies, no significant changes were noted. At rest, no patient had pulmonary hypertension. At 100 W, seven patients had elevated pulmonary artery pressures, three of them probably caused, in part, by left ventricular dysfunction. CONCLUSION: Significant stenosis/occlusions of one or two PV do not create pulmonary hypertension at rest during long-term follow-up. However, seven of the 11 patients develop pulmonary hypertension during exercise. All three patients with stenosis/occlusions of two PV were affected.     

儿童房性心动过速的电生理标测和射频导管消融

目的报道儿童房性心动过速（房速）的电生理标测及射频导管消融的疗效。方法43例患儿（男性23例,女性20例）,年龄2～14（7．1±3．1）岁,其中33例为无休止房速,17例伴有明显的左心室扩大及慢性心力衰竭。所有患儿均进行电生理标测,在最早激动点进行导管射频消融。结果39例自发或诱发房速,局灶起源36例（右心房26例,左心房10例）,先天性心脏病后大折返房速3例。35例（89．7％）患儿消融术即刻成功,消融术中及术后无严重并发症发生。平均随访（25．2＋-13．5）个月,34例（87．2％）患儿不服药亦无房速发作,其余均获得明显改善。14例左心室重度扩大及射血分数减低患儿心脏大小及功能恢复正常。结论儿童房速可经导管消融消除或获得明显改善。     

Malignant pheochromocytoma lacking clinical features of catecholamine excess until the late stage

A malignant pheochromocytoma is described in a 71-year-old man. Osseous metastases became manifest 12 years after successful removal of the primary tumor which originated in paraganglionic tissue near the right adrenal gland. Although the patient had no symptoms of catecholamine excess initially, hypertension, tachycardia and excessive sweating appeared several months before his death, concomitantly with a sharp increase in noradrenaline secretion due to an accelerated growth of metastatic tumors. Since there is no histologic criterion of malignancy in this neoplasm, it would be prudent to consider every case of pheochromocytoma as potentially malignant and to follow-up carefully for a long time after removal of the primary tumor.     

Long Term Follow-Up After Surgical Removal of Pheochromocytoma - Observations in 61 Patients

89 patients were operated on for pheochromocytoma. 61 patients (37 women and 24 men) were available for extended follow-up. The final survey, performed 79.1±66.9 months postoperatively, provided data on survival, blood pressure tumor recurrence, malignant metastatic lesions, cardiovascular complications and coexisting diseases. There were 4 deaths during the follow-up period, including 2 instances of malignant pheochromocytoma. Permanent normalization of blood pressure was achieved in 38 patients (62.3%). This hypotensive effect was noted in 79.2% of patients with preoperative paroxysmal hypertension and in 40.8% of those with sustained hypertension. Permanent or re-developing postoperative hypertension was noted in 23 (37.7%) patients. This includes 4 cases of malignant pheochromocytoma, 4 cases of recurrent benign pheochromocytoma and 15 cases of essential hypertension. Cardiovascular complications during follow-up were rare and concerned the patients with essential hypertension diagnosed postoperatively.     

Pheochromocytoma presenting as diabetic ketoacidosis

Pheochromocytoma is a rare form of secondary hypertension and may be potentially lethal if left untreated. The classical symptoms are paroxysmal hypertension, headaches, palpitations and sweating. They are caused by sudden catecholamine release. Hyperglycemia is reported in some patients with pheochromocytoma but diabetic ketoacidosis is an extremely rare complication of pheochromocytoma with only four cases reported. We report a case of a young woman with pheochromocytoma manifested as diabetic ketoacidosis.     

Prospective assessment after pediatric cardiac ablation: recurrence at 1 year after initially successful ablation of supraventricular tachycardia

OBJECTIVES: A multicenter prospective study was performed to assess the results and risks associated with radiofrequency ablation in children. This report focuses on recurrences following initially successful ablation. METHODS: Patients recruited for the study were aged 0 to 16 years and had supraventricular tachycardia due to accessory pathways or atrioventricular nodal reentrant tachycardia (AVNRT), excluding patients with more than trivial congenital heart disease. A total of 481 patients were recruited into the prospective cohort and were followed at 2, 6, and 12 months following ablation. RESULTS: There were 517 successfully ablated substrates out of 540 attempted (95.7%). Loss to follow-up for individual substrates was 3.3%, 10.6%, and 21.2% at 2, 6, and 12 months, respectively. Recurrence was observed in 7.0%, 9.2%, and 10.7% of these substrates at 2, 6, and 12 months, respectively (adjusted for loss to follow-up as an independent source of data censoring). Recurrence rate varied by substrate location (24.6% for right septal, 15.8% for right free wall, 9.3% for left free wall, and 4.8% for left septal), as well as for AVNRT versus all others (4.8% vs 12.9%) at 12 months. The recurrence rate was higher for substrates ablated using power control but was not a function of whether isoproterenol was used for postablation testing. CONCLUSIONS: Recurrence after initially successful ablation occurs commonly in children. It is least common after AVNRT ablation and most common following ablation of right-sided pathways. These results serve as a benchmark for the time course of recurrence following initially successful ablation of supraventricular tachycardia in children.     

Renovaascular hypertension and Von Recklinghausen neurofibromatosis

This clinical case illustrates the diagnosis of a secondary cause of hypertension in a patient with Von Recklinghausen's disease. The hypertension resulted from a complex malformation of the right renal artery and dysplasic stenosis of the left inferior polar artery treated successfully by simple angioplasty. This case illustrates the high proportion of vascular (renal artery dysplasia, coarctation of the aorta) and endocrine (pheochromocytoma) causes of hypertension in patients with neurofibromatosis.     

Radiofrequency ablation of idiopathic left ventricular tachycardia in children

INTRODUCTION: Nowadays radiofrequency catheter ablation is an alternative to medical treatment in adult patients with idiopathic left ventricular tachycardia. AIM: To asses indications, results and long term follow-up of using this technique in children. : Radiofrequency catheter ablation was performed in five consecutive patients without structural heart disease, mean age 8.6+/-7.1 years (range, 1.3 to 17) and suffering from resistance to medical treatment left ventricular tachycardia (2.4+/-0.9 antiarrhythmic drugs per patient). Palpitations and syncope were the clinical manifestations in four patients while congestive heart failure in the other one. Six types of tachycardia were identified in the five-patient group. All of them responded to intravenous verapamil. There were 3 incessant tachycardias and the other three were paroxysmal ones. The ablation site was selected using activation mapping during tachycardia and pace-mapping. The Tachycardia cycle length was 275+/-123 ms and showed right bundle branch block with superior axis (left in 4 and right in 2 cases). The ablation target was located in the mid-septal region of the left ventricle in 3 cases, in the apical and inferior septal region in 2 other cases and in the anterior free wall in the other one. Local activation times preceded in 33+/-13 ms at QRS beginning and with a 12/12 agreement pattern in 5 cases and 9/12 in 1, in whom ablation was unsuccessful. At follow-up, the 4 patients with effective ablation have been tachycardia-free for 35.8+/-17 months. CONCLUSIONS: Radiofrequency catheter ablation is a useful method of treatment in children with idiopathic left ventricular tachycardia, including those under two years old.     

Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma

Pheochromocytoma is a rare but important tumor of chromaffin cells that is frequently considered in the evaluation of hypertension, arrhythmias, or panic disorder and in the follow-up of patients with particular genetic diseases. This report provides an update about the genetics, neurochemical diagnosis, localization by imaging, and surgical management of pheochromocytoma. Specific mutations of the RET proto-oncogene cause familial predisposition to pheochromocytoma in multiple endocrine neoplasia type II, and mutations in the von Hippel-Lindau tumor suppressor gene cause familial disposition to pheochromocytoma in von Hippel-Lindau disease. Recent findings demonstrating extraordinarily high sensitivity of plasma levels of metanephrines for detecting pheochromocytoma have led to an algorithm for clinical diagnostic steps. Nuclear imaging approaches, such as(123) I-metaiodobenzylguanidine scintigraphy and 6-[(18) F]fluorodopamine positron emission tomography, enhance both diagnosis and localization of the tumor, as described in an algorithm for patients with positive biochemical test results. Since pheochromocytoma is often benign, surgical resection by laparoscopic adrenalectomy can be curative. Areas requiring further work include determining appropriate follow-up of patients with familial pheochromocytoma, elucidating the bases for phenotypic differences, improving both specificity and sensitivity of biochemical tests, optimizing cost-effectiveness of diagnostic imaging, and testing the risk for tumor recurrence after partial adrenalectomy.     

Primary tumors of the heart. Diagnostic, anatomic and therapeutic aspects

Primary cardiac tumours are rare. They are usually benign, the most common ones being left atrial myxomas. The authors report their experience of 16 cardiac tumours operated between 1978 and 1985. The patients were 12 adults and 4 children. The tumours were benign in 14 cases and malignant in 2 cases. Complete (14 cases) or incomplete ablation of the tumour was carried out under cardiopulmonary bypass with an early mortality of 6.25 per cent (1 case) and late mortality of 12.5 per cent (the two malignant tumours). The tumours were identified as myxomas in 11 cases, rhabdomyomas in 2 cases, fibroma in 1 case and malignant sarcomas in 2 cases. The average follow-up period of the 13 survivors is 30 months (range 4 months to 5 years) with excellent clinical and anatomical results. Clinical and paraclinical diagnosis of these tumours does not pose any major problems nowadays because of the reliability of the methods of investigation. However, the nature of the tumour is not always predictable and the operative findings are fundamental, not so much for the treatment which is relatively stereotyped but for the prognosis. Age is not a significant prognostic factor as excellent results may be obtained in the very young and the very old despite a sometimes precarious preoperative clinical condition. The benign or malignant nature of the tumour is the only real factor which affects the prognosis.     

Catecholamine-producing tumors]

We report 93 patients with catecholamine producing tumors that were analyzed at the Hormone Laboratory of the Institute of Cardiology. They are 75 pheochromocytoma patients and 18 children with neuroblastoma. Fluorimetric methods were used to measure urinary and plasma catecholamines on neuroblastoma and pheochromocytoma patients. Dopamine high excretion (mean value 2889 micrograms/24 hs), was constantly observed in the neuroblastoma children as were adrenaline and noradrenaline in the benign and malignant pheochromocytoma patients. The mean values for the malignant tumours were 53 for adrenaline and 1436 micrograms/24 hs for noradrenaline. Structural and biochemical differences of the catecholamine producing tumours are reflected on the clinical manifestations which are observed in the patients bearing such neoplasms.     

Metastases but not cardiovascular mortality reduces life expectancy following surgical resection of apparently benign pheochromocytoma

The treatment of choice for non-metastatic pheochromocytoma is surgical resection. Its goals are to abolish catecholamine hypersecretion, normalize blood pressure, and prevent further tumor growth or progression to metastatic disease. Data on long-term mortality and morbidity after pheochromocytoma surgery are limited. We here report a retrospective study on the long-term outcome after surgery for apparently benign pheochromocytoma at the Radboud University Nijmegen Medical Centre. Data on clinical presentation, treatment, post-surgical blood pressure and recurrence, metastasis and death were collected of 69 consecutive patients (January 1966-December 2000; follow-up: until death or January 2006). Survival was compared with survival of a matched reference population. Two patients died of surgical complications. All ten patients with metastatic disease (including three diagnosed at first surgery) died. At follow-up, 40 patients were alive and recurrence free and three patients were lost to follow up. Two patients experienced a benign recurrence. Mean+/-s.d. follow-up was 10.2+/-7.5 (median 9, range 1-38) years. Kaplan-Meier estimates for 5- and 10-year survival since surgery were 85.8% (95% CI: 77.2-94.4%) and 74.2% (95% CI: 62.0-86.4%) for patients versus 95.5 and 89.4% in the reference population (P<0.05). Sixty-four percent of all patients with hypertension prior to surgery showed a significant decrease in blood pressure, but remained hypertensive after surgery. In conclusion, compared with the general population patients have a reduced life expectancy following pheochromocytoma surgery, due to their risk of developing metastatic disease. Only one-third becomes normotensive without antihypertensive medication. Therefore, lifelong follow-up is warranted.     

老年人阵发性心房颤动的导管消融治疗

为评价老年人阵发性心房颤动 (PAF)行导管消融治疗的可行性和疗效 ,选择药物无法控制或不能耐受的PAF患者 5 6例 ,男 4 1例、女 15例 ,年龄 6 5 .7± 10 .1(6 0～ 74 )岁 ,无器质性心脏病 4 6例 ,合并高血压 7例 ,高血压及糖尿病 1例 ,高血压及冠心病 1例 ,冠心病 1例。均经食管超声心动图检查排除左房血栓。据消融技术的演进及患者入选的时间顺序 ,采用不同的消融方法 (点消融术、超声球囊肺静脉电隔离术、肺静脉节段性消融电隔离术 )。 3～ 6个月后评价疗效。结果 :5 6例患者 ,5 5例完成消融术 :点消融术 4例 ,成功 1例 ,无效 2例 ,心包积血 1例 ;超声球囊肺静脉电隔离术 14例 ,成功 7例 ,有效 5例 ,无效 2例 ,无肺静脉狭窄 ;肺静脉节段性消融电隔离术 37例 ,成功11例 ,有效 2 3例 ,无效 3例 ,左下肺静脉开口 >30 %狭窄 1例。结论 :导管消融治疗老年人PAF是安全有效的 ,肺静脉电隔离术使疗效明显提高 ,但仍未令人满意。     

Radiofrequency catheter ablation of right ventricular outflow tachycardia in children and adolescents

Objectives. The current study reviews the safety and efficacy of radiofrequency catheter ablation for the treatment of right ventricular outflow tachycardia in children and adolescents and describes a modified method for mapping the tachycardia focus.Background. Although radiofrequency catheter ablation has proved highly effective for the treatment of supraventricular tachycardia during childhood and adolescence, its application in children with idiopathic right ventricular outflow tachycardia has been limited.Methods. Six children (mean [±SD] age 10.6 ± 2.4 years, range 6 to 16) with right ventricular outflow tachycardia underwent seven radiofrequency catheter ablation procedures. The mean tachycardia cycle length was 323 ± 24 ms (range 300 to 360). Two multipolar catheters were positioned in the right ventricular outflow tract to map the tachycardia focus.Results. Radiofrequency catheter ablation was successful in five (83%) of the six children (95% confidence interval 36% to 99%). At successful ablation sites, local endocardial activation times preceded the surface QRS onset by 46 ± 5 ms (range 37 to 57), and there was concordance of the 12-lead pace map and the electrocardiogram (ECG) in 11 (one patient) to 12 ECG leads (four patients). One patient developed complete right bandle branch block during radiofrequency catheter ablation. There were no additional complications and no clinical recurrences over a mean follow-up period of 12.7 ± 3.8 months (range 9 to 22).Conclusions. These results suggest that radiofrequency catheter ablation is a safe effective treatment for right ventricular outflow tachycardia during childhood and adolescence. In addition, tachycardia mapping may be enhanced by use of a multipolar right ventricular outflow catheter technique.     

Predictors of atrial fibrillation termination and clinical success of catheter ablation of persistent atrial fibrillation

The termination of persistent atrial fibrillation (AF) during catheter ablation has been associated in some, but not all, studies with reduced arrhythmia during clinical follow-up. We sought to determine the rate of persistent AF termination achievable with a stepwise ablation strategy, the predictors of AF termination, and the clinical outcomes associated with termination and nontermination. A total of 143 consecutive patients (age 62 ± 9 years, AF duration 5.7 ± 5.2 years) with persistent and longstanding persistent AF resistant to antiarrhythmic medication who presented in AF for catheter ablation were studied. Ablation was done with a stepwise approach, including pulmonary vein isolation, followed by complex fractionated atrial electrogram ablation and ablation of resultant atrial tachycardias. Clinical follow-up was then performed after a 2-month blanking period to assess arrhythmia recurrence, defined as AF or atrial tachycardia lasting ≥ 30 seconds. AF termination by ablation was achieved in 95 (66%) of the 143 patients. Multivariate predictors of AF termination included longer baseline AF cycle length (p <0.001) and smaller left atrial size (p = 0.002). AF termination by ablation was associated with both a lower incidence of arrhythmia recurrence after a single procedure without antiarrhythmic drugs (p = 0.01) and overall clinical success (single or multiple procedures, with or without antiarrhythmic drugs; p = 0.005). On multivariate analysis, the predictors of overall clinical success included AF termination by ablation (p = 0.001), a shorter ablation duration (p = 0.002), younger age (p = 0.02), male gender (p = 0.03), and the presence of hypertension (p = 0.03). In conclusion, among patients with persistent AF, termination of AF by ablation can be achieved in most patients and is associated with reduced recurrence of arrhythmia.     

Pancreatic neuroendocrine tumours

Pancreatic neuroendocrine tumours are rare tumours ( approximately 1/100,00 population/year) of which 60% are non-functioning. Except for insulinoma all types are malignant in >50% of cases. In multiple endocrine neoplasia (MEN)1, pancreatic neuroendocrine tumours occur in 40-80% of patients and are mostly non-functioning tumours or gastrinomas. Insulinomas are benign in approximately 90%, solitary in 95% of sporadic cases whilst multiple in 90% of MEN1 patients. In contrast approximately 50% gastrinomas and the majority of non-functioning pancreatic neuroendocrine tumours are malignant. Pancreatic neuroendocrine tumours occur in 10-15% of patients with Von Hippel-Lindau (VHL) and are frequently multiple (>30%). Surgical excision is a key aspect of treatment for all cases of sporadic gastrinoma and if >2.5 cm in MEN1. Insulinomas are enucleated if solitary and may require pancreatectomy if multiple. Non-functioning tumours should also be resected if sporadic and if >2 cm in MEN1 or if >2-3 cm in VHL. Tumours <1cm require yearly follow-up by CT or MRI from an early age in VHL. The local treatment for liver metastases is now well established and options include liver resection, chemoembolisation and radiofrequency ablation. Systemic therapies have also been better defined and include radionuclide therapy against somatostatin receptors or MIBG and chemotherapy especially for poorly differentiated tumours. A number of novel agents are currently in clinical development.     

Cardiac pheochromocytoma. Failure of classic non-invasive diagnostic methods

We report an exceptional case of cardiac pheochromocytoma which raised problems of localization. A 30-year old man who for several years had been hypertensive was admitted for attacks of paroxysmal hypertension. Very high levels of urinary catecholamines suggested a diagnosis of pheochromocytoma, but no tumour was found at computerized tomography (CT) and metaiodobenzylguanidine (MIBG) scintigraphy. However, regional venous samplings detected two para-carotid phaeochromocytomas which were surgically removed. Thereafter, the symptoms persisted and investigations were resumed. As new regional venous samplings persisted and investigations were resumed. As new regional venous samplings showed high levels of catecholamines in the right atrium, a mediastinal and, chiefly, cardiac phaeochromocytomas was suspected. No tumour was visible at CT or ultrasonography and another MIBG scintigraphy proved negative. Coronary angiography showed a very large tumour behind the left atrium, well supplied by the circumflex artery and by a branch of the right coronary artery. The patient was operated upon and is now totally asymptomatic after a 9-month follow-up. This case emphasizes the value of invasive methods (i.e. regional venous sampling and coronary angiography) in the localization of this ectopic tumour. In most cases, however, phaeochromocytomas can be localized by MIBG scintigraphy.