Gennaro Favia

Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma.

BACKGROUND Recurrence of adrenal cortical carcinoma (ACC) after radical surgery is a common finding. Although successful reoperations have been reported with encouraging results, most published experiences are anecdotal and based on few cases. We report the results of surgical treatment for recurrent ACC in a multiinstitutional series. METHODS One hundred eighty-eight cases of ACC were collected in a national registry. A complete follow-up was obtained in 179 cases. At initial diagnosis 92 patients had local disease (stage I or II). One hundred seventy patients underwent surgical treatment, considered radical in 140; in this group, recurrent disease was observed in 52 cases (37%) after a mean disease-free interval of 21.7 months. RESULTS Adjuvant chemotherapy was ineffective in ameliorating the prognosis. The mean survival in 20 patients who underwent reoperation was significantly higher (15.85 +/- 14.9 months) than in nonreoperated cases (3.2 +/- 2.9 months). Five-year actuarial survival in reoperated patients is significantly better than in nonreoperated patients (49.7% versus 8.3%, respectively). CONCLUSIONS Although the prognosis of this tumor is still poor, surgery is the only effective therapy; reoperation allows survival comparable to that observed in patients without recurrent disease. An aggressive strategy for recurrent ACC is advisable until prospective studies demonstrate a real effectiveness for chemotherapy.

Parathyroid Carcinoma: Sixteen New Cases and Suggestions for Correct Management

AbstractWe undertook a retrospective study in 16 patients with parathyroid carcinoma, with the aim of conveying experience from management of this rare cause of hyperparathyroidism (HPT). From 1980 to 1996 we operated on 309 patients with HPT, 290 of whom had primary HPT, and parathyroid carcinoma was diagnosed in 16 (5.2%) cases. In none was the malignancy diagnosed preoperatively. The average serum calcium and parathyroid hormone levels were significantly higher ( p < 0.05) than in patients with parathyroid adenoma, and the mean tumor size was 2.9 cm (median 2.5 cm, range 1.5–4.5 cm). Twenty-eight operations were performed with resulting normalization of serum calcium levels for more than 6 months in 11 patients. Six patients presented prolonged postoperative hypocalcemia (2–10 months), and five patients had persistent HPT. Ten patients experienced recurrent disease; the median disease-free period was 24 months (range 4–72 months). None of the patients was treated with chemotherapy, one patient underwent radiation therapy (50 Gy in 25 sessions) but required reoperation for local recurrence 4 months later. Three patients are still alive (two with recurrence). Average survival was 40 months (median 31 months, range 11–131 months).

Adrenalectomy may improve cardiovascular and metabolic impairment and ameliorate quality of life in patients with adrenal incidentalomas and subclinical Cushing's syndrome

BACKGROUND Adrenalectomy represents the definitive treatment in clinically evident Cushings syndrome; however, the most appropriate treatment for patients with subclinical Cushings syndrome (SCS) with an adrenal incidentaloma remains controversial. This study was aimed to assess whether adrenalectomy may improve cardiovascular and metabolic impairment and quality of life compared with conservative management. METHODS Twenty patients with adrenal incidentaloma underwent laparoscopic adrenalectomy for SCS, whereas 15 were managed conservatively. Hormonal laboratory parameters of corticosteroid secretion, arterial blood pressure (BP), glycometabolic profile, and quality of life (by the SF-36 questionnaire) were compared at baseline and the end of follow-up. RESULTS The 2 groups were equivalent concerning all the examined parameters at baseline. In the operative group, laboratory corticosteroid parameters normalized in all patients but not in the conservative-management group (P < .001). In operated patients, a decrease in BP occurred in 53% of patients, glycometabolic control improved in 50%, and body mass index decreased; in contrast, no improvement or some worsening occurred in the conservative-management group (P < .01). SF-36 evaluation improved in the operative group (P < .05). CONCLUSION Adrenalectomy can be more beneficial than conservative management in SCS and may achieve remission of laboratory hormonal abnormalities and improve BP, glycemic control, body mass index, and quality of life.

Pheochromocytoma, a rare cause of hypertension: long-term follow-up of 55 surgically treated patients.

Abstract. Pheochromocytoma is a rare tumor that is found in only 0.1% of patients with diastolic hypertension. We analyze the results of our experience in management of pheochromocytomas and long-term results of its surgical treatment. From 1977 to 1996 we operated on 55 patients with a pheochromocytoma: 29 males and 27 females with an average age of 41 years (range 10–63 years). In 44 (80.0%) patients episodic hypertension or paroxysms were observed; 7 (12.7%) patients had permanent hypertension, and 4 (7.3%) had a normal arterial blood pressure (ABP). 131/123 I-MIBG scintigraphy (33 patients) and magnetic resonance imaging (12 patients) showed 100% sensitivity and computed tomography (47 patients) 97.9% sensitivity. At operation five (9.1%) tumors were bilateral, five extraadrenal, and five multiple. In four (7.3%) patients an association with familial syndromes (three MEN-IIb, one von Recklinghausen disease) was observed. Five (9.1%) malignant tumors were discovered, and two patients are still alive 30 and 104 months after surgery, one of them with relapse. In 43 (78.2%) patients we preferred a flank incision, and no intraoperative deaths occurred. Mean follow-up was 88 months (6–232 months) with recurrence in only 1 (2.0%) of 50 patients without malignancy. In patients with benign pheochromocytomas the recurrence rate did not seem to be elevated in our series. Nevertheless, because the lifelong follow-up requires only annual 24-hour urinary catecholamine measurement (less than

CT-scan, MRI and image-guided FNA cytology of incidental adrenal masses.

40 per patient per year) and periodic ABP measurements, it is suggested for all patients who undergo surgery for pheochromocytoma.

Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism

AIM The aim of this study was to compare the usefulness of computed tomography (CT)-scan, magnetic resonance imaging (MRI), and fine-needle aspiration (FNA) cytology in patients with incidentally discovered adrenal masses. PATIENTS AND METHODS Thirty-four consecutive patients (six men and 28 women, median age of 47 years, range 26-80) with non-functioning adrenal masses of 2 cm or more (median 3.5 cm, range 2-9) were studied. All patients underwent CT-scan, MRI, and image-guided FNA cytology using spinal-type narrow-gauge needles prior to further procedures. Nineteen patients underwent adrenalectomy. RESULTS Final pathology showed 13 benign adrenal lesions, four adrenocortical carcinomas, and two unsuspected adrenal metastases. Fifteen patients who did not have surgery were considered definitively as having benign adrenal lesions since the mass was unchanged on CT-scans performed during follow-up. The sensitivity, specificity, and positive predictive value were 66.7, 85.7, and 50.0%, for CT-scan, 83.3, 92.9, and 71.4% for MRI, and 83.3, 100, and 100% (p<0.05) for FNA cytology, respectively. CONCLUSIONS Image-guided FNA cytology is a safe and sensitive procedure that may reveal unsuspected adrenal malignancies, and should be performed in all patients with incidentally discovered adrenal masses of more than 2 cm in size.

Adrenocortical Carcinoma: Is Prognosis Different in Nonfunctioning Tumors? Results of Surgical Treatment in 31 Patients

CDC73 (HRPT2) germline mutations are responsible for more than half of cases of hyperparathyroidism-jaw tumor syndrome (HPT-JT) and for a subset of familial isolated HPT (FIHP). We performed a clinical, genetic, and histopathologic study in three unrelated Italian kindreds with HPT-JT and FIHP. We identified three germline inactivating mutations of the CDC73 gene in the probands and affected patients of the three kindreds, but also in some asymptomatic subjects. HPT-JT and FIHP patients had similar laboratory, clinical, and demographic features and shared primary HPT and other neoplasms, the most common of which was uterine polyposis. Genetic analysis of tumor samples demonstrated a second somatic CDC73 mutation only in a parathyroid adenoma and no cases with the loss of the wild-type allele or methylation of the CDC73 promoter, even though immunohistochemical analysis demonstrated the loss of nuclear parafibromin expression in all tumors, including a uterine polyp. In conclusion, our results indicate that FIHP and HPT-JT associated with CDC73 mutations do not have distinct clinical, genetic, and histopathologic features, but may represent variants of the same genetic disease. This study also confirms that uterine involvement represents a clinical manifestation of the syndrome.

The usefulness of preoperative ultrasonographic identification of nonrecurrent inferior laryngeal nerve in neck surgery

Abstract. From 1980 to 1998 a series of 265 patients with adrenal tumors underwent surgery, with an adrenocortical carcinoma found in 31 (11.7%). Altogether, 17 (54.8%) patients (group A) had Cushing syndrome (n= 15) or virilization (n= 2), and 14 (45.2%) patients (group B) had nonfunctioning adrenal tumors. Tumor staging was as follows: (groups A/B): stage I, n= 5 (3/2), stage II, n= 14 (9/5), stage III, n= 5 (1/4), stage IV, n= 7 (4/3) patients. There were 12 (38.7%) men and 19 (61.3%) women (median age 51 years, range 25–73 years), and the size of the mass ranged from 3.5 to 20.0 cm (median 8.0 cm), with no differences (p= NS) between groups A and B. Two (6.4%) patients (stage IV) did not undergo surgery and received only palliative drug treatment; 6 (19.4%) were treated with debulking surgery; 15 (48.4%) had unilateral adrenalectomy; and 8 (25.8%) had an extended adrenalectomy. Eighteen (58.0%) patients underwent adjuvant postoperative mitotane treatment, and in 8 (25.8%) patients one or more reoperations for recurrence were required. Nine (29.0%) patients are still alive with a mean follow-up of 34 months; 22 (71.0%) died 2 to 60 months (median 20 months) after surgery. The overall 2- and 5-year survival rates were 62.1% and 10.3%, with no difference (p= NS) between groups A and B. The survival rates at the 1- and 3-year follow-ups were 90.3% and 32.3% (stages I and II) and 71.0% and 6.5% (stages III and IV). In conclusion, adrenocortical carcinoma remains a highly malignant tumor, and stage III–IV patients still have a poor prognosis; but nonfunctioning tumors do not seem to be more aggressive.

High risk of malignancy in patients with incidentally discovered adrenal masses: accuracy of adrenal imaging and image-guided fine-needle aspiration cytology.

Backgrounds and aimsNonrecurrent inferior laryngeal nerve (ILN) represents a risk factor for injury during neck surgery. It is associated to arterial abnormalities (absence of the brachiocephalic trunk and arteria lusoria) that can be identified by ultrasonography. The aim of the study was to verify the usefulness of preoperative ultrasonography in the research of nonrecurrent ILN by the means of identification of arterial abnormalities and the impact on ILN morbidity.Patients and methodsThe study included 750 patients who underwent neck surgery with right-side ILN dissection. A preoperative ultrasonography aimed to identify arterial abnormalities associated to nonrecurrent ILN was performed in 400 patients (Group A) while no preoperative attempts were performed in the remaining patients (Group B). Patients’ characteristics, time for intraoperative identification of the ILN, and morbidity were compared.ResultsFive and four nonrecurrent ILN were identified in groups A and B, respectively (p = NS). Preoperative ultrasonography correctly predicted nonrecurrent ILN in all cases (accuracy 100%). Nonrecurrent ILN palsy never occurred in group A, while three cases occurred in group B (p < 0.05). The mean time for intraoperative identification of both nonrecurrent and normally recurrent ILN was significantly shorter in group A (p < 0.01).ConclusionsPreoperative ultrasonography can correctly identify nonrecurrent ILN, allowing earlier nerve identification and prevention of injuries.

Results of iterative surgery for persistent and recurrent parathyroid carcinoma

AIMS AND BACKGROUND The incidental finding of nonfunctioning adrenal masses (incidentalomas) is common, but no reliable criteria in differentiating between benign and malignant adrenal masses have been defined. The aim of this preliminary study was to assess the usefulness of adrenal imaging and image-guided fine-needle aspiration cytology in patients with nonfunctioning adrenal incidentalomas with the aim of excluding or confirming malignancy before surgery. METHODS Forty-two consecutive patients (18 men and 24 women; median age, 54 years; range, 25-75 years) with incidentally discovered adrenal masses of 3 cm or more in the greatest diameter were prospectively enrolled in the study. All patients underwent helical computerized tomography scan and image-guided fine-needle aspiration cytology, 33 (78.6%) underwent magnetic resonance imaging, and 26 (61.9%) underwent norcholesterol scintigraphy before adrenalectomy. RESULTS The revised final pathology showed 30 (71.4%) benign (26 adrenocortical adenomas, of which 3 were atypical, 2 ganglioneuromas, and 2 nonfunctioning benign pheochromocytomas) and 12 (28.6%, 95% CI = 15-42) adrenal malignancies (8 adrenocortical carcinomas and 4 unsuspected adrenal metastases). The definitive diagnosis of adrenocortical carcinoma was made according to Weiss criteria and confirmed on the basis of local invasion at surgery or metastases. The sensitivity, specificity and accuracy were 75%, 67% and 83% for computerized tomography scan, 92%, 95% and 94% for magnetic resonance imaging, 89%, 94% and 92% for norcholesterol scintigraphy, and 92%, 100% and 98% for fine-needle aspiration cytology. The sensitivity and accuracy of image-guided fine-needle aspiration cytology and magnetic resonance imaging together reached 100%. Immediate periprocedural complications of fine-needle aspiration cytology occurred in 2 (4.7%) patients: self-limited pneumothorax (n = 1), and severe pain (n = 1) requiring analgesic therapy. No postprocedural or late complications were observed. CONCLUSIONS With the aim of selecting for surgery patients with a non-functioning adrenal incidentaloma of 3 cm or more in diameter, the combination of magnetic resonance imaging and fine-needle aspiration cytology should be considered the strategy of choice.