Franco Lumachi

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).

Sensitivity and positive predictive value of CT, MRI and 123I-MIBG scintigraphy in localizing pheochromocytomas: a prospective study.

AimTo establish a standardized non-invasive imaging protocol for patients with pheochromocytoma undergoing surgery. MethodsA series of 32 consecutive patients (16 men, 16 women; median age 43 years, range 15–71 years) with biochemically confirmed pheochromocytoma underwent computed tomography (CT) scanning, magnetic resonance imaging (MRI) and meta-[123I]iodobenzylguanidine (MIBG) whole-body scintigraphy prior to adrenalectomy or excision of extra-adrenal tumour (paraganglioma). ResultsAt final pathology no malignant pheochromocytomas were found. The tumour was right-sided in 16 (50%) patients, left-sided in 13 (41%), extra-adrenal (sympathetic ganglia, upper abdomen) in two (6%) and bilateral in one (3%) patient. Overall, the median greatest diameter (size) of the tumour was 35 mm (range, 15–90 mm). The sensitivity of CT, MRI and MIBG scintigraphy was 90%, 93% and 91%, and the specificity was 93%, 93% and 100%, respectively. The three patients with false negative scintigraphy had an intra-adrenal tumour, ranging from 20 to 50 mm in size. The presence of necrosis within the mass might justify the lack of significant uptake of radiopharmaceutical in two patients, and the small size (15 mm) of the mass in the other. There were two false positive results with both CT and MRI, and no false positive MIBG scintigraphy, which had the highest (100%) positive predictive value. The combination of MRI+MIBG scintigraphy reached 100% sensitivity and positive predictive value. ConclusionOur data suggest that this imaging protocol should be used in all patients with biochemically confirmed pheochromocytoma.

Endocrine Therapy of Breast Cancer

Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause-like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer.

Treatment of Estrogen Receptor-Positive Breast Cancer

Estrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately 70% of human breast cancers (BCs) are hormone-dependent and ER-positive. The introduction of adjuvant systemic therapy led to a significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with ER+ tumors, who may receive ET alone or in combination with cytotoxic therapy. Adjuvant ET currently consists of (i) ovarian suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs). In patients with ER+ tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective than adjuvant chemotherapy alone. Tamoxifen is the best established SERM, has favorable effects on BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For these reasons, other SERMs have been developed. Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus. The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs. In postmenopausal patients with ER+ BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront therapy. Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging.

Temozolomide in Patients with Glioblastoma at Second Relapse after First Line Nitrosourea-Procarbazine Failure: A Phase II Study

Objectives: To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. Methods: Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m2/daily for 5 days every 4 weeks. Results: The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14–42%) and 8% (CI = 2–27%), respectively, with a median TTP of 11.7 weeks (CI = 9–22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7–31%). Conclusion: TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM.

Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in patients with insulin-dependent diabetes mellitus

The aims of this study were to evaluate the prevalence of osteopenia and the relationships between osteocalcin (OC), bone alkaline phosphatase (bALP), and bone mineral density (BMD) in patients with insulin‐dependent diabetes mellitus (IDDM). A group of 18 patients (median age 47, range 36–51) with uncomplicated IDDM (Group A) were matched by sex, age, and body mass index with 21 healthy control volunteers (Group B). All subjects underwent osteodensitometry with measurement of BMD at the lumbar spine and femoral neck. Osteopenia was present in 11 (61.1%) and 2 (9.5%) of Group A and B patients (P= 0.01), respectively. Both OC (28.4 ± 16.4 versus 41.2 ± 14.6 ng/mL; P= 0.005) and bALP (51.3 ± 11.8 versus 61.7 ± 10.6 U/L; P= 0.006) serum levels were significantly lower in patients with IDDM. BMD did not correlate with either OC or bALP. In conclusion, osteopenia is common among patients with IDDM, but the relationship between bone formation markers and BMD is still unclear.

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

Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism

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

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

OBJECTIVE To compare the effectiveness of cyproterone acetate, finasteride, and spironolactone in the treatment of idiopathic hirsutism. DESIGN Prospective randomized clinical study. SETTING University hospital. PATIENT(S) Forty-one women (median age, 21 years [range, 18-34 years]) with idiopathic hirsutism who had requested to use an oral contraceptive. INTERVENTION(S) Patients were randomly assigned to receive cyproterone acetate (12.5 mg/d for the first 10 days of the cycle), finasteride (5 mg/d), or spironolactone (100 mg/d) for 12 months. Follow-up was done at the end of therapy. MAIN OUTCOME MEASURE(S) Ferriman-Gallwey score before treatment, at 6 and 12 months of treatment, and 1 year after the end of treatment, and androgenic profile before and after treatment. RESULT(S) At the end of therapy, the Ferriman-Gallwey score decreased by 38.9%, 38.6%, and 38.5% in patients who used cyproterone acetate, finasteride, and spironolactone, respectively. One year after therapy, the Ferriman-Gallwey score of patients who used spironolactone was significantly lower (6.74 +/- 1.41) than that of patients who used either cyproterone acetate (7.92 +/- 1.08), or finasteride (9.08 +/- 0.99). The androgenic profile did not change significantly during treatment. CONCLUSION(S) In patients with idiopathic hirsutism, the short-term results of treatment with cyproterone acetate, finasteride, and spironolactone are similar, but spironolactone is effective for a longer time.

Medical Treatment of Malignancy-Associated Hypercalcemia

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.