Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial.

High serum levels of testosterone and estradiol, the bioavailability of which may be increased by Western dietary habits, seem to be important risk factors for postmenopausal breast cancer. We hypothesized that an ad libitum diet low in animal fat and refined carbohydrates and rich in low-glycemic-index foods, monounsaturated and n-3 polyunsaturated fatty acids, and phytoestrogens, might favorably modify the hormonal profile of postmenopausal women. One hundred and four postmenopausal women selected from 312 healthy volunteers on the basis of high serum testosterone levels were randomized to dietary intervention or control. The intervention included intensive dietary counseling and specially prepared group meals twice a week over 4.5 months. Changes in serum levels of testosterone, estradiol, and sex hormone-binding globulin were the main outcome measures. In the intervention group, sex hormone-binding globulin increased significantly (from 36.0 to 45.1 nmol/liter) compared with the control group (25 versus 4%,; P < 0.0001) and serum testosterone decreased (from 0.41 to 0.33 ng/ml; -20 versus -7% in control group; P = 0.0038). Serum estradiol also decreased, but the change was not significant. The dietary intervention group also significantly decreased body weight (4.06 kg versus 0.54 kg in the control group), waist:hip ratio, total cholesterol, fasting glucose level, and area under insulin curve after oral glucose tolerance test. A radical modification in diet designed to reduce insulin resistance and also involving increased phytoestrogen intake decreases the bioavailability of serum sex hormones in hyperandrogenic postmenopausal women. Additional studies are needed to determine whether such effects can reduce the risk of developing breast cancer.

Serum level of the soluble form of the CD30 molecule identifies patients with Hodgkin's disease at high risk of unfavorable outcome.

Preliminary reports suggested a prognostic significance for serum levels of soluble CD30 (sCD30) in patients with Hodgkin's disease (HD). In this study, we investigated the prognostic impact of sCD30 concentration at diagnosis in relation to the other recognized prognostic parameters in 303 patients with HD observed in three different institutions between 1984 and 1996. sCD30 levels were correlated with stage, presence of B symptoms, and tumor burden. High sCD30 levels entailed a higher risk of poor outcome, and the event-free survival (EFS) probability at 5 years for patients with sCD30 levels >/=100 and less than 100 U/mL was 59.9% (95% confidence interval [CI], 40.6% to 65.9%) and 87.5% (95% CI, 81.5% to 91.6%), respectively (P < .001). On the basis of the results of univariate analysis of 14 pretreatment characteristics, we included five prognostic factors (high sCD30 serum level, stage III-IV, B symptoms, low hemoglobin level, and age >/=50 years) into a multivariate model. High sCD30 and advanced stage were independently associated with an unfavorable prognosis. Their combined evaluation identified patients at high risk (stages III and IV and sCD30 >/=100 U/mL: EFS, 46.9%) and low risk (stages I and II with sCD30 <100 U/mL: EFS, 88. 7%) of treatment failure (P < .001). We conclude that the combined evaluation of sCD30 serum level and stage at presentation identifies patients with HD at high risk of an unfavorable outcome.

Soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease: outcome and clinical implications.

The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete remission (CR) and in predicting disease relapse. Between August 1988 and June 1993 sIL-2R serum levels were measured in 174 untreated patients; in 137 of them evaluation was repeated at the end of treatment and in 132 also during the follow-up. Baseline sIL-2R levels (mean+/-standard error) were significantly higher in patients than in 65 healthy control subjects (1842+/-129 U ml(-1) vs 420+/-10 U ml(-10, P< 0.0001). At the end of treatment 135 out of 137 evaluated patients achieved complete response (CR) and their mean sIL-2R serum levels were significantly lower than those at diagnosis (635+/-19 U ml(-1) vs 1795+/-122 U ml(-1), P=0.0001). After a median follow-up of 5 years, sIL-2R remained low in 114 patients in continuous CR, while they increased in 9 out of 12 patients (75%) who relapsed. However, a temporary increase was also observed in six patients (5%) still in CR. Treatment outcome in terms of freedom from progression was linearly related to sIL-2R levels. Our study confirms that patients with untreated HD have increased baseline levels of sIL-2R compared with healthy subjects and that their pretreatment values may be an indication of disease outcome similar to other conventional prognostic factors, such as number of involved sites, presence of B symptoms and extranodal extent.

Malignant pheochromocytoma in multiple endocrine neoplasia type 2B syndrome. Case report and review of the literature.

A malignant behavior (i.e., distant metastatic spread) has been recorded in 3-4% pheochromocytomas occurring in the context of multiple endocrine neoplasia type 2A syndrome, but has never been documented in patients with the type 2B form. In this report we describe a case of malignant pheochromocytoma arising in the latter syndrome setting. The patient, a white young male, had the full-blown syndrome, including multicentric, bilateral medullary thyroid carcinoma metastatic to regional lymph nodes, mucosal neuromas, digestive ganglioneuromatosis, marfanoid habitus, and bumpy lips. Three and a half years after surgical resection of an apparently benign adrenal pheochromocytoma he developed widespread osseous metastases. The presence of hypertensive crises and high urinary catecholamine excretion rates, coupled to moderate hypercalcitoninemia, normal circulating carcinoembryonic antigen levels, negative whole-body 99mTc-(V) dimercaptosuccinic acid scan, and absence of neck or mediastinal disease by magnetic resonance imaging, proved that the metastases were from his previous adrenal and not thyroid tumor. Furthermore, since the bone metastases strongly accumulated 131I-metaiodobenzylguanidine, several courses of the radiocompound were given, which resulted in an objective, though partial, tumor regression.

A dose-finding study of lanreotide (a somatostatin analog) in patients with colorectal carcinoma.

BACKGROUND: Laboratory data suggest that insulin-like growth factor-1 (IGF-1) may stimulate the growth of different human tumors. At least in acromegalic patients, somatostatin (SMS) analogs, such as lanreotide, suppress the serum levels of growth hormone (GH) and IGF-1. METHODS: To evaluate the tolerability and biologic activity of different doses of lanreotide in patients with advanced colorectal carcinoma, consecutive groups of 3 patients each were subcutaneous treated with lanreotide at doses of 1, 2, 3, 4, 5, or 6 mg three times a day for 2 months. In the event of Grade 3 side effects, 3 additional patients were treated with the same dose before the next dose escalation. Serum samples were obtained on Days 0, 15, 30, and 60 for serum GH, IGF-1, and lanreotide assessment. RESULTS: Twenty-four patients were enrolled and all were evaluable. Except for the 3 and 6 mg doses, for which the observation of a Grade 3 side effect required that an additional three patients be treated, it was sufficient to treat 3 patients at each dose. The overall incidence of side effects was as follows: changes in bowel habits, 83%; abdominal cramps, 79%; diarrhea, 17%; vomiting, 17%; nausea, 21%; steatorrhea, 78%; hyperglycemia, 35%; laboratory hypothyroidism, 39%; gallstones, 13%; and weight loss, 17%. No evidence of an increase in the incidence, intensity, or duration of side effects was observed with dose escalation. Serum IGF-1 levels were as follows: Day 15: 63%, 60%, and 67% of the baseline values for the low (1-2 mg), intermediate (3-4 mg), and high (5-6 mg) dose groups, respectively; Day 30: 63%, 59%, and 51%, respectively; and Day 60: 73%, 69%, and 47%, respectively. Serum lanreotide levels declined during treatment in all of the dose groups (90 ng/mL on Day 15, and 35 ng/mL on Day 60 for the 5-6 mg group; 10 ng/mL on Day 15, and 1.5 ng/mL on Day 60 for the 1-2 mg group). No antitumor activity or tumor marker reduction was observed. CONCLUSIONS: No increase in toxicity was observed when subcutaneous lanreotide doses were escalated to 6 mg three times a day for 2 months. The highest doses seemed to maintain reduced serum IGF-1 levels; with the lowest doses, a "rebound" in serum IGF-1 levels was observed during treatment. Nevertheless, intermittent subcutaneous injections do not ensure constant serum drug concentrations over time.

Ambulatory follow-up of aortic dissection: comparison between computed tomography and biplane transesophageal echocardiography.

UNLABELLED: Aim of the study was to assess the relative usefulness of transesophageal echocardiography (TEE) and X-ray computed tomography (CT) in the follow-up of patients who survived an aortic dissection. MATERIALS AND METHODS: We evaluated 44 patients (age = 57 +/- 12 years) with treated aortic dissection: 14 had a De Bakey type I, 20 a type II and 1 patient a type III dissection treated surgically: 1 patient had a type I, 1 a type II and 7 a type III dissection treated medically. All entered an outpatient follow-up program with serial evaluations at 1, 6 and 12 months after initial diagnosis by dual noninvasive imaging protocol. A contrast-enhanced CT scan and a TEE with biplane probe were performed on the same day and in random order. RESULTS: A total of 252 evaluations with both CT and TEE were considered. A completely normal study was found in 45 TEE and 48 CT evaluations. The following abnormal findings could be documented by one or both techniques: thrombus in the false lumen (TEE: n = 48; CT: n = 45 evaluations); intimal flap (TEE and CT: n = 68); aortic dilatation (TEE and CT: n = 15); pericardial effusion (TEE and CT: n = 3); aortic pseudoaneurysm (TEE: n = 2; CT: n = 3); isthmic coarctation (TEE and CT: n = 1). Regarding the presence or absence of these abnormalities, which are within the diagnostic domain of both imaging techniques, the results were fully concordant in 245 studies, and discordant in 7, with an overall agreement of 97%. In addition, some abnormal findings could be detected by TEE only: aortic insufficiency (n = 36); intimal tear (n = 25); spontaneous echocontrast effect in the false lumen (n = 39 evaluations). Other abnormal findings could be detected by CT only: a pleural effusion in 4, a truncus anonymous dissection in 1, a pseudoaneurysm due to suture dehiscence of the distal anastomosis of the ascending aorta in 1 evaluation (which yielded ambiguous results by TEE, with turbulent flow departing from the graft). CONCLUSION: Both CT and TEE are atraumatic, safe and accurate techniques for serial follow-up imaging of patients treated for aortic dissection. Information provided by CT is largely redundant, rather than additive, to that provided by TEE. The latter should be probably preferred for shorter imaging time, accuracy and convenience, although CT might still play a role in selected cases of ambiguous TEE results.

Chronic effects of subcutaneous interleukin-2 therapy on soluble interleukin-2 receptors in advanced small cell lung cancer.

The increase in IL-2 receptor serum levels is one of the most typical changes in immune parameters during IL-2 cancer immunotherapy. To better define the effects of prolonged IL-2 injection on SIL-2R levels, we evaluated 7 advanced small cell lung cancer patients who received IL-2 subcutaneously at a daily dose of 9 x 10(6) IU/m2/12h for two days followed by 3 x 10(6) IU/m2/12h for 18 days (5 days/week for 4 weeks). Moreover, four patients were also evaluated during the second IL-2 cycle. Venous blood samples were drawn before and at weekly intervals during IL-2 therapy. Mean SIL-2R serum levels rapidly increased with the start of IL-2 injection, and they were significantly higher than the baseline levels throughout the immunotherapy cycle. The increase in mean SIL-2R levels was higher in patients with progressive disease than in those with response or stable disease, but the difference was not significant. Finally, the increase in mean SIL-2R concentrations during the second IL-2 cycle was not significantly different from that seen during the first one. The present study confirms that IL-2 administration determines an evident increase in SIL-2R levels; moreover, it would demonstrate that re-exposure to IL-2 after a rest period does not induce a more pronounced SIL-2R release.

[Renal angioplasty in the treatment of renovascular hypertension. A comparison of results and the authors' own experience]. / L'angioplastica renale nel trattamento dell'ipertensione renovascolare. Confronto dei risultati e delle esperienze personali.

From 1986 to 1989, 68 patients with 79 stenoses (11 bilateral, 4 unilateral) underwent renal angioplasty in the Radiology Departments of Udine (34 cases) and Pisa (34 cases). Fifty-eight patients were arteriosclerotic (mean age 58) and 21 fibrodysplastic (mean age 32). The fibrodysplastic lesions were treated in Pisa. Recovery was obtained in 64/68 patients and 75/79 stenoses (residual stenosis less than 20%). Renovascular hypertension was cured or reduced in 57/64 cases. The angiographic follow-up (mean 15 months) of 54/75 stenoses demonstrated recurrence in 2/19 fibrodysplastic and in 6/35 arteriosclerotic lesions; 2 patients underwent angioplasty and 2 surgery: one patient per group exhibited no change in hypertension values. Thus, we believe that hypertension should be better defined (e.g. by selective reninemia sampling and Ace-inhibitor renal scintigraphy). The follow-up (mean 22 months) of hypertension in 48/64 patients (arteriosclerotic: fibrodysplastic = greater than 33/15) showed complete recovery in 8/33 and in 10/15 cases (24% and 66%, respectively); a significant improvement was obtained in 15/33 and in 2/15 cases (45% and 14%, respectively). Our results confirmed the higher efficacy of renal angioplasty in the treatment of fibrodysplastic lesions; as for arteriosclerotic lesions, angioplasty has been observed to improve vascularization rather than to cure hypertension.

Differential diagnosis between osteitis condensans ilii and sacroiliitis.

Sacroiliitis of seronegative spondyloarthropathy may sometimes show on pelvis plain films findings indistinguishable from those of osteitis condensans ilii. Computed tomography (CT) can differentiate earlier than plain radiography between the 2 conditions; furthermore, it should also be possible to make this differentiation clinically. The aim of our study was to verify whether the criteria recently proposed by the European Spondylarthropathy Study Group (EESG) for the classification of spondyloarthropathy are useful. CT scans through the synovial part of the sacroiliac joints of 7 consecutive patients meeting the ESSG criteria and showing typical findings of osteitis condensans ilii on plain films were mixed with those of 15 consecutive patients with osteitis condensans ilii not meeting the ESSG criteria. Scans were examined for joint space and surface abnormalities blindly and independently by 2 observers. Six patients in the spondyloarthropathy group and one in the osteiitis condensans ilii group showed clear erosions and/or joint space narrowing of less than 2 mm in at least one joint. The difference was statistically significant (p less than 0.001). Our results suggest that by using criteria valid for the whole group of seronegative spondyloarthropathies, it is possible to differentiate clinically between seronegative spondyloarthropathies with sacroiliitis mimicking osteitis condensans ilii and "true" osteitis condensans ilii.

Computed tomography of the sacroiliac joints in four patients with Behçet's syndrome--confirmation of sacroiliitis.

In order to reduce the subjective factor in evaluating sacroiliac joint radiographs we further evaluated changes seen on standard plain films of patients suffering from Behçet's syndrome (BS) by using computed tomography (CT). Sacroiliac joint films of 20 consecutive patients with BS were mixed with those of 20 consecutive control patients and read blindly and independently by two observers. Six patients with BS met the New York criteria for sacroiliitis. Of the control patients, one had monolateral grade 1 sacroiliitis and two revealed findings consistent with osteitis condensans ilii. CT confirmed the diagnosis of sacroiliitis in patients with BS showing a high degree in at least one joint. The results of the present study suggest that the use of CT for BS patients showing sacroiliac joint changes on pelvic plain films may limit the confusion which exists about this finding in BS.

[Loco-regional transcatheter thrombolysis]. / Trombolisi loco-regionale transcatetere.

Eight cases of recent arterial thrombosis (average time of symptoms: 11 days) are considered: 2 popliteal and 6 prosthetic thromboses (2 aorto-bifemoral and 4 femoropopliteal by-passes). After percutaneous catheterization, with catheter tip either in contact with or inside the thrombus, urokinase was locally injected (200,000 UI bolus, and 75,000 UI with slow infusion for 24 +/- 72 hours); general heparin treatment was also administered. PTA was employed in 2 cases (1 surgical anastomosis and 1 popliteal thrombosis). Arterial recanalization was always obtained within 72 hours in 2 aorto-bifemoral and in 1/4 femoropopliteal by-passes. Patency was also obtained in the 2 popliteal thrombosis.

[Post-traumatic arterio-venous popliteal aneurysm]. / Aneurisma popliteo artero-venoso post-traumatico.

A case of artero-venous pseudo-aneurysm caused by traumatic aetiology is reported. After a description of the case and a review of the literature, the pathogenesis, clinical aspects and therapy of acquired artero-venous fistulas are discussed.