Rita Massa

Carcinoid syndrome in bronchial adenoma

Summary Two patients with bronchial adenomas and the carcinoid syndrome are reported. In addition, sixty-four similar cases were collected from the literature. Metastases in the liver or other organs are necessary to produce the carcinoid syndrome in the majority of the cases. However, in a few patients the primary tumor itself can lead to the onset of the typical symptoms. The measurement of the 5-HIAA level in the urine is now considered the most valuable method of diagnosis. Conversely, the serum serotonin level is not a precise index. The ideal management of a bronchial carcinoid is total excision even when metastases are present in the liver, since in some cases these can be removed. Furthermore, the patients can be treated more easily with drugs and they have a better prognosis.

Detection of colon cancer with 99mTc-labeled bombesin derivative (99mTc-leu13-BN1)

Breast, prostate, and lung cancer have been successfully detected with 99mTc bombesin (99mTc-leu13-BN1), the radiopharmaceutical that our group developed from synthesis to diagnostic trials. Overexpression of bombesin receptors (BNRs) in colon cancer is well known: the aim of this study was to assess whether or not colon cancer can be detected with a 99mTc-leu13-BN1 scan. Thirteen (13) patients, 7 of whom with known rectal cancer and 6 scheduled to undergo endoscopic removal of polyps for suspicion of colon cancer, were studied with a 99mTc-leu13-BN1 scan. Dynamic, single photon emission computed tomography, and whole-body scans were performed within 1 hour, before discharge of radioactivity from the liver into the duodenum. Sixteen (16) of 17 colorectal cancer locations were detected with a 99mTc-leu13-BN1 scan with 94.1% sensitivity. Six (6) lesions were benign: 1 Crohns disease, 1 polyp with mild dysplasia, 4 polyps with simple hyperplasia; 99mTc-leu13-BN1 scans were positive in two nontumoral lesions, Crohns disease, and mild dysplasia and true negative in 4: specificity was 67%. Of the 7 patients with known rectal cancer, 5, who underwent operations instead of radiation therapy, showed lymph-node invasion on 99mTc-leu13-BN1 scans. Operations confirmed the scintigraphic staging. 99mTc-leu13-BN1 is taken up by colon cancer. Scans are sensitive, although scarcely specific. 99mTc-leu13-BN1 allows for node-invasion detection.

Intrarenal Hemodynamic Parameters Correlate with Glomerular Filtration Rate and Digital Microvascular Damage in Patients with Systemic Sclerosis

OBJECTIVES To evaluate intrarenal arterial stiffness by Doppler ultrasound and examine the correlation between renal Doppler indices, glomerular filtration rate, and digital microvascular damage in systemic sclerosis patients. METHODS Thirty systemic sclerosis patients and 30 healthy controls were enrolled in this study. Doppler indices of intrarenal arterial stiffness, peak systolic flow velocity, end diastolic flow velocity, resistive index, pulsative index, and systolic/diastolic (S/D) ratio were measured on the interlobar artery of both kidneys. Glomerular filtration rate was measured using Tc(99m) diethylenetriamine pentaacetic acid (DTPA). Equation 7 from the Modification of Diet in Renal Disease was used to estimate glomerular filtration rate. Nailfold videocapillaroscopy findings were classified as early, active, and late patterns. RESULTS The intrarenal arterial stiffness, evaluated by Doppler indices, was higher in systemic sclerosis patients than healthy controls. In systemic sclerosis patients pulsative index (r = -0.69), resistive index (r = -0.75), and S/D ratio (r = -0.74) showed a negative correlation with measured glomerular filtration rate (P < 0001). High correlation (P = 0008) was observed between measured and estimated glomerular filtration rate (r = 0.55). Pulsative index, resistive index, and S/D ratio significantly increased with progression of capillaroscopic damage. Conversely, measured glomerular filtration rate significantly decreased with capillaroscopic damage progression. CONCLUSIONS Doppler indices of intrarenal arterial stiffness are noninvasive diagnostic tests to evaluate renal damage in SSc patients. Intrarenal arterial stiffness and glomerular filtration rate correlate with capillaroscopic microvascular damage.

Plasma Endothelin-1 Levels in Patients with Aldosterone-Producing Adenoma and Pheochromocytoma

The aim of the study was to evaluate possible changes of plasma endothelin-1 levels (ET-1) in patients with hypertension secondary to primary aldosteronism and pheochromocytoma. We enrolled in the study: 12 patients affected by aldosterone-producing adenoma (5 M and 7 W; mean age 42.1 +/- 17.2 years); 8 patients with pheochromocytoma (5 M, 3 W; mean age 36.2 +/- 17.1 years); 15 patients with essential hypertension (9 M, 6 W; mean age 48.5 +/- 10 years). We also enrolled a normal control group (8 M, 12 W; mean age 34.2 +/- 11 years). The mean plasma ET-1 concentrations in patients with pheochromocytoma were significantly higher (23.9 +/- 5.2 pg/ml) than those in normal subjects (7.3 +/- 1.9 pg/ml), in patients with primary aldosteronism (12.1 +/- 3.8 pg/ml) and in patients with essential hypertension (9.2 +/- 3 pg/ml); p < 0.001, respectively. The present investigation demonstrates that in human adrenal hypertension patients with pheochromocytoma have increased circulating ET-1 levels respect to patients with aldosterone-producing adenoma.

Carotid body tumors: radioguided surgical approach

BackgroundCarotid body tumours (CBTs) are very rare lesions which should be treated as soon as possible even when benign since small tumour size permits easier removal and lower incidence of perioperative complications and recurrence. Malignant forms are rare and they can be identified by lymph node invasion and metastases in distant locations. The need of reliable and effective diagnostic modalities for both primary CBTs and its metastases or recurrence is evident.The present study reviews our experience and attempt to define the role of colour coded ultrasound (CCU) and Somatostatin receptor scintigraphy (SRS) with Indium-111-DTPA-pentetretide (Octreoscan®) using both planar and single photon emission tomography (SPECT) technique in the diagnosis and follow-up of these uncommon lesions within a multidisciplinary approach.MethodsFrom 1997 to 2008, 12 patients suffering from 16 CBTs (4 bilateral) were investigated by CCU and SRS-SPECT before and after surgery. All tumours were grouped according to Shamblins classification in order to assess the technical difficulties and morbidity of surgical resection on the ground of their size and relationship with the carotid arteries. Intraoperative radiocaptation by Octreoscan®) was also carried out in all cases to evaluate the radicality of surgery. All perioperative scans were evaluated by the same nuclear medicine physician.ResultsPreoperatively CCU showed CBTs (four were not palpable) with a sensitivity of 100%. Radioisotope imaging identified the CBTs as chemodectomas in 15 cases while no radioisotopic uptake was detected in 1 vagus nerve neurinoma. No evidence of metastasis or multicentricity were seen by total body radioisotopic scans. Combined data from CCU and SRS-SPECT allowed to determine tumour size in order to select 7 larger tumours which were submitted to selective preoperative embolization.Intraoperatively Octreoscan demonstrated microscopic tumour leftovers promptly removed in 1 case and an unresectable remnant at the base of the skull in another case.During follow-up CCI and radioisotope scans showed no recurrence in 14 cases and a slightly enlargement of the intracranial residual as detected during surgery in 1 patient.ConclusionCCU may allow an early and noninvasive detection of CBTs and hence safer operations. The combined use of CCU and SRS-SPECT provide useful data to identify those tumours and to evaluate their extent and carotid arteries infiltration. Radioisotope imaging is a sensitive modality to detect metastases and lymph node involvement that are markers of CBT malignancy. After surgery CCU and SRS-SPECT can be accurate modalities for surveillance for an early detection of CBTs recurrence.

Evaluation of Chronic Kidney Disease Epidemiology Collaboration equation to estimate glomerular filtration rate in scleroderma patients

OBJECTIVE Renal involvement in SSc is often subclinical and chronic kidney disease (CKD) develops, with slow worsening of glomerular filtration rate (GFR). The present investigation was undertaken in order to study how well the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) correlates with measured GFR (mGFR) in a group of SSc patients with serum creatinine (sCr) in the normal range. METHODS Forty-one scleroderma patients (37 females and 4 males) with a median age of 46 years were enrolled. GFR was measured using technetium-99 m DTPA (Tc-99 m DTPA). The modified Cockroft-Gault formula, 4- and 7-variable Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations were used for estimated GFR (eGFR). RESULTS mGFR showed a median value of 84 ml/min (range 32.8-121.2 ml/min). Seven patients had reduced GFR (<60 ml/min), 19 had GFR within 60-90 ml/min and 15 had GFR >90 ml/min. The results showed mild correlation between the BSA-modified Cockroft-Gault and mGFR (P > 0.05), mild statistically significant correlation with 4-variable MDRD (P < 0.05), high statistically significant correlation with 7-variable MDRD (P = 0.01), but the greatest correlation was obtained using CKD-EPI (P = 0.002). No correlation with age, disease duration or subset of disease was found. CONCLUSIONS In scleroderma patients with normal sCr value, CKD-EPI is a useful formula to assess GFR.

Breast cancer takes up 99mTc bombesin. A preliminary report

Background Several tumors including lung, prostate, ovarian, colon, and exocrine pancreatic cancer show receptors for the amphibian neurotransmitter and growth factor bombesin (BN) and its mammalian counterparts gastrin-releasing peptide and neuromedin B. Also breast cancer has been reported to show such receptors: the presence of BN receptors in primary breast cancer has been demonstrated on cultured cells and by autoradiography on breast tissue samples. Authors who have studied BN receptors in breast cancer do not agree on their frequency in primary cancer, but indicate that 100% of metastatic breast cancers show such receptors. Methods We examined three primary breast cancer patients with 99mTc BN and 99mTc sestamibi one week before surgery. One of them showed axillary node invasion. The same acquisition technique was used for breast and chest imaging with both radiopharmaceuticals, whereas total body images were acquired only with 99mTc BN. Also the administered radioactivity was different: 20 mCi of 99mTc sestamibi and 5-8 mCi of 99mTc BN. Dynamic images were acquired for 20 mins after iv injection with the patient in ventral decubitus and the gamma camera positioned in lateral view, as is generally done in Khakhalis prone scintimammography. Anterior chest images were acquired for 30 mins. Prone scintimammography was performed one hour after administration of both tracers. ROIs were drawn on tumors and surrounding breast with the same technique in order to calculate the tumor to breast ratio (T/B). In addition, total body scan was performed one hour and three hours after 99mTc BN administration. All three patients underwent breast conserving surgery with lymphadenectomy. Postoperative pathologic assessment showed the following T and N stages in the three patients: T1bN0, T1cN0. and T1cN1. Results All three cancers were imaged with both tracers. The T/B of 99mTc BN was always higher than that of 99mTc sestamibi. Chest uptake was always much higher with 99mTc sestamibi than with 99mTc BN. Comparison between 99mTc BN and 99mTc sestamibi images gave other intriguing results: in the N1 patient both tracers clearly imaged the invaded node, but on the 99mTc BN image the primary tumor was larger than on the 99mTc sestamibi image and the node was smaller. It is known that 99mTc BN is not taken up by vessels and inflammatory tissue. The time activity curves of the two tracers were significantly different in all patients, with an increase in 99mTc BN uptake in the first three to five minutes, followed by a less sharp uprise of the curve, quite similar to a plateau. Conclusions Our first impression is that 99mTc BN is a useful breast cancer seeking agent and very promising for lymph node staging.

False-positive diagnosis of adrenal pheochromocytoma on iodine-123-MIBG scan

I-123 metaiodobenzylguanidine (I-123 MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. In this rare case report, we describe a definite adrenocortical adenoma that demonstrated false-positive uptake at I-123 MIBG scintigraphy and a remarkable accumulation of 75-SE-6-beta-selenomethyl-norcholesterol.

Adrenomedullin Levels are High in Primary Aldosteronism due to Adenoma and Decline after Surgical Cure

The aim of the study was to evaluate the possible changes in plasma adrenomedullin (AM) levels in patients with primary aldosteronism before and after surgical resection. The study included 13 patients affected by aldosterone-producing adenoma (9 women, 4 men; mean age 36.2+/-14.2 years) and 20 healthy control subjects (7 women, 13 M; mean age 31.8+/-12.4 years). Unilateral adrenalectomy was performed in all patients and adrenal mass consisted of a benign adrenal cortical adenoma. The mean plasma AM concentrations in patients with primary aldosteronism (36.2+/-19.3 pg/ml) were significantly (p < 0.0001) higher than those of normal subjects (13.2+/-6.2 pg/ml). In these patients the plasma AM levels significantly (p < 0.0001) reduced after surgical removal of the tumours (14.9+/-7.6 pg/ml). In all patients with aldosterone-producing adenoma, tumour diameter correlated with the plasma AM concentrations (r=0.631; p < 0.021). In conclusion, the present investigation shows that in primary aldosteronism due to adrenal adenoma plasma AM levels are higher at the moment of diagnosis and decline after successful adrenal operation.

Clinical experience with pheochromocytoma in a single centre over 16 years.

AbstractBackground: Pheochromocytoma and paraganglioma are rare tumours of neuroectodermal origin. Pheochromocytoma occurs in 0.1–2% of people with hypertension, while the incidence rises to 4–5% in patients with incidental adrenal mass. Aim: To analyse the presentation, diagnosis and localization, pathology, molecular genetic aspects, surgical management and long-term outcome of a large series of patients with pheochromocytoma referred to a single centre. Methods: From 1992 to 2008, we observed 91 patients with pheochromocytoma, 70 (77%) with the sporadic form and 21 (23%) with the hereditary form. In the group with the hereditary form, the mean age at diagnosis was significantly lower than the mean age of the group with the sporadic form (38 vs 48 years; p < 0.001). Results: Eighty (88%) patients with pheochromocytoma were symptomatic and the classical triad of palpitations, headache and diaphoresis was present in 30% of patients. In 12% of patients, the pheochromocytoma was discovered during radiological images (adrenal incidentaloma). The unilateral adrenal localization was observed in 78% of patients, bilateral in 15% and extra-adrenal in 7% of patients. All pheochromocytoma patients underwent surgical procedure and the laparotomic approach was used in 49 (53%) patients, while the laparoscopic approach was performed in 42 (47%) patients. Pheochromocytoma was benign in 86 patients (93%) [mean size was 4.3 cm] and the malignant form was found in five patients (7%) [mean size was 10 cm]. Conclusions: These data from a large cohort of patients are consistent with those reported in the literature and show that pheochromocytoma is an in important challenge for clinicians.