G Boni

Long-acting depot lanreotide in the treatment of patients with advanced neuroendocrine tumors

Long-acting depot forms of somatostatin analogs administered by intramuscular injections are now available for the treatment of neuroendocrine tumors (NETs). In the present study, we investigated the efficacy and tolerability of a slow-release form of lanreotide in patients with advanced NETs. From July 1996 to January 1999, 25 patients with advanced NETs (12 carcinoids, 13 endocrine pancreatic tumors) were enrolled in the study. Thirteen patients were pretreated with subcutaneous octreotide, chemotherapy, or hepatic metastasis alcoholization. All the patients had measurable disease. Seventeen patients were symptomatic and 20 patients had elevated serum and/or urine markers. Octreotide scintigraphy was positive in 23 of 25 patients. Lanreotide was administered as intramuscular injections at the dose of 30 mg every 2 weeks until there was objective, biochemical, or symptomatic tumor progression. Objective partial responses (PRs) were documented in 2 patients (8%), whereas 10 patients (40%) had tumor stabilization. The PRs were observed in patients with midgut carcinoids, of whom one was pretreated with subcutaneous octreotide. The response duration was 21+ and 24+ months in responding patients; the median duration of disease stabilization was 8.5 months (range, 4-21+). The overall biochemical response rate was 42%, including 2 complete responses (CRs) (10.5%) and 6 PRs (31.5%); all biochemical responses were observed mostly in patients with carcinoid tumors; the duration of response was 18+ and 30+ months for CRs; the median duration of biochemical response was 7 months (range, 4-18+) for PRs. The overall symptomatic response rate was 70% with a median duration of 7.5, 18, and 18+ months for diarrhea, abdominal pain, and flushing, respectively. Median duration of lanreotide treatment was 10 months (range, 2-30+). No significant side effects were reported. Depot lanreotide 30 mg shows significant efficacy in terms of objective response rate and in biochemical and symptomatic control, in pretreated patients as well as nonpretreated patients with advanced NETs. Tolerability is good, with good patient compliance.

Long-term prognostic value of 18F-FDG PET in patients with locally advanced rectal cancer previously treated with neoadjuvant radiochemotherapy

OBJECTIVE The purpose of this study was to assess the prognostic value of (18)F-FDG PET performed at restaging in patients with locally advanced rectal cancer who previously underwent neoadjuvant radiochemotherapy. SUBJECTS AND METHODS Eighty-eight patients with histologically proven rectal cancer classified at clinical TNM stages II and III were enrolled. Six weeks after radiochemotherapy completion, all patients were restaged by sonography, CT, MRI, endoscopy, and (18)F-FDG PET. Surgery was performed in all patients within 8-9 weeks from completion of radiochemotherapy. Median follow-up after surgery was 38 months (range, 6-66 months). RESULTS The 5-year overall survival and disease-free survival were 83% and 73%, respectively. Cox multivariate analysis showed that only two parameters at restaging were independent prognostic predictors of both overall survival and disease-free survival: pathologic stage and, especially, after radiochemotherapy (18)F-FDG PET findings. The 5-year overall survival was 91% in patients with a negative PET after radiochemotherapy versus 72% in those with a positive PET (p = 0.024) after radiochemotherapy, whereas disease-free survival was 81% and 62% (p = 0.003) for those with the negative and positive PET findings, respectively. Statistical data were further enhanced when combining the pathologic stage with the (18)F-FDG PET results: 95% 5-year overall survival in the PET-negative pathologic stages 0 and I patients versus 70% in PET-positive pathologic stages II-IV patients (p = 0.001), whereas disease-free survival was 93% and 65% (p = 0.0003) for the negative and positive PETs, respectively. CONCLUSION In patients with locally advanced rectal cancer previously treated with neoadjuvant radiochemotherapy, the combined evaluation of pathologic stage and after-radiochemotherapy (18)F-FDG PET at restaging identified a subgroup of patients characterized by good response to radiochemotherapy and a more favorable prognosis. In these patients, a conservative surgical approach might be considered.

A pilot study of the role of TC-99 radionuclide in localization of pulmonary nodular lesions for thoracoscopic resection

OBJECTIVE Video-assisted thoracic surgery (VATS) is an interesting and emerging procedure for diagnosis and treatment of peripheral pulmonary nodules. However, thoracoscopy has limits in the detection of small nodules, below the pleural surface, deep in the lung parenchyma, which cannot be seen as much as palpated. Methods to localize such lesions, including the methylene blue injection or the introduction of a hooked-wire under the radiological vision, have some advantages but a lot of limitations. We are developing a new technique for the detection of pulmonary nodules smaller than 2 cm, deep in the lung parenchyma. METHODS The technique consisted of a intra-lesional injection of 0.3 ml of solution of 99m Tc-labelled human serum albumin microspheres (5-10 MBq) under the CT-scan guide, 2 h before surgery. During thoracoscopy a 11 mm diameter-collimated probe connected to a gamma ray detector (Scinti Probe MR 100 - Pol. hi.tech., Aquila - Italy), is introduced by a 11.5 mm trocar and the pleural surface of the suspected area was scanned. A hot-spot indicated the presence of the injected nodule and as a consequence, the area to be resected. RESULTS from June 1997 to June 1999 we treated 39 patients with small pulmonary nodules. The patients were 27 men and 12 women with a mean age of 60.8 years (range: 13-80). In 19 cases the anamnesis was positive for synchronous or metachronous malignant neoplasm. The mean surgical procedure length was 50 min (range 20-100 min). In all the cases the nodule was resected and the resection margins were pathologically free of tumour. The mean post-operative hospital stay was 3 days (range 2-6 days). Histological examination showed 21 benign lesions and 18 malignant lesions (seven metastases and 11 primary lung cancers). Nine pts with primary lung carcinoma underwent a completion lobectomy by open surgery. CONCLUSIONS Radiolocalization by gamma-probe allows the detection and exeresis of small nodules in a easy and safe way. Future and predictable advances in radio-marked monoclonal antibodies, as well as in the development of endoscopic beta-detector probe, will offer a more effective method for detection of primary and metastatic tumours, targets of thoracoscopic resections.

Early Results of Transmyocardial Revascularization With a Holmium Laser

BACKGROUND Transmyocardial laser revascularization (TMLR), a surgical technique designed to improve perfusion in the ischemic myocardium by creating transmural channels, has been performed thus far using a carbon dioxide laser, with apparently gratifying early results. We have investigated clinically TMLR using a holmium laser as sole therapy for patients with coronary artery disease that is not amenable to traditional treatment such as coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. METHODS From November 1995 to December 1996, 16 patients underwent TMLR using a holmium laser. Their mean age was 68 +/- 6 years and 75% were men. Previous coronary artery bypass grafting or percutaneous transluminal coronary angioplasty had been performed in 81% and 31% of the patients, respectively. Before operation, their mean anginal class was 3.4 +/- 0.5 and their mean left ventricular ejection fraction was 0.49 +/- 0.06. Six patients had unstable angina. RESULTS There were no operative deaths. The mean duration of TMLR was 27 +/- 13 minutes and the mean duration of the entire operation was 120 +/- 40 minutes. There were no major postoperative complications and the mean hospital stay was 8 +/- 4 days. There were 2 late deaths, 1 that occurred 40 days after TMLR as a result of stroke and 1 that occurred 4 months after TMLR as a result of myocardial infarction. Current survivors have been followed up for a mean of 10 +/- 4 months (range, 3 to 15 months), with 7 patients followed up for 1 year. At last follow-up, the mean anginal class had decreased to 1.8 +/- 0.7 (p = 0.001) and the patients had increased exercise tolerance and a reduced number of hospitalizations. However, no statistically significant changes in the percentage of segments with fixed or reversible ischemia and no statistically significant differences in the viability scores of lased and nonlased segments were observed. CONCLUSIONS Transmyocardial laser revascularization using a holmium laser is a simple technique with low operative risk and low morbidity. Early results confirm that clinical improvement is obtained in most patients, although significant changes in myocardial perfusion are not evident in the short term.

Recombinant human thyroid-stimulating hormone is effective for radioiodine ablation of post-surgical thyroid remnants.

ObjectiveTo investigate whether recombinant human thyroid-stimulating factor (rhTSH) is effective for the radiometabolic ablation of post-surgery thyroid remnants, using low doses of 131I. Patients and methodsThe study included two groups of patients enrolled consecutively: group 1 consisted of 52 patients with papillary cancer or minimally invasive follicular cancer (stage I and II), and group 2 consisted of 41 patients with the same stage of disease. All patients underwent a total thyroidectomy. Group 1 received 1.11 GBq (30 mCi) 131I for post-surgical remnants ablation with the aid of rhTSH, while group 2, in the hypothyroid state, received the same amount of radioiodine. To minimize iodine interference, all patients remained on a low iodine diet for 2 weeks and L-thyroxine (L-T4) was stopped for 4 days in the group of patients treated with the aid of rhTSH. To investigate 131I uptake in this group, a tracer dose was administered 3 h after the second injection of rhTSH and the uptake was evaluated at 24 h just before administration of the therapeutic dose. 131I was also measured in the patients treated in the hypothyroid state just before the therapeutic dose was given. ResultsAfter 1 year both groups were studied by using whole-body scintigraphy (WBS) and measuring thyroglobulin after rhTSH. In group 1, WBS was negative in 76.9% (40 patients), while thyroglobulin-stimulated levels were <1.0 ng · ml−1 in 86.5% (45 patients). In Group 2, WBS was negative in 75.6% (31 patients), while thyroglobulin-stimulated levels were <1 ng · ml−1 in 78.0% (32 patients). 131I uptake was 2.29±0.45 in the group treated with the aid of rhTSH, and 3.30±0.7 in the group treated in the hypothyroid state (P=0.2). No patients treated with the aid of rhTSH and with the short stoppage of L-T4 experienced symptoms of hypothyroidism, and free thyroxine (FT4) and thyroid-stimulating hormone levels remained normal. ConclusionsOur data confirm that, when the interference of iodine is minimized, rhTSH is highly effective for the treatment of post-surgical thyroid remnants using a low dose of 131I.

Intraoperative radioguided sentinel lymph node biopsy in non-small cell lung cancer

OBJECTIVES The aim of this study was to determine the accuracy and the role of the sentinel lymph node (SLN) technique in patients with early non-small cell lung cancer (NSCLC). METHODS This study was carried out on 29 consecutive patients (M/F = 24:5, mean age 65.9 +/- 7.1 years) with resectable NSCLC (Stage IA-IB). Intraoperative injection with a (99m)Tc-nanocolloid suspension was performed in the first ten patients; the following patients were injected under computed tomography scan guidance. A total dose of 37 MBq (1 ml) was administered in two to four divided aliquots (depending on the size), injected in the periphery of the tumour. Intraoperative radioactivity counting started a mean of 1 h (range 50-70 min) after the injection. The SLN was defined as the node with the highest count rate using a handheld gamma probe counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic and immunohistochemistry (IHC) examination. RESULTS Three of the 29 patients did not have NSCLC (two benign lesions, and one metastatic breast tumour) and were excluded. The SLN was identified in 25/26 (96.1%) patients (a total of 31 SLNs); 7/31 (22.5%) of the SLNs were positive for metastatic involvement after histologic and IHC examination. One inaccurately identified SLN was encountered (3.8%). CONCLUSIONS These preliminary results demonstrate the feasibility of this procedure in identifying the first site of potential nodal metastases of NSCLC. The actual clinical impact of this procedure remains to be elucidated by further investigation in larger groups of patients.

Intraoperative sentinel lymph node mapping in stage I non-small cell lung cancer: detection of micrometastases by polymerase chain reaction §

OBJECTIVE We previously reported the results achieved in detecting sentinel lymph nodes (SLN). We applied the molecular techniques (RT-PCR) to improve the detection of micrometastasis in order to evaluate an improvement of staging in early non-small cell lung cancer (NSCLC) patients (pts). METHODS This study was carried out on 22 consecutive NSCLC pts with stage I disease. A dose of 37MBq (1 ml (99m)Tc-nanocolloid suspension) was administered. The intralesional injection was performed under CT-guidance (7 pts), by using bronchoscopy (5 pts), VATS (2 pts) and at time of the thoracotomy (8 pts). RT-PCR analysis for cytokeratin 7 and 19 (CK7-CK19) was used to identify tumour-derived material in lymph nodes (LN). Each SLN was bisected: half was used for conventional examination (H&E staining/by immunohistochemistry (IHC), half was snap-frozen to -80 degrees C for RNA-detection of CK7 and CK19. RESULTS SLN was detected in 16 out of 19 pts. In three pts SLN was not identified (due to an incorrect technique). Conventional pathologic examination showed stage I disease in 13 pts, T3N0 disease in 1 pt, N2 in 5 pts. The IHC analysis identified micrometastasis in seven pts (two evaluated N0 according to H&E staining). RT-PCR analysis, performed in 10/16 pts, identified micrometastasis in 6 pts (3 pts evaluated N0 disease by H&E ; 1 of these evaluated N0 even by IHC). All N2 patients relapsed. One patient (N0 pts after H&E and IHC analysis) with positive CK7 and CK19 expression by RT-PCR analysis relapsed (systemic relapse) 3 months after surgery. CONCLUSIONS SLN technique could provide a subgroup of patients in which the use of RT-PCR could be applied on a well-focused target. This approach may be useful for stratifying histologically N0 patients into higher risk and lower risk groups.

Radionuclide Evaluation of the Lower Gastrointestinal Tract

This review outlines the technical aspects and diagnostic performance parameters of nuclear medicine procedures used on patients with disorders of the lower gastrointestinal tract, with the exclusion of techniques using tumor-seeking radiopharmaceuticals. Chronic disorders of the lower gastrointestinal tract often reduce the quality of life because of discomfort from constipation or diarrhea. Five classes of radionuclide procedures are used to characterize these disorders: transit scintigraphy, searches for ectopic gastric mucosa in Meckels diverticulum, scintigraphy of active inflammatory bowel disease, scintigraphic defecography, and scintigraphy to detect sites of gastrointestinal bleeding. Protocols for these procedures and their relative merit in patient management are discussed, with special emphasis on their potential for semiquantitative assessment of the pathophysiologic parameter investigated. Quantitation is particularly relevant for prognostic purposes and for monitoring the efficacy of therapy.

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease

BackgroundThe incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves.Methods and ResultsForty-five consecutive patients (33 men and 12 women; 53±6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis >50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamonds algorithm) was low (45.6%±12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3%±10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4%±4.3% (p<0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3%±5.5% (p<0.003), a level that appeared significantly higher than that of model 2 (p<0.016).ConclusionBoth noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.

111In Platelet Scintigraphy for the Noninvasive Detection of Carotid Plaque Thrombosis

Background and Purpose— Thrombosis on atherosclerotic lesions in the large extracranial arteries is the main cause of embolization in the distal cerebral circulation and thus is involved in the pathogenesis of ischemic stroke. The assessment of biological characteristics of lesions that are predictive of thrombotic complications might help in stratification of the risk for stroke but is currently imperfect. Methods— We compared the performance of 111In-platelet scintigraphy with blood pool subtraction, ultrasound-based tissue texture analyses, and transcranial Doppler techniques in their ability to predict the occurrence of superficial thrombosis or the presence of a lipid pool in carotid artery plaque specimens removed at the time of carotid endarterectomy in 22 patients with unilateral carotid artery stenosis of >70%. Results— Positivity at 111In-platelet scintigraphy was present in 8 patients and correctly identified the presence of thrombosis superimposed on a complicated plaque. Neither tissue texture analysis nor emboli detection by transcranial Doppler, performed in 12 patients, significantly identified plaque thrombosis. None of the techniques used were able to detect the presence of a significant lipid pool inside the plaque. Conclusions— Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.