Metabolic responses in non-small cell lung cancer after hypofractionated stereotactic radiotherapy PET and hypofractionated radiotherapy.

BACKGROUND: The aim of our study was to evaluate the pattern of local failure after stereotactic body radiotherapy (SBRT) of non small cell lung cancer (NSCLC) lesions relating to different type of 18F-FDG positron emission tomography (PET) response. METHODS: Thirteen NSCLC patients for a total of 15 lesions (primary early or locally advanced and metastases) underwent PET before and 6 months after SBRT. Maximum standard uptake value (SUVmax) <2.5 was considered as cut off for complete response (CR) while lesion reduction > or =50% with residual value above 2.5 for partial response (PR). RESULTS: With a median follow up of 30 months pre- and post-SBRT mean SUV max values were 8.2 (range 14.2-3.7) and 2.4 (range 12.9-0), respectively. No "in field recurrence" was observed while 3 cases of "out field recurrence" occurred as regional nodes progression at 7.8 and 14 months after treatment. Three years overall survival, local control and distant metastases free survival were respectively 66.7%, 63.3% and 44.4%. Actuarial 75% and 53.3% 3-year local control, 60% and 40% 3-years distant metastases free survival were observed for complete and partial PET response, respectively, after SBRT. Thereafter, 60% and 50% 3-year overall survival were observed for complete and partial response. CONCLUSIONS: Clinical results were significantly better for "responder" than "non responder" and for "complete" than "partial response" group. Moreover, our data seem to confirm that a significant subset of patients maintain a low metabolic activity without developing local relapse on longer follow up.

Radiolabelled somatostatin analogs for diagnosis and radio-guided surgery of neuroendocrine breast cancer undetectable with conventional imaging procedures.

Some neoplasms are classified as primary neuroendocrine tumours (NETs) because of their positivity for neuroendocrine markers [chromogranins A and B (CgA, CgB) and neuron-specific enolase (NSE)]. Neuroendocrine differentiation has been reported, for example, in both "in situ" and infiltrating breast cancer. Diagnosis of NET is bio-humoral (CgA, NSE, synaptophysin) and instrumental. Even if the final diagnosis is made by open biopsy, radionuclide imaging using radiolabelled somatostatin analogs, such as In-111 pentetreotide, may detect neuroendocrine primary tumours and metastases before they become detectable using traditional and advanced imaging modalities [mammography (MX), ultrasound (US) and magnetic resonance imaging (MRI)]. When neuroendocrine breast lesions are not detectable, radio-guided surgery (RGS) is able to localise cancer. We report a case of a woman with a palpable lymph node in the left axilla. She underwent a US-guided lymph node biopsy, which was positive for massive metastases, probably of neuroendocrine breast origin. Mammary plus axillary US showed only lymphadenopathy in the left axilla. MX and breast MRI were negative. Neoplastic markers (CEA, CA 15.3, CA 125 and CA 19.9) were negative too. On the other hand, neuroendocrine markers (NSE and CgA) were positive. A whole body scintigraphic scan plus thorax and abdomen single photon emission computed tomography (SPECT) with In-111 pentetreotide (222 MBq; 6 mCi) showed an uptake in the left mammary gland. No other pathological localisations were observed. The day after the intravenous injection of In-111 pentetreotide, the patient underwent RGS breast tumour resection and left axillary lymphadenectomy. In conclusion, we would like to emphasise: (1) the role of radionuclide imaging for the detection of breast NETs in relation to conventional diagnostic procedures; (2) the role of RGS in localising and removing a non-palpable breast NET that was undetectable with the use of conventional imaging techniques.

Reliability and accuracy of sentinel node biopsy in cutaneous malignant melanoma.

AIMS AND BACKGROUND: The aims of this study were 1) to investigate whether sentinel lymph node (SLN) biopsy could become the method of choice for the early detection of metastatic disease in patients with malignant melanoma and 2) to identify those patients with lymph node metastases who could benefit from regional lymphadenectomy. METHODS AND STUDY DESIGN: Our study started in March 1998 and involved 110 patients with primary cutaneous malignant melanoma stage I or II (AJCC) in whom the primary lesion had been surgically removed no more than 90 days previously. On the day of lymph node dissection patients were given an intradermal injection of colloid particles of human serum albumin labeled with technetium-99m and an injection of isosulfan blue. The surgical procedure was usually performed with local anesthesia but in some cases locoregional or general anesthesia was preferred. Contralateral and ipsilateral lymphatic areas were scanned with a hand-held gamma camera (Scintiprobe MR 100) to measure the background and identify the hot point indicating the location of the sentinel node to direct the incision. RESULTS: The combined use of lymphoscintigraphy, isosulfan blue and gamma probe allowed us to identify sentinel nodes in 108 of 110 patients (98.18%) while the SLN was blue in only 90 cases (81.81%). The SLN was positive for metastases in 13 of the 108 patients (12.03%) and regional and distal lymphadenectomy was performed in all of them. The distribution of positive SLNs by primary lesion thickness was as follows: 0.76-1.5 mm: one positive SLN/44 patients (2.27%); 1.51-4 mm: six positive SLNs/51 patients (11.7%); > 4 mm: six positive SLNs/15 patients (40%). Only four of 12 patients with ulcerated cutaneous melanoma had positive SLNs. The patients in our study underwent follow-up visits every four months. The median follow-up was 481 days (range, 97-1271 days). CONCLUSIONS: In patients with primary cutaneous melanoma the histological status of the SLN accurately reflects the presence or absence of metastatic disease in the relevant regional lymph node basin. Complete lymph node dissection should only be performed in patients with positive SLNs. Patients with lesions > 4 mm are likely to develop recurrences and to die of systemic disease, so in these patients the usefulness of SLN biopsy is questionable. In conclusion, sentinel node mapping is a rational approach for the selection of patients who might benefit from early lymph node dissection of the affected basin.

Sentinel node study in early breast cancer.

Since October 1997 60 patients with early breast cancer (T <3 cm) were studied. All patients underwent lymphoscintigraphy with two types of colloid: the first (17 pts) with a particle size <1,000 nm; the second (43 pts) with a particle size <80 nm. The standard procedure consists of injection, on the day before surgery, of 70 MBq of the smaller nanocolloid in 0.4 cc saline divided over four sites, around the lesion or subdermally around the surgical scar. We utilize a low-energy, high-resolution LFOV camera for scintigraphy and a probe specific for the sentinel node during surgery. In 56/60 patients (93.3%) lymphoscintigraphy showed the sentinel node (SN). In two cases the SN was not detected presumably because of lymphatic interruption by an old surgical scar; in the other two cases the sites of injection were too close to the SN, thus masking it. In five cases (9%) the SN was not visualized with the surgical probe but in two of these drainage to the internal mammary chain was observed. The apparently lower sensitivity of intraoperative localization was due to the extra-axillary lymphatic drainage or to the vicinity of the SN to the primary lesion. The SN proved to be metastatic in 12 cases. No false-negative SNs were found. In five cases (10%) the radiolabeled lymph node was the only node containing tumor cells (micrometastases): this result depends on the combined use of hematoxylin-eosin and rapid cytokeratin staining. The application of blue dye was useful for easier identification of the SN but did not allow detection of more SNs. Our preliminary results are extremely encouraging. Considering that at the early stages of breast cancer the likelihood of lymph node metastases is low (20% in our series) and no false negative were reported in this study, we conclude that with SN biopsy axillary lymph node dissection can be avoided, making surgery less aggressive but maintaining accuracy.

Bone marrow imaging in plasma cell dyscrasias: review of 130 cases.

Skeletal radiography, bone and bone marrow scintigraphy have been performed in 130 patients with plasma cell dyscrasias (119 multiple myeloma, 9 MGUS and 2 Waldenström disease). Our results confirm: 1) that radiography is much more sensitive than scintigraphy in the identification of the lesions typical of myeloma, but in the first stage bone scintigraphy and especially bone marrow scintigraphy are more sensitive than x-ray for the detection of regions affected by focal lesions; 2) that bone scintigraphy is of particular value in detecting some abnormalities in specific sites not fully visualized by x-ray; 3) that bone marrow scintigraphy is a valuable diagnostic tool in the early stage of myeloma, especially for evaluating the progression of the disease, because it is able to demonstrate not only focal lesions, but also bone marrow expansion. We believe that bone marrow scintigraphy may be a useful technique in the early diagnosis and follow-up of multiple myeloma, particularly in the detection of unusual forms (i.e., "smouldering" myeloma), but it remains only an "additional" technique for bone imaging.

[Bone marrow scintigraphy in multiple myeloma. A comparison with bone scintigraphy and skeletal radiology]. / La scintigrafia midollare nel mieloma multiplo. Confronto con la scintigrafia ossea e la radiologia scheletrica.

The radiographic patterns of the skeleton of 73 patients affected by multiple myeloma (MM) were compared to the correspondent scintigraphic findings. Whole body scans were performed using 99m Tc-diphosphonates (bone scintigraphy), and 99m Tc-microcolloids (bone marrow scintigraphy). The results indicate that: a) radiography is more sensitive and accurate than scintigraphy in detecting typical myeloma-related bone lesions; b) bone scintigraphy is useful in detecting alterations in particular locations--i.e., sternum, ribs, scapulae, etc.--which are difficult to demonstrate by plain X-rays; moreover, the recovery of the fractures can be visualized; c) bone marrow scintigraphy is employed to demonstrate the presence of marrow expansion, of cold/hot spots, and relative marrow uptake, related to phagocytic activity. Since in adult men red marrow is confined to the epiphysis of long bones and to the spine, all the diseases affecting bone marrow cause medullary expansion/reduction, which are both easily detected by specific radiopharmaceuticals. The peripheral expansion is clearly documented especially in distal humeri and femora since marrow uptake is included, in healthy adults, in the axial and proximal appendicular skeleton. In spite of its yielding unique information, bone marrow scintigraphy remains an additional technique of bone scan, because of its low diagnostic accuracy.

[Radioisotope evaluation of splenic hemocatheretic activity in a group of thalassemic patients after embolization]. / Valutazione radioisotopica dell'attività emocateretica splenica in un gruppo di pazienti talassemici sottoposti ad embolizzazione.

Seven patients with thalassemia major underwent splenic embolization in order to assess splenic mass and function before and after treatment. Red blood cells, marked "in vitro" and chemically denatured with BMHP were also used to assess the blood parameters related to splenic function i.e. pretransfusional haemoglobin (Nb) and mean blood consumption (BC). The results show a statistically significant difference (p less than 0.01) for Hb and erythrocyte clearance before and after embolization. Before embolization no statistically significant correlations were found between the parameters examined, whereas after embolization there was a linear correlation at the limit of significance between BC and clearance half-time. The radionuclide method is proposed as safe and reproducible. Unlike blood chemical tests it also provides immediate information on the effects of embolization and a reliable parameter for follow-up.

[Serum level of the tumor marker CA 125 in ovarian pathology]. / Concentrazione sierica del marker tumorale CA-125 nella patologia ovarica.

The tumor marker CA-125 is an embryonal glycoprotein detectable in tissues derived from celomatic epithelium. Serum CA-125 was determined by RIA in 66 patients with various ovarian pathologies (16 malignant at stage III-IV and 50 benign). Six patients with ovarian carcinoma were monitored during the first week after surgery and chemotherapy for a total of 150 days of treatment. We observed that CA-125 serum level is consistently above the normal range (greater than 35 U/ml) in all malignant diseases. In benign pathology, levels above the normal were found to be represented almost exclusively by ovarian endometriosis. Furthermore, the results demonstrate that chemotherapy alone is capable of lowering CA-125 serum levels. This tumor marker may be of great advantage in diagnosis and follow-up of ovarian malignancy.

[Value and limitations of scintigraphy of the hand in rheumatoid arthritis]. / Valore e limiti della scintigrafia della mano in corso di artrite reumatoide.

99mTc-polyphosphate joint imaging of the hand has been performed in 18 patients, with evidence of inflammatory joint disease, but without any significant radiographic lesions, which might be related to rheumatoid arthritis. The hand scans were compared to clinical and radiographic data. An year after, the same subjects were re-examined, with both the radionuclide imaging and radiography. Scintigraphy has been shown to be significantly more sensitive for detecting inflammatory joint disease than x-ray, especially in the early stage of rheumatoid arthritis. Although radionuclide imaging is non specific (activity is increased also in osteoarthritis, trauma, metabolic bone disease, infarction, etc.). Radiography is highly specific but relatively non sensitive.

[Comparison between traditional skeletal radiography and total body bone scintigraphy in the diagnosis of multiple myeloma]. / Confronto tra la radiologia scheletrica tradizionale e la scintigrafia ossea total body nella diagnosi di mieloma multiplo.

28 patients with multiple myeloma were examined by skeletal x-ray and 99Tcm-diphosphonate bone scan. Using both techniques, a total of 70 myelomatous bone lesions was found in 13 (46,5%) of the 28 patients: 69 bone lesions were detected by radiography and 33 by radionuclide imaging. Results indicate that x-ray is superior to bone scan, approximately twice, in detecting myeloma-related bone lesions. The low sensitivity of bone scan in myeloma can most likely be explained by the particular nature of myelomatous bone lesions. Multiple myeloma is almost always osteolytic, with very little new bone formation and extensive osteoclast activity related to osteoclast activating factor, whereas skeletal uptake of 99Tcm-diphosphonate seems to be related mainly to osteoblastic process. An exception to this general finding is the rib fractures, in which the two methods are equally reliable. These findings suggest that radiography is the method of first choice in obtaining a skeletal survey in patients with multiple myeloma.

[Determination of cerebral blood flow using non-diffusible tracers]. / Determinazione del flusso ematico cerebrale con traccianti non diffusibili.

A program for the evaluation of cerebral blood flow based on the analysis of the time activity curves is presented. The method is based on the Meier and Zierler formula, applying the partition coefficents suggested by Lassen et al. for the corrections deriving from the use of non-diffusible indicators (99Tcm-DTPA). Particular attention is given to the smoothing of the time-activity curve (using Legendre's polynomials) and to the correction function for reflux. The computation procedures and their validity is discussed.

[Cholangioscintigraphy in diagnosing biliary atresia]. / La colangioscintigrafia nella diagnosi di atresia delle vie biliari.

The authors present five cases of suspected congenital biliary atresia. In four cases cholescintigraphy with 99Tcm-HIDA allowed a safe preoperative diagnosis, confirmed at operation. Therefore this procedure most be considered essential in the diagnosis of congenital jaundice and in the postoperative evaluation of hepatic-porto-enterostomy function.

[Scintiscanning with technetium-99m pertechnetate in the diagnosis of Meckel's diverticulum]. / La scintigrafia con tecnezio99m pertecnetato nella diagnosi di diverticolo di Meckel.

Personal experience with technetium99m pertecnetate scanning in the diagnosis of Meckel's diverticulum is reported. The data reported indicate that the scan can be considered positive when the lower right quadrant of the abdomen shows a definite accumulation of radioactivity. Of 12 children examined, 4 responses were positive. These 4 patients were submitted to surgery and this confirmed the presence of Meckel's diverticulum containing gastric mucosa, and of an ulcer in the adjacent ileal mucosa. After discussing the clinical value of the investigation and having examined the problem of false positives and false negatives, in relation to reported data, it is concluded that scanning with technetium has a vital role to play in the diagnosis of haemorrhage due to Meckel's diverticulum.

A radiopharmaceutical in the diagnosis of congenital biliary atresia.

Diethyl-HIDA, a new hepatobiliary radiopharmaceutical labeled with 99mTc, was used in the preoperative diagnosis of biliary atresia and in the postoperative evaluation of hepatic-porto-enterostomy function. The good results obtained in the four first cases suggest extensive use of the method, with the aim of a more precocious and more attendable diagnosis.

A 3,3',5'-triiodothyronine (reverse T3) radioimmunoassay.

In this paper are reported the results obtained by a simple, reproducible and sensitive rT3 RIA, in unextracted serum, using the PEG separation technique. The linear correlation coefficient of the results obtained from extracted and unextracted sera, in a population of 60 adults and 35 child controls was 0.984, with a minimal spread of the data.

Preoperative diagnosis of Meckel's diverticulum with 99mTc-pertechnetate.

99mTc-pertechnetate scintigraphy of the digestive tract was performed on 4 children with intestinal bleeding. Two of them showed a focal uptake in the right lower abdominal quadrant and a diagnosis of bleeding Meckel's diverticulum was confirmed by surgery. This procedure being easy to perform, non-invasive and remunerative, should be systematically applied in paediatric intestinal bleeding.