Structural, pathophysiological and clinical aspects of diagnostic imaging in breast recurrence: the breast after treatment.

In the last decades the outcome of women with breast cancer has been significantly modified partially as a result of screening which has facilitated earlier diagnosis and consequently allowed a conservative surgical approach. Today diagnostic imaging is generally based on Mammography (Mx), with a minor role for ultrasounds and Magnetic Resonance (MR). In this scenario, dominated by morphostructural techniques, there is a secondary role for radionuclide procedures both using gamma emitters or Positron Emission Tomography (PET) with F-18 Fluorodeoxyglucose (FDG) or other radiotracers beyond FDG. After surgery and allied treatments, including radiotherapy, the diagnosis of breast recurrence has become a difficult challenge, because of the several factors simultaneously and/or sequentially involved. In the diagnosis of local recurrence, Mx remains the first diagnostic step together with a clinical visit, as alternative approaches yield more unsatisfactory results. Nevertheless as Mx is affected by a low sensitivity, it is important to better evaluate the capabilities of functional imaging utilizing MR and Nuclear Medicine, to allow an earlier and more accurate detection. In this paper we analyze structural, pathophysiological and the clinical background to diagnostic imaging in local breast recurrence to better understand basic problems, to facilitate more effective utilization of diagnostic tools.

Questions and answers: what can be said by diagnostic imaging in neuroendocrine tumors?

The neuroendocrine tumors (NET) of the gastro-entero-pancreatic area (GEP) represent a heterogeneous group of malignancies from the histologic, clinico-laboratoristic (functioning and non-functioning variants), and therapeutic point of view. It is an issue becoming more frequent for the diagnostic imager, being radiologist as well as nuclear physician. Imaging (together with biopsy) plays a key role in the diagnostic assessment and staging (including grading and prognostic definition), in evaluating response to treatment, and in follow-up of GEP-NET. Multislice computed tomography (MSCT), octreoscan and PET-CT are the most widely diffuse and accurate imaging modalities employed in this setting. Other methods, such as Magnetic Resonance and Endoscopic Ultrasound, may also play a significant role.

Less frequent requests for In-111 pentreotide and its brothers of endocrinological interest.

The somatostatin receptor scintigraphy (SRS), using octreotide radiolabelled with 111In (octreoscan, OCTs), is a consolidated diagnostic procedure in patients with neuroendocrine tumors. A higher accuracy has been demonstrated with single photon emission computed tomography-CT, while a further improvement has been obtained with positron emission tomography (PET)-CT, using somatostatin analogues radiolabeled with 68Ga, significantly increasing the number of detected lesions. Although the well-known presence of an OCTs uptake in many benign diseases, when in an active phase, the application of SRS in these patients did not find any clinical relevance yet. In this paper we discuss two fields of endocrinological interest where SRS could play a clinical role. In patients with Graves exophtalmos, the capability to differentiate between active and non-active disease can be helpful in define prognosis and therapeutic strategies. In patients with endocrine paraneoplastic syndromes (PNS), SRS can help in finding the underlying neoplasm, contributing to its characterization as premise to a therapeutic choice. The possible role of a surgery guided by OCTs is also explained and suggested. The incremental value of PET-CT with Ga-68 peptides is hypothesized to reduce the number of unknown neoplastic lesions frequently present in patients with PNS.

The non tumour uptake of (111)In-octreotide creates new clinical indications in benign diseases, but also in oncology.

The use of somatostatin (SS) analogues in humans takes advantage by the availability of many related chemical forms that can be used for receptor therapy and, after radiolabelling, for diagnostic imaging and radionuclide therapy. The first proposed radiocompound, yet clinically widely diffuse, has been (111)In-octreotide (OCT), followed by positron emission tomography (PET) and beta emitter tracers. The main field of clinical applications is in neuroendocrine tumours (NET), starting by the demonstration of SS receptors (SSR) on the majority of NET, particularly on gastroenteropancreatic (GEP) tumours. Uptake of SS analogues can also be due to a SSR expression on non malignant cells when activated, as lymphocytes, macrophages, fibroblasts , vascular cells. Because of this uptake clinical indications can be found also in active benign diseases, as Grave's ophthalmopathy, rheumatoid arthritis, histiocitosis, sarcoidosis, idiopatic pulmonary fibrosis. Moreover, these cells can also determine the OCT in vivo uptake in tumours non expressing in vitro SSR, as non-snall cell lung cancer (NSCLC). Because of a different kinetic respect to SCLC a differential histotype diagnosis could be obtained. Starting from this premise OCT can also allows radioguided surgery in tumours non expressing SSR. Finally a relevant clinical role can be defined in the a priori recruitment and as marker of therapeutic efficacy in all the therapeutic strategies utilizing SSR, both in malignant and benign diseases.

Is there a role for positron emission tomography imaging in the early evaluation of prostate cancer relapse?

The patient population with a rising prostate specific antigen (PSA) post-therapy with no evidence of disease on standard imaging studies currently represents the second largest group of prostate cancer patients. Little information is still available regarding the specificity and sensitivity of positron emission tomography (PET) tracers in the assessment of early biochemical recurrence. Ideally, PET imaging would allow one to accurately discriminate between local vs nodal vs distant relapse, thus enabling appropriate selection of patients for salvage local therapy. The vast majority of studies show a relatively poor yield of positive scans with PSA values < 4 ng ml(-1). So far, no tracer has been shown to be able to detect local recurrence within the clinically useful 1 ng ml(-1) PSA threshold, clearly limiting the use of PET imaging in the post-surgical setting. Preliminary evidence, however, suggests that 11C-choline PET may be useful in selecting out patients with early biochemical relapse (PSA < 2 ng ml(-1)) who have pelvic nodal oligometastasis potentially amenable to local treatment. The role of PET imaging in prostate cancer is gradually evolving but still remains within the experimental realm. Well-conducted studies comparing the merits of different tracers are needed.

Role of dynamic sentinel node biopsy in penile cancer: our experience.

BACKGROUND AND OBJECTIVES: We report our initial experience with a relatively new technique, the so-called "dynamic sentinel node biopsy", in patients with penile cancer. METHODS: From January 2001 to February 2003, 17 consecutive patients with bilateral, clinically node negative penile cancer were enrolled. Dynamic sentinel node biopsy was followed by local excision of the primary lesion or penile amputation during the same session. Standard inguinal node dissection was performed 4 weeks after the first operation in all the patients. RESULTS: Pre-operative lymphoscintigraphy revealed no sentinel nodes in 1, unilateral sentinel nodes in 5, and bilateral in 11 patients. Metastases were noted in 5 out of 16 patients (31.25%), bilaterally in 3 of them. Among the five patients with sentinel node metastasis, this was the only tumor positive lymph node in one patient. In all cases with negative dynamic sentinel node biopsy, no metastatic nodes were found at the following inguinal node dissection. Therefore, the technique showed a 100% negative predictive value and an 88% sensitivity. CONCLUSIONS: We believe that dynamic sentinel node biopsy is a minimally invasive procedure that can be easily performed. The goal is to offer the possibility of less extensive surgery for selected low risk patients.

[Early evaluation using PET-FDG of the efficiency of neoadjuvant radiochemotherapy treatment in locally advanced neoplasia of the lower rectum]. / Valutazione precoce con PET-FDG della efficacia del trattamento radiochemioterapico neoadiuvante nelle neoplasie del retto inferiore localmente avanzate.

BACKGROUND AND PURPOSE: Preoperative chemoradiation allows downstaging of locally advanced rectal cancer and in selected patients also a sufficient downsizing to ensure sphincter preservation. Selection of patients warranting a preoperative approach is improved by magnetic resonance imaging (MRI) which is able to define the involvement of mesorectal circumferential margin. Similarly it would be crucial to define the response to chemoradiation during the treatment but traditional morphologic imaging techniques may fail in differentiating neoplastic tissue from scarring. PET-FDG has been successfully used in the detection of metastatic colorectal cancer allowing imaging of deposits as small as 0.5 cm and may have a role in evaluating early response to chemoradiation. METHODS: In the present study, in patients with T3-T4 rectal cancer undergoing preoperative chemoradiation PET-FDG and flow cytometry analysis on endoscopic biopsy specimen have been performed before, during and after preoperative chemoradiation. RESULTS: Chemoradiation treatment has been successful in terms of downsizing and downstaging of the tumor. PET-FDG was able to demonstrate local response at only ten-fifteen days after the beginning of neoadjuvant therapy, also identifying non responding patients. CONCLUSIONS: FDG-PET may have a role in defining the response to chemoradiation and modulate the treatments strategy in patients with advanced rectal cancer.

[Immunological imaging using tagged octreotide]. / Imaging immunologico con octreotide marcato.

The diagnostic use of radiolabeled octreotide has shown that somatostatin receptor scintigraphy can be successfully used in various neoplasms with a strictly neuroendocrine derivation, because of a good correlation between in vitro receptor expression and in vivo uptake. Moreover, 111In-Octreotide uptake has been demonstrated in various pathologies owing to the receptorial expression on cell elements such as lymphocytes, fibroblasts and endothelium. Although main diagnostic role is in neuroendocrine tumours, octreotide can be also used to obtain an immunological imaging in other fields. The presence of type 2 receptors on activated lymphocytes has stimulated the use of somatostatin in both the treatment and diagnosis of disease activity in patients with Graves' ophthalmopathy. Somatostatin analogs have been successfully used for the treatment and imaging of various tumours of thymic origin. Our research group has evaluated the possible clinical role of octreotide scintigraphy in paediatric patients with thymic hyperplasia after chemotherapy for lymphoma. Even if not routinely applicable, these approaches offer interesting diagnostic, prognostic and therapeutic prospects.

[Role of somatostatin analogs in the treatment of neuroendocrine tumours]. / Ruolo degli analoghi della somatostatina nella teapia dei tumori neuroendocrini.

Current therapeutic approaches in neuroendocrine tumours include surgery, radiotherapy and polychemotherapy. Different metabolic patterns of neuroendocrine tumours allow the use of a wide range of diagnostic options in nuclear medicine, due to the presence of a wide spectrum of radiotracers electively concentrating in these neoplasms. Nuclear medicine, and in particular 111In Octreotide (OCT) scintigraphy, 123I Methaiodobenzylguanidine (MIBG) and pentavalent 99mTc-DMSA (V-DMSA), together with biohumoral markers, are currently able to locate tumours also not detectable using traditional diagnostic techniques. Somatostatin analogs, such as octreotide have become increasingly important over the years in the treatment of patients with neuroendocrine tumours. At present the therapeutic use of somatostatin analogs can be schematised as 1) pharmacological treatment (with cold octreotide); 2) surgical treatment (radioguided surgery); 3) radiometabolic treatment (with marked octreotide). The development of new synthetic molecules and new radiocompounds will probably open up interesting scenarios in the near future.

Receptor imaging with 111In-pentreotide and 123I-methoxybenzamide, and inhibition tests with octreotide and bromocriptine of mixed growth hormone/prolactin-secreting pituitary tumors.

We have performed pituitary scintigraphy with 111In-pentreotide (OCT), a somatostatin analogue, and with metoxybenzamide (IBZM) by 123I-IBZM in two patients affected by mixed growth hormone/prolactin-secreting pituitary tumors. Short-term growth hormone (GH) inhibition by a single injection of OCT (100 micrograms s.c.), and short-term prolactin (PRL) inhibition by oral administration of 2.5 mg of bromocriptine (BCR), were also performed in both patients. The first patient, a 26 year old man, showed intense tumor uptake of 123I-IBZM scintigraphy, whereas 111In-OCT scintigraphy showed moderate tumor uptake. Five hours after the BCR inhibition test, a fall of 83% in PRL plasma levels (from 8,336 micrograms/L to 1,417 micrograms/L), and of 91.6% in GH plasma levels (from 39.5 micrograms/L to 3.3 micrograms/L) were observed. OCT inhibition test suppressed GH plasma levels from 36 micrograms/L to 3.5 micrograms/L. The patient was submitted to treatment with BCR and OCT. A dramatic shrinkage of the tumor was seen after six months of therapy. The lesion disappeared one year after the start of therapy. The second patient, a 64 year old man, showed intense uptake at 111In-OCT scintigraphy, while 123I-IBZM uptake was not observed. A test dose of BCR resulted in an acute fall of PRL (from 145 micrograms/L to 118 micrograms/L), but not of GH. A test dose of OCT decreased the GH plasma level from 61 micrograms/L to 4.5 micrograms/L. The patient was submitted to treatment with BCR and OCT that resulted in a computed tomography and magnetic resonance imaging decrease of 45% of tumor volume one year after the start of therapy. Our results suggest that both suppression tests with OCT and BCR, and scintigraphic studies in vivo with 123I-IBZM and 111In-OCT can be predictive for the effectiveness of therapies with dopamine agonists and/or SS-analogs in patients with mixed PRL/GH-secreting pituitary tumors. Further studies are required to evaluate the role of suppressive tests in selecting patients for appropriate clinical treatments.