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Biomedical subjects

Giovanni Paganelli

Publications and source records attributed to Giovanni Paganelli.

At least 37 records · Page 2Linked to original sources
PubMed2005

Conservative treatment of breast cancer: its evolution.

BACKGROUND: Over recent decades, breast carcinoma surgery has witnessed a considerable evolution. The extent of surgery undertaken has progressively reduced, leading to less disfigurement and a significant improvement in quality of life, thereby offering women considerable motivation to seek early diagnosis. From an oncological perspective, outcome was found to be equally effective, and this key observation provided us with significant impetus to investigate the effects of reducing the radiotherapy field. PATIENTS AND METHODS: We present the achievements made so far in the conservative treatment of breast carcinoma, based on experiences at the European Institute of Oncology in Milan and, prior to 1994, at the Milan Cancer Institute. RESULTS AND DISCUSSION: Conservative surgery of breast carcinoma, both in the breast and in the axillary nodes, has yielded very good results in terms of overall survival and impact on quality of life. The reduction of the radiation field, conducted in our Institute by means of electron intraoperative radiotherapy (ELIOT), is currently the subject of evaluation via a randomised trial.

Breast Neoplasms↗
PubMed2005

Intratumoral delivery of mitoxantrone in association with 90-Y radioimmunotherapy (RIT) in recurrent glioblastoma.

Twenty-six recurrent Glioblastoma (rGBM) patients sequentially treated at the National Neurological Institute 'C Besta' were enrolled for a second surgery in order to remove recurrent tumor and to place an Ommaya reservoire to allow local delivery of chemotherapy and local pre-targeted radio-immunotherapy (RIT). All patients had partial tumor resection and 75% of them had a residual tumor mass after exeresis larger than 2 cm. After surgery all patients were managed with a second line systemic chemotherapy (PCV). Moreover the protocol scheduled two cycles of local RIT (90 Yttrium 5- 25 mCi per cycle) with a 10 week interval. Locoregional mitoxantrone chemotherapy was locally delivered as a single dose of 4 mg every 20 days. Responses to treatment were assessed by monthly neurological examination and by MRI or contrast-enhanced CT scan performed every 2 months. For the whole group of patients the PFS after second surgery at 6 and 12 months was 61% and 22%, respectively and survival after recurrence at 6, 12 and 18 months was 80%, 53% and 42%, respectively. Neither major side effects occurred systemically nor related on the place of local injections. The percentage of long-term survivors was very high: 42% of patients were still alive at 18 months. We stress the concept that the combined treatments could be more effective if delivered into a smaller residual tumor mass and probably in an adjuvant setting, before tumour recurrence.

Adolescent↗
PubMed2005

Sentinel node biopsy in breast cancer: early results in 953 patients with negative sentinel node biopsy and no axillary dissection.

Sentinel node biopsy in patients with breast carcinoma accurately predicts the axillary nodal status. However, in some 6% of patients with negative sentinel nodes the remaining axillary nodes harbour metastases. Our purpose was to observe a large number of patients who did not undergo an axillary dissection after a negative sentinel node biopsy for the appearance of overt axillary metastases. 953 patients treated from 1996 to 2000, with negative sentinel nodes not submitted to axillary dissection, were followed-up to 7 years, with a median follow-up of 38 months. Fifty-five unfavourable events occurred among the 953 patients, 37 (4%) related to the primary breast carcinoma. Three cases of overt axillary metastases were found: they received total axillary dissection and are presently alive and well. The 5 year overall survival rate of the whole series was 98%. Patients with negative sentinel node biopsies not submitted to axillary dissection show during follow-up a rate of overt axillary metastases that is lower than that expected.

Adult↗
PubMed2005

Predicting the risk for additional axillary metastases in patients with breast carcinoma and positive sentinel lymph node biopsy.

OBJECTIVE: To assess whether the risk for nonsentinel node metastases may be predicted, thus sparing a subgroup of patients with breast carcinoma and a positive sentinel lymph node (SLN) biopsy completion axillary lymph node dissection (ALND). SUMMARY BACKGROUND DATA: The SLN is the only involved axillary lymph node in the majority of the patients undergoing ALND for a positive SLN biopsy. A model to predict the status of nonsentinel axillary lymph nodes could help tailor surgical therapy to those patients most likely to benefit from completion ALND. METHODS: All the axillary sentinel and nonsentinel lymph nodes of 1228 patients were reviewed histologically and reclassified according to the current TNM classification of malignant tumors as bearing isolated tumor cells only, micrometastases, or (macro)metastases. The prevalence of metastases in nonsentinel lymph nodes was correlated to the type of SLN involvement and the size of the metastasis, the number of affected SLNs, and the prospectively collected clinicopathologic variables of the primary tumors. RESULTS: In multivariate analysis, further axillary involvement was significantly associated with the type and size of SLN metastases, the number of affected SLNs, and the occurrence of peritumoral vascular invasion in the primary tumor. A predictive model based on the characteristics most strongly associated with nonsentinel node metastases was able to identify subgroups of patients at significantly different risk for further axillary involvement. CONCLUSIONS: Patients with the most favorable combination of predictive factors still have no less than 13% risk for nonsentinel lymph node metastases and should be offered completion ALND outside of clinical trials of SLN biopsy without back-up axillary clearing.

Adult↗
PubMed2005

Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs.

A new treatment modality for inoperable or metastasized gastroenteropancreatic tumors is the use of radiolabeled somatostatin analogs. Initial studies with high doses of [(111)In-diethylenetriaminepentaacetic acid (DTPA)(0)]octreotide in patients with metastasized neuroendocrine tumors were encouraging, although partial remissions were uncommon. Another radiolabeled somatostatin analog that is used for peptide receptor radionuclide therapy (PRRT) is [(90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)(0),Tyr(3)]octreotide. Various phase 1 and phase 2 PRRT trials have been performed with this compound. Despite differences in the protocols used, complete and partial remissions in most of the studies with [(90)Y-DOTA(0),Tyr(3)]octreotide were in the same ranges, 10%-30%; these ranges were higher than those obtained with [(111)In-DTPA(0)]octreotide. Treatment with the newest radiolabeled somatostatin analog, [(177)Lu-DOTA(0),Tyr(3)]octreotate, which has a higher affinity for the subtype 2 somatostatin receptor, resulted in complete or partial remissions in 30% of 76 patients. Tumor regression was positively correlated with a high level of uptake on OctreoScan imaging, a limited hepatic tumor mass, and a high Karnofsky performance score. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all (111)In-, (90)Y-, or (177)Lu-labeled somatostatin analogs that have been used for PRRT. The results obtained with [(90)Y-DOTA(0),Tyr(3)]octreotide and [(177)Lu-DOTA(0),Tyr(3)]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the duration of the therapy response for both radiopharmaceuticals is more than 2 y. These data compare favorably with those for the limited number of alternative treatment approaches.

Animals↗
PubMed2004

Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours.

Somatostatin receptors are over-expressed in many tumours, mainly of neuroendocrine origin, thus enabling treatment with somatostatin analogues. Almost a decade of clinical experience of receptor radionuclide therapy with the analogue (90)Y-[DOTA](0)-Tyr(3)-octreotide [(90)Y-DOTATOC] has now been obtained at a few centres of excellence. This review reports on the present state of the art of receptor radionuclide therapy and discusses new perspectives.

Animals↗
PubMed2004

Sentinel node detection in pre-operative axillary staging.

The concept of sentinel lymph node biopsy in breast cancer surgery is based on the fact that the tumour drains in a logical way via the lymphatic system, from the first to upper levels. Since axillary node dissection does not improve the prognosis of patients with breast cancer, sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 patients. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Subdermal or peritumoural injection of small aliquots (and very low activity) of radiotracer is preferred to intratumoural administration, and (99m)Tc-labelled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. The success rate of radioguidance in localising the sentinel lymph node in breast cancer surgery is about 97% in institutions where a high number of procedures are performed, and the success rate of lymphoscintigraphy in sentinel node detection is about 100%. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when necessary, immune staining with anti-cytokeratin antibody. Nowadays, lymphoscintigraphy is a useful procedure in patients with different clinical evidence of breast cancer.

Axilla↗
PubMed2004

Targeted bone marrow radioablation with 153Samarium-lexidronam promotes allogeneic hematopoietic chimerism and donor-specific immunologic hyporesponsiveness.

BACKGROUND: Transplantation tolerance, defined as acceptance of a graft by an otherwise fully immunocompetent host, has been an elusive goal. Although robust tolerance has been achieved by the induction of stable hematopoietic chimerism after bone marrow transplantation, lethal or sublethal radiation conditioning used to induce long-term chimerism precludes its clinical use. We studied whether targeted delivery of radiation to bone marrow could allow for bone marrow cell (BMC) engraftment, chimerism, and donor-specific tolerance in the absence of the side effects associated with external irradiation. METHODS: We administered a radioactive bone-seeking compound (Samarium-Lexidronam, Quadramet, Berlex Laboratories, Wayne, NJ) together with transient T-cell costimulatory blockade to recipient mice. Allogeneic BMCs were given 7 or 14 days after preconditioning. Costimulatory blockade was obtained by the use of an anti-CD154 antibody for 4 weeks. Chimerism was assessed by flow cytometry. Mice then received donor-specific and third-party skin grafts. Graft survival was analyzed with mechanisms of donor-specific hyporesponsiveness. RESULTS: High levels of stable chimerism across an allogeneic barrier were achieved in mice by a single administration of Samarium-Lexidronam, transient T-cell costimulatory blockade, and BMC transplantation. A large percentage of chimeric animals retained donor-derived skin grafts for more than 120 days without requiring additional immunosuppression, suggesting that harsh cytotoxic preconditioning is not necessary to achieve stable chimerism and donor specific hyporesponsiveness. Analysis of the T-cell repertoire in chimeras indicates T-cell deletional mechanisms. CONCLUSIONS: These data broaden the potential use of BMC transplantation for tolerance induction and argue for its potential in treating autoimmune diseases.

Animals↗
PubMed2004

Lymphoscintigraphic and intraoperative detection of the sentinel lymph node in breast cancer patients: the nuclear medicine perspective.

The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94-97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T(1a-b) breast cancers, with size < or =1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients.

Breast Neoplasms↗
PubMed2004

Radioimmunotherapy in advanced ovarian cancer: is there a role for pre-targeting with (90)Y-biotin?

OBJECTIVES: Despite recent advances in the management of ovarian cancer, this tumor remains the leading cause of death among gynecologic malignancies. Moreover, advanced ovarian carcinoma has a poor prognosis, thus requiring new therapeutic modalities. Previous studies have indicated a survival advantage for ovarian cancer patients (pts) treated with radioimmunotherapy (RIT). Pre-targeting RIT, based on the avidin-biotin system, has been the objective of previous studies performed by our group. PATIENTS AND METHODS: In the present study, the therapeutic efficacy and toxicity of RIT in 38 advanced ovarian cancer patients have been retrospectively evaluated. RIT was performed according to the following three-step protocol: biotinylated monoclonal antibodies (MoAb) and avidin were intraperitoneally (ip) injected (1st and 2nd step), and 12-18 h later (90)Y-labeled biotin either iv or ip was injected as 3rd step. Sixteen out of 38 patients were treated by intraperitoneal injection only, whereas other 22 pts received the combined treatment (ip + iv); the dose range was 10-100 mCi of (90)Y-biotin. RESULTS: Both of the two therapy regimens were well tolerated; no acute side effects were observed. Two patients (5%) showed temporary hematological grade III-IV toxicity. As regards to the therapeutic efficacy, in the ip group we observed 6% of objective tumor reduction, stabilization in 31% of pts, and progression in 50%. In the group of combined treatment, 9% of patients achieved objective responses, 32% showed stable disease, and 41% had a progression. CONCLUSIONS: These data show the excellent tolerability (maximum tolerated dose (MTD) has not been determined yet) and the potential therapeutic role of RIT in advanced ovarian cancer. Patients with minimal residual disease would probably take the best advantages of RIT with (90)Y-biotin (electrons). These data warrant further prospective studies.

Adult↗
PubMed2004

Receptor radionuclide therapy with 90Y-DOTATOC in patients with medullary thyroid carcinomas.

UNLABELLED: Metastatic medullary thyroid cancer (MTC) shows a progressive course. Surgery is the only curative treatment. In advanced disease, chemo- and radiotherapy show poor results. Newly developed somatostatin analogue [DOTA0,Tyr3]octreotide (DOTATOC) labeled to 90Y is administered in patients with endocrine tumors expressing somatostatin receptors, like MTC. Preliminary studies demonstrated that 90Y-DOTATOC could be safely administered, resulting in objective responses in 27% of patients. AIMS: To evaluate the efficacy of 90Y-DOTATOC therapy in metastatic MTC patients with positive OctreoScan, progressing after conventional treatments. Twenty-one patients were retrospectively evaluated after therapy, receiving 7.5-19.2 GBq in 2-8 cycles. RESULTS: Two patients (10%) obtained a complete response (CR), as evaluated by CT, MRI and/or ultrasound, while a stabilization of disease (SD) was observed in 12 patients (57%); seven patients (33%) did not respond to therapy. The duration of the response ranged between 3-40 months. Using biochemical parameters (calcitonin and CEA), a complete response was observed in one patient (5%), while partial response in five patients (24%) and stabilization in three patients (14%). Twelve patients had progression (57%). Complete responses were observed in patients with lower tumor burden and calcitonin values at the time of the enrollment. CONCLUSIONS: This retrospective analysis is consistent with the literature, regarding a low response rate in medullary thyroid cancers treated with 90Y-DOTATOC. Patients with smaller tumors and higher uptake of the radiopeptide tended to respond better. Studies with 90Y-DOTATOC administered in earlier phases of the disease will help to evaluate the ability of this treatment to enhance survival. New more specific peptides and new isotopes will also represent the key of a better treatment of MTC.

Adult↗
PubMed2004

Clinical utility of 99mTc-Sestamibi scintimammography in the management of equivocal breast lesions.

The aim of this study was to assess the utility of 99mTc-sestamibi scintimammography (SM) in patients with suspected primary or recurrent breast cancer. Forty-four (44) breast lesions (17 with suspected recurrence of disease) in 40 patients were included into the study. In these patients, the results of conventional diagnostic methods were equivocal or inconclusive. Twenty-one (21) lesions were palpable and 23 lesions were not. Histological examinations performed during the follow-up revealed malignancy in 24 specimens. SM correctly identified 21 of them, as well as 12 true negatives. There were 8 false-positive studies; therefore, the sensitivity of SM was 87.5%, specificity was 60%, positive predictive value (PPV) was 72.4%, and the negative predictive value (NPV) was 80%. The sensitivity in palpable lesions was 100%; three (3) false negatives, 1 recurrence, and 2 cancers, all of them nonpalpable. In conclusion, SM is useful in equivocal palpable lesions for resolving diagnostic uncertainty after conventional examination, and can limit the number of surgical interventions for benign disease. However, its use in nonpalpable tumors is not recommended.

Adult↗
PubMed2004

Sentinel node biopsy in male breast cancer.

OBJECTIVE: Male breast cancer is a rare disease and axillary status is the most important prognostic indicator. Lymphoscintigraphy associated with gamma-probe guided surgery has been proved to reliably detect sentinel nodes in female patients with breast cancer. This study evaluates the feasibility of the surgical identification of sentinel node by using lymphoscintigraphy and a gamma-detecting probe in male patients, in order to select subjects who would be suitable for complete axillary lymphadenectomy. METHODS: Colloid human albumin labelled with 99Tc was administered to 18 male patients with breast cancer and clinically negative axillary lymph nodes. Lymphoscintigraphy was performed the day before surgery. An intraoperative gamma-detecting probe was used to identify sentinel nodes during surgery. RESULTS: Lymphoscintigraphy and biopsy of the sentinel node were successful in all cases. A total of 20 sentinel nodes were removed. Pathological examinations showed 11 infiltrating ductal carcinomas, two intraductal carcinomas and five intracystic papillary carcinomas. Six patients (33%) had positive sentinel node (micrometastases were found in three patients). These patients underwent axillary dissection; in five of them (83%) the sentinel node was the only positive node. Twelve patients (67%) showed negative sentinel nodes; in all of them no further surgical treatments were planned. CONCLUSIONS: As in women, lymphoscintigraphy and sentinel node biopsy under the guidance of a gamma-detecting probe proved to be an easy method for the detection of sentinel nodes in male breast carcinoma. In male patients with early stage cancer, sentinel node biopsy might represent the standard surgical procedure in order to avoid unnecessary morbidity after surgery, preserving accurate staging of the disease in the axilla.

Aged↗
PubMed2003

A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer.

BACKGROUND: Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer, the efficacy and safety of sentinel-node biopsy require validation. METHODS: From March 1998 to December 1999, we randomly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection (the axillary-dissection group) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases (the sentinel-node group). RESULTS: The number of sentinel nodes found was the same in the two groups. A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group (32.3 percent), and in 92 of the 259 patients in the sentinel-node group (35.5 percent). In the axillary-dissection group, the overall accuracy of the sentinel-node status was 96.9 percent, the sensitivity 91.2 percent, and the specificity 100 percent. There was less pain and better arm mobility in the patients who underwent sentinel-node biopsy only than in those who also underwent axillary dissection. There were 15 events associated with breast cancer in the axillary-dissection group and 10 such events in the sentinel-node group. Among the 167 patients who did not undergo axillary dissection, there were no cases of overt axillary metastasis during follow-up. CONCLUSIONS: Sentinel-node biopsy is a safe and accurate method of screening the axillary nodes for metastasis in women with a small breast cancer.

Adult↗
PubMed2003

A new biotin derivative-DOTA conjugate as a candidate for pretargeted diagnosis and therapy of tumors.

The synthesis of a new biotin derivative, the (CO) reduced N-aminohexyl biotinamido derivative, designed to be serum biotinidase resistant, and its conjugation to the chelator DOTA through an amide bond at one of the four carboxymethyl chains are described. The (90)Y-labeled conjugate was able to bind avidin at different Av/conjugate molar ratios with good results. The preclinical results indicate that this new biotin-DOTA conjugate is a good candidate for pretargeted diagnosis and therapy of tumors.

Antineoplastic Agents↗
PubMed2003

Characterization of poultry egg-white avidins and their potential as a tool in pretargeting cancer treatment.

Chicken avidin and bacterial streptavidin are proteins used in a wide variety of applications in the life sciences due to their strong affinity for biotin. A new and promising use for them is in medical pretargeting cancer treatments. However, their pharmacokinetics and immunological properties are not always optimal, thereby limiting their use in these applications. To search for potentially beneficial new candidates, we screened egg white from four different poultry species for avidin. Avidin proteins, isolated from the duck, goose, ostrich and turkey, showed a similar tetrameric structure, similar glycosylation and stability against both temperature and proteolytic activity of proteinase K as chicken avidin. Biotin-binding properties of these avidins, measured using IAsys optical biosensor, were similar to those found in avidin from the chicken. Three of these novel avidins, however, showed different immunological cross-reactivities when compared with chicken avidin. The patient sera responses to duck, goose and ostrich avidins were also lower than those observed for chicken and turkey avidins. Our findings suggest that the use of these proteins offers advantages over chicken avidin and bacterial streptavidin in pretargeting applications.

Animals↗