Luciano Feggi

Clinical and Therapeutic Importance of Sentinel Node Biopsy of the Internal Mammary Chain in Patients with Breast Cancer: A Single-Center Study with Long-Term Follow-Up

BackgroundWe evaluated the incidence of sentinel lymph nodes (SLNs) in the internal mammary chain, calculated the lymphoscintigraphy and surgical detection rates, and evaluated the clinical effect on staging and the therapeutic approach in patients with breast cancer.MethodsThe study involved 741 women diagnosed with breast cancer eligible for the SLN technique. Lymphoscintigraphy was performed on the day before the operation by peritumoral injection of 99mTc-labeled nanocolloid. During the operation, a gamma probe was used to detect the SLN, which was then removed.ResultsA total of 719 SLNs were found in the axillary chain and 72 in the internal mammary chain. Preoperative lymphoscintigraphy showed 107 hot spots in the internal mammary chain, but only 72 SLNs in 65 patients were identified by the gamma probe and then removed with no complications. Of these 65 patients, 10 had a positive internal mammary chain SLN on final pathologic examination, whereas 55 patients had ≥1 negative SLNs on final pathologic analysis. Thirty-five (53%) of 65 patients had also an axillary SLN, but only 5 patients (8%) had a positive SLN on pathologic analysis.ConclusionsEvaluation of the SLNs in the internal mammary chain may provide more accurate staging in breast cancer patients. If an internal mammary sampling is not performed, patients may be understaged. This technique may allow better selection of those patients who will be submitted to adjuvant locoregional radiotherapy.

Whole-Body Biodistribution and Radiation Dosimetry of the New Cardiac Tracer 99mTc-N-DBODC

Our purpose was to evaluate the safety profile and biodistribution behavior in healthy human volunteers of the new myocardial perfusion tracer bis[(dimethoxypropylphosphanyl)ethyl]ethoxyethylamine N,N′-bis(ethoxyethyl)dithiocarbamato nitrido technetium(V) (99mTc-N-DBODC). Methods: Ten healthy male volunteers were injected with 99mTc-N-DBODC under both stress and rest conditions. Anterior and posterior planar γ-camera images were collected at 5, 30, 60, 240, and 1,440 min after injection, with organ uptake quantified by region-of-interest analysis. Tracer kinetics in body fluids were determined by collecting blood and urine samples at different time points. Results: After injection, 99mTc-N-DBODC showed significant accumulation in the myocardium and prolonged retention. Under rest conditions, uptake in the heart, lungs, and liver at 5 min after injection was 1.67% ± 0.13%, 1.16% ± 0.07%, and 10.85% ± 1.72%, respectively, of administered activity. Under stress conditions, heart uptake was significantly higher (2.07% ± 0.22%). Radioactivity in the liver decreased to 3.64% ± 0.98% and 2.37% ± 0.48% at 60 and 240 min, respectively, after injection. This rapid liver clearance led to favorable heart-to-liver ratios, reaching values of 0.74 ± 0.13 at rest and 1.26 ± 0.28 during exercise 60 min after tracer administration. Radiation dose estimates were comparable to those obtained with other myocardial perfusion cationic compounds. Conclusion: The high uptake in the myocardium and the fast liver washout of 99mTc-N-DBODC will allow SPECT images of the left ventricle to be acquired early and with excellent quality.

Primary Breast Cancer Features Can Predict Additional Lymph Node Involvement in Patients with Sentinel Node Micrometastases

ObjectiveThe aim of this retrospective study was to identify biological features of primary breast cancer from which to predict the presence of further axillary involvement in patients bearing micrometastases in the sentinel lymph node (SLN).MethodsFrom a starting group of 690 patients, we isolated patients with micrometastases in the SLN. Those patients were classified according to the presence/absence of further metastases in nonsentinel lymph nodes (NSLNs). We examined primary tumor features to identify any relevant difference. Analysis of primary tumors evaluated histology, tumor size, lymphovascular invasion, mitotic index (Mib-1), estrogen and progesterone receptor status (ER/PR status), C-erb B-2 (HER-2/neu) expression and amplification, and p53 expression. Chi square analysis for statistical significance was applied.ResultsOf the original 690 patients, 296 showed some kind of metastases in the SLN; 238 patients had gross metastases in the SLN. After axillary lymph node dissection (ALND), 102 patients (43%) had NSLNs with metastases, and 136 (57%) had negative axillary non-sentinel nodes. Another 58 patients harbored solitary micrometastases in the SLN. After ALND, 8 (14%) patients had further NSLN involvement, and 50 (86%) had negative axillary nodes.ConclusionsAnalysis of the primary breast lesion in patients with micrometastatic SLN and metastatic NSLNs revealed the presence of lymphovascular invasion, Mib-1 index > 10%, and tumor size > 2 cm. Patients without lymphovascular invasion, Mib-1 < 10% and T size < 2 cm could avoid further ALND.

Sentinel node biopsy in the evaluation of the internal mammary node chain in patients with breast cancer.

Aims and Background In patients with breast cancer the presence of internal mammary chain (IMC) metastases changes tumor staging, and the occurrence of IMC drainage is quite common in breast cancer. Nevertheless, IMC dissection is not a routine procedure in modern surgical approaches towards breast cancer. We therefore need minimally invasive techniques for accurate assessment of the IMC nodal basin. The aim of this study was to investigate whether sentinel node biopsy (SLNB) could offer a solution. Methods and Study Design From November 1997 to June 2001 143 female patients who were eligible for breast cancer surgery were included in the study. All patients had T1 breast cancer and clinically negative axillae. Patients were submitted to preoperative lymphoscintigraphy with subsequent SLNB. We used a 99m-technetium nanocolloid tracer (Nanocoll®) that was injected peritumorally so as to have about 10 MBq of radioactivity at the time of surgery. Scintigraphy was performed about 17 hours after tracer administration. During surgery, lymphoscintigraphic imaging and a gamma ray detection probe were used to locate the sentinel node. Histological examination after embedding in paraffin was usually requested and multilevel sectioning of the sentinel node (SLN) was performed, with hematoxylin and eosin staining and immunohistochemistry. Results Preoperative lymphoscintigraphy localized SLNs in the IMC basin in 27 of 143 patients (18.9%). Harvesting of IMC-SLNs based on lymphoscintigraphy results was successful in 20 of 27 patients (74.1 %). Histological examination revealed micrometastases in four of the 20 harvested nodes. One of these patients showed no axillary drainage and no axillary lymph node dissection was therefore performed. In the remaining three patients also axillary SLNs were harvested, which turned out be free from metastatic involvement. Conclusions In our experience lymphoscintigraphy with SLNB was an accurate method to detect IMC metastases in patients with breast cancer. We recommend peritumoral tracer injection and a reasonable interval between injection and scintigraphy. IMC-SLN biopsy did not result in any serious additional complications or morbidity. In our study this approach led to improved cancer staging: four of 20 harvested IMC-SLNs proved to be micrometastatic. None of these four patients had metastatic axillary SLNs. Exclusive drainage to the IMC is present in only a small number of breast cancer patients, and our results suggest that it is possible to avoid unnecessary axillary node dissection in such cases.

Prognostic and therapeutic impact of sentinel node micrometastasis in patients with invasive breast cancer.

Aims and Background Locoregional lymph node status is one of the most important prognostic factors determining the need for adjuvant chemotherapy in patients with breast cancer. Many authors have reported that micrometastases were not detected by routine sectioning of lymph nodes but were identified by multiple sectioning and additional staining. Among lymph node-negative patients 15-20% had an unfavorable outcome at five years from primary surgery. Sentinel lymph node (SLN) biopsy is an accurate technique for identifying axillary metastases because the pathologist utilizes hematoxylin-eosin (H-E) staining together with immunohistochemistry (IH) to examine all lymph node sections. Sentinel node micrometastasis has therefore become an important tumor-related prognostic factor. Methods and Study Design From November 1997 to October 2001 we examined in 210 patients the pathological features of primary breast lesions and SLN metastases and we correlated these with the tumor status of non-SLNs in the same axillary basin. We applied IH examination to both SLNs and non-SLNs of patients who were negative for metastasis by standard H-E examination. Results In this study lymph node staging was based on SLN findings, primary tumor size, and the presence of peritumoral lymphovascular invasion (LVI). We found 18 SLN micrometastases (9%) in 210 patients and one of these (5.5% of patients with SLN micrometastasis) also had one non-SLN metastasis: this patient had LVI and a larger primary tumor than patients with SLN micrometastasis without non-SLN metastasis. We also found 24 SLN macrometastases (11.5%) in 210 patients and 13 of these (54.2% of patients with SLN macrometastases) had one or more non-SLN metastases. Conclusions According to the results reported in the literature, tumor cells are unlikely to be found in non-SLNs when the primary lesion is small and SLN involvement micrometastatic (5.5% in our experience, 7% in Giulianos). Our findings suggest that axillary lymph node dissection may not be necessary in patients with SLN micrometastasis from T1 lesions.

Pitfalls in scintigraphic detection of neuroendocrine tumours

We report 4 cases of abnormal results using iodine-123 metaiodobenzylguanidine (123I-mIBG) or technetium-99m (V) dimercaptosuccinic acid (99mTc(V)-DMSA) scintigraphy in the diagnosis and follow-up of presumed neuroendocrine tumours. The present series consisted of 2 false-positive cases (1 adenomatous polyp of the caecum with mIBG and 1 follicular adenoma of the thyroid with DMSA) and 2 cases of anomalous uptake of (V)-DMSA in a non-neuroendocrine tissue.

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.

Radio-guided selective compartment neck dissection improves staging in papillary thyroid carcinoma: A prospective study on 345 patients with a 3-year follow-up

BACKGROUND Prospective uncontrolled study to investigate in papillary thyroid carcinoma (PTC) patients: (1) Distribution of lymph node metastases within the neck compartments, (2) factors predicting lymph nodes metastases, and (3) disease recurrence after thyroidectomy associated with radio-guided selective compartment neck dissection (RSCND). METHODS We studied 345 consecutive PTC patients operated on between February 2004 and October 2011 at the S. Anna University Hospital, Ferrara (Italy). Patients with cervical lymph node metastases on preoperative ultrasonography and fine needle aspiration cytology were excluded. All patients underwent total thyroidectomy associated with SLN identification followed by RSCND in the SLN compartment, without SLN frozen section. RESULTS In patients with lymph node metastases, metastatic nodes were not in the central neck compartment in 22.6% of the cases. The presence of infiltrating or multifocal PTC was a predicting factor for lymph nodes metastases. The median follow-up was 35.5 months. RSCND was associated with a false-negative rate of 1.1%, a persistent disease rate of 0.6%, and a recurrent disease rate of 0.9%. The permanent dysphonia rate was 1.3%. CONCLUSION RSCND associated with total thyroidectomy may improve: (1) the locoregional lymph node staging, and (2) the identification of the site of lymphatic drainage within the neck compartments. Thus, considering the high false-negative rate of sentinel lymph node biopsy (SLNB), a radio-guided technique in PTC patients may guide the lymphadenectomy (ie, RSCND) to increase the metastatic yield and improve staging of the disease rather than avoid prophylactic lymphadenectomy (ie, SLNB).

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 <1000 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.

Radio-guided surgery in recurrent renal hyperparathyroidism: Report of a case

It has been demonstrated that radio‐guided surgery offers several advantages in treating primary hyperparathyroidism. Even if it is considered less helpful in renal hyperparathyroidism, it could be of tremendous advantage in the treatment of persistent or recurrent secondary hyperparathyroidism.