Clinical considerations on sentinel node biopsy in melanoma from an Italian multicentric study on 1,313 patients (SOLISM-IMI).

BACKGROUND: Although widely used for the management of patients with cutaneous melanoma, the sentinel lymph node (SLN) biopsy (SNB) procedure raises several issues. This study was designed to investigate: the predictive factors of SLN status, the false-negative (FN) rate, and patients' prognosis after SNB. PATIENTS AND METHODS: This is an observational, prospective study conducted on a large series of consecutive patients (n = 1,313) enrolled by 23 Italian centers from 2000 through 2002. A commonly shared protocol was adopted for the SNB surgical procedure and the SLN pathological examination. RESULTS: The SLN positive and false-negative (FN) rates were 16.9% and 14.4%, respectively (median follow-up, 4.5 years). At multivariable logistic regression analysis, the frequency of positive SLN increased with increasing Breslow thickness (p < 0.0001) and decreased in patients with melanoma regression (p = 0.024). At the multivariable Cox regression analysis, SLN status was the most important prognostic factor (hazards ratio (HR) = 3.08) for overall survival; the other statistically significant factors were sex, age, Breslow thickness, and Clark's level. Considering SLN and NSLN status, including FN cases, we identified four groups of patients with different prognoses. The 5-year overall survival of patients with positive SLNs was 71.3% in those with negative nonsentinel lymph nodes (NSLNs) and 50.4% if NSLNs were positive. CONCLUSIONS: Regression in the primary melanoma seems to be a protective factor from metastasis in the SLN. When correctly calculated, the SNB FN rate is 15-20%. Furthermore, the SNB is important to more precisely assess the prognosis of patients with melanoma.

Sentinel node biopsy in pediatric soft tissue sarcomas of extremities.

BACKGROUND: Sentinel Node Biopsy is an established staging technique in many adult malignancies. However, only few reports describe this procedure for the evaluation of regional lymph nodes in childhood and adolescents. Our experience with sentinel node biopsy in soft tissue sarcomas of extremities in children is reported. METHODS: Seventeen children were evaluated with sentinel node biopsy between 2002 and 2007: 11 at initial surgery, 5 at primary re-excision, 1 at local relapse. The diagnosis was rhabdomyosarcoma in 5 and other soft tissue sarcomas in 12: Ewing/PNET sarcoma 6, epithelioid sarcoma 1, malignant peripheral-nerve-sheath tumor 1, undifferentiated sarcoma 1, myxoid liposarcoma 2, adult-type fibrosarcoma 1. Primary sites included lower limbs (8), upper limbs (9). Mapping of nodes was performed with lymphoscintigraphy plus intra-operative injections with blue-dye in 14 cases, with lymphoscintigraphy and intra-operative injections alone in 2 and 1, respectively. RESULTS: Of the 17 lymphatic regions (9 axilla, 8 inguinal), 16 were identified with lymphoscintigraphy, 15 by intra-operative injections. Thirty-five lymph nodes were removed. Nodes were positive for metastasis in two patients with alveolar rhabdomyosarcoma and undifferentiated sarcoma. There were no complications. No further lymph node metastases were recognized either at diagnosis or during the follow-up (6-78 months). CONCLUSIONS: Sentinel node biopsy was technically feasible, reliable, and free of complications. It could be an alternative to aggressive or random biopsies for extremity rhabdomyosarcoma and it can contribute to define those non-rhabdomyosarcoma soft tissue sarcomas that spread to regional nodes.

Subcellular distribution and metabolism studies of the potential myocardial imaging agent [99mTc(N)(DBODC)(PNP5)]+.

UNLABELLED: 99mTc(N)-DBODC5 is the lead compound of a new series of monocationic 99mTc(N)-based potential myocardial imaging agents that exhibit original biodistribution properties. This study was addressed to elucidate the mechanisms of distribution, retention, and elimination of this promising 99mTc(N)-agent. METHODS: The sex-related in vitro and in vivo stability and the subcellular distribution of 99mTc(N)-DBODC5 were investigated. Studies were performed by considering binding to the serum proteins; stability in rat serum, human serum, and rat liver homogenates; and the chemical integrity of the complex after extraction from rat tissues such as heart, liver, and kidney, as well as from intestinal fluids and urine. The effect of cyclosporin A on the in vivo pharmacokinetic properties of 99mTc(N)-DBODC5 was also evaluated. Subcellular distribution of 99mTc(N)-DBODC5 in ex vivo rat heart was determined by standard differential centrifugation techniques. RESULTS: No significant in vitro serum protein binding and no notable biotransformation of the native compound into different species by the in vitro action of the serum and liver enzymes was evidenced. In vivo experiments showed that sex affects the pharmacokinetic profile of the 99mTc(N)-complexes including metabolism and excretion. Chromatographic profiles of 99mTc(N)-radioactivity extracted from tissues and fluids of female rats were always coincident with the control. Conversely, a small percentage of metabolized species was detected by high-performance liquid chromatography in liver extracts of male rats. Furthermore, administration of cyclosporin A caused a significant reduction of lung, liver, and kidney washout along with a considerable variation in activity distribution in the intestinal tract in both male and female rats, thus indicating a possible implication of Pgp transporters in determining the biologic behavior of 99mTc(N)-DBODC5. However, this phenomenon was more pronounced in females. Subcellular distribution studies showed that 86.3% +/- 7.4% of 99mTc(N)-DBODC5 was localized into mitochondrial fraction as a result of the interaction with the negative membrane potential. CONCLUSION: Evidence showing that the new 99mTc(N)-myocardial tracers behave as multidrug resistance-associated protein P-glycoprotein substrates, combined with their selective mitochondrial accumulation, strongly supports the possibility that diagnostic application of 99mTc(N)-DBODC5 can be extended to tumor imaging and noninvasive multidrug resistance studies.

99Tc Nanocolloid sentinel node procedure in thyroid carcinoma.

PURPOSE: The purposes of this study were to investigate the efficacy of radiocolloid lymphoscintigraphy and of handheld gamma probe procedure for sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC) and to evaluate its results in clinical staging. MATERIALS AND METHODS: Sixty-five PTC consecutive patients entered the study. Patients underwent radiocolloid lymphoscintigraphy before surgery. Intraoperative sentinel lymph node (SLN) localization was performed using a handheld gamma probe. They were followed up at 2, 6 months, and yearly. RESULTS: SLN metastases were diagnosed in 52%. Fifty-one patients underwent ablative 131-I therapy. The mean Tireoglobulin level in N0 vs N1 cases was 2.2 ng/ml vs 4.73 (p = 0.03) and 0.68 vs 2.1 ng/ml (p = 0.005) before and after 131-I therapy, respectively. CONCLUSIONS: In patients classified N0 by SLNB, ablative 131-I therapy could be avoided.

Papillary thyroid carcinoma: factors influencing recurrence and survival.

BACKGROUND: The prognosis of patients with papillary thyroid carcinoma (PTC) is usually favorable; however, a subset of patients can develop local recurrence or distant metastases. The aim of this study was to evaluate the prognostic factors influencing the recurrence and the survival rate in 950 PTC patients. MATERIALS AND METHODS: From 1990 to 2005, 950 consecutive patients affected by PTC were operated on at our Department. We analyzed the prognostic role of the following parameters: gender, age at initial treatment, extent of thyroid surgery, node dissection, tumor size, node metastases, distant metastases, stage, and 131-I therapy. RESULTS: Seventy-nine patients (8.3%) developed locoregional or distant metastases after an average follow-up of 7.8 years (range 2-17 years); in particular local recurrence was observed in 25 cases and distant metastases in 54 cases. The global 10- and 15-year survival rates were 91.38% and 88.69%, respectively. At univariate analysis, all variables were significantly correlated with recurrence (P = .001) except gender (P = .3); moreover, gender (P = .2), node dissection (P = .5), and node metastases (P = .06) were not significant on 10- and 15-year survival. At multivariate analysis the age at first treatment, T4, M+, stage IV, the extent of thyroid surgery, and the 131-I therapy resulted to be significant and independent prognostic factors (P < .001). CONCLUSION: Our data, in disagreement with other staging systems, suggest that gender does not play a significant role both in recurrence and survival. Moreover, the 131-I therapy was a statistically significant prognostic factor at univariate and multivariate analyses.

Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake.

OBJECTIVE: Papillary thyroid cancers (PTCs) with no iodine uptake have an aggressive behaviour and a poor prognosis. The aim of our study was to characterize, at molecular level, a subset of PTC with no 131 iodine ((131)I) uptake. DESIGN AND METHODS: Forty-eight cancer tissues were divided into three groups: Group 1, 28 primary cancers; Group 2, 7 recurrences capable of trapping (131)I; and Group 3, 13 recurrences incapable of trapping (131)I. mRNA levels of thyroid genes (sodium/iodide symporter NIS, thyroglobulin, thyroperoxidase and pendrin) and glycolytic metabolism genes (GLUT-1, hexokinase I and II) and BRAF mutations were evaluated in the different groups. RESULTS: Cancers with no (131)I uptake had slightly reduced NIS, significantly reduced thyroglobulin (P < 0.01), thyroperoxidase (P = 0.01) and pendrin (P = 0.03) and significantly increased GLUT-1 (P = 0.01) gene expression levels; and a high frequency of BRAF mutations (77%). BRAF(V600E) mutation, in both primary and metastatic thyroid cancers, is associated with a marked drop in thyroperoxidase (29-fold) and pendrin (20-fold) expression and a considerable increase (five-fold) in GLUT-1 expression. CONCLUSIONS: (1) The loss of (131)I uptake in recurrences depends not only on a decrease in NIS gene, but possibly on a reduction in the molecules regulating its intracellular metabolism; (2) the high GLUT-1 gene expression supports the use of positron emission tomography with specific tracers in clinical management of such cancers; and (3) BRAF(V600E) point mutations may lead to less differentiated phenotypes, suggesting a worse prognosis.

Contribution of SLN investigation with 99mTc-nanocolloid in clinical staging of thyroid cancer: technical feasibility.

PURPOSE: It is a matter of controversy whether prophylactic lymph node dissection improves prognosis and survival in papillary thyroid carcinoma (PTC) patients without suspicion of lymph node metastases either clinically or on ultrasonography. It is possible that in such patients the use of lymphatic mapping and sentinel lymph node (SLN) biopsy, as are employed for other tumours, will be of assistance. The aim of this study was to evaluate the feasibility of preoperative 99mTc-nanocolloid lymphoscintigraphy and an intra-operative SLN procedure in the management of PTC patients. METHODS: Twenty-five consecutive patients were entered in the study between April 2005 and October 2005. All had a preoperative diagnosis of malignancy obtained by fine-needle aspiration cytology (FNAC), without clinical or ultrasonographic evidence of loco-regional lymph node involvement. Patients underwent preoperative lymphoscintigraphy after the injection of 99mTc-nanocolloid [median 6 MBq (range 4-9 MBq) in 0.1-0.2 ml saline injected intratumorally under ultrasound guidance] and an intra-operative SLN procedure using a hand-held gamma probe. Surgery was performed by the same surgeon in all patients. RESULTS: Preoperative lymphoscintigraphy identified at least one SLN in all patients. During surgery, using the gamma probe, the surgeon was able to find at least one SLN in all cases. A good correlation was found between preoperative imaging and probe results. Metastasis was found in at least one SLN in 12 (48%) patients. In seven (28%) patients the involved SLN was the most radioactive SLN, while in five (20%) patients a less radioactive SLN was involved by malignancy. Ten of these 12 patients had only micrometastases (<2 mm). Micrometastases were found in the most radioactive SLN in six cases and in less radioactive SLNs in four cases, while in two patients more lymph nodes visualised at lymphoscintigraphy ipsilateral to the primary tumour were sites of metastasis. CONCLUSION: The rate of nodal involvement was very high in our series: in 48% of patients at least one metastatic lymph node was found. From a technical point of view the intra-operative SLN procedure in PTC patients was easy to perform, without major intra-operative complications. Our promising preliminary experience needs to be confirmed in larger series of patients series with longer follow-up.

Correlation between melphalan pharmacokinetics and hepatic toxicity following hyperthermic isolated liver perfusion for unresectable metastatic disease.

BACKGROUND: In the present work, we report on the results of our pilot study of hyperthermic isolated hepatic perfusion (IHP) with melphalan alone for patients with unresectable metastatic liver tumors refractory to conventional treatments, with particular regard to the correlation between pharmacokinetic findings and hepatic toxicity. PATIENTS AND METHODS: Inclusion criteria were unresectable liver metastases, hepatic parenchyma replacement

Radio-guided surgery for non-131I-avid thyroid cancer.

OBJECTIVE: In this paper we report in a larger series the use of radio-probe-guided surgery (RGS) in nonradioiodine avid, well-differentiated thyroid cancer (DTC). DESIGN: Thirty-seven patients with locoregional recurrent, nonradioiodine avid DTC were studied with (99m)Tc-sestamibi directed RGS using a handheld gamma probe as an intraoperative detector. OUTCOME: Twenty-three women and 14 men were followed after RGS for 35.4 +/- 12.5 months (range 9-57). There were 33 papillary (one "tall" cell variant), 2 follicular, and 2 Hürthle cell cancers. In 7 patients, thyroid cancer recurred in the neck while cervical lymph node metastases were found in 31 patients (one patient had papillary cancer in both the thyroid bed and cervical lymph nodes). Sixty-six discrete nodules ranging from 6 to 45mm (mean tumor diameter, 18.4 +/- 8.5mm) were identified by both high-resolution ultrasound and (99m)Tc-sestamibi probe-guided RGS. After RGS, Tg (thyroglobulin) fell in 33 of 37 patients and mean target=nontarget sestamibi uptake ratios decreased in all 37 patients ( p < 0.0001). CONCLUSION: These data confirm our earlier observations that a (99m)Tc-sestamibi intraoperative gamma probe can be used to identify and guide resection of recurrent tumor and involved lymph nodes in locoregional metastases of nonradioiodine-avid thyroid cancer.

Radioguided surgery of parathyroid adenomas and recurrent thyroid cancer using the "low sestamibi dose" protocol.

PURPOSE: The aim of this study was to establish the clinical efficacy of the "low sestamibi dose" (LSD) protocol to perform thyroid and parathyroid radioguided surgery in a large series of patients homogeneously studied and operated on by the same surgeon. The LSD protocol was initially developed in our center to cure primary hyperparathyroid (PHPT) patients with a high likelihood of a solitary parathyroid adenoma (PA) by minimally invasive radioguided surgery (MIRS). Since then, the same protocol has been applied to differentiated thyroid cancer (DTC) patients with 131I-negative, but sestamibi-positive, locoregional recurrent disease in order to obtain radical radioguided extirpation of tumoral lesions at reoperation. STUDY DESIGN: We reviewed the clinical charts of 453 consecutive patients referred at the surgical department at Padova University (Padova, Italy) to investigate a PHPT or a DTC recurrence: 336 patients (74.2%) met the inclusion criteria for radioguided surgery, and these patients were analyzed for the aim of this study. There were 298 patients affected by PHPT with a high likelihood of a solitary sestamibipositive PA and 38 DTC patients affected by 131I-negative, but sestamibi-positive, locoregional recurrence. All patients underwent a preoperative imaging work-up, including sestamibi scintigraphy (doubletracer subtraction scan in PHPT patients and single-tracer, wash-out scan in DTC patients) and high-resolution neck ultrasonography (US). The LSD protocol we developed consists of the intravenous injection of a very low (1 mCi) sestamibi dose in the operating theater just 10 minutes before commencing intervention for the purpose of radioguided surgery only. At variance with the traditional "high (20-25 mCi) sestamibi dose (HSD)" protocol in which imaging and radioguided surgery are obtained in the same day, in the LSD protocol, imaging and radioguided surgery are performed in different days. The LSD protocol allows some advantages over the HSD protocol: (1) more time for acquiring and interpreting preoperative imaging (planar scintigraphy, single-photon emission computed tomography [SPECT], US); (2) an accurate selection of patients to whom MIRS is offered, especially in countries where the prevalence of nodular goiter with sestamibi-avid thyroid nodules (exclusion criteria for MIRS) is relatively high, as in mid-south-European countries; (3) it facilitates the work planning in the operating theater (bilateral neck exploration requires an operating time of at least double to that of MIRS); and (4) the radiation exposure dose to operating theater personnel is very low-substantially negligible, using the LSD protocol: This aspect assumes great importance in countries where radioproteximetric rules are stringent, as in Europe. RESULTS: PHPT patients. MIRS was successfully performed by a 1.5-2-cm skin incision in 287 of 298 PHPT patients (96.3%) in whom such an approach was scheduled on the basis of preoperative imaging, including 41 of 57 patients (71.9%) who had previously received thyroid or unsuccessful parathyroid surgery in another center. No case of major intraoperative complication was recorded. No case of persistent or recurrent PHPT was observed during postsurgical follow-up. DTC patients. A total of 79 metastatic lesions were intraoperatively detected by the gamma probe and successfully removed (68 of them had been correctly visualized at preoperative sestamibi scintigraphy). During subsequent follow-up, 18 patients (72%) were considered disease-free, whereas 7 had persistent disease (increased serum thyroglobulin levels). The radiation exposure dose to the surgeon using the LSD protocol was 1.2 uSi/hour, that is, 20-30-fold lower than that delivered with the HSD protocol used for PHPT patients and with the 131I protocol used for DTC patients with recurrence. CONCLUSIONS: On the basis of our data, it can be concluded that the LSD protocol is a safe and effective protocol to perform in both MIRS in PHPT patients and radioguided reoperation in DTC patients with 131I-negative recurrence. Furthermore, from a radioproteximetric point of view, in comparison with other radioguided protocols used for the same purposes, the LSD protocol minimizes the radiation-exposure dose to the surgeon and operating theater personnel.

The impact of lymphoscintigraphy technique on the outcome of sentinel node biopsy in 1,313 patients with cutaneous melanoma: an Italian Multicentric Study (SOLISM-IMI).

UNLABELLED: An observational multicentric Italian trial on sentinel node biopsy (SNB) in melanoma patients was performed to diffuse a common SNB protocol nationwide (Italy). We report herein the results of this trial. The influence of some technical aspects on the outcome of SNB was also investigated, because a certain degree of variability was accepted in performing lymphoscintigraphy. METHODS: From January 2000 to December 2002, 1,313 consecutive patients with primary cutaneous melanoma (Breslow thickness, >1.0 mm or <1.0 mm but with ulceration, Clark level IV-V, presence of regression) were enrolled by 23 centers. One half to 1 mL of 99mTc-labeled human albumin colloid, at a suggested dosage of 5-15 or 30-70 MBq, was injected intradermally, closely around the scar, the same day or the day before SNB. Intraoperatively, Patent blue was associated when a definitive wide excision of the primary was required. A positive sentinel node (SN) was defined when containing melanoma cells detected by either hematoxylin-eosin or immunohistochemistry (S100 and HMB45 antibodies). All patients underwent regular follow-up. False-negative cases were considered when lymph node metastases occurred in the same lymphatic basin of SN biopsy (SNB) during follow-up. A quality control program has been performed for the surgical procedure and for the histologic diagnosis. RESULTS: The SN identification rate was 99.3%. The axilla was the site of the SN in 52.5% of the cases. The mean number of SNs was 2.0 (range, 1-17) and only 1 node was removed in 45.4%. The positivity and false-negative rates were 16.9% and 14.7%, respectively (median follow-up, 31 mo). On multivariate analysis (logistic and linear regression) only the number of peritumor injections was inversely associated with the number of excised SNs (P = 0.002), whereas none of the technical variables showed an independent impact on SN status when Breslow thickness was included as a control variable. CONCLUSION: The number of peritumor injections seems to influence the outcome of lymphoscintigrapy in melanoma patients undergoing SNB. If these results are confirmed in a controlled trial, 3 injections at least should be recommended.

Analysis of technical and clinical variables affecting sentinel node localization in patients with breast cancer after a single intradermal injection of 99mTc nanocolloidal albumin.

AIM: To investigate the technical, clinical and pathological findings that can, potentially, affect pre-operative lymphoscintigraphy in visualizing sentinel lymph node (SLN) and intra-operative probe detection of SLN in patients with breast cancer. METHODS: One hundred and forty-two consecutive female patients with, clinically, a solitary, small breast cancer and clinically N0 axilla were enrolled. Preoperative lymphoscintigraphy was performed by a single intradermal injection of 99mTc nacolloidal albumin (Nanocoll) the day before surgery. For radioguided surgery two gamma probes with diameters of 11 mm and 15 mm, and set up with a count rate ranging from 1 to 4 s were used. The following variables were evaluated: patient's age, radiotracer dose, volume of injectate, primary tumour location, primary tumour size, and presence and extension of axillary nodal metastases. RESULTS: Lymphoscintigraphy showed high sensitivity in visualizing the SLN (98% success rate) and it resulted in a rapid technique since SLN was visualized within 30 min from injection in 85.21% of cases for the whole series. The probe detection rate was also very high (97.8% success rate): the mean per cent uptake in the SLN was 0.98. Statistical analysis showed that no parameter was found to have significantly influenced either SLN visualization at lymphoscintigraphy or SLN probe detection at surgery. CONCLUSION: In our experience, lymphoscintigraphy performed by a single intradermal injection of Nanocoll was an effective and rapid technique for visualizing axilla SLNs in breast cancer patients. Moreover, this technique appeared to be independent of any technical, clinical and pathological findings.

Hypoxic antiblastic stop-flow limb perfusion: clinical outcome and pharmacokinetic findings of a novel treatment for in transit melanoma metastases.

Hypoxic antiblastic stop-flow perfusion (SFP) has recently been proposed as a therapeutic option for patients with locally advanced tumors. We report on the clinical and pharmacological results of our prospective study of limb SFP for the treatment of in transit melanoma metastases. Twenty-three patients with limb-sited melanoma metastases were treated with melphalan (10 mg/l) based pelvic (n=11, group A) or femoral (n=12, group B) SFP under hypoxic conditions. Systemic and locoregional toxicity, tumor response rate, and local progression-free survival were analyzed. Melphalan concentrations were measured in the perfusate and systemic circulation during SFP, and after 30-min hemofiltration. Perfusate-to-plasma leakage was assessed using a scintigraphic method. No postoperative deaths occurred. Mild locoregional toxicity was observed in 5 patients (18%), and systemic toxicity was mild to severe in 8 patients (30%), the incidence being higher in group A. Tumor response rate (complete + partial response) and time to local disease progression were significantly different in group A and B (9% vs 58% and 7 vs 13 months, respectively). The pharmacokinetic study showed that pelvic SFP was associated with a higher leakage rate and a lower area under the curve ratio than femoral SFP (44% vs 31% and 5.6 vs 9.8, respectively). Limb SFP is a feasible and relatively simple procedure. Toxicity and tumor response rates strictly depend upon drug leakage control. Further efforts should be made to exploit the potential anti-tumor activity of this novel locoregional drug delivery system.

Minimally invasive radioguided parathyroidectomy: an attractive therapeutic option for elderly patients with primary hyperparathyroidism.

BACKGROUND AND AIM: Surgery for primary hyperparathyroidism (PHPT) due to a solitary parathyroid adenoma (PA) is moving from traditional bilateral neck exploration (BNE) towards the use of limited neck exploration. The aim of the present study was to define the efficacy of minimally invasive radioguided surgery (MIRS) in PHPT patients with a high probability of a solitary PA with particular regard to benefits achievable in elderly patients. PATIENTS AND METHODS: The study population included a total of 266 consecutive PHPT patients who had undergone surgery at our centre between September 1999 and February 2003. Preoperative imaging consisted of [Tc]pertechnetate/Tc sestamibi (TcO4/sestamibi) scintigraphy and neck ultrasound obtained in the same session. One hundred and eighty-seven patients from the whole series (75 of whom were older than 65 years) with a high scan/ultrasound probability of a solitary PA, a high PA sestamibi uptake, and a normal thyroid gland were selected for MIRS. The other 79 patients were selected for traditional BNE. The intra-operative technique was based on the injection of a low dose (37 MBq) of sestamibi in the operating theatre a few minutes before the beginning of intervention and on the use of an 11 mm collimated gamma probe. RESULTS: MIRS was successfully performed in 97.8% of all PHPT patients selected for this type of surgery and, in particular, in 100% of the subgroup (n=75) of elderly patients. MIRS required a mean operating time of 35 min and a mean hospital stay of 1.2 days; that is, approximately half of that required for traditional BNE. Moreover, local anaesthesia was successfully performed in 27 patients, 19 of whom were >65 years with concomitant invalidating diseases contraindicating general anaesthesia. No major surgical complications were recorded. Transitory hypocalcaemia was observed in 9% of cases treated with MIRS compared with 27% of patients treated with BNE. CONCLUSION: MIRS can be accurately planned in elderly PHPT patients with a solitary PA on the basis of a TcO4/sestamibi scan and neck ultrasound. MIRS has been proven to be safe and effective in our experience, and allows a significant reduction of operating and recovery time, as well as the possibility of using local anaesthesia, especially in elderly patients with concomitant invalidating diseases.

Metabolic and cardiovascular parameters in type 1 diabetes at extreme altitude.

PURPOSE: The American Diabetes Association states that physical activity can be performed by individuals with Type 1 diabetes. Nevertheless, extreme altitude mountaineering represents a demanding challenge. We present the metabolic and cardiovascular parameters found in individuals with Type 1 diabetes during the ascent to Cho Oyu located at a height of 8201 m. METHODS: Six individuals with Type 1 diabetes and 10 matched controls participated in the expedition. Both groups were evaluated before and after 4 h of trekking for vital indices, blood gases, acute mountain sickness, and metabolic control at 0, 3700, and 5800 m. RESULTS: No difference between the groups was observed in acute mountain sickness scores. There was a progressive elevation in basal heart rates in both groups at increasing altitude while no changes were observed in mean blood pressures. After the 3 h of trekking, a significant increase in heart rate was observed in the controls at 0 m whereas a significant decrease in blood pressure was observed at higher altitude only in controls. HbA1c levels were worse after the expedition in both groups. A progressive increase in insulin requirement was observed in subjects with Type 1 diabetes (38 +/- 6 U x d(-1) at 0 m to 51 +/- 6 at 4200 m, P < 0.001). At an altitude of 5800 m, there was a significant increase in blood lactate concentration, independently of the activity level in the two groups. CONCLUSIONS: At extreme altitude, highly motivated trekkers with Type 1 diabetes but free from long-term complications present metabolic and cardiovascular parameters comparable with those of control subjects despite a worsening in metabolic control. This type of physical activity must be accompanied by careful glucose monitoring.

Natural history, diagnosis, treatment and outcome of papillary thyroid microcarcinoma (PTMC): a mono-institutional 12-year experience.

The clinical and histopathological records of 149 consecutive patients with papillary thyroid microcarcinoma (PTMC), homogeneously studied and operated on by the same surgeon in the period 1990 to 2001, were reviewed. After a mean 6.5-year follow-up, three cases of loco-regional recurrence (2%) were observed. These three patients had all undergone partial thyroidectomy only and tumour relapse occurred in the residual thyroid tissue. No recurrence was observed in patients treated by total thyroidectomy and I. At variance with other reported series, no lymph node recurrence was observed in our series, in particular in the group of 23 patients with evidence of nodal metastases at initial diagnosis (three of whom were revealed by I scan after surgery). Therefore, a preventive effect of I treatment in our patient population can be hypothesized. However, prolonged follow-up will be necessary to clarify this. Due to the inability of current imaging modalities to select pre-operatively PTMC patients at risk for recurrence (presence of thyroid capsular invasion, multifocality and microscopic lymph node metastases), it appears reasonable to offer the patient total thyroidectomy when a pre-operative diagnosis of PTMC is reached. Moreover, the policy of our thyroid cancer centre is that, in these patients, post-surgical I scan should be obtained in order to detect unknown metastatic deposits, and I treatment should also be considered in patients with poor clinical and histopathological prognostic factors. In contrast, in patients operated on for benign thyroid disease and with delayed diagnosis of PTMC at definitive histopathological examination, re-operation might be avoided in the presence of unifocal disease without thyroid capsular invasion and with ultrasound-'normal' residual thyroid tissue. Close clinical and ultrasound follow-up is recommended, especially in patients who have undergone conservative surgery only.

Sentinel node biopsy for breast cancer: is it already a standard of care? A survey of current practice in an Italian region.

BACKGROUND: Although sentinel node biopsy (SNB) is becoming the standard approach for axillary staging in patients with small breast cancer, criteria for patient selection and some technical aspects of the procedure have yet to be clearly defined. The aim of the present survey was therefore to investigate the way in which SNB is used by general surgeons working in the Veneto region, Italy. METHODS: A 29-item questionnaire regarding various aspects of SNB practice was mailed to surgeons in charge of breast surgery in all the 56 surgical centres of the region. RESULTS: The rate of response to the questionnaire was 82.1% (n = 46); 69.6% (n = 32) of the respondents routinely perform SNB in their clinical practice. Most of the interviewed surgeons (93.5%) expressed the belief that the acceptable false negative rate should be < or =5%. However, among the surgeons who perform SNB, only 34.4% performed more than 20 SNB during the learning phase. Indications are limited to tumours of < or =1 cm by 31.2% (n = 10) of respondents, < or =2 cm by 46.9% (n = 15) and < or =3 cm by 21.9% (n = 7). Almost all respondents (93.7%) agreed that a clinically positive axilla is a contraindication to SNB, while opinions differed widely concerning other potential contraindications. In most of the centres considered, SN identification is undertaken on the day before surgery using a subdermal injection of 30-50 MBq of 99mTc-albumin-nanocolloid followed by lymphoscintigraphy. CONCLUSIONS: SNB is currently performed in the majority of hospitals in the Veneto region. However, the training phase and criteria used for patient selection differ from centre to centre. Certified training courses and shared guidelines are therefore highly desirable.