Radio-guided Surgery for Non-131 I-avid Thyroid Cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63206/1/thy.2006.16.1105.lowlink.pdf_v03.pd

Feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi protocol

Aim of the present study was to investigate the feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi dose protocol compared to conventional "high 740 MBq (20 mCi) (99m)Tc-sestamibi dose protocol" in patients with primary hyperparathyroidism (PHPT). The data of focused radioguided surgery obtained in a group of 320 consecutive PHPT patients with high probability of the presence of a solitary parathyroid adenoma (PA) were studied. All patients underwent preoperative imaging work-up of double-tracer (99m)Tc-pertechnetate/(99m)Tc-sestamibi subtraction parathyroid scintigraphy (Sestamibi scintigraphy) and high resolution neck ultrasound (US). In 301/320 patients (96.6%) focused minimally invasive radioguided surgery was successfully performed by administering a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi dose in the operating room 10 minutes before operation. No major intraoperative complications were recorded. Focused radioguided surgery required a mean time of 32 min and a mean hospital stay of 1.2 days. Local anesthesia was applied in 75 patients, 66 of whom (88%) were patients older than 65 years with comorbidities contraindicating general anesthesia. No case of persistent or recurrent PHPT was observed during post-surgical follow-up (range = 18–70 months; mean +/- SD = 15.3 +/- 9.1 months). Radiation exposure dose to the operating surgeon was 1.2 μSi/hour with the "low 37 MBq (1 mCi) (99m)Tc-sestamibi dose", and less than 1.0 μSi/hour for the other operating-room personnel. Focused low dose radioguided parathyroidectomy is a safe and effective means to localize parathyroid adenomas in patients affected by solitary PA thus reducing by 20 fold the radiation exposure dose to the patients and operating room personnel

Role of gamma probes in performing minimally invasive parathyroidectomy in patients with primary hyperparathyroidism: optimization of preoperative and intraoperative procedures

OBJECTIVE: In the last decade, surgery of primary hyperparathyroidism (HPT) due to a solitary adenoma has moved on from the traditional wide bilateral neck exploration (BNE) to more limited approaches such as unilateral neck exploration and minimally invasive parathyroidectomy. DESIGN: To define the role of intraoperative gamma probe and injection of a low (99m)Tc-MIBI dose in performing minimally invasive radio-guided surgery (MIRS) in HPT patients with a solitary parathyroid adenoma. METHODS: From September 1999 to July 2002, 214 patients with primary HPT entered the study. All patients were preoperatively investigated by a (99m)Tc-pertechnetate/MIBI subtraction scan and high-resolution neck ultrasound. The intraoperative technique we developed differs from other previously described techniques being based on the injection of a low (37 MBq) MIBI dose in the operating theatre a few minutes before the beginning of intervention. RESULTS: On the basis of scan/ultrasound findings 147 patients were selected for a MIRS and 144 of them (98%) were successfully treated by this approach: a solitary parathyroid adenoma was removed through a small 2-2.5 cm skin incision with a mean operative time of 35 min, and a mean hospital stay of 1.2 days. In the other 67 patients with scan/ultrasound evidence of concomitant nodular goiter (n=45) or multi-gland disease (n=13) or with a negative scan (n=9), the gamma probe was utilized during a traditional BNE. A low 37 MBq MIBI dose proved to be sufficient to perform a MIRS; moreover it delivered to the patient and surgeon a low, negligible, radiation exposure dose. CONCLUSIONS: The combination of a (99m)Tc-pertechnetate/MIBI subtraction scan and neck ultrasound appears to be an accurate imaging protocol in selecting primary HPT patients as candidates for a MIRS. A MIBI dose as low as 37 MBq injected in the operating theatre just before the start of surgery appears to be adequate to perform radio-guided surgery

Low-blood lymphocyte number and lymphocyte decline as key factors in COPD outcomes: a longitudinal cohort study

Background: Smokers with and without chronic obstructive pulmonary disease (COPD) are at risk of severe outcomes like exacerbations, cancer, respiratory failure, and decreased survival. The mechanisms for these outcomes are unclear; however, there is evidence that blood lymphocytes (BL) number might play a role. Objective: The objective of this study is to investigate the relationship between BL and their possible decline over time with long-term outcomes in smokers with and without COPD. Methods: In 511 smokers, 302 with COPD (COPD) and 209 without COPD (noCOPD), followed long term, we investigated whether BL number and BL decline over time might be associated with long-term outcomes. Smokers were divided according to BL number in high-BL (=1, 800 cells/µL) and low-BL (<1, 800 cells/µL). Clinical features, cancer incidence, and mortality were recorded during follow-up. BL count in multiple samples and BL decline over time were calculated and related to outcomes. Results: BL count was lower in COPD (1, 880 cells/µL) than noCOPD (2, 300 cells/µL; p < 0.001). 43% of COPD and 23% of noCOPD had low-BL count (p < 0.001). BL decline over time was higher in COPD than noCOPD (p = 0.040). 22.5% of the whole cohort developed cancer which incidence was higher in low-BL subjects and in BL decliners than high-BL (31 vs. 18%; p = 0.001) and no decliners (32 vs. 19%; p = 0.002). 26% in the cohort died during follow-up. Furthermore, low-BL count, BL decline, and age were independent risk factors for mortality by Cox regression analysis. Conclusion: BL count and BL decline are related to worse outcomes in smokers with and without COPD, which suggests that BL count and decline might play a mechanistic role in outcomes deterioration. Insights into mechanisms inducing the fall in BL count could improve the understanding of COPD pathogenesis and point toward new therapeutic measures

Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M1 muscarinic receptor

Established therapy in Alzheimer’s disease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M1 muscarinic receptors found in higher concentrations in the cortex and hippocampus. Adverse effects, due to indiscriminate activation of other muscarinic receptor subtypes, are common. M1 muscarinic positive allosteric modulators/allosteric agonists such as BQCA offer an attractive solution, being exquisitely M1-selective over other muscarinic subtypes. A common difficulty with allosteric ligands is interpreting SAR, based on composite potency values derived in the presence of fixed concentration of agonist. In reality these values encompass multiple pharmacological parameters, each potentially and differentially sensitive to structural modification of the ligand. We report novel BQCA analogues which appear to augment ligand affinity for the receptor (pKB), intrinsic efficacy (τB), and both binding (α) and functional (β) cooperativity with acetylcholine. Ultimately, development of such enriched SAR surrounding allosteric modulators will provide insight into their mode of action

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 ≤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 ≤1 cm by 31.2% (n = 10) of respondents, ≤2 cm by 46.9% (n = 15) and ≤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

Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism

BACKGROUND: The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism. METHODS: This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99m Tc-MIBI scintigraphy- Intraoperative iPTH monitoring was routinely done. RESULTS: Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99m Tc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate. CONCLUSION: Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99m Tc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice