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Ann Surg. 2003 May; 237(5): 722–731. doi: 10.1097/01.SLA.0000064362.58751.59. | PMCID: PMC1514518 |
Copyright © 2003 Lippincott Williams & Wilkins, Inc. Sestamibi Scanning and Minimally Invasive Radioguided Parathyroidectomy Without Intraoperative Parathyroid Hormone Measurement Richard E. Goldstein, MD, PhD,*§ Dean Billheimer, PhD,† William H. Martin, MD,‡ and Ken Richards, MD* From the Divisions of *Surgical Oncology and
†Biostatistics;
the ‡Department of Nuclear Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; and the
§Division of Surgical Oncology, University of Louisville, Louisville, Kentucky
Objective To evaluate the results of a large series of patients undergoing minimally invasive radioguided parathyroidectomy (MIRP) in which routine use of the intraoperative parathyroid hormone assay was not used, and to investigate characteristics between patients who had positive preoperative parathyroid scans versus those with negative scans. Summary Background Data The technique of parathyroidectomy has traditionally involved bilateral exploration of the neck under general endotracheal anesthesia. Parathyroid imaging using technetium-99m sestamibi (MIBI) has evolved and can localize the adenomas in 80% to 90% of patients. The MIRP technique combines parathyroid scintigraphy with a hand-held gamma detector used intraoperatively to guide the surgeon to the adenoma in patients with positive MIBI scans. Central to this technique or other unilateral approaches is a positive MIBI scan. Methods One hundred seventy-three atients with primary hyperparathyroidism operated on by a single surgeon between January 1998 and July 2002 were included. One hundred twelve patients underwent the MIRP procedure and by definition had a positive preoperative parathyroid scan. The technique involved injecting 20 mCi MIBI 1 hour before the surgical procedure in patients who preoperatively had positive MIBI imaging. Patients had the choice of general or MAC anesthesia. Using an incision of less than 4 cm, the dissection to the adenoma was guided by the Navigator 11-mm probe. These 112 patients and 4 additional patients who for various reasons did not have the MIRP procedure yet had positive MIBI scans were compared to 57 patients who had clearly negative MIBI parathyroid imaging. Results Follow-up data were available for 108 of 112 patients who underwent MIRP. No patients had persistent hypercalcemia. The long-term success rate for the MIRP group was 98%. Fifty-two percent of the MIRP procedures were performed using MAC anesthesia. Overall, gland weight and serum PTH were related to the probability of a positive MIBI scan. Multiple logistic regression revealed that females were more likely to exhibit positive scans than were males for any fixed serum PTH level. For females, there was a significant relationship between increasing serum parathyroid hormone and a positive MIBI scan. Conversely, in males, the relationship between scan positivity and serum parathyroid hormone was weaker. Conclusions The MIRP technique without routine intraoperative serum parathyroid hormone measurement resulted in an excellent cure rate for primary hyperparathyroidism. As the MIRP technique as well as other techniques for unilateral cervical exploration are predicated on a positive parathyroid scan, the possible effect of gender on the sensitivity of MIBI scintigraphy for the detection of parathyroid adenomas warrants further investigation. Primary hyperparathyroidism is a benign but sometimes devastating disease. There is concern that the incidence of primary hyperparathyroidism is increasing, with its prevalence approaching 1% in elderly women. 1 Causes include single and double adenomas, multiglandular hyperplasia of a primary and secondary nature, and rarely parathyroid carcinoma. The traditional surgical approach designed to cure patients of this disease has involved careful exploration of the central neck with the intent of first identifying all four parathyroid glands before resecting any glands that appear to be enlarged. To facilitate such a dissection, general endotracheal anesthesia has been necessary. Surgical judgment and expertise have been significant factors, and skilled endocrine surgeons have reported cure rates of 97% to 99% using this approach. 2,3In the past decade, improvements with parathyroid imaging and the development of a miniaturized hand-held gamma probe have allowed new surgical techniques in the management of patients with primary hyperparathyroidism. Dual-phase technetium-99m sestamibi (MIBI) parathyroid scintigraphy has increased the sensitivity for detecting parathyroid adenoma to 91%, with a specificity of 98.8%. 4 This improvement in parathyroid imaging combined with the development of hand-held gamma probes led to the technique of minimally invasive radioguided parathyroidectomy (MIRP). 5 This procedure, predicated on a positive sestamibi parathyroid scan, allows the surgeon to be guided down to the parathyroid adenoma using the hand-held gamma probe, often without the need for general endotracheal anesthesia. Since the initial report, the technique has been further refined and validated in a large series of patients undergoing initial parathyroid surgery, 6 as well as in patients undergoing reoperative parathyroid surgery. 7 Angelos 8 and Goldstein et al. 9 have also reported the successful application of this technique to patients with primary hyperparathyroidism. In addition to operative success, use of the procedure has resulted in decreased operative time, length of hospital stay, and hospital charges. 4,9 These results support the conclusion that the MIRP procedure can now be considered a standard procedure to be offered to patients with primary hyperparathyroidism. Another development in the past decade that has contributed to an additional choice of procedure for patients with primary hyperparathyroidism has been the quick intraoperative parathyroid hormone assay (iPTH). 10 The current assay can yield a serum parathyroid hormone (PTH) determination in less than 15 minutes. Using the iPTH assay in patients who had successful preoperative localization of a parathyroid adenoma based on a positive parathyroid scan, Irvin et al. 11 and Carty et al. 12 have performed unilateral exploration of the neck with high rates of success. Udelsman et al. used the term “minimally invasive parathyroidectomy” (MIP) for a scan-based unilateral cervical exploration under cervical block using the iPTH determination to confirm the cure. 13 Recently Udelsman reported on results of over 250 MIPs, with a 99% cure rate. 14 Flynn et al. 15 combined the MIRP technique with the iPTH assay and reported excellent results in a small series of patients. The purpose of the current study was to evaluate the results of a large series of MIRPs in which iPTH was not routinely used, and to investigate characteristics between patients who had positive scans and thus were candidates for a MIRP versus those with negative scans. One hundred seventy-three patients with primary hyperparathyroidism operated on by a single surgeon between January 1998 and July 2002 were included in this study. A diagnosis of primary hyperparathyroidism was based on hypercalcemia and an elevated serum intact parathyroid hormone level. One hundred twelve patients underwent the MIRP procedure and by definition had a positive preoperative parathyroid scan. These 112 patients and 4 additional patients who for various reasons did not have the MIRP procedure performed yet had positive MIBI scans were compared to 57 patients who had clearly negative parathyroid scans. These patients with negative scans were ultimately determined to have single parathyroid adenomas. Patients with equivocal scans as well as patients with secondary hyperparathyroidism or multiglandular hyperplasia were excluded from the analysis. All patients with primary hyperparathyroidism underwent dual-phase imaging consisting of the acquisition of anterior and anterior oblique planar images 15 minutes after intravenous injection of 20 to 25 mCi 99mTc-sestamibi (0.3 mCi/kg for obese patients). Similar views were acquired 60 to 150 minutes postinjection using identical acquisition parameters. The initial anterior image was acquired for 5 minutes and at least 500,000 counts using a low-energy, high-resolution collimator, a 128 × 128 matrix with a 1.6 zoom, and an energy window of 140 keV ± 10% (). Ideally, these scans were obtained on the day of, but before, the patient’s preoperative office visit. However, in the first half of the study period, most patients were imaged on the day of their surgical procedure, and the delayed scans were obtained at 60 minutes postinjection. The change in the algorithm allowed more time for surgical options to be discussed with the patient and resulted in more efficient operating room utilization. All scans were reviewed by the attending nuclear radiologist and the surgeon. Patient who had a MIBI scan interpreted as demonstrating a single focus of pathologically increased activity in the neck (positive) were considered eligible for the MIRP procedure. If MIRP was chosen, the patient was reinjected with MIBI, 20 mCi, 30 to 60 minutes before the start of the surgical procedure and was not reimaged. 5 Unless contraindicated, the patient was given the choice of IV sedation (monitored anesthesia care [MAC]) or general endotracheal anesthesia. IV sedation consisted of midazolam and propofol plus local application of lidocaine with epinephrine with the addition of 10% sodium bicarbonate into the subcutaneous tissue of the anterior neck below the level of the thyroid notch. An incision 2.5 to 4.0 cm was made in a transverse direction two fingerbreadths above the sternal notch. It was slightly weighted toward the expected side of the adenoma. Minimal subplatysmal planes were created and the strap muscles were divided in the midline and then dissected off the inferior aspect of the thyroid lobe on the side of the parathyroid adenoma. 5 The dissection from this point on was guided by the hand-held gamma probe, with an 11-mm head specifically designed for neck surgery (Navigator, US Surgical, Inc., Norwalk, CT). Care was taken to be aware of the recurrent laryngeal nerve; however, given the limited dissection, the nerve was identified less than half the time. Once the targeted gland was removed, the radioactivity of the presumed adenoma was measured ex vivo with the probe directed away from the patient and compared to counts obtained by slowly tracking the probe over the central neck. If the ex vivo radioactivity totaled at least 20% of the remaining background counts 6,7 and there was no significant step-up of counts in any quadrant of the neck, the dissection was terminated and the incision closed without a drain. Patients were discharged home on calcium supplementation. If the procedure was performed under MAC, virtually all patients were discharged within 5 hours of procedure completion. If patients had general endotracheal anesthesia, most patients remained in the hospital overnight and were discharged the following morning. Data were obtained by reviewing hospital and office records and contacting referring physicians. For information on any patient who was beyond the 90-day postoperative period, data were obtained only if consent was given by the patient through an IRB-approved protocol. Comparisons related to MIBI imaging were made with 57 patients with primary hyperparathyroidism who had negative preoperative parathyroid scans and who subsequently underwent bilateral neck explorations under general endotracheal anesthesia. Data were collected from 116 patients testing positive by MIBI scintigraphy and 57 patients testing negative. Parameters included preoperative serum PTH, preoperative serum calcium, excised gland weight, parathyroid location, and patient demographics (age, gender, race). Descriptive statistics were computed to summarize the distributions of measured outcomes. The logarithmic transformation was used to correct for skewness in distributions of serum PTH and excised gland weight. Independent sample t tests were used to evaluate group differences in measured outcomes, while the Pearson chi-square test was used to evaluate associations between binary outcomes. Logistic regression was used to evaluate the influence of gland weight, serum PTH, and serum calcium on the probability of scan positivity. Distributional and model fit considerations led to use of log transformations of weight and serum PTH as independent variables. Multiple logistic regression was used to evaluate the joint influence of two potential predictors on the odds of scan positivity. Specifically, when testing patient sex difference for the influence of serum PTH on scan positivity, the full model interaction was first evaluated. Although the interaction term was not statistically significant at the 0.05 level, separate logistic regression models were fit to describe female and male data. All hypothesis tests were judged significant at the 0.05 level. Data are expressed as means ± SEM. Demographics The MIRP group consisted of 112 patients with a mean age of 59 ± 1 year; 83 (74%) were women. One hundred eight (96%) were white and four were African American. One patient with MEN1 had previously undergone two parathyroid procedures and was referred with recurrent disease. Six other patients had undergone seven prior parathyroid procedures; five were referred with persistent disease and one was referred with recurrent disease. An additional seven patients had undergone previous thyroid procedures (four had thyroid cancer), two had previous I-131 treatments, and one patient had sustained a recurrent laryngeal nerve injury. One patient had atomic radiation exposure. Nine patients had diabetes, seven patients had benign thyroid disease, and two had Addison’s disease. Two additional patients had known family members with parathyroid disease but were not known to be from a MEN family. The scan-negative group consisted of 57 patients with a mean age of 61 ± 2 years; 32 (56%) were women. Fifty-three (92%) were white and three were African American. No patients had MEN syndrome. Two patients had undergone previous parathyroid procedures; one was referred with recurrent disease and one had persistent disease. No patients had undergone prior thyroid procedures. Diagnosis The average preoperative serum calcium level in the MIRP group was 11.1 ± 0.1 mg/dL and the serum PTH level was 186 ± 20 pg/mL. In the scan-negative group, the preoperative serum calcium level was 11.1 ± 0.1 mg/dL (P = NS vs. MIRP) and the serum PTH level was 123 ± 9 pg/mL (P = .003 vs. MIRP). By definition, all patients in the MIRP group had positive preoperative MIBI scans. In addition, 13 patients had additional preoperative imaging; 5 had CT scans, 3 of which were positive; 8 had sonography, 5 of which were positive, and 3 had MRI, 2 of which were positive. By definition, no patients in the scan-negative group had positive MIBI scans. Signs and Symptoms The signs and symptoms of patients who underwent the MIRP procedure are listed in Table 1. Despite the relatively mild hypercalcemia, only 8% of the patients could be prospectively considered asymptomatic, and one of those had renal stones 9 years before MIRP; one additional patient categorized as asymptomatic did have mild hypertension. The three most common manifestations consistent with primary hyperparathyroidism were fatigue (43%), bone loss (33%), and renal stones (24%) | Table 1. SIGNS AND SYMPTOMS ASSOCIATED WITH PRIMARY HYPERPARATHYROIDISM IN PATIENTS WHO UNDERWENT MINIMALLY INVASIVE RADIOGUIDED PARATHYROIDECTOMY |
Operative Data Sixty-five (58%) of the MIRP procedures were started as MAC. Seven were converted to general endotracheal anesthesia during the procedure without complications. Four patients became restless and could not cooperate, two patients were uncomfortable, and one had a large adenoma that required significantly more exposure. Forty-seven (42%) of the MIRP procedures were started and completed under general endotracheal anesthesia. Twenty-four of these (51%) were purely patient choice. Thus, potentially, 79% of patients could have had an attempt at MAC anesthesia. Other reasons for the choice of general endotracheal anesthesia included obesity (n = 10), anxiety disorders (n = 3), pediatric age group (n = 2), sleep apnea (n = 1), expected large tumor size (n = 2), kyphotic neck (n = 2), and other (n = 3). 99mTc-Sestamibi Imaging Results Table 2 depicts the location reported for the parathyroid adenomas based on the preoperative MIBI parathyroid imaging as well as the actual location of the adenoma. There was complete concordance 77% of the time between predicted and actual location. However, scans did predict the correct side 100% of the time; the errors primarily were in misinterpreting superior adenomas as inferior adenomas. | Table 2. LOCATION OF PARATHYROID ADENOMA |
Pathology and Postoperative Results Final pathology was consistent with a single adenomas in 111/112 patients in the MIRP group and all 57 patients in the scan-negative group. One patient in the MIRP group with MEN1 syndrome had a hyperplastic gland. The mean weight of the adenomas in the MIRP group was 1,361 ± 166 mg (range 70–11,700 mg). The mean weight of the adenomas in the scan-negative group was 492 ± 63 mg (range 80–2,850 mg) (P < .0001 vs. MIRP). Follow-up serum calcium and serum PTH levels were available in 108 (96%) and 75 (67%) of the 112 patients, respectively. The mean serum calcium and serum PTH levels were 9.3 ± 0.1 mg and 68 ± 5 pg/mL. The highest most recent serum calcium values were between 10.2 and 10.6 mg/dL in five patients. However, three of those had serum PTH levels within the low-normal range (average 27 pg/mL, with normal range of 10–65 pg/mL). One patient had a serum calcium level of 10.3 mg/dL with a serum PTH of 55 pg/mL 1 year after resection of a 1,750-mg adenoma. A second patient had a serum calcium level of 10.6 mg/dL 2 years out from MIRP after an initial follow-up serum calcium level of 9.3 mg/dL. A serum PTH level was not available on this patient. This patient had a 600-mg adenoma resected. Thus, potentially, two (1.9%) patients have recurrent disease, yielding an overall success rate of 98.1%. Complications No patients who underwent MIRP sustained temporary or permanent recurrent laryngeal nerve injuries. Two patients had bone hunger not requiring readmission to the hospital. One patient had bone hunger after MIRP, requiring readmission to the hospital. This had been anticipated as she presented with a spontaneous femur fracture and had multiple brown tumors on bone scan. In one case, the adenoma was located where the scan had indicated, but the probe failed to detect the radioactivity in the operating room. One other patient underwent reexploration on postoperative day 2 after the serum calcium level failed to fall into the normal range and the preoperative scan had demonstrated a second, though less intense, area of intensity. Reexploration including thyroid lobectomy failed to reveal an adenoma, and the serum calcium level normalized later that day and remained normal. One patient had a transient ischemic attack on postoperative day 7 that resolved; one patient had a hematoma that did not require drainage; and one patient had a seroma requiring needle drainage in the office. Statistical Comparisons The independent sample t tests (after logarithmic data transformation) indicated that gland weight (P < .0001) and serum PTH concentration (P = .003) distributions differed significantly between the scan-positive and scan-negative groups. The median gland weight () for scan-positive patients was approximately twice that for scan-negative patients (750 mg vs. 320 mg). The middle 50% (25th to 75th percentile) of scan-positives was 340 to 1,400 mg, while the middle 50% of scan-negatives was 220 to 600 mg. The median serum PTH concentration () was approximately 25% greater in scan-positive (128 pg/mL) than in scan-negative (101 pg/mL) patients. There was no significant difference in median serum calcium levels () between scan-positive and scan-negative patients. Similarly, adenoma location (data not shown) had no effect on scan positivity. In analyzing the effect of gender on scan positivity, 73% of females were scan-positive, whereas only 55% of males had positive scans (P = .017). Gland weight was the most important single predictor of scan positivity among the measured variables. The odds of a positive scan increased with increasing weight (P < .0001): as weight doubled, the odds of a positive scan increased by a factor of 2.7 (95% confidence interval, 1.7–4.1). Increasing serum PTH level was also significantly related to the odds of detection (P = .003). As serum PTH concentration doubled, the odds of a positive scan increased by a factor of 2.1 (95% confidence interval, 1.3–3.6). Preoperative serum calcium level did not show a significant relationship with odds of a positive scan (P = .9). Multiple logistic regression revealed that females were more likely to exhibit positive scans than were males for any fixed serum PTH level (P = .004). Separate regression models were created for men and women (). For females, there was a significant relationship between increasing serum PTH and scan positivity (P = .003). At a serum PTH concentration of 100 pg/mL, the probability of detection was approximately 67%. This increased to 86% when the serum PTH level was 200 pg/mL. Conversely, in males, the relationship between scan positivity and serum PTH was weaker (P = .28). At a serum PTH concentration of 100 pg/mL, the probability of detection for males was 48%; it increased slightly to 58% at 200 pg/mL. Of adenomas with a weight of 400 mg or less, MIBI scintigraphy detected the adenomas in 25/43 female patients (58%) but only 8/22 (36%) male patients. The smallest adenoma detected by MIBI scintigraphy in a female was 70 mg; the smallest adenoma detected by MIBI scintigraphy in a male was 200 mg. The clear trend in the management of primary hyperparathyroidism over the past half-decade has been toward directed unilateral neck exploration. One unilateral approach, MIRP, was developed by Norman and Chheda 5 and relies on the technetium-99m sestamibi radiopharmaceutical and a hand-held gamma probe to provide both a targeted approach to the parathyroid adenoma and functional confirmation of completeness. Goldstein et al. 9 reported on their initial experience with MIRP in which all 20 patients were cured and most were able to undergo the procedure without general endotracheal anesthesia. More recently, Murphy and Norman 6 reported a 100% cure rate after a large series of MIRPs performed at a single institution. Norman and Denham 7 also reported on the specific application of the MIRP procedure to reoperative parathyroid surgery. Again, the success rate of the 21 patients who underwent MIRP was 100%. A second unilateral approach favored by a number of endocrine surgeons 11,12,14,16 relies on the iPTH assay to confirm cure after resection of the presumed adenoma. Recently, Udelsman has used the term “minimally invasive parathyroidectomy” (MIP) in referring to this approach combined with cervical block anesthesia. 13The current study of 112 patients is the largest report to date on the MIRP procedure outside the report by Murphy and Norman. 6 In follow-up extending to 4 years, no patient had persistent hyperparathyroidism, and the long-term cure rate was 98%. Complications were minimal and over half of the procedures were completed under MAC anesthesia. These percentages will likely increase as surgeons become more comfortable and competent with this approach and patients become more accepting of MAC anesthesia. Although Murphy and Norman 6 reported no failures and no false-positive MIBI scans, 17 the current study includes two probable late failures and one false-positive scan. Nevertheless, false-positive scans are not common, and careful correlation of the imaging findings with patient history and physical examination can aid in the interpretation of these scans. While some surgeons have combined the MIRP technique with the iPTH assay, 15 it remains to be determined whether the addition of the assay is complementary to the procedure. 18 Although the additional cost of adding routine iPTH assays varies, a study at Vanderbilt University concluded that the net additional cost of the assay, assuming it was used on a minimum of 100 cases per year, was $40,000 annually. This calculation included the assumption that the equipment and technician remained in the laboratory and did not come to the operating room in a dedicated manner. To date, it has been our approach to use the iPTH assay only in highly selected cases, primarily in complicated reoperative settings, suspicion of multigland disease, and when specifically requested. In one case, MIBI scintigraphy detected what appeared to be a single enlarged gland in a patient with a family history suggestive of familial hyperparathyroidism. Using a radioguided assisted approach, an enlarged parathyroid gland was resected from the location predicted by the scan. However, using the iPTH assay, the serum PTH level did not fall 50% and the contralateral neck was explored, revealing a second enlarged gland. This particular case demonstrated a false-negative MIBI scan. Whether one relies on the iPTH assay or the gamma probe to provide functional evidence that another adenoma or multigland hyperplasia does not exist after excision of the gland identified by MIBI imaging, there will be some failures. Garner and Leight 19 and Gordon et al. 20 demonstrated that the iPTH assay will not totally eliminate failures. One central question is whether the cure rates for primary hyperparathyroidism of 97% to 99% 2,3 reported with careful bilateral exploration by highly experienced endocrine surgeons can be improved on, and whether such a goal should be the major focus of our efforts. When Udelsman compared his results of standard bilateral parathyroidectomy to MIP, there was no statistical difference in cure rates (97% to 99%, respectively). 14 Proving that any type of procedure is significantly better when both have excellent cure rates is difficult. If one wanted to demonstrate that a particular procedure with an almost perfect “cure rate” of 99.5% was significantly better than one with a “cure rate” of 98%, one would need 994 patients per group to detect this difference with 80% power at a 0.05 significance level. Although it is possible that even larger series or multi-institutional studies may detect a statistically significant advantage to scan-directed unilateral parathyroidectomies, the additional advantage in terms of cure rates may be small. Given that it is unlikely that any parathyroid procedure now, or in the future, will always result in cure, the primary advantages of the MIRP procedure should be viewed in the context of patient safety, comfort, length of hospital stay, and costs. In a previous study by Goldstein et al., 9 the MIRP procedure significantly decreased length of stay, operative time, operative charges, and hospital charges compared to standard bilateral exploration under general endotracheal anesthesia. Reduced costs have also reported by others for the MIRP 4 as well as for the MIP procedure. 14The unifying factor in almost all unilateral approaches performed in the United States has been the necessity for a positive preoperative parathyroid scan. The current study included an analysis of the demographic features that might contribute to scan positivity. While the serum PTH level and gland weight were significantly correlated with the probability of a positive scan, it was also determined that the parathyroid adenomas of men were less likely, given the same gland weight and serum PTH level, to be detected by MIBI scintigraphy when compared to those of women. The fact that the interaction term in the statistical analysis was not significant suggests that the same process is involved in scan positivity for men and women; however, there exists a difference in sensitivity between genders. 99mTc-sestamibi used to identify parathyroid glands is distributed in proportion to blood flow and sequestered intracellularly within the mitochondria. 21 The large number of mitochondria present in the cells of most parathyroid adenomas may be responsible for the high isotope uptake and may reflect an increased metabolic rate in adenomas compared to normal parathyroid glands and surrounding thyroid tissue. 22 The increased ability to detect parathyroid adenomas in women may reflect increased metabolic activity in these adenomas compared to those of men. Given that the incidence of primary hyperparathyroidism is significantly higher in women than men, 23,24 and that adenomas in females appear to be easier to detect scintigraphically, one could hypothesize that the hormonal environment may contribute to both the increased incidence of the disease and the increased metabolic activity of the adenomas in women. Data as to whether estrogen receptors are present in parathyroid tissue are conflicting. 25,26 Although neither Udelsman 14 nor Norman 6 reported finding gender as a predictive factor in parathyroid scanning, it is not clear whether these investigators specially evaluated this relationship using sophisticated statistical tools. Larger series will be needed to further evaluate this preliminary finding. However, if it is borne out in future series, it may suggest methods to improve scanning as well as suggest mechanisms related to the etiology of primary hyperparathyroidism. Although a successful and safe procedure is paramount, the primary drive for unilateral explorations ultimately may center on patient convenience, perception, and cost. This may be particularly true in an era when many patients identified with primary hyperparathyroidism have minimal symptoms. The early discharge from the hospital associated with MIRP reflects the relative comfort these patients have as a result of the smaller incision, the decreased extent of dissection, and the avoidance of general anesthesia. The current study demonstrates that MIRP is a safe and efficacious procedure. The apparent influence of gender on parathyroid scan positivity deserves further investigation. Discussion Dr. J. Kenneth Jacobs (Nashville, TN): I rise to compliment Dr. Goldstein on a study well done and on the excellent results that he has obtained. The value of preoperative localization of an adenoma by the use of the sestamibi scan is obvious both to the casual parathyroid surgeon as well as to the experienced parathyroid surgeon. I feel the use of the gamma probe, however, is of little value and adds only to the cost of the procedure. The injection of a sestamibi isotope at Vanderbilt costs $340 and does not seem to aid in more quickly finding the adenoma. Remember, it is the larger adenomas that are the ones that yield the positive scans, and these larger ones are usually not difficult to find, especially if the sestamibi scan preoperatively has localized the area of the adenoma. I see no advantage to local anesthesia either from the standpoint of cost, but certainly not from the standpoint of patient comfort, surgeon comfort, and length of stay in the hospital. Presently, we see our patients 4 to 6 hours after completion of the parathyroidectomy and find most are ready for discharge without an overnight stay. I am at a loss to understand one segment of Dr. Goldstein’s results. What has happened to the 8% to 10% group of patients repeatedly reported in the literature to have “double adenomas”? As none of Dr. Goldstein’s patients were found to have a double adenoma, it would seem to me that this 8% to 10% segment of patients will have recurrences in the future. I personally find it necessary to visually inspect all four glands or to utilize intraoperative rapid PTH assays to confirm removal of all hypersecreting parathyroid tissue. Thus, I ask Dr. Goldstein, will not this group of patients develop recurrent hypercalcemia in the future? Dr. Robert Udelsman (New Haven, CT): I would like to congratulate my colleague Dr. Goldstein for another very nice presentation on the management of hyperparathyroidism using a gamma probe. As he knows, I do not employ the probe. I do view it, however, as a technique that is of great interest, and I follow his work carefully. I have three specific questions for you, Dr. Goldstein. The first has to do with your sestamibi scans. Your overall scan success rate was 65%. Yet there are several series now that show positive scan rates much higher than that and particularly emphasize the importance of using SPECT (single photon emission computed tomography). And I note you don’t use that. My question is, why? Why don’t you push your nuclear medicine doctors to use this? As I believe that is the state of the art for that scan. The second comment I have is, the cure rate for primary hyperparathyroidism is defined as a curative procedure 6 months postoperatively. I would like to encourage you to present your long-term follow-up results to confirm your short-term results, which are really quite excellent. Finally, you note a significant gender predilection for positive scans in that 73% of your female patients had positive scans while only 55% of your male patients had positive scans. When I read the manuscript, this intrigued me. It suggested there is a gender difference in the mitochondria in parathyroid glands in men versus women. Because of that, I went back and looked at our own data. We had a series of 833 consecutive patients, of whom 656 underwent sestamibi scans. The overall scan-positive rate was 81%. The scan-positive rate in women was 81.8%; in the men it was 79.1%. In other words, there was no gender difference for positive scans. I am not sure why your patients are different than ours, but I challenge you to explain that. Dr. George l. Irvin, III (Miami, FL): The stated purpose of Dr. Goldstein’s paper was to evaluate the results of patients undergoing a so-called minimally invasive radioguided parathyroidectomy without the use of the intraoperative hormone assay and based only on the sestamibi scan for localization. From this presentation and a review of his manuscript, which he was kind enough to allow me to see, I would like to make these comments. First, in his series, two thirds of his patients had positive scans, clearly localizing the offending gland. Parathyroidectomy was successful in 98% of these patients. Let’s face it: When it’s easy, it’s easy. You really don’t need a probe. When they are that big and you know where they are, you can go through a small incision and pop it out like taking a nine-iron and chipping it up on the green. It is very easy. That is not the problem. The problem is the 57 patients, clearly one third of the entire group of his hyperparathyroid patients, whose scans were negative, plus those that were equivocal and not included in his data. These patients were subjected to the traditional bilateral neck dissection without the stated advantages of the lesser procedure. Here is where the use of the rapid intraoperative parathyroid hormone assay is clear. We use it on all patients, whether the scan is positive or not. The intraoperative PTH assay can help localize the hyperfunctioning gland by differential venous sampling, by fine-needle aspiration and examination by assay of the sampled tissue which you cannot recognize or identify, and by confirming the complete excision of all hypersecreting tissue. To understand this better, we looked at our series of 415 primary hyperthyroid patients who had undergone this procedure with an intraoperative assay and preoperative scan and found that 20% of these patients had scans that were negative or at least incorrect in localization of the hypersecreting parathyroid glands. Using the intraoperative PTH assay, we were able to achieve operative success in 57% of these scan-negative or equivocal patients with a unilateral or, in your terms, a minimally invasive procedure. In line with this, it seems more fair to examine all patients, not just those that have clear-cut localization, and you must include the more difficult ones when you are evaluating any procedure such as your minimally invasive radioguided parathyroidectomy. Most surgeons report operative success based on a normal serum calcium level 6 months or more after surgery. If your calcium level goes up before 6 months, that is an operative failure in most parathyroid literature. Although some of your patients have been followed for up to 4 years, could you be more specific, as Dr. Udelsman asked, about the number of patients in your series that were followed for at least 6 months to tell us what the operative success rate was? Now that Dr. Goldstein has moved a little north of Nashville, I hope he can get his new institution to obtain a rapid intraoperative PTH assay so that he can take full advantage of this useful surgical adjunct. Dr. Richard E. Goldstein (Nashville, Tennessee): Let me start first with Dr. Brennan’s comments and questions. I think he really hits the nail right on the head in that while people argue about one method versus a different method, central issues are costs, how fast we get people home, how they feel, and how fast they return to work. We have previously shown in our MIRP studies that doing focused approaches cuts down on hospital charges, hospital costs, and patient stay in the hospital. Those same findings have been echoed by Dr. Udelsman’s study in which he looked at length of stay and cost using the MIRP technique. Let me move on to Dr. Udelsman’s question. Yes, we are concerned that our scan positivity rate of 65% or so is lower than what has been reported by others in the literature. However, I think multiple factors can attribute to that. We are certainly looking at that. But as we have shown from the study, the size of the adenomas, the PTH levels, and also gender, can affect the role of positivity. It is also possible that the pattern of referral can affect scan positivity at certain institutions. If, in fact, you are getting patients sent in from different regions of the country and they have been previously scanned and found to be positive, those patients may contribute to higher positivity rates reported from particular institutions. I think that patterns of referral could also affect analysis of effects of gender on scan positivity. I will next deal with Dr. Irvin’s comments in that I think that we are looking at the same thing to some extent, just from different sides of the glass. The main purpose of this study really stems from my philosophical belief that what we are doing with this field is predicated on whether people have positive or negative scans. If in fact they have positive scans, we have very nice options for them that allow them to have very directed surgical procedures performed and we get them home from the hospital quickly. So the purpose of this study was to ask what are the factors that may be attributed to those people who have negative scans and therefore cannot be offered single-sided approaches? And there is, I think, no doubt that patients who have both sides of their neck explored are more sore, do have a slightly longer surgical procedure, and, as both we have shown before and Dr. Udelsman has shown, those patients do stay in the hospital longer. As far as Dr. Jacobs’ comments, I personally do find the probe helpful. I don’t find it necessary all the time, but I think one could also argue that the quick PTH assay is not needed all the time. You have a positive scan, you find a large adenoma, almost certainly (this is what this data shows) those patients are cured taking out the single adenoma. The probe can be very helpful for patients who have deep adenomas down deep in the tracheal-esophageal groove and it allows to you make a smaller incision. I would also want to make a comment that it is very nice to have the quick PTH assay. But not all medical centers have this modality. There is also a certain cost to having them. A lot more hospitals, I would venture to say, have hand-held gamma probes for use not just in parathyroid surgery but hand-held gamma probes that are being mainly used for sentinel node mapping. So I think that this technique is probably more applicable to most hospitals than those that would want to implement the quick PTH assay. Dr. Jacobs also asked about double adenomas. I think his quoted figure of 8% to 10% as the incidence of double adenomas would be considered very high by most people. We, in fact, did have a few double adenomas in the scan negative group. 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