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Parathyroidectomy outcomes according to operative approach
The American Journal of Surgery 193 (2007) 368 –373
Scientific paper
Parathyroidectomy outcomes according to operative approach Todd D. Beyer, M.D., Carmen C. Solorzano, M.D., Fred Starr, M.D., Naris Nilubol, M.D., Richard A. Prinz, M.D.* Rush University Medical Center, Chicago, IL, USA Manuscript received August 12, 2006; revised manuscript Septmeber 20, 2006 Presented at the 49th Annual Meeting of the Midwest Surgical Association, Mackinac Island, MI, August 6 –9, 2006
Abstract Background: Parathyroidectomy for primary sporadic hyperparathyroidism (psHPT) has evolved with advances in preoperative gland localization and intraoperative parathyroid hormone (ioPTH) monitoring to minimally invasive approaches (MIPS). Methods: Two hundred twenty patients underwent parathyroidectomy for psHPT. Forty-nine patients underwent bilateral neck exploration (BNE) (group 1), 60 patients underwent BNE with ioPTH monitoring (group 2), and 111 patients underwent MIPS with ioPTH monitoring (group 3). Results: At 3 months postoperatively, mean serum calcium and intact parathyroid hormone (PTH) levels were similar between groups, and eucalcemia rates were 100%, 100%, and 99%. The ultimate rates of persistent disease and recurrence were also similar. Operative time was shorter in group 3 compared to group 2 (P ⬍ .001) but not group 1. Frozen sections and patient charges were significantly lower in group 3 compared to groups 1 and 2 (P ⬍ .005). Conclusion: Parathyroidectomy for psHPT is highly successful with these techniques. When a MIPS approach can be done, it is potentially quicker and associated with lower patient charges. © 2007 Excerpta Medica Inc. All rights reserved. Keywords: Hyperparathyroidism; Parathyroidectomy; Minimally invasive; Bilateral exploration; Intraoperative PTH; Outcome
The surgical approach of parathyroidectomy for primary sporadic hyperparathyroidism (psHPT) continues to evolve. In the latter part of the 20th century, routine exploration of all 4 parathyroid glands (bilateral neck exploration [BNE]) emerged as the gold standard. Experienced endocrine surgeons reported cure rates of greater than 95% with a less than 1% chance of recurrent laryngeal nerve injury or permanent hypoparathyroidism and essentially no mortality [1– 4]. Since 65% to 85% of psHPT is caused by a single adenoma, the need for BNE was questioned, and limited exploration (MIPS) was evaluated. To minimize exploration, accurate localization of the abnormal gland is paramount. Sestamibi scanning and cervical ultrasound are the preferred modalities, but they can be inaccurate in multigland disease. The development of intraoperative parathy-
* Corresponding author. 1653 W. Congress Pkwy., General Surgery, Jelke 785, Chicago, IL 60612. Tel.: ⫹1-312-942-6379; fax: ⫹1-312-9422867. E-mail address: [email protected]
roid hormone monitoring [5] (ioPTH) has added a functional and objective guide to determine the extent of resection and predict surgical cure. Many authors have now demonstrated that MIPS can achieve high surgical cure rates and low complication rates when compared to BNE [7–12]. This retrospective study compares the outcomes of 3 different approaches to parathyroidectomy: BNE, BNE with ioPTH monitoring, and MIPS with ioPTH monitoring. Methods Over a period of 58 months, 220 patients with psHPT underwent initial parathyroidectomy at a single institution. The patients were retrospectively segregated into 3 groups based on surgical approach with intention to treat. The patients were consecutive within groups but not between groups. Forty-nine patients underwent a planned BNE (group 1), 60 patients underwent a planned BNE with ioPTH monitoring (group 2), and 111 patients underwent an ioPTH guided minimally invasive approach (group 3). Outcomes from some patients in groups 1 and 2 were previously reported from this institution [1].
0002-9610/07/$ – see front matter © 2007 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.09.023
T.D. Beyer et al. / The American Journal of Surgery 193 (2007) 368 –373
The patients in group 1 all underwent BNE prior to the availability of ioPTH at our center. Some required a simultaneous thyroidectomy. Group 2 included patients who had BNE with ioPTH monitoring prior to our use of minimally invasive techniques, as well as patients who demonstrated contraindications to MIPS (negative localization, discordant localization, and the need for simultaneous thyroidectomy). During all bilateral explorations, an attempt was made to identify 4 parathyroid glands, and glands were excised based on gross appearance and morphology. In group 2, similar criteria were applied; however, ioPTH monitoring was also used to confirm biochemical cure. All patients in group 3 had an initial focused exploration guided by ioPTH monitoring during which 1 or 2 unilateral glands were visualized through a small incision. Candidates for MIPS were patients in whom the localization study(ies) suggested a single abnormal gland. The approach was converted to BNE if an abnormal gland was not identified and/or if the ioPTH did not drop appropriately. A true positive ioPTH (Immulite DPC, Los Angeles, CA) result following gland excision was defined as a greater than 50% drop from the peak pre-excision value at 5 or 10 minutes after gland removal with the final value within normal range (12 to 72 pg/mL). The patients in group 3 who required conversion from a focused approach to BNE remained in the study based on intention to treat. Although BNE was not a contraindication to same-day discharge, most of these patients were routinely admitted for 23 hour observation, especially if they also had a concomitant total thyroidectomy. MIPS patients were offered same-day discharge provided the operation was uncomplicated. Patients were routinely placed on oral calcium supplementation postoperatively until serum levels and/or subjective symptoms excluded critical hypocalcemia during the immediate postoperative period. Localization with sestamibi scanning and/or ultrasonography was done in all group 3 patients. In groups 1 and 2, preoperative localization was not usually done. A serum calcium level was obtained within 14 days of surgery as was a serum intact parathyroid hormone (PTH) level for those patients treated since 2001. Serum calcium and PTH levels were again measured at 1 to 3 months after parathyroidectomy when possible. Surgical success was based on a postoperative reduction in serum calcium to normal (range 8.7 to 10.7 mg/dL) or subnormal levels. Long-term cure was defined as sustained eucalcemia from 6 months to most recent follow-up. Persistent hyperparathyroidism (HPT) diagnosed within 6 months of surgery and recurrent HPT presenting after 6 months were both considered operative failures. Hypoparathyroidism was defined persistently low serum PTH (⬍10 pg/mL) lasting beyond 3 months and requiring oral vitamin D supplements to maintain normocalcemia. Eucalcemic PTH elevation was defined as an elevated serum PTH with normal or low serum calcium. Partial gland excisions were retrospectively defined as biopsies (diagnostic) when less than 50% was removed and as subtotal excisions (therapeutic) when greater than 50% was removed. Patients were considered to have multigland disease if more than 1 gland was totally/subtotally excised or if a single gland excision resulted in operative failure. Study end points included rates of eucalcemia at 3 months, cure and failure rates, operative time, number of
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Table 1 Patient demographics and preoperative studies
No. of patients Age (y) Male Female Mean serum Ca (mg/dL) Mean serum PTH (pg/mL) Mean creatinine (mg/dL) 24-hour urine Ca (mg)* Mean minimum T score† No. patients T score ⬍ ⫺2.0†
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
49
60
58 ⫾ 11 10 (20%) 39 (80%) 11.2 ⫾ 0.9 168 ⫾ 153 1.0 ⫾ 0.3 271 ⫾ 108 ⫺1.4 ⫾ 1.4 6/19 32%
61 ⫾ 15 9 (15%) 51 (85%) 11.2 ⫾ 1.0 193 ⫾ 165 1.0 ⫾ 0.4 229 ⫾ 135 ⫺1.7 ⫾ 1.0 15/34 44%
111 58 ⫾ 14 26 (23%) 85 (77%) 11.0 ⫾ 0.9 175 ⫾ 158 1.0 ⫾ 0.3 366 ⫾ 219 ⫺1.5 ⫾ 1.5 21/57 37%
P
NS NS NS NS NS NS NS NS NS
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); Ca ⫽ calcium; PTH ⫽ intact parathyroid hormone; NS ⫽ not significant. * Data available in 49/220 patients. † Data available in 110/220 patients.
frozen sections, total glands removed, the rate of recurrent laryngeal nerve (RLN) injury, and patient charges. Permanent RLN injury was defined retrospectively based on 3 factors: nerve injury identified at the time of operation, postoperative respiratory difficulty requiring tracheostomy for longer than 6 to 12 months, and prolonged voice changes not resolving in 6 to 12 months. Total charge was based on the hourly rate of anesthesia and operating room (including instruments) times the operative time, the number of intraoperative frozen sections, the number of ioPTH assays performed, the preoperative localization studies, and overnight hospital charges. Statistical analysis was performed on SSPS software (SPSS Inc., Chicago, IL) using chi-square, Fisher’s exact test, one-way analysis of variance, Kruskal-Wallis test, 2-sample t test, and Wilcoxon rank sum, with P values less than .05 being statistically significant. This retrospective study was approved by the Rush University Institutional Review Board. Results Preoperative patient demographics, serum calcium and PTH levels, urinary calcium levels, renal function, and bone mineral density were similar between groups (Table 1). Urinary calcium levels and bone mineral density were available on 49/220 and 110/220 patients, respectively. At 2 weeks postoperatively (Table 2), mean calcium values were significantly lower in group 1 (8.9 ⫾ 0.9 mg/dL; P ⫽ .009) compared to groups 2 (9.4 ⫾ 0.9 mg/dL) and 3 (9.2 ⫾ 0.7 mg/dL). In groups 1 through 3, respectively, 46/46 (100%), 58/58 (100%), and 99/100 (99%) patients achieved eucalcemia. PTH was not routinely measured at this postoperative time interval early in the study and was excluded from analysis. Seventeen patients were unavailable for follow-up. At 1 to 3 months postoperatively, mean serum calcium and PTH levels were similar (Table 3). Data wer available for 160/220 (73%) patients. Surgical success at this interval, based on eucalcemia, was 32/32 (100%), 52/52 (100%), and
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Table 2 Early postoperative results (within 2 weeks)
Mean serum Ca (mg/dL) Mean serum PTH (pg/ml) Eucalcemia
Table 4 Results of parathyroidectomy at last follow-up
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
P
8.9 ⫾ 0.9 N/A 46/46 100%
9.4 ⫾ 0.9 N/A 58/58 100%
9.2 ⫾ 0.7 47 ⫾ 46 99/100 99%
.009 N/A NS
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); Ca ⫽ calcium; PTH ⫽ intact parathyroid hormone; NS ⫽ not significant; N/A ⫽ not applicable.
75/76 (98.7%). Seven patients had transient postoperative hypercalcemia together with a low PTH level, which resolved following cessation of oral calcium supplements. The incidence of eucalcemic PTH elevation was 25%, 37%, and 45% in groups 1, 2, and 3, respectively, with a trend toward a higher incidence in group3 compared to group 1 (P ⫽ .055). Hypoparathyroidism was found in 0/32, 2/52 (3.8%), and 2/76 (2.6%) patients in groups 1, 2, and 3, respectively. Table 4 summarizes outcomes for all groups based on most recent follow-up. Data were available in 219 patients. Follow-up was shortest in group 3 (3.7 ⫾ 5.6 months) compared to groups 1 (11.9 ⫾ 21.2) and 2 (8.2 ⫾ 17.7). Mean serum calcium and PTH levels were similar in each group. Sustained eucalcemia was achieved in 47/49 (95.9%), 60/60 (100%), and 109/111 (98.2%) patients in groups 1, 2, and 3, respectively. Persistent disease was found in a total of 2 patients in group 3 only (1.8%). One patient had a single adenoma removed via a minimally invasive approach and was found within 3 to 6 months to have persistent disease following brief eucalcemic PTH elevation. The ioPTH showed an 82% reduction at 10 minutes post gland excision. Eight months after her initial operation, the patient underwent a successful subtotal parathyroidectomy to treat multigland hyperplasia. The second patient had double adenomas removed during a MIPS converted to BNE. The ioPTH levels never dropped following Table 3 One- to 3-month postoperative results
Mean serum Ca (mg/dL) Mean serum PTH (pg/mL) Eucalcemia Eucalcemic elevated PTH Hypoparathyroid
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
P
9.3 ⫾ 0.7 74 ⫾ 62 32/32 100% 8/32 25% 0/32 0/32
9.5 ⫾ 0.6 83 ⫾ 98 52/52 100% 19/52 37% 2/52 3.8%
9.3 ⫾ 0.6 73 ⫾ 79 75/76 99% 34/76 45% 2/76 2.6%
NS NS NS .055* NS
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); Ca ⫽ calcium; PTH ⫽ intact parathyroid hormone; NS ⫽ not significant. * Group 1 vs. group 3.
Mean follow-up (mo) Mean serum Ca (mg/dL) Mean serum PTH (pg/mL) Eucalcemia Persistent disease Recurrent disease
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
P
11.9 ⫾ 21.2 9.1 ⫾ 0.7 77 ⫾ 64 47/49 95.9% 0
8.2 ⫾ 17.7 9.4 ⫾ 0.6 80 ⫾ 101 60/60 100% 0 1.8% 0
3.7 ⫾ 5.6 9.3 ⫾ 0.6 61 ⫾ 46 108/110 98.2% 2/110 NS 0
NS NS NS NS
2/49 4.1%
NS NS
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); Ca ⫽ calcium; PTH ⫽ intact parathyroid hormone; NS ⫽ not significant.
gland excisions and predicted operative failure. She had hypercalcemia immediately after surgery and at 3 months and is awaiting re-exploration. Two patients were found to have recurrent HPT after operation. Both patients were in group 1 (4.1%) and had single adenomas removed during their initial operation. Both demonstrated persistent eucalcemic PTH elevation prior to recurrence, which was diagnosed at 8 and 90 months. One of these patients underwent re-exploration, at which time a second adenoma was removed, and is cured. The other patient declined re-operation and has mild hypercalcemia. Table 5 summarizes intraoperative data. Twenty-eight procedures (25%) in group 3 were converted from a minimally invasive approach to a BNE. There were significant differences between groups regarding operative time, frozen sections, and patient charges (P ⬍ .001). Paired analysis demonstrated that the operations in group 3 (119 ⫾ 59 minutes) were significantly shorter than those in group 2 only (129 ⫾ 48 minutes; P ⬍ .001) and were associated with significantly fewer intraoperative frozen sections (1.2 ⫾ 2.1) compared to groups 1 (3.8 ⫾ 1.9; P ⬍ .001) and 2 (2.1 ⫾ 1.7; P ⬍ .001). The mean numbers of glands totally or subtotally excised per patient were not significantly different. Of the glands totally excised, size and weight were also similar. There was a trend toward less multi-gland disease in those patients in group 3 undergoing a minimally invasive approach (29% vs. 30% vs. 19%). A significantly greater number of patients in group 3 were discharged on the day of surgery (0 vs. 13% vs. 47%; P ⬍ .001). Total charges were significantly lower in group 3 compared to groups 1 and 2 ($4956 ⫾ 556 vs. $4757 ⫾ 1134 vs. $3708 ⫾ 1728; P ⬍ .001). Significantly more patients in group 2 had combined parathyroid and thyroid procedures (20% vs. 48% vs. 4 %; P ⬍ .001). Excluding those patients who underwent concomitant thyroidectomy from analysis, the total charges remained lower in group 3 ($3667 ⫾ 1737) compared to groups 1 ($4787 ⫾ 455; P ⬍ .001) and 2 ($4272 ⫾ 1080; P ⫽ .03); however, the operative time was no longer significantly different (111 ⫾ 29 vs. 121 ⫾ 41 vs. 117 ⫾ 58 minutes; P ⫽ .75). The overall incidence of permanent RLN injury was 2/220 (0.9%). Both patients were in group 2. One patient
T.D. Beyer et al. / The American Journal of Surgery 193 (2007) 368 –373
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Table 5 Intraoperative data
Operative time (minutes) No. frozen sections Mean no. ioPTH samples Mean no. glands excised Mean gland size (cm) Mean gland weight (mg) Total charges ($) No. patients autotransplanted Permanent RLN injury Same-day discharge Single gland disease Multi gland disease Thyroid surgery
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
P
129 ⫾ 48 3.8 ⫾ 1.9 N/A 1.43 ⫾ 0.82 1.9 ⫾ 0.9 1358 ⫾ 1585 4956 ⫾ 556 4/49 8% 0
151 ⫾ 61 2.1 ⫾ 1.7 4.8 ⫾ 0.9 1.35 ⫾ 0.66 1.8 ⫾ 1.0 1647 ⫾ 3645 4757 ⫾ 1134 3/60 5% 2/60 3% 8/60 13% 41/60 68% 18/60 30% 29/60 48%
119 ⫾ 59 1.2 ⫾ 2.1 4.9 ⫾ 1.5 1.34 ⫾ 0.82 1.8 ⫾ 0.7 1457 ⫾ 1609 3708 ⫾ 1728 2/111 2% 0
.001* .001* NS NS NS NS .001* NS
52/111 47% 91/111 82% 19/111 17% 4/111 4%
⬍.001
0 34/49 69% 14/49 29% 10/49 20%
NS
.104 .097 ⬍.001
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); RLN ⫽ recurrent laryngeal nerve; NS ⫽ not significant.
had a recognized injury at the time of operation, and 1 patient required a postoperative tracheostomy for respiratory difficulty. Three additional patients (1.4%) experienced transient postoperative vocal hoarseness, which resolved within 6 to 12 months and likely represented temporary RLN injury. These 3 patients now have normal voices. Comments Despite evolutionary changes in surgical approach, the success of parathyroidectomy continues to be based on postoperative normalization of serum calcium. Sustained eucalcemia beyond 6 months suggests cure. BNE with 4-gland visualization and biopsy relies on gland size and appearance to identify abnormal parathyroid glands and determine the extent of resection for surgical success. The use of intraoperative PTH assay, made practical by Irvin and Deriso [6], provided a biochemical adjunct to confirm cure by ensuring that all hyperfunctioning parathyroid tissue was removed. Thus, a functional component was added to the intraoperative decision algorithm, allowing surgical exploration to be minimized when appropriate. To become familiar with the use of ioPTH assays, some surgeons have used ioPTH as an adjunct to BNE. Starr et al from our center compared 50 patients undergoing BNE to another 50 patients undergoing BNE with ioPTH. Although the use of ioPTH significantly reduced the need for intraoperative frozen sections, the operative times and surgical success rates were similar, suggesting that the addition of ioPTH to intraoperatively assess gland function added little benefit to the success of a bilateral exploration [3]. Other studies have demonstrated that routine use of ioPTH not only improves outcomes, but also facilitates a limited exploration. Irvin et al compared ioPTH-guided limited parathyroidectomy with BNE in more than 700
patients and showed that ioPTH increased overall success from 94% to 97% [4]. Similar rates of success using MIPS compared to BNE have been reported by other investigators [7–13]. On the other hand, additional studies from Stalberg et al and Jacobson et al indicate that ioPTH monitoring may not improve the results of MIPS when localization studies are good, and patients are carefully selected [14,15]. End points other than cure have been examined. Some high-volume centers are observing a lower incidence of multi-gland disease in those patients undergoing limited explorations compared to BNE [4,16]. Yet, reported failure and recurrence rates between groups are so far similar. Are pathological glands being missed and left behind during focused explorations despite the functional adjunct of ioPTH? Will recurrence rates be higher? Alternatively, are more glands being removed during BNE which are grossly abnormal yet not hypersecretory? These and other questions remain unanswered. In this study, a high success rate was found regardless of the surgical approach. Although the mean serum calcium levels 14 days after operation were within normal range in all groups, the mean value in group 1 (BNE) was significantly lower. One possible explanation is that parathyroid glands are temporarily injured after biopsy. This is supported by the greater number of frozen sections in group 1. The mean number of glands removed in each group was similar. Although the mean duration of follow-up between groups was variable, we identified 2 patients with persistent disease and 2 patients with recurrence. Both patients with persistent HPT were in group 3 (1.8%), and both patients with recurrent HPT were in group 1 (4.7%). Recurrences in the other groups may not be evident due to shorter lengths of follow-up. One of the failures was predicted by a true negative ioPTH result and immediate postoperative hyper-
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calcemia. In groups 1, 2, and 3, the rates of sustained eucalcemia at last follow-up were 95.9%, 100%, and 98.2%, respectively. Not every patient was available for follow-up beyond 6 months (particularly in group 3), and defining those eucalcemic patients as cured should be done with caution. In all 220 patients, the rates of persistent disease and recurrence were each 2/220 (0.9%). Similar to other studies, there was a trend toward less multi-gland disease in the MIPS group. This can be explained by patient selection and surgical approach. Our indications for a planned BNE include discordant localization, negative studies, studies with more than 1 abnormal focus, or need for thyroidectomy. Multi-gland disease is more likely when localization studies are not clear cut. Group 3 patients had significantly shorter operative times, fewer frozen sections, lower overall charges, and a greater likelihood to have outpatient procedures. The difference in operative time observed in this study may be associated with the difference in concomitant thyroid procedures and should be interpreted cautiously. The lower charges appear associated with the trend toward outpatient surgery. Due to the expense of required localization studies, monetary savings are potentially lost in MIPS patients who are not discharged on the day of surgery. Conclusion In experienced hands, parathyroidectomy for psHPT is highly successful regardless of surgical approach with no significant differences in rates of success or recurrence, although follow-up is limited. A MIPS approach is potentially quicker and associated with lower patient charges. References [1] Starr FL, DeCresce R, Prinz RA. Use of intraoperative parathyroid hormone measurement does not improve success of bilateral neck exploration for hyperparathyroidism. Arch Surg 2001;136:536 – 42. [2] van Heerden JA, Grant CS. Surgical treatment of primary hyperparathyroidism: an institutional perspective. World J Surg 1991; 15:688 –92. [3] Low RA, Katz AD. Parathyroidectomy via bilateral cervical exploration: a retrospective review of 866 cases. Head Neck 1998;20: 583–7. [4] Irvin GL 3rd, Solorzano CC, Carneiro DM. Quick intraoperative parathyroid hormone assay: surgical adjunct to allow limited parathyroidectomy, improve success rate, and predict outcome. World J Surg 2004;28:1287–92. [5] Nussbaum SR, Thompson AR, Hutcheson KA, et al. Intraoperative measurement of parathyroid hormone in the surgical management of hyperparathyroidism. Surgery 1988;104:1121–7. [6] Irvin GL 3rd, Deriso GT. A new, practical intraoperative parathyroid hormone assay. Am J Surg 1994;168:466 – 8. [7] Westerdahl J, Lindblom P, Bergenfelz A. Measurement of intraoperative parathyroid hormone predicts long-term operative success. Arch Surg 2002;137:186 –90. [8] Inabnet WB 3rd, Dakin GF, Haber RS, et al. Targeted parathyroidectomy in the era of intraoperative parathormone monitoring. World J Surg 2002;26: 921–5. [9] Carneiro DM, Irvin GL 3rd. Late parathyroid function following successful parathyroidectomy guided by intraoperative hormone assay (QPTH) compared with the standard bilateral neck exploration. Surgery 2001;128: 925–9. [10] Udelsman R, Donovan PI, Sokoll LJ. One hundred consecutive minimally invasive parathyroid explorations. Ann Surg 2000;232:331–9. [11] Vignali E, Picone A, Materazzi G, et al. A quick intraoperative parathyroid hormone assay in the surgical management of patients
[12] [13] [14]
[15]
[16]
with primary hyperparathyroidism: a study of 206 consecutive cases. Eur J Endocrinol 2002;146:783– 8. Miura D, Wada N, Arici C, et al. Does intraoperative quick parathyroid hormone assay improve the results of parathyroidectomy? World J Surg 2002;26:926 –30. Chen H, Eberhard M, Starling JR. A comprehensive Evaluation of perioperative adjuncts during minimally invasive parathyroidectomy: which is most reliable? Ann Surg 2005;242:375– 80. Stalberg P, Sidhu S, Sywak M, et al. Intraoperative parathyroid hormone measurement during minimally invasive parathyroidectomy: does it “value-add” to decision-making? J Am Coll Surg 2006; 203:1– 6. Jacobson SR, Van Heerden JA, Farley DR, et al. Focused cervical exploration for primary hyperparathyroidism without intraoperative parathyroid hormone monitoring or use of the gamma probe. World J Surg 2004;28:1127–31. Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg 2005;132:359 –72.
Discussion Steven A. DeJong, M.D. (Maywood, IL): There are probably centers in the country that have decided because of low volume parathyroid work, that they simply can’t afford the use of intraoperative PTH with their patients. Can you tell us in the patients that underwent bilateral exploration, how often did the use of intraoperative parathyroid hormone analysis change what you did? It has been the assumption that the procedure using a bilateral exploration is only cost effective if we send patients home the same day. Is this possible to conclude from your data? Eucalcemic parathyroid elevation was the highest in your unilateral exploration group. Do you think that this phenomenon predicts future persistent or recurrent parathyroid disease, and how long should this phenomenon go on before a surgeon gets concerned that there may be persistent or recurrent disease present? How has your work changed your operative approach at your hospital in caring for these patients? Todd D. Beyer, M.D.: The surgical objective for the patient’s in group 2 was to perform a bilateral exploration while at the same time assessing the efficacy of intraoperative PTH monitoring. So although the hormone monitoring was evaluated at the time of surgery, it did not necessarily alter the surgical outcome or the course of the operation. In some of the latter cases in group 2, the role of intraoperative PTH monitoring became more active, lateralizing perhaps the gland from the left to the right and also ultimately predicting biochemical cure. The goal and design of this study was not so much to assess the impact of intraoperative PTH monitoring on bilateral exploration versus a focused approach. But in examining group 2, the primary way that hormone monitoring could impact the ultimate outcome of surgery would be in the number of glands removed. Patients in that group who had more than 1 gland removed, roughly two-thirds of those patients, had an initial true negative result on their hormone monitoring, which would prompt additional exploration in looking for other glands. Perhaps another way to look at this question would be if you are planning to do a bilateral exploration from the start, could the use of hormone monitoring be eliminated? Although this
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study was not designed to answer that question, the addition of hormone monitoring to a bilateral exploration does reduce the number of intraoperative frozen sections required for success. Does it improve the success of the operation as a whole? I don’t think we can really safety answer that from this data. I think a key element to success of this operation that can’t be overlooked is the personal experience of the surgeon and their ability to recognize an abnormal parathyroid gland, particularly in multi-gland disease. One of the major elements to the charge savings that were seen in group 3 is due to the ability to discharge these patients on the same day. We feel that without hypercalcemia, a patient does not have persistent or recurrent disease. Eucalcemic PTH elevation has been widely reported, widely observed and speculated upon. Although it can precede recurrence, I don’t think it necessarily predicts recurrence. It is more closely associated with other variables, disease severity, adenoma size, renal function, vitamin D status, bone density, and severity of bone disease. We monitor these patients more closely postoperatively for evidence of hypercalcemia and we give them calcium and vitamin D supplementation. We have some early data that shows that this might accelerate the normalization process postoperatively. Success, regardless of approach, is high in experienced hands, and I think an area where we can strive to improve upon would be in getting some of these patients home the same day, if at all possible.
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Herb Chen, M.D. (Madison, WI): Your group 3 probably had a higher incidence of single adenomas present. If you analyze your data just looking at patients with single adenomas, perhaps those differences and charges would disappear, and really what you are seeing is you have more patients with single adenomas in the last group, which you are able to send home and thus charges are much less. Todd D. Beyer, M.D.: I think it is possible that since we tend to equate single gland disease to successful closed approach with same day discharge, perhaps those variables might be similar if not interchangeable or they might reflect one another. So by eliminating those patients who are discharged the same day, we weren’t necessarily eliminating those with a single gland, but maybe got quite close to that. Christopher R. McHenry, M.D. (Cleveland, OH): The focused approach is dependent upon the accuracy of your preoperative localization studies, and dependent on whether or not you find they have associated thyroid disease as you mentioned. In patients that present to you with primary hyperparathyroidism, what percent of patients are you actually able to do a focused parathyroidectomy? Todd D. Beyer, M.D.: In this study, we did not exactly look at that number, but historically based on other studies, I think it can be in the range of 60% to 75%. So based on the pathophysiology of the disease and the accuracy of the localization studies, the vast majority of patients are candidates for a minimally invasive approach.
Scientific paper
Parathyroidectomy outcomes according to operative approach Todd D. Beyer, M.D., Carmen C. Solorzano, M.D., Fred Starr, M.D., Naris Nilubol, M.D., Richard A. Prinz, M.D.* Rush University Medical Center, Chicago, IL, USA Manuscript received August 12, 2006; revised manuscript Septmeber 20, 2006 Presented at the 49th Annual Meeting of the Midwest Surgical Association, Mackinac Island, MI, August 6 –9, 2006
Abstract Background: Parathyroidectomy for primary sporadic hyperparathyroidism (psHPT) has evolved with advances in preoperative gland localization and intraoperative parathyroid hormone (ioPTH) monitoring to minimally invasive approaches (MIPS). Methods: Two hundred twenty patients underwent parathyroidectomy for psHPT. Forty-nine patients underwent bilateral neck exploration (BNE) (group 1), 60 patients underwent BNE with ioPTH monitoring (group 2), and 111 patients underwent MIPS with ioPTH monitoring (group 3). Results: At 3 months postoperatively, mean serum calcium and intact parathyroid hormone (PTH) levels were similar between groups, and eucalcemia rates were 100%, 100%, and 99%. The ultimate rates of persistent disease and recurrence were also similar. Operative time was shorter in group 3 compared to group 2 (P ⬍ .001) but not group 1. Frozen sections and patient charges were significantly lower in group 3 compared to groups 1 and 2 (P ⬍ .005). Conclusion: Parathyroidectomy for psHPT is highly successful with these techniques. When a MIPS approach can be done, it is potentially quicker and associated with lower patient charges. © 2007 Excerpta Medica Inc. All rights reserved. Keywords: Hyperparathyroidism; Parathyroidectomy; Minimally invasive; Bilateral exploration; Intraoperative PTH; Outcome
The surgical approach of parathyroidectomy for primary sporadic hyperparathyroidism (psHPT) continues to evolve. In the latter part of the 20th century, routine exploration of all 4 parathyroid glands (bilateral neck exploration [BNE]) emerged as the gold standard. Experienced endocrine surgeons reported cure rates of greater than 95% with a less than 1% chance of recurrent laryngeal nerve injury or permanent hypoparathyroidism and essentially no mortality [1– 4]. Since 65% to 85% of psHPT is caused by a single adenoma, the need for BNE was questioned, and limited exploration (MIPS) was evaluated. To minimize exploration, accurate localization of the abnormal gland is paramount. Sestamibi scanning and cervical ultrasound are the preferred modalities, but they can be inaccurate in multigland disease. The development of intraoperative parathy-
* Corresponding author. 1653 W. Congress Pkwy., General Surgery, Jelke 785, Chicago, IL 60612. Tel.: ⫹1-312-942-6379; fax: ⫹1-312-9422867. E-mail address: [email protected]
roid hormone monitoring [5] (ioPTH) has added a functional and objective guide to determine the extent of resection and predict surgical cure. Many authors have now demonstrated that MIPS can achieve high surgical cure rates and low complication rates when compared to BNE [7–12]. This retrospective study compares the outcomes of 3 different approaches to parathyroidectomy: BNE, BNE with ioPTH monitoring, and MIPS with ioPTH monitoring. Methods Over a period of 58 months, 220 patients with psHPT underwent initial parathyroidectomy at a single institution. The patients were retrospectively segregated into 3 groups based on surgical approach with intention to treat. The patients were consecutive within groups but not between groups. Forty-nine patients underwent a planned BNE (group 1), 60 patients underwent a planned BNE with ioPTH monitoring (group 2), and 111 patients underwent an ioPTH guided minimally invasive approach (group 3). Outcomes from some patients in groups 1 and 2 were previously reported from this institution [1].
0002-9610/07/$ – see front matter © 2007 Excerpta Medica Inc. All rights reserved. doi:10.1016/j.amjsurg.2006.09.023
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The patients in group 1 all underwent BNE prior to the availability of ioPTH at our center. Some required a simultaneous thyroidectomy. Group 2 included patients who had BNE with ioPTH monitoring prior to our use of minimally invasive techniques, as well as patients who demonstrated contraindications to MIPS (negative localization, discordant localization, and the need for simultaneous thyroidectomy). During all bilateral explorations, an attempt was made to identify 4 parathyroid glands, and glands were excised based on gross appearance and morphology. In group 2, similar criteria were applied; however, ioPTH monitoring was also used to confirm biochemical cure. All patients in group 3 had an initial focused exploration guided by ioPTH monitoring during which 1 or 2 unilateral glands were visualized through a small incision. Candidates for MIPS were patients in whom the localization study(ies) suggested a single abnormal gland. The approach was converted to BNE if an abnormal gland was not identified and/or if the ioPTH did not drop appropriately. A true positive ioPTH (Immulite DPC, Los Angeles, CA) result following gland excision was defined as a greater than 50% drop from the peak pre-excision value at 5 or 10 minutes after gland removal with the final value within normal range (12 to 72 pg/mL). The patients in group 3 who required conversion from a focused approach to BNE remained in the study based on intention to treat. Although BNE was not a contraindication to same-day discharge, most of these patients were routinely admitted for 23 hour observation, especially if they also had a concomitant total thyroidectomy. MIPS patients were offered same-day discharge provided the operation was uncomplicated. Patients were routinely placed on oral calcium supplementation postoperatively until serum levels and/or subjective symptoms excluded critical hypocalcemia during the immediate postoperative period. Localization with sestamibi scanning and/or ultrasonography was done in all group 3 patients. In groups 1 and 2, preoperative localization was not usually done. A serum calcium level was obtained within 14 days of surgery as was a serum intact parathyroid hormone (PTH) level for those patients treated since 2001. Serum calcium and PTH levels were again measured at 1 to 3 months after parathyroidectomy when possible. Surgical success was based on a postoperative reduction in serum calcium to normal (range 8.7 to 10.7 mg/dL) or subnormal levels. Long-term cure was defined as sustained eucalcemia from 6 months to most recent follow-up. Persistent hyperparathyroidism (HPT) diagnosed within 6 months of surgery and recurrent HPT presenting after 6 months were both considered operative failures. Hypoparathyroidism was defined persistently low serum PTH (⬍10 pg/mL) lasting beyond 3 months and requiring oral vitamin D supplements to maintain normocalcemia. Eucalcemic PTH elevation was defined as an elevated serum PTH with normal or low serum calcium. Partial gland excisions were retrospectively defined as biopsies (diagnostic) when less than 50% was removed and as subtotal excisions (therapeutic) when greater than 50% was removed. Patients were considered to have multigland disease if more than 1 gland was totally/subtotally excised or if a single gland excision resulted in operative failure. Study end points included rates of eucalcemia at 3 months, cure and failure rates, operative time, number of
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Table 1 Patient demographics and preoperative studies
No. of patients Age (y) Male Female Mean serum Ca (mg/dL) Mean serum PTH (pg/mL) Mean creatinine (mg/dL) 24-hour urine Ca (mg)* Mean minimum T score† No. patients T score ⬍ ⫺2.0†
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
49
60
58 ⫾ 11 10 (20%) 39 (80%) 11.2 ⫾ 0.9 168 ⫾ 153 1.0 ⫾ 0.3 271 ⫾ 108 ⫺1.4 ⫾ 1.4 6/19 32%
61 ⫾ 15 9 (15%) 51 (85%) 11.2 ⫾ 1.0 193 ⫾ 165 1.0 ⫾ 0.4 229 ⫾ 135 ⫺1.7 ⫾ 1.0 15/34 44%
111 58 ⫾ 14 26 (23%) 85 (77%) 11.0 ⫾ 0.9 175 ⫾ 158 1.0 ⫾ 0.3 366 ⫾ 219 ⫺1.5 ⫾ 1.5 21/57 37%
P
NS NS NS NS NS NS NS NS NS
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); Ca ⫽ calcium; PTH ⫽ intact parathyroid hormone; NS ⫽ not significant. * Data available in 49/220 patients. † Data available in 110/220 patients.
frozen sections, total glands removed, the rate of recurrent laryngeal nerve (RLN) injury, and patient charges. Permanent RLN injury was defined retrospectively based on 3 factors: nerve injury identified at the time of operation, postoperative respiratory difficulty requiring tracheostomy for longer than 6 to 12 months, and prolonged voice changes not resolving in 6 to 12 months. Total charge was based on the hourly rate of anesthesia and operating room (including instruments) times the operative time, the number of intraoperative frozen sections, the number of ioPTH assays performed, the preoperative localization studies, and overnight hospital charges. Statistical analysis was performed on SSPS software (SPSS Inc., Chicago, IL) using chi-square, Fisher’s exact test, one-way analysis of variance, Kruskal-Wallis test, 2-sample t test, and Wilcoxon rank sum, with P values less than .05 being statistically significant. This retrospective study was approved by the Rush University Institutional Review Board. Results Preoperative patient demographics, serum calcium and PTH levels, urinary calcium levels, renal function, and bone mineral density were similar between groups (Table 1). Urinary calcium levels and bone mineral density were available on 49/220 and 110/220 patients, respectively. At 2 weeks postoperatively (Table 2), mean calcium values were significantly lower in group 1 (8.9 ⫾ 0.9 mg/dL; P ⫽ .009) compared to groups 2 (9.4 ⫾ 0.9 mg/dL) and 3 (9.2 ⫾ 0.7 mg/dL). In groups 1 through 3, respectively, 46/46 (100%), 58/58 (100%), and 99/100 (99%) patients achieved eucalcemia. PTH was not routinely measured at this postoperative time interval early in the study and was excluded from analysis. Seventeen patients were unavailable for follow-up. At 1 to 3 months postoperatively, mean serum calcium and PTH levels were similar (Table 3). Data wer available for 160/220 (73%) patients. Surgical success at this interval, based on eucalcemia, was 32/32 (100%), 52/52 (100%), and
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Table 2 Early postoperative results (within 2 weeks)
Mean serum Ca (mg/dL) Mean serum PTH (pg/ml) Eucalcemia
Table 4 Results of parathyroidectomy at last follow-up
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
P
8.9 ⫾ 0.9 N/A 46/46 100%
9.4 ⫾ 0.9 N/A 58/58 100%
9.2 ⫾ 0.7 47 ⫾ 46 99/100 99%
.009 N/A NS
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); Ca ⫽ calcium; PTH ⫽ intact parathyroid hormone; NS ⫽ not significant; N/A ⫽ not applicable.
75/76 (98.7%). Seven patients had transient postoperative hypercalcemia together with a low PTH level, which resolved following cessation of oral calcium supplements. The incidence of eucalcemic PTH elevation was 25%, 37%, and 45% in groups 1, 2, and 3, respectively, with a trend toward a higher incidence in group3 compared to group 1 (P ⫽ .055). Hypoparathyroidism was found in 0/32, 2/52 (3.8%), and 2/76 (2.6%) patients in groups 1, 2, and 3, respectively. Table 4 summarizes outcomes for all groups based on most recent follow-up. Data were available in 219 patients. Follow-up was shortest in group 3 (3.7 ⫾ 5.6 months) compared to groups 1 (11.9 ⫾ 21.2) and 2 (8.2 ⫾ 17.7). Mean serum calcium and PTH levels were similar in each group. Sustained eucalcemia was achieved in 47/49 (95.9%), 60/60 (100%), and 109/111 (98.2%) patients in groups 1, 2, and 3, respectively. Persistent disease was found in a total of 2 patients in group 3 only (1.8%). One patient had a single adenoma removed via a minimally invasive approach and was found within 3 to 6 months to have persistent disease following brief eucalcemic PTH elevation. The ioPTH showed an 82% reduction at 10 minutes post gland excision. Eight months after her initial operation, the patient underwent a successful subtotal parathyroidectomy to treat multigland hyperplasia. The second patient had double adenomas removed during a MIPS converted to BNE. The ioPTH levels never dropped following Table 3 One- to 3-month postoperative results
Mean serum Ca (mg/dL) Mean serum PTH (pg/mL) Eucalcemia Eucalcemic elevated PTH Hypoparathyroid
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
P
9.3 ⫾ 0.7 74 ⫾ 62 32/32 100% 8/32 25% 0/32 0/32
9.5 ⫾ 0.6 83 ⫾ 98 52/52 100% 19/52 37% 2/52 3.8%
9.3 ⫾ 0.6 73 ⫾ 79 75/76 99% 34/76 45% 2/76 2.6%
NS NS NS .055* NS
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); Ca ⫽ calcium; PTH ⫽ intact parathyroid hormone; NS ⫽ not significant. * Group 1 vs. group 3.
Mean follow-up (mo) Mean serum Ca (mg/dL) Mean serum PTH (pg/mL) Eucalcemia Persistent disease Recurrent disease
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
P
11.9 ⫾ 21.2 9.1 ⫾ 0.7 77 ⫾ 64 47/49 95.9% 0
8.2 ⫾ 17.7 9.4 ⫾ 0.6 80 ⫾ 101 60/60 100% 0 1.8% 0
3.7 ⫾ 5.6 9.3 ⫾ 0.6 61 ⫾ 46 108/110 98.2% 2/110 NS 0
NS NS NS NS
2/49 4.1%
NS NS
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); Ca ⫽ calcium; PTH ⫽ intact parathyroid hormone; NS ⫽ not significant.
gland excisions and predicted operative failure. She had hypercalcemia immediately after surgery and at 3 months and is awaiting re-exploration. Two patients were found to have recurrent HPT after operation. Both patients were in group 1 (4.1%) and had single adenomas removed during their initial operation. Both demonstrated persistent eucalcemic PTH elevation prior to recurrence, which was diagnosed at 8 and 90 months. One of these patients underwent re-exploration, at which time a second adenoma was removed, and is cured. The other patient declined re-operation and has mild hypercalcemia. Table 5 summarizes intraoperative data. Twenty-eight procedures (25%) in group 3 were converted from a minimally invasive approach to a BNE. There were significant differences between groups regarding operative time, frozen sections, and patient charges (P ⬍ .001). Paired analysis demonstrated that the operations in group 3 (119 ⫾ 59 minutes) were significantly shorter than those in group 2 only (129 ⫾ 48 minutes; P ⬍ .001) and were associated with significantly fewer intraoperative frozen sections (1.2 ⫾ 2.1) compared to groups 1 (3.8 ⫾ 1.9; P ⬍ .001) and 2 (2.1 ⫾ 1.7; P ⬍ .001). The mean numbers of glands totally or subtotally excised per patient were not significantly different. Of the glands totally excised, size and weight were also similar. There was a trend toward less multi-gland disease in those patients in group 3 undergoing a minimally invasive approach (29% vs. 30% vs. 19%). A significantly greater number of patients in group 3 were discharged on the day of surgery (0 vs. 13% vs. 47%; P ⬍ .001). Total charges were significantly lower in group 3 compared to groups 1 and 2 ($4956 ⫾ 556 vs. $4757 ⫾ 1134 vs. $3708 ⫾ 1728; P ⬍ .001). Significantly more patients in group 2 had combined parathyroid and thyroid procedures (20% vs. 48% vs. 4 %; P ⬍ .001). Excluding those patients who underwent concomitant thyroidectomy from analysis, the total charges remained lower in group 3 ($3667 ⫾ 1737) compared to groups 1 ($4787 ⫾ 455; P ⬍ .001) and 2 ($4272 ⫾ 1080; P ⫽ .03); however, the operative time was no longer significantly different (111 ⫾ 29 vs. 121 ⫾ 41 vs. 117 ⫾ 58 minutes; P ⫽ .75). The overall incidence of permanent RLN injury was 2/220 (0.9%). Both patients were in group 2. One patient
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Table 5 Intraoperative data
Operative time (minutes) No. frozen sections Mean no. ioPTH samples Mean no. glands excised Mean gland size (cm) Mean gland weight (mg) Total charges ($) No. patients autotransplanted Permanent RLN injury Same-day discharge Single gland disease Multi gland disease Thyroid surgery
Group 1 BNE
Group 2 BNE and ioPTH
Group 3 MIPS and ioPTH
P
129 ⫾ 48 3.8 ⫾ 1.9 N/A 1.43 ⫾ 0.82 1.9 ⫾ 0.9 1358 ⫾ 1585 4956 ⫾ 556 4/49 8% 0
151 ⫾ 61 2.1 ⫾ 1.7 4.8 ⫾ 0.9 1.35 ⫾ 0.66 1.8 ⫾ 1.0 1647 ⫾ 3645 4757 ⫾ 1134 3/60 5% 2/60 3% 8/60 13% 41/60 68% 18/60 30% 29/60 48%
119 ⫾ 59 1.2 ⫾ 2.1 4.9 ⫾ 1.5 1.34 ⫾ 0.82 1.8 ⫾ 0.7 1457 ⫾ 1609 3708 ⫾ 1728 2/111 2% 0
.001* .001* NS NS NS NS .001* NS
52/111 47% 91/111 82% 19/111 17% 4/111 4%
⬍.001
0 34/49 69% 14/49 29% 10/49 20%
NS
.104 .097 ⬍.001
BNE ⫽ bilateral neck exploration; ioPTH ⫽ intraoperative parathyroid hormone; MIPS ⫽ minimally invasive parathyroid surgery (focused); RLN ⫽ recurrent laryngeal nerve; NS ⫽ not significant.
had a recognized injury at the time of operation, and 1 patient required a postoperative tracheostomy for respiratory difficulty. Three additional patients (1.4%) experienced transient postoperative vocal hoarseness, which resolved within 6 to 12 months and likely represented temporary RLN injury. These 3 patients now have normal voices. Comments Despite evolutionary changes in surgical approach, the success of parathyroidectomy continues to be based on postoperative normalization of serum calcium. Sustained eucalcemia beyond 6 months suggests cure. BNE with 4-gland visualization and biopsy relies on gland size and appearance to identify abnormal parathyroid glands and determine the extent of resection for surgical success. The use of intraoperative PTH assay, made practical by Irvin and Deriso [6], provided a biochemical adjunct to confirm cure by ensuring that all hyperfunctioning parathyroid tissue was removed. Thus, a functional component was added to the intraoperative decision algorithm, allowing surgical exploration to be minimized when appropriate. To become familiar with the use of ioPTH assays, some surgeons have used ioPTH as an adjunct to BNE. Starr et al from our center compared 50 patients undergoing BNE to another 50 patients undergoing BNE with ioPTH. Although the use of ioPTH significantly reduced the need for intraoperative frozen sections, the operative times and surgical success rates were similar, suggesting that the addition of ioPTH to intraoperatively assess gland function added little benefit to the success of a bilateral exploration [3]. Other studies have demonstrated that routine use of ioPTH not only improves outcomes, but also facilitates a limited exploration. Irvin et al compared ioPTH-guided limited parathyroidectomy with BNE in more than 700
patients and showed that ioPTH increased overall success from 94% to 97% [4]. Similar rates of success using MIPS compared to BNE have been reported by other investigators [7–13]. On the other hand, additional studies from Stalberg et al and Jacobson et al indicate that ioPTH monitoring may not improve the results of MIPS when localization studies are good, and patients are carefully selected [14,15]. End points other than cure have been examined. Some high-volume centers are observing a lower incidence of multi-gland disease in those patients undergoing limited explorations compared to BNE [4,16]. Yet, reported failure and recurrence rates between groups are so far similar. Are pathological glands being missed and left behind during focused explorations despite the functional adjunct of ioPTH? Will recurrence rates be higher? Alternatively, are more glands being removed during BNE which are grossly abnormal yet not hypersecretory? These and other questions remain unanswered. In this study, a high success rate was found regardless of the surgical approach. Although the mean serum calcium levels 14 days after operation were within normal range in all groups, the mean value in group 1 (BNE) was significantly lower. One possible explanation is that parathyroid glands are temporarily injured after biopsy. This is supported by the greater number of frozen sections in group 1. The mean number of glands removed in each group was similar. Although the mean duration of follow-up between groups was variable, we identified 2 patients with persistent disease and 2 patients with recurrence. Both patients with persistent HPT were in group 3 (1.8%), and both patients with recurrent HPT were in group 1 (4.7%). Recurrences in the other groups may not be evident due to shorter lengths of follow-up. One of the failures was predicted by a true negative ioPTH result and immediate postoperative hyper-
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calcemia. In groups 1, 2, and 3, the rates of sustained eucalcemia at last follow-up were 95.9%, 100%, and 98.2%, respectively. Not every patient was available for follow-up beyond 6 months (particularly in group 3), and defining those eucalcemic patients as cured should be done with caution. In all 220 patients, the rates of persistent disease and recurrence were each 2/220 (0.9%). Similar to other studies, there was a trend toward less multi-gland disease in the MIPS group. This can be explained by patient selection and surgical approach. Our indications for a planned BNE include discordant localization, negative studies, studies with more than 1 abnormal focus, or need for thyroidectomy. Multi-gland disease is more likely when localization studies are not clear cut. Group 3 patients had significantly shorter operative times, fewer frozen sections, lower overall charges, and a greater likelihood to have outpatient procedures. The difference in operative time observed in this study may be associated with the difference in concomitant thyroid procedures and should be interpreted cautiously. The lower charges appear associated with the trend toward outpatient surgery. Due to the expense of required localization studies, monetary savings are potentially lost in MIPS patients who are not discharged on the day of surgery. Conclusion In experienced hands, parathyroidectomy for psHPT is highly successful regardless of surgical approach with no significant differences in rates of success or recurrence, although follow-up is limited. A MIPS approach is potentially quicker and associated with lower patient charges. References [1] Starr FL, DeCresce R, Prinz RA. Use of intraoperative parathyroid hormone measurement does not improve success of bilateral neck exploration for hyperparathyroidism. Arch Surg 2001;136:536 – 42. [2] van Heerden JA, Grant CS. Surgical treatment of primary hyperparathyroidism: an institutional perspective. World J Surg 1991; 15:688 –92. [3] Low RA, Katz AD. Parathyroidectomy via bilateral cervical exploration: a retrospective review of 866 cases. Head Neck 1998;20: 583–7. [4] Irvin GL 3rd, Solorzano CC, Carneiro DM. Quick intraoperative parathyroid hormone assay: surgical adjunct to allow limited parathyroidectomy, improve success rate, and predict outcome. World J Surg 2004;28:1287–92. [5] Nussbaum SR, Thompson AR, Hutcheson KA, et al. Intraoperative measurement of parathyroid hormone in the surgical management of hyperparathyroidism. Surgery 1988;104:1121–7. [6] Irvin GL 3rd, Deriso GT. A new, practical intraoperative parathyroid hormone assay. Am J Surg 1994;168:466 – 8. [7] Westerdahl J, Lindblom P, Bergenfelz A. Measurement of intraoperative parathyroid hormone predicts long-term operative success. Arch Surg 2002;137:186 –90. [8] Inabnet WB 3rd, Dakin GF, Haber RS, et al. Targeted parathyroidectomy in the era of intraoperative parathormone monitoring. World J Surg 2002;26: 921–5. [9] Carneiro DM, Irvin GL 3rd. Late parathyroid function following successful parathyroidectomy guided by intraoperative hormone assay (QPTH) compared with the standard bilateral neck exploration. Surgery 2001;128: 925–9. [10] Udelsman R, Donovan PI, Sokoll LJ. One hundred consecutive minimally invasive parathyroid explorations. Ann Surg 2000;232:331–9. [11] Vignali E, Picone A, Materazzi G, et al. A quick intraoperative parathyroid hormone assay in the surgical management of patients
[12] [13] [14]
[15]
[16]
with primary hyperparathyroidism: a study of 206 consecutive cases. Eur J Endocrinol 2002;146:783– 8. Miura D, Wada N, Arici C, et al. Does intraoperative quick parathyroid hormone assay improve the results of parathyroidectomy? World J Surg 2002;26:926 –30. Chen H, Eberhard M, Starling JR. A comprehensive Evaluation of perioperative adjuncts during minimally invasive parathyroidectomy: which is most reliable? Ann Surg 2005;242:375– 80. Stalberg P, Sidhu S, Sywak M, et al. Intraoperative parathyroid hormone measurement during minimally invasive parathyroidectomy: does it “value-add” to decision-making? J Am Coll Surg 2006; 203:1– 6. Jacobson SR, Van Heerden JA, Farley DR, et al. Focused cervical exploration for primary hyperparathyroidism without intraoperative parathyroid hormone monitoring or use of the gamma probe. World J Surg 2004;28:1127–31. Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg 2005;132:359 –72.
Discussion Steven A. DeJong, M.D. (Maywood, IL): There are probably centers in the country that have decided because of low volume parathyroid work, that they simply can’t afford the use of intraoperative PTH with their patients. Can you tell us in the patients that underwent bilateral exploration, how often did the use of intraoperative parathyroid hormone analysis change what you did? It has been the assumption that the procedure using a bilateral exploration is only cost effective if we send patients home the same day. Is this possible to conclude from your data? Eucalcemic parathyroid elevation was the highest in your unilateral exploration group. Do you think that this phenomenon predicts future persistent or recurrent parathyroid disease, and how long should this phenomenon go on before a surgeon gets concerned that there may be persistent or recurrent disease present? How has your work changed your operative approach at your hospital in caring for these patients? Todd D. Beyer, M.D.: The surgical objective for the patient’s in group 2 was to perform a bilateral exploration while at the same time assessing the efficacy of intraoperative PTH monitoring. So although the hormone monitoring was evaluated at the time of surgery, it did not necessarily alter the surgical outcome or the course of the operation. In some of the latter cases in group 2, the role of intraoperative PTH monitoring became more active, lateralizing perhaps the gland from the left to the right and also ultimately predicting biochemical cure. The goal and design of this study was not so much to assess the impact of intraoperative PTH monitoring on bilateral exploration versus a focused approach. But in examining group 2, the primary way that hormone monitoring could impact the ultimate outcome of surgery would be in the number of glands removed. Patients in that group who had more than 1 gland removed, roughly two-thirds of those patients, had an initial true negative result on their hormone monitoring, which would prompt additional exploration in looking for other glands. Perhaps another way to look at this question would be if you are planning to do a bilateral exploration from the start, could the use of hormone monitoring be eliminated? Although this
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study was not designed to answer that question, the addition of hormone monitoring to a bilateral exploration does reduce the number of intraoperative frozen sections required for success. Does it improve the success of the operation as a whole? I don’t think we can really safety answer that from this data. I think a key element to success of this operation that can’t be overlooked is the personal experience of the surgeon and their ability to recognize an abnormal parathyroid gland, particularly in multi-gland disease. One of the major elements to the charge savings that were seen in group 3 is due to the ability to discharge these patients on the same day. We feel that without hypercalcemia, a patient does not have persistent or recurrent disease. Eucalcemic PTH elevation has been widely reported, widely observed and speculated upon. Although it can precede recurrence, I don’t think it necessarily predicts recurrence. It is more closely associated with other variables, disease severity, adenoma size, renal function, vitamin D status, bone density, and severity of bone disease. We monitor these patients more closely postoperatively for evidence of hypercalcemia and we give them calcium and vitamin D supplementation. We have some early data that shows that this might accelerate the normalization process postoperatively. Success, regardless of approach, is high in experienced hands, and I think an area where we can strive to improve upon would be in getting some of these patients home the same day, if at all possible.
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Herb Chen, M.D. (Madison, WI): Your group 3 probably had a higher incidence of single adenomas present. If you analyze your data just looking at patients with single adenomas, perhaps those differences and charges would disappear, and really what you are seeing is you have more patients with single adenomas in the last group, which you are able to send home and thus charges are much less. Todd D. Beyer, M.D.: I think it is possible that since we tend to equate single gland disease to successful closed approach with same day discharge, perhaps those variables might be similar if not interchangeable or they might reflect one another. So by eliminating those patients who are discharged the same day, we weren’t necessarily eliminating those with a single gland, but maybe got quite close to that. Christopher R. McHenry, M.D. (Cleveland, OH): The focused approach is dependent upon the accuracy of your preoperative localization studies, and dependent on whether or not you find they have associated thyroid disease as you mentioned. In patients that present to you with primary hyperparathyroidism, what percent of patients are you actually able to do a focused parathyroidectomy? Todd D. Beyer, M.D.: In this study, we did not exactly look at that number, but historically based on other studies, I think it can be in the range of 60% to 75%. So based on the pathophysiology of the disease and the accuracy of the localization studies, the vast majority of patients are candidates for a minimally invasive approach.