Minimally invasive focused parathyroidectomy without using intraoperative parathyroid hormone monitoring or gamma probeM Haciyanli1, H Genc1, N Damburaci1, G Oruk2, P Tutuncuoglu2, N Erdogan3
1 Ataturk Training and Research Hospital, Second Surgery, Izmir, Turkey
2 Endocrine,Izmir, Turkey
3 Radiology Clinics, Izmir, Turkey
Background : Minimally invasive parathyroidectomy (MIP) is widely used worldwide for the treatment of primary hyperparathyroidism (pHPT). It is usually combined with a perioperative adjunct for high success rate. Aim : To demonstrate that MIP can be successfully performed in a selected group of patients with presumabally solitary adenoma as the cause of pHPT without using any perioperative adjuncts. Settings and Design : A prospective data analysis of two surgeons' series from a teaching hospital in Turkey. Materials and Methods : Of the 47 patients referred with a diagnosis of pHPT during January 2004-May 2008, 30(63%) patients with sporadic pHPT with presumed solitary adenoma were included for analysis. These patients underwent MIP via focused lateral ( n=24) or anterior ( n=6) approach. Preoperative localization was done using 99 mTc-labelled sestamibi scan and ultrasonography. Only patients with concordant tests for single adenoma were selected for MIP. Serum parathyroid hormone and calcium levels were measured postoperatively and at follow-up visits. Statistical Analysis : Parametric data presented were analyzed with Excel XP (Microsoft, Redmond, WA, USA). Results : Barring one patient, all other patients were initially biochemically cured by MIP. One patient remained hypercalcemic, who was found to have a second adenoma at the second operation. During a mean follow-up of 16 (3-55) months, all patients were normocalcemic with a mean serum calcium level of 9.4 (8.9-10.2) mg/dl. Parathormone levels were persistantly elevated only in one patient (3.4%). No postoperative permanent complication was encountered. Conclusion : The results of MIP achieved in high-volume endocrine surgery centers can be replicated in low-volume center without any intraoperative adjuncts, in patients with overt clinical pHPT and concordant results of sestamibi and ultrasound.
Keywords: Adjunct, intraoperative, invasive, minimally, parathyroidectomy
Primary hyperparathyroidism (pHPT) is a common endocrine disease successfully treated by surgery. It is commonly caused by a solitary adenoma.  Because of the advancements in the localization studies and perioperative adjuncts, minimally invasive parathyroidectomy (MIP) has been accepted as the treatment of choice ahead of bilateral four-gland exploration. MIP is a general term and includes mini-incision focused procedures, videoassisted parathyroidectomy, endoscopic procedures and minimally invasive radio-guided parathyroidectomy.  Generally, MIP comprises the scan-directed removal of an abnormal gland with the assesment of the completeness of the removal using one of the perioperative adjuncts. However, the necessity of applying these adjuncts has been recently questioned.  This study was undertaken to demonstrate whether MIP can be successfully performed in a selected patient population who had presumabaly a solitary adenoma without using any perioperative adjuncts in a low-volume center.
The study group comprised consecutive 30/47 patients who were referred to our clinic for surgical treatment of pHPT between January 2004 and May 2008. All information was collected prospectively. Biochemical diagnosis was based on blood calcium, phosphorus and parathormone measurements. All patients underwent estimation of serum vitamin D levels, 24-h urinary calcium excretion and bone mineral dansiometry analysis. Once the diagnosis was confirmed, patients underwent preoperative localization with 99 mTc-labelled sestamibi (SM) scan and ultrasonography (USG) of the neck as per routine hospital practice. A repeat focused USG was performed preoperatively to guide the incision and to select the operative approach.
Patient selection: Inclusion criteria were narrow and included the absence of multiple endocrine neoplasia or familial disease, absence of concurrent thyroid disease requiring surgery, and lack of characteristics suggestive of carcinoma. Patients with persistant or recurrent pHPT or those who had undergone neck surgery previously were not operated with focused technique. Patients underwent MIP when the two localization studies were concordant and reported a single diseased gland. Thirty patients met the inclusion criteria and written, informed consent for MIP was obtained from all patients who were informed on the risk of conversion to a bilateral four-gland exploration as well as possible 2-3% risk of failure. Surgery was recommended to all symptomatic and asymptomatic patients who fullfit the criteria mentioned in NIH 2002 concensus guidelines.  All operations were performed by the first two authors of this paper.
Surgical technique: General anesthesia or laryngeal mask anesthesia was employed. MIP was undertaken using the focused anterior approach (FAA) and focused lateral approach (FLA) through 2- to 3-cm incision [Figure 1]. The FAA was performed via a midline incision approaching the more anteriorly located adenoma by seperating the linea alba, similar to bilateral neck exploration but without any flaps. The FLA involved a lateral incision placed directly over the site of adenoma and the gland is approached through the seperation between anterior border of the sternoclaidomastoid muscle and the lateral border of the strap muscles.
Once the enlarged, abnormal gland was identified, it was resected with intact capsule and incision was lengthened to remove large glands intact when needed (n = 3). Some but not all were sent for intraoperative frozen section analysis for confirmation of the parathyroid tissue (n = 5). Any intraoperative adjunct such as quick parathormone assay or gammaprobe was not used.
The size of the glands was measured in the operation room and greatest dimensions were recorded. All patients were considered for discharge 24 hr post surgery. PTH and calcium levels were checked on the morning following the surgery. Calcium tablets were given as and when needed. All patients were seen in the outpatient clinic at one and six month interval post-surgery and were assessed for symptoms, complications and final histological diagnosis. Serum PTH and calcium levels were measured at each visit. Vitamin D levels determined, when needed. Biochemical cure was defined as the normocalcemia after the operation independent from the serum PTH levels.
Parametric data presented were analyzed with Excel XP-2003 (Microsoft, Redmond, WA, USA). Continuous data are presented as mean and standard deviation (mean ± SD).
During the aforementioned period, 47 patients were operated for the diagnosis of pHPT. Forty-three had the sporadic disease and 4 had familial disease. 30 patients had MIP, 15 patients had standart bilateral neck exploration due to various reasons and two patients had unilateral exploration [Table 1]. Final pathology was solitary adenoma (SA) in 78.7%, hyperplasia (HP) in 12.7%, double adenoma (DA) in 4.3% and carcinoma in 4.3%. Among the overall group, thirty (63.8%) patients had a highly suggestive localization studies for single adenoma (i.e. concordant Sestamibi and US) and considered to be eligible for MIP.
The results of the patients having thyroid disease requiring surgery, suspicion of cancer (a patient with the highest PTH level and tumor invading the thyroid on USG) and MEN were not considered for further evaluations. SM scanning and USG showed single gland disease in 32 and 31 of the remaining 35 patients, respectively.
Initially USG and SM scanning was concordant only in 23 patients and USG was negative in seven patients. For the final assessment and to guide the incision and the type of operation, a repeat neck USG was performed by an experienced radiologist (N.E.) and one of the surgeons (M.H. or H.G) just prior to the operation with the known SM scan result. A probable adenoma was additionally located among them and those were accepted as concordant SM and US result and all underwent MIP either using FLA (n = 24) or FAA (n = 6). The study group, therefore, comprised 30 patients. One of the other SM positive 2 patients was treated with unilateral neck exploration and all others were treated by standard bilateral neck exploration.
The study group consisted of 21 women and 9 men with a mean age of 52.36 ± 9.64 years (range 39-86 years). All patients had a biochemical diagnosis of HPT with mean preoperative serum calcium level of 11.63 ± 1.06 mg/dl (range: 10.6-15.7 mg/dl; normal 8.8 to10.6 mg/dl) and serum PTH level was 192.16 ± 245.68 pg/ ml (range: 85 to 1446 pg/ml; normal 12 to 65 pg/dl).
In MIP group, SM scanning and USG were suggestive of a single diseased gland correctly in 29 (96.7%) patients. The bilateral disease was missed in one patient (3.3%).
MIP was successfully performed in all patients and all parathyroid tumors were extracted with intact capsules despite the small incision. The mean gland size was 2.0 (0.7-4.3) cm. The mean operative time was 42 (range: 18-76) min. There were no intraoperative complications and no drain was placed. Postoperative minimal wound hematoma occured in a patient which resolved spontaneously. Transient symptomatic hypoparathyroidism was encountered in one patient. Postoperative calcium levels in the next morning after the operation were normal in all, except two patients. One of them became normocalcemic in 72 h but the other patient had a documented persistent (11.4 mg/dl) hypercalcemia and she underwent bilateral neck exploration and a second adenoma was detected on the same side, which was subsequently resected. She was normocalcemic thereafter. The overall cure rate was 96.7%.
The patients were followed for an average of 16 (range: 3-55) months. All patients were normocalcemic with a mean calcium of 9.4 (8.9-10.2) mg/dl at the latest follow-up and were deemed to be biochemically cured. Parathormone levels were above the normal limits in two patients (6.7%) at the last visit and they were detected to have vitamin D deficiency. One of them showed normalization of PTH levels subsequently after the supplement therapy with vitamin D but the other patient did not show normalization of PTH levels.
Surgical treatment for pHPT has undergone a radical change in the last decade. Better localization techniques have generated a move toward less invasive surgery. MIP for pHPT is a safe and effective procedure with excellent cure rates (similar cure rates with BNE of > 95%) in experienced hands. Although various methods of MIP has been available, mini-incision focused approach was developed as an alternative to more complex endoscopic or video-assisted techniques and is the current method of choice for an overwhelming majority of members of the International Association of Endocrine Surgeons. MIP is minimal not only due to a smaller (2.5 cm) incision but also because it involves minimal tissue dissection, enables an operation under local anesthesia at outpatient setting, lowers hospital costs, lowers the incidence of hypocalcemia compared with the standart bilateral exploration. , It also provides a better scar cosmetically and a less painful postoperative course. Its only major disadvantage includes the possible risk of missing multiglandular disease.
As a solitary adenoma is the cause of pHPT in more than 80% of the patients, MIP depends on the accurate demonstration of the diseased gland preoperatively. Sestamibi parathyroid scanning and USG were used as the preoperative localization studies in our hospital. Sestamibi has sensitivity and specificity of 90 and 98% respectively.  We entirely relied on the fact that when SM scan was used in combination with USG, and when both were concordant on the diseased gland, sensitivity rises 95% or more. , It was 96.7% in this study. USG can be highly accurate, as in our study and it also provides detailed information about the anatomic relationships between an enlarged parathyroid gland and surrounding structures and provides information that can be used to select the site for incision. Although USG is efficient and noninvasive, the sensitivity is highly dependent on the experience of the individual sonographer. Combination of the experience and knowing the SM result, we detected seven SA which were missed at first USG examination. Another possible explanation for high detection rate with USG was that diagnosis of HPT at an early stage is infrequently made in Turkey and this may lead to a more advanced disease and larger glands at the time of diagnosis [Table 2]. ,, Recently Kirdak et al.,  reported that adenoma size were larger in Turkish patients than United States patients. As the gland size gets larger, localization becomes easier.  Undergoing a repeat USG is not expensive in Turkey (almost US$12/examination).
Traditionally, some institutions have been using perioperative adjuncts such as gamma probe or intraoperative parathyroid hormone measurement to confirm the adequacy of resection for successful MIP. Minimally invasive radio-guided parathyroidectomy uses a gamma probe to determine the site of incision, guide the dissection and evaluate the completeness of the removal. However, in the era of improved preoperative localization and IOPTH monitoring, the routine use of radioguidance has been abandoned at many centers. ,
As PTH has a short half life, intraoperative measurement of PTH (IOPTH) has been proposed as a biochemical marker for the completeness of the resection.  A fall in PTH levels of more than 50%, 10 to 15 min after removing the hyperfunctioning gland, is generally accepted as demonstration of the completeness of surgery.  Although several authors claim that IOPTH measurements are necessary for MIP to have high cure rates, ,,,, others have found the use of IOPTH unnecessary based on low cost effectiveness and lack of improved cure rates in a selected group of patients. , Underestimation of extent of resection, non-availability of standardized guidlines regarding timing and frequency of PTH determination during surgery and false-positive and false-negative results associated with IOPTH estimation are some of the other limitations cited. ,,
The assay, however, may be useful in complicated cases with persistant or disease. It may also be useful in the Sestamibi directed, nonconcordant patients.
We performed MIP with a 97% success rate without using any intraoperative adjuncts. Our results are equivalent to those obtained at other centers [Table 3]. ,,,,,, Our results were also comparable to results in most other published series using both standard bilateral exploration (> 95%) and MIP and employing IOPTH measurement, a nuclear probe or both (97-98%). Haciyanli et al.,  and others  showed previously that either IOPTH or preoperative imaging studies were not a reliable predictor in double adenoma cases. Rewieving our one failure, if we used IOPTH, again there would be 50% chance to miss the second abnormal gland. Moreover, there might be some unnecessary conversions to bilateral neck explorations with the probable false negative IOPTH results.
Our study has shown that MIP is a feasible procedure even in a low-volume center where facilities for performing adjunct investigations may not be available. Thus, the excellent results of MIP achieved in high-volume endocrine surgery centers can be also reproduced in low-volume centers without any intraoperative adjuncts provided appropriate selection of patients is undertaken. We have also demonstrated that MIP was associated with shorter duration of surgery and discharge at 24 h post-surgery, even though general anesthesia was used.
[Table 1], [Table 2], [Table 3]