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Minimally invasive parathyroidectomy
Ronald C. Merrell (Chirurgia, 99 (6): 499-502)
Primary hyperparathyroidism is a disorder of calcium metabolism brought on by excess secretion of parathyroid hormone. In the United States 28/100,000 develop the condition each year. This translates into an incidence of 1:2,000 persons with a predilection for women over men of 3:1. The condition is due to a single benign tumor of one of the four parathyroid glands in 85% of cases (1-3). Most patients are asymptomatic and are diagnosed by routine screening that includes serum calcium. The criteria for diagnosis include elevated plasma calcium with a concomitant elevation of the PTH hormone measured by a midmolecule assay. There is really no physiologic or any other pathophysiologic mechanism to have both ionized calcium and PTH elevated at the same time other than primary hyperparathryoidism. The diagnosis can be confirmed in marginal cases by measuring the urine excretion of calcium over 24 hours. If there is an excretion of greater than 150 mg/24 hours with elevated calcium and PTH the possibility of Familial Hypocalciuric Hypercalcemia is excluded.
The only treatment for primary hyperparathyroidism is surgical resection of the abnormal parathyroid tissue. However, with such a prevalent disease surgical treatment of all patients is not reasonable. Certainly the majority of patients are asymptomatic anyway and the benefits of treatment may be marginal. However, symptomatic patients with renal stones, bone pain or fracture, severe fatigue, aggravated acid peptic disease or pancreatitis are destined for operation unless there are compelling contraindications to anesthesia.
There are consensus criteria offered by the National Institutes of Health in the US for management of asymptomatic patients. These were updated in 2002 (4-6). It seems safe to follow patients in the younger age group with less than a 1.0-mg/dl elevation, no stones seen on ultrasound of the kidney and less than 2.0SD units bone loss on bone densitometry. Repeat testing is done annually and about 30% of patients will ultimately require operation for interim failure to meet criteria.
The standard operation for parathyroidectomy for the last 40 years has been neck exploration with identification of all four parathyroids and resection of any enlarged glands using frozen section pathology to confirm the surgeon's visual suspicions. In the case of single gland disease only the abnormal gland is removed (7).
In 1993 Irwin et al, refined the intraoperative decision by applying a radioimmunoassay for PTH (8). A 50% drop from preoperative levels 10 minutes after resecting correlated with pathology cure. This assay invited surgeons to consider halting the exploration if the radioimmunoassay predicted the operation need not go any further. In fact, the legendary CA Wang at Massachusetts General Hospital had made a similar recommendation in the 1950's (9-12). He suggested that based upon the surgeon's judgment in collaboration with the pathologist an exploration could be unilateral if abnormal tissue was resected and other ipsilateral gland seemed normal. This recommendation never was fully applied because of the concern for double adenoma.
Shortly after the availability of intraoperative PTH analysis a scan was introduced to identify abnormal parathyroid tissue. There had been earlier scans with radioactive methionine, and a Thallium/Technetium subtraction scan but these had not had the sensitivity and specificity desired. The Sestamibi scan was introduced by Dr Coakley in 1989 and took advantage of the faster washout of contrast by thyroid than the abnormal parathyroid (13-14). Furthermore the scan utilized planimetry with the SPECT (single photon emission computed tomography) camera for serial examination of the neck to determine position relative to the thyroid gland. This scan will detect an isolated adenoma about 80% of the time (15-18). Since 85% of patients have a single adenoma and the test has an accuracy of 80% the product to these two predicts that some 2/3 of patients with primary hyperparathyroidism can have a scan to identify the position of the abnormal gland.
This scan has invited surgeons to design less invasive procedures to remove tissue identified by scan and to move away from the full neck exploration to identify all four glands. The standard operation has enjoyed a success rate of 95% (1) and therefore it was bold to propose an operation that could be better for patients. However, minimally invasive surgery that could reduce incisions, avoid general anesthesia and have fewer surgical complications could indeed be better than the standard operation. However, the scan costs an average of $2,400 and seems a gratuitous expense for technology unless some advantage can be demonstrated. Routine use of the scan was not advocated in the beginning and is not now. Selective identification of patients for scan is more and more refined and generally applies to patients for whom minimally invasive surgery seems clinically desirable.
There are several procedures that carry the name minimally invasive. The operation recommended by Dr. Norman involved using a gamma probe in much the same way one performs a sentinel node biopsy in breast cancer or melanoma (17). The probe guides the surgeon to the contrast administered before the operation and if there is localization the area of suspicion may be approached with local anesthesia and removed. This procedure is very effective if the gland is detected by the probe. However, the dissection is perhaps not as anatomical as a formal dissection. Also the logistics of patient injection prior to operation adds a complexity.
Dr. Udelsman utilized Sestamibi scanning and explored only the suspected side through a small collar incision under cortical block anesthesia. His results were spectacular and his dissection was thoroughly anatomical (19-20). An incision described by Chaffanjon in Grenoble (21) has been popular for a lateral approach under local
anesthesia with excellent anatomical display. This is probably the operation most commonly intended when MIS is mentioned. The procedure entails a very small incision and only local anesthesia is employed. Patients are generally sent home the same day. Results for all the minimally invasive procedures are comparable to the 95% success of standard operation (1, 2, 22). However, incisions are smaller and it is intuitive that limitation of the dissection to one side of the neck reduces the probability of nerve injury.
Furthermore, with no dissection of a flap beneath the platysma the surgeon virtually precludes the possibility of a clinically important neck hematoma.
In the interest of advancing MIS surgery in the neck, Michel Gagner, an intrepid pioneer, designed a procedure whereby the neck tissues were insufflated with CO2 and a laparoscope was introduced through a trocar incision for minimal dissection and resection of a parathyroid tumor. This report made it clear that CO2 is a superb dissection tool. However, a general anesthetic was required (23-27).
Currently there are several sound reasons to essay a minimally invasive parathyroidectomy. There were always patients with compelling complications of primary hyperparathyroidism who were extraordinary risks for general anesthesia. Surely, the patients with strong indications for operation and yet barriers to a safe anesthetic were excellent candidates. Many elderly, frail patients with altered mental state due to hypercalcemia, severe bone disease or incipient renal failure due to nephrocalcinosis can be treated with a local anesthetic with great optimism for improvement. Then there are those patients who had failed previous exploration. Guiding the second operation with a Sestamibi scan is patently logical (17). In addition there are patients who have had previous neck surgery for whom extensive dissection in scar might represent an increased possibility of a surgical injury. A minimally invasive procedure for such a patient clearly has merit. Finally there is the patient with a phobia for anesthesia or a strong attraction to the newest in techniques and the briefest possible hospital stay. This patient usually comes to the surgeon with experience in minimally invasive parathyroidectomy and requests an evaluation. If the enthusiasm becomes general perhaps all patients will have scans and consider MIS parathyroidectomy. There are certain patients, however, for this is not reasonable. Anyone who cannot cooperate for a local anesthetic is not going to be a candidate for the safest of the MIS procedures. This would certainly include patients with claustro- phobia or dementia.
Table 1 - A comparison of new and old guidelines for parathyroid surgery in asymptomatic primary
hyperparathyroidism
Measurement
Guidelines (1990)
Guidelines (2002)
Serum calcium (above upper limit of normal)
1-1.6 mg/dl
1.0 mg/dl
24-h urinary calcium
> 400 mg
>400 mg
Creatinine clearance
Reduced by 30%
Reduced by 30%
Bone mineral density
z-score <-2.0 (forearm)
t-score <-2.5 at any site
Age
<50
<50
Surgery is also indicated in patients for whom medical surveillance is neither desired nor possible.

Reprinted from J Clin Endocrinol Metab, December 2002, 87(12):5353-5361 Bilezikian et al. Asymptomatic Primary Hyperparathyroidism. Copyright 2002, The Endocrine Society.
The role of intraoperative PTH assay may not be as all-inclusive as anticipated. In centers with excellent pathologists and excellent systems for intraoperative consultation a frozen section diagnosis can be rendered in 20 minutes at a cost similar to that of the assay and accomplished in perhaps 30 minutes. That includes the 20-minute assay conducted 10 minutes after resection of the suspected adenoma. There is no question the pathology approach will miss a rare second adenoma not seen by the scan. However, the assay is prone to occasional errors as well.
The evaluation for MIS is indeed a SPECT Sestamibi scan. If the scan clearly indicates the site of the lesion a recommendation for MIS can be made and operation goes forward with confidence. However, if the scan is equivocal, it is best considered negative and not sufficient for MIS guidance. If the scan is negative or equivocal it is important that patients and physicians realize that the scan is a localization tool and not a diagnostic tool. The diagnosis of primary hyperparathyroidism is made on biochemical grounds and not scans. If the scan is negative, the patient still has the disease and treatment is still indicated. Only a full neck exploration is appropriate.
The two excellent reports in this issue emphasize the evolving surgical approach to parathyroid surgery. Diaconescu et al, have used the laparoscopic approach with videoscopic visualization and manipulation in a four-gland case with gasless dissection. This is a very important report since many of the secondary hyperparathyroidism patients are exceptional surgical risks and MIS would benefit them. Their second patient with a parathyroid adenoma was similarly cured.
In the report from the group of Prof. Marescaux in Strasbourg a case report of a mediastinal ade-noma allows a wonderful discussion of the limitation of neck dissection and the various approaches. They used a median sternotomy to find the errant gland. Occasionally, thoracoscopy can be successful.
Both these studies encourage us to move forward in an orderly and evidence-based manner to improve the management of patients with a common disease. Since the incidence of this condition rises with age and greatly aggravates the osteoporosis of age, increasing attention to primary hyperparathyroidism and its fragile victims is warranted.
References
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