Unilateral neck exploration for primary hyperparathyroidism

Focused unilateral cervical exploration is a controversial alternative to conventional bilateral neck exploration for primary hyperparathyroidism (HPT) due to solitary adenoma. Development of preoperative localization techniques, notably isotope scintigraphy and small-part, real-time ultrasonography, has increased preoperative parathyroid tumor identification. Critics of scan directed unilateral neck exploration argue it may overlook enlarged parathyroid glands on the unexplored side, increasing the incidence of persistent and recurrent hypercalcemia. Our experience of this operation and prolonged follow-up of patients, however, confirm that it does not increase risk of persistent or recurrent HPT if a strict selection protocol is observed. This ensures the confident further development of minimally invasive surgical procedures for HPT based on the principle of a focused exploration following preoperative localization of the parathyroid adenoma.     

Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial

OBJECTIVE: To compare unilateral and bilateral neck exploration for primary hyperparathyroidism in a prospective randomized controlled trial. SUMMARY BACKGROUND DATA: Based on the assumption that unilateral neck exploration for a solitary parathyroid adenoma should reduce operating time and morbidity, a variety of minimally invasive procedures have challenged the idea that bilateral neck exploration is the gold standard for the surgical treatment of primary hyperparathyroidism. However, to date, no open prospective randomized trial has been published comparing unilateral and bilateral neck exploration. METHODS: Ninety-one patients with the preoperative diagnosis of primary hyperparathyroidism were randomized to unilateral or bilateral neck exploration. Preoperative scintigraphy and intraoperative parathyroid hormone measurement guided the unilateral exploration. Gross morphology and frozen section determined the extent of parathyroid tissue resection in the bilateral group. The primary end-point was the use of postoperative medication for hypocalcemic symptoms. RESULTS: Eighty-eight patients (97%) were cured. Histology and cure rate did not differ between the two groups. Patients in the bilateral group consumed more oral calcium, had lower serum calcium values on postoperative days 1 to 4, and had a higher incidence of early severe symptomatic hypocalcemia compared with patients in the unilateral group. In addition, for patients undergoing surgery for a solitary parathyroid adenoma, unilateral exploration was associated with a shorter operative time. The cost for the two procedures did not differ. CONCLUSIONS: Patients undergoing a unilateral procedure had a lower incidence of biochemical and severe symptomatic hypocalcemia in the early postoperative period compared with patients undergoing bilateral exploration. Unilateral neck exploration with intraoperative parathyroid hormone assessment is a valid surgical strategy in patients with primary hyperparathyroidism with distinct advantages, especially for patients with solitary parathyroid adenoma.     

Unilateral neck exploration for primary hyperparathyroidism: Analysis of a controversy using a mathematical model

Most endocrine surgeons explore both sides of the neck and identify all parathyroid glands when operating on patients with primary hyperparathyroidism. Others, however, advocate the unilateral approach, i.e., if an adenoma and a normal gland are identified, the contralateral side is not explored. We analyzed the strategy of the unilateral approach using a mathematical model to determine the variables that influence the probability of missing a tumor on the unexplored side of the neck. Assuming the frequency of single adenoma is 80%, hyperplasia 14%, double adenomas 4%, triple adenomas 1%, and carcinoma 1%, and the probability of missing a tumor on the explored side is 5%, we found that: 1. Only 41% of the patients treated by the unilateral approach undergo unilateral exploration. This is increased to 62% when a localization study with a sensitivity of 80% is used pre-operatively. 2. The probability of missing a tumor on the unexplored side of the neck parallels the prevalence of multiple adenomas. Half of the patients with triple adenomas and two-thirds of the patients with double adenomas will have a missed tumor when treated by the unilateral approach. 3. Patients who undergo unilateral exploration have an additional 7% to 8% probability of missing a tumor that would have been found if bilateral exploration is performed. This risk is lowered to 2% by a pre-operative localization study that is 80% sensitive. 4. A prospective study will require 684 patients, randomized to the unilateral or bilateral approach, to have an 80% statistical power (=0.05, =0.20) of detecting a difference between a 5% and a 10% risk of missing a tumor.

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Resumen La mayoría de los cirujanos endocrinos exploran ambos lados del cuello e identifican todas las paratiroides cuando intervienen pacientes con hiperparatiroidismo primario. Otros, sin embargo, preconizan el abordaje unilateral: cuando se identifican un adenoma y una glándula normal no se explora el otro lado. Por ello nos propusimos analizar el abordaje unilateral utilizando un modelo matemático para determinar las variables que influencian la probabilidad de no detectar un tumor en el lado no explorado. Asumiendo que la frecuencia de un adenoma único es 80%, de hiperplasia 14%, de adenomas dobles 4%, de adenomas triples 1%, de carcinoma 1%, y 5% la probabilidad de no detectar un tumor en el lado que se explora, encontramos que: 1. En sólo 41% de los pacientes tratados mediante el abordaje unilateral se efectúa exploración unilateral, frecuencia que aumentó a 62% cuando se utilizó un estudio preoperatorio de localización con sensibilidad de 80%. 2. La probabilidad de no detectar un tumor en el lado no explorado es igual a la de los adenomas múltiples. La mitad de los pacientes con adenoma triples y dos tercios de los pacientes con adenomas dobles resultan con un tumor no detectado cuando se realiza el abordaje unilateral. 3. Los pacientes sometidos a exploración unilateral tienen una probabilidad adicional de 7 a 8% de no detección de un tumor que habría sido identificado con una exploración bilateral. Tal riesgo se disminuye a 2% mediante un estudio preoperatorio de localización que posea 80% de sensibilidad. 4. Un estudio prospectivo requiere disponer de 684 pacientes para ser randomizados al abordaje unilateral o al bilateral para lograr un potencial estadístico de 80% (=0.05,=0.20) en la detección de una diferencia de 5% a 10% en el riesgo de no identificar la presencia de un tumor.

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Résumé La plupart des chirurgiens explorent la région cervicale de façon bilatérale et identifient toute les glandes parathyroïdes au cours de l'intervention pour hyperparathyroïdie primaire. D'autres, toutefois, plaident pour un abord unilatéral et, lorsqu'un adénome et une glande normale sont identifiés, n'explorent pas la région controlatérale. Nous avons analysé la stratégie de l'abord unilatéral à l'aide d'un modèle mathématique afin de déterminer les variables qui augmentent la probabilité de méconnaître une tumeur dans la région cervicale inexplorée. En estimant les fréquences d'adénome unique à 80%, d'hyperplasie à 14%, de double adénome à 4%, de triple adénome à 1% et de carcinome à 1% ainsi que la probabilité de méconnaître une tumeur dans la région inexplorée à 5%, nous avons trouvé que: 1) seulement 41% des patients traités par abord unilatéral subissent une exploration unilatérale. Ce pourcentage passe à 62% quand une exploration topographique avec une sensibilité de 80% est pratiquée en préopératoire. 2) la probabilité de méconnaître une tumeur de la région cervicale non explorée est parallèle à la prévalence des adénomes multiples. La moitié des patients ayant un triple adénome et 2/3 des patients ayant un double adénome peuvent avoir une tumeur méconnue s'ils sont traités par un abord unilatéral. 3) les patients qui bénéficient d'une exploration unilatérale ont une probabilité augmentée de 7 à 8% d'avoir une tumeur méconnue qui aurait été trouvée si une exploration bilatérale avait été réalisée. Ce risque diminue à 2% lorsqu'une exploration topographique d'une sensibilité de 80% est réalisée en préopératoire. 4) une étude prospective randomisée unilatérale ou bilatéral nécessiterait 684 patients pour avoir une puissance statistique de 80% (=0,05, =0,20) pour mettre en évidence une différence entre les risques de méconnaître une tumeur de 5% et de 10%.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.     

Hypocalcemia after neck exploration for untreated primary hyperparathyroidism

Hypocalcemia after neck exploration for hyperparathyroidism is an important postoperative management issue. With increasing acceptance of less invasive surgical approaches, hypocalcemia is less frequent. This study was conducted to evaluate postoperative hypocalcemia after current surgical exploration techniques in patients with untreated primary hyperparathyroidism. From the University of Louisville parathyroid database, charts of patients undergoing surgery for untreated primary hyperparathyroidism from May 1, 1998 to May 30, 2004 were reviewed. Data was analyzed based on age, sex, preoperative calcium and parathyroid hormone levels, preexisting diseases, and extent of neck exploration. One hundred sixty-nine patients were identified with adequate data for analysis. Transient postoperative hypocalcemia occurred in 21 per cent (36/169) for the total group, in 18 per cent (22/125) after minimally invasive radio-guided parathyroidectomy, and in 32 per cent (14/44) after bilateral neck exploration. Patients with postoperative hypocalcemia had a statistically significant association with older age and pre-existing hypertension. Patients with postoperative hypocalcemia were more likely to have undergone longer surgical procedures and were more likely to have had pre-existing diabetes and mental disorders. These findings were not statistically significant and were considered trends. The frequency of osteoporosis in the hypocalcemia group was increased but was not significant. Transient hypocalcemia occurred in 21 per cent of patients after parathyroid surgery. It was more likely after bilateral neck exploration, a longer duration of surgery, and with hypertension, diabetes, and mental disorders.     

Video-assisted neck exploration for primary and secondary hyperparathyroidism

Background: Minimally invasive surgery (MIS) for primary hyperparathyroidism includes unilateral neck exploration, access via a totally endoscopic approach, and access via a video-assisted procedure. We report herein our initial experience with the video-assisted neck exploration procedure for primary (PHPT) and secondary hyperparathyroidism (SHPT). Methods: Between June 1999 and May 2000, 35 patients were selected for PHPT (n = 25) and SHPT (n = 10). In all cases, video-assisted neck exploration was performed under general anesthesia, leading to selective adenoma removal in PHPT or subtotal parathyroid resection in SHPT. Patient selection was based on the preoperative localization studies (ultrasonography and sestamibi scintigraphy). Results: Five of the 25 patients operated on for PHPT (20%) and three of the 10 patients who underwent surgery for SHPT (30 %) were converted to a conventional surgical technique. The mean operative times in PHPT and SHPT were 48.9 ± 18.7 min and 136.8 ± 18.7 min, respectively. The recurrent laryngeal nerve was identified in 45% of the patients. The median size and weight of the resected parathyroid glands were 1.8 cm (range, 0.9-2.5) and 1 g (range, 0.5-7), respectively. The length of skin incision was 24 ± 1.2 mm. All but one patient are currently cured, with a median follow-up of 6 months (range, 2-13). Postoperative complications included hematoma and transient hoarseness in one patient each (2.85%). The median pain intensity, based on the visual analogue scale (VAS) method, as measured at postoperative day 1 was 0.5 (range, 0-3.6). In the PHPT group, the postoperative hospital stay was <24 h for 30% of the patients and <48 h for 80% of them. conclusion: video-assisted unilateral and bilateral neck exploration is feasible and safe; it represents an attractive and promising minimally invasive approach in phpt and shpt when the surgeon follows the same rules used in the standard conventional approach. its early benefits and long-term results still need to be compared to those of the conventional procedure in a randomized trial.     

Unilateral versus bilateral neck exploration for primary hyperparathyroidism: five-year follow-up of a randomized controlled trial

OBJECTIVE: To compare long-term patient outcome in a prospective randomized controlled trial between unilateral and bilateral neck exploration for primary hyperparathyroidism (pHPT). SUMMARY BACKGROUND DATA: Minimal invasive and/or focused parathyroidectomy has challenged the traditional bilateral neck exploration for pHPT. Between 1997 and 2001, we conducted the first unselected randomized controlled trial of unilateral versus bilateral neck exploration for pHPT. The results showed that unilateral exploration is a surgical strategy with distinct advantages in the early postoperative period. However, concerns have been raised that limited parathyroid exploration could increase the risk for recurrent pHPT during long-term follow-up. METHODS: Ninety-one patients with the diagnosis of pHPT were randomized to unilateral or bilateral neck exploration. Preoperative scintigraphy and intraoperative parathyroid hormone measurement guided the unilateral exploration. Gross morphology and frozen section determined the extent of parathyroid tissue resection in the bilateral group. Follow-up was performed after 6 weeks, 1 year, and 5 years postoperatively. RESULTS: Seventy-one patients were available for 5-year follow-up. There were no differences in serum ionized calcium and parathyroid hormone, respectively, between patients in the unilateral and bilateral group. Overall 6 patients have been found to have persistent (n = 3) or recurrent (n = 3) pHPT; 4 patients in the unilateral group (3 of these 4 patients were bilaterally explored) and 2 patients in the bilateral group. Three of 6 failures were unexpectedly found to have multiple endocrine neoplasia mutations. One patient with solitary adenoma in the bilateral group still required vitamin D substitution 5 years after surgery. CONCLUSION: Unilateral neck exploration with intraoperative parathyroid hormone assessment provides the same long-term results as bilateral neck exploration, and is thus a valid strategy for the surgical treatment of pHPT.     

Increasing trend of bilateral neck exploration in primary hyperparathyroidism

BackgroundBilateral neck exploration was the standard operation for primary hyperparathyroidism. With improvements in preoperative localization and use of intraoperative PTH (ioPTH) monitoring, minimally invasive unilateral neck exploration has been widely adopted. This study evaluates the trend in parathyroidectomies for primary hyperparathyroidism.MethodsParathyroidectomy for sporadic primary hyperparathyroidism was analyzed from 2010 to 2017. Exclusion criteria included previous neck surgery and concomitant procedures. The operations were classified as unilateral exploration (UE), UE converted to bilateral exploration (BE), or BE. Variables included preoperative and intraoperative factors. Outcomes included persistence, recurrence, permanent hypocalcemia and recurrent laryngeal nerve (RLN) injury.ResultsFour hundred thirty-one patients were reviewed. Since 2010, the rate of BE has increased from 30% to 50%. Disease duration, presence of bone disease, negative localization, baseline ioPTH <100, and ≥2 abnormal glands have increased. Mean operative time has not changed over time. Two percent of patients had persistent disease, <1% had recurrent disease, and 2% have had reoperation. Nine percent had temporary hypoparathyroidism, and 15 patients had temporary RLN injury.ConclusionsThis study shows an increasing trend in BE for primary hyperparathyroidism. This increase was associated with lower baseline intraoperative parathyroid hormone (ioPTH) levels and smaller gland size. The operative approach for parathyroidectomy should be individualized and surgeons should not hesitate to perform BE when needed.     

Initial neck exploration for untreated hyperparathyroidism

This study represents the experience of the Department of Surgery at the University of Louisville over a 21-year interval. Many aspects of surgical management of hyperparathyroidism have changed over the last 2 decades; controversies regarding the extent of exploration and the value of preoperative localization studies remain unresolved. One hundred ninety-three patients underwent neck exploration for hyperparathyroidism from 1976 to 1997. Data were collected from four University of Louisville-affiliated hospitals by independent evaluators. One hundred sixty patients with untreated hyperparathyroidism underwent neck exploration. Preoperative localization was carried out in 52 per cent (83 of 160). The exact location of the abnormal gland was indicated in 55 per cent (46 of 83), and the correct side of the neck was identified in 74 per cent (61 of 83). Technetium sestamibi scan was most reliable and identified the abnormality in 83 per cent (24 of 29). The average operative time with preoperative localization was 118 minutes compared with 137 minutes without preoperative localization. Intraoperative methylene blue was used in 42 of 160 neck explorations. Average operative time with methylene blue was 102 minutes compared with 124 minutes without methylene blue. Thirty-seven per cent (59 of 160) of patients underwent unilateral neck exploration. Sixty-three per cent (101 of 160) underwent bilateral exploration. Successful exploration was conducted in 98 per cent of the unilateral group and 91 per cent of the bilateral group. Postoperative local complications were essentially the same in both groups (3%), whereas temporary hypocalcemia occurred in 24 per cent (24 of 101) of the bilateral group compared with 3 per cent (2 of 59) of the unilateral group. We conclude that neck exploration for hyperparathyroidism is a highly successful, safe treatment with no mortality and minimal morbidity. Preoperative localization studies modestly reduced the duration of surgery without improving outcome.     

Parathyroid exploration for primary hyperparathyroidism

Parathyroidectomy was studied retrospectively in 107 patients with primary hyperparathyroidism. This condition was diagnosed by measuring both the total serum calcium and ultrafilterable calcium (non-protein-bound) levels. The identification of ultrafilterable calcium is an important adjunct to parathyroid surgery as it allows the diagnosis of hyperparathyroidism when the total serum calcium level is normal. The surgical technique for selective parathyroidectomy and multiple biopsies was uniform. Parathyroid adenoma was discovered in 73 patients, diffuse hyperplasia in 26 and combined disease in 8. Postoperatively, two patients suffered from permanent hypocalcemia and three had hypercalcemia.     

The use of pre-operative scan prior to neck exploration for primary hyperparathyroidism

A group of patients with diagnosed primary hyperparathyroidism (PHP) in Auckland between 1982 and 1986 is reviewed. Of the 119 patients, 55 had pre-operative scanning, 36 had no scanning prior to surgery and 29 were managed conservatively. Of the 52 patients who had pre-operative localization with ultrasound scanning, only 27 (52%) had their adenoma correctly predicted upon neck exploration. Of the 14 patients investigated with thallium-201 and technetium-99m (T1/Tc) subtraction scanning, 10 (71%) had their adenoma positively identified in the predicted locations, whereas the cause of the parathyroid pathology was correctly identified in 33 of the 36 patients (92%) who had surgery alone with no pre-operative scanning. In 11 patients both ultrasound and T1/Tc subtraction scanning were employed. In eight patients the results of the two scanning modalities agreed, and in seven of these eight patients the adenoma was correctly predicted (six single adenomas and one with double adenoma). In the three patients in whom the results of the two modalities differed, the T1/Tc subtraction scanning correctly predicted the site of the adenoma in two patients and in the third patient (with a small 223 mg adenoma) both modalities were incorrect. Of the six patients with histologically proven parathyroid hyperplasia, only three had pre-operative localization with ultrasound alone, and all three had incorrect predictions (one false positive for adenoma, and two false negative scans). Overall the results cast doubt over the usefulness of pre-operative scanning as a routine investigation prior to initial neck exploration for primary hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Success of preoperative imaging and unilateral neck exploration for primary hyperparathyroidism.

The surgical treatment of hyperparathyroidism has become controversial with the recent advent of reliable preoperative imaging modalities. This study examines the efficacy and economy of using preoperative imaging studies to localize the pathology and allow for unilateral neck exploration. From January 1990 to May 1996, a total of 91 patients with primary hyperparathyroidism were treated at Swedish Medical Center in Seattle, WA, by 2 surgeons. Eighty-six nuclear scintigraphy studies were performed, of which 44 were technetium 99m sestamibi (Tc-99m-sestamibi) scans and 42 were thallium 99m technetium (Th-99m-Tc) scans. The overall sensitivity for Tc-99m-sestamibi was 91% (40/44), and that for Th-99m-Tc scans was 81% (34/42). Ultrasound examination revealed a sensitivity of 80% (66/82). There was a statistically significant difference in surgical time between the unilateral and bilateral neck explorations (45 minutes, P < 0.0001). Unilateral neck exploration for hyperparathyroidism has been successful in curing hypercalcemia 93% (85/91) of the time with the use of preoperative imaging studies. Tc-99m-sestamibi is a reliable tool for planning the initial unilateral neck exploration for treatment of primary hyperparathyroidism.     

Risk assessment for severe postoperative hypocalcaemia after neck exploration for primary hyperparathyroidism.

BACKGROUND AND AIMS: A further development of the risk profile for severe postoperative hypocalcaemia after surgery for primary hyperparathyroidism (pHPT) was made with the aim of expanding the group of patients who can be discharged safely after 23 hours. METHODS: Prospective study with 156 consecutive pHPT patients (158 operations) during 2001 and 2002. Risk factors for postoperative severe hypocalcaemia (ionised calcium < 1 mmol/L), were (1) preoperative concentration of parathyroid hormone (PTH) > 35 pmol/L (five times the upper reference value, reference range 1.1 to 6.9), (2) history of previous neck surgery, (3) biopsy/excision of > 2 parathyroid glands or (4) concomitant thyroid surgery. RESULTS: The risk factors showed a sensitivity of 100 % (9/9). In 110 of the operations (70%) no risk factors were identified. Postoperative calcium levels were significantly lower after 48 operations with risk factor(s) identified, as compared to the group without risk factors (p < 0.01). Seven of 17 patients (41%) with PTH > 35 pmol/L developed severe postoperative hypocalcaemia. Two of 31 patients (6%) with PTH < 35 pmol/L in the presence of other risk factor(s) developed severe postoperative hypocalcaemia. CONCLUSION: Patients with no risk factor can safely been discharged from hospital on the first postoperative day. Patients with preoperative concentration of PTH > 35 pmol/ L (five times the upper reference value) should stay in hospital until nadir level of calcium is reached. Patients with concentration of parathyroid hormone less than 35 pmol/ L in the presence of other risk factor(s) may have an early discharge from hospital (second postoperative day) combined with outpatient measurements of calcium levels.     

The actual role of bilateral neck exploration in the treatment of primary hyperparathyroidism

Surgery is the only curative treatment for primary hyperparathyroidism (pHPT). Surgical exploration is recommended for all patients with biochemically documented pHPT and signs or symptoms of the disease. Some patients are asymptomatic, others have subtle symptoms that disappear after parathyroid surgery. Felix Mandl successfully performed the first parathyroidectomy in 1925, using a bilateral neck exploration (BNE) with examination of all four glands and this remained the procedure of choice for pHPT into the 1990s. As over 80% of pHPT cases are due to a single parathyroid adenoma, many authors have questioned the need of BNE and have proposed directed unilateral approaches, termed "mini-invasive parathyroidectomies". The aim of this report is to define which is the actual role of the conventional surgical approach to pHPT.     

单侧探查术治疗甲状旁腺腺瘤所致的甲状旁腺功能亢进症

目的 评价单侧手术探查治疗甲状旁腺腺瘤的效果。方法 总结1986-1999年20例患者的全部临床资料,对20例患者通过影销售量学诊断定位,行单侧探查术并与双侧探查术疗效进行对比。结果 除1例推测为双腺瘤患者手术失败外,其余效果均满意。结论 中国人由甲状旁腺腺瘤引起的甲状旁腺功能亢进症病变多在一侧,行单侧探查有一定优点。     

Causes of the failed cervical exploration for primary hyperparathyroidism

Over a period of 42 years, 581 patients with presumed hyperparathyroidism underwent an initial cervical exploration. Abnormal parathyroid glands were removed from 495 patients (85.2%). There was a greater probability of operative success in women, patients over 50 years of age, and patients with hypercalcemia, hypertension, or nonspecific abdominal pain. There was no association of operative outcome with some of the "classic" manifestations of hyperparathyroidism--peptic ulcer disease, neuropsychiatric symptoms, pancreatitis, bone disease, or urolithiasis. The probability of surgical success improved with time, increasing from 56 per cent in the 1950s to 97 per cent in the present decade. This improvement appears to be related to greater operative experience, since all four parathyroid glands were more likely to be found with increased experience, and there was a strong correlation between finding four parathyroids and achieving persistent normocalcemia. The most common causes of operative failure were inaccurate calcium assays (the patient was not truly hypercalcemic), an inappropriate diagnosis ("normocalcemic hyperparathyroidism"), and surgical inexperience. These three factors accounted for at least three fourths of all negative explorations. More accurate diagnostic studies, and careful exploration by an experienced surgeon should maximize the probability of a successful operation for primary hyperparathyroidism.