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.     

Unilateral neck exploration for primary hyperparathyroidism

The operative approach to primary hyperparathyroidism due to a single adenoma remains controversial. We evaluated our experience with 75 patients presenting with primary hyperparathyroidism between January 1979 and September 1988. Prior to 1985 all patients underwent bilateral exploration. During this period, ultrasonographic localization in 6 patients proved highly accurate. Subsequently, routine preoperative ultrasonographic localization was used and patients were prospectively evaluated for the following: (1) incidence of unilateral exploration, (2) accuracy of ultrasonographic localization, (3) incidence of complications, and (4) operative time. Localization permitted unilateral exploration in 19 of 36 patients, although its accuracy depended on the interest of the radiologist involved. Institution A had an accuracy of 92%, while institution B had an accuracy of only 43%. There were fewer complications with unilateral exploration, and operative time was significantly less. Unilateral exploration based on preoperative ultrasonographic localization is recommended as the initial approach to primary hyperparathyroidism due to a single adenoma.     

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.     

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.     

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: 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.     

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.     

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.     

Clinical outcomes and fiscal consequences of bilateral neck exploration for primary idiopathic hyperparathyroidism without preoperative radionuclide imaging or minimally invasive techniques

BACKGROUND: Radionuclide imaging-directed, minimally invasive parathyroid operation is promoted in the surgical literature and public domain as the fastest, most successful, and cheapest means of treating primary idiopathic hyperparathyroidism. The validity of these claims is unproven. This study reviews the treatment outcome results of a large series of patients treated with standard parathyroid operation without preoperative localization studies. Cost comparisons are made between this series and previous reports of selected patients in whom preoperative radionuclide imaging preceded minimally invasive parathyroid operation. METHODS: Diagnosis, treatment, and outcome data for 688 consecutive patients undergoing first neck exploration for primary idiopathic hyperparathyroidism were prospectively collected. All patients in our series underwent standard bilateral neck exploration without preoperative localization studies. Intraoperative methylene blue was used to aid identification of all parathyroid glands. Surgical findings, pathological diagnosis, operative time, length-of-stay, and treatment success data were collected. Cost data were calculated for our series using the identical calculations used in previous reports. Our outcome and calculated cost data were compared with previous reports by centers advocating scan-directed, minimally invasive parathyroid operation. RESULTS: Of 2,752 predicted total glands, 2,520 (91.6%) were identified using standard neck exploration without radionuclide localization studies. Single adenoma, with at least 1 normal gland, was found in 542 patients (78.8%), with 8 in a fifth gland. Multiple-gland hyperplasia was identified in 98 patients (14.2%) and of these 22 (3.2%) were double adenomas. Ten patients had parathyroid carcinoma (1.5%), and all received definitive surgical treatment during the primary operation. Cure rates were assessed by measurement of normal serum calcium and parathyroid hormone levels at 3 and 12 months after operation, and were 97.7% in our series. Mean operating time for the entire series was 65 minutes, decreased to 35 minutes in patients with single adenomas, and mean recovery room time was 30 minutes. Mean total costs for patients undergoing standard exploration for single adenoma was US dollars 1,107, and increased to US dollars 1,243 when patients with multigland disease, hyperplasia, or malignancy were included. CONCLUSIONS: Our series demonstrates operative times and treatment outcomes with costs that are approximately one-third less than those for scan-directed, minimally invasive operation for primary idiopathic hyperparathyroidism. Thus, claims that scan-directed parathyroid operation is the cheapest, fastest, and most successful means of treatment are not supported by these data.     

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.     

Neglected bilateral femoral neck fracture associated with pregnancy and primary hyperparathyroidism

We report a case of neglected bilateral femoral neck fracture related with transient osteoporosis in pregnancy (TOP) and primary hyperparathyroidism, in a 33-year-old female who presented with a fracture of both femoral necks without any history of trauma 20 days after delivery. Her pain was at first accepted as common musculoskeletal discomfort following labour, and the final diagnosis was made only 25 days after fracture. She was treated with primary internal fixation with cannulated lag screws and received medical treatment for hyperparathyroidism and TOP. She was followed up for 29 months following the operation. No complications, and more specifically no avascular necrosis (AVN) were noted during this time interval. The patient made a complete functional recovery. We would like to emphasize that major medical problems may be underdiagnosed during the last pregnancy trimester and postpartum period. Delay in the diagnosis and treatment of a femoral neck fracture is an important but not a decisive factor for the development of AVN.     

Causes of failed primary exploration and technical aspects of re-operation in primary hyperparathyroidism

Hypercalcemia was corrected in 62 (90%) of 69 patients after re-operation for primary hyperparathyroidism during a mean follow-up of 6.3 years. Failed primary exploration was mainly due to inadequate visualization of the pathological parathyroid glands, often in association with misleading or absent peroperative histology. Other causes included seeding of parathyroid adenoma tissue, truly recurrent adenomas, and recurrent hyperplasia, especially in patients with multiple endocrine neoplasia type 1. A considerable number of parathyroid glands missed at the primary operations were subsequently found in essentially normal positions. Ectopic superior glands were most frequently positioned para-esophageally or retro-esophageally, while abnormally placed inferior glands were generally situated within or close to the thymus. Glands in 3 patients were dissected from around the large vessels in the mediastinum. Concomitant thyroid procedures during the primary operation yielded few abnormal parathyroids and made the re-exploration considerably more difficult. We suggest a semilateral approach and caudal identification of the recurrent laryngeal nerve to reduce the hazards of difficult parathyroid re-operations. Mediastinal exploration may require total removal of the thymus and careful dissection of the middle mediastinum.

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Resumen El hiperparatiroidismo primario (HPT) es diagnosticado y operado con frecuencia creciente. Además, la cirugía paratiroidea actualmente es practicada con mayor frecuencia en casos de hipercalcemia moderada, lo cual resulta en una tasa relativamente elevada de pacientes con hiperplasia y leve aumento del tamaño de la glándula. La exploración en tales casos puede ser más difícil de lo que generalmente se percibe, y puede verse asociada con resultados menos buenos en comparación con los que emanan de centros de referencia. La cirugía reoperatoria es un desafío que atrae considerable atención. Pero ha sido menor el interés sobre los problemas histológicos y quirúrgicos que pueden dar lugar a HPT persistente o recurrente. Ante esta perspectiva de creciente frecuencia de reoperaciones paratiroideas, nos propusimos examinar nuestro material clínico, con énfasis en las causas de las fallas en el curso de la exploración primaria, así como en los aspectos técnicos de la cirugía reoperatoria paratiroidea. La hipercalcemia resultó corregida en 62 de 69 (90%) pacientes en un seguimiento promedio de 6.3 años después de efectuada una reoperación por HPT primario. La falla de la exploración primaria se debió principalmente a visualización inadecuada de las glándulas paratiroideas patológicas, con frecuencia asociada con histología peroperatoria equívoca o ausente. Otras causas incluyeron la siembra de tejido paratiroideo adenomatoso, adenomas verdaderos recurrentes e hiperplasia recurrente, especialmente en los casos de neoplasia endocrina múltiple tipo l. Un número considerable de glándulas paratiroideas no identificadas en las operaciones primarias fueron halladas subsiguientemente en ubicaciones esencialmente normales. Las glándulas superiores ectópicas se ubicaron más frecuentemente en posición para o retroesofágica, en tanto que las glándulas inferiores ectópicas aparecieron generalmente ubicadas dentro o muy cerca del timo. Tres glándulas estaban ubicadas en el mediastino, alrededor de los grndes vasos. Los procedimientos quirúrgicos efectuados concomitantemente sobre la glándula tiroides en el curso de la operación primaria produjeron pocas glándulas paratiroideas anormales e hicieron que la reexploración fuera considerablemente más difícil. Sugerimos el abordaje semilateral y la identificación caudal del nervio laríngeo recurrente con el fin de disminuir los riesgos en las difíciles reoperaciones paratiroideas. La exploración mediastinal puede hacer mecesaria la remoción total del timo y la disección meticulosa del mediastino medio.

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Résumé L'hypercalcémie a pu être corrigée après réintervention pour hyperparathyroïdie primaire chez 62 des 69 patients (90%) avec un suivi moyen de 6.3 ans. La principale raison de l'échec de la première intervention était une visualisation insuffisante des glandes parathyroïdes pathologiques, souvent associée à une interprétation histologique préopératoire douteuse ou absente. D'autres causes sont l'ensemencement du tissu parathyroïde adénomateux lors de l'intervention, des récidives adénomateuses vraies et la récidive de l'hyperplasie surtout dans le cadre des néoplasies endocrines multiples de type 1. Unnombre considérable de glandes parathyroïdes non trouvées lors de la première intervention étaient en fait en position quasi anatomique. Les glandes supérieures ectopiques étaient essentiellement localisées en position para- ou rétroesophagienne, alors que les glandes inférieures ectopiques étaient plutôt situées dans ou près du thymus. Dans trois cas, on a trouvé les glandes ectopiques autour des gros vaisseaux dans le médiastin. Le fait de pratiquer un geste contemporain sur la thyroïde lors de la première intervention a peu influencé sur l'exploration des parathyroides mais a rendu la réexploration plus difficile. Nous suggèrons une approache chirurgicale unilatérale, avec identification du nerf récurrent par le bas pour réduire les risques de la réopération des parathyroïdes. L'exploration médiastinale peut nécessiter l'exérèse de la totalité du thymus et une dissection soigneuse du médiastin moyen.

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

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.     

The undescended "parathymus". An occasional cause of failed neck exploration for hyperparathyroidism.

Arrested descent of the inferior parathyroid gland ("parathymus") during embryologic development may leave the gland stranded high in the neck. Adenomas of such undescended glands are a rare cause of primary hyperparathyroidism, but they may not be uncommon among patients who have already had a failed cervical exploration. Unless the surgeon is aware of this entity, he will probably overlook it. If one is to find these tumors, it is necessary to extend the dissection upward above the superior pole of the thyroid gland, sometimes as far as the angle of the jaw. Adenomas of undescended "parathymus" glands were encountered in seven patients during a recent 20 month (May 1975 through December 1976) surgical experience encompassing 414 primary operations and 27 reoperations for hyperparathyroidism. These tumors were found at initial exploration in one patient and at reoperation in six patients. The individual case histories are presented to illustrate the difficulties posed by this anatomic variant.     

Preoperative sestamibi localization combined with intraoperative parathyroid hormone assay predicts successful focused unilateral neck exploration during surgery for primary hyperparathyroidism

A retrospective review of 54 cases of primary hyperparathyroidism operated upon by five general surgeons at Santa Barbara Cottage Hospital between March 1998 and March 2001 was performed to determine whether positive preoperative sestamibi localization (PSL) of a solitary adenoma combined with intraoperative parathyroid hormone assay (IOPHA) could predict successful focused unilateral neck exploration. A solitary adenoma was found in each of 50 patients (93%). PSL for solitary adenomas had an accuracy of 87 per cent, positive predictive value (PPV) of 96 per cent, sensitivity of 90 per cent, and specificity of 50 per cent. Forty-five patients (83%) achieved a 50 per cent reduction in IOPHA at 10 minutes after excision of a solitary adenoma for an accuracy of 85 per cent, PPV of 97 per cent, sensitivity of 88 per cent, and specificity of 50 per cent. All patients remain eucalcemic. The combination of PSL and IOPHA resulted in a PPV of 97.5 per cent and a sensitivity of 100 per cent. From these data we conclude that a focused unilateral neck exploration could have been performed successfully in 78 per cent of the cases.