At present, both domestic and foreign countries agree that surgery is the most effective way to treat hyperparathyroidism. In the author’s opinion, most clinicians have mastered the technical points of general parathyroid surgery with accurate preoperative localization; however, there is still a blind spot in the understanding and technique of surgical treatment for those who have difficulty in detecting parathyroid glands during surgery. In addition, there are great difficulties in preserving or removing parathyroid glands in recurrent parathyroid disease or reoperation for thyroid disease. Therefore, with the development of medical technology and the increase in the detection rate of parathyroid disease, as a clinician as long as you master the technical points of difficult parathyroid surgery, you will be able to relieve more patients with parathyroid disease. 1.1 Diagnosis and localization of parathyroid disease For parathyroid disease, according to typical clinical manifestations, symptoms, signs and auxiliary examination, it should not be difficult to make a clear diagnosis, if combined with B ultrasound, CT and other examinations for preoperative localization, the operation process will be smoother to find and resect the lesion. When the parathyroid glands are not diseased, it is very difficult to detect the parathyroid glands by ultrasound or CT. However, when the parathyroid glands are diseased and abnormally enlarged, the sensitivity of these imaging tests can reach 72% ~ 85%. In recent years, ultrasound has been recognized as the most commonly used test for preoperative localization of parathyroid glands. High-resolution ultrasound is highly sensitive for preoperative parathyroid localization in patients with hyperparathyroidism. Ultrasound has a sensitivity of 70% to 92.5% for glands located in the retroesophagus, mediastinum, carotid sheath, or elsewhere, but it is difficult or impossible to detect glands that are only slightly enlarged. For parathyroid adenomas that cannot be identified by ultrasound, 99Tcm-methoxyisobutylisocyanide (MIBI) imaging can be used as a complementary test.99Tcm-MIBI can clearly localize parathyroid adenomas based on the difference in the rate at which the nuclide is contoured from the thyroid gland and the parathyroid adenoma, and has the greatest diagnostic value in the diagnosis of ectopic parathyroid adenomas. Preoperative nuclear scans of the neck, chest, and mediastinum are required to detect ectopic parathyroid glands.Rodgers et al. concluded that four-dimensional computed tomography (4D-CT) provides detailed anatomic information about parathyroid adenomas and allows more precise localization with greater sensitivity than preoperative ultrasound localization.Winters et al. concluded that ultrasound-guided placement of a guidewire to determine the location of the diseased parathyroid gland improves the accuracy of parathyroid surgery. This method makes it relatively easy to perform parathyroid surgery when preoperative or intraoperative localization is difficult, and Mariette et al. suggest that a combination of imaging techniques, such as MIBI visualization and ultrasound, can be used for preoperative localization of high-functioning parathyroid adenomas. However, it should be clear that there is a possibility of false-positive results with any of these tests. Although there are so many ways to localize the parathyroid glands preoperatively, it is sometimes difficult to find the diseased parathyroid glands during the actual surgery. In addition, some primary hospitals do not have the technology and equipment such as 99Tcm-MIBI visualization and 4D-CT, which also increase the difficulty of the surgical treatment of parathyroid diseases. 1.2, Exploration of parathyroid glands that are difficult to find intraoperatively For patients with accurate preoperative localization of lesion parathyroid glands, different surgical methods can be adopted according to different situations. For lesions located in the neck, a transverse neck neck collar incision can be used to resect the lesion more smoothly; if the lesion is located in the thymus or the anterior mediastinum, the parathyroid glands can be resected in the open chest. The resection of lesion parathyroid glands that are preoperatively located in the neck but difficult to detect and ectopic during surgery is the current difficulty in parathyroid surgery. In order to remove the lesions and treat parathyroid disease effectively and thoroughly, the operative field should be explored in an orderly, comprehensive and thorough manner. The upper parathyroid glands are often fixed in the posterior aspect of the upper pole of the thyroid gland, and they can be easily found within 1 cm of the intersection of the recurrent laryngeal nerve and the superior thyroid artery. Because the upper parathyroid glands undergo very limited displacement during embryonic development, the upper parathyroid glands are rarely ectopic. When ectopic, it is commonly found in the tracheoesophageal groove, posterior mediastinum, retropharynx, or thyroid gland. Typically, 99% of the glands in the upper parathyroid gland are located immediately adjacent to the thyroid gland, with 77% at the cricothyroid cartilage, 22% behind the upper pole of the thyroid gland, and 1% located in the retropharynx or posterior esophagus.Welling et al. reported a case of a patient with primary hyperparathyroidism in which intraoperative cervical exploration did not reveal any diseased glands; however, 4D-CT examination revealed hyperplastic parathyroid glands bilaterally in the retropharyngeal region. . The inferior parathyroid glands are usually located near the inferior pole of the thyroid gland in the “parathyroid hot zone” with a diameter of 2 cm centered 1 cm above the intersection of the recurrent laryngeal nerve and the inferior thyroid artery. However, the location of the inferior parathyroid glands is highly variable and requires careful identification. 20% of patients have ectopic parathyroid glands, with the most common ectopic location being in the thymus sheath (15%), and rarely in the thyroid gland (1%-4%), anterior mediastinum, submandibular, tracheo-esophageal sulcus, posterior oesophagus, and carotid artery sheaths. According to other data, 44% of parathyroid glands are located in the anterior aspect of the inferior pole of the thyroid gland, 26% are located in the thymus tissue below the thyroid gland, 17% are located in the subxiphoid fat, and 6% are located near the carotid artery division. Therefore, in cases where the diagnosis of parathyroid lesions is clear preoperatively and no clear lesion is seen intraoperatively, the possibility of ectopic parathyroid lesions should be noted, and possible ectopic sites need to be explored. In patients in whom the presence of a diseased parathyroid gland has been identified on preoperative ultrasound and in whom careful exploration of the retropharynx and tracheoesophageal groove does not reveal a suspected diseased upper parathyroid gland, exploration of the posterior aspect of the upper mediastinum should be performed. If the inferior parathyroid glands are not found intraoperatively, the cervical root, thymus and anterior superior mediastinum should be carefully explored; if both the superior and inferior parathyroid glands are not found, the carotid sheath should be incised for exploration; if the diseased parathyroid glands may be in the ipsilateral thyroid, thyroid lobectomy is feasible to identify the lesion. In the author’s opinion, intraoperative exploration of the parathyroid glands should be combined with the operator’s own and the patient’s actual situation, and the order of exploration should be flexibly mastered. 1.2.1 Exploration of the thyroid region Strip the thyroid gland between the true and false peritoneum of the thyroid gland, retain the upper and lower thyroid arteries as much as possible, in order to preserve the blood supply of the thyroid gland and avoid innocent injury to the thyroid gland. Dissect the middle thyroid vein and further separate the thyroid peritoneum toward the posterior side of the thyroid gland. After sufficiently freeing the thyroid gland, the thyroid gland was drawn medially. Since the position of the upper parathyroid glands is relatively fixed and the position of the lower parathyroid glands is more variable, the upper parathyroid glands were explored first, followed by the lower parathyroid glands, and if no lesion was detected, the upper and lower extremes of the thyroid glands should be continued to be explored postero-laterally and anteriorly, and even intra-thyroidally. The possibility of a diseased parathyroid gland should be considered if a mass of the size described in the preoperative examination is found by palpation. 1.2.2 Probing the area around the vascular sheath Before probing this area, the recurrent laryngeal nerve should be exposed throughout to avoid injury to the recurrent laryngeal nerve. Probe the tracheo-esophageal groove for the presence of a mass; if a mass is present, free excision of the mass should be performed, and intraoperative rapid frozen section examination should be performed to confirm whether it is a diseased parathyroid gland. If no abnormality is detected, the tracheoesophageal groove and the surrounding tissues of the carotid sheath are freed to fully reveal the carotid sheath, and special attention should be paid to the presence of a mass within the carotid sheath, and the parathyroid glands may be ectopically located within the carotid sheath. The inferior parathyroid glands originate from the third gill bursa, and many ectopic third gill bursas are due to abnormal embryologic migration. It is this that can lead to a high rate of ectopic ectasia from the mandible to the periphery of the inferior thyroid vascular sheath of 2%. 1.2.3, Exploration of areas outside the carotid sheath The area outside the carotid sheath can be equated to the location of the cervical lymph nodes in zones II, III, and IV. The ectopic rate of the parathyroid glands in this area is relatively low, but it is very necessary to explore this area for surgeries in which intraoperative detection of the parathyroid glands is difficult. 1.2.4 Probing around the posterior-lateral esophagus After the previous exploration, no lesion is still found, but according to the patient’s clinical manifestations and laboratory tests suggesting the presence of a definite lesion, it is necessary to continue to the posterior side of the neck, i.e., the posterior and lateral esophagus, for exploration. If a reddish-brown or yellowish-brown mass is found, the presence of a lesion can be confirmed. It is also difficult to determine preoperatively the presence of a lesion that is heterogeneously located in the posterior esophagus. In the author’s opinion, for preoperative localization, if the location of the lesion is suggested to be deeper, preoperative barium esophagography can be considered. If the lesion is located heterogeneously in the posterior or lateral esophagus, it can show an image of the esophagus narrowing or protruding toward the wall due to compression, and the surgery will become relatively easy. Intraoperative detection of parathyroid hormone (PTH) is considered to be an important innovation in the surgical treatment of hyperparathyroidism (HPT), and is capable of determining whether or not all lesions of the parathyroid glands have been completely resected, with a sensitivity of 100% and an accuracy of 87.1%. This method was used to detect PTH values in blood drawn 5 and 10 min after removal of suspicious lesions before and during surgery, respectively. In general, if the intraoperative PTH level decreased by more than 50% compared with the preoperative level, it indicated that the diseased parathyroid gland had been successfully removed. This method has increased the success rate of primary parathyroidectomy from 93% to 98%. Similarly, for parathyroidectomies with difficult intraoperative findings, the nature of the explored mass is more clearly defined, improving the success rate of the procedure. It is worth noting that when exploring the superior parathyroid glands, the superior laryngeal nerve and the recurrent laryngeal nerve should be avoided as much as possible to avoid postoperative hoarseness or choking on water, which may cause unnecessary pain to the patient. When exploring the posterior esophagus or around the carotid artery, it is necessary to operate carefully, avoiding the use of an electric knife, and should try to detach the carotid artery as much as possible to avoid rupture of the carotid artery during the operation or the occurrence of postoperative esophageal fistula. In order to avoid the occurrence of postoperative hypokalemia, attention must be paid to protect the blood supply of parathyroid glands during intraoperative exploration, and parathyroid autotransplantation should be performed if necessary. 2.Technical points of surgery for recurrent parathyroid disease. During surgery for recurrent parathyroid disease, intraoperative localization or resection of the parathyroid glands is also very difficult, because the surgical field of patients who undergo surgery again has extremely severe tissue adhesions, and it is not easy to find normal anatomical gaps, and the ectopic parathyroid glands are pulled due to the adhesions, which makes the surgery difficult. Surgical treatment of recurrent parathyroid disease is not common at home and abroad. In general, in patients with parathyroid adenomas, removal of the diseased parathyroid glands terminates the damage of HPT and is less likely to recur after surgery.The recurrence of HPT depends mainly on the pathological characteristics of the parathyroid tissue retained during the initial surgical treatment. Patients with a family history of primary hyperparathyroidism (PHPT) or postoperative multiple endocrine gland disease (MGD) are prone to recurrence.Tonlinaga et al. have had experience with more than 1,700 surgical procedures, most of which were performed with total parathyroidectomy + parathyroid forearm transplantation, with a recurrence rate of approximately 21.4% at 10 years postoperatively, with recurrences almost exclusively caused by overgrowth of the grafts, and with 1.4 percent of patients require neck re-exploration surgery. For experienced surgeons, the success rate of reoperation for recurrent parathyroid disease is as high as 95%. The postoperative recurrence rate for patients who have undergone initial surgery for PHPT is estimated to be 5% to 10%. When reoperating for such patients, first, the diagnosis should be clarified before surgery. By taking medical history and perfect preoperative examination, the surgeon should clarify whether there is a possibility of MGD. If the preoperative examination determines that it is a single glandular lesion, the gland can be removed directly. If MGD is highly suspected or confirmed, another surgery should be performed to fully explore the gland. Intraoperative testing for PTH can rule out MGD.Secondly, exact localization of the lesion is required. Preoperative and intraoperative testing must be used to localize the lesion.4D-CT is accurate and sensitive for preoperative localization of recurrent parathyroid surgery. Preoperative placement of a localization guidewire under the guidance of B ultrasound or CT can reduce the operating time of recurrent parathyroid surgery, alleviate the pain of patients, and improve the success rate of surgery. Especially when 99Tcm-MIBI imaging cannot locate the parathyroid glands clearly, the parathyroid glands can be localized by placing the localization guidewire. Finally, fine intraoperative operation is needed. The incidence of permanent recurrent laryngeal nerve injury and hypoparathyroidism during surgery for recurrent parathyroid disease is 10% and 20%, respectively. The difficulty of surgical treatment lies in the adhesion of the surrounding tissues during reoperation, making it even more difficult to find the parathyroid glands, which are not easy to find in the first place. Therefore, the operator should be familiar with the local anatomy of the neck, carefully separate the adherent tissues, pay attention to the protection of the recurrent laryngeal nerve, and clearly resect the lesion. In conclusion, when performing difficult parathyroidectomy, the following points should be noted: ① clear preoperative diagnosis, which is very important, only a clear diagnosis of the presence of HPT, it is possible to perform parathyroidectomy. ② intraoperative precise identification of diseased parathyroid glands, if no lesion is found, the exploration should be carried out in a certain order, so as not to miss; exploration should follow the principle of “four from three careful”, that is, “from front to back, from top to bottom, from outside to inside, from easy to difficult, careful identification, careful dissection, careful removal “. (3) The parathyroid glands need to be accurately identified intraoperatively in order to decide whether to further explore other glands. As the parathyroid glands are surrounded by adjacent vital blood vessels, nerves and organs, they need to be carefully dissected to avoid unnecessary injury. This makes difficult parathyroid surgery relatively easy.