ENDOCRINE SURGERY - PART 5 docx

Figure 2 A technetium-99m–sestamibi scan demonstrated marked uptake in the chest in this 78-year-old woman with hyperparathyroidism on early chest (a), transverse (b), and sagittal (c) views. On CT scan (d) a nodule was noted adjacent to the aortic arch. A parathyroid adenoma was excised (e) through a limited anterior parasternal incision (Chamberlain approach). Roses274 parasternal approach. More recently, video-assisted thoracoscopy has successfully allowed excision of mediastinal parathyroid adenomas that were precisely localized preoperatively (96,97). Special considerations apply to the patient treated for parathyroid cancer or likely to have parathyroma- tosis. Patients who had previous treatment for para- thyroid carcinoma may develop recurrent disease in the neck. Localizing studies in patients with recurrent parathyroid carcinoma may be helpful but do not detect all foci of disease (27). In patients with familial histories of hyperparathyroidism as well as with MEN syndromes, prior procedures may lead to the implanta- tion of hyperplastic parathyroid tissue in the surgical field. Meticulous assessment of the prior surgery, a more extensive use of localizing procedures, and more complete and thorough explorations may be required to ablate hyperplastic parathyroid tissue in this situa- tion, and once again, the intraoperative QPTH may have particular efficacy. 10 SUCCESS AND MORBIDITY Results of large series (Table 2) from centers that have acquired significant experiences with reoperative cases indicate a success rate in the 80–90% range. In the largest series of 222 patients from the NIH, as detailed by Jaskowiak and associates (16), a success rate of 97% was reported. A more significant rate of permanent hy- poparathyroidism clearly resulted from these proce- dures than from primary operations. The NIH series reported a rate of 12%, Thompson and associates 13% (17), and Shen and associates 1% (15). Vocal cord paral- ysis rates in the 5% range have been reported, certainly higher than primary operations, where this complica- tion is rare (98). Certainly the cost of reoperative sur- gery is more significant (99). All of these considerations make attention to detail especially important for re- operative cases. Most impor tantly, the challenges of reoperative cases provide compelling incentives for as thorough, expeditious, and successful an approach to the initial procedure as possible (100–102). REFERENCES 1. van Heerden JA, Grant CS. Surgical treatment of pri- mary hyperparathyroidism: an institutional perspec- tive. World J Surg 1991; 15:688–692. 2. Bauer W, Federman DD. Hyperparathyroidism epit- omized: case of Captain Charles E. Martell. Metab- olism 1962; 11:21–30. 3. Martin JK, van Heerden JA, Edis AJ, Dahlin DC. Per- sistent postoperative hyperparathyroidism. Surg Gyne- col Obstet 1980; 151:764–768. 4. McGarity WC, Goldman AL. Reoperation for primary hyperparathyroidism. Ann Surg 1981; 194:134–139. 5. Muller H. True recurrence of hyperparathyroidism: proposed criteria of recurrence. Br J Surg 1975; 62:556– 559. 6. Rudberg C, Akerstrom G, Palmer M, et al. Late results of operation for primary hyperparathyroidism in 441 patients. Surgery 1986; 99:643–651. 7. Chan FKW, Koberle LMC, Thys-Jacobs S, Bilezikian JP. Differential diagnosis, causes and management of hypercalcemia. Curr Problems Surg 1997; 34:449–523. 8. Heath H III. Familial benign (hypocalciuric) hyper- calcemia: a troublesome mimic of mild primary hyper- parathyroidism. Endocrinol Metab Clin North Am 1989; 18:723–740. 9. Marx SJ, Stock JL, Attie MF, et al. Familial Table 2 Results of Reoperations for Persistent or Recurrent Hyperparathyroidism Author(s) (Ref.) Year No. of patients % Cured Wang (12) 1977 112 91 Brennan and Norton (29) 1985 175 90 Grant et al. (10) 1986 157 89 Levin (43) 1989 81 91 Cheung et al. (102) 1989 83 86 Rothmund et al. (100) 1990 70 96 Carty and Norton (13) 1991 206 95 Jarhult et al. (64) 1993 93 82 Rodriguez et al. (14) 1994 152 93 Shen et al. (15) 1996 102 95 Jaskowiak et al (16) 1996 222 97 Mariette et al. (65) 1998 38 92 Thompson et al. (17) 1999 124 88 Reoperation For Primary Hyperparathyroidism 275 hypocalciuric hypercalcemia: recognition among pa- tients referred after unsuccessful parathyroid explora- tion. Ann Intern Med 1980; 92:351–356. 10. Grant CS, van Heerden JA, Charboneau JW, et al. Clinical management of persistent and/or recurrent pri- mary hyperparathyroidism. World J Surg 1986; 10:555– 565. 11. Consensus Development Conference Panel. Diagnosis and management of asymptomatic primary hyperpara- thyroidism: Consensus Development Conference State- ment. Ann Intern Med 1991; 114:593–597. 12. Wang CA. Parathyroid re-exploration: a clinical and pathological study of 112 cases. 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Parathyroid adenomas studied by digital subtraction angiography. Radiology 1984; 153:449–451. 55. Krudy AG, Doppman JL, Miller DL, et al. Detection of mediastinal parathyroid glands by nonselective digital arteriography. AJR 1984; 142:693–695. 56. Sugg SL, Fraker DL, Alexander R, et al. Prospective evaluation of selective venous sampling for para- thyroid hormone concentration in patients undergoing reoperations for primary hyperparathyroidism. Sur- gery 1993; 114:1004–1010. 57. Miller DL, Doppman JL, Krudy AG, et al. Local- ization of parathyroid adenomas in patients who have undergone surgery: Part II. Invasive procedures. Radiology 1987; 162:133–137. 58. Nilsson BE, Tisell LE, Jansson S, Zackrisson BF, Lindstedt G, Lundberg PA. Parathyroid localization by catheterization of large cervical and mediastinal veins to determine serum concentrations of intact parathyroid hormone. World J Surg 1994; 18:605–611. 59. Granberg PO, Hamberger B, Johanson G, et al. Selective venous sampling for localization of hyper- functioning parathyroid glands. Br J Surg 1988; 73: 118–123. 60. Miller DL, Doppman JL, Chang R, et al. Angio- graphic ablation of parathyroid adenomas: lessons from a 10-year experience. Radiology 1987; 165:601– 607. 61. Harmon CR, Grant CS, Hay ID, et al. Indications, technique and efficacy of alcohol injection of enlarged parathyroid glands in patients with primary hyper- parathyroidism. Surgery 1998; 124:1011–1020. 62. Weber CJ, Sewell CW, McGarity WC. Persistent and recurrent sporadic primary hyperparathyroidism: his- topathology, complications and results of operation. Surgery 1994; 116:991–998. 63. WadstromC,ZedeniusJ,GuineaA,ReeveTS, Delbridge L. Reoperative surgery for recurrent or persistent primary hyperparathyroidism. Aust NZ J Surg 1998; 68:103–107. 64. Jarhult J, Nordenstrom J, Perbeck L. Reoperation for suspected primary hyperparathyroidism. Br J Surg 1993; 80:453–456. 65. 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Ann Surg 1986; 203:282–285. 99. Doherty GM, Weber B, Norton JA. Cost of unsuc- cessful surgery for primary hyperparathyroidism. Sur- gery 1994; 116:954–958. 100. Rothmund M, Wagner PK, Seesko H, Zielke A. Les- sons from reoperations in 55 patients with primary hyperparathyroidism. Dtsch Med Wochenschr 1990; 115:1579–1585. 101. Poole GV Jr, Albertson DA, Myers RT. Causes of the failed cervical exploration for primary hyperparathy- roidism. Am Surg 1988; 54:553–557. 102. Cheung PSY, Borgstrom A, Thompson NW. Strategy in reoperative surgery for hyperparathyroidism. Arch Surg 1989; 124:676–680. Roses278 21 Parathyroid Carcinoma John A. Olson, Jr. Duke University Medical Center, Durham, North Carolina, U.S.A. 1 DEFINITION Parathyroid carcinoma (PC) is a rare, malignant neo- plasm of the parathyroid glands that causes parathyroid hormone–dependent hypercalcemia. The distinction between primary hyperparathyroidism due to the com- mon parathyroid adenoma and the rare parathyroid carcinoma is rarely made on clinical grounds. Parathy- roid carcinoma may be identified during surgery, but the diagnosis is made only after careful histopatholog- ical examination of the resected specimen or at recur- rence months or years following resection. A diagnosis of parathyroid carcinoma is made with certainty by the demonstration of direct invasion of adjacent tissues, synchronous or metachronous cervical lymph node, or distant metastases. 2 EPIDEMIOLOGY 2.1 Incidence and Prevalence Parathyroid carcinoma is rare; the true incidence of this disease in the general population is unknown. It repre- sents 1% of cases of primary hyperparathyroidism in the United States and up to 5% of cases in published series from Japan and Italy (2–4). Fewer than 300 cases of parathyroid carcinoma were reported in the English literature prior to 1992, and an additional 100 cases have been reported in 16 published papers since 1992 (5). The largest series of parathyroid carcinoma pub- lished to date documents 286 cases of parathyroid cancer registered over a 10-year period in the National Cancer Data Base in the United States, representing 0.005% of all cases in this registry (Fig. 1) (6). 2.2 Demographic Features The female-to-male ratio is 1:1 for parathyroid carcino- ma. This is in sharp contrast to the female preponde- rence (3–4:1) observed in primary hyperparathyroidism due to sporadic benign parathyroid adenomas. The mean age of presentation of parathyroid carcinoma in most series is between 48 and 53 years, nearly a decade lower than the average age at presentation of benign parathyroid adenoma (Table 1). It has been reported in children less than 15 years of age (6–8). There is no racial predilection. It is unclear whether the higher incidence of parathyroid carcinoma in series of from Japan and Italy reflects true ethnic differ- ences in disease susceptibility or differences in diagnos- tic criteria. 3 RISK FACTORS 3.1 Environmental Environmental risk factors for parathyroid carcinoma are unknown. Reports of parathyroid carcinoma devel- oping in patients with a history of head and neck irra- 279 diation support a role for ionizing radiation–induced genetic mutations in this disease (9,10). 3.2 Genetic Parathyroid carcinoma has been reported as a feature of both familial isolated hyperparathyroidism (FIHP) and familial hyperparathyroidism–tumor jaw syndrome (FHPT-TJ). These inherited diseases are likely caused by the same gene, located on chromosome 1q25-31 (11– 13). In these syndromes, hyperparathyroidism is inherited in an autosomal dominant fashion. Familial HPT can also occur in the context of several other diseases, including multiple endocrine neoplasia type 1 (MEN1) and ty pe 2 (MEN2); however, parathyroid carcinoma is not a feature of the MEN syndromes. Streeten et al. reported two cases of parathyroid carcinoma and two cases of atypical parathyroid adeno- mas in a family with primary hyperparathyroidism with apparent autosomal dominant transmission (14). Con- stitutional karyotypes were normal in all four patients, although three chromosomal abnormalities (a recipro- cal translocation between chromosomes 3 and 4, triso- my 7, and a pericentric inversion in chromosome 9) were identified in cultured parathyroid carcinoma tissue from one patient. There was no evidence of ras gene mutations, PTH gene rearrangement, or allelic loss from the MEN1 locus on chromosome 11q13 in tumor DNA from one case of PC and one of atypical adenoma. Wassif et al. described 19 members of a large four- generation family with autosomal dominant FIHP (15). DNA markers closely linked to the MEN1 and MEN2A loci and the prepro-PTH gene excluded linkage to these syndromes. In one individual a parathyroid carcinoma Figure 1 Overall percentage survival from parathyroid car- cinoma over a 10-year period (N = 134). (Data from Ref. 6.) Table 1 Selected Series of Parathyroid Carcinoma with 10 or More Patients Author/institution (Ref.) Year Study type Pathology review Female:male ratio Average age, yr (range) Hundahl et al./ United States (6) 1985–1995 National registry 286 No 1:1 55 (14–88) Sandelin et al./ Sweden (3) 1968–1990 International registry 95 Yes 1:1 55 (20–83)F 52 (24–78)M Schantz and Castleman (8) 1930–1972 Single institution review 70 Yes 1:1 44 (13–84) Shane et al./ Columbia (2) 1966–1982 Literature review 62 No 1:1 48 (18–73) Holmes et al./NIH (7) 1933–1968 Literature review 50 No 1:1 44 (12–72) Wang and Gaz/ MGH (29) 1948–1983 Single institution review 28 No 1:1 45 (28–72) Wynne et al./ Mayo Clinic (31) 1920–1991 Single institution review 43 Yes 1:1 54 (29–78) Favia et al./Padua 1980–1996 Single institution review 16 Yes 1:2 61 (30–78) Levin et al./UCSF (39) 1966–1985 Single institution review 10 Yes 1:2 49 (23–68) Anderson et al./ MDACC (48) 1968–1982 Single institution review 15 Yes 1:1 (27–61) Chow et al./PMH, Toronto (47) 1958–1996 Single institution review 10 Yes 1:1 53 (14–72) Olson280 was found after recurrence of hypercalcemia, leading these investigators to conclude that FIHPT is a genet- ically and clinically dist inct entity with an increased risk of malignant transformation of parathyroid tumors. 3.3 Secondary Hyperparathyroidism Parathyroid carcinoma has been described in several patients with secondary hyperparathyroidism (sHPT) due to end-stage renal disease. This observation sug- gests that chronic stimulation of the parathyroid glands may lead to parathyroid carcinoma (16,17). The devel- opment of asymmetrical nodular parathyroid growth in hyperplastic glands in sHPT supports the notion that chronic parathyroid stimulation can lead to neoplastic transformation of parathyroid cells (18). Parathyro- matosis, the implantation and growth of hyperplastic parathyroid glands following tumor spillage during para-thyroidectomy, is a well-recogni zed outcome fol- lowing parathyroidectomy for benign sHPT (19). Whe- ther this phenomenon represents parathyroid cancer in these patients with sHPT is unclear. The observation that benign parathyroid tissue may grow heterotopi- cally and cause recurrent hyperparathyroidism supports the contention that not all parathyromatosis represents parathyroid carcinoma (40). 4 ETIOLOGY AND PATHOGENESIS The cause of parathyroid carcinoma is unknown. An association of parathyroid carcinoma with FIHP sug- gests a genetic predisposition. The a ssociation with se- condary HPT also suggests that chronic parathyroid stimulation or environmen tal factors are also important in the pathogenesis of parathy roid carcinoma. Isolated instances of synchronous parathyroid carcinoma and adenoma have been reported (20); however, the largest pathological review of parathyroid carcinoma reported no cases of parathyroid carcinoma developing in a pre- existing parathyroid adenoma or hyperpla sia (8). Oncogenes implicated in the pathogenesis of para- thyroid carcinoma include the cell cycle regulators, retinoblastoma (Rb) gene, and P53. Several investiga- tors have report ed somatic loss of the DNA at the Rb locus using polymorphic DNA markers (21–23) and decreased immunohistochemical staining of Rb protein in parathyroid carcinoma (21,24). However, other stud- ies have failed to identify such loss, and mutations in this gene have not been reported (25) . Loss of DNA in the region of P53 and abnormal P53 immunostaining have also been described in a small number of parathyroid carcinomas, although mutations in P53 have not been described (26). Mutations in PRAD1 (cyclin fused to PTH promoter in 5% of parathyroid adenomas), menin (MEN1), and ret (MEN2A), genes associated with benign parathyroid neoplasia have not been reported in parathyroid carcinoma. 5 CLINICAL PRESENTATION 5.1 Symptoms and Signs Virtually all patients with parathyroid carcinoma are symptomatic at the time of diagnosis. Symptoms reflect marked hypercalcemia and significanty elevated para- thyroroid hormone, rather than local effects of tumor growth (Table 2). These symptoms are similar to ad- vanced hyperparathyroidism and most commonly in- clude polyuria, polydypsia, weakness and fatigue, nausea and vomiting, dyspepsia and constipation (2). Depression and psychosis are also commonly described. Rare asymptomatic patients with nonfunctioning para- thyroid carcinoma have been reported; such patients present with a neck mass without clinical or biochemical features of hyperparathyroidism (27,28). Most patients with parathyroid cancer have severe renal and skeletal manifestations of hyperparathyroid- ism. This syndrome is again similar to the presentation of longstanding benign primary hyperparathyroidism, before the widespread use of the multichannel blood analyzer. Since most patients diagnosed today with hyperparathyroidism are asymptomatic, patients with severe symptoms and hypercalcemic crisis may be sus- pected of having parathyroid cancer (1). Up to 15% of Table 2 Clinical Features of Parathyroid Carcinoma Feature Frequency (%) Bone disease 46–73 Nephrolithiasis 30–64 Renal insufficiency 21, Pancreatitis 10–15 Weakness 8 Nausea and vomiting 5 Peptic ulcer 8–18 Hypercalcemic crisis 14 Local recurrence 25–30 Lymphatic metastases 10–15 Distant metastases 25–30 Hypercalcemia (>14 mg/dL) 40–70 Palpable neck mass 30–50 Vocal cord paralysis 15 Source: Refs. 7, 8, 29. Parathyroid Carcinoma 281 patients present in hypercalcemic crisis, with dehydra- tion, mental status changes, and profoundly elevated serum calcium (>14 mg/dL) (29). The clinical manifes- tations of severe hypercalcemia are variable and reflect altered central nervous system (CNS), cardiovascular, and gastrointestinal physiology (30). CNS dysfunction is characterized by confusion, impaired cognition, ob- tundation, and coma in severe cases. Cardiovascular effects include hypertension an d a shortened QT inter- val on electrocardiogram. Gastrointestinal symptoms such as anorexia, nausea, vomiting, and occasionally pancreatitis can be present. A palpable neck mass is uncommon in benign parathyroid disease and its pres- ence usually indicates the presence of a thyroid nodule. In contrast, a palpable neck mass is reported in 32–50% of patients with parathyroid carcinoma. This finding, in conjunction with very high PTH levels, should raise the suspicion of parathyroid cancer in hypercalcemic patients (29,31,32). Patients with parathyroid carci- noma may infrequently present with vocal cord paraly- sis, hoarsness, or dysphagia because of locally advanced disease involving the recurrent laryngeal nerve, esoph- agus, or trachea. 5.2 Laboratory Tests Hypercalcemia is the hallmark feature of parathyroid carcinoma. Hypercalcemia in these cases is often severe; between 39 and 75% of patients with parathyroid car- cinoma have a serum calcium concentration greater than 14 mg/dL (1). Patients with parathyroid carcinoma also have significant elevations of parathyroid hormone (5–70 times normal range) (2,20). Associated laboratory abnormalities include hypophosphatemia, elevated alkal ine phosphatase, and hyperchloremic metabolic acidosis due to bicarbonate excretion in the urine. 5.3 Imaging The routine use of preoperative localization studies in hyperparathyroid patients without a history of prior neck surgery is controversial. Until recently, imaging studies to preoperatively locate enlarged parathyroid glands were discouraged. However, recent data sug- gest that 99 Tc sestamibi identifies parathyroid adeno- mas with high sensitivity and may be used to select patients for directed parathyroidectomy with good suc- cess (32,33). Localization studies are clearly useful in reoperative parathyroidectomy, a small percentage of which is performed for recurrent parathyroid carci- noma. When parathyroid carcinoma is suspected on clinical grounds, preoperative imaging may be indicated to assess involvement of contiguous structures or to identify distant metastases. Effective noninvasive imag- ing studi es to identify parathyroid tissue include 99 Tc sestamibi scanning, ultrasound, computed tomography (CT) scan, magnetic resonance (MR) imaging, and FDG-PET. In selected cases, invasive imaging with selective venous sampling for parathyroid hormone may be useful. Despite an abundance of literature re- garding the effectiveness of these imaging modalities in benign parathyroid disease, the experience with var- ious approaches to imaging parathyroid carcinoma is anecdotal. Although frequently repo rted for localizing parathy- roid adenomas, 99 Tc sestamibi has been reported in only a few cases of primary and recurrent parathyroid carci- noma. Aigner was one of the first to describe focal Tc- 99m–MIBI uptake in parathyroid carcinoma (34). Sub- sequently, Al Sobhi reported a case of locally recurrent parathyroid carcinoma with involved lymph nodes that was localized by Tc-99m–sestamibi imaging and was confirmed surgically and pathologically (35) Neumann and colleagues also described a 65-year-old man with recurrent hyperparathyroidism after resect ion of para- thyroid carcinoma. However, double-phase Tc-99m– sestamibi scintigraphy gave misleading localization and the location and extent of the parathyroid carcino- ma were correctly detected by PET using 18F-fluoro- deoxyglucose (36). More recently, Favia et al. reported true positive findings (93.7% sensitivity) for sestamibi in 15 of 16 patients with parathyroid carcinoma (4). This compared favorably to ultrasound (11 of 13 true pos- itive, 85% sensitivity) and CT scan (4 of 4 true positive, 100% sensitivity) for localizing parathyroid carcinoma. Based on limited publis hed experience, Tc-99m–sesta- mibi should be considered to localize suspected primary or recurrent parathyroid carcinoma. High-frequency (10 MHz) ultrasonography has been reported for preoperative localization and for differ- entiating parathyroid carcinoma from adenoma (37). On ultrasound, parathyroid carcinomas are ovoid or round with a lobulated contour. They are predominant- ly hypoechoic relative to the adjacent thyroid but may contain both hypoechoic and hyperechoic regions and cystic spaces. Gross invasion of surrounding structures may be seen. In their series of over 70 parathyroid neo- plasms imaged with ultrasound, Hara et al. reported that a depth-width ratio greater than or equal to 1 was identified in 15 (94%) of the 16 cases of carcinoma, whereas only 3 (5%) of the 61 adenomas had a similar ratio (38). Ultrasonographic features of parathyr oid carcinoma include large, inhomogeneous, hypoechoic masses with lobulated con tours. In contrast, parathy- Olson282 roid adenomas appear as small, homogeneous, hypo- echoic masses with smooth borders. 6 DIAGNOSIS A high index of suspicion is required to prospectively identify malignant parathyroid disease (Table 3). A relative predisposition of males and younger patients to parathyroid cancer versus benign parathyroid disease has been noted; however, these trends are usually not helpful in assessing individual patients. Parathyroid cancer should be suspected during para- thyroidectomy when a firm, grey enlarged parathyroid gland is encountered. In these cases, the gland is fixed to surrounding structures and is difficult to dissect from adjacent tissues. This is in sharp contrast to benign para- thyroid adenomas, which are the oval, soft, reddish- brown, and are easily dissected from the thyroid. Ma- lignant parathyroid glands can be quite large, weighing up to 120 g. The discovery of pathological cervical ade- nopathy or frank invasion of nearby structures confirms the presence of parathyroid carcinoma. Despite these seemingly obvious criteria, a diagnosis of parathyroid carcinoma is rendered at the primary operation in only 15–80% of cases (3,6). A pathological diagnosis of grossly unapparent parathyroid cancer can be quite difficult. The most commonly accepted criteria to differentiate parathy- roid carcinoma from adenoma were initially proposed by Schantz and Castleman (8). Pathological featu res of parathyroid carcinoma include a trabecular cell pat- tern, mitotic figures, thick fibrous bands, and capsular and blood vessel invasion. (Figs. 2–4). However, para- thyroid adenomas may also have some of these fea- tures, making them unreliable and the diagnosis of parathyroid carcinoma in these cases uncertain (39). Other parameters, including nuclear diameter, tumor aneuploidy, Rb and P53 gene express ion, Ki-67 expres- sion, and gelatinase mRNA expression, have been pro- posed as specific tests for parathyroid carcinoma, yet none has provided superior discriminating power over histopathology (1). The most certain method of diag- nosis of a malignant tumor of the parathyroid is the identification of local tissue invasion or the presence of nodal or distant metastases. Consequently, a diagnosis of parathyroid carcinoma may be made following lo- cal or systemic recurrence of parathyroid carcinoma months to years following resection of a presumed be- nign parathyroid adenoma. Even then, local recurrence does not necessarily confirm the presence of carcino- ma since autotransplanted benign parathyroid adeno- mas have been shown to proliferate ectopically (40). 7 NATURAL HISTORY Owing to the rarity of the disease, there have been few independent studies to define the natural history of this disease (29,41). Most published series reveal that para- thyroid carcinoma is an indolent, yet tenacious malig- nancy. Parathyroid carcinoma is most prone to direct, local spread, with metastases to cervical lymph nodes occurring late in the disease. Distant metastasis to the lungs and liver and occasionally, bone, adrenals, and pancreas is usually a late event (29,42). Untreated, parathyroid carcinoma proceeds slowly, and patients often experience progressive decline sec- ondary to severe hyperparathyroidism. Morbidity and mortality are usually due to metabolic complications of hypercalcemia including uremia, arrhythmias, chronic wasting, hypercalcemic crisis, and pancreatitis (7). Morbidity due to mass effect of invasion of contiguous structures is less frequent. 8 TREATMENT 8.1 Surgery Aggressive surgical resection is the treatment of choice for primary parathyroid carcinoma. The initial opera- tion for localized disease includes en bloc removal of the parathyroid tumor, the ipsilateral thyroid lobe, and any adherent tissue. Long-term studies have shown that 50% or more of patients with parathyroid cancer will be cured by adequate surgical resection. The most important factor related to cure is en bloc surgical re- section without rupture or tumor spillage (29). In a careful analysis of factors predicting survival, the extent of surgical resection (i.e., tumor excision vs. tumor excision with either thyroid lobectomy or total thyroid- ectomy) correlated significantly with overall survival from parathyroid cancer (3). Table 3 Clinical Features Suggestive of Parathyroid Carcinoma Severe renal/bone manifestations Hypercalcemic crisis Calcium > 14 mg/dL Intact PTH > 5 times normal Palpable neck mass Male sex Parathyroid Carcinoma 283 [...]... management World J Surg 1998; 22(12):12 25 1230 Shane E Parathyroid carcinoma In: Bilezikian JP, Marcus R, Levine MA, eds The Parathyroids San Diego: Academic Press, 2001 :51 5 52 5 Parathyroid Carcinoma 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Hundahl SA, Fleming ID, Fremgen AM, Menck HR Two hundred eighty-six cases of parathyroid carcinoma treated in the US between 198 5- 1 9 95: a National Cancer Data Base Report... and Gaz/MGH (29) Holmes et al./NC (7) Wynne et al./Mayo Clinic (31) 286 95 70 62 28 46 43 60 84 60 NR 24–264 NR 83(14–228) Recurrence (%) Median time to recurrence (months) Survival at 5/ 10 years (%) Median survival (months) NR 42 31 NR 39 81 67 NR 33 (1–228) NR 36 18 NR 28 (3–228) 85. 5/49.1 85/ 70 43/43 69/NR 50 / 35 44/22 50 /13 69 /56 NR 28 NR NR 91 60 36 with recurrence are infrequently cured, with death... 1994; 219 (5) :57 4 57 9 Aigner RM, Fueger GF, Lax S A case of parathyroid carcinoma visualized on Tc-99m-sestamibi scintigraphy Nuklearmedizin 1997; 36(7): 256 – 258 Al Sobhi S, Ashari LH, Ingemansson S Detection of metastatic parathyroid carcinoma with Tc-99m sestamibi imaging Clin Nucl Med 1999; 24(1):21–23 288 36 Neumann DR, Esselstyn CB, Kim EY Recurrent postoperative parathyroid carcinoma: FDG-PET and... Epithelkorperchertumors Wien Klin Wschr 19 25; 38:1343–1344 Duh QY Surgical approach to primary hyperparathyroidism: bilateral approach In: Clark O, Duh QY, eds Textbook of Endocrine Surgery Philadelphia: Saunders, 1997: 357 –363 Tibblin SA, Bondeson AG, Ljunberg O Unilateral parathryoidectomy in hyperparathyroidism due to single adenoma Ann Surg 1982; 1 95: 2 45 252 Russel CF, Laird JD, Fergusson WR Scan-directed unilateral... during endoscopic neck surgery with CO2 insufflation Arch Surg 2001; 136(7): 822–827 Rubino F, Pamoukian VN, Zhu JF, Deutsch H, Inabnet WB, Gagner M Endoscopic endocrine neck surgery with carbon dioxide insufflation: the effect on intracranial 296 pressure in a large animal model Surgery 2000; 128(6): 10 35 1042 25 Miccoli P, Bendinelli C, Berti P, Vignali E, Pinchera A, Marcocci C Video-assisted versus conventional... of other glands is not performed or is limited These con- 2 PATIENTS AND METHODS During a 5- year period (1998–2002) we operated on 52 8 patients with primary hyperparathyroidism in the division of endocrine surgery at Hopital de la Timone in Marseille Major contraindications included the presence of a large goiter or previous thyroid/parathyroid surgery All cases of sporadic primary hyperparathyroidism... 8(4) :54 7 55 1 46 Obara T, Okamoto T, Ito Y, Yamashita T, Kawano M, Nishi T, et al Surgical and medical management of patients with pulmonary metastasis from parathyroid carcinoma Surgery 1993; 114(6):1040–1048 47 Chow E, Tsang RW, Brierley JD, Filice S Parathyroid carcinoma—the Princess Margaret Hospital experience Int J Radiat Oncol Biol Phys 1998; 41(3) :56 9 57 2 48 Anderson BJ, Samaan NA, Vassilopoulou-Sellin... video-assistee par abord laterocervical Ann Chir 1999; 53 :302–306 Cougard P, Goudet P, Osmak L, Ferrand L, Letourneau ´ B, Brun JM La video-cervicoscopie dans la chirurgie de ´ l’hyperparathyroı¨ die primitive Etude preliminaire portant sur 19 patients Ann Chir 1998; 52 :8 85 889 Gauger PG, Reeve TS, Delbridge LW Endoscopicallyassisted minimally invasive parathyroidectomy Br J Surg 1999; 86: 156 3– 156 6... adrenal cortex possesses a unique ability to 21-hydroxylate the steroid nucleus, a prerequisite in the aldosterone and cortisol synthetic pathways The cortisol pathway requires subsequent 1 7- and 11-h-hydroxylation, whereas the aldosterone pathway requires only 11-hhydroxylation and the introduction of an aldehyde group at the C-18 position (Fig 1) 3 05 306 and is also increased in the presence of congenital... five capsular tears necessitating a Table 2 Causes for Conversions in 42 Cases from 300 Video-Assisted Parathyroidectomies Adenomas not found Difficult dissections Multiglandular disease False-negative rPTH False-positive MIBI False-positive U/S 11 7 10a 3 10 1 RPTH: rapid parathyroid hormone assay; MIBI: methyl-iodo-benzyl iguanine nuclear scan; U/S: cervical ultrasonography a Diagnosed by rPTH conversion . adenomas. Surgery 19 95; 118: 11 15 1124. 24. Kraimps J-L, Duh Q-Y, Demeure M, Clark OH. Hy- perparathyroidism in multiple endocrine neoplasia syn- drome. Surgery 1992; 112:1080–1088. 25. Clark. 1994; 116: 954 – 958 . 100. Rothmund M, Wagner PK, Seesko H, Zielke A. Les- sons from reoperations in 55 patients with primary hyperparathyroidism. Dtsch Med Wochenschr 1990; 1 15: 157 9– 158 5. 101. Poole. parathy- roidectomy. Ann Surg 1994; 219 (5) :57 4 57 9. 34. Aigner RM, Fueger GF, Lax S. A case of parathyroid carcinoma visualized on Tc-99m-sestamibi scintigra- phy. Nuklearmedizin 1997; 36(7): 256 – 258 . 35.