Abstract
A solitary benign adenoma is responsible for primary hyperparathyroidism (pHPT) in nearly 80% of the cases. The other 20% of pHPT occurs as a result of parathyroid multiglandular disease. A good proportion of these patients belong to familial forms of pHPT. In recent decades, mutations in specific genes have been identified as responsible for various hereditary types of pHPT [1]. All of them are inherited as an autosomal dominant trait, and, as opposed to the sporadic HPT, they occur in children or in young adults. Some of these forms arise in the context of a genetic syndrome, others are nonsyndromic. These forms include: multiple endocrine neoplasia (MEN) types 1, 2A, and 4; familial hypocalciuric hypercalcemia (FHH); autosomal dominant moderate hyperparathyroidism (ADMH); neonatal severe hyperparathyroidism (NSHPT); hyperparathyroidism-jaw tumor syndrome (HPT-JT); familial isolated hyperparathyroidism (FIHPT) (Tables 14.1 and 14.2). The accurate and prompt diagnosis of these genetic conditions is crucial to plan appropriate surveillance of the carriers of the genetic mutations and to perform the correct surgical management. Research on the mutations is also useful for the identification of the family members (theoretically 50% of the offspring) who do not harbor the mutation and can avoid unnecessary biochemical, radiological and instrumental investigations. The determination as to which patients with pHPT the mutational analysis should be recommended to is controversial. The current guidelines suggest that the following situations require mutational analysis: individuals with pHPT before 45 years of age; patients at any age with presence of other endocrine tumors; multiglandular parathyroid disease at any age; presence of a parathyroid carcinoma at any age. In Table 14.3, a flowchart for the approach to a selective mutational analysis on the basis of clinical, biochemical and pathological data is shown. If the mutation of the genes involved in hereditary pHPT is found, the genetic analysis should be offered to all the first-degree relatives [2, 3].
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Marx SJ, Simonds WF, Agarwal SK et al (2002) Hyperparathyroidism in hereditary syndromes: special expression and special managements. J Bone Mineral Res 17(Suppl 2): 37–43
Eastell R, Brandi ML, Costa AG et al (2014) Diagnosis of asymptomatic primary hyperparathyroidism: Proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 99:3570–3579
Falchetti A, Marini F, Giusti F et al (2009) DNA-based test: when and why to apply it to primary hyperparathyroidism clinical phenotypes. J Intern Med 266:69–83
Bilezikian JP, Brandi ML, Eastell R et al (2014) Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab 99:3561–3569
Nilubol N, Weinstein L, Simonds WF et al (2012) Preoperative localizing studies for initial parathyroidectomy in MEN1 syndrome: is there any benefit? World J Surg 36:1368–1374
Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 6:5658–5671
Skogseid BS, Eriksson B, Lundqvist G et al (1991) Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. J Clin Endocrinol Metab 73:281–287
Marx S, Spiegel AM, Skarulis MC et al (1998) Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Int Med 129:484–494
Goudet P, Cougard P, Verges B et al (2001) Hyperparathyroidism in multiple endocrine neoplasia type 1: surgical trends and results of a 256-patien series from Groupe d’Etude des Nèoplasies Endocriniennes Multiples Study Group. World J Surg 25:886–890
Lemos MC, Thakker RV (2008) Multiple endocrine neoplasia type 1 (MEN 1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat 29:22–32
Burgess JR, David R, Greenaway TM et al (1999) Osteoporosis multiple endocrine neoplasia type 1. Arch Surg 134:1119–1123
Norton JA, Venzon DJ, Berna MJ et al (2008) Prospective study of surgery for primary hyperparathyroidism in multiple endocrine neoplasia-type 1 and Zollinger-Ellison syndrome. Ann Surg 247:501–510
Thakker RV, Newey PJ, Walls GV et al (2012) Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 97:2990–3011
Marx SJ, Menczel J, Campbell G et al (1991) Heterogenous size of the parathyroid glands in familial multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf) 35:521–526
O’Riordain DS, O’Brien T, Grant CS et al (1993) Surgical management of primary hyperparathyroidism in multiple endocrine neoplasia types 1 and 2. Surgery 114:1031–1037
Tonelli F, Marcucci T, Fratini G et al (2007) Is total parathyroidectomy the treatment of choice for hyperparathyroidism in multiple endocrine neoplasia type1? Ann Surg 246: 1075–1082
Kraimps JL, Quan-Yang D, Demeure M, Clark OH (1992) Hyperparathyroidism in multiple endocrine neoplasia syndrome. Surgery 112: 1080–1088
Arnalsteen LC, Alesina PF, Quireux JL et al (2002) Long-term results of less than total parathyroidectomy for hyperparathyroidism in multiple endocrine neoplasia type 1. Surgery 132:1119–1125
Montenegro FL, Lourenco DM Jr, Tavares MR et al (2012) Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center. Clinics 67:131–139
Wang CA (1976) The anatomic basis of parathyroid surgery. Ann Surg 183:271–275
Singh Ospina N, Sebo TJ, Thompson GB et al (2015) Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1. Case report and review of the literature. Clin Endocrinol (Oxf) [Epub ahead of print] doi:10.1111/cen.12714
Gibril F, Chen Y, Schrump DS et al (2003) Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type I. J Clin Endocrinol Metab 88:1066–1081
Burgess JR, Giles N, Shepherd JJ (2001) Malignant thymic carcinoid is not prevented by transcervical thymectomy in multiple endocrine neoplasia type I. Clin Endocrinol 55:689–693
Powel AC, Alexander HR, Pingpank JF et al (2008) The utility of routine transcervical thymectomy for multiple endocrine neoplasia type 1-related hyperparathyroidism. Surgery 144:874–884
Schreinemakers JM, Pietreman CR, Scholten A et al (2011) The optimal surgical tretment for primary hyperparathyroidism in MEN1 patients: a systematic review. World J Surg 35:1993–2005
Pieterman CR, van Hulsteijn LT, den Heijer M et al (2012) Primary hyperparathyroidism in MEN1 patients. A cohort study with longterm follow-up on preferred surgical procedure and the relation with genotype. Ann Surg 255:1171–1178
Udelsman R, Akestrom G, Biagini c et al (2014) The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 99:3595–3606
Edis AJ, Van Heerden JA, Scholz DA (1979) Results of sub-total parathyroidectomy for primary chief cell hyperplasia. Surgery 86:462–469
Prinz RA, Gamvros OP, Sellu D et al (1981) Subtotal parathyroidectomy for primary chief cell hyperplasia of the multiple endocrine neoplasia type 1 syndrome. Surgery 193:26–29
Van Heerden JA, Kent RB, Sizemore GW et al (1983) Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes. Surgical experience. Arch Surg 118:533–536
Goretzi PE, Dotzenrath C, Roeher HD et al (1991) Management of primary hyperparathyroidism caused by multiglandular disease. World J Surg 15:693–697
Hellman P, Skogseid B, Juhlin C et al (1992) Findings and long-term results of parathyroid surgery in multiple endocrine neoplasia type 1. World J Surg 16:718–725
Janson S, Tisell LE (1994) Total parathyroidectomy and parathyroid transplantation into subcutaneous fat tissue in the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1. Acta Chir Austriaca 26(Suppl 112):23–26
Thompson NW, Sandelin K (1994) Technical considerations in the surgical management of primary hyperparathyroidism caused by multiple gland disease (hyperplasia). Acta Chir Austriaca 26(Suppl 112):16–19
Grant CS, Weaver A (1994) Treatment of primary parathyroid hyperplasia: representative experience at Mayo Clinic. Acta Chirur Austriaca 26(Suppl 112):41–44
Nilsson O, Ahlman H, Tisell LE (1994) Autotransplantation of parathyroid tissue into subcutaneous fat in the treatment of hyperparathyroidism in MEN-1. Abstracts of the Fifth International Workshop on multiple endocrine neoplasia. Stockholm Archipelago, Sweden, 29 June—2 July 1994
Hellman P, Skogseid B, Oberg K et al (1998) Primary and reoperative parathyroid operations in hyperparathyroidism of multiple endocrine neoplasia type 1. Surgery 124:993–999
Dotzenrath C, Cupisti K, Goretzki PE et al (2001) Long-term biochemical results after operative tretment of primary hyperparathyroidism associated with multiple endocrine neoplasia types I and IIa: is more or less extended operation essential? Eur J Surg 167:173–178
Elaraj DM, Skarulis MC, Libutti SK et al (2003) Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery 134: 858–865
Hubbard JGH, Sebag F, Maweja S et al (2006) Subtotal parathyroidectomy as an adequate treatment for primary hyperparathyroidism in multiple endocrine neoplasia type 1. Arch Surg 141:235–239
Waldmann J, Lopez CL, Langer P et al (2010) Surgery for multiple endocrine neoplasia type 1-associated primary hyperparathyroidism. Br J Surg 97:1528–1534
Balsalobre Salmeron MD, Rodriguez Gonzalez JM, Fornos JS et al (2010) Causes and treatment of recurrent hyperparathyroidism after subtotal parathyroidectomy in the presence of multiple endocrine neoplasia 1. World J Surg 34:1325–1331
Nilubol N, Weisbrod AB, Weinstein LS et al (2013) Utility of intraoperative parathyroid monitoring in patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism undergoing initial parathyroidectomy. World J Surg 37:1966–1972
Lairmore TC, Govednik CM, Quinn CE et al (2014) A randomized, prospective trial of operative treatments for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery 156:1326–1335
Wells SA Jr, Farndon JR, Dale JK et al (1980) Long term evaluation of patients with primary parathyroid hyperplasia managed by total parathyroidectomy and heterotopic autotransplantation. Ann Surg 192:451–458
Malmaeus J, Benson L, Johansson H et al (1986) Parathyroid surgery in the multiple endocrine neoplasia type 1 syndrome: choice of surgical procedure. World J Surg 10:668–672
Dralle H, Sheuemann GFW (1994) How to handle the parathyroid glands in multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2)? Surgical approach to uniglandular vs multiglandular disease in hereditary primary hyperparathyroidism. Acta Chir Austriaca 26(Suppl 112): 35–38
Versnick M, Popadich A, Sidhu S et al (2013) Minimally invasive parathyroidectomy provides a conservative surgical option for multiple endocrine neoplasia typ1-primary hyperparathyroidism. Surgery 154:101–105
Carneiro PD, Slorzano CC, Irvin GL (2006) Consequences of targeted parathyroidectomy guided by localization studies without intraoperative parathyroid hormone monitoring. J Am Coll Surg 202:715–722
Proye C. Chirurgie de l’hyperparathyroidie des néoplasies endocriniennes multiples de type 1 et des autres hyperparathyroidies génétiquememnt déterminées (2001) Med Hyg 59:1660–1673
Yavuz S, Simonds WF, Weinstein SL et al (2012) Sleeping parathyroid tumor: rapid hyperfunction after removal of the dominant tumor. J Clin Endocrinol Metab 97:1834–1841
Casanova D, Sarfati E, De Francisco A et al (1991) Secondary hyperparathyroidism: diagnosis of site of recurrence. World J Surg 15:546–549
Knudsen L, Brandi L, Daugaard H et al (1996) Five to 10 years after total parathyroidectomy and autotransplantation of parathyroid tissue: evaluation of parathyroid function by use of ischaemic blockade manouvre. Scand J Clin Lsb Invest 56:47–51
Kivlen MH, Bartlett DL, Libutti SK et al (2001) Reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1. Surgery 130:991–998
Singh Ospina N, Thompson GB, Lee RA et al (2015) Safety and efficacy of percutaneous parathyroid ethanol ablation in patients with recurrent primary hyperparathyroidism and multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 100 E87-E90
Nemeth EF, Steffey ME, Hammerland LG et al (1998) Calcimimetic with potent and selective activity on the parathyroid calcium receptor. Proc Natl Acad Sci USA 95:4040–4045
Lindberg JS, Moe SM, Goodman WG et al (2003) The calcimimetic AMG073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Kidney Int 63:248–254
Falchetti A, Cilotti A, Vagelli L et al (2008) A patient with MEN1-associated hyperparathyroidism, responsive to Cinacalcet. Nat Clin Pract Endocrinol Metab 4:351–357
Moyes VJ, Monson J P, Chew SL et al (2010) Clinical use of Cinacalcet in MEN1 hyperparathyroidism. Int J Endocrinol 2010:906163 doi:10.1155/2010/906163
Filopanti M, Verga U, Ermetici F et al (2012) MEN1-related hyperparathyroidism: response of cinacalcet and its relationship with the calcium-sensing receptor gene variant Arg990Gly. Eur J Endocrinol 167:157–164
Giusti F, Cianferotti L, Gronchi G et al Cinacalcet therapy in patients affected by primary hyperparathyroidism associated to Multiple Endocrine Neoplasia type 1 (MEN1). Endocrine [Epub ahead of print] doi:10.1007/s12020-015-0696-5
Kloos RT, Eng C, Evans DB et al (2009) Medullary cancer: management guidelines of the American Thyroid Association. Thyroid 19:565–612
Raue F, Buhr H, Dralle H et al (2006) Long-term outcome in 46 gene carriers of hereditary medullary carcinoma after prophylactic thyroidectomy: impact of individual RET genotype: Eur J Endocrinol 155:229–236
Mulligan LM, Eng C, Healey CS et al (1994) Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN2A and FMTC. Nat Genet 6:70–74
Schfuffenecker I, Virally-Monod M, Brohet R et al (1998) Risk and penetrance of primary hyperparathyroidism in multiple endocrine neoplasia type 2A families with mutations at codon 634 of the RET proto-oncogene. Groupe d’etude des tumeurs à calcitonine. J Clin Endocrinol Metab 83:487–491
Gagel RB, Tashjian AHJ, Cummings T et al (1988) The clinical outcome of prospective screening for multiple endocrine neoplasia type 2A: an 18-age year experience. New Engl J Med 318:478–484
Mallette LE (1994) Management of hyperparathyroidism in the multiple endocrine neoplasia syndromes and other familial endocrinopathies. Endocrinol Metab Clin North Am 23:19–36
Herfarth KKF, Bartsch D, Doherty JM et al (1996) Surgical management of hyperparathyroidism in patients with multiple endocrine neoplasia type 2A. Surgery 120:966–974
Marcucci T, Fratini G, Nesi G et al (2006) Hyperplasia of parathyroid gland in a five-year old child Clin Cases Min Bone Metab 3:188–191
Posada-Gonzalez M, Gomez-Ramirez J, Luque-Ramirez M et al (2014) Nonfunctional metastatic parathyroid carcinoma in the setting of multiple endocrine neoplasia type 2A syndrome. Surg Res Practice 2014:731481 doi:10.1155/2014/731481
Raue F, Kraimps JL, Dralle H et al (1995) Primary hyperparathyroidism in multiple endocrine neoplasia type 2A. J Inter Med 238:369–373
Kraimps JL, Denizot A, Carnaille B et al (1996) Primary hyperparathyroidism in multiple endocrine neoplasia type IIa: retrospective French multicentric study. World J Surg 20:808–813
Wells SA, Chi DD, Toshima K et al (1994) Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2a. Ann Surg 220:237–250
Moley JF (1996) Invited commentary of ref. 74. World J Surg 20:820–821
Decker RA, Geiger JD, Cox CE et al (1996) Prophylactic surgery for multiple endocrine neoplasia type IIa after genetic diagnosis: is parathyroid transplantation indicated? World J Surg 20:814–820
Pellegata NS, Quintanilla-Martinez L, Siggelkow H et al (2006) Germ-line mutations in p27(kip1) cause a multiple endocrine neoplasia syndrome in rats and human. Proc Nat Acad Sci USA 103:15558–15563
Tonelli F, Giudici F, Giusti F et al (2014) A heterozygous frameshift mutation in exon 1 of CDK1B gene in a patient affected by MEN4 syndrome. Europ J Endocrinol 171:K7–K17
Jackson CE (1958) Hereditary hyperparathyroidism associated with recurrent pancreatitis. Ann Intern Med 49:829–836
Bradley KJ, Hobbs MR, Buley ID et al (2005) Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome. J Intern Med 257:18–26
Parfitt J, Harris M, Wright JM et al (2015) Tumor suppressor gene mutation in a patient with a history of hyperparathyroidism-jaw tumor syndrome and healed generalized osteitis fibrosa cystica: a case report and genetic pathophysiology review. J Oral Maxillofac Surg 73: 194.e1–9
Cascòn A, Huarte-Mendicoa C V, Javier Leandro-Garcia L et al (2011) Detection of the first gross CDC73 germline deletion in an HPT-JT syndrome familiy. Genes Chromosome Cancer 50:922–929
Pichardo-Lowden AR, Manni A, Saunders BD et al (2011) Familial hyperparathyroidism due to a germline mutation of the CDC73 gene: implications for management and age-appropriate testing of relatives at risk. Endocr Pract 17:602–609
Metha A, Patel D, Rosenberg A et al (2014) Hyperparathyroidism-jaw tumor sundrome: results of operative management. Surgery 156:1315–1325
Quinn CE, Healy J, Lebastchi AH et al (2015) Modern experience with aggressive parathyroid tumors in a high-volume New England referral center. J Am Coll Surg 220:1054–1062
Barry MK, van Heerden JA, Grant CS et al (1997) Is familial hyperparathyroidism a unique disease? Surgery 122:1028–1033
Carling T, Udelsman R (2005) Parathyroid surgery in familial hyperparathyroid disorders. J Intern Med 257:27–37
Huang SM, Duh Q Y, Shaver J et al (1997) Familial hyperparathyroidism without multiple endocrine neoplasia. World J Surg 21:22–28
Iacobone M, Masi G, Barzon L et al (2009) Hyperpareathyroidism-jaw tumor syndrome: a report of three large kindred. Langenbecks Arch Surg 394:817–825
Sarquis MS, Silveira LG, Pimenta FJ et al (2008) Familial hyperparathyroidism: surgical outcome after 30 years of follow-up in three families with germline HRPT2 mutations. Surgery 146:630–640
Foley TP Jr, Harrison HC, Arnaud CD, Harrison HE (1972) Familial benign hypercalcemia. J Pediatr 81:1060–1067
Marx SJ (1980) Familial hypocalciuric hypercalcemia. New Engl J Med 303:810–811
Chattopadhyay N, Brown EM (2006) Role of calcium-sensing receptor in mineral ion metabolism and inherited disorders of calcium sensing. Molecular Gen Metabol 89:189–202
Hannan FM, Nesbit MA, Zhang C et al (2012) Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. Hum Mol Genet 368:2476–2486
Nesbit MA, Hannan FM, Howles SA et al (2013) Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. Nat Genet 45:93–97
Heath H (1989) Familial benign (hypocalciuric) hypercalcemia. A troublesome mimic of mild primary hyperparathyroidism. Endocrinol Metab Clin North Am 18:723–740
Volpe A, Guerriero A, Marchetta A et al (2009) Familial hypocalciuric hypercalcemia revealed by chondrocalcinosis. Joint Bone Spine 76:708–710
Fukumoto S, Chikatsu N, Okazaki R et al (2001) Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia. Diagn Mol Pathol 10:242–247
Christensen SE, Nissen PH, Vestergaard P et al (2008) Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow-up study on methods. Clin Endocrinol (Oxf) 69:713–720
Marx SJ, Stock JL, Attie MF et al (1980) Familial hypocalciuric hypercalcemia: recognition among patients referred after unsuccessful parathyroid exploration. Ann Intern Med 92:351–356
Carling T, Szabo E, Bai M et al (2000) Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmatic tail of the calcium receptor. J Clin Endocrinol Metab 85:2042–2047
Szabo E, Hellman P, Lundgreen E et al (2002) Parathyroidectomy in familial hypercalcemia with clinical characteristics of primary hyperparathyroidism and familial hypocalciuric hypercalcemia. Surgery 131:257–263
Szabo E, Carling T, Hessman O, Rastad J (2002) Loss of heterozygotis in parathyroid glands of familial hypercalcemia with hypercalciuria and point mutaion in calcium receptor. J Clin Endocrinol Metab 87:3961–3965
Hannan FM, Nesbit MA, Christi PT et al (2010) A homozygous inactivating calcium-sensing receptor mutation, Pro339Thr, is associated with isolated primary hyperparathyroidism: correlation between location of mutations and severity of hypercalcaemia. Clin Endocrinol (Oxf) 73:715–722
Pratt EL, Geren BB, Neuhaser EB (1947) Hypercalcemia and idiopathic hyperplasia of parathyroid glands in infant. J Pediatr 30:388–399
Hillman DA, Scriver CR, Pedvis S et al (1964) Neonatal familial primary hyperparathyroidism New Engl J Med 270:483–490
Fox L, Sadowsky J, Pringle KP et al (2007) Neonatal hyperparathyroidism and pamidronate therapy in an extremely premature infant. Pediatrics 120:1350–1354
Brown EM (2010) Clinical utility of calcimimetics targeting the extracellular calcium-sensing receptor (CaSR). Biochem Pharmacol 80:297–307
Gannon AW, Monk HM, Levine MA (2014) Cinacalcet monotherapy in neonatal severe hyperparathyroidism: a case study and review. J Clin Endocrinol Metab 99:7–11
Alagaratnam S, Brain C, Spoudeas H et al (2014) Surgical treatment of children with hyperparathyroidism: single center experience. J Ped Surg 49:1539–1543
Simmonds WF, James-Newton LA, Agarwal SK et al (2002) Familial isolated hyperparathyroidism: clinical and genetic characteristic in 36 kindreds. Medicine 2002; 81:1–26
Warner I V, Nyholf DR, Busfield F et al (2006) Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3-14. J Med Genet 43:e12
Carneiro DM, Irvin GL, Inabnet WB (2002) Limited versus radical parathyroidectomy in familial isolated primary hyperparathyroidism. Surgery 132:1050–1055
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer-Verlag Italia
About this chapter
Cite this chapter
Brandi, M.L., Tonelli, F. (2016). Genetic Syndromes Associated with Primary Hyperparathyroidism. In: Gasparri, G., Palestini, N., Camandona, M. (eds) Primary, Secondary and Tertiary Hyperparathyroidism. Updates in Surgery. Springer, Milano. https://doi.org/10.1007/978-88-470-5758-6_14
Download citation
DOI: https://doi.org/10.1007/978-88-470-5758-6_14
Publisher Name: Springer, Milano
Print ISBN: 978-88-470-5757-9
Online ISBN: 978-88-470-5758-6
eBook Packages: MedicineMedicine (R0)