Three-dimensional printed titanium pseudo-prosthesis for the treatment of a tumoral bone defect

Abstract

Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocytic cells with a granulomatous appearance that generally affects children. The etiology of LCH is still unknown. However, it has been associated with exposure to certain solvents, smoking, and a family history of cancer, thyroid disease, or LCH.1Bethesda (MD): National Cancer Institute (US).https://www.cancer.gov/types/langerhans/patient/langerhans-treatment-pdqDate: 2021Google Scholar Its estimated annual prevalence is of 1 case per 560,000 adults.27Wang S. Zhang W. Na S. Zhang L. Lang Z. Langerhans cell histiocytosis of the clavicle a case report and review of the literature.Medicine. 2014; 93: e117https://doi.org/10.1097/MD.0000000000000117Crossref PubMed Scopus (6) Google Scholar Three forms of presentation have been described: located in the skeleton as solitary or multiple eosinophilic granuloma, chronic disseminated disease such as Hand-Schueller-Christian disease, and acute subacute diffuse disease such as Letterer-Siwe disease.8Gavioli F. Salvadori G. Sernia O. Histiocytosis X. 3 different cases: eosinophilic granuloma, Hand-Schueller-Christian disease, Abt-Letterer-Siwe disease.Ann Osp Maria Vittoria Torino. 1985; 28: 56-78PubMed Google Scholar In the adult population, LCH frequently presents as a lytic bone lesion.13Lian C. Lu Y. Shen S. Langerhans cell histiocytosis in adults: a case report and review of the literature.Oncotarget. 2016; 7: 18678https://doi.org/10.18632/oncotarget.7892Crossref PubMed Scopus (31) Google Scholar,27Wang S. Zhang W. Na S. Zhang L. Lang Z. Langerhans cell histiocytosis of the clavicle a case report and review of the literature.Medicine. 2014; 93: e117https://doi.org/10.1097/MD.0000000000000117Crossref PubMed Scopus (6) Google Scholar It may appear in short bones, ribs, pelvis, vertebral bodies, clavicle, and scapula. It may also develop in the diaphysis of long bones. However, the location of LCH in the hands and feet is very uncommon, and its presence in the clavicle is extremely rare.27Wang S. Zhang W. Na S. Zhang L. Lang Z. Langerhans cell histiocytosis of the clavicle a case report and review of the literature.Medicine. 2014; 93: e117https://doi.org/10.1097/MD.0000000000000117Crossref PubMed Scopus (6) Google Scholar The diagnosis can be confirmed with a core needle biopsy. An extension study should be made to detect any systemic diseases or dissemination. Various therapeutic options have been used in the management of LCH depending on the severity of the disease. These options have ranged from observation to chemotherapy, surgery, radiotherapy, photodynamic therapy, immunotherapy, and stem cell transplant.1Bethesda (MD): National Cancer Institute (US).https://www.cancer.gov/types/langerhans/patient/langerhans-treatment-pdqDate: 2021Google Scholar,16Morimoto A. Oh Y. Shioda Y. Kudo K. Imamura T. Recent advances in langerhans cell histiocytosis.Pediatr Int. 2014; 56: 451-461https://doi.org/10.1111/ped.12380Crossref PubMed Scopus (60) Google Scholar The use of low doses of radiotherapy has been found to achieve good results.10Kriz J. Eich H.T. Bruns F. Heyd R. Schäfer U. Haverkamp U. et al.Radiotherapy in langerhans cel histiocytosis – a rare indication in a rare disease.Radiat Oncol. 2013; 8: 233https://doi.org/10.1186/1748-717X-8-233Crossref PubMed Scopus (24) Google Scholar A combination of vinblastine and steroids has also been used for the treatment of LCH; however, no standard chemotherapy has been established for the management of LCH in adults.25Tazi A. Lorillon G. Haroche J. Neel A. Dominique S. Aouba A. et al.Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study.Orphanet J Rare Dis. 2017; 12: 95https://doi.org/10.1186/s13023-017-0651-zCrossref PubMed Scopus (43) Google Scholar Nevertheless, a surgical resection with clean margins is usually the recommended treatment. On the other hand, the use of three-dimensional (3D) printing represents a technological advance that is progressively becoming more popular in orthopedic surgery and traumatology. This technique is increasingly being used in surgical planning and in the reproduction of predesigned templates that serve as osteotomy guides in joint replacement procedures.6Fan H. Fu J. Li X. Pei Y. Li X. Pei G. et al.Implantation of customized 3-D printed titanium prosthesis in limb salvage surgery: a case series and review of the literature.World J Surg Oncol. 2015; 13: 308https://doi.org/10.1186/s12957-015-0723-2Crossref PubMed Scopus (81) Google Scholar,15McCulloch R.A. Frisoni T. Kurunskal V. Donati D.M. Jeys L. Computer navigation and 3D printing in the surgical management of bone sarcoma.Cell. 2021; 10: 195https://doi.org/10.3390/cells10020195Crossref PubMed Scopus (4) Google Scholar,17Mulford J.S. Babazadeh S. Mackay N. Three-dimensional printing in orthopaedic surgery: review of current and future applications.ANZ J Surg. 2016; 86: 648-653https://doi.org/10.1111/ans.13533Crossref PubMed Scopus (70) Google Scholar,20Punyaratabandhu T. Liacouras P.C. Pairojboriboon S. Using 3D models in orthopedic oncology: presenting personalized advantages in surgical planning and intraoperative outcomes.3D Printing Med. 2018; 4: 12https://doi.org/10.1186/s41205-018-0035-6Crossref PubMed Google Scholar,24Skelley N.W. Smith M.J. Ma R. Cook J.L. Three-dimensional printing technology in orthopaedics.J Am Acad Orthop Surg. 2019; 27: 918-925https://doi.org/10.5435/JAAOS-D-18-00746Crossref PubMed Scopus (9) Google Scholar In this study, we present a novel application for 3D printing in orthopedic surgery, using a 3D printed porous titanium graft for the treatment of a bone defect after an extensive resection of the middle third of the clavicle in a patient with LCH. The patient was a previously healthy 37-year-old man who worked as a maintenance laborer, with no known drug allergies, and smoker of 20 cigarettes per day. He previously attended the emergency department of another hospital presenting with a 3-week history of shoulder pain. An x-ray of the clavicle was performed in which a small lytic lesion appears on the middle third of the clavicle (Fig. 1, A). However, this lesion was not initially detected, and the patient was treated with oral analgesics and discharged. Two months later, the patient presented in our center with a 3-month history of left clavicular pain and swelling without previous trauma. Clinical examination revealed a tender mass located on the left supraclavicular fossa associated with local edema. The patient was febrile, and the active and passive mobilization of his left shoulder was painful. However, the neurovascular examination of the left upper extremity was normal. This patient provided consent for publication of this case report. Plain x-rays revealed an evolved and displaced pathological fracture involving the middle third of the left clavicle associated with a well-defined 2.5-cm lytic lesion. The tumor appeared to spare bone cortices (Fig. 1, B). The blood tests showed a mild white cell count increase (23 × 10 ˆ 9 / L), an unaltered c-reactive protein, and negative tumor markers. Given the pathological nature of the fracture and the smoking history of the patient, our initial differential diagnosis was of metastasis vs. bone cyst. Accordingly, a chest x-ray was performed showing no evidence of any pulmonary disease. The patient was then subjected to an intralesional resection and curettage, and samples were collected for pathological analysis. The bone defect was then filled with synthetic and bioactive bone graft substitute (GlassBONE, Noraker, France), and the fracture synthesized with an anatomical clavicular plate (DePuy Synthes, Raynham, MA, USA). Postoperative x-rays showed a satisfactory reduction of the fracture (Fig. 1, C). The pathological analysis confirmed the diagnosis of LCH (ie, eosinophilic granuloma subtype). Then, a positron emission tomography–computer tomography was performed to detect any other possible lesions. The positron emission tomography–computer tomography revealed the presence of pathological trace uptake in the middle third of the left clavicle (SUV max 4.15). No other metabolic abnormalities were detected. The case was then presented in our institutional musculoskeletal tumor committee to determine the best therapeutic strategy. Several options were considered including observation, wide resection with oncological margins followed by reosteosynthesis using an autologous bone graft, radiotherapy, and wide resection followed by a clavicular reconstruction using a 3D printed porous titanium graft “pseudo-prosthesis”. After taking in consideration the patient's age and the tumor's location and after discussing the available options with the patient, we decided to proceed with the clavicular reconstruction using a 3D printed “pseudo-prosthesis”. We contacted the 3D design company 4DiMedical (Ortoplus, Malaga, Spain). A fine-cut computer tomography scan was then performed to make a detailed 3D reconstruction of the clavicle which included the previously synthesized bone and the 2.5-cm tumoral lesion (Fig. 1, D). Then, a customized cutting template was printed to perform the clavicular osteotomy with clean 14-mm proximal and distal oncological margins. The cutting template was adapted to a 1.3-mm saw blade and included holes for its fixation with 1.8-mm Kirschner wires (Fig. 2, A and B). We then printed a 3D porous titanium pseudo-prosthesis resembling the size and shape of the resected area. Its trabecular titanium structure was designed to facilitate bone growth through the implant (Fig. 2, C and D). This pseudo-prosthesis also included a medial and lateral intramedullary fin to provide additional rotational stability. The patient was subjected to a brachial plexus block of the left upper extremity. The patient was then positioned in a “chair bed” position. A longitudinal incision was made over the previous scar. A progressive dissection was made to expose the previously used anatomical clavicular plate (DePuy Synthes, Raynham, MA, USA). The plate was then extracted, and the clavicle was exposed. A 3D printed biocompatible resin (MED610) radio-opaque cutting guide was positioned on the clavicle and fixed with four 1.8-mm Kirshner wires. A 62-mm long osteotomy was performed, achieving a complete excision of the tumor with oncological margins (Fig. 3, A–C). Then, the intramedullary canal was drilled proximally and distally using a 2-mm burr. The titanium implant (Ti6AL4V) was positioned following the “press-fit” method. Once the implant was stabilized, the clavicle was fixed using an anatomical clavicular plate (DePuy Synthes, Raynham, MA, USA) and locking screws. The implant's trabeculas were filled with bioactive bone graft substitute (GlassBONE, Noraker, France) (Fig. 3, D–F). Finally, the wound was washed with normal saline, and the wound was closed with 2-0 and 3-0 Vicryl. The final histopathology report confirmed the diagnosis of LCH with disease-free margins. The operated extremity was immobilized in a sling until the removal of the sutures 2 weeks after surgery. Then, pendular exercises of the shoulder and passive physiotherapy were initiated. The operated extremity was kept non–weight-bearing, and efforts were avoided. No postoperative complications were observed, and the evolution of the wound was satisfactory. At 3 months after surgery, the patient presented with a complete range of motion and no pain on palpation or mobilization. The patient was authorized to initiate progressive loading of the operated extremity and to resume his regular physical activities. On his last follow-up appointment, 2 years after surgery, the patient led a normal life without any type of functional limitation; he had a Constant score of 100 and a disabilities of the arm, shoulder, and hand score of 2.5 (Fig. 4, A–D). His follow-up x-ray was also satisfactory (Fig. 4, E). Langerhans histiocytosis is a rare disease in adults.13Lian C. Lu Y. Shen S. Langerhans cell histiocytosis in adults: a case report and review of the literature.Oncotarget. 2016; 7: 18678https://doi.org/10.18632/oncotarget.7892Crossref PubMed Scopus (31) Google Scholar It is difficult to determine its incidence in this age group because most of the published reports have been focused on the pediatric population. In children, LCH has been found to be more common in males (male-female ratio of 2:1). However, in the adult population, this ratio may vary depending on the series. According to the Rizzoli Institute,18Picci P. Manfrini M. Fabbri N. Gambarotti M. Vanel D. Atlas of musculoskeletal tumors and tumorlike lesions. The Rizzoli Case Archive, 2014Crossref Google Scholar the diagnosis of LHC progressively decreases with age (ie, 55% of the cases with LHC occur between 0 and 9 years, 30% between 10 and 19 years, 8% between 20 and 29 years, and 5% between 30 and 39 years). The treatment of LHC depends on the extent of the disease and may range from curettage and corticosteroid injection, polymethyl methacrylate filler, to local radiotherapy and systemic chemotherapy in certain cases. The clavicle is a rare site of LHC.26Verbist B. Geusens E. Brys P. Verslegers I. Samson I. Sciot R. et al.Langerhans cell histiocytosis of the clavicle: a case report.Eur Radiol. 1998; 8: 1357-1358Crossref PubMed Scopus (7) Google Scholar Most of LHC reports in the literature involving this bone were treated by curettage of the lesion, steroids, and plate fixation. However, relapses often require adjuvant radiotherapy.10Kriz J. Eich H.T. Bruns F. Heyd R. Schäfer U. Haverkamp U. et al.Radiotherapy in langerhans cel histiocytosis – a rare indication in a rare disease.Radiat Oncol. 2013; 8: 233https://doi.org/10.1186/1748-717X-8-233Crossref PubMed Scopus (24) Google Scholar,27Wang S. Zhang W. Na S. Zhang L. Lang Z. Langerhans cell histiocytosis of the clavicle a case report and review of the literature.Medicine. 2014; 93: e117https://doi.org/10.1097/MD.0000000000000117Crossref PubMed Scopus (6) Google Scholar Some authors have postulated that a combination of surgery with localized radiotherapy would be the best therapeutic if the presence of residual disease is confirmed.3Abla O. Rollins B. Ladisch S. Langerhans cell histiocytosis: progress and controversies.Br J Haematol. 2019; 187: 559-562https://doi.org/10.1111/bjh.16099Crossref PubMed Scopus (6) Google Scholar4Baumgartner I. Von Hochstetter A. Baumert B. Luetolg U. Follath F. Langerhanś-cell histiocytosis in adults.Med Pediatr Oncol. 1997; 28: 9-14Crossref PubMed Scopus (195) Google Scholar In our case, the presence of residual disease would have been an indication for local radiotherapy. However, we believed that the eradication of the tumor was possible without exposing the patient to radiation if the lesion was completely resected. Therefore, we decided to perform a second excision with oncological margins and a subsequent reconstruction of the clavicle with the intercalary titanium pseudo-prosthesis. The location of the lesion required a resection that could have compromised the anatomical function of the left upper limb.2Abbot L.C. Lucas D.B. The function of the clavicle: its surgical significance.Ann Surg. 1954; 140: 583-597Crossref PubMed Scopus (58) Google Scholar However, the titanium pseudo-prosthesis provided adequate mechanical stability and continuity and preserved the functionality of the clavicle. The use of the titanium pseudo-prosthesis avoided exposure to radiotherapy in our relatively young patient. In a previous study, Kriz et al determined that the possible indications for radiotherapy in LHC would be in case of unresectable lesions, if the resection compromised the anatomical function, recurrent or progressive lesions, adjuvant treatment followed by incomplete or marginal resection, as well as pain or symptoms that compromise the quality of life.10Kriz J. Eich H.T. Bruns F. Heyd R. Schäfer U. Haverkamp U. et al.Radiotherapy in langerhans cel histiocytosis – a rare indication in a rare disease.Radiat Oncol. 2013; 8: 233https://doi.org/10.1186/1748-717X-8-233Crossref PubMed Scopus (24) Google Scholar However, radiotherapy can induce secondary leukemias, malignant meningiomas, osteosarcomas, and breast, lung, and thyroid malignancies over time.5Braunstein S. Nakamura J.L. 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Surgical treatment of clavicular malignancies.J Shoulder Elbow Surg. 2011; 20: 295-300https://doi.org/10.1016/j.jse.2010.05.009Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Several methods have been traditionally used for the reconstruction of bone defects in orthopedic surgery. These include leaving the bone defect and the use of bone allografts and vascularized bone grafts. However, the risk of bacterial infection has been estimated to be of 11.7% for large allografts and 0.7% for small grafts.28Zamborsky R. Svec A. Bohac M. Kilian M. Kokavec M. Infection in bone allograft transplants.Exp Clin Transpl. 2016; 5: 484-490Google Scholar The use of bone allografts could also result in nonunion rates in approximately 21% of the cases.22Scaglione M. Fabbri L. Dell'Omo D. Gambini F. Guido G. Long bone nonunions treated with autologous concentrated bone marrow-derived cells combined with dried bone allograft.Musculoskelet Surg. 2014; 98: 101-106https://doi.org/10.1007/s12306-013-0271-2Crossref PubMed Scopus (26) Google Scholar Moreover, vascularized bone allografts are technically demanding and are associated with a significant morbidity on the donor site.7Friedrich J.B. Moran S.L. Bishop A.T. Woods C.M. Shin A.Y. Free vascularized fibular graft salvage of complications of long-bone allograft after tumor reconstruction.J Bone Joint Surg Am. 2008; 90: 93-100https://doi.org/10.2106/JBJS.G.00551Crossref PubMed Scopus (54) Google Scholar,9Hartman H.M. Spauwen P.H.M. Jansen J.A. Donor-site complications in vascularized bone flap surgery.J Invest Surg. 2002; 15: 185-197https://doi.org/10.1080/08941930290085967Crossref PubMed Scopus (81) Google Scholar,11Lenoir H. Williams T. Kerfant N. Robert M. Le Nen D. Free vascularized fibular graft as a salvage procedure for large clavicular defect: A two cases report.Orthop Traumatol Surg Res. 2013; 99: 859-863https://doi.org/10.1016/j.otsr.2013.06.004Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Thus, the use of 3D printing in orthopedic surgery and traumatology could become an additional surgical option in the management of complex fracture reconstructions. Moreover, this technique could provide accurate bone cutting guides in oncological surgery that could help perform precise osteotomies with disease-free margins based on preoperative imaging. It could also help produce customized osteosynthesis plates and print replicates of the operated bone.17Mulford J.S. Babazadeh S. Mackay N. Three-dimensional printing in orthopaedic surgery: review of current and future applications.ANZ J Surg. 2016; 86: 648-653https://doi.org/10.1111/ans.13533Crossref PubMed Scopus (70) Google Scholar In addition, it could be used to replace bone segments with implants of an equal size, shape, and volume. This could be particularly easier to achieve in cases affecting small bones, exposed to lower mechanical demands. In this case, the implant successfully replaced the bone defect of the clavicle, preserving its continuity and original length. Consequently, the strength and functionality of the affected extremity were preserved. Moreover, the empty spaces within the trabecular structure of the implant could facilitate the formation of woven bone. These spaces may be also filled with bone substitutes to enhance the osteogenesis process. Finally, the use of 3D printing to reproduce intercalary segments for the replacement of bone defects is a promising field that needs further development. This new technique could provide an additional therapeutic tool that could minimize the morbidity associated with other conventional treatments. The use of a 3D printed pseudo-prosthesis achieved an excellent clinical and functional outcome in the treatment of a large bone defect, after a resection of an LCH of the clavicle. 3D printed pseudo-prostheses could be useful instruments for the treatment of bone defects after large bone resections in musculoskeletal tumors.