IntroductionGiant cell tumor of bone (GCTB) is an intermediate, locally aggressive but rarely metastasizing tumor, representing 5% of primary bone tumors and 20% of benign bone tumors [1]. It occurs mostly between the ages of 30–50 years and rarely arises in the immature skeleton. There is a slight predominance for female patients [1, 2]. At presentation, 15–20% of patients have a pathologic fracture due to substantial cortical destruction followed by relatively minor trauma. GCTB is typically seen solitary, mostly located in the meta-epiphyseal region of long bones (85%), but may also occur in the axial skeleton (10%) or occasionally in the small bones of hands and feet (5%) [2, 3]. At

the latter location, so-called giant cell lesion of the small bones – a different entity – should be considered [4]. Approximately 1–4% of otherwise conventional patients develop pulmonary metastases [3, 4, 5, 6, 7, 8]. These metastases often have relatively indolent behavior. Multifocal GCTB is rare, appearing either simultaneously or metachronously. Malignant transformation has been described in <1% of all GCTBs and may be either primary (i.e., sarcomatous progression) or, more commonly, secondary (mostly radiation induced) [1]. There is a strong correlation between the surgical margins and the rate of recurrence, dependent on whether intralesional curettage, marginal or wide resection is used [9].

Due to the t y pical m e t a - e p i p h y s e a l l o c at i o n , h owever, wide resection may r e s u l t i n a m a j o r f u n c t i o n a l d e f i c i t . Hence, intralesional

1Department Of Orthopedics, Subharti Medical College, Meerut , India

Address of CorrespondenceSandeep Kumar, A GF 90, Ansal town, modipuram, meerut-250110 U.P.E-mail: drbaliyan051284@gmail.com

Efficacy of Hydrogen Peroxide as Adjuvant in Preventing Recurrence of Giant Cell Tumor of Bone

Aim: To study the effect of hydrogen peroxide (3%) as an adjuvant in preventing local recurrence of giant cell tumor of bone.Material & Methods: 32 cases of giant cell tumor treated during 2010 -16 were taken in this study initially. 3 cases which could not be followed for minimum of 2 years and 6 cases which were lost to follow up were excluded from study. Also cases involving spine, pelvis and other inaccessible sites were not taken. Thus the present study includes 21 cases of giant cell tumor. The age of patient varies from 18 to 45 yrs. Most patients belong to age group 20-30. Male: Female ratio was 12: 9. In our study, distal femur and distal end radius were the most commonly affected sites (n- 7) each. Lesions around knee(distal femur and proximal tibia) constitutes nearly half of cases. The commonest presenting symptom was swelling associated with pain. All the cases were managed by curettage/en-bloc resection followed by irrigation of cavity with hydrogen peroxide 3%, which was left for 2 minutes .The cavity was thoroughly irrigated with normal saline and filled using bone graft and /or bone graft substitutes or reconstructed using autologous bone.Results: In total 5 patients showed recurrence, 4 in first year and 1 in second year of follow up. 4(25%) of 16 treated by curettage and G bone/autogenous bone grafting showed recurrence. Out of 5 cases of en-bloc resection with/without reconstruction 1 (20%) recurred.Conclusion: We conclude that hydrogen peroxide is a cheap, easily available and effective adjuvant for giant cell tumor bone. It reduces recurrence and results are comparable to PMMA, phenol and cryotherapy. The combination of adjuncts (PMMA, burring, H2O2) reduces the likelihood of recurrence compared to curettage alone and therefore should be recommended as the standard treatment.Keyword: giant cell tumor, hydrogen peroxide, extended curettage

Abstract

Original Article

Rohan Jain¹, Sandeep Kumar¹, Anuj Gupta¹, Arunim Swarup¹, Rimjhim Shrimal¹

© 2017 by Journal of Bone and Joint Diseases | Available on www.jbjdonline.com | doi:10.13107/jbjd.0971-7986This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits

unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Journal of Bone and Joint Diseases| Oct - Dec 2017 | 32;(3):17-21

Dr.Rohan Jain Dr. Sandeep Kumar

Dr. Anuj Gupta Dr. Arunim Swarup

Dr. Rimjhim Shrimal

curettage has become the most recommended treatment [10]. The main problem in the management of GCTB is local recurrence after surgical treatment: 27–65% after isolated curettage [2, 3]; 12–27% after curettage with adjuvants such as high-speed burr, phenol, liquid nitrogen, or polymethyl methacrylate (PMMA) [2, 11, 12, 13]; and 0–12% after en bloc resection [2, 14]. The introduction of local adjuvant therapy, such as cementation, cryosurgery, or phenolization, in combination with careful removal of the tumor using a large bone window and high-speed burrs has lead to a significant reduction in recurrence rates [10, 15, 16, 17, 18, 19]. The current study was planned to evaluate the effect of hydrogen peroxide (H2O2) on local recurrence.

Material and MethodA total of 32 cases of histologically proven cases of giant cell tumor treated during 2010–2016 were taken in this study initially. The diagnosis was based on clinical picture, radiological appearance and was confirmed preoperatively by fine needle aspiration cytology in all cases. The histological examination of curetted material was done to exclude any doubt. 3 cases which could not be followed for minimum of 2 years and 6 cases which were lost to follow-up were excluded from the study. Furthermore, cases involving spine, pelvis and other inaccessible sites were not obtained. Thus, the present study includes 21 cases of giant cell tumor. The age of patient varies from 18 to 45 years. Most patient belong to age group 20-30 (n =14) followed by 10–20 (n = 4). Male:female – 12:9 (Fig. 1). In our study, distal femur and distal end radius were the most commonly affected sites (n = 7) each. Lesions around knee (distal femur and proximal tibia) constitute nearly half of cases. 3 cases were of giant cell tumor affecting, namely, greater trochanter, metacarpal, and proximal humerus (Fig. 2). The most common presenting symptom was swelling associated with pain. Pain was aggravated by activity and relieved by rest.

When destruction progressed then pain became constant. The sequence of events was pain, swelling, and pathological fracture. Duration of symptoms varied from 3 months to 1 year. Pathological fracture was seen in two cases. All the cases were managed by curettage/en bloc resection followed by irrigation of cavity with hydrogen peroxide 3%, which was left for 2 MIN. The cavity was thoroughly irrigated with normal

saline and filled using bone graft and/or bone graft substitutes or reconstructed using autologous bone. The tumors were classified into three histological grades according to the Campanacci et al. [20] Typical (Grade I) have loosely packed stroma with no atypism, few mitotic figures, and no hyperchromatism. Uniformly distributed, numerous giant cells having multiple nuclei are seen. Aggressive (Grade II) have compact stroma with atypism, frequent mitotic figures, and hyperchromatism. The giant cells are less in number unevenly distributed with lesser nuclei. Malignant (Grade III) are frankly sarcomatous with very compact stroma, marked mitosis, and marked hyperchromatism. The giant cells are occasional with few nuclei. In our series, 2 cases were graded typical (Grade I), 16 cases as aggressive (Grade II), and 3 cases as malignant tumor (Grade III). The follow-up was between a minimum of 2–6 years. Pre-operative and post-operative radiographs of all patients were examined. The site and size of the lesion were noted in subsequent follow-up. Patient showing clinical evidence of recurrence or increase in the clinical or radiological size of lesion was labelled as recurrence.

Results (Table 1)Curettage and G-bone/autogenous bone grafting (n = 16)This treatment was adopted in well-contained tumors where radiologically the cortex was not deficient. It was the most commonly adopted treatment method. However, 4 cases (25.0%) recurred in this group. Out of 4 recurrences, one was advised amputation, 2 having GCT distal end radius was managed by en bloc resection and reconstruction using fibular graft. One involving proximal tibia was managed by re-curettage and G-bone grafting successfully.

En bloc resection with/without reconstruction (n = 4) This procedure was done in 4 cases. Three cases of tumor

Jain R et al

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Figure 2: Distribution of tumor.Figure 1: Age distribution.

Figure 3: (a) Giant cell tumor distal radius, preoperatively. (b) 3 years follow-up after surgery.

Figure 4: (a) Giant cell tumor distal radius, preoperatively. (b) 3 months post-operative after surgery.

involving the lower end of radius, en bloc resection was done, and reconstruction was done by replacing it with ipsilateral upper end of fibula with arthrodesis of wrist. In one case limb salvage surgery by en bloc resection of distal femur was performed with turbinoplasty and knee arthrodesis using long K nail. En bloc resection alone was done in single patient having aggressive GCT of the distal femur, which soon recurred and finally, amputation was performed. Out of 5, 1 (20%) recurred. In total 5 patients showed recurrence, 4 in 1st year and 1 in 2nd year of follow-up. 4 (25%) of 16 treated by curettage and G-bone/autogenous bone grafting showed recurrence. Out of 5 cases of en bloc resection with/without reconstruction 1 (20%) recurred (Fig. 3 and 4).

DiscussionGiant tumors are locally aggressive, and some may be malignant [21,22]. The benign form of GCT has the intriguing feature of being able, in rare instances, to

metastasize despite otherwise benign characteristics [23,24]. The malignant variety of GCT has been defined as a sarcomatous growth that is either primarily juxtaposed to a typical benign focus or occurs after a prolonged interval at the site of a previously treated and documented focus [9,26,27]. The concept of staging of musculoskeletal sarcoma is being debated at present. The tumor, node, and metastasis system of classification is not applicable to GCT because anatomically GCTs remain intra-compartmental for a long time within the well-formed capsule of the periosteum and fibrous tissue [28]. A histological grading of GCT was first devised by Jaffe et al [21]. They intended to relate the histological features with the clinical course of the tumor, to predict the outcome on that basis. Their grading has subsequently proved to be unreliable [22,23,29]. Despite some overlap in histological appearances, a majority of GCTs fell into three divisible groups, namely, typical, aggressive, and malignant. Many observers currently believe that histology alone is a poor index to prognosticate and to predict clinical behaviour of tumor [26,29,30]. Even clinically and radiographically, GCTs have a wide spectrum. Some lesions grow very slowly and are rarely seen to undergo necrosis, scarring. Others, on the contrary, are rapidly aggressive. The tumor may reach the joint surface, enter the joint space and invade the contiguous bone. This can occur in many ways.

Hence, in addition to the histological criteria, radiological appearance has an important role in the prognosis of a case. The mean age of presentation was 26.5 years (18–45). Presentation was most common in third decade. This is in accordance with previous studies [31-33]. Male-female ratio in our study was 1.33:1. Campanacci reported an equal sex ratio for GCT [7]. We found 10 (47.6%) of our lesions around the knee joint with 7 (33.33%) cases in distal end femur and 3 (14.28%) in the upper end of tibia. Prognosis of GCT around knee joint is vital from a functional point of view. This has been shown by other authors as well [32-34]. Pathological fracture was seen in 2 (9.52%) of our patients, both in lower end of femur. It’s presence, however, did not affect the final functional outcome in our study. Recurrence was considered to be present when there was progressive increase in symptoms such as pain and swelling along with histologically proven recurrence from same site by fine-needle aspiration cytology. Chen et al. [35] found that there is a significant linear association between the area of affected subchondral bone before surgery and the functional outcome at final follow-up for patients treated with curettage and bone grafting. According to Schajowicz [36],

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Table 2: Recurrence rates reported after curettage of giant cell tumors of bone

Author Year Tumor

characteristics

Adjuvants Number of

patients

Recurrence

rates (%)

Capanna et

al. [38]

1990 None 280 45

Prosser et

al. [39]

2005 Stage 1 and 2 None 61 7

Stage 3 None 52 29

Recurrent None 29 34

Capanna et

al. [38]

1990 PMMA 187 19

O'Donnell

et al. [40]

1994 PMMA 49 24

Turcotte et

al. [34]

2002 PMMA 62 19

Capanna et

al. [38]

1990 Phenol 147 19

Su et al.

[42]

2004 Phenol 56 18

Capanna et

al. [38]

1990 Cryotherapy 20 19

Malawer et

al. [32]

1999 Primary Cryotherapy 86 2.3

Recurrent Cryotherapy 16 37.5

Zhen et al.

[25]

2004 Zinc chloride 92 13

Capanna et

al. [38]

1990 Phenol+PMMA 33 3

Lackman et

al. [41]

2005 Stage 2 and 3

only

Phenol+PMMA 63 6

W ard and

Li. [43]

2002 H2O2+phenol+

electrocautery

+PMMA (in half)

24 8

PMMA: Polymethyl methacrylate cement. “*None” may include the use of a high-speed burr,

which some authors consider an adjuvant

Table 1: Distribution of Surgical Proced ure

Surgical procedure No. of cases Recurrence (%)

Curettage and G-bone/autogenous

bone grafting

16 4 (25)

En bloc resection ±reconstruction 5 1 (20)

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curettage alone is an inadequate oncologic procedure for GCT but associated with better functional outcome compared to en bloc excision. Treatment is a balance between oncological adequacy and functional utility of the limb. Curettage with G- bone/autologous bone grafting was done in 76.19 % of our patients, this being the most common modality of treatment in the series. En bloc resection with/without reconstruction was done in 23.81%. Curettage with bone grafting was the most common modality in primary cases (76.19%) while En bloc resection was the most common treatment for recurrent lesions (60%). Pathological fracture was not a contraindication to curettage and bone grafting in this study as was opined by Dreinhofer [37]. Curettage in GCT is usually followed by adjuvant therapy either to achieve a more thorough tumor kill. We used hydrogen peroxide 3% with curettage. In our study,

total recurrence is 5 (23.80%) out of 21 primary cases treated. When we compare these with other studies, the recurrence rates are significantly less than those without the use of adjuvants and are comparable with PMMA, phenol, cryotherapy, but are inferior than that of zinc chloride, PMMA + phenol, and hydrogen peroxide + phenol + electrocautery + PMMA.

ConclusionWe conclude that hydrogen peroxide is a cheap, easily available, and effective adjuvant for giant cell tumor bone. It reduces recurrence and results are comparable to PMMA, phenol, and cryotherapy. The combination of adjuncts (PMMA, burring, H2O2) reduces the likelihood of recurrence compared to curettage alone and therefore should be recommended as the standard treatment.

Jain R et al

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How to Cite this Article

Jain R, Kumar S, Gupta A, Swarup A, Shrimal R. Efficacy of Hydrogen Peroxide as Adjuvant in Preventing Recurrence of Giant Cell Tumor of Bone. Journal of Bone and Joint Diseases Oct - Dec 2017;32(3):17-21 .

Conflict of Interest: NILSource of Support: NIL