Outcome Based on Metastatic Humerus and Surgical Fixation: Finding of a Systematic Review

A B S T R A C T

Background: As for treating metastatic humerus, open reduction with internal fixation (ORIF), intramedullary nail fixation as well as reconstruction of endoprosthesis act as the approaches with highest frequency in surgeries. In the current study, the postoperative complications and functional outcomes were compared after 3 operating treatments for metastatic humerus by performing a meta-analysis.
Methods: An electronic search of relevant studies was done on December 29, 2015 and rigorously screened them according to inclusion and exclusion criteria. The summary results of the included studies were pooled using a random-effects mode.
Results: A total of 21 studies were included for analysis. we evaluated the functional outcome according to the MSTS score, found that the upper limb function apparently returned after surgery. For local complications, the overall reoperation rate after endoprosthetic reconstruction (95%CI 0.06-0.11) ranged from 0-14%, 0-9% after intramedullary nailing (95%CI 0.04-0.08), and 0-8% after ORIF (95%CI 0.05-0.24). The rate of re-operation for failed fixations ranged from zero to 10% after reconstruction of endoprosthesis (95%CI 0.03-0.07), 0-6% after intramedullary nailing (95%CI 0.01-0.04), and was 0-19% in all studies after ORIF (95%CI 0.02-0.19), while that for dislocations ranged from 0% to 8% after reconstruction of endoprosthesis (95%CI 0.02-0.05), and 0-5% after intramedullary nailing (95%CI 0.01-0.04).
Conclusions: Compared with the high rate of reoperation due to ORIF, those of intramedullary nail fixation and endoprosthetic construction are of comparability. The findings in the current study is applicable for aiding to make appropriately surgical decision to improve the living quality of patients in the remainder of their lives.

Keywords

Humerus, surgical fixation, meta-analysis

Introduction

The humerus is secondary to the femur in long bone site affected by bone metastases, and the proximal and diaphysis are commonly sites [1]. Bone metastases, particularly lytic disease, cause ache and finally broken bones, and the surgery aiming to ameliorate discomfort and restore function are frequently required [2, 3]. The orthopedic surgery including open reduction with internal fixation (ORIF) using screws and plates, intramedullary nail fixation as well as reconstruction of endoprosthesis and many more approaches is applicable to treating metastatic humerus [4]. The surgical plan is not made by the patient together with their doctors, but also partially dependent on whether to undergo pathological fracture, overall survival, metastasizing sites and sizes, as well as functional outcomes in expectancy and operational complications [5]. Several papers in the literature described that the three most common treatments including ORIF, intramedullary nail fixation as well as reconstruction of endoprosthesis are helpful in metastatic humerus [6]. However, relatively few have been reported about postoperative arm recovery, reoperations and complications. And thus, require large cohorts to adequately compare the three most common treatments. The review focuses: (1) to provide an up-to-date report about comparing outcome among the three surgical strategies, and (2) to clarify the outcome of postoperative arm recovery, the local and systemic complication rate for metastatic humerus.

Table 1: Characteristics of All Patients With Metastatic Humerus Per Study (%).

Author, year	Implant	Patients	humerus	Pathological fractures	Median age	Minimum follow-upm	One year survival in (%)
Lewallen RP et al (1982)	IMN	55	55	--	--	--	10Ma
Capanna R et al (1988)	EPR	20	19	--	--	--	--
Yazawa Y et al (1990)	IMN	166	41	30	62	24	40%
Fuhrmann RA et al (2000)	EPR	22	22	--	57	47a	--
Gebhart, M. et al (2001)	EPR+IMN	56	55	31	62	1	9a
Bickels J et al (2002)	EPR	134	12	--	--	24	--
Bauze AJ, et al (2003)	IMN	31	31	25	67	--	--
Bauze AJ et al (2006)	EPR+IMN	96	77	--	63	8a	43.5%
Thai DM et al (2008)	EPR	154	37	--	59	--	69.5%
Scotti, C. et al (2008)	EPR	40	40	12	67	--	70%
Cannon CP et al (2009)	EPR	83	67		55	24	55.8%
Piccioli A et al (2010)	EPR+IMN	85	87	76	59	8.3a	67.3%
Siegel, H.J. et al (2010)	ORIF	32	23	--	52	17.6a	--
Raiss, P. et al (2010)	EPR	43	30	--	60	38a	77%（2）
Griffiths, D. et al (2011)	EPR	68	30	--	53	71a	--
Wedin R et al (2012)	EPR+IMN+ ORIF	214	204	173	67	8a	40%
Henrichs MP et al (2014)	EPR	82	26	--	63	--	94.7%
Pruksakorn D et al (2015)	EPR+ ORIF	27	27	--	--	16a	91.7%
Janssen SJ et al (2016)	EPR+IMN+ ORIF	295	292	237	63	4a	49%
Choi ES et al (2016)	IMN	32	32	21	--	14.2a	48%
Schmolders J et al (2016)	EPR	30	21	--	--	26a	83%

--, not available; EPR, endoprosthesis; IMN, intramedullary nail; ORIF, open reduction internal fixation.

a Mean age.

m In months.

Table 2. Functional Outcome Per Implant Type for Metastatic Humerus (%).

Author, year	Implant	Follow-up (Months)	Patients	Outcome measure	Median score (Range)
Scotti, C. et al (2008)	EPR	30	40	MSTS	73.1a (69.9-76.3)
Cannon CP et al (2009)	EPR	24	67	MSTS	63a(40-83)
Piccioli A et al (2010)	EPR IMN	8	26 57	MSTS	73a 79a
Raiss, P. et al (2010)	EPR	38	30	MSTS	19a(7-27)
Griffiths, D. et al (2011)	EPR	71	30	MSTS	72.3a(53.3- 100)
Choi ES et al (2016)	IMN	14.2	32	MSTS	27.7a(27.0-28.5)
Pruksakorn D et al (2015)	ERP	16	16	MSTS	33-77
Siegel, H.J. et al (2010)	ORIF	17.6	23	MSTS	94.6 a(86-99)

MSTS, musculoskeletal tumor society score; EPR, endoprosthesis; IMN, intramedullary nail; ORIF, open reduction internal fixation.

^a Mean score.

Methods and Materials

Our results were reported in line with the guidelines from the preferred reporting items for PRISMA statement [7].

I Search Strategy

A systematic search was performed in the PubMed, Embase, Clinical Evidence, Up To Date and Cochrane libraries for studies on December 29, 2015 using the search terms: (“metastatic” OR “metastases”) AND (“humerus”) AND (“surgery” OR “surgeries” OR “operatio*” OR “operativ*” OR “surgical*” OR “resection*” OR “intramedull*” OR “osteosynth*” OR “fixation*” OR “arthroplas*” OR “endoprosth*” OR “prosth*”) in all fields without any limitation and yielded 2265 articles (Figure 1). All publications were loaded on to the software of Medical literature King and the ‘find duplicates’ application was performed.

II Inclusion and exclusion criteria

Two reviewers (FHL, WJ) independently reviewed titles and abstracts and subsequently full texts on the basis of predetermined criteria. Disagreements were resolved following assessment by consensus. Inclusion criteria: (i) Studies that described postoperative complication and functional outcomes after treating metastasizing humerus were included. (ii) We included studies reporting on three surgical approaches including ORIF, intramedullary nail fixation as well as reconstruction of endoprosthesis for metastatic proximal humerus. (iii) Only English language studies were included. Exclusion criteria: (i) Meeting abstracts, case report, letters and technique papers were excluded. (ii) Studies including indiscernible treatment arms or unclear regions of metastatic lesion in long bones were also excluded. (iii) We excluded studies with less than 10 patients within surgical approaches. Additionally, authors were contacted if studies within indiscernible reported outcomes or unclear regions of metastatic lesion were published after the year 1985 [8-12]. The qualities of these included researches by predetermined standards-prospective design publicity, bias of loss to follow-up, study of outcomes, basic line, appropriateness standards for selecting patients, comparing treatment arms were independently assessed by two reviewers (FHL, WJ).

III Outcomes of Interest and Data Extraction

We extracted the following information from each articles: the author, year of publication, sample size, median age, sex, surgical techniques, lesions, the mean follow up period, the distribution of primary tumor, quantity of existing and imminent pathological fracture, duration of follow-up and one year survival. In addition, three outcomes of interest were extracted to assess the efficacy of the three surgical techniques.
• Postoperative physical function based on the measure.
• The local complications including reoperation caused by fixation failure (such as: loosened implants, disunion, fractures of implants or near implants), deep infection (including surgical debridement with or without hardware removal) and tumor relapse or progression.
• All proposed general complications whatever the treating outcomes are.

IV Study Characteristics

A total of 21 studies were included for analysis (Figure 1) [2-4, 6, 11-24]. We found that retrospective designs existed in entire researches and 16 (76%) studies included properly standards and approaches of patient selection which resulted in a selection bias. Uncertain methods were present in 9 (43%) studies for comparison of techniques. Only 9 (43%) studies were described more fully for outcome and 8 (38%) studies were considered as having bias resulting from probably elevated loss to follow-up (Figure 2).

V Metastatic Proximal Femoral Fractures and the Features of Patients

The age range of the participants from the entire 21 researches which reported 1228 pathological changes in humerus was 52 to 61 (Table 1). The most common primary tumors included Breast (21.9%), Lung (14.0%), Myeloma and Lymphoma (14.2%) and Kidney (14.3%). The unknown primary tumor type accounted for 15.1% of the cases (Figure 3, Appendix 1). In the 21 studies, there were 15 studies reporting on 455 endoprostheses (418 [91.9%] proximal humerus, 2 [0.4%] Midhumerus, 7 [1.5%] distal humerus and not specified in 28 [6.2%]); 15 studies reporting on 620 intramedullary nails (190 [30.7%] proximal humerus, 278 [44.8%] Midhumerus, 8 [1.3%] distal humerus and not specified in 144 [23.2%]) and 4 studies reporting on 153 ORIFs (53 [34.6%] proximal humerus, 50 [32.7%] Midhumerus, 39 [25.5%] distal humerus and not specified in 11[7.2%]). (Appendix 2).

Results

I Functional Outcome

The endoprosthetic reconstruction was reported on functional outcome for the MSTS score in six studies (209 participants). The range of the mean values of MSTS scores was 19%-73.1% while that of the follow-up duration was 8-71 months. The range of the scores among individuals participating the research was 7%-100% (Table 2).

Both researches show functional outcome for the scores of MSTS after intramedullary nail fixation. One reported a mean value of 79 among 57 participants after 8 months, while the other reported the value of 27.7 (27.0-28.5) in 32 patients after 14.2 months. One study demonstrated that the average score of MSTS after the 23 patients receiving ORIF was 94.6% ranged from 86% to 99% and the follow-up duration was 17.6 months.

II Local Complications

For the patients receiving endoprosthetic reconstruction, the global rate of reoperation was ranged from 0-14%, while those for the patients receiving ORIF and intramedullary nail fixation were 0-8% and 0-9% respectively. It was indicated by the results of Meta-analysis that the respective pooled rates of reoperation for ORIF, intramedullary nail fixation as well as endoprostheses were (95%CI 0.05-0.24), (95%CI 0.04-0.08) as well as (95%CI 0.06-0.11) (Figure 4). The funnel plots and Egg’s plots demonstrated low risk of publication bias based on total reoperation rates as an outcome measure (Figure 5, Figure 6).

The ranges of reoperation rates after fixation failure by ORIF, intramedullary nail fixation as well as reconstruction of endoprosthesis were 0-19%, 0-6% as well as 0-10%. The results of Meta-analysis indicated that the reoperation rates of patients receiving ORIF, intramedullary nail fixation as well as endoprostheses were (95%CI 0.02-0.19), (95%CI 0.01-0.04) as well as (95%CI 0.03-0.07) (Figure 7). The ranges of reoperation rates due to deep infection in patients receiving ORIF, intramedullary nail fixation as well as endoprostheses were 0-2%, 0-2% and 0-9%. The results of Meta-analysis indicated that the reoperation rates of patients receiving ORIF, intramedullary nail fixation as well as endoprostheses were (95%CI 0.01-0.06), (95%CI 0.01-0.03) as well as (95%CI 0.02-0.07) (Figure 8). The ranges of reoperation rates due to dislocations in patients receiving intramedullary nail fixation and endoprostheses were 0-5% and 0-8%, respectively. The results of Meta-analysis indicated reoperation rates of (95%CI 0.02-0.05) for endoprostheses, and (95%CI 0.01-0.04) for intramedullary nails. In the ORIF group, only one patient required reoperation due to dislocations (Figure 9) [4]. There were 10 cases required reoperation because of tumor recurrence or progression in three surgical techniques. The recurring tumors included: 3 renal tumor, 1 colorectal tumor, 1 lung tumor, as well as undefined tumors in the rest 5 cases. There were causes else including hematoma (2) after endoprosthetic reconstruction; nonunion after intramedullary nailing (9) and ORIF (1) in the overall reoperation rates [4, 6, 15].

III Systemic Complications

Only partially studies reported systemic complications including pneumonia, pulmonary embolism, cerebrovascular accident, respiratory failure, intraoperative mortality and so on. However, with these limited data the impact of surgical approaches for outcomes could not be sufficiently analyzed (Table 3).

Table 3: Local and Systemic Complication Rates Per Implant Type for Metastatic Humerus.

Author, year	Implant	humerus	Pathological fractures	Deep infection	Fixation failure	Disloc.	Recurr.	Reop.	Sys. comp.
Lewallen RP et al (1982)	IMN	55	--	0(0)	0(0)	3(5)	0(0)	3(5)	--
Capanna R et al (1988)	IMN	19	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Yazawa Y et al (1990)	IMN	41	--	0(0)	1(2)	1(2)	0(0)	2(5)	--
Fuhrmann RA et al (2000)	EPR	22	--	0(0)	0(0)	0(0)	0(0)	1(5)	0
Gebhart, M. et al (2001)	EPR	17	--	0(0)	0(0)	0(0)	0(0)	0(0)	0(0)
Gebhart, M. et al (2001)	IMN	38	--	0(0)	1(3)	0(0)	0(0)	1(3)	0(0)
Bickels J et al (2002)	EPR	12	--	1(8)	0(0)	0(0)	0(0)	1(8)	--
Bauze AJ, et al (2003)	IMN	31	25	0(0)	2(6)	0(0)	0(0)	2(6)	--
Thai DM et al (2006)	EPR	26	--	0(0)	0(0)	1(4)	0(0)	1(4)	----
Thai DM et al (2006)	IMN	51	--	0(0)	0(0)	0(0)	1(2)	1(2)	--
Camnasio F et al (2008)	EPR	37	--	0(0)	3(8)	0(0)	0(0)	3(8)	--
Scotti, C. et al (2008)	EPR	40	12	0(0)	3(8)	1(3)	0(0)	4(10)	--
Cannon CP et al (2009)	EPR	67	--	1(1)	0(0)	0(0)	1(1)	2(3)	--
Piccioli A et al (2010)	EPR	30	--	0(0)	0(0)	0(0)	1(4)	1(4)	--
Piccioli A et al (2010)	IMN	57	--	0(0)	2(4)	0(0)	3(5)	5(9)	--
Siegel, H.J. et al (2010)	ORIF	23	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Raiss, P. et al (2010)	EPR	30	--	1(3)	1(3)	1(3)	0(0)	3(10)	--
Griffiths, D. et al (2011)	EPR	30	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Wedin R et al (2012)	EPR	35	--	2(6)	1(3)	1(3)	0(0)	4(11)	--
Wedin R et al (2012)	IMN	148	--	3(2)	3(2)	0(0)	0(0)	11(7)	--
Wedin R et al (2012)	ORIF	21	--	0(0)	4(19)	0(0)	0(0)	5(24)	--
Henrichs MP et al (2014)	EPR	26	--	0(0)	0(0)	2(8)	0(0)	2(8)	--
Pruksakorn D et al (2015)	EPR	16	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Pruksakorn D et al (2015)	ORIF	11	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Janssen SJ et al (2016)	EPR	46	--	4(9)	0(0)	0(0)	0(0)	5(11)	--
Janssen SJ et al (2016)	IMN	148	--	1(1)	2(1)	1(1)	2(1)	10(7)	--
Janssen SJ et al (2016)	ORIF	98	--	2(2)	3(3)	1(1)	2(2)	10(10)	--
Choi ES et al (2016)	IMN	32	21	0(0)	1(3)	0(0)	0(0)	1(3)	0(0)
Schmolders J et al (2016)	EPR	21	--	1(2)	2(10)	0(0)	0(0)	3(14)	--

Discussion

Analyzing outcomes after the common operative treatments including endoprosthetic reconstruction, intramedullary nailing, and ORIF could contribute to intervene surgically for metastatic humerus. We aimed to make appropriately surgical decision to improve the living qualities of the remainder of the patients’ lives by comparing the three among common operative treatments. The general and local complications as well as the functional outcomes were analyzed.

We found that there was wide variation in the criteria applied for functional outcome measures and the MSTS score is most frequently used. There were 8 studies in 21 studies where MSTS score was applied. Additional we didn’t directly assess functional outcome of three operative treatments due to the limited number of studies and the discordant follow-up period. The functional outcome indicated that the upper limb function apparently returned after surgery, however the degree to improvement was unknown. Furthermore, both the preoperative and postoperative functional levels were included. Additionally, the outcome assessors completing the evaluation on the functional outcomes of the patients shouldn’t overestimate function and underestimate pain, but also measurement of living qualities, such as the instrument of EQ-5D or SF-36 were considered [25]. It was discovered that ORIF exhibited the maximized general rate of reoperation, in spite of the limitation in direct comparisons of local complication among operating treatments. The endoprosthetic reconstruction and intramedullary nailing have a lower overall reoperation rate. Furthermore, we found that revision surgery for failure of fixation was more frequent after ORIF, and revision surgery due to deep infections seemed more frequent after endoprostheses. Reoperations resulting from dislocations was relatively rare in three surgical treatments. We consider that intramedullary nailing has become the acceptable alternative for treatment of metastatic humerus in the metastatic diaphyseal humeral lesion of the patients whose expected live durations were shorter than half a year. Prosthetic arthroplasty is appropriate to reconstruct proximal humeral neck or head injuries, injuries with massive osseous losses in proximal humerus, or injuries resisting to radiotherapy. It is also suitable for the patients whose expected life durations were desirable, that is, longer than half a year. Additionally, total elbow prostheses can be a suitable alternative for injuries with massive osseous losses in distal humerus.

Our study has five main limitations. Firstly, although we searched five large literature databases, several relevant articles might be omitted since which were not included in the above-mentioned databases. However, we didn’t find other publications after we had extensively screened the bibliographies of these articles. Secondly, several researches including uncertain lesions or the reason for revision surgery were excluded [26, 27]. However, we also energetically contacted author for primary data. The study would be excluded only if the author didn’t be contacted. Thirdly, the elements of these studies including the type of implants, the surgical technique, postoperative rehabilitation, location of the lesion and extend of bone destruction probably varied and we didn’t perform subgroup analysis based on these factors which leaded selection bias. Efforts were made to focus on humerus metastasis with the aim of minimizing the bias. Fourthly, whether adjuvant treatment-radiotherapy and chemotherapy should be considered as an important limitation. Finally, it is important to determine a strict follow-up protocol. The follow-up protocol varied might cause attrition bias. Despite of the shortcomings, meta-analysis is proved to be an appropriate way to estimate the pooled rates of reoperation of each operating technique since the result of which is normally the initial appealing result thus is usually perfectly reported.

General complications reported with the highest frequency include pneumonia, pulmonary embolism, cerebrovascular accident and respiratory failure. However, we didn’t perform meta-analysis between surgical treatments in systemic complication due to poor quality of reporting data. We considered that future studies including uniform kinds and treatment consequences of systemic complications for one limb per one patient should be more clear [28, 29].

Conclusion

In the current work, the postoperative complications and functional outcomes of three operating treatments for metastatic humerus are analysed. Compared with the high rate of reoperation due to ORIF, those of intramedullary nail fixation and endoprosthetic construction are of comparability. The findings in the current study is applicable for aiding to make appropriately surgical decision to improve the living quality of patients in the remainder of their lives.

Acknowledgement

This work was supported by the Key Project of Medical-Science Research of Hebei Province [20180564] and the Project of the Natural Science Foundation of Hebei Province [H2019206309].

Disclosure

The authors declare that they have no competing interests.

Article Info

Article Type

Research Article

Publication history

Received: Sat 09, Nov 2019
Accepted: Wed 18, Dec 2019
Published: Fri 27, Dec 2019

Copyright

© 2023 Helin Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.COR.2019.06.14

Author Info

Hongzeng Wu Helin Feng Jianfa Xu Jianjun Xun Qianqian Zhang Yi Zhao

Corresponding Author

Helin Feng
Department of Orthopedics, The Fourth Hospital of Hebei Medical University, 12 Health Road, Shijiazhuang, Hebei 050011, P. R. China

Figures & Tables

Table 1: Characteristics of All Patients With Metastatic Humerus Per Study (%).

Author, year	Implant	Patients	humerus	Pathological fractures	Median age	Minimum follow-upm	One year survival in (%)
Lewallen RP et al (1982)	IMN	55	55	--	--	--	10Ma
Capanna R et al (1988)	EPR	20	19	--	--	--	--
Yazawa Y et al (1990)	IMN	166	41	30	62	24	40%
Fuhrmann RA et al (2000)	EPR	22	22	--	57	47a	--
Gebhart, M. et al (2001)	EPR+IMN	56	55	31	62	1	9a
Bickels J et al (2002)	EPR	134	12	--	--	24	--
Bauze AJ, et al (2003)	IMN	31	31	25	67	--	--
Bauze AJ et al (2006)	EPR+IMN	96	77	--	63	8a	43.5%
Thai DM et al (2008)	EPR	154	37	--	59	--	69.5%
Scotti, C. et al (2008)	EPR	40	40	12	67	--	70%
Cannon CP et al (2009)	EPR	83	67		55	24	55.8%
Piccioli A et al (2010)	EPR+IMN	85	87	76	59	8.3a	67.3%
Siegel, H.J. et al (2010)	ORIF	32	23	--	52	17.6a	--
Raiss, P. et al (2010)	EPR	43	30	--	60	38a	77%（2）
Griffiths, D. et al (2011)	EPR	68	30	--	53	71a	--
Wedin R et al (2012)	EPR+IMN+ ORIF	214	204	173	67	8a	40%
Henrichs MP et al (2014)	EPR	82	26	--	63	--	94.7%
Pruksakorn D et al (2015)	EPR+ ORIF	27	27	--	--	16a	91.7%
Janssen SJ et al (2016)	EPR+IMN+ ORIF	295	292	237	63	4a	49%
Choi ES et al (2016)	IMN	32	32	21	--	14.2a	48%
Schmolders J et al (2016)	EPR	30	21	--	--	26a	83%

--, not available; EPR, endoprosthesis; IMN, intramedullary nail; ORIF, open reduction internal fixation.

a Mean age.

m In months.

Table 2. Functional Outcome Per Implant Type for Metastatic Humerus (%).

Author, year	Implant	Follow-up (Months)	Patients	Outcome measure	Median score (Range)
Scotti, C. et al (2008)	EPR	30	40	MSTS	73.1a (69.9-76.3)
Cannon CP et al (2009)	EPR	24	67	MSTS	63a(40-83)
Piccioli A et al (2010)	EPR IMN	8	26 57	MSTS	73a 79a
Raiss, P. et al (2010)	EPR	38	30	MSTS	19a(7-27)
Griffiths, D. et al (2011)	EPR	71	30	MSTS	72.3a(53.3- 100)
Choi ES et al (2016)	IMN	14.2	32	MSTS	27.7a(27.0-28.5)
Pruksakorn D et al (2015)	ERP	16	16	MSTS	33-77
Siegel, H.J. et al (2010)	ORIF	17.6	23	MSTS	94.6 a(86-99)

MSTS, musculoskeletal tumor society score; EPR, endoprosthesis; IMN, intramedullary nail; ORIF, open reduction internal fixation.

^a Mean score.

Table 3: Local and Systemic Complication Rates Per Implant Type for Metastatic Humerus.

Author, year	Implant	humerus	Pathological fractures	Deep infection	Fixation failure	Disloc.	Recurr.	Reop.	Sys. comp.
Lewallen RP et al (1982)	IMN	55	--	0(0)	0(0)	3(5)	0(0)	3(5)	--
Capanna R et al (1988)	IMN	19	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Yazawa Y et al (1990)	IMN	41	--	0(0)	1(2)	1(2)	0(0)	2(5)	--
Fuhrmann RA et al (2000)	EPR	22	--	0(0)	0(0)	0(0)	0(0)	1(5)	0
Gebhart, M. et al (2001)	EPR	17	--	0(0)	0(0)	0(0)	0(0)	0(0)	0(0)
Gebhart, M. et al (2001)	IMN	38	--	0(0)	1(3)	0(0)	0(0)	1(3)	0(0)
Bickels J et al (2002)	EPR	12	--	1(8)	0(0)	0(0)	0(0)	1(8)	--
Bauze AJ, et al (2003)	IMN	31	25	0(0)	2(6)	0(0)	0(0)	2(6)	--
Thai DM et al (2006)	EPR	26	--	0(0)	0(0)	1(4)	0(0)	1(4)	----
Thai DM et al (2006)	IMN	51	--	0(0)	0(0)	0(0)	1(2)	1(2)	--
Camnasio F et al (2008)	EPR	37	--	0(0)	3(8)	0(0)	0(0)	3(8)	--
Scotti, C. et al (2008)	EPR	40	12	0(0)	3(8)	1(3)	0(0)	4(10)	--
Cannon CP et al (2009)	EPR	67	--	1(1)	0(0)	0(0)	1(1)	2(3)	--
Piccioli A et al (2010)	EPR	30	--	0(0)	0(0)	0(0)	1(4)	1(4)	--
Piccioli A et al (2010)	IMN	57	--	0(0)	2(4)	0(0)	3(5)	5(9)	--
Siegel, H.J. et al (2010)	ORIF	23	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Raiss, P. et al (2010)	EPR	30	--	1(3)	1(3)	1(3)	0(0)	3(10)	--
Griffiths, D. et al (2011)	EPR	30	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Wedin R et al (2012)	EPR	35	--	2(6)	1(3)	1(3)	0(0)	4(11)	--
Wedin R et al (2012)	IMN	148	--	3(2)	3(2)	0(0)	0(0)	11(7)	--
Wedin R et al (2012)	ORIF	21	--	0(0)	4(19)	0(0)	0(0)	5(24)	--
Henrichs MP et al (2014)	EPR	26	--	0(0)	0(0)	2(8)	0(0)	2(8)	--
Pruksakorn D et al (2015)	EPR	16	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Pruksakorn D et al (2015)	ORIF	11	--	0(0)	0(0)	0(0)	0(0)	0(0)	--
Janssen SJ et al (2016)	EPR	46	--	4(9)	0(0)	0(0)	0(0)	5(11)	--
Janssen SJ et al (2016)	IMN	148	--	1(1)	2(1)	1(1)	2(1)	10(7)	--
Janssen SJ et al (2016)	ORIF	98	--	2(2)	3(3)	1(1)	2(2)	10(10)	--
Choi ES et al (2016)	IMN	32	21	0(0)	1(3)	0(0)	0(0)	1(3)	0(0)
Schmolders J et al (2016)	EPR	21	--	1(2)	2(10)	0(0)	0(0)	3(14)	--

Figure 1: A flow diagram of study selection.

Figure 2: The global qualities of all researches contained in this work and all of which possessed retrospective designs.

Figure 3: The distribution of primary tumors with data included in appendix two.

Figure 4: The meta-analysis with global rates of reoperation (black solid rhombuses) for each treatment arm and research which include the confidence interval of 95% [95% CI] expressed as a black horizontal line that crosses the solid rhombuses. ORIF refers to Open Reduction with Internal Fixation. The estimated percentages of the variations in the therapeutic evaluation resulting from heterogenetic nature across researches are demonstrated by the I-squared statistics. The changed scale of percentages on the x-axis is worth to be noted.

Figure 5: The funnel plots demonstrating low risk of publication bias based on total reoperation rates as an outcome measure.

Figure 6: The Egg’s plots demonstrating low risk of publication bias based on total reoperation rates as an outcome measure.

Figure 7: The meta-analysis with rates of reoperation for fixation failure (black solid rhombuses) for each treatment arm and research which include the confidence interval of 95% [95% CI] expressed as a black horizontal line that crosses the solid rhombuses. ORIF refers to Open Reduction with Internal Fixation. The estimated percentages of the variations in the therapeutic evaluation resulting from heterogenetic nature across researches are demonstrated by the I-squared statistics. The changed scale of percentages on the x-axis is worth to be noted.

Figure 8: The meta-analysis with rates of reoperation for deep infections (black solid rhombuses) for each treatment arm and research which include the confidence interval of 95% [95% CI] expressed as a black horizontal line that crosses the solid rhombuses. ORIF refers to Open Reduction with Internal Fixation. The estimated percentages of the variations in the therapeutic evaluation resulting from heterogenetic nature across researches are demonstrated by the I-squared statistics. The changed scale of percentages on the x-axis is worth to be noted.

Figure 9: The meta-analysis with rates of reoperation for dislocations (black solid rhombuses) for each treatment arm and research which include the confidence interval of 95% [95% CI] expressed as a black horizontal line that crosses the solid rhombuses. ORIF refers to Open Reduction with Internal Fixation. The estimated percentages of the variations in the therapeutic evaluation resulting from heterogenetic nature across researches are demonstrated by the I-squared statistics. The changed scale of percentages on the x-axis is worth to be noted.

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