3D printing personalized guide plate in the management of recurrent intramuscular venous malformations: A single center experience

Abstract

Objective

This study aimed to investigate the feasibility and effectiveness of 3D printing personalized guide plate in the management of recurrent intramuscular venous malformations (IVM).

Methods

Fifteen patients with recurrent IVM were retrospectively assessed. 3D-slicer software was used to extract and reconstruct the imaging data from CT and/or MRI to highlight the morphology, size, and puncture depth of the lesion. With the guidance of personalized plate, complete excision of the IVM was adopted along the pre-marked (methylene blue, MB) margin.

Results

Personalized guide plate matched involved extremity well, and MB-puncture approach was consistent with preoperative design. All IVMs were removed radically in one single session. Complete pain relief was obtained in all cases postoperatively.

Conclusion

The application of 3D printing guide plate can be safe, effective, and reliable to confirming the precise margin of IVM, renders a promising technique with a high practical value in resection of recurrent lesion.

Keywords

intramuscular venous malformations recurrent personalized guide plate 3D printing children

Introduction

Venous malformation (VM), a benign low-flow vascular malformation, usually manifests as a palpable subcutaneous swelling varying in volume with the change of venous pressure.^1–3 Most of VM can be observed at birth and related to somatic mutation and development of dysplastic veins.^4,5 Due to its low-flow nature and lack of venous valve, thrombosis or phlebolith can often be found in VM, resulting in local venous engorgement and pain.^6,7 VM may be focal, multifocal, or involving any part of the body, but cannot involute spontaneously. Of these, intramuscular venous malformation (IVM) is a rare type of vascular malformation, but always mistaken as other subcutaneous benign tumor for similar presentation, such as lipoma, neurofibroma, or hemangioma. IVM usually invades one single muscle group, among which masseter muscle is mostly affected.^8,9 For the diagnosis of IVM, information from imaging findings such as ultrasonography (US) is mostly used. Besides, contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are conducted for both anatomical location and size examination of IVM.^10,11

For the management of extensive IVM, sclerotherapy (including dehydrated alcohol, polidocanol, lauromacrogol, and bleomycin) has been gradually preferred in terms of its effectiveness in endothelial cells and low toxicity in surrounding tissues.^12–14 In contrast, surgical resection is still recommended for cases of localized IVM accompanied by phleboliths or thromboses, causing compression symptoms.^15,16 Despite ideal posttreatment outcomes, local recurrence of IVM is not uncommonly encountered.^17,18 For achieving symptomatic improvement but not complete remission, multiple and repeated sessions of sclerotherapy are essential in recurrent cases, which are always unacceptable by patients. Although CT/MRI may provide general information of location and extent, small size and unclear border of some recurrent IVM lesions make both surgical exploration and intraoperative identification difficult.

With the development of digital medicine, the extensive application of 3D printing guide plate in surgical navigation for orthopedic surgery has gained increasing attention. Through the guide plate, resection or reconstruction surgery can be performed precisely based on preoperative planning, which is beneficial for surgical accuracy and efficiency.^19,20 However, although new insights using 3D printed technology become incorporated in the management of arteriovenous malformation in recent years, it is worth noting that there is still a lack of clinical study on the impact of 3D printing guide plate in treating IVM.^21,22 Herein, this research intends to introduce our center’s experience in using 3D printing personalized guide plate for both intraoperative localization and precise removal of recurrent IVM.

Patients and methods

This retrospective study was carried out for collected data of 15 patients presented to our center with IVM between January 2018 and June 2022. All cases suffering with local recurrence after previous treatment with sclerotherapy or surgical resection were included in this research. IVM lesions from these cases were detected in single muscle group of the extremities by US, contrast-enhanced CT and/or MRI. The most common IVM location in this study was lower extremity (eight in thigh and five in calf), and two IVMs were located in upper extremities (one in upper arm and one in forearm). Pain (exertion and/or rest) was the major clinical presentation owing to IVM in this cohort. The patient clinical features (gender, age, IVM location, involved muscle, size, pain, phleboliths, and previous management) were recorded in Table 1. Inclusion criteria included as follow: (1) recurrent IVM; (2) impalpable lesion; (3) localized lesion; (4) pain. Exclusion criteria included as follow: (1) refusal to surgery; (2) complicated with other vascular malformation; (3) less than 6 months of follow-up. All parents of IVM patients signed informed consent forms. This research was approved by the Ethics Committee of the Children’s Hospital of Nanjing Medical University.

Table 1.

Clinical features of 15 cases before treatment.

Caes no.	Gender	Age (yr)	Location of IVM	Muscle involved	Size (cm)	Pain		Intralesional phleboliths	Previous management
Caes no.	Gender	Age (yr)	Location of IVM	Muscle involved	Size (cm)	Rest	Exertion	Intralesional phleboliths	Previous management
1	M	8	Left calf	Gastrocnemius	2.1 × 1.6	+	+	+	Lauromacrogol sclerotherapy
2	F	12	Right thigh	Rectus femoris	2.4 × 2	+	+	+	Polidocanol sclerotherapy
3	M	14	Right thigh	Biceps femoris	3 × 2	+	+	+	Polidocanol sclerotherapy
4	M	10	Right calf	Soleus	2.2 × 1.4	−	+	−	Resection
5	M	9	Left thigh	Vastus lateralis	2.5 × 1.2	−	+	−	Ethanol sclerotherapy
6	F	10	Left thigh	Rectus femoris	3 × 1.5	+	+	+	Resection
7	M	8	Right upper arm	Biceps brachii	2.2 × 1.6	−	+	−	Polidocanol sclerotherapy
8	M	12	Left thigh	Vastus medialis	3.0 × 2.1	−	+	+	Lauromacrogol sclerotherapy
9	M	10	Right forearm	Brachioradialis	2.3 × 1.4	−	+	+	Bleomycin sclerotherapy
10	F	12	Right calf	Tibialis anterior	2.4 × 2.0	−	+	+	Polidocanol sclerotherapy
11	F	8	Right thigh	Semitendinosus	2.6 × 2.1	+	+	+	Polidocanol sclerotherapy
12	M	9	Left calf	Peroneus longus	1.6 × 1.2	−	+	−	Ethanol sclerotherapy
13	M	11	Right thigh	Rectus femoris	3.0 × 2.5	+	+	+	Resection
14	M	12	Left thigh	Biceps femoris	2.6 × 2.4	−	+	+	Bleomycin sclerotherapy
15	M	9	Right calf	Soleus	2.8 × 2.2	−	+	−	Ethanol sclerotherapy

Abbreviations: M: male; F: female; IVM: intramuscular venous malformation.

Preoperatively, on the basis of CT and/or MRI data of IVM, 3D-slicer (Open source software application) was used to extract and reconstruct the imaging data, to highlight the morphology, size, and puncture depth of the lesion, and to create the 3D printing personalized guide plate (Figure 1(a)–(c)). 3D printer parameters: positioning and printing accuracy: X/Y/Z axis = 0.01 mm/100 mm; printing layer thickness = 0.1–0.2 mm. The location of guide pin holes was designed at 5 mm outside the lesion, so that MB could be injected into surrounding muscle of IVM to mark the precise boundary for resection without residual lesion. 3D printing personalized guide plate was sterilized by H₂O₂ (58%) plasma sterilization at the temperature of 50°C for 55 min, and followed by drying for 15 min.

Figure 1.

Puncture location simulation and 3D printing personalized guide plate. (a) The design of the puncture guide plate. (b) 3D reconstruction for both morphology and size of IVM lesion. (c) Demonstration of puncture depth for each MB injection. (d) 3D printing personalized guide plate with guide pin holes and windows. (e) According to guidance of puncture depth, MB was injected through the pin holes to mark the borders of IVM. (f) The margin points of IVM with blue-dyeing was marked clearly, and the lesion was resected intactly. IVM, Intramuscular venous malformation. MB, Methylene blue. Arrow head, margin point marked by MB.

Under general anesthesia, the guide plate was placed on the surface of involved extremity, according to the anatomical skin morphology of the adjacent joint. Through each pin hole, 0.05–0.1 mL methylene blue (MB, 2 mL: 20 mg, Jumpcan Pharmaceutical Co., Ltd., Taixing, China) was injected into the muscle according to computed puncture depth. The windows on the guide plate were designed for the convenience of observing MB injection, and even for an alternative room for puncture. Immediately following MB marking, an optimal skin incision was performed on the surface of IVM region. All margin points of intramuscular lesion with blue-dyeing could be easily observed in a direct visualization. With protection of functional vessels and nerves, complete excision of the IVM was adopted along the MB-marked margin (Figure 1(d)–(f)). Subsequently, irrigation and hemostasis were performed carefully. Evaluation of postoperative clinical outcomes included residual lesion, pain, incision length, operative duration, and complications. All patients enrolled in this study were followed at least 6 months after surgery, and MRI or US was repeated postoperatively to assess for any local recurrence.

Results

The postoperative clinical results were summarized in Table 2. All cases had their diagnosis confirmed of IVM by both preoperative imaging examination and postoperative pathology. The male to female ratio was 11:4, with the age range from 8 to 14 years. No history of trauma related to IVM lesion was found in this cohort.

Table 2.

Postoperative clinical outcomes.

Case no.	Gender	Age (yr)	Residual lesion	Pain		Incision length (cm)	Operative duration (minute)	Complications	Follow-up (month)
Case no.	Gender	Age (yr)	Residual lesion	Rest	Exertion	Incision length (cm)	Operative duration (minute)	Complications	Follow-up (month)
1	M	6	–	–	–	2.5	40	–	10
2	F	12	–	–	–	2.8	45	–	12
3	M	14	–	–	–	3.5	40	–	9
4	M	10	–	–	–	2.5	25	Scar hyperplasia	10
5	M	7	–	–	–	3.0	40	–	8
6	F	10	–	–	–	3.5	45	Wound infection	8
7	M	4	–	–	–	3.2	35	–	14
8	M	12	–	–	–	3.5	30	–	8
9	M	8	–	–	–	3.0	35	Fever	10
10	F	12	–	–	–	3.0	45	–	10
11	F	7	–	–	–	3.2	30	–	12
12	M	5	–	–	–	2.0	40	–	6
13	M	8	–	–	–	3.5	35	–	8
14	M	12	–	–	–	3.2	30	–	10
15	M	8	–	–	–	3.5	40	Scar hyperplasia	12

Abbreviations: M: male; F: female.

All IVMs were located accurately and removed radically in one single session without residual lesion, and no damage of functional vessel or nerve was observed in this research (Figures 2 and 3). After surgery, complete pain (rest and/or exertion) relief was obtained in all cases. All operations in this research were performed successfully. The operative duration was from 25–45 min (mean: 37 min), and the incision length was from 2.0–3.5 cm (mean: 3.04 cm). Pathological examination of excised specimens demonstrated extensive dilated thin-walled vessels, and intralesional phleboliths were found in 10 cases. Temporary MB-related pigmentations were visible at the surgery sites in all cases, and faded away spontaneously within 1 month.

Figure 2.

A 10-year-old male patient suffered with recurrent IVM in right calf, and previous surgical resection was performed in other hospital 12 months ago. (a) Clinical appearance preoperatively. (b) Preoperative MRI finding: the medial side of the right calf was involved by a IVM of the soleus. (c) Demonstration of puncture depth. (d) 3D printing personalized guide plate with guide pin holes. (e) MRI postoperatively. (f) Pathology postoperatively. IVM, Intramuscular venous malformation. MRI, magnetic resonance imaging.

Figure 3.

A 14-year-old male patient suffered with painful IVM in right thigh. Previous polidocanol sclerotherapy was performed in other hospital 6 months ago, but no significant reduction of the lesion can be observed. (a) Clinical appearance preoperatively. (b) Preoperative MRI finding: the back of the right thigh was involved by an IVM of the biceps femoris. (c) Demonstration of puncture depth. (d) 3D printing personalized guide plate with guide pin holes. (e) MRI postoperatively. (f) Pathology postoperatively. IVM, Intramuscular venous malformation. MRI, magnetic resonance imaging.

For complications, two patients with scar hyperplasia, one patient with fever, and one patient with wound infection were managed satisfactorily by symptomatic treatment. Neither local recurrence nor MB allergy was recorded with a postoperative follow-up from 6 to 14 months (mean: 9.8 months).

Discussion

For the management of localized IVM with sclerotherapy failure, surgical resection is the preferred option for its complete removal of lesion, which always provides ideal efficacy.^23,24 Notably, conventional surgical resection may result in residual IVM or even small lesion miss, and intraoperative resection plane cannot be controlled delicately. Therefore, confirming the precise margin of IVM lesion during operation is crucial in surgical resection. Characteristics of IVM, such as deep location, irregular shape, and small size, pose challenges to surgeon’s judgment on lesion margin. Although preoperative enhanced CT and MRI may indirectly offer the location information of IVM, some clinical surgeons advocate palpation of tenderness and pain before anesthetic as more effective way to localize the lesion.²⁵ Apparently, this physical judgment technique based on subjective experience is a test for young surgeons, and lack of accuracy for defining the border of IVM lesion.

Additional strategies, including the application of preoperative percutaneous embolization of localized VM with N-butyl cyanoacrylate (n-BCA) glue followed by surgical resection to reduce intraoperative bleeding, have been described as safe and efficacious.^26,27 However, radiation exposure and unknown effectiveness in intramuscular lesions inhibit this procedure in management of IVM in children. Unlike our technique, this hybrid method is often in need of multidisciplinary cooperation (interventional radiologists and vascular surgeons). Besides, as one of potential complications in this treatment, unintended embolization caused by glue migration cannot be ignored.

In recent year, 3D printing guide plate has been widely applied in reconstructive surgery for its improvement of personalization, accuracy, and safety of the operation.^28,29 Wu et al.³⁰ reported the use of percutaneous needle guide plate can perform safe and individualized tumor biopsy of acetabulum. It was also used in tumor resection and reconstruction in the field of thoracic surgery, which promoted surgeons’ understanding of thoracic wall tumor location, morphology, and invasion range.³¹ Wu et al.³² introduced a technique using 3D printing osteotomy guide plate as a safe and effective strategy to lower both complication risk and recurrence rate after hemibone resection.

To our knowledge, this study is the first clinical report on application of 3D printing guide plate in the management of recurrent IVM in children. We used the personalized plate to guide both site and depth of MB injection for marking the boundary of IVM. On basis of preoperative design, the skin morphology of the adjacent joint for the guide placement was determined, so that the guide plate can be accurately placed on the surface of IVM lesion. To ensure the safe margin for resection, the MB injection points set up were 5 mm outside the lesion. Besides, 0.1 mL of MB in each point is enough for visual recognition inside the muscle, too much dose of MB may cause large area of blue-dyeing, and thus cloud surgeon’s judgment on resection margin. Neither residual lesion nor local recurrence was observed in all cases. With the application of guide plate, the average operative duration (37 min in average) and incision length (3.04 cm in average) were markedly short, which were acceptable to most patients. It is worth mentioning that CT/MRI still plays key role in characterizing IVM and defining its general extent preoperatively, and our technique can be used as an ideal supplement to these traditional imaging examinations for more direct localization of lesion during the operation. With the guidance of 3D printing plate, surgeons may remove the lesion precisely in a direct visualization. However, it cannot be performed separately without data from CT/MRI. Phleboliths is thought to be one of risk factors associated with painful presentation in IVM, which only can be observed by imaging examinations or postoperative pathology. The potential mechanisms currently considered is that intralesional thrombosis resulted from low-flow environment leads to formation of phlebolith, stimulating the pain pathway.³³ Eivazi et al.³⁴ reported that intervention of localized intravascular coagulopathy in VM may prevent phlebolith formation. Phleboliths can be managed by surgical excision when contributing to the aggravation of pain.^35,36 In this study, intralesional phleboliths were found in 10 cases (66.7%), and removed intactly by our technique.

The limitations of our study include its small sample size and lack of prospective research. What cannot be neglected, application of 3D printing guide plate could impose extra financial burdens for patients. At our center, this technique has not been performed for nonfocal or diffused lesion, further investigation in its effectiveness in these main types of IVM needs to be facilitated in the future. In addition, due to low incidence IVM, the control group without guide plate was not included in our research.

Conclusions

Based on the 3D printing technology, the use of personalized guide plate can be safe, effective, and reliable to confirming the location of IVM, especially for recurrent lesions. It has high practical value and can help shorten both operative duration and incision length, which deserves the clinical application.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The studies involving human participants were reviewed and approved by Ethics Committee of the Children’s Hospital of Nanjing Medical University.

Guarantor

WS.

Informed consent

Informed consent was received for publication of the figures in this article.

Contributorship

WS revised the manuscript and approved the final manuscript as submitted. WS, JC and SJ performed the surgery and conducted the data analyses. JX and SJ performed postoperative follow-up and analyzed the data. TH wrote a draft of the article and edited the figures and tables. TH and SJ contributed to this work equally.

ORCID iD

Tao Han

References

Hage

Chick

JFB

Srinivasa

, et al. Treatment of venous malformations: the data, where we are, and how it is done. Tech Vasc Interv Radiol 2018; 21: 45–54.

Markovic

Shortell

. Venous malformations. J Cardiovasc Surg (Torino) 2021; 62: 456–466.

Johnson

Richter

. Surgical considerations in vascular malformations. Tech Vasc Interv Radiol 2019; 22: 100635.

Goines

Boscolo

. A xenograft model for venous malformation. Methods Mol Biol 2021;2206:179–192.

Limaye

Kangas

Mendola

, et al. Somatic activating PIK3CA mutations cause venous malformation. Am J Hum Genet 2015; 97: 914–921.

Hung

JWS

Leung

MWY

Liu

CSW

, et al. Venous malformation and localized intravascular coagulopathy in children. Eur J Pediatr Surg 2017; 27: 181–184.

Hein

Mulliken

Kozakewich

HPW

, et al. Venous malformations of skeletal muscle. Plast Reconstr Surg 2002; 110: 1625–1635.

Kim

Lew

Sim

. Intramuscular vascular malformation of the temporalis muscle: a case report and review of the literature. Ann Dermatol 2014; 26: 428–430.

Childs

Emory

. Successful treatment of intramuscular venous malformation with image-guided radiofrequency ablation. J Vasc Interv Radiol 2012; 23: 1391–1393.

10.

Chowdhury

Haque

Kawsar

, et al. Surgical management of scalp arterio-venous malformation and scalp venous malformation: an experience of eleven cases. Indian J Plast Surg 2013; 46: 98–107.

11.

Abdel Razek

AAK

Albair

Samir

. Clinical value of classification of venous malformations with contrast-enhanced MR angiography. Phlebology 2017; 32: 628–633.

12.

Seront

Vikkula

Boon

. venous malformations of the head and neck. Otolaryngol Clin North Am 2018; 51: 173–184.

13.

Bianchini

Camilli

Furgiuele

. intramuscular venous malformations of the upper and lower limbs: indications and outcomes of sclerotherapy. Cardiovasc Intervent Radiol 2018;41:1505–1512.

14.

Weitz-Tuoretmaa

Keski-Nisula

Rautio

, et al. Quality of life and clinical results after endovascular sclerotherapy: a comparison between intra- and extramuscular low-flow venous malformations. Phlebology 2021; 36: 226–232.

15.

Wieck

Nowicki

Schall

, et al. Management of pediatric intramuscular venous malformations. J Pediatr Surg 2017;52:598–601.

16.

Kwon

Lim

Pyon

, et al. Surgical treatment of masseteric venous malformations and outcomes. J Craniofac Surg 2014; 25: 680–684.

17.

Murakami

Ogata

Miyano

, et al. An enlarged intramuscular venous malformation in the femoral region successfully treated with complete resection. Int J Surg Case Rep 2016; 21: 83–86.

18.

Tabuenca Del Barrio

Gasparini

Devoto

. Intramuscular cavernous venous malformation of extraocular muscles. Fractionated stereotactic radiotherapy as a therapeutic alternative. Arch Soc Esp Oftalmol (Engl Ed) 2020; 95: 293–296.

19.

Deng

, et al. A novel anatomical locking guide plate for treating acetabular transverse posterior wall fracture: a finite element analysis study. Orthop Surg 2022; 14: 2648–2656.

20.

Park

Kang

Kim

, et al. The application of 3D-printing technology in pelvic bone tumor surgery. J Orthop Sci 2021; 26: 276–283.

21.

Thawani

Pisapia

Singh

, et al. Three-dimensional printed modeling of an arteriovenous malformation including blood flow. World Neurosurg 2016; 90: 675–683.

22.

Wang

, et al. A three-dimensional color-printed system allowing complete modeling of arteriovenous malformations for surgical simulations. J Clin Neurosci 2020; 77: 134–141.

23.

Hassanein

Mulliken

Fishman

, et al. Venous malformation: risk of progression during childhood and adolescence. Ann Plast Surg 2012; 68: 198–201.

24.

Kim

Ryu

Lee

, et al. The effects of surgical treatment and sclerotherapy for intramuscular venous malformations: a comparative clinical study. Arch Plast Surg 2021; 48: 622–629.

25.

Chen

Vrazas

Penington

. Surgical management of intramuscular venous malformations. J Pediatr Orthop 2021; 41: e67–e73.

26.

Polites

Watanabe

Scorletti

, et al. Single-stage embolization with n-butyl cyanoacrylate and surgical resection of venous malformations. Pediatr Blood Cancer 2020; 67: e28029.

27.

Tieu

Ghodke

, et al. Single-stage excision of localized head and neck venous malformations using preoperative glue embolization. Otolaryngol Head Neck Surg 2013; 148: 678–684.

28.

Sun

Shen

, et al. Computer-assisted navigation: its role in intraoperatively accurate mandibular reconstruction. Oral Surg Oral Med Oral Pathol Oral Radiol 2016; 122: 134–142.

29.

, et al. Clinical application and accuracy analysis of 3D printing guide plate based on polylactic acid in mandible reconstruction with fibula flap. Ann Transl Med 2021; 9: 460.

30.

Liu

Wang

, et al. Application of 3D printing individualized guide plates in percutaneous needle biopsy of acetabular tumors. Front Genet 2022; 13: 955643.

31.

Chen

, et al. Application of 3D printing technology to thoracic wall tumor resection and thoracic wall reconstruction. J Thorac Dis 2018; 10: 6880–6890.

32.

Yang

Liu

, et al. 3D printing guide plate for accurate hemicortical bone tumor resection in metaphysis of distal femoral: a technical note. J Orthop Surg Res 2021;16:343.

33.

Dompmartin

Acher

Thibon

, et al. Association of localized intravascular coagulopathy with venous malformations. Arch Dermatol 2008; 144: 873–877.

34.

Eivazi

Fasunla

Guldner

, et al. Phleboliths from venous malformations of the head and neck. Phlebology 2013; 28: 86–92.

35.

Chen

Yang

, et al. Risk factors associated with pain in patients with venous malformations of the extremities. Vasc Med 2019; 24: 56–62.

36.

Pessanha

Delgado-Miguel

Alves

, et al.

Venous malformations: what do phleboliths tell us in the pediatric population?

Pediatr Surg Int 2022;38:1501–1506.