A Novel Minimally Invasive Ultrasound-Guided ...

A Novel Minimally Invasive Ultrasound-Guided Technique to Biopsy Supraspinatus Tendon Richard J. Murphy, MRCS (Eng), Benjamin John Floyd Dean, MRCS (Ed), Kim Wheway, RGN, Bridget Watkins, RGN, Mark E. Morrey, MD, and Andrew Jonathan Carr, FRCS, FMedSci A lack of access to the tendon tissue has proved a significant obstacle in developing our understanding of the pathogenesis of rotator cuff tendinopathy. In this article, we describe a new minimally invasive technique that may be used to biopsy the supraspinatus tendon in the outpatient clinic or in the operating theater. Oper Tech Orthop 23:56-62 C 2013 Elsevier Inc. All rights reserved. KEYWORDS rotator cuff, supraspinatus, biopsy, tendinopathy, ultrasound

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he histologic and molecular changes in painful human tendinopathy have become more fully characterized in recent years.1-3 Historically, a scientific understanding of tendinopathy has relied on the work carried out on cadavers or biopsy specimens removed at the time of tendon surgery. Early pioneering work by Neer4 and Codman and Akerson5 on rotator cuff tendinopathy (RCT) utilized open surgical biopsy techniques to more fully understand this disorder. Nevertheless, despite advances, the study of cadaveric and surgical biopsy specimens has limitations. Cadaveric tissue lacks a clinical history to accurately phenotype the individual from whom the tissue was obtained. Furthermore, with this method, there is the potential for tissue changes to occur postmortem before laboratory analysis has occurred. A serious limitation with the use of surgical tissue is that specimens represent a relatively end stage of the disease process, in which mechanical failure of the tendon has already occurred. Owing to the limitations of these techniques, novel, minimally invasive biopsy techniques have been developed to sample a tendon at multiple stages throughout the evolution of a tendinopathy. These minimally invasive biopsy techniques are a significant reason for recent progress in our understanding of tendino-

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK. One or more of the authors are funded by the Musculoskeletal Biomedical Research Unit of the National Institute for Health Research (RM, BD, AC), the Jean Shanks Foundation (BD), and the Orthopaedic Research UK (BD). Address reprint requests to B.J.F. Dean, MRCS (Ed), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD, UK. E-mail: benjamin. [email protected]

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1048-6666/13/$-see front matter & 2013 Elsevier Inc. All rights reserved. doi:http://dx.doi.org/10.1053/j.oto.2013.05.003

pathy and have been developed, and well described, in both Achilles and patellar tendinopathy.6-12 In contrast, for the shoulder, sampling of intact, tendinopathic supraspinatus tendon has been limited to very few studies. In an early study by Tillander et al13 large 4 4 mm biopsies were taken from the middle portion of the supraspinatus tendon during subacromial decompression surgery. Unfortunately, the location of these biopsies does not represent the common site of failure in the supraspinatus and such large biopsies are not ethically feasible to take in studies today. Tuoheti et al14 obtained tissue from the insertion region of the supraspinatus tendon. However, the study was limited to 5 tissue samples and was carried out during open subacromial decompression surgery, an operation rarely performed now because of the widespread use of arthroscopic techniques. Furthermore, control tissue used in RCT studies has also been limited to the subscapularis or cadaveric tendon. Subscapularis tendon is different in its anatomy, function, and pathology relative to the supraspinatus and thus does not represent a faithful control.13,15–20 Finally, similar to the work by Tillander et al13 with open biopsies, efforts to sample tissue from the supraspinatus tendon for controls has only been undertaken using large biopsies that are no longer ethically justifiable. As a direct result of the difficulty in accessing wellphenotyped tissue samples from the spectrum of RCT, there is a distinct lack of tissue studies investigating earlier stages of the condition. Regrettably, this is precisely the stage of disease when patients present with symptomatic shoulders with intact or only partially torn tendons. In addition to this, there are no published investigations on the biological effects of treatments for RCT by means of tissue analysis before and after a treatment intervention. Therefore, although there is good evidence describing the changes in both patient-reported outcome

A novel minimally invasive ultrasound guided technique

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measures and radiological outcomes following certain common treatments such as steroid injection and rotator cuff repair, next to nothing is known about the tissue changes that result. Owing to the aforementioned limitations, we have developed a novel, minimally invasive, ultrasound-guided rotator cuff tendon sampling technique to allow for direct analysis of the full spectrum of diseased tissue. Not only does this enable better characterization of the tissue changes that occur with the onset, progression, and treatment of RCT, but it also allows access to the ideal control tissue with which to compare diseased samples. The purpose of this article is to describe a novel minimally invasive ultrasound-guided technique developed specifically to obtain biopsies of the supraspinatus footprint where the tendon attaches to the bone of the greater tuberosity of the humerus.

The biopsy technique may be performed using local anesthesia in the outpatient clinic or under general anesthesia in the operating theater. For the purposes of this article, the procedure has been described for the outpatient setting, making translation to the operating room relatively straight forward. It is important that the room has adequate space to seat the patient, provide for instrumentation, and carry out the biopsy. The surgeon performing the biopsy must be competent in performing ultrasound assessment of the rotator cuff. This can be achieved by the attendance of formal training followed by a period of independent learning according to a specifically designed protocol.21 Some useful landmarks for conducting the biopsy have been illustrated later. It is inadvisable to embark upon the use of this technique without adequate ultrasound experience.

Development

Anatomy

To develop an accurate, reproducible, safe, and well-tolerated biopsy method for sampling the rotator cuff tendons a number of factors should be considered including the sampling device used, technical aspects of the biopsy process, and participantrelated factors. A number of steps were taken to address each of these areas to ensure that each variable in the sampling process was optimized. This development process included the use of sequential models before the technique was finally successfully tested in human trial participants (REC reference number: 09/ H0605/111). It is beyond the scope of this article to describe the development process in further detail as we wish to focus on the technical details of the final validated technique.

The most frequent site for rotator cuff tear development is the bony insertion of the supraspinatus tendon. Tears typically begin at the junction between supraspinatus and the greater tuberosity, usually sparing the anterior edge (the so called “rotator cable”) which borders the rotator interval and bicipital groove anteriorly.22,23 Therefore, it is this region (approximately 5-10 mm posterior to the anterior edge of the tendon) that is biopsied. The anterior landmark, the biceps brachii tendon, is extremely useful in identifying the leading edge of the supraspinatus, as it would always lie just posterior to the groove.24 Ultrasonographically, the footprint of the supraspinatus is clearly identifiable just lateral to the articular margin on the greater tuberosity (Fig. 1). These landmarks offer clear reference points in 2 orthogonal planes that can then be used to orientate a linear ultrasound probe in the longitudinal plane of the supraspinatus tendon fibers at a point in the mid substance of the tendon approximately 5-10 mm posterior to the rotator interval. The long-axis view of the supraspinatus is demonstrated in Figure 1 with and without the biopsy needle present. Figures 2 and 3 demonstrate a normal and abnormal footprint, respectively; the smooth bony surface in the normal footprint and the obvious defect in the bony surface present in the abnormal footprint can be noted.

Informed Consent Patients undergoing tendon biopsy should be aware of exactly what the procedure entails and its associated risks. It is important to check that the patient is not allergic to local anesthetic and warn of the small risk of adverse reactions to this drug. There must also be adequate medical backup on site in case of a severe drug reaction. Obviously, the injection of the local anesthetic is slightly uncomfortable and there is a wait of 20 minutes until the biopsy is performed. It is worth warning the patient that the biopsy instrument does make a noise similar to a loud stapler and it may be worth demonstrating this noise to the patient in some cases. The patient needs to be aware that a very small skin incision of around 2 mm is made and there is a small theoretical risk of infection associated with this. It is explained that the tendon biopsy is about the size of a grain of rice and that removing this amount of tendon does not significantly alter the strength of the tendon. Although we have not seen a single case of infection or tendon rupture after more than 200 biopsies, it is important that the patient is aware that these small theoretical complications may occasionally happen. The routine recovery is explained, including the need to take things easy while the local anesthetic is in effect and the need to keep the plaster on for 24 hours. Normal activities can be resumed on the day following the biopsy.

Setting

Equipment Ultrasound machine and appropriate probe suitable for musculoskeletal ultrasound. Local anesthetic—8 ml of 2% lignocaine. Blue 23-gauge needle and 10-ml syringe (for local injection). Permanent marker pen (to circle entry point location). Sterile probe cover kit with ultrasound gel and rubber bands (Fig. 5). Scalpel (No11-type blade) (Fig. 5). Alcohol wipe. Bard Magnum Core Biopsy device with needle (14-gauge green needle of 10-cm length) (Figs. 4 and 5). Sterile drape with circular hole and adhesive under surface (Fig. 5).

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Subcutaneous Fat

Deltoid Muscle Bursa Supraspinatus Tendon Greater Tuberosity Humeral Head

Subcutaneous Fat Deltoid Muscle

Path of Biopsy Needle

Bursa Supraspinatus Tendon

Greater Tuberosity

Humeral Head

Figure 1 (A) Long-axis view of the supraspinatus footprint: diagram and ultrasound. (B) Long-axis view showing path of biopsy needle into footprint: diagram and ultrasound.

White 19-gauge needle (for approximate biopsy needle line) (Fig. 5). Appropriate pots for tendon biopsy (eg 10% formalin for fixation). Sterile gauze swabs 5 5 (Fig. 5). One small dressing. One trolley with a sterile drape. One friendly assistant (to distract patient).

Procedure—Local Anesthetic Administration

Figure 2 Long-axis ultrasound view showing normal supraspinatus footprint.

Figure 3 Long-axis ultrasound view showing abnormal supraspinatus footprint.

While facing the US machine, the patient is seated in a slightly reclined position with the procedural forearm placed behind the back. The chair used should have no arms to accommodate this position which places the arm in internal rotation and allows for direct access to the footprint of the supraspinatus for


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Figure 4 Core biopsy needle shown in open and closed positions.

biopsy. Our preference is for the surgeon to hold the ultrasound probe with the nondominant hand allowing the dominant hand to be used to operate the biopsy instrumentation. The setup positions for the right and left shoulders are demonstrated in Figures 6 and 8, respectively, assuming a right hand–dominant surgeon. The shoulder is then scanned to identify the leading edge of supraspinatus and its respective footprint. The biopsy site itself is then located 5-10 mm posterior to leading edge of the supraspinatus. The degree of internal rotation may need to be modified depending on patient anatomy. For example, if one cannot identify the leading edge of the supraspinatus using the biceps tendon as a landmark, then a reduction of internal rotation is usually sufficient to allow for adequate visualization. The anatomy is demonstrated in Figure 1 in a diagram and with

an ultrasound image. The local anesthetic is then injected into the skin, subcutaneous tissue, and subacromial bursal space. When injecting deep into the bursa, it is important to envisage the optimal angle at which the biopsy needle would be aligned relative to the supraspinatus. The infiltration of local anesthetic can be visualized on the ultrasound. Upon needle removal, a marking pen is used to identify the appropriate skin entry point for the biopsy needle. A small dressing is then applied and about 35 minutes allowed to elapse while the local anesthetic takes action. During this time, the patient may return to the waiting room while the room is then prepared for the biopsy.

Procedure—Biopsy The equipment is laid out on the trolley before the patient is brought back into the room after local anesthesia delivery. The

Figure 5 Equipment needed for biopsy, clockwise from top left— sterile probe cover kit with ultrasound gel and rubber bands, sterile drape, gauze swabs, scalpel, white needle, biopsy instrument, and biopsy needle. (Color version of the figure is available online.)

Figure 6 Biopsy of a patient’s right supraspinatus. (Color version of the figure is available online.)

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R.J. Murphy et al. applied temporarily and pressure applied to prevent any bleeding. Finally, the swab is replaced with a light dressing.

Aftercare and Patient-Reported Experiences The patient is told to keep the dressing in place for 24 hours to keep the wound clean and dry. The patient is advised to avoid any heavy or strenuous activity for the remainder of the day, while normal activities may resume on the following day. The patient is also encouraged to take paracetamol or acetaminophen for any soreness and to contact the clinical team if they have any concerns over the following days. We recently audited the experiences of 28 patients who had supraspinatus biopsies performed 3 months following subacromial decompression surgery. Most patients experienced either no pain (7 patients) or mild discomfort (12 patients) during the biopsy. Of the 9 patients who experienced pain during the biopsy, 5 described this as “some pain,” 3 as a “lot of pain,” and 1 as “considerable pain.” The only other symptoms described during the biopsy were faintness or light-headedness (3 patients). The only biopsy-related complications were mild bruising (5 patients) and mild redness (2 patients); these all resolved within 1 week of the biopsy. When asked whether they would consider having another biopsy: 9 responded “yes, definitely,” 15 “probably,” 3 were “unsure,” and 1 replied Figure 7 Right supraspinatus biopsy being performed, showing surgeon inspecting ultrasound imaging screen. (Color version of the figure is available online.)

patient is positioned as before to allow optimal visualization of the supraspinatus footprint. The surgeon practices good aseptic technique with hand washing and sterile glove application. Next, the biopsy instrument is assembled by inserting the biopsy needle into the instrument housing. The device is then cocked and the safety catch applied. Following assembly of the biopsy device, the skin is prepared and draped in a typical sterile fashion with alcohol, ChloraPrep, or similar preparatory agent. Gel is applied to the ultrasound probe by the assistant and the sterile probe cover is then applied by the surgeon and secured using rubber bands. The surgeon then applies the probe in the longitudinal axis of supraspinatus to obtain an optimal view of the biopsy site. A small stab incision is now made in the longitudinal axis of the probe in the previously marked circle. An empty 18-gauge needle is then used to rehearse the trajectory of the biopsy needle. The safety catch on the biopsy instrument is then released and the biopsy needle is introduced so as to achieve the optimal trajectory through the footprint. It is important to ensure that the needle is at the correct angle as too deep a trajectory may result in the needle hitting the bone, whereas too shallow a trajectory may result in the needle skiving off the surface of the tendon. Throughout the procedure, the surgeon must keep a very close eye on the ultrasound display to ensure that there is no loss of the positioning (Fig. 7). The biopsy instrument is then fired and the tendon specimen retrieved (Fig. 9). A gauze swab is

Figure 8 Biopsy of a patient’s left supraspinatus. (Color version of the figure is available online.)


61 As always, there is concern when conducting tissue sampling that the very act of taking tissue weakens the tendon and predisposes to subsequent tears. Nevertheless, since the inception of this technique and more than 200 biopsies, we have not found this to be the case. In fact, the information gleaned from this biopsy technique has allowed for the advancement of the genetic and molecular characterization of tendinopathy in the shoulder.25 Furthermore, with this biopsy technique, it has now become possible to study the effects of our interventions in far greater detail than was ever previously imaginable.

References Figure 9 Tendon biopsy specimen, as seen on the needle.

“probably not.” These results show that the biopsy is generally a well-tolerated procedure and that most patients would consider having another biopsy performed in the future.

Discussion As RCT is such a significant problem for the ageing population, an adequate way of studying the evolution of the pathology has become obligatory. Unfortunately, unlike the Achilles and patellar tendon, minimally invasive biopsy techniques to allow sampling of tissue without harm to the patient are lacking. Our technique of biopsy of the rotator cuff allows for direct sampling of the major tendon pathology with little risk to the patient. Figure 10 shows the histologic results of the biopsy technique with the light micrography of tendon samples from 1 individual stained with hematoxylin and eosin. There are numerous options in terms of analyzing the biopsied tendon including basic histologic stains, immunohistochemistry, and reverse transcription polymerase chain reaction.

Figure 10 Histologic section stained with hematoxylin and eosin (200 magnification).

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62 21. Murphy RJ, Daines MT, Carr AJ, et al: An independent learning method for orthopaedic surgeons performing shoulder ultrasound to identify full-thickness tears of the rotator cuff. J Bone Joint Surg Am 95:266-272, 2013 22. Hijioka A, Suzuki K, Nakamura T, et al: Degenerative change and rotator cuff tears. An anatomical study in 160 shoulders of 80 cadavers. Arch Orthop Trauma Surg 112:61-64, 1993

23. Kim HM, Dahiya N, Teefey SA, et al: Location and initiation of degenerative rotator cuff tears: An analysis of three hundred and sixty shoulders. J Bone Joint Surg Am 92:1088-1096, 2010 24. Jacobson JA: Shoulder US: Anatomy, technique, and scanning pitfalls. Radiology 260:6-16, 2011 25. Chaudhury S, Holland C, Porter D, et al: Torn human rotator cuff tendons have reduced collagen thermal properties on differential scanning calorimetry. J Orthop Res 29:1938-1943, 2011