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Di-agnosis of metastatic humeral bone lesions and alternatives for treatment vary depending on whether the pa-tient has a large impending lesion or complete fracture, which region of the

Trang 1

Frank J Frassica, MD, and Deborah A Frassica, MD

Abstract

Metastases to bone are the most

fre-quent cause of destructive lesions to

the skeleton in adults The most

com-mon primary malignancies that

me-tastasize to bone are breast, lung,

kid-ney, and prostate carcinoma The typical

distribution of metastatic lesions is to

the spine, ribs, pelvis, and proximal

limb girdles.1 However, almost any

primary malignancy may metastasize

to bone, and any bone in the body may

be involved In the upper extremity,

the most common location is the

hu-merus, usually the proximal third or

the diaphysis Lesions in the distal third

of the humerus are less common and

typically occur in patients with

my-eloma or lung or renal carcinomas

Di-agnosis of metastatic humeral bone

lesions and alternatives for treatment

vary depending on whether the

pa-tient has a large impending lesion or

complete fracture, which region of the

bone is affected, the extent of overall

disease, the histologic diagnosis, and

the nature of prior treatment

Diagnosis Presentation and Evaluation

Several distinct presentations of up-per extremity metastatic disease can occur Patients with known metastatic disease may have either an asymp-tomatic or a painful and disabling le-sion A small percentage without a known history of cancer may present with a destructive bone lesion second-ary to an occult primsecond-ary tumor Com-plete fractures secondary to metastatic lesions often occur after very minor trauma, such as rolling over the arm

in bed, a minor fall, opening a jar, or other simple activities The presence

of substantial arm or shoulder pain

in the patient with a history of can-cer indicates the possibility of bone metastases Common characteristics include pain at rest, night pain, and pain unresponsive to anti-inflam-matory medications and narcotics

During evaluation, the clinician must determine whether the pain is

secondary to bone metastases or to nononcologic sources, such as gleno-humeral arthritis or rotator cuff ten-dinosis, which also manifest as dif-fuse discomfort, night pain, difficulty with sleeping on the affected side, and limited use of the upper extremity secondary to pain Plain radiographs are the first step in evaluation An an-teroposterior view of the shoulder and humerus is done to assess the proximal half of the humerus and scapula, and a scapular axillary view

is made to evaluate the glenoid and coracoid process If the discomfort ex-hibits a radicular pattern or if the shoulder pain extends proximally into the neck, radiographs of the cer-vical spine should be obtained If plain radiographs do not show a de-structive lesion and bone metastases are suspected, technetium Tc 99m (99mTc) bone scanning or magnetic res-onance imaging (MRI) may be done

99mTc bone scanning is an excellent modality for screening the cervical spine and shoulder girdle, especially when previous scans are available for comparison MRI of the shoulder can differentiate pain secondary to

rota-Dr F Frassica is Chairman and Robert A Rob-inson Professor, Department of Orthopaedic Sur-gery, Johns Hopkins University, Baltimore, MD.

Dr D Frassica is Assistant Professor of Oncol-ogy, Department of Radiation OncolOncol-ogy, Johns Hopkins University.

Reprint requests: Dr Frank J Frassica, c/o Elaine

P Henze, Room A672, 4940 Eastern Avenue, Baltimore, MD 21224-2780.

Copyright 2003 by the American Academy of Orthopaedic Surgeons.

Metastatic bone disease is the most common cause of destructive bone lesions in

adults, and involvement of the humerus is common Patients with destructive

le-sions involving <50% of the cortex are treated nonsurgically with external beam

irradiation Patients with diaphyseal lesions involving50% of the cortex or those

with pain after irradiation can be treated with intramedullary nailing to achieve

rigid fixation Although closed intramedullary nailing is used most often, open

nail-ing with methylmethacrylate is appropriate for destructive lesions in which rigid

fixation cannot be achieved with closed nailing Plate fixation is acceptable when

adequate proximal and distal cortical bone is present for screw purchase, although

proximal humeral lesions usually are treated with prosthetic arthroplasty

Postop-erative external beam irradiation can help prevent disease progression and

subse-quent loss of fixation However, when disease progression persists or rigid internal

fixation is not feasible because of extensive bone destruction, wide resection and

re-construction with a custom prosthesis can be done.

J Am Acad Orthop Surg 2003;11:282-288

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tor cuff tendinosis from that of

met-astatic disease and can identify bone

marrow infiltration by tumor cells

and rotator cuff inflammation Short

tau inversion recovery (STIR) or a

T2-weighted fast spin-echo fat-saturated

sequence is the optimal method for

assessing tumor presence Although

computed tomography (CT) is

sensi-tive in detecting cortical bone

destruc-tion in the scapula and humerus, its

use is limited because it cannot

de-tect marrow invasion in the absence

of bone destruction However, CT is

more accurate than other diagnostic

tools in determining structural

com-promise

Criteria for Impending Fracture

Determining the risk for

patholog-ic fracture is subjective and depends

on many factors, including the

pat-tern of bone destruction, location in

the bone, response of the host bone,

and anticipated loading conditions

Most classification systems2-6used to

predict areas at risk of fracture are

based on the amount of cortical bone

destruction measured on

anteropos-terior and lateral radiographs Bone

destruction of 25% of the cortical

di-ameter has a low risk of fracture (Fig

1, A); bone destruction of 75% of the

cortical diameter is associated with a

high risk of fracture.2-4When bone

de-struction is between these extremes,

the risk of fracture is more difficult to

predict Most surgeons consider that

≥50% bone destruction indicates

im-pending fracture (Fig 1, B)

Mirels4developed a 12-point

scor-ing system based on the location,

type, and amount of bone destruction

and the presence or absence of

ac-tivity-related pain Combined scores

of 9, 8, and 7 respectively had a 33%,

15%, and 4% risk of fracture There

was a low risk of fracture in patients

with <50% cortical bone destruction

Although this is an objective scoring

method, many surgeons do not use

the Mirels system because of the

jectivity of the variables and the

sub-stantial overlap between the fracture

and nonfracture groups, which un-derscores the difficulty in predicting risk of fracture

Mirels4 showed that purely lytic bone metastases have a much higher risk of fracture than do purely blas-tic metastases (often seen in patients with metastatic breast and prostate carcinoma) However, many patients have a combination of lytic and blas-tic metastases Lesions in the proxi-mal humeral metaphysis are less prone to fracture than are those in the diaphysis or in the transition zone be-tween the metaphysis and diaphysis (in the region of the insertion of the pectoralis major muscle)

The anticipated loading of the up-per extremity is also an important consideration A patient with an iso-lated metastasis in the humerus can easily protect against overloading the upper extremity during the course of irradiation and/or chemotherapy In contrast, a patient with substantial concomitant lower-extremity disease requiring protected weight bearing

with crutches or a walker may sub-ject the upper extremity to increased loading In such a situation, internal fixation may be necessary to prevent fracture

Nonsurgical Management

Most humeral metastases that have not fractured can be managed with external beam irradiation without surgery The decision may be depen-dent on the histology of the tumor Patients are counseled to avoid pro-vocative activities that may lead to fracture while the lesion heals Pa-tients generally undergo 1 week to 2 weeks of external beam irradiation (usually 3,000 cGy in 10 fractions).7,8

If the isolated lesion occurs in a pa-tient with an excellent prognosis, a longer course of treatment may be recommended in an effort to provide more durable local control Treatment

of humeral metastases with a single dose of 800 cGy can be successful in reducing pain in patients with termi-nal disease and short life expec-tancies;9-12 this is especially useful when patient transport to the radia-tion therapy facility is difficult Al-though tumor progression generally halts after the completion of irradi-ation, activity should be modified for

2 to 3 months Patients can continue activities of daily living such as eat-ing, cleaneat-ing, batheat-ing, and changing clothes, but exertions such as tennis, changing a tire, opening tight jars, overhead throwing, and swinging an

ax are discouraged

Patients with complete fractures are poor candidates for nonsurgical treatment Fracture braces and casts are not effective in controlling dis-comfort, and patients avoid using their extremities because of pain In contrast with nonpathologic

humer-al fractures, which hehumer-al quickly, com-plete fractures secondary to

metastat-ic bone disease heal very slowly if it all Flemming and Beals13and Doug-lass et al14reported poor results with

Figure 1 A,Anteroposterior radiograph of the proximal humerus in a patient with breast cancer showing a predominantly blastic le-sion with a small amount of cortical bone de-struction This patient would be an excellent candidate for external beam irradiation.

B,Anteroposterior radiograph of a humeral lesion in a patient with metastatic prostate cancer showing ≥ 50% cortical bone destruc-tion This lesion meets the criteria of impend-ing fracture.

Trang 3

nonsurgical management of

patho-logic humeral fractures and later

characterized the results of closed

management as “unsatisfactory,

pro-ducing limited use, incomplete pain

relief, and unpredictable healing.”13

Surgical Management

Preoperative Planning

The general medical condition of

the patient must be assessed before

surgery Terminally ill patients

(antic-ipated survival, <2 to 3 weeks) are

poor candidates, unlikely to benefit

from the surgery Although there are

no absolute criteria to predict

surviv-al of the patient with metastatic bone

disease, poor prognostic factors

in-clude hypercalcemia, substantial

cy-topenia from bone marrow failure,

cachexia, and poor performance

sta-tus

Careful preoperative planning is

essential The cervical spine should

be carefully assessed for destructive

lesions so that injury can be avoided

while anesthetizing or positioning the

patient, and plain radiographs or a

re-cent 99mTc bone scan should be

re-viewed The entire humerus should

be viewed with plain radiography in

two orthogonal planes to determine

if there are multiple lesions

Position-ing the end of the fixation device at

a site of diseased bone must be

avoid-ed so that fracture does not occur in

this transition zone when the patient

begins using the extremity CT and

MRI scans generally are not needed

for preoperative planning However,

if plain radiographs are equivocal as

to the presence of cortical destruction

in regions designated to receive the

fixation device, MRI can be used to

confirm the presence of disease

Because patients with metastatic

bone disease may survive only 3 to

12 months, the goal of surgery is to

attain rigid and durable internal

fix-ation and, accordingly, immediate

postoperative use of the upper

ex-tremity Rigid fixation can be

achieved with a variety of internal fix-ation or prosthetic devices These de-vices can be used with or without methylmethacrylate Fracture healing should not be necessary to achieve functional stability

Device Selection

The selection of the reconstruction device, such as an intramedullary nail, plate, or prosthesis, depends on the area of humeral involvement and the degree of bone destruction When selecting a fixation method, it is con-venient to divide the humerus into three regions: (1) proximal metaphy-seal, (2) metadiaphyseal and diaphy-seal, and (3) distal metadiaphyseal and metaphyseal (supracondylar) (Fig 2)

Proximal Metaphyseal Region

Complete or impending fractures

of the proximal humerus usually are managed with a humeral endopros-thesis Intramedullary nails are diffi-cult to use in the proximal metaphy-sis because rigid proximal fixation cannot be achieved Plate fixation is likewise ineffective for solid fixation because of the thin and compromised cortical bone

The surgical procedure is similar

to that for a nonpathologic fracture,

in which a deltopectoral approach is used to osteotomize the humeral head For a pathologic fracture, the proximal fragments are excised The proximal humeral metaphysis is carefully curetted to remove all of the gross tumor but not the cortical shell or periosteal tissues The hu-merus is prepared through the en-tire diaphysis to receive a long-stem prosthesis The prosthesis is care-fully cemented in place so that the cement does not enter the soft tis-sues; extravasation through hu-meral defects might result in neuro-logic or vascular injury A long-stem prosthesis spanning the diaphysis to the supracondylar region is gener-ally used to maximize protection of the entire humeral shaft

Metadiaphyseal and Diaphyseal Region

Metadiaphyseal and diaphyseal lesions can be managed with either intramedullary nail or plate fixation Both methods are effective, and the choice of implant rests with the indi-vidual surgeon Each technique has specific advantages and disadvan-tages

Intramedullary Nail Fixation

In-tramedullary nailing, the most pop-ular method used for humeral shaft lesions, can be done either closed or open through an anterograde or ret-rograde approach The major advan-tage of intramedullary nail fixation is that it can protect a long segment of the humerus When augmented with methylmethacrylate, it also can pro-vide rigid fixation of a long segment

of diseased bone Other advantages include a low risk of implant failure and the fact that the nail can be placed

Figure 2 Different regions of the humerus are amenable to fixation with various

devic-es (1) Proximal metaphyseal region—head and anatomic neck region: prosthetic arthro-plasty with a Neer-type endoprosthesis; sur-gical neck: either prosthetic arthroplasty with aNeer-typeprosthesisorRushrodwithmeth-ylmethacrylate supplementation (2) Metadi-aphyseal and diMetadi-aphyseal region: intramedul-lary nailing or plate fixation (3) Distal metadiaphyseal and metaphyseal (supra-condylar) region: either plate fixation or crossed flexible nails.

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in a closed manner The major

disad-vantage of anterograde

intramedul-lary nailing is the mandatory incision

and repair of the rotator cuff Many

patients experience residual rotator

cuff tendinitis and weakness

Prom-inent hardware (proximal

interlock-ing screws or the tip of the nail) can

cause persistent symptoms.

Intramedullary nail fixation can be

used for destructive bony lesions

from 2 to 3 cm below the level of the

greater tuberosity (proximal one sixth

of the humerus) to approximately 5

cm above the olecranon fossa.15

An-terograde or retrograde nailing may

be used; care must be taken to

pro-tect areas of bone destruction.16 To

achieve rigid fixation, there must be

at least 4 to 5 cm of intramedullary

nail on either side of the lesion with

intact cortices surrounding its

prox-imal and distal ends An intramedul-lary nail can be used for more prox-imal or distal lesions if the fixation can

be made rigid with an interlocking screw or methylmethacrylate If the bone destruction occurs in the supra-condylar region of the distal

humer-us, plate fixation or crossed flexible nails can be used

The amount and location of the bone destruction must be carefully as-sessed Closed nailing is an excellent technique for both impending and complete fractures Proximal and dis-tal locking is recommended to ensure rigid fixation for complete fractures

Patients with intact cortices after nail-ing may be treated with proximal in-terlocking alone or with proximal and distal interlocking (Fig 3) With the closed technique, augmentation with methylmethacrylate generally is not necessary However, for severe bone destruction with no remaining corti-ces over a length of 3 to 6 cm, open nailing with curettage of the tumor and methylmethacrylate can be con-sidered to supplement the fixation

Open nailing is done with a tech-nique similar to closed nailing The fracture site can be approached through an anterolateral or posterior incision or, if the entire humerus needs to be exposed, through a del-topectoral approach proximally and the anterolateral approach distally A portion of the deltoid insertion is el-evated off the humerus, and the bra-chialis muscle is split to expose the humeral shaft After either exposure,

a cortical window is made through the area of bone destruction, and all

of the gross tumor is removed with curettes The humerus is prepared to receive the nail, as in the closed tech-nique The open fixation can be sup-plemented with methylmethacrylate (Fig 4)

After the nail is inserted over a guide wire, the entire humerus is im-aged to verify satisfactory length and fracture reduction The nail is then withdrawn into the proximal frag-ment to a level just above the point

where the cement augmentation is to end The cement is mixed, placed in the cement gun, and injected through

a small insertion tube first into the distal fragment, then the proximal fragment The guide wire is

general-ly left in the proximal and distal frag-ments The fracture is reduced and the nail advanced into the distal frag-ment Interlocking screws then can be placed if necessary If sufficient ce-ment has been injected into the dis-tal fragment to secure the nail, an interlocking screw can be placed proximally to augment stability in the proximal fragment

Plate Fixation Plate fixation is also

an acceptable technique for impend-ing and complete fractures of the proximal metadiaphyseal and di-aphyseal region (Fig 5) A major ad-vantage of plate fixation is that the ro-tator cuff is not disturbed as it is with anterograde intramedullary nailing Disadvantages of plate fixation in-clude more blood loss than with

Figure 3 A, Anteroposterior radiograph

showing a destructive humeral diaphyseal

le-sion with ≥ 50% cortical bone destruction.

B,The lesion was managed with closed

in-tramedullary nailing with proximal

interlock-ing Distal interlocking was not used because

the medial cortex was intact after nail

place-ment.

Figure 4 A, Anteroposterior radiograph showing a pathologic fracture with >90%

cor-tical bone destruction B, The fracture was

man-aged with open nailing, methylmethacrylate supplementation, and proximal interlocking.

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closed nailing, the potential for

radi-al nerve injury, and inability to

pro-tect as much humeral length as with

intramedullary nailing.16When

con-sidering plate fixation, the

radio-graphs must be studied carefully to

determine that at least three screws

can be placed in normal cortical bone

on either side of the fracture When

there is diffuse involvement of the

hu-merus, intramedullary nailing is a

better choice because a plate may not

provide solid fixation

The exposure for plate fixation can

be done through an anterolateral or

posterior approach A cortical

win-dow is created large enough to curette

the gross tumor Care must be taken

not to remove an excessive amount

of normal bone; otherwise, it will be

difficult to achieve rigid fixation in the

remaining cortical bone The cement

can be applied before or after the in-ternal fixation, but it is easier to re-duce the fracture and place the inter-nal fixation device first To obtain good apposition of bone ends, irreg-ular fracture ends can be shortened

if necessary Once the plate is applied, the screws that span the defect are re-moved, and cement is placed by hand into the defect The screws can be re-placed while the cement is curing or

by drilling and tapping once the ce-ment hardens

Distal Metadiaphyseal and Metaphyseal Region

Lesions within 2 to 4 cm of the olecranon fossa are best managed with plate fixation Neither anterograde nor retrograde nails can provide rigid fix-ation in these distal lesions Plating through a posterior triceps muscle–

splitting approach is very effective when the distal fragment is large enough to receive three 4.5-mm screws Distal lesions that involve the supracondylar area are difficult to manage Fixation can be achieved with medial and lateral plates, flexible nails inserted from the epicondyles, or pros-thetic arthroplasty

Postoperative Management

After prophylactic fixation or sur-gical treatment of a pathologic frac-ture, radiation therapy to the site of the lesion and the implanted device

is recommended to decrease the risk

of continued bone destruction (which could lead to increased pain), loosen-ing of the fixation, and the need for additional surgery.17In a study of 64 procedures in 60 patients, Townsend

et al17found that the addition of ex-ternal beam irradiation to surgery

sig-nificantly (P = 0.02) improved

func-tional outcome There was also a

significantly (P = 0.035) higher risk of

the need for a second surgical proce-dure in patients who did not receive postoperative radiation The dose of radiation is similar to that used when treating patients nonsurgically (3,000 cGy in 10 fractions over 1 week to 2

weeks) Treatment is generally de-layed to 10 days after surgery so that the skin incision can heal

Patients may begin range of mo-tion movement of the elbow and shoulder during the first postopera-tive week If the patient has not pre-viously undergone radiation therapy, the sutures or staples are removed 2 weeks after surgery If the patient has previously received radiation, the su-tures are left in place for

approximate-ly 4 weeks

Alternative Surgical Techniques

Rush rods can be used for very proximal (within 3 cm of the

humer-al head) fractures at the surgichumer-al neck.18 There is too little proximal bone in this region for intramedullary nail fixation The proximal hook of the Rush rod is anchored in the rotator cuff, and the fixation is

supplement-Figure 5 A,Anteroposterior radiograph of

a patient with prostate cancer showing a

met-astatic diaphyseal lesion with >90% cortical

bone destruction B, The lesion was managed

with plate fixation and methylmethacrylate

augmentation.

Figure 6 A humeral lesion in a patient with metastatic renal cell cancer was treated with intramedullary nailing and external beam

ir-radiation A, Anteroposterior radiograph

show-ing disease progression and fracture (arrow) around the nail just below the locking screw.

B,The patient was treated with resection and custom proximal humeral arthroplasty.

Trang 6

ed with methylmethacrylate If the

hook protrudes, it can cause

symp-toms with overhead activity; if it is

driven through the proximal cortical

bone, there will be less purchase in

the proximal fragment Flexible nails

also have been used for diaphyseal

and proximal metadiaphyseal

le-sions.19

Custom proximal humeral

prosthe-ses can be used selectively when large

segments of bone need to be resected.20

Resection is usually reserved for

pa-tients with progressive disease after

external beam irradiation or in patients

with failed internal fixation and poor

bone stock Some custom modular

de-vices allow the restoration of length

of the humerus with immediate rigid

fixation after resection of variable

lengths of the proximal humerus (Fig

6) Other devices have been designed

to permit resection and reconstruction

of the diaphysis in the presence of an

intact proximal humeral segment.21

These designs, with medullary stems

cemented into the proximal and

dis-tal intramedullary canals, are still in

development and are associated with

complication rates as high as 25%.22

Results

Pain relief can be reliably obtained in

>90% of patients treated with rigid fixation.21-23 Redmond et al15 de-scribed good to excellent pain relief

in 12 of 13 patients treated with in-tramedullary nail fixation for

humer-al pathologic fractures In 10 patients with documented postoperative range of motion, there was a mean of 101° of abduction (range, 55° to 180°) and a mean of 98° of forward flexion (range, 45° to 170°) Of the 13 patients,

11 recovered use of the arm for activ-ities of daily living.15Dijkstra et al16

retrospectively compared nail and plate fixation in 37 patients with 38 pathologic humeral fractures There was good to excellent subjective pain relief in approximately 90% of the pa-tients treated with either method The authors also reported early fixation failure secondary to angular

deformi-ty and rotational instabilideformi-ty in patients treated with intramedullary nails without proximal and distal lock-ing.16Most treatment failures are sec-ondary to disease progression or

ear-ly loss of fixation.17Patients with renal

cell carcinoma are especially prone to disease progression and often are treated with higher initial doses of ra-diation (4,500 cGy) to reduce the risk

of early failure

Summary

Metastatic disease of the humerus is common, and effective management can improve the quality of life for can-cer patients Nonsurgical treatment with external beam irradiation is used for symptomatic lesions with <50% cortical bone destruction With≥50% cortical bone destruction, intramed-ullary nailing is the most common method of both prophylactic and frac-ture fixation Locked intramedullary nails can provide rigid fixation with early pain relief Methylmethacrylate can be used to aid in the reconstruc-tion of defects caused by the surgi-cal treatment of large lesions and to improve fixation Plate fixation also can be used for diaphyseal and dis-tal lesions Immediate rigid fixation

is necessary to achieve consistently good pain relief

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