Diagnostic

Accuracy

of

Fine

Needle

Biopsy

for

Metastatic

Melanoma

and

Its

Implications

for

Patient

Management

Background

The

use

of

fine

needle

biopsy

-LRB-

FNB

-RRB-

for

the

diagnosis

of

metastatic

melanoma

can

lead

to

the

early

removal

and

treatment

of

metastases

reduce

the

frequency

of

unnecessary

surgery

and

facilitate

the

staging

of

patients

enrolled

in

clinical

trials

of

adjuvant

therapies

In

this

study

the

accuracy

of

FNB

for

the

diagnosis

of

metastatic

melanoma

was

investigated

Fine

needle

biopsy

-LRB-

FNB

-RRB-

is

frequently

used

in

the

diagnostic

workup

of

clinically

or

radiologically

detected

mass

lesions

that

are

suspicious

for

metastatic

melanoma

By

determining

whether

they

represent

metastatic

melanoma

the

use

of

FNB

in

melanoma

patients

can

expedite

detection

of

metastases

leading

to

earlier

removal

and

treatment

facilitate

the

staging

of

patients

enrolled

in

clinical

trials

of

adjuvant

therapies

-LRB-

particularly

in

deep-seated

lesions

-RRB-

reduce

the

frequency

of

unnecessary

surgery

and

assist

in

the

planning

of

the

most

appropriate

surgery

FNB

is

a

swift

minimally

invasive

and

cost-effective

technique

employed

in

the

diagnostic

workup

of

mass

lesions

occurring

in

a

wide

variety

of

organs

The

technique

has

been

extensively

evaluated

in

assessing

the

nature

of

lesions

located

in

the

tissues

of

the

breast

thyroid

lung

liver

pancreas

lymph

nodes

salivary

glands

and

kidneys

among

other

locations

There

have

been

several

previous

case

studies

assessing

the

use

of

FNB

in

patients

with

melanoma

The

majority

of

these

studies

lacked

sufficient

case

numbers

to

precisely

determine

the

diagnostic

accuracy

of

FNB

However

in

Perry

and

analyzed

almost

FNBs

from

melanoma

patients

and

found

the

procedure

to

be

accurate

with

a

sensitivity

of

and

a

specificity

of

Since

this

study

there

have

been

important

changes

in

the

procedure

including

improvements

in

immunochemical

characterization

and

radiological

guidance

In

Voit

and

published

a

study

of

FNBs

from

melanoma

patients

with

palpable

suspicious

lymph

nodes

or

small

lesions

that

were

only

detectable

by

ultrasound

B-scan

examination

Although

the

authors

reported

a

sensitivity

of

and

a

specificity

of

the

sensitivity

depended

on

lesion

size

The

objective

of

this

retrospective

cohort

study

was

to

evaluate

the

diagnostic

accuracy

of

the

FNB

procedure

in

the

detection

of

metastatic

melanoma

To

accomplish

this

a

very

large

consecutive

sample

was

collected

of

FNBs

performed

on

melanoma

patients

who

attended

the

Sydney

Melanoma

Unit

-LRB-

SMU

-RRB-

Sydney

Australia

This

large

sample

also

allowed

evaluation

of

the

effect

of

several

clinicopathologic

features

and

factors

related

to

the

procedure

on

the

diagnostic

accuracy

of

FNB

MATERIALS

AND

METHODS

Patients

For

all

patients

with

melanoma

who

attended

the

SMU

and

gave

informed

consent

clinical

and

histologic

details

of

their

disease

were

recorded

on

the

SMU

database

and

follow-up

information

was

entered

prospectively

Patients

with

suspicious

clinically

palpable

or

radiologically

identified

mass

lesions

detected

by

a

variety

of

imaging

modalities

were

further

investigated

by

FNB

All

SMU

patients

who

underwent

an

FNB

that

had

been

reported

by

cytopathologists

from

the

Department

of

Anatomical

Pathology

at

the

Royal

Prince

Alfred

Hospital

in

Sydney

Australia

between

January

and

December

were

identified

from

the

SMU

database

and

their

clinical

records

and

FNB

reports

were

reviewed

Details

of

the

patients

are

provided

in

Table

TABLE

Patient

characteristicsCharacteristicn

Sex

Age

at

melanoma

diagnosis

-LRB-

y

-RRB-

Cancer

diagnosis

Other

cancer

More

than

one

other

cancer

No

of

primary

melanoma

lesions

No

of

FNBs

Total

no

of

FNB

fine

needle

aspiration

biopsy

FNB

Procedure

For

palpable

lesions

the

FNBs

were

performed

by

the

reporting

cytopathologist

or

a

trainee

pathologist

under

their

supervision

Following

localization

and

stabilization

of

the

lesion

with

one

hand

a

hollow

bore

needle

-LRB-

or

-RRB-

was

inserted

directly

into

the

mass

and

the

needle

was

moved

swiftly

in

and

out

for

approximately

seconds

Aspiration

with

a

syringe

was

not

used

in

the

vast

majority

of

cases

hence

our

preference

for

the

term

fine

needle

biopsy

and

fine

needle

aspiration

biopsy

In

our

experience

the

use

of

a

needle

without

an

attached

syringe

allows

better

control

of

the

movement

of

the

needle

Furthermore

aspiration

often

yields

blood

promotes

clotting

and

hampers

optimal

interpretation

of

cytologic

detail

The

procured

material

was

ejected

from

the

needle

onto

glass

slides

by

pushing

air

from

a

syringe

through

the

needle

The

material

was

spread

evenly

across

the

slide

using

another

glass

slide

One

slide

was

air-dried

and

stained

immediately

with

Diff-Quik

-LRB-

Lab

Aids

Narrabeen

NSW

Australia

-RRB-

and

another

fixed

in

alcohol

and

later

stained

by

the

Papanicolaou

method

Residual

material

was

washed

into

Hanks

balanced

salt

solution

for

later

preparation

of

cell

blocks

using

the

serum-prothrombin

or

by

cytocentrifuge

preparations

to

be

used

for

immunochemistry

The

air-dried

slides

were

examined

by

the

cytopathologist

at

the

time

of

the

procedure

Further

passes

were

performed

if

necessary

depending

on

the

amount

and

type

of

cellular

material

obtained

Review

of

Clinical

Material

and

Follow-up

The

accuracy

of

the

FNB

procedure

in

diagnosing

metastatic

melanoma

was

evaluated

by

two

reference

standards

a

-RRB-

histopathologic

evaluation

of

the

excised

lesion

-LRB-

cases

-RRB-

or

b

-RRB-

follow-up

in

those

cases

for

which

histologic

material

was

not

available

-LRB-

cases

-RRB-

The

duration

of

follow-up

was

months

or

greater

-LRB-

mean

months

median

months

range

months

-RRB-

in

cases

In

six

cases

the

length

of

follow-up

was

less

than

months

-LRB-

mean

months

median

months

range

months

-RRB-

The

mass

was

considered

benign

if

it

was

stable

in

size

or

resolved

after

clinical

follow-up

Cytodiagnosis

Cytodiagnoses

were

categorized

as

positive

suspicious

or

negative

for

metastatic

melanoma

-LRB-

Table

-RRB-

Cases

were

considered

positive

for

metastatic

melanoma

if

the

specimen

included

sufficient

numbers

of

well-preserved

malignant

cells

with

typical

cytological

features

pigment

and/or

confirmatory

immunochemistry

for

a

confident

diagnosis

of

melanoma

to

be

made

On

verification

these

samples

were

classified

as

truly

positive

-LRB-

n

-RRB-

or

falsely

positive

-LRB-

n

-RRB-

TABLE

Categories

of

cytodiagnosesCharacteristicTotal

n

ConfirmedNot

confirmedPositive

for

Metastatic

Melanoma

Malignant

cells

Suspicious

for

Metastatic

Melanoma

Malignant

cells

suspicious

for

Malignant

cells

unknown

Suspicious

for

Negative

for

Metastatic

Melanoma

Malignant

cells

other

No

malignant

cells

other

cells

No

malignant

cells

scant

other

No

malignant

cells

no

other

No

malignant

cells

procedure

not

Samples

that

contained

cells

from

unclassified/unspecified

malignancies

or

cases

categorized

as

suspicious

for

melanoma

-LRB-

those

with

small

numbers

of

atypical

cells

poorly

preserved

cells

and

cells

that

lacked

specific

features

of

melanoma

such

as

cytoplasmic

pigment

and

where

insufficient

material

was

present

for

immunochemistry

-RRB-

were

classified

as

suspicious

for

metastatic

melanoma

These

were

determined

to

be

true

suspicious

-LRB-

n

-RRB-

or

falsely

suspicious

-LRB-

n

-RRB-

results

after

verification

FNBs

classified

as

negative

for

metastatic

melanoma

contained

no

material

that

could

be

diagnosed

as

metastatic

melanoma

They

included

cases

containing

malignant

cells

diagnosed

as

another

neoplasm

or

b

-RRB-

various

amounts

of

cellular

material

from

the

tissue

of

the

site

that

was

sampled

After

verification

these

procedures

were

found

to

be

either

true

negative

-LRB-

n

-RRB-

or

false

negative

-LRB-

n

-RRB-

Statistical

Analysis

All

analyses

were

performed

using

the

S-PLUS

software

package

-LRB-

Insightful

Corporation

Seattle

WA

-RRB-

and

Microsoft

Excel

version

-LRB-

Microsoft

Redmond

WA

-RRB-

Diagnostic

accuracy

of

FNB

for

metastatic

melanoma

was

measured

by

the

sensitivity

and

specificity

of

the

test

The

effect

of

the

type

of

tissue

involved

by

melanoma

anatomic

location

and

clinicopathologic

and

procedural

factors

were

analyzed

These

factors

included

features

of

the

primary

melanoma

such

as

tumor

thickness

dermal

mitotic

rate

presence

of

ulceration

predominant

cell

type

and

histopathologic

subtype

of

melanoma

patient

attributes

such

as

sex

American

Joint

Committee

on

Cancer

-LRB-

AJCC

-RRB-

International

Union

Against

Cancer

-LRB-

UICC

-RRB-

stage

age

at

FNB

and

location

of

the

FNB

-LRB-

local

or

distant

to

the

primary

lesion

-RRB-

aspects

of

the

FNB

procedure

such

as

number

of

needle

passes

needle

size

the

experience

-LRB-

based

on

caseload

-RRB-

of

the

reporting

cytopathologist

year

of

procedure

use

of

immunostains

and

presence

of

necrosis

Statistical

significance

was

determined

by

the

confidence

intervals

-LRB-

CIs

-RRB-

of

these

parameters

When

comparing

different

samples

a

two-sample

test

for

binomial

proportions

was

used

All

equations

used

have

been

described

elsewhere

RESULTS

In

the

study

period

consecutive

FNBs

were

performed

in

patients

Nineteen

FNBs

-LRB-

of

all

FNB

cases

-RRB-

were

excluded

from

the

analysis

because

the

procedure

could

not

be

performed

i.e.

no

aspirate

was

obtained

-LRB-

Table

-RRB-

In

half

of

these

cases

the

lesion

could

not

be

located

-LRB-

inappropriate

referrals

-RRB-

but

patient

pain

tolerance

and

difficulties

with

the

procedure

also

contributed

TABLE

Fine

needle

biopsy

procedures

that

could

not

be

performedLocationExplanation

for

failureConfirmationHistologyLeft

neckUnable

to

locate

lesionNegative

follow-up

Left

face

-LRB-

subcutis

-RRB-

PainNot

confirmed

Right

faceUnable

to

locate

lesionNot

confirmed

Left

neck

-LRB-

LN

-RRB-

Unable

to

locate

lesionNegative

surgeryNo

evidence

of

malignancyRight

breastAdjacent

to

prothesisNegative

follow-up

Right

neckPainNot

confirmed

Right

axilla

-LRB-

LN

-RRB-

Unable

to

locate

lesionNegative

follow-up

Right

neckPainNegative

surgeryNo

evidence

of

malignancyLeft

neck

-LRB-

LN

-RRB-

PainNegative

follow-up

Left

neck

-LRB-

LN

-RRB-

Unable

to

locate

lesionNegative

follow-up

Right

groinPainNegative

surgeryNo

evidence

of

malignancyLeft

axilla

-LRB-

LN

-RRB-

Unable

to

locate

lesionPositive

surgeryMelanomaRight

axilla

-LRB-

LN

-RRB-

Unable

to

locate

lesionNegative

follow-up

Right

neck

-LRB-

LN

-RRB-

PainNot

confirmed

Left

axilla

-LRB-

LN

-RRB-

Unable

to

locate

lesionNot

confirmed

Left

neckUnable

to

locate

lesionNegative

follow-up

ThyroidUnable

to

locate

lesionNegative

follow-up

Right

axilla

-LRB-

LN

-RRB-

Unable

to

locate

lesionNegative

follow-up

Right

sternum

-LRB-

LN

-RRB-

Unable

to

locate

lesionNot

confirmed

LN

lymph

node

Verification

of

the

remaining

FNBs

was

partial

in

-LRB-

-RRB-

the

true

disease

status

was

confirmable

by

either

histopathologic

evaluation

of

the

excised

lesion

or

by

clinical

follow-up

-LRB-

Fig.

-RRB-

A

total

of

FNBs

were

verified

by

histopathologic

evaluation

of

the

excised

lesion

all

confirmed

positive

FNBs

and

FNBs

with

false-positive

or

negative

results

were

verified

histologically

In

those

cases

-LRB-

mostly

FNBs

with

negative

results

-RRB-

where

histopathologic

material

was

not

available

-LRB-

cases

-RRB-

verification

was

made

by

clinical

follow-up

The

mass

was

considered

benign

if

it

was

stable

in

size

or

if

it

resolved

after

clinical

follow-up

The

duration

of

follow-up

was

months

in

cases

and

to

months

in

cases

Of

the

verified

FNBs

-LRB-

-RRB-

were

palpation-guided

FNBs

performed

by

trainee

cytopathologists

or

cytopathologists

while

-LRB-

-RRB-

were

image-guided

FNBs

performed

by

radiologists

or

other

physicians

FIG.

Flow

diagram

showing

fine

needle

biopsy

-LRB-

FNB

-RRB-

result

distribution

A

total

of

FNBs

-LRB-

-RRB-

could

not

be

verified

this

was

due

to

loss

to

follow-up

particularly

by

death

in

patients

with

advanced

metastatic

melanoma

uncertainty

regarding

sites

-LRB-

where

FNBs

from

more

than

one

site

were

obtained

at

the

same

visit

to

the

clinic

-RRB-

and

where

there

were

multiple

metastases

which

led

to

uncertainty

in

lesion

location

and

the

correlation

of

FNB

and

histopathologic

results

Unconfirmed

FNBs

differed

from

confirmed

procedures

in

several

ways

They

were

more

likely

to

be

from

lesions

located

in

visceral

organs

or

to

be

in

patients

with

AJCC/UICC

stage

IV

disease

FNBs

with

inconclusive

cytodiagnoses

were

more

likely

to

be

followed

up

with

clinical

observation

or

further

biopsy

Confirmation

of

FNBs

was

unaffected

by

the

year

of

procedure

the

number

of

needle

passes

during

sampling

the

use

of

immunostains

the

reporting

cytopathologist

or

the

age

or

sex

of

the

patient

Approximately

of

the

patients

were

diagnosed

with

additional

cancers

-LRB-

most

commonly

breast

cancer

colorectal

cancer

and

chronic

lymphocytic

leukaemia

-RRB-

with

some

suffering

from

multiple

types

of

other

cancers

Multiple

primary

melanomas

occurred

in

an

eighth

of

this

patient

population

Almost

a

third

of

the

patients

underwent

multiple

FNBs

These

procedures

were

performed

both

concurrently

and

sequentially

There

were

FNB

procedures

for

metastatic

melanoma

with

histologic

verification

or

clinical

follow-up

The

overall

sensitivity

was

-LRB-

CI

-RRB-

and

the

specificity

was

-LRB-

CI

-RRB-

Five

cases

were

determined

to

be

false

positive

resulting

in

a

false-positive

rate

of

-LRB-

Table

-RRB-

The

false-negative

rate

was

with

no

metastatic

melanoma

identified

in

FNB

cases

in

which

metastatic

melanoma

was

identified

by

later

histologic

evaluation

-LRB-

Fig.

-RRB-

TABLE

fine

needle

biopsy

findings

for

metastatic

melanomaCytodiagnosisHistologyLocationCommentMelanomaMetastatic

adenocarcinomaRight

axillary

-LRB-

LN

-RRB-

MelanomaMetastatic

papillary

carcinomaLeft

supraclavicular

fossa

-LRB-

LN

-RRB-

MelanomaHematomaLeft

axilla

MelanomaChronic

osteomyelitisLeft

skull

-LRB-

bone

-RRB-

positiveaMelanomaMetastatic

adenocarcinomaRight

axilla

LN

lymph

histiocytes

were

identified

in

the

excision

specimen

which

probably

caused

the

misdiagnosis.FIG

Distribution

of

false-negative

fine

needle

biopsy

-LRB-

FNB

-RRB-

cytodiagnoses

The

large

numbers

of

confirmed

cases

permitted

detailed

analysis

of

this

procedure

for

metastatic

melanoma

The

effect

of

FNB

site

was

studied

-LRB-

Table

-RRB-

Lymph

node

tissue

was

the

most

common

site

for

FNB

evaluation

with

procedures

of

them

confirmed

The

sensitivity

and

specificity

of

FNB

for

metastatic

melanoma

in

lymph

nodes

were

not

significantly

different

compared

with

that

for

all

sites

However

the

sensitivity

for

FNBs

performed

on

lymph

nodes

located

in

the

axilla

was

approximately

less

compared

with

FNBs

performed

on

lymph

nodes

in

other

locations

-LRB-

z

P

-RRB-

Increased

FNB

sensitivity

-LRB-

by

-RRB-

was

found

when

the

procedure

was

performed

on

lesions

located

in

the

skin

and

subcutis

compared

with

other

sites

However

this

was

only

of

borderline

significance

-LRB-

z

P

-RRB-

Too

few

confirmed

FNBs

were

conducted

on

visceral

organs

-LRB-

n

-RRB-

to

allow

conclusions

to

be

drawn

regarding

the

success

of

the

procedure

in

these

locations

TABLE

Diagnostic

accuracy

of

FNB

Effect

of

tissue

type

and

anatomic

locationLocationnConfirmed

TPFNTSFSFPTNSn

-LRB-

CI

-RRB-

Sp

-LRB-

CI

-RRB-

All

-LRB-

-RRB-

-LRB-

-RRB-

Lymph

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

a

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Skin

and

b

-LRB-

-RRB-

Head

and

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Visceral

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

TP

true

positive

FN

false

negative

TS

true

suspicious

FN

false

suspicious

FP

false

positive

TN

true

negative

SN

sensitivity

SP

specificity

CI

confidence

interval.aAxilla

lymph

nodes

had

significantly

reduced

sensitivity

compared

with

other

sites

-LRB-

z

P

-RRB-

bSkin

and

subcutis

FNBs

had

significantly

increased

sensitivity

compared

with

other

sites

-LRB-

z

P

-RRB-

Fifteen

clinicopathologic

and

procedural

factors

were

analyzed

to

assess

their

effect

on

the

diagnostic

accuracy

of

FNB

for

metastatic

melanoma

-LRB-

Table

-RRB-

The

FNB

confirmation

rate

was

similar

for

all

clinicopathologic

factors

with

the

exception

of

AJCC/UICC

stage

and

location

-LRB-

distant

or

regional

to

the

primary

lesion

-RRB-

as

described

above

TABLE

Diagnostic

accuracy

of

fine

needle

biopsy

effect

of

clinicopathologic

factorsFactorNConfirmed

TPFNTSFSFPTNSN

-LRB-

CI

-RRB-

SP

-LRB-

CI

-RRB-

All

-LRB-

-RRB-

-LRB-

-RRB-

AJCC/UICC

stage

at

FNB

Stage

-LRB-

-RRB-

-LRB-

-RRB-

Stage

-LRB-

-RRB-

-LRB-

-RRB-

Stage

-LRB-

-RRB-

-LRB-

-RRB-

Stage

-LRB-

-RRB-

-LRB-

-RRB-

Location

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Use

of

immunochemistry

a

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Year

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Sex

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Age

at

FNB

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

No

of

FNB

attempts

b

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Needle

sizec

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Necrosis

present

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Pathologist

caseload

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

d

-LRB-

-RRB-

-LRB-

-RRB-

First

primary

Breslow

thickness

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

First

primary

ulceration

e

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

First

primary

lesion

mitotic

rate

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

to

-LRB-

-RRB-

-LRB-

-RRB-

to

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

First

primary

lesion

histologic

subtype

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

First

primary

lesion

predominant

cell

type

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

TP

true

positive

FN

false

negative

TS

true

suspicious

FN

false

negative

FP

false

positive

TN

true

negative

SN

sensitivity

SP

specificity

CI

confidence

interval

SSM

superficial

spreading

melanoma

NM

nodular

melanoma.aFNBs

that

used

immunostains

had

significantly

increased

sensitivity

compared

with

those

that

did

not

-LRB-

z

P

-RRB-

bFNBs

obtained

in

one

pass

had

significantly

increased

sensitivity

compared

with

FNBs

which

required

more

than

one

pass

-LRB-

z

P

-RRB-

cThe

size

of

the

needle

used

for

the

FNB

procedure

was

not

known

in

cases.dFNBs

reviewed

by

a

cytopathologist

who

reported

cases

had

significantly

increased

sensitivity

compared

with

FNBs

reported

by

cytopathologists

who

had

reported

cases

-LRB-

z

P

-RRB-

eFNBs

obtained

from

patients

with

an

ulcerated

first

primary

lesion

had

increased

sensitivity

compared

with

FNBs

from

patients

without

ulcerated

first

primary

lesions

-LRB-

z

P

-RRB-

Patients

with

an

ulcerated

primary

lesion

experienced

slightly

better

FNB

test

sensitivity

compared

to

those

with

no

ulceration

-LRB-

z

P

-RRB-

AJCC/UICC

stage

anatomic

location

year

of

procedure

needle

size

sex

age

at

FNB

primary

lesion

thickness

dermal

mitotic

rate

predominant

cell

type

histologic

subtype

of

melanoma

and

presence

of

necrosis

did

not

affect

the

diagnostic

accuracy

of

the

test

-LRB-

Table

-RRB-

Three

factors

related

to

the

conduct

of

the

procedure

affected

FNB

test

accuracy

These

were

the

number

of

needle

passes

needed

to

collect

the

sample

the

number

of

FNBs

for

metastatic

melanoma

the

cytopathologist

had

reported

during

the

study

period

-LRB-

caseload

-RRB-

and

the

use

of

immunostains

Samples

that

required

only

one

attempt

at

FNB

had

a

sensitivity

increase

by

compared

to

samples

with

more

than

one

attempt

-LRB-

z

P

-RRB-

Sensitivity

fell

in

a

linear

manner

with

each

subsequent

attempt

-LRB-

Fig.

-RRB-

Cytopathologists

who

had

caseloads

of

FNBs

-LRB-

cytopathologists

-RRB-

had

greater

FNB

test

sensitivity

by

about

compared

to

those

who

had

reported

FNBs

-LRB-

cytopathologists

-RRB-

-LRB-

z

P

-RRB-

Finally

FNB

tests

in

which

immunostains

were

used

had

better

sensitivity

-LRB-

z

P

-RRB-

-LRB-

Table

-RRB-

FIG.

Sensitivity

of

fine

needle

biopsy

-LRB-

FNB

-RRB-

in

the

diagnosis

of

metastatic

melanoma

Sensitivity

is

reduced

in

a

linear

manner

as

the

number

of

FNB

attempts

needed

to

obtain

the

sample

increases

Bars

confidence

intervals

DISCUSSION

Metastatic

melanoma

is

an

aggressive

tumor

with

a

high

mortality

rate

Patients

with

primary

melanomas

that

are

at

high

risk

of

metastasizing

who

attend

the

SMU

are

followed

closely

for

evidence

of

metastatic

disease

with

radiological

investigations

and

regular

clinical

follow-up

Early

surgery

for

metastatic

disease

may

lead

to

longer

disease-free

periods

and

may

ultimately

improve

survival

in

some

of

these

patients

This

underscores

the

importance

of

early

detection

of

metastatic

disease

In

some

melanoma

treatment

centers

FNB

has

been

used

for

many

years

to

verify

clinically

suspicious

lesions

and

radiological

abnormalities

in

patients

with

melanoma

prior

to

traumatic

or

costly

surgical

or

adjuvant

treatment

FNB

is

a

cost-effective

rapid

procedure

that

is

well

tolerated

by

patients

when

performed

by

proficient

operators

However

the

ability

of

the

test

to

accurately

diagnose

suspicious

lesions

as

metastatic

melanoma

has

been

infrequently

studied

Sensitivity

and

specificity

are

measures

that

are

used

extensively

in

the

FNB

literature

They

were

chosen

as

the

best

measures

of

diagnostic

accuracy

of

FNBs

in

patients

with

melanoma

because

of

the

binary

quality

of

the

data

In

this

study

a

large

number

of

consecutive

FNB

procedures

-LRB-

-RRB-

for

metastatic

melanoma

were

analyzed

with

procedures

confirmed

by

either

histopathology

after

surgical

resection

or

by

clinical

follow-up

This

cohort

represents

more

FNB

procedures

in

melanoma

patients

than

all

previous

reported

series

combined

The

overall

sensitivity

of

FNB

for

metastatic

melanoma

was

and

the

specificity

was

These

results

are

superior

to

those

obtained

by

Perry

and

in

their

study

of

-LRB-

confirmed

-RRB-

cases

of

metastatic

melanoma

FNB

more

than

years

ago

-LRB-

sensitivity

of

and

specificity

of

-RRB-

Other

similar

case

series

did

not

have

the

power

to

determine

the

true

diagnostic

accuracy

of

FNB

because

of

their

low

numbers

of

FNBs

-LRB-

between

and

confirmed

cases

-RRB-

Voit

and

examined

FNBs

for

metastatic

melanoma

and

found

the

technique

to

be

highly

sensitive

-LRB-

-RRB-

at

their

institution

However

regional

node

basins

in

their

patient

population

were

routinely

evaluated

by

ultrasound

B-scan

and

a

third

of

FNB

cases

were

performed

under

ultrasound

guidance

Studies

of

FNB

are

frequently

retrospective

investigations

and

thus

verification

bias

may

be

a

hazard

in

these

studies

Not

only

are

there

different

reference

tests

which

are

determined

by

the

results

of

the

FNB

procedure

namely

histopathology

after

surgical

resection

for

all

positive

FNB

tests

and

clinical

follow-up

for

most

negative

procedures

but

verification

is

also

partial

Not

every

consecutive

FNB

can

be

verified

Differential

verification

can

lead

to

overestimation

of

the

measures

of

diagnostic

accuracy

This

bias

is

related

to

the

quality

of

the

reference

tests

Confirmation

of

melanoma

metastases

by

histopathologic

examination

of

tissue

removed

after

surgery

is

better

at

identifying

true

disease

status

than

clinical

follow-up

of

patients

with

negative

FNB

results

Melanoma

metastases

may

regress

spontaneously

resulting

in

failure

to

identify

all

false-negative

results

by

clinical

follow-up

or

they

may

cause

truly

positive

findings

to

be

incorrectly

classified

as

false

positives

if

the

lesion

resolves

before

it

is

excised

or

during

In

this

study

there

were

differences

in

those

FNBs

that

were

verified

by

the

reference

tests

compared

with

those

that

were

not

Unconfirmed

FNBs

were

more

often

performed

on

nonpalpable

lesions

in

visceral

sites

and

in

patients

with

advanced

disease

Verification

rates

of

negative

positive

and

suspicious

FNBs

were

and

respectively

Despite

the

high

specificity

rate

as

a

result

of

the

large

number

of

confirmed

biopsy

samples

five

false-positive

findings

were

detected

-LRB-

Table

-RRB-

The

cytologic

features

of

these

cases

have

been

reviewed

in

more

detail

elsewhere

In

all

cases

misinterpretation

of

the

cellular

material

had

occurred

three

of

which

were

found

to

be

adenocarcinoma

Two

of

these

represented

metastatic

breast

adenocarcinoma

in

axillary

nodes

and

one

was

a

metastatic

papillary

adenocarcinoma

of

renal

origin

Two

other

false-positive

cases

were

caused

by

the

misinterpretation

of

large

histiocytes

or

reactive

fibroblasts

as

metastatic

melanoma

cells

In

FNBs

no

metastatic

melanoma

cells

were

identified

cytologically

however

the

presence

of

metastatic

melanoma

was

subsequently

identified

by

histopathologic

examination

-LRB-

false

negatives

-RRB-

-LRB-

Fig.

-RRB-

Astute

clinical

and/or

radiologic

surveillance

results

in

the

detection

of

small

suspicious

lymph

nodes

Difficulties

in

performing

FNBs

on

such

small

suspicious

lymph

nodes

contribute

to

some

of

the

false-negative

diagnoses

-LRB-

particulary

small

mobile

axillary

nodes

-RRB-

In

fact

approximately

a

third

-LRB-

n

-RRB-

of

these

biopsy

samples

-LRB-

which

were

reported

as

no

malignant

cells

identified

-RRB-

did

not

contain

any

cellular

material

suggesting

that

an

absence

of

sampling

of

the

malignant

cells

was

the

reason

for

the

false-negative

result

Further

investigation

is

usually

necessary

to

identify

the

cause

of

the

mass

lesion

Surgical

examination

is

usually

the

next

step

when

the

index

of

clinical

suspicion

is

high

There

were

several

sources

of

difficulty

in

performing

the

FNB

procedure

for

metastatic

melanoma

Often

it

occurred

when

there

was

a

failure

to

locate

the

suspicious

lesion

because

of

its

small

size

or

its

location

was

not

communicated

with

adequate

precision

Failure

to

identify

metastatic

melanoma

occurred

when

cellular

material

showed

too

few

typical

morphologic

characteristics

of

metastatic

melanoma

or

these

characteristics

were

destroyed

or

masked

by

necrosis

The

large

number

of

confirmed

FNB

in

this

study

permitted

the

analysis

of

subgroups

Most

FNB

for

metastatic

melanoma

were

performed

in

lymph

nodes

as

well

as

skin

and

subcutaneous

tissues

No

difference

in

sensitivity

was

noted

among

these

tissue

groups

However

FNBs

of

lymph

nodes

of

the

axilla

were

significantly

less

sensitive

compared

with

those

performed

at

other

sites

and

with

FNBs

performed

in

lymph

nodes

of

the

groin

and

neck

A

number

of

factors

are

likely

to

contribute

to

the

low

sensitivity

of

FNBs

performed

in

the

axilla

including

the

greater

difficulty

in

gaining

access

to

and

locating

lymph

nodes

particularly

those

high

in

the

axilla

and

the

presence

of

large

amounts

of

fatty

tissue

in

axillary

lymph

nodes

-LRB-

horseshoe

nodes

-RRB-

Fifteen

clinicopathologic

factors

were

examined

for

their

effect

on

the

accuracy

of

FNB

for

metastatic

melanoma

most

of

which

had

no

effect

on

the

diagnostic

accuracy

of

the

test

However

the

following

four

variables

did

influence

the

sensitivity

of

the

FNB

procedure

-LRB-

-RRB-

Ulceration

of

the

primary

lesion

led

to

a

small

increase

in

the

sensitivity

of

the

test

-LRB-

P

-RRB-

-LRB-

-RRB-

Additional

needle

passes

were

performed

if

the

initial

sampling

failed

to

obtain

sufficient

cellular

material

thus

the

number

of

needle

passes

is

an

indicator

of

the

difficulty

in

obtaining

a

sample

from

a

specific

lesion

FNBs

that

were

performed

in

only

one

needle

pass

were

found

to

have

superior

sensitivity

than

those

which

required

additional

passes

to

obtain

an

adequate

sample

Furthermore

the

sensitivity

of

the

test

seemed

to

decrease

in

a

linear

manner

with

each

subsequent

pass

-LRB-

-RRB-

Training

and

experience

have

been

shown

to

significantly

influence

the

interpretation

of

FNB

of

the

breast

and

in

this

study

we

found

that

the

caseload

-LRB-

i.e.

level

of

experience

-RRB-

of

the

cytopathologist

who

reviewed

the

slides

influenced

the

sensitivity

of

the

test

Those

cytopathologists

who

reviewed

metastatic

melanoma

FNB

samples

in

the

study

period

performed

better

Those

cytopathologists

who

performed

reviews

seemed

to

do

as

well

as

those

who

had

a

caseload

of

to

cases

-LRB-

-RRB-

The

use

of

immunostains

was

associated

with

improved

sensitivity

of

the

test

However

this

may

reflect

the

fact

that

immunochemistry

was

only

performed

in

those

cases

in

which

a

sufficiently

high

cellular

yield

was

obtained

in

which

case

it

may

have

been

the

high

cellular

yield

that

lead

to

an

improvement

in

sensitivity

rather

than

the

use

of

immunostains

per

se

The

diverse

cytological

presentation

of

metastatic

melanoma

may

also

be

a

factor

in

the

association

of

the

use

of

immunochemistry

with

increased

sensitivity

Nasiell

et

al.

found

that

immunochemical

characterization

was

necessary

to

conclusively

diagnose

of

metastatic

melanomas

that

presented

with

an

equivocal

cytological

picture

However

immunological

characterization

can

not

be

considered

definitive

when

the

FNB

lacks

typical

cytologic

features

expected

of

metastatic

melanoma

For

example

one

of

the

false-positive

cases

exhibited

positivity

whereas

two

of

the

false-negative

FNBs

contained

melanoma

cells

that

seemed

to

be

negative

This

suggests

that

cytopathologists

should

be

cautious

when

reporting

the

results

of

immunostains

on

limited

samples

Our

study

shows

that

FNB

for

metastatic

melanoma

is

a

procedure

with

very

high

specificity

and

good

sensitivity

Several

clinicopathologic

factors

were

found

to

influence

the

diagnostic

accuracy

of

the

test

for

metastatic

melanoma

These

included

factors

relating

to

the

original

primary

melanoma

lesion

location

of

the

sampled

lesion

and

factors

relating

to

the

performance

of

the

test

The

SMU

employs

an

on-demand

FNB

service

with

assessment

of

the

cytologic

material

and

delivery

of

a

provisional

result

to

the

clinician

at

the

time

of

the

patient

's

visit

This

helps

guide

subsequent

diagnostic

and

therapeutic

measures

and

it

reduces

costs

-LRB-

e.g.

by

decreasing

the

need

for

additional

patient

visits

to

the

clinic

-RRB-

A

multidisciplinary

approach

involving

clinicians

pathologists

and

radiologists

enables

an

efficient

and

cost-effective

management

strategy

in

melanoma

patients

B I O B I I O O B O O O O O O O O O O B I I O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O B I I O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B I O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O

diagnosis
diagnostic accuracy
fine needle biopsy
melanoma
pathology


Closed reduction and percutaneus Kirschner wire fixation for the treatment of dislocated calcaneal fractures : surgical technique , complications , clinical and radiological results after 2 -- 10 years Introduction To reduce complications , a minimally invasive technique for the treatment of dislocated intraarticular fractures of the calcaneus was used . Therefore previously described closed reduction and internal fixation techniques were combined and modified . Introduction A fracture of the calcaneus allowed to heal in improper anatomical position leads to static and dynamic malfunctions of the whole foot with consequent limited load bearing capacity and walking ability -LSB- 4 , 29 -RSB- . The associated pain leads to a significant impairment in quality of life . The goal of therapy for calcaneal fractures is the elimination of pain and restoration of walking ability for patients with normal foot shape and the ability to wear normal footwear . At present , there are multiple operative procedures for the treatment of calcaneal fractures . The procedures can be differentiated by approach , implant type and whether the treatment is one - or two-stages . Recently , open procedures using internal fixation have been favored for surgical therapy of the calcaneus -LSB- 2 , 5 , 9 , 15 , 17 , 23 , 24 , 26 -RSB- . A possible complication of an open procedure is the disturbance of wound healing with skin and soft tissue necrosis -LSB- 2 -RSB- and the possibility of cutaneous flaps -LSB- 5 , 8 , 9 , 15 , 17 -RSB- . In addition to posttraumatic arthritis in the lower ankle and adjoining joints , there are reports of osteitis of the calcaneus -LSB- 2 , 5 , 17 -RSB- . Advanced osteitis of the calcaneus can require a calcanectomy -LSB- 15 -RSB- or amputation of the lower leg -LSB- 9 , 17 -RSB- . In an effort to reduce the complications that can occur with an open procedure , we have combined and modified previously described closed reduction and internal fixation techniques -LSB- 14 , 27 , 28 -RSB- to create a minimally invasive technique . The aim of this study was to evaluate the clinical and radiographic results of our minimally invasive surgical treatment of intraarticular fractures of the calcaneus at 2 -- 10 years postoperatively . We then compared our results to the results of both open and minimally invasive surgical techniques found in the literature . Material and methods Patients A total of 88 patients with 92 closed , dislocated and intraarticular fractures of the calcaneus were consecutively treated with a minimally-invasive technique developed at our institution by modifying and combining the procedures of Westhues -LSB- 27 -RSB- , Poigenfürst and Buch -LSB- 14 -RSB- , and Wondrák -LSB- 28 -RSB- . All the surgeries were performed without the use of bone graft . The average age at time of calcaneal fracture was 46.1 years -LRB- range 18 -- 82 years -RRB- and most patients were male -LRB- 71.6 % -RRB- . The cause of fracture was a fall from varying heights in 75 -LRB- 85.2 % -RRB- of cases and a motor vehicle accident in 13 -LRB- 14.8 % -RRB- of cases . From this group of patients , 63 -LRB- 71.6 % -RRB- patients with 67 fractures were available for retrospective examination with an average follow-up time of 5.7 years -LRB- range 2 -- 10 years -RRB- . Twenty-five patients were unavailable for follow-up examination ; 12 patients who satisfied with the result of the surgery did not wish to participate in the study due to age or unwillingness to travel to the hospital , 7 patients were at an unknown address and 6 patients deceased . Examination All the medical records , radiographs , pre - and post-operative computed tomography scans were available for the entire study group . Traumatic soft tissue damage was determined using the classification method of Tscherne and Oestern -LSB- 25 -RSB- . In addition to radiographic evaluation using the calcaneus lateral , calcaneus axial and Broden views at 20 ° and 40 ° -LSB- 3 -RSB- , all the patients obtained a bilateral calcaneal preoperative CT scan for fracture classification and surgical planning . Fractures were evaluated by the classification scale of Sanders et al. -LSB- 17 , 18 -RSB- . The duration of surgery , as well as the time the X-ray image intensifier used , were noted as operative data . For postoperative evaluation of the reduction , radiographs of the calcaneus in lateral , axial , Broden 20 ° and 40 ° -LSB- 3 -RSB- views were obtained . At the last follow-up evaluation , a CT scan of both calcanei was obtained to examine the geometry of the calcaneus and to evaluate arthritic changes in the lower ankle joint . For a reconstruction of the calcaneal posterior facet to be considered satisfactory a joint deviation of ≤ 2 mm had to be seen radiographically on the postoperative radiographs . For the evaluation of the clinical results , the Zwipp score was used -LSB- 30 -RSB- . Statistical analysis For statistical analysis the Fisher 's exact test and the Chi-square test were used . Perioperative treatment and surgical technique After a calcaneal fracture was diagnosed , the lower leg was evaluated . If the soft tissue was in good condition , primary surgery performed . In cases of severe swelling with potential soft tissue damage NSAIDs , local cryotherapy and active movement exercises determined the course of therapy . Once the soft tissue was in good condition , surgery was performed . The patient was placed prone on the traction table under general anaesthesia or spinal anaesthesia without arrest of blood supply . After application of the calcaneus wire for traction in the dorso-cranial plane , the varus or valgus malaligment of the back foot was corrected with the wire positioned orthogonally to the longitudinal axis of the calcaneus . To achieve correct placement , the surgeon pulled at the traction bow with the knee bent along the longitudinal axis of the calcaneus . The subsequent traction in the plantar plane was performed with the leg stretched . Once placed in the proper orientation , the traction bow was connected to the retaining jig of the traction table -LRB- traction of 20 kg -RRB- . The surgeon then held the heel of the patient with both hands and applied compression both medially and laterally with his thenar muscle to reduce the main medial and lateral fragments . With the use of the X-ray image intensifier , the restoration of Böhler 's angle and the reduction of the posterior facet were verified . A Steinmann pin was put with the pointed end into a universal chuck and the other end into the dorso-lateral calcaneus beneath the posterior facet with a stab incision -LRB- Fig. 1a -RRB- . For reduction of the posterior facet , the traction wire was used as a hypomochlion -LRB- Fig. 1b -RRB- . The anatomical restoration of the posterior facet was verified with use of the Brodén radiographic views -LRB- 20 ° and 40 ° -RRB- . The reduction of the calcaneus was verified by examining the lateral radiographic view -LRB- Fig. 2a -RRB- . The fragments were fixed with percutaneus Kirschner wires , which were arranged conically into the talus and/or cuboid -LRB- Fig. 2b -RRB- . All of the main fragments to be reduced were held in place by the Kirschner wires and the arch of foot was held until the bone healed -LSB- 28 -RSB- . The wires were bent above the skin level , the wire traction removed and the stab incision closed with sutures . Fig. 1The Steinmann pin is placed into the dorso-lateral calcaneus above the traction wire -LRB- left side -RRB- . For the reduction of the posterior facet , the traction wire is used as a hypomochlion -LRB- right side -RRB- . The hematome is drained though the stab incisionFig . 2Intraoperative lateral radiograph of a dislocated calcaneal fracture before reduction -LRB- left side -RRB- . After reduction the fragments are fixed with percutaneus Kirschner wires -LRB- right side -RRB- Postoperatively , a dorsal lower leg splint was applied for immobilization and the lower portion of the operative side was elevated . On the first postoperative day , the patient was mobilized on crutches with no weight bearing on the operative side . Depending on pain levels , the patient began with active dorsal extension and plantar flexion in the upper ankle joint . The radiographic controls , -LRB- upper ankle joint anterior and lateral , calcaneus axial Brodén views -LSB- 25 -RSB- -RRB- were performed immediately postoperative , and again 2 and 8 weeks postoperative . After the fracture was healed , the Kirschner wires were removed . Partial weight bearing began after the eighth postoperative week at 20 kg and was increased up to full weight bearing by the twelfth postoperative week -LRB- Fig. 3 -RRB- . Fig. 3Clinical example . a Preoperative lateral radiograph of an intraarticular , displaced calcaneal fracture -LRB- left side -RRB- . The preoperative CT scan shows a Sanders Type II AC fracture on the coronal reconstruction -LRB- right side -RRB- . b Lateral radiograph taken 2.5 years postoperatively . The patient had a Zwipp score of 166 points -LRB- left side -RRB- . Anatomical reconstruction of the posterior facet was achieved -LRB- right side -RRB- . This coronal CT image shows the anatomical reconstruction of the posterior facet with no joint deviation Results Fifty-five of the 88 -LRB- 62.5 % -RRB- patients suffered exclusively from calcanal fractures . Thirty-three of the 88 -LRB- 37.5 % -RRB- patients had multiple injuries . Twenty of the 33 -LRB- 61 % -RRB- patients with multiple injuries had local co-injuries such as fractures of the upper ankle joint , tarsus and front-foot . In 83 of the 92 calcaneal fractures , the soft tissue injury was graded as 1 ° or 2 ° ; in 9 fractures , the soft tissue injury was graded as 3 ° . In eight cases , including three patients with multiple injuries , surgery was performed immediately on the day of the trauma . Length of surgery averaged 61 min -LRB- range 20 -- 175 min -RRB- and screening time averaged 115 s -LRB- range 20 -- 454 s -RRB- . To obtain proper retention of the fracture , between 4 and 7 Kirschner wires were used . The Kirschner wires were removed with or without local anaesthesia at an average of 10 weeks -LRB- range 7 -- 15 weeks -RRB- as an outpatient procedure . Full weight bearing was achieved at an average of 15 weeks postoperative . Sanders classification Sanders type II , III and IV fractures were diagnosed -LRB- Table 1 -RRB- . All the patients had a joint deviation of at least 2 mm . Patients with type I non-dislocated fractures were treated conservatively and were therefore not included in this study . Reconstruction of the posterior facet was verified radiographically in 13 of 15 -LRB- 86.7 % -RRB- type II fractures , in 47 of 52 -LRB- 90.4 % -RRB- type III fractures and in 16 of 25 -LRB- 64 % -RRB- type IV fractures immediately postoperatively -LRB- Table 1 -RRB- . Table 1Patients with immediate postoperative reconstruction of the posterior facet by Sanders fracture classificationSanders fracture classification -LRB- N = 92 -RRB- Radiological reconstruction of posterior facet achievedType II15 -LRB- 16.3 % -RRB- 13 -LRB- 86.7 % -RRB- Type III52 -LRB- 56.5 % -RRB- 47 -LRB- 90.4 % -RRB- Type IV25 -LRB- 27.2 % -RRB- 16 -LRB- 64.0 % -RRB- The Zwipp score of 67 patients at the last follow-up evaluation The Zwipp score of the 67 patients available for follow-up averaged 130/200 points -LRB- range 48 -- 186 points -RRB- which is considered a good result -LSB- 30 -RSB- . Regardless of fracture type , 41 -LRB- 61.2 % -RRB- of the 67 patients had a very good or good result , 24 -LRB- 35.8 % -RRB- patients had a satisfactory result and 2 -LRB- 3 % -RRB- patients had a bad result . The worst clinical results occurred with type IV fractures -LRB- Table 2 -RRB- . Thirty -LRB- 44.8 % -RRB- patients considered their treatment outcome very good or good , 28 -LRB- 41.8 % -RRB- as satisfactory and sufficient and 9 -LRB- 13.4 % -RRB- as insufficient . Table 2Clinical and radiological results at last follow-up evaluation by Sanders fracture classificationSanders fracture classificationVery good or good resultArthritis in lower ankle jointNormal Böhler angle achievedOverall6741 -LRB- 61.2 % -RRB- 33 -LRB- 49.3 % -RRB- 47 -LRB- 70.1 % -RRB- Type II 6 -LRB- 8.9 % -RRB- 4 -LRB- 66.7 -RRB- 1 -LRB- 16.7 % -RRB- 5 -LRB- 83.3 % -RRB- Type III 39 -LRB- 58.2 % -RRB- 29 -LRB- 74.4 % -RRB- 12 -LRB- 30.8 % -RRB- 31 -LRB- 79.5 -RRB- Type IV 22 -LRB- 32.8 % -RRB- 8 -LRB- 36.4 % -RRB- 20 -LRB- 90.9 % -RRB- 11 -LRB- 50.0 % -RRB- Thirty-seven -LRB- 55.3 % -RRB- of the 67 patients had no pain while full weight bearing or could walk at least 4 h without pain at last follow-up evaluation . Nine -LRB- 13.4 % -RRB- patients had constant pain . Thirty-three -LRB- 49.3 % -RRB- patients had a range of motion in the upper ankle joint identical to that of the non-affected side . Thirty-four -LRB- 50.7 % -RRB- patients had a restricted range of motion of up to 15 ° and more than half -LRB- 58.2 % -RRB- of the patients had achieved more than 75 % of their total range of motion in the lower ankle joint . Forty-three -LRB- 64.2 % -RRB- of 67 patients were able to wear normal shoes while 5 -LRB- 7.4 % -RRB- used shoes with an unroll aid . Nineteen -LRB- 28.3 % -RRB- patients had obtained orthopaedic shoes on their own at last follow-up . Two -LRB- 3 % -RRB- of 67 patients had arthritis of the upper ankle joint at last follow-up . Independent of fracture type 33 -LRB- 50.2 % -RRB- patients had arthritic changes in the lower ankle joint and 14 -LRB- 20.89 % -RRB- cases had arthritic changes in the calcaneocuboidal joint -LRB- Table 2 -RRB- . Böhler 's angle was restored in 70.1 % -LRB- 47 of 67 -RRB- of the cases -LRB- Table 2 -RRB- . A total of 85.1 % -LRB- 57 of 67 -RRB- cases had a reduction in calcaneal height to within 10 % when compared to the non-operative side . Additionally , a reduction in the length of the calcaneus occurred within 10 in 94 % -LRB- 63 of 67 -RRB- of cases when compared to the non-operative side . Thirty-eight -LRB- 56.8 % -RRB- of the 67 patients had a widening of the calcaneus to within 10 % compared to the opposite side . Complications Of the 92 surgically treated calcaneus fractures , 76 -LRB- 82.6 % -RRB- healed without complications . In nine -LRB- 9.8 % -RRB- cases , superficial skin infections , perforations of the Kirschner wires and bone dystrophy occurred and healed without any further complications . Significant complications occurred in six -LRB- 6.5 % -RRB- cases : three cases had osteitis of the calcaneus , one case had dislocation of the fracture requiring revision surgery and two cases had peroneal tendon impingement . Three cases of osteitis healed through conservative therapy with oral antibiotics and the two patients with impingement of the peroneal tendon refused any operative intervention . Using our method , disturbance of wound healing with skin and soft tissue necrosis requiring operative intervention was not observed . Additionally , no lower leg amputations and no total or partial calcanectomies had to be performed . Statistical analysis Using the Chi-square test a statistical significant correlation was found between the fracture type and the incidence of subtalar arthritis -LRB- p < 0.0268 -RRB- . Using the same test there was no statistical significant correlation found between the fracture type and quality of reduction -LRB- p > 0.6522 -RRB- , between fracture type and clinical result -LRB- p > 0.3204 -RRB- and between fracture type and Böhler 's angle -LRB- p > 0.5488 -RRB- . However , a statistical significant correlation was found between the clinical result and subtalar arthritis -LRB- p < 0.0013 -RRB- and between the incidence of subtalar arthritis and quality of reduction when using the Fisher ` s exact test -LRB- p < 0.0003 -RRB- . Discussion To correct deformations of the calcaneus , spare the soft tissue and lower the complication rate , indirect and less invasive reduction and fixation techniques to treat calcaneal fractures have been developed -LSB- 7 , 10 , 12 -- 14 , 16 , 19 , 21 , 22 -RSB- . Besides techniques with percutaneous reduction and internal K-wire fixation -LSB- 7 , 14 , 16 , 21 -RSB- percutaneous reduction techniques with external fixation are described in the literature -LSB- 12 , 13 , 19 , 22 -RSB- . In our department we have combined and modified previously described closed reduction and internal fixation techniques -LSB- 14 , 27 , 28 -RSB- to create a minimally invasive technique . This method used the lower joint surface of the talus as a guide for remodeling the posterior facet and reconstruction of the calcaneus . A multiple of different evaluation scores makes a comparison of the clinical results with published results difficult -LSB- 11 , 17 , 20 , 30 -RSB- . Using the Zwipp score , 61.3 % of the cases -LRB- 41 of 67 -RRB- treated by our modified method had good or very good results regardless of fracture type . In 38.7 % -LRB- 26 of 67 -RRB- of cases , a satisfactory or bad result was achieved . After open reduction and internal fixation with a plate , Rammelt et al. -LSB- 15 -RSB- and Boack et al. -LSB- 2 -RSB- reported good and very good results in 65 and 66 % of cases , respectively with the use of the ± 200 Zwipp score . Boack et al. -LSB- 2 -RSB- presented satisfactory or bad clinical results in 34 % of cases also using the Zwipp score . Sanders et al. -LSB- 18 -RSB- showed that under application of a lateral approach followed by internal fixation with a plate , the worst clinical results occurred with type IV fractures . In this study the worst clinical results were achieved in the treatment of type IV fractures although within our cases no statistical significant correlation between fracture type and clinical result could be demonstrated -LRB- Table 2 -RRB- . Patient satisfaction is an essential criterion for the successful treatment of calcaneus fractures . With a comparable follow-up period of 5.4 years , Thermann et al. -LSB- 23 -RSB- reported that 48.3 % of patients viewed their treatment outcome as good or very good after open reduction of their calcaneus fractures , 37.3 % of patients judged their treatment outcome as satisfactory and sufficient and 14.4 % judged their outcome as insufficient . Our treatment method had comparable results with 44.8 % of patients considering their treatment outcome very good or good , 41.8 % as satisfactory and sufficient and 13.4 % as insufficient . At last follow-up evaluation , 64.2 % of patients in this study were able to wear normal shoes while 28.4 % required orthopaedic shoes . Comparably , in the study by Therman et al. -LSB- 23 -RSB- , 68.7 % of the patients wore normal shoes and 16.8 % required orthopaedic shoes . Overall , satisfactory mobility of the joints adjoining the calcaneus was achieved with our surgical technique . In approximately half of our patients , complete range of motion in the upper ankle joint was achieved and in the lower ankle joint , approximately 60 % of patients had no or low movement restriction . Similar mobility in the upper and lower ankle joints has been reported in the literature after open reduction and osteosynthesis with a plate -LSB- 5 , 23 -RSB- . However , Buch -LSB- 6 -RSB- reported a worse range of motion in the upper and lower ankle joint after performing a percutaneus wire osteosynthesis in 100 calcaneal fractures with a varus or valgus deviation of the back foot occurring in half of the cases . In this study , malpositions of the back foot of more than 5 ° were diagnosed in 6 -LRB- 9 % -RRB- cases of the 67 cases . Clinically relevant changes in the axis of the front foot were not observed . The radiological evaluation of the joints adjoining the calcaneus showed arthritic changes in the upper ankle joint in two of our cases . Half of our cases showed arthritic changes in the lower ankle joint and in approximately a fifth of our evaluated cases , arthritic changes were found in the calcaneocuboidal joint . In our study , 66.7 % of type-II fractures and 98 % of type-III/IV fractures showed arthritic changes in the lower ankle joint . These results are similar to those presented by Thermann et al. -LSB- 23 -RSB- , who showed arthritic changes in the lower ankle joint in 65.2 % of type-II fractures and in 81.7 % of type III/IV fractures . Regardless of fracture type , anatomical restoration of the joint surface or a joint deviation of up to 2 mm of the posterior facet was achieved postoperatively in 82.1 % of cases . A total of 86.7 % of type-II fractures and 72.8 % of type-III/IV fractures achieved anatomical restoration of the posterior facet . These results are comparable to those presented in the literature with open reduction and internal fixation with plates or screws -LSB- 2 , 17 , 23 -RSB- . In this study , the average length of the surgery was 61 min . This is considerably less than the average length of surgeries utilizing open reduction and internal fixation of 139 and 168 min -LSB- 2 , 20 -RSB- . In 9.8 % of cases , complications such as superficial skin infections , perforation of the Kirschner wires and bone dystrophy healed with conservative therapy or after removal of the Kirschner wires . This rather insignificant rate of complications is similar to those described in the literature after operative treatment of calcaneal fractures utilizing a minimally invasive technique -LSB- 7 , 16 , 21 -RSB- . The rate of significant complications in this study was 6.5 % . In two cases , an impingement of the peroneal tendon occurred . One case had a dislocation of the fragments requiring revision surgery . Three cases had infections of the calcaneus and were related to a traumatic soft tissue injury that healed with conservative therapy . With open reduction , skin and soft tissue necrosis -LSB- 2 -RSB- with possible cutaneous flaps have been reported in scattered cases -LSB- 5 , 8 , 9 , 15 , 17 -RSB- . Folk et al. -LSB- 9 -RSB- demonstrated that in 25 % of cases , wound complications required an additional surgery after open reduction of calcaneus fractures 84 % of the time . Abidi et al. -LSB- 1 -RSB- reported wound healing disturbances in 33 % of cases following open reduction and internal fixation of calcaneal fractures . There have also been reports in the literature of partial or total calcanectomies -LSB- 15 -RSB- , including amputations , as a result of calcaneal osteitis after open reduction -LSB- 9 , 17 -RSB- . Sanders et al. -LSB- 17 -RSB- considered a lower leg amputation if a patient suffered continual osteitis . In the current study no disturbances of wound healing , skin or soft tissue necrosis that required microsurgical intervention were observed . In this study no statistical significant correlation could be found between fracture type and the ability to restore Böhler ` s angle . However , regardless of fracture type Stulik et al. -LSB- 21 -RSB- showed similar results using a comparable minimally invasive technique while Thermann et al. -LSB- 23 -RSB- had worse results following open reduction with internal fixation . In our study , there was a slight reduction in the height and length of the operated calcaneus when compared to the non-operated side . With our closed reduction and internal fixation technique , more than half of the cases had a widening of the calcaneus of more than 10 % when compared to the opposite side , which is an unsatisfactory result . At the same time only two patients had an impingement of the peroneal tendon that the patients considered tolerable . In summary , we presented a minimally invasive technique for the treatment of intraarticular , dislocated calcaneus fractures and were able to produce results comparable to open techniques with a lower rate of serious complications . In the majority of cases , an almost identical Böhler angle and geometry of the calcaneus was achieved when compared to the opposite side at the time of last follow-up . Simple removal of the Kirschner wires and shorter surgery time decrease patient stress and must be recognized as an advantage of this minimally invasive technique . Thus , we feel that our minimally invasive technique is a viable alternative for the treatment of intraarticular , dislocated calcaneal fractures .

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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A database for medicinal plants used in the treatment of diabetes and its secondary complications Effective treatment of diabetes is increasingly dependent on active constituents of medicinal plants capable of controlling hyperglycemia as well as its secondary complications . Sensing the importance of documenting such medicinal plants , here we describe a web database containing information -LRB- name , literature citation , active compounds and few related full text articles -RRB- of the diabetes medicinal plants exhibiting hypoglycemic , antioxidant and antimicrobial effects . Background Diabetes mellitus is possibly the world 's largest growing metabolic disorder and around 30 million people around the world suffer from this disorder . -LSB- 1 -RSB- Diabetes can be defined as a group of syndromes characterized by hyperglycemia , altered metabolism of lipids , carbohydrates and proteins . -LSB- 2 -RSB- The complications of diabetes include vascular diseases , eye disorders , renal disorders and a host of secondary infections . -LSB- 3 -RSB- The treatment of diabetes with synthetic drugs is generally not preferred because of its high cost and the range of side effects caused . Hence development of traditional or alternative medicine is needed . Herbal drugs constitute an important part of traditional medicine and literature shows that there are more than 400 plant species showing antidiabetic activity . -LSB- 4,5 -RSB- Our interest is to study these anti diabetic medicinal plants . Research findings suggest that many of these plants control diabetes by exhibiting hypoglycemic and antioxidant effects . The secondary infections associated with diabetes are also restricted to antimicrobial effect by plant products . Sensing the opportunities provided and in an effort to translate research into technology , this database ` DIAB ' was created to document the research literature available on these medicinal plants and their active compounds . Methodology Step 1 : Data collection Data of antidiabetic plants were collected from various literature sources such as PubMed -LSB- 6 -RSB- , ScienceDirect -LSB- 7 -RSB- , Biomed Central -LSB- 8 -RSB- Springerlink -LSB- 9 -RSB- , Scirus -LSB- 10 -RSB- , Wiley journals -LSB- 11 -RSB- and also from folklore medicinal usage . The current dataset contains information for about 258 genus and 287 species of plants exhibiting antidiabetic effect . Of these 287 antidiabetic plants , 129 species show proven antioxidant effect and 53 species exhibit antimicrobial effect besides their hypoglycemic activity . Step 2 : Database Design The database is developed using MS Access as back-end and ASP.NET as front-end on a Windows platform and updated regularly . Step 3 : Features of DIAB Three separate links -LRB- antidiabetic , antioxidant , and antimicrobial -RRB- are provided to access the literature citations of antidiabetic plants showing hypoglycemic , antioxidant and antimicrobial properties respectively . The record entry consists of the following literature : plant name , part investigated , authors and abstract . The ` Active principles ' link provides information -LRB- plant name , part investigated , active compounds and properties -RRB- on the 46 compounds isolated from the antidiabetic medicinal plants . The ` Articles ' link provides few free text articles for further reading . A screen shot of the database is given in figure 1 . Utility In the current scenario there are several other databases which give information on medicinal plant name , distribution , drugs formulated and usage in treatment of diabetes . We believe that the freely available database called DIAB will give supplementary information on the antidiabetic plants capable of controlling some secondary complications . This database finds utility to the scientific community for a quick review on plants for diabetes medicinal plant research and provides enormous scope for development of drugs . Future development We plan to refine and keep updating this database and hopefully a link solely for indigenous plants will be made available in the nearest future . The database will also be modified to develop provisions to search the database to identify plants of interest using keywords .

O B O B I O O O O O B O O O O O O O B O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O B O O O O O B O O O O O O O O O O O O O B B I O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O B O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O B O B I O O O O O O O O O B O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O

diabetes
medicinal plants
database
literature
active principles
antioxidant
antimicrobial properties