Download - The Role of White Cell Count and c
-
8/18/2019 The Role of White Cell Count and c
1/39
THE ROLE OF WHITE CELL COUNT AND C-REACTIVE PROTEIN
IN THE DIAGNOSIS OF ACUTE APPENDICITIS
Khan MN, Davie E, Irsha K De!ar"#en" $% Genera& S'r(er), Wisha* Genera& H$s!i"a&, Wisha*, Lanar+shire UK
a.+(r$'n/ Despite recent advances in diagnostic medicine, the diagnosis of appendicitis isstill doubtful in a number of cases. Majority of the clinicians rely on their clinical examinationstrengthened by the laboratory tests. This study was carried out to find out the specificity andsensitivity of white cell count (W! and "#eactive $rotein (#$! in diagnosingappendicitis in patients presenting with right iliac fossa pain. Me"h$s/ % total of &' patientswere included in this study that presented in the hospital with acute right iliac fossa pain andlater on operated and had appendicectomy. The histopathology data was collected to find out
the fre)uency of negative appendicectomy. %ccording to the histopathology reports these patients were grouped into three sub"groups as normal appendix, inflamed appendix or perforated*gangrenous appendix. % record was +ept of the W and #$ levels of these patients on admission. Res'&"s/ % total of &' patients were included in this study and out of them - had a normal appendix giving an over all negative appendicectomy rate of /.0.1ut of these were male and &2 were female, male to female ratio being 3&.. The age
range was &"- with a median age of &/. %mong the &&& patients who had appendicitis, 2had a ruptured *perforated appendix and &2 had an inflamed appendix. 1ver all the W waselevated in 4' patients and #$ was elevated in 24 cases. The cut off value for white cellcount was x 52 * 6. The reactive protein levels were calculated by immunoturbidimetrictest and the cut off value was ta+en as .-mg*dl. The sensitivity and specificity of W in thisstudy was 40 and 2&. 0 and that for #$ was -'.20 and 4.- 0. C$n.&'si$n3 7oth the
inflammatory mar+ers i.e. W and "reactive protein can be helpful in the diagnosis, whenmeasured together as this increases their positive predictive value.Ke) *$rs/ appendicitis, white cell count, reactive protein
INTRODUCTION
%cute appendicitis is still one of the commonest surgical emergencies. The diagnosis is primarily clinical. & %typical patient is one presenting with right lower abdominal pain, nausea and vomiting and has got tenderness
and guarding in right iliac fossa on examination. 8owever these sign 9 symptoms are not very specific for appendicitis and can mimic any other acute abdominal condition. The picture is more confused by the variable position of the appendix./ Despite advances in diagnostic modalities the diagnosis is still doubtful in 5"/5 0 of cases.' %nd the definite diagnosis of appendicitis still remains a clinical decision. , augmented by appropriatetests. % high degree of diagnostic accuracy is re)uired to reduce the incidence of negative appendicectomieswhich still remains around &5 0.2 1ne study has shown an incidence of '50 in women of reproductive age
group.- %cute appendicitis is a disease of young adults.4 :t is rare below years of age but people are vulnerableto it in extremes of their age and complication rate is higher in those groups. :t is more common in males ascompared to females. :t used to be called as the disease of developed countries with an association of high protein inta+e, but the incidence is also increasing in developing countries. % study reported it to be around
.*555 for males and .'*555 for females.
%part from a careful history and clinical examination, total white cell count has remained an important
factor in the definite diagnosis of appendicitis. ;arious studies have shown that this can be very non"specific attimes.5 #ecently interest has grown in other inflammatory mar+ers which could be helpful in diagnosingappendicitis. #$ is one of them. This study was conducted to chec+ the sensitivity and specificity of the whitecell count and #$ in patients presenting with right iliac fossa pain.
MATERIAL AND METHODS
This study was carried out at Wishaw
-
8/18/2019 The Role of White Cell Count and c
2/39
" perforated*gangrenous appendixTheir blood results were reviewed and a note of W and #$ levels was made. The sensitivity and
specificity of these tests were calculated according to the following formulas,
=ensitivity > True $ositives* True $ositives ? @alse Aegatives=pecificity > True Aegative* True Aegative ? @alse $ositiveThe cut off value for white cell count was x52*6. This value was selected arbitrarily as it
corresponds to the elevated W. The reactive protein levels were calculated by immunoturbidimetric testand the cut off value was ta+en as .-mg*dl. This cut off value was ta+en in light of the previous research whichshowed it to be highly accurate.
RESULTS
% total of &' patients were included in this study and out of them - had a normal appendix giving an over allnegative appendicectomy rate of /.0. 1ut of these were male and &2 were female, male to female ratio being 3&., again highlighting the fact that the diagnosis of appendicitis is straightforward in men but could be just a guess in females. The age range was &"- with a median age of &/. %mong the &&& patients who hadappendicitis, 2 had a ruptured *perforated appendix and &2 had an inflamed appendix. 1ver all the W waselevated in 4' patients and #$ was elevated in 24 cases. The sensitivity and specificity of W in this study
was 4 0 and 2&. 0 and that for #$ was -'.2 and 4.- 0. The positive predictive values for W and #$were &0 and 20 respectively (pB5.55!.
Ta0&e-1/ Ana&)sis $% *hi"e .e&& .$'n" #eas're#en"s in !a"ien"s *i"h RIF !ain
-
&2
2
White ell ount
#aised/ 2 4
White ell ount
Aormal& 5 5-
patients with normal appendix patients with inflammed appendix
patients with perforated*gangrenous appendix
=ensitivity > 4.0, =pecificity > 2&.0$ositive predictive value > &0
Degree of freedom 3 &, hi =)uare > /'.&$ B 5.55 , hence the distribution is significant
DISCUSSION
Majority of the patients with acute appendicitis present with right sided lower abdominal pain and nausea andvomiting, but these symptoms are very non"specific. :n fact any acute abdominal condition can mimicappendicitis and hence the list of differential diagnosis is long and hence removal of a normal appendix is notunusual.
Ta0&e-2/ Ana&)sis $% CRP #eas're#en"s in !a"ien"s *i"h RIF !ain
-
&2
2
#$ #aised 2 4 4-
#$ Aormal /' 5 patients with normal appendix
patients with inflammed appendix
patients with perforated*gangrenous appendix=ensitivity > -'.20, =pecificity > 4.-0
$ositive predictive value > 20
Degree of freedom > &, hi =)uare > 2-.
$ B 5.55 , hence distribution is significant.
% high degree of diagnostic accuracy is re)uired to reduce the incidence of negative appendicectomies
which still remain around &5 0. 1ne study has shown the diagnostic accuracy of acute appendicitis of 250 inwomen of reproductive age group.& The implications can be two folds. @irstly although appendicectomy isconsidered to be a safe operation it still has got associated complications, most noticeable among them arewound infection, intra abdominal abscess, adhesions and bowel obstruction and pulmonary complications from
general anaesthesia.
=econdly, the group of patients who have persistent symptoms after the operation areunsatisfied with the health care they received and are a burden on the hospital resources.
-
8/18/2019 The Role of White Cell Count and c
3/39
To improve the diagnostic accuracy surgeons have relied on a good history and sound clinicalexamination augmented by laboratory investigations ranging from simple blood tests loo+ing at the white cellcount, to modern sophisticated investigations including computerised tomography, ultrasonography, peritoneal
aspirations, barium enema and laparoscopy./"2 7ut all these investigations have their demerits. They areinvasive, time consuming, operator dependent and not very freely available everywhere. %mong all theseloo+ing at the W has been very favourite test for the surgeons in deciding for probability of appendicitis
although studies have shown it to have a low specificity.-
The )uestion of specificity and sensitivity of thesetests remains open.
To improve the sensitivity and specificity surgeons have tried se)uential leu+ocyte counts and
neutrophil3 lymphocytic ratio.4" #ecently attention has been focussed on other inflammatory mar+ers whichcan be raised in appendicitis, #$ ("reactive protein! being one of them. #$ was identified in 5 and isregarded as the acute phase protein. :t has been studied as a screening device for inflammation , a mar+er for disease activity and as a diagnostic adjunct. &5 =everal studies have addressed the accuracy of #$ in diagnosingappendicitis and it is agreed that its level increases in appendicitis and this increase is related to the severity of appendiceal inflammation. 8owever #$ levels may be elevated in patients with complications from
pneumonia, pelvic inflammatory disease, and urinary tract infections. This study showed that white cell count and #$ both are sensitive in diagnosing acute inflammation but they are not very specific. ombining the two tests together the specificity and positive predictive valueincreases. The measurement of #$ is useful in the diagnosis of acute appendicitis. :n this study we have -
patients in group :, where the appendix was found normal. :n & of these patients both values were in the normalrange. The accuracy of these tests increases with the increasing severity of inflammation. :n group ::: where the
appendix was found to be perforated or gangrenous, only - patients out of 4- had normal values of either #$or W. :n both groups :: and ::: no patients were found with #$ or W with in normal range. We wouldrecommend that if in a patient presenting with right iliac fossa pain, both #$ and W are normal thediagnosis of appendicitis is very unli+ely.
REFERENCES
. $al C, Chan %. %ppendicitis3 a continuing challenge. $a+ Med %ssoc 4E/4(-!34"&.&. %bbassi %, =hah F. %cute appendicitis in children. =urg $a+istan 4E&3&4"5
. Davenport M. %cute abdominal pain in children. 7M 2E&(-5&!3/4"'5
/. Delic , =av+ovic %, :sa+ovic G. ;ariations in the position and point of origin of vermiform appendix. Med %rch &55&E'2(!3'"4.
'. %nderson # , 8ugander % ,
-
8/18/2019 The Role of White Cell Count and c
4/39
-
8/18/2019 The Role of White Cell Count and c
5/39
The systemic inflammation-based neutrophil–
lymphocyte ratio: Experience in patients with cancer
Graeme J.K. Guthrie
,
Kellie A. Charles
,
Campbell S.D. Roxburgh
,
Paul G. Horgan
,
Donald C. McMillan
,
Stephen J. Clarke
Abstract
There is increasing and consistent evidence that cancer-associated inflammation is a key determinant of outcome
in patients with cancer. Various markers of inflammation have been examined over the past decade in an attempt
to refine stratification of patients to treatment and predict survival. One routinely available marker of the systemic
inflammatory response is the neutrophil–lymphocyte ratio (NLR), which is derived from the absolute neutrophil
and absolute lymphocyte counts of a full blood count. To date, over 60 studies (>37,000 patients) have examined
the clinical utility of the NLR to predict patient outcomes in a variety of cancers. The present systematic review
examines and comments on the clinical utility of the NLR. The NLR had independent prognostic value in (a)
unselected cohorts (1 study of >12,000 patients), (b) operable disease (20 studies, >4000 patients), (c) patients
receiving neoadjuvant treatment and resection (5 studies, >1000 patients), (d) patients receiving
chemo/radiotherapy (12 studies, >2000 patients) and (e) patients with inoperable disease (6 studies, >1200
patients). These studies originated from ten different countries, in particular UK, Japan, andChina. Further,
correlative studies (15 studies, >8500 patients) have shown that NLR is elevated in patients with more advanced
or aggressive disease evidenced by increased tumour stage, nodal stage, number of metastatic lesions and as
such these patients may represent a particularly high-risk patient population. Further studies investigating the
Jump to Section
http://www.croh-online.com/http://www.croh-online.com/http://www.croh-online.com/
-
8/18/2019 The Role of White Cell Count and c
6/39
tumour and host-derived factors regulating the systemic inflammatory response, in particular the NLR, may
identify novel treatment strategies for patients with cancer.
Keywords:
Cancer,Tumour-stage,Neutrophil lymphocyte ratio, Survival
1. Introduction
Cancer is the leading cause of disease worldwide with 12.7million new cancer cases diagnosed worldwide in
2008 [1]. More than one in three people will develop some form of cancer in their lifetime and it remains the
leading cause of death with 7.6million cancer deaths worldwide recorded in 2008 [1], far exceeding deaths from
other diseases such as heart disease and stroke [1]. Despite intense research activity outcomes from malignancy
remain poor for the most common cancers.
In recent years there have been significant advances in cancer treatment. However, the appropriate stratification
of cancer patients and subsequent allocation to surgical, oncological and palliative treatments remains a
challenge. Until recently, the prediction of outcome has relied almost exclusively on accurate staging of the
tumour. Indeed, many studies have attempted to refine TNM staging using tumour-associated criteria.
It is now widely recognised that outcomes in patients with cancer are not determined by tumour characteristics
alone, and that patient-related factors are also key to outcome. In the last decade, it has become increasingly
apparent that cancer-associated inflammation is a key determinant of disease progression and survival in most
cancers[[2],[3]]. In particular, the host response in the form of systemic inflammation has been shown to
independently predict outcome. The basis of this is not altogether clear, however a marked systemic inflammatory
response is associated with important patient-related factors such as nutritional, functional and immunological
decline.
In recent years many studies have investigated the most commonly used measures of the systemic inflammatoryresponse and their potential use in stratifying cancer patients.
For example, there is good evidence that markers of the acute phase response, particularly C-reactive protein
and albumin, are both sensitive and reliable markers of systemic inflammation in cancer patients[4]. Indeed, the
last decade has seen the evolution of a prognostic scoring system, the Glasgow Prognostic Score (GPS) based
on the combination of these acute phase proteins that provides objective, reliable prognostic information for both
operable and inoperable cancers [5]. Indeed, this scoring system has been validated in a variety of clinical
scenarios and is now recognised to have prognostic value, independent of tumour-based factors[5].
Jump to Section
http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Cancer&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Tumour-stage&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Neutrophil%20lymphocyte%20ratio&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Neutrophil%20lymphocyte%20ratio&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Survival&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Survival&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Cancer&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Tumour-stage&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Neutrophil%20lymphocyte%20ratio&seriesISSN=1040-8428http://www.croh-online.com/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=series&searchText=Survival&seriesISSN=1040-8428
-
8/18/2019 The Role of White Cell Count and c
7/39
It is also well established that the systemic inflammatory response is associated with alterations in circulating
white blood cells, specifically the presence of neutrophilia with a relative lymphocytopaenia [[6],[7]]. In addition,
haematological tests are carried out routinely for cancer patients in a variety of clinical scenarios, and as such
represent an easily measurable objective parameter able to express the severity of the systemic inflammatory
response in patients with cancer. Indeed, Walsh et al., investigated the prognostic value of the neutrophil–
lymphocyte ratio (NLR), in their centre, because C-reactive protein concentrations were not routinely performed
as part of pre-treatment assessment[8].
In recent years, and in a similar way to the GPS[5], many research groups have investigated the value of the
haematological components of the systemic inflammatory response specifically for use in predicting outcome,
and have reported that the individual components of the differential white cell count, specifically the neutrophil
and lymphocyte counts, may have clinical utility in predicting survival [9]. Indeed, the combination of these
haematological components of the systemic inflammatory response, as the neutrophil–lymphocyte ratio (NLR),
has been reported to have prognostic value in a variety of cancers[[4],[10]].
Therefore the aim of the present review was to provide a concise overview of the NLR studies in patients with
cancer and comment on the current and future clinical utility of this simple objective systemic inflammation-based
score.
2. ethod
This systematic review of published literature was undertaken according to a pre-defined protocol. The primary
outcome of interest was the relationship between the neutrophil–lymphocyte ratio and cancer outcome (overall
survival/cancer-specific survival/disease recurrence or response to treatment). The secondary outcomes of
interest were the associations between the NLR and other clinical, pathological or inflammatory characteristics.
A literature search, using appropriate free text and medical subject heading (MeSH) terms, was made of the US
National Library of Medicine (MEDLINE), theExcerpta Medica database (EMBASE), theCochrane Database of
Systematic Reviews (CDSR) for articles reporting the prognostic value of the NLR with regard to cancer outcome
(June 2005–October 2012).
On completion of the online search, the titles and abstracts were examined before full text was obtained for
studies with potential relevance. Of these, studies which had examined the prognostic value of NLR in solid organ
malignant disease were included while review articles, studies relating to duplicate data sets, studies not available
in English language and those published in abstract form only were excluded. The bibliographies of all included
articles were subsequently hand-searched to identify any additional studies of interest. Studies were selected
after review by the authors.
Jump to Section
http://www.croh-online.com/http://www.croh-online.com/http://www.croh-online.com/http://www.croh-online.com/http://www.croh-online.com/http://www.croh-online.com/http://www.croh-online.com/
-
8/18/2019 The Role of White Cell Count and c
8/39
Study heterogeneity precluded a meaningful meta-analysis and the results are presented in descriptive form only.
For each group of studies a weighted average hazard ratio for an incremental increase in the NLR was calculated
by multiplying the hazard ratio reported in the study by the number of patients in the study. The product of this
multiplication was added to the products of other studies in the group and the total was divided by the total
number of all the patients in the group studies.
!. "tudies of the pro#nostic $alue of the %&'( in unselected cohorts of patients with cancer
Three studies, comprising data on 21,193 patients reported the prognostic value of the NLR in unselected cohorts
of patients with cancer (Table 1, Refs. [[11],[16],[17]]). Two studies specifically assessed the prognostic value of
the NLR, while one compared the NLR with other well recognised markers of the systemic inflammatory response
in cancer, notably C-reactive protein, albumin, and platelets and their combinations in the prognostic scores
mGPS and platelet-lymphocyte ratio (PLR). Two studies examined markers of systemic inflammation across all
tumour types while the remaining one investigated its prognostic value in breast cancer. NLR was associated with
disease-free and overall survival in two studies and was reported as an independent predictor of survival along
with the derived NLR (dNLR) in one study. Despite being relatively similar, the threshold chosen to define an
elevated NLR differed across all three studies, ranging from >3.33 to >5, and therefore calculation of a weighted
average hazard ratio for an incremental change in NLR was not appropriate.
Table 1Studies of the prognostic value of the NLR in unselected cohorts of
patients with cancer.
Stud
y
Centr
e
Tumou
r site n
HR ( p-
value)
Thresh
old Comments
Azab et
al. [16
New
!or"
#$SA%
&reast '16 (.)*
#+,.,,,
1%
-'.'' levated NLR was associated with
the elderl/0 larger tuours0 and
ore advanced stage
2roctor
[11
3lasgow
#$4%
5arious )*7 1.7
#+,.,,1%
-* levated NLR #-*% was associated
with reduced * /ear 8S and 9:S
2roctor
[1
3lasgow
#$4%
5arious 1;01
1)
1.*;
#+,.,,1%
-( NLR and dNLR were associated with
reduced 8S and 9:S independent
of age0 se< and deprivation. NLR
superior to dNLR
DFS, disease-free survival; OS, overall survival.
Jump to Section
http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0005http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0005
-
8/18/2019 The Role of White Cell Count and c
9/39
In conclusion, there is evidence that the NLR has prognostic value in a variety of tumour types. Although the NLR
is associated with survival, other markers of the systemic inflammatory response, notably the GPS/mGPS, may
be superior predictors of survival. Indeed, a recent large cohort study (Glasgow Inflammation Outcome Study)
reported that the mGPS had superior prognostic value over the NLR in differentiating good from poor prognostic
groups in a variety of tumour types [11].
More recently, the components of a number of systemic inflammation-based scores (neutrophils, lymphocytes,
platelets, C-reactive protein and albumin) have been compared in a large unselected cohort of patients with
cancer. Of these components, only neutrophils, platelets, C-reactive protein and albumin were shown on
mutivariate survival analysis to have independent prognostic value [12]. These results may explain the reported
superiority of the GPS over the NLR.
). "tudies of the pro#nostic $alue of the %&' in patients with operable cancer
Thirty-four studies, comprising data on 12,426 patients have investigated the prognostic value of the neutrophil–
lymphocyte ratio in patients with a variety of solid organ malignancies including colorectal, gastric, oesophageal,
pancreatic, liver, urological and gynaecological cancers(Table 2, Refs.[[8],[18],[19],[20],[21],
[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[4
4],[45],[46],[47],[48],[49]]). Interestingly, the threshold that defined an elevated NLR differed across these thirty
four studies with >5 being the most commonly used threshold (n=16 studies).
Table 2Studies of the prognostic value of the NLR in patients with operable
cancer.
Study Centre
Tumour
site n
HR ( p-
value)
Thresh
old Comments
9ing et
al. [1)
3uangdo
ng#=hina%
=olorectal 1(1 (.))
#,.,,'%
-( levated NLR associated with
reduced 9:S and an independentprognostic factor and not
associated with
clinicopathological
characteristics
4won et
al. [17
&usan
#4orea%
=olorectal ;,, #Non>
signi?ca
nt%
-* levated NLR associated with
lower 8S on univariate anal/sis
onl/. NLR not associated with
clinicopathological factors or
stage of disease
Neal et
al. [;,
Leicester
#$4%
=olorectal ;,; ;.,*
#,.,,1%
-* NLR associated with post
operative orbidit/ and 8S on
Jump to Section
http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0010http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0010http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0010
-
8/18/2019 The Role of White Cell Count and c
10/39
univariate anal/sis
@alsh et
al. [)
Suol"
#$4%
=olorectal ;', #+,.,,1% -* NLR - * associated with 8S and
=S survival on univariate anal/sis
Leitch et
al. [;1
3lasgow
#$4%
=olorectal ;'' #Non>
signi?ca
nt%
-* NLR associated with other
easures of s/steic
inBaation but not prognostic
in priar/ operable disease
Callappa
et al. [;;
Darrow
#$4%
=olorectal ;7 1.)1
#,.,;)%
-* levated NLR independentl/
associated with survival
Dalazun
et al. [;'
Leeds
#$4%
=olorectal ((, ;.;6
#+,.,,1%
-* levated NLR0 age and nuber of
etastases were independent
prognostic factors
3oez et
al. [;(
Leeds
#$4%
=olorectal *,1 1.'
#,.,';%
-* levated NLR associated with
recurrence
Dung et
al. [;*
Eao>!uan
#Eaiwan%
=olorectal 1,(
,
1.;7
#,.,1;%
-* NLR associated with signi?cantl/
worse 8S #* /ears%. NLR
associated with advancing age
#-6*%0 E(b cancer0 elevated =A
and tuour
obstructionFperforation. NLR not
associated with histological
subt/pe0 tuour size0 tuour
grade
=hiang et
al. [;6
Lin"ou
#Eaiwan%
=olorectal ''
1
1.'1
#,.,1'%
-' levated NLR was associated
with clinicopathological factors
associated and with outcoe
$bu"ata
et al. [;
Eo"/o
#Gapan%
3astric 1* *.)
#+,.,,1%
-* NLR independentl/ prognostic
and associated with E>stage0
tuour size0 presence of l/ph
nodes0 and pathological stage
Aizawa etal. [;)
4ashiwa#Gapan%
3astric ;6; ;.;1#,.,1;%
-'.; NLR was an independentprognostic factor. NLR increased
in a E>stage dependent anner
Gung et
al. [;7
3wangHu
#4orea%
3astric ;7' 1.6*
#,.,17%
-; levated NLR signi?cantl/
associated with 8S and 9:S in
later stage gastric cancer.
levated NLR associated with
advanced E>stage0 and larger
tuour size
Rashid et
al. [',
9erb/
#$4%
8esophag
eal
;7( I -'.* NLR not associated with tuour
factors or with disease
-
8/18/2019 The Role of White Cell Count and c
11/39
recurrence or survival
@ang et
al. ['1
3uangzh
ou
#=hina%
3astric ';( ;.';
#,.,1(%
-* 32S ore prognostic than NLR
Cohri et
al. [';
Esu
#Gapan%
3astric '* ;.)
#+,.,,,
1%
-;.; NLR independentl/ associated
with prognosis together with
tuour size0 advanced E>stage in
relativel/ earl/ stage gastric
cancer
Shiada
et al. [''
Eo"/o
#Gapan%
3astric 1,;
)
1.)*
#,.,,'%
-( NLR was an independent
prognostic factor and increased
in a t>stage dependent anner
3arcea etal. ['(
Leicester#$4%
2ancreas ( I -* NLR signi?cantl/ associated withrecurrence0 and was ore
prognostic than coponents
alone
&hatti et
al. ['*
9erb/
#$4%
2ancreas )( 1.)
#,.,;'%
-( NLR reported an independent
prognostic factor for survival and
not associated with tuour
characteristics
Sith et
al. ['6
Liverpool
#$4%
2ancreas 11, I =ontinuou
s
No relationship between NLR and
survival
@ang et
al. ['
3uangzh
ou
#=hina%
2ancreas 1 ;.*(
#,.,,6%
-* NLR independentl/ associated
with 8S
3oez et
al. [')
Leeds
#$4%
=holangio>
carcinoa
; 1.)
#,.,,)%
-* levated NLR associated with
poorer 9:S0 and associated with
larger tuours0 intrahepatic
satellite lesions0 icrovascular
invasion and l/ph node
involveent
4inoshita
et al. ['7
Eo"/o
#Gapan%
Liver 1*, I -* Along with 32S and 32S0 NLR
was associated with reduced 8S.
NLR not independentl/
associated with 8S
Cotour
a et al.
[1'
:u"uo"a
#Gapan%
Liver 1*) 6.;(
#,.,,,;%
-( Jncreasing NLR associated with
D== recurrence. Associated with
other ar"ers of s/steic
inBaation
Sa"ai et
al. [(,
Aoori
#Gapan%
Lung ;' #Non>
signi?ca
=ontinuou
s
NLR had no signi?cant
relationship with recurrence or
-
8/18/2019 The Role of White Cell Count and c
12/39
nt% survival
Sarraf et
al. [(1
London
#$4%
Lung 1) 1.1
#,.,,(%
-* NLR associated with E>stage and
was an independent predictor of
outcoe
Eoita et
al. [(;
Ci/aza"i
#Gapan%
Lung ;)( #
-
8/18/2019 The Role of White Cell Count and c
13/39
colorectal cancer. The relationship between the neutrophil–lymphocyte ratio and pathological features in
colorectal cancer was inconsistent.
Only two studies reported a significant direct association between the NLR and T-stage while associations with
other tumoural factors including tumour size, differentiation and tumour location were reported in one study. With
regard to the threshold defining an elevated NLR, the most consistently used threshold was >5 (eight studies),
one study used a threshold of >4, and another study used a threshold of >3. Of the studies using the most
common threshold (>5), the weighted average hazard ratio for an incremental increase in the NLR was 1.4.
Seven studies, (six gastric and one oesophageal), comprising data on 2715 patients investigated the prognostic
value of the NLR in operable gastro-oesophageal cancer[[27],[28],[29],[30],[31],[32],[33]]. These studies were
from Japan (4), the UK (1), China (1) and Korea (1). The majority of studies reported that NLR was an
independent predictor of survival in operable gastro-oesophageal cancer. Four studies reported an associationbetween elevated NLR and tumour variables, in particular, NLR was reported to increase with T-stage. The
threshold used to define an elevated NLR was inconsistent with each study in oesophageal disease utilising a
different threshold, ranging from >2 to >5. Given the heterogeneity of thresholds used in this group of studies it
was not appropriate to calculate the weighted average hazard ratio for an incremental increase in the NLR.
There were four studies, comprising data on 445 patients investigating the prognostic value of the NLR in
pancreatic cancer [[34],[35],[36],[37]]. Three of these were from the UK and one was from China. Two studies
reported that NLR was an independent predictor of overall survival, however this was not the case for disease-
free survival. In addition, there were no reports of a significant association between clinicopathological variables
and NLR. Interestingly, the study by Wang and colleagues [33] reported that the NLR was significantly associated
with markers of functional decline, including poor performance status and weight loss. The threshold used to
define an elevated NLR was >5 in two studies, >4 in one study, and one study used continuous measurement of
the NLR in the analysis.
Of the two studies using the most commonly used threshold of >5 only one reported a hazard ratio and therefore
it was not appropriate to calculate the weighted average hazard ratio for an incremental increase in the NLR.
Three studies, comprising data on 335 patients investigated the prognostic value of the NLR in hepatocellular
carcinoma[[13],[39],[40]]. Two of these studies were from Japan, and one was from the UK. Two studies
reported the NLR to be associated with overall survival and one study by Gomez et al.[38] reported and elevated
NLR (>5) to be associated with development of satellite lesions, microvascular invasion, and nodal disease. As in
other studies of operative disease at least one group reported that the acute phase protein response appears to
have superior prognostic value. The threshold used to define an elevated NLR was >5 in two studies, and >4 in
one study. Of the two studies using the most commonly used threshold of >5 only one reported a hazard ratio and
therefore it was not appropriate to calculate the weighted average hazard ratio for an incremental increase in the
NLR.
-
8/18/2019 The Role of White Cell Count and c
14/39
Four studies, comprising data on 786 patients, three from Japan and one from the UK, reported the prognostic
value of the NLR in lung cancer patients undergoing resection [[40],[41],[42],[43]]. Three studies reported a
significant association between elevated NLR and survival. Elevated NLR was reported as an independent
prognostic variable in two of these studies. Interestingly, a study by Tomita and colleagues reported that a
combined score using C-reactive protein and NLR was an independent predictor of survival. However, in this
study they report that an elevated C-reactive protein was associated with longer survival, contrary to the
published literature on the prognostic value of C-reactive protein in many solid organ malignancies[4]. The
threshold used to define an elevated NLR was >2.5 in two studies, >5 in one study and as a continuous variable
in one study. Only one study used the most commonly used threshold of >5 and so calculation of the weighted
average hazard ratio was therefore not appropriate.
Four studies, comprising data on 715 patients reported the prognostic value of the NLR in urothelial malignancy
[[44],[45],[46], [47]]. All of these studies were from Japan. Three studies reported that elevated NLR was an
independent predictor of survival, with one study reporting an association with disease-free survival. No
associations with tumoural factors were reported. The threshold used to define an elevated NLR was >2.7 in two
studies, 2.5 in one study and as a continuous variable in one study. None of these studies used the most
common threshold of >5. Given the heterogeneity of the thresholds used calculation of the weighted average
hazard ratio was not appropriate.
One study, comprising data on 192 patients reported the prognostic value of the NLR in gynaecological
malignancy[48]. This study was from Korea. The pre-treatment NLR was associated with overall and disease-
free survival in one study and was reported as an independent prognostic factor together with advancing stage
and increasing age, (HR=8.42 [95% CI: 1.09–64.84], p=0.041).
There was one study of the prognostic value of the NLR in patients with soft tissue sarcoma[49]. This study by
Idowu and colleagues reported an association between pre-operative NLR and disease-free survival. Along-with
tumour grade, NLR was associated with overall survival (HR=4.24 [95% CI: 1.14–15.82], p=0.031).
In conclusion, the last decade has seen the accumulation of good evidence supporting associations between the
neutrophil–lymphocyte ratio and outcome in patients with operable disease, in particular gastrointestinal cancer.
However, while pre-operative NLR is associated with both disease-free and overall-survival in some studies there
is a lack of consistent evidence for its value as an independent predictor of survival, particularly in early stage and
less aggressive disease. Other markers of the systemic inflammatory response, in particular the mGPS, appear
to have stronger prognostic value in these patients.
Jump to Section
-
8/18/2019 The Role of White Cell Count and c
15/39
*. "tudies of the pro#nostic $alue of the %&' in patients with operable cancer who recei$ed
neoad+u$ant therapy
Six studies, comprising data on 1044 patients have reported the prognostic value of the NLR in patients who
received neo-adjuvant therapy and subsequently underwent cancer resection (Table 3, Refs. [[50],[51],[52],
[53],[54],[55]]).
Table 3Studies of the prognostic value of the NLR in patients with operable
cancer who received neoadHuvant therap/.
Stud
y Centre
Tumour
site n
HR ( p-
value)
Thresh
old Comments
@ang
[*,
3uangdon
g #=hina%
D== 1,
1
;.6*
#+,.,,1%
-' levated NLR independentl/
associated with poor 9:S
Dalazun
[*1
New !or"
#$SA%
Liver 1*
,
17.77
#,.,,*%
-* levated NLR associated with
increased ris" of recurrence and
death
&ertuzz
o [*;
&ologna
#Jtal/%
Liver ;1
7
17.1(
#+,.,,1%
-* levated NLR associated with
lower 8S. levated NLR and C5J
negativel/ aected 9:S. levated
NLR and C5J were independentprognostic factors
Sato
[*'
Shizuo"a
#Gapan%
8esophag
eal
)' ;.)'
#,.,('%
-;.; NLR associated with pathological
response to neoadHuvant
cheotherap/
Ci/ata
[*(
8sa"a
#Gapan%
8esophag
eal
1*
;
#Non>
signi?can
t%
-( levated NLR associated with
survival but not independentl/
prognostic
Sharaiha [**
New !or"#$SA%
8esophageal
''7
;.;6#+,.,,1%
-* levated NLR associated withworse 9:S and 8S independent of
tuour t/pe
DFS, disease-free survival; OS, overall survival.
Three of these studies, comprising data on 470 patients, were in hepatocellular carcinoma (HCC)[[50],[51],[52]].
One study was from the USA, one was from Italy, and one from Japan. Among these studies it was consistently
reported that elevated NLR was associated with increased risk of recurrence and risk of death. Although the
thresholds for an elevated NLR differed in one of these studies it was consistently reported that elevated NLR was
http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0015http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0015
-
8/18/2019 The Role of White Cell Count and c
16/39
an independent predictor of both disease-free and overall survival in hepatocellular carcinoma. Interestingly, two
of these studies reported a significant relationship between NLR and microvascular invasion in HCC. The
threshold used to define an elevated NLR was >5 in two studies, and >3 in one study. The weighted average
hazard ratio for an incremental increase in the NLR in the two studies using the most commonly used threshold of
>5 was 19.49.
Three studies, comprising data on 574 patients, reported the prognostic value of NLR in patients with
oesophageal cancer [[53],[54],[55]]. Two studies were from Japan while one was from the USA. In patients
receiving neoadjuvant chemotherapy followed by resection it was reported that elevated NLR was associated with
survival. Interestingly, while the study by Sato and colleagues reported an independent association between the
NLR and pathological response to treatment, the study by Sharaiha and colleagues reported no association
between the NLR and response to treatment. However, both these studies reported an association between
elevated NLR and poor prognosis with Sharaiha and colleagues reporting elevated NLR as an independent
prognostic factor regardless of tumour type.
The threshold used to define an elevated NLR was >5 in one study, >4 in one study, and >2.2 in one study and
therefore it was not appropriate to calculate the weighted average hazard ratio for an incremental increase in the
NLR between these studies.
In conclusion, in patients receiving neoadjuvant chemotherapy followed by surgery it was consistently reported
that NLR predicts recurrence and overall survival. Interestingly, there was inconsistency with regard to the ability
of the NLR to predict pathological response to treatment in this group of patients.
,. "tudies of the pro#nostic $alue of the %&' in patients recei$in# chemoradiotherapy
Twelve studies, comprising data on 2156 patients, reported the prognostic value of the NLR in patients with
cancer receiving chemotherapy, radiotherapy or a combination of both (Table 4, Refs. [[56],[57],[58],[59],[60],
[61],[62],[63],[64],[65],[66],[67]]). Three studies, comprising data on 579 patients, reported the prognostic
value of the NLR in patients with colorectal cancer receiving chemotherapy [[56],[57],[58]]. The NLR was
reported to have prognostic value independent of tumour stage for both overall and disease-free survival in all of
these studies. One study was from Australia, one was from the UK, and one further study was from the USA. The
threshold used to define an elevated NLR was >5 in two studies, and >2.6 in one study. The weighted average
hazard ratio for an incremental increase in the NLR in the two studies using the most commonly used threshold of
>5 was 2.75.
Table 4Studies of the prognostic value of the NLR0 in cancer patients receiving
cheoFradiotherap/.
Jump to Section
http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0020http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0020
-
8/18/2019 The Role of White Cell Count and c
17/39
Study Centre
Tumou
r site n
HR
( p-
valu
e)
Thresh
old Comments
=arruther
s et al.
[*6
3lasgow
#$4%
Rectal 11
*
(.1
#,.,,;%
-* levated NLR - * associated with
decreased 8S0 and 9:S
=hua et
al. [*
S/dne/
#Australia
%
Appendice
al
1
(
#,.,1% -* Low NLR associated with iproved
9:S and 8S. NLR0 =R2 and 2LR all
predicted 8S and 9:S on univariate
anal/sis
4ishi et
al. [*)
Ee and post>treatent NLR
independentl/ associated with 1>0
'>0 *>/ear survival
=edres et
al. [*7
&arcelona
#Spain%
Lung 1
1
1.*
#,.,1*%
-* Association with E and N stage0 but
no association between NLR and
nuber of etastatic sites0
perforance status0 t/pe of
cheotherap/0 use of
glucocorticoids. levated NLR
independentl/ associated with poor
8S and 9:S. 2atients with elevated
NLR that noralised following
treatent had better survival
4ao et al.
[6,
=oncord
#Australia
%
Lung 1
'
;.
#+,.,,
1%
-* NLR treatent
associated with shorter 8S and 9:S
Aliustaogl
u et al.
[6(
Jstanbul
#Eur"e/%
3astric 16
)
#,.,,1% -;.*6 levated NLR was associated with
8S
An et al. 3uangdo 2ancreatic 7* (.(7 -* levated pre>treatent NLR
-
8/18/2019 The Role of White Cell Count and c
18/39
[6* ng
#=hina%
#,.,1'% associated with poor 8S and an
independent predictor of 8S in
patients receiving cheotherap/
4eizan
et al. [66
&altiore
#$SA%
Renal 1'
'
#+,.,,
1%
-' NLR associated with 8S and 9:S
=hua et
al. [6
S/dne/
#Australia
%
5arious 6) ;
#,.,1%
-* =obined 32SFNLR score predicted
8S. NLR that noralised after three
doses of cheotherap/ associated
with iproved 8S
DFS, disease-free survival; OS, overall survival.
Five studies, comprising data on 1113 patients, reported the prognostic value of NLR in patients with thoracic
malignancy receiving chemotherapy [[59],[60],[61],[62],[63]]. These studies were from Japan (1), Australia (1),
Spain (1), Korea (1), and China (1). In this group the pre-treatment NLR was consistently reported to be of
prognostic value both for disease-free and overall survival. Further, the post-treatment NLR was also reported to
be prognostic in this group of patients, in particular the study by Lee and colleagues reported that post-treatment
NLR was independently prognostic for disease-free and overall survival. In addition, the NLR was consistently
associated with response to treatment and prediction of survival. Studies by Kao et al. and Cedres et al. both
reported that normalisation of the NLR following chemotherapy was predictive of improved survival while those
patients with a persistently elevated NLR post-therapy was associated with a worse overall survival.
The threshold used to define an elevated NLR was >5 in two studies, >4.744 in one study, >3.25 in one study,
and >2.63 in one study. The weighted average hazard ratio for an incremental increase in the NLR in the two
studies using the most commonly used threshold of >5 was 2.1.
There was one study reporting the prognostic value of the NLR in gastric cancer[64] (n=168), one in pancreatic
cancer [65] (n=95), one in renal cancer[ 66] (n=133), and one further study reporting the prognostic value of the
NLR in a variety of solid organ malignancies[67] (n=68). Interestingly the threshold used to determine an
elevated NLR varied across all studies, ranging from >2.56 to >5.
In the gastric cancer study by Aliustaoglu et al. [64] it was reported that an elevated NLR (>2.56) was associated
with overall survival but was not an independent predictor of survival. In the pancreatic study it was reported that
an elevated pre-treatment NLR (>5) was an independent predictor of overall survival (HR 4.489, p=0.013). In
renal cancer patients elevated NLR (>3) was also associated with overall and disease-free survival but was not
an independent predictors of survival. Interestingly, the study by Chua and colleagues reported the independent
prognostic value of the NLR (HR 2.0, p=0.010) and that a scoring system using both the NLR and the GPS was
a strong predictor of overall survival. Similar to other studies this study also reported that a normalised NLR post-
treatment was associated with improved overall survival.
-
8/18/2019 The Role of White Cell Count and c
19/39
In conclusion, both the pre- and post-treatment NLR have been reported to be of prognostic value in patients with
more advanced cancer who receive chemotherapy. Pre-treatment NLR was associated with survival across a
variety of tumour types.
Interestingly, at least 3 studies reported that normalisation of the NLR post-treatment was associated with
improved survival. Further, a combined scoring system using the NLR and the GPS was reported to be a strong
predictor of overall survival.
. "tudies of the pro#nostic $alue of the %&' in patients with inoperable cancer
Six studies, comprising data on 1248 patients reported the prognostic value of the NLR in patients with
inoperable cancer (Table 5, Refs. [[68],[69],[70],[71],[72]]). Two studies were in advanced colorectal cancer and
comprised data on 399 patients, one study was from Japan and another from Australia. Both studies reported an
association between elevated NLR and poorer survival in advanced colorectal cancer. In addition, both studies
reported an association with hypoalbuminaemia and that elevated NLR was an independent predictor of worse
survival. Both of these studies used the most commonly used threshold (>5) to determine an elevated NLR. Over
these two studies the weighted average hazard ratio for an incremental increase in the NLR was 1.9.
Table 5Studies of the prognostic value of the NLR0 in cancer patients with
inoperable cancer.
Study Centre
Tumou
r site n
HR
( p-
value
)
Thresh
old Comments
4ane"o
et al.
[6)
Eo"/o
#Gapan%
=olorecta
l
*, (.'7
#,.,,1'
%
-* NLR independentl/ associated with
8S. levated NLR and
h/poalbuinaeia associated with
poor 8S and 9:S
=hua et
al. [6
S/dne/
#Australia%
=olorecta
l
'(
7
1.6
#,.,1%
-* NLR independent predictor of 8S.
LowFNoral NLR associated with
iproved clinical bene?t and
response to treatent
CcNall/
et al.
[67
8hio
#$SA%
D== 1,
'
#,.,;1% -* NLR independentl/ associated with
8S
Duanget al.
3uangzho D== 1( #,.,(1% -'.' levated NLR independentl/associated with poor survival in
Jump to Section
http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0025http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#tbl0025
-
8/18/2019 The Role of White Cell Count and c
20/39
[, u #=hina% * patients with unresectable D==
Geong et
al. [1
Seoul
#4orea%
3astric 1,
(
#,.,'% -' levated NLR and 32S were
independent prognostic factors
@ang et
al. [;
9alian
#=hina%
5ariet/ (7
1.'*
#,.,1(%
-' levated NLR associated with
survival. NLR associated with E>
stage0 tuour t/pe
DFS, disease-free survival; OS, overall survival.
Two studies, comprising data on 248 patients, were in advanced hepatocellular cancer, one from the USA and
one from China. Both studies reported that elevated NLR was an independent predictor of survival in advanced
disease. However each study used a different threshold for determining an elevated NLR, >5 and >3.3,respectively.
One study from Korea reported that an elevated NLR (>3) and mGPS were independent predictors of survival in
advanced gastric cancer.
A large study (n=497) from China reported the prognostic value of the NLR in patients with a variety of tumours
with bony metastases. They reported that elevated NLR together with tumour type was associated with worse
survival and was an independent prognostic factor in patients with bony metastases (HR 1.348, p=0.014).
In conclusion, in patients with advanced, inoperable disease the NLR reliably predicts poorer survival.
/. 'elationships between clinicopatholo#ical factors and %&'
Several of the studies identified in this review examined factors associated with an elevated NLR. In unselected
patients with breast cancer elevated NLR was associated with advancing age, larger tumours, and stage of
disease. Further, increasing tumour stage was also associated with elevated NLR in patients with operable
cancers, namely colorectal, gastro-oesophageal hepatocellular, lung. In addition, factors that represent more
aggressive tumour behaviour, such as increased tumour size, microvascular and lymphatic invasion, lymph node
involvement, number of metastatic lesions and elevated CEA concentrations, were associated with elevated NLR.
Conversely, a number of studies failed to report a relationship between NLR and tumour characteristics.
Only one study in patients receiving chemotherapy (either neoadjuvant or combined chemotherapy/radiotherapy)
has reported that NLR was associated with T-stage and nodal status but not with number of metastatic lesions,
performance status, type of chemotherapy or use of glucocorticoid medication Further, only a single study in
inoperable cancer examined factors associated with NLR and reported that NLR>3 was associated with
Jump to Section
-
8/18/2019 The Role of White Cell Count and c
21/39
increased tumour stage, tumour type, increasing age, and female gender, but not lymph node metastasis or high
CEA or alkaline phosphatise concentrations.
0. iscussion
The hypothesis that haematological markers of the systemic inflammatory response, in particular the neutrophil–
lymphocyte ratio, reliably predict survival in patients with malignancy is one that has garnered a lot of interest in
the last decade. Many groups have investigated the prognostic value of the NLR in a variety of tumours and at
differing stages of disease.
It is clear that there are important associations between the NLR and other markers of the systemic inflammatory
response in patients with operable cancer, in particular with elevated C-reactive protein and hypoalbuminaemia.
While there is good evidence for the prognostic value of the combination of these acute phase proteins in the
mGPS (with its standard thresholds) in early stage disease, the prognostic value of the NLR in isolation is not so
robust in operable cancer, for example in colorectal cancer only four of eleven studies reported NLR as
independently prognostic with an weighted average hazard ratio of 1.4.
It appears that the NLR is more consistently independently prognostic in patients with upper gastrointestinal
malignancy, a group of solid organ malignancies that tend to present at a later stage with more advanced
features. In addition, the association between NLR and T-stage in these tumours appears to be more robust than
in earlier stage, less aggressive cancers. Similarly, the NLR is more consistently prognostic in more advanced
states such as those patients requiring chemotherapy or who have inoperable disease.
Thus, despite the heterogeneous groups of cancer patients within which these relationships have been examined,
a consistent finding in this review was that NLR may reflect a more advanced stage of disease with potentially
more aggressive tumour behaviour. The mechanism that links tumour and host biology remains unclear however,
recent studies have proposed potential mediators linking the tumour and host interaction.
Of particular interest is the emerging role of pro-inflammatory cytokines in the plasma of patients with elevated
NLR (>5) and the observation that these inflammatory cytokines may establish and perpetuate a tumour
microenvironment favouring aggressive tumour behaviour. Recently, a number of studies have undertaken
measurements of circulating cytokines together with the NLR[[13],[14]]. This data offers a unique insight into the
mechanisms underlying an elevated NLR, for example Motomura et al. showed that an elevated NLR was
associated with an increase in IL-17[13] and an increase in the peritumoural infiltration of macrophages. Kantola
and co-workers reported that an elevated NLR was associated with elevated circulating concentrations of IL-1ra,
IL-6, IL-7, IL-8, IL-12, MCP-1, PDGFBB. Taken together, these elevated cytokine concentrations and increased
tumour macrophage infiltration would suggest that the NLR reflects, at least in part, the up-regulation of the
Jump to Section
-
8/18/2019 The Role of White Cell Count and c
22/39
innate immune response. Despite the increasing evidence that pro-inflammatory cytokines play a significant role
in the tumour-host interaction that may influence tumour behaviour these links require further investigation.
With regard to those patients receiving chemotherapy the NLR was consistently reported to have prognostic
value, particularly in patients with lung cancer. In addition, NLR was consistently reported to predict response to
treatment. Further, it has been reported by at least two studies that normalisation of the NLR post-treatment was
significant with those patients not normalising their NLR having a worse prognosis.
These observations are important as the ability of clinicians to predict both response to treatment and value of
treatment after one cycle may help decide both which patients should commence treatment and those who have
responded after one cycle of treatment. This would have important clinical utility as it would potentially identify
those patients in whom aggressive chemotherapy may be futile.
The importance of such an ability to determine more accurately which patients should receive chemotherapy is
important for both quality of life and survival as reported in recent study by Temel et al. [15]. However, the
literature regarding post-treatment measurement of the NLR appears limited and inconsistent and therefore
further longitudinal studies of the prognostic value of the NLR are warranted.
Given these observations it is therefore reasonable to propose that this commonly measured haematological test
could be used as a biomarker in patients who require adjunctive treatment or who do not appear clinically to be
suitable for surgical intervention and would therefore be useful in the improved stratification of patients with
cancer.
While these observations may be of clinical importance, it is important to note that there was considerable
heterogeneity in the thresholds used to determine an elevated NLR across these studies. A threshold of >5 was
the most consistently used, however a variety of thresholds have been reported both in operable disease, in those
receiving chemotherapy, and in inoperable disease. The heterogeneity of the thresholds used makes a conclusion
regarding the clinical utility of the NLR somewhat difficult and further work utilising the most common threshold of
>5 should be considered in an attempt to refine whether this simple measure of the systemic inflammatory
response is reliable as a prognostic marker in the clinical setting.
Interestingly, recent work has proposed that the combination of measures of the systemic inflammatory response
may be a powerful predictor of outcome in cancer. At least one study in the current review has proposed the use
of a combined score using the NLR and markers of the acute phase response and reported that it has improved
value in patients with cancer. Further, a recent large prospective cohort study has reported the use of a combined
biomarker score that has prognostic value in patients with cancer.
Therefore, further studies are required to investigate the prognostic value of such a combined score using
established routinely measured prognostic markers of the systemic inflammatory response, namely C-reactive
protein, albumin, neutrophil and lymphocyte counts.
-
8/18/2019 The Role of White Cell Count and c
23/39
onflict of interest
There is no conflict of interest to declare.
'e$iewers
Akiyoshi Kinoshita, MD, Division of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, 4-11-
1 Izumihon-cho, Komae-shi, Tokyo 201-8601, Japan.
Mitsuru Ishizuka, MD, Department of Gastroenterological Surgery, Dokkyo Medical University, 880 Kitakobayashi,
Mibu, Tochigi 321-0293, Japan.
Basem Azab, MD, Staten Island University Hospital, Department of Medicine, 475 Seaview Avenue, New York,
Staten Island 10305, United States.
'eferences
1. CancerStats. http://www.cancerresearchuk.org. 2005–2009.
;. Hanahan, D. and Weinberg, R.A.The hallmarks of cancer.Cell. 2000; 100: 57–70
o View in Article
o | Abstract
o | Full Text
o | Full Text PDF
o | PubMed
o | Scopus (14582)
'. Hanahan, D. and Weinberg, R.A.Hallmarks of cancer: the next generation.Cell. 2011; 144: 646–674
Jump to Section
Jump to Section
Jump to Section
http://www.cancerresearchuk.org/http://www.cancerresearchuk.org/http://www.cancerresearchuk.org/http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0010http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0010http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=abstract&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=abstract&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=fulltext&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=fulltext&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=pdf&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=pdf&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=10647931&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=10647931&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-0034614637&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-0034614637&cf=http://www.cancerresearchuk.org/http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0010http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=abstract&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=fulltext&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2FS0092-8674(00)81683-9&cf=pdf&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=10647931&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-0034614637&cf=
-
8/18/2019 The Role of White Cell Count and c
24/39
o View in Article
o | Abstract
o | Full Text
o | Full Text PDF
o | PubMed
o | Scopus (10114)
(. Roxburgh, C.S. and McMillan, D.C.Role of systemic inflammatory response in predicting survival
in patients with primary operable cancer.Future Oncology. 2010; 6: 149–163
o View in Article
o | CrossRef
o | PubMed
o | Scopus (243)
*. McMillan, D.C.The systemic inflammation-based Glasgow Prognostic Score: A decade of
experience in patients with cancer.Cancer Treatment
Reviews. 2012;DOI:http://dx.doi.org/10.1016/j.ctrv.2012.08.003(PII: S0305-7372(12)00171-5 [Epub ahead of
print])
o View in Article
o | Scopus (112)
6. Gabay, C. and Kushner, I.Acute-phase proteins and other systemic responses to
inflammation.New England Journal of Medicine. 1999; 340: 448–454
o View in Article
o | CrossRef
o | PubMed
o | Scopus (3191)
. Zahorec, R.Ratio of neutrophil to lymphocyte counts – rapid and simple parameter of systemic
inflammation and stress in critically ill.Bratislavske Lekarske Listy. 2001; 102: 5–14
http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0015http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0015http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=abstract&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=abstract&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=fulltext&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=fulltext&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=pdf&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=pdf&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=21376230&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=21376230&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-79952284127&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-79952284127&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0020http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0020http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.2217%2Ffon.09.136&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.2217%2Ffon.09.136&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=20021215&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=20021215&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-75149189004&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-75149189004&cf=http://dx.doi.org/10.1016/j.ctrv.2012.08.003http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0365http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0365http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_5_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-84876986843&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_5_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-84876986843&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0030http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0030http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1056%2FNEJM199902113400607&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1056%2FNEJM199902113400607&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=9971870&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=9971870&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-0033545342&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-0033545342&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0015http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=abstract&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=fulltext&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.cell.2011.02.013&cf=pdf&site=cellhttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=21376230&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-79952284127&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0020http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.2217%2Ffon.09.136&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=20021215&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-75149189004&cf=http://dx.doi.org/10.1016/j.ctrv.2012.08.003http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0365http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_5_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-84876986843&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0030http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1056%2FNEJM199902113400607&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=9971870&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-0033545342&cf=
-
8/18/2019 The Role of White Cell Count and c
25/39
o View in Article
o | PubMed
). Walsh, S.R., Cook, E.J., Goulder, F., Justin, T.A., and Keeling, N.J.Neutrophil–lymphocyte ratio as a
prognostic factor in colorectal cancer. Journal of Surgical Oncology. 2005; 91: 181–184
o View in Article o | CrossRef
o | PubMed
o | Scopus (334)
7. Schmidt, H., Suciu, S., Punt, C.J.A., Gore, M., Kruit, W., Patel, P. et al.Pretreatment levels of
peripheral neutrophils and leukocytes as independent predictors of overall survival in patients withamerican joint committee on cancer stage iv melanoma: results of the EORTC 18951 biochemotherapy
trial. Journal of Clinical Oncology. 2007; 25: 1562–1569
o View in Article
o | CrossRef
o | PubMed
o | Scopus (89)
1,. Clarke, S.J., Chua, W., Moore, M., Kao, S., Phan, V., Tan, C. et al.Use of inflammatory markers to
guide cancer treatment.Clinical Pharmacology and Therapeutics. 2011; 90: 475–478
o View in Article
o | CrossRef
o | PubMed
o | Scopus (29)
11. Proctor, M.J., Morrison, D.S., Talwar, D., Balmer, S.M., Fletcher, C.D., O’Reilly, D. et al.A comparison
of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome
Study.European Journal of Cancer. 2011; 47: 2633–2641
o View in Article
o | Abstract
o | Full Text
http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0035http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0035http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=11723675&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=11723675&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0040http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0040http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1002%2Fjso.20329&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1002%2Fjso.20329&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=16118772&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=16118772&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-24344442821&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-24344442821&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0045http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0045http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1200%2FJCO.2006.09.0274&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1200%2FJCO.2006.09.0274&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=17443000&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=17443000&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-34248218014&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-34248218014&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0050http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0050http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1038%2Fclpt.2011.122&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1038%2Fclpt.2011.122&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=21775983&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=21775983&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-80052028980&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-80052028980&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0055http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0055http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.ejca.2011.03.028&cf=abstract&site=ejc-sitehttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.ejca.2011.03.028&cf=abstract&site=ejc-sitehttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.ejca.2011.03.028&cf=fulltext&site=ejc-sitehttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.ejca.2011.03.028&cf=fulltext&site=ejc-sitehttp://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0035http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=11723675&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0040http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1002%2Fjso.20329&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=16118772&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-24344442821&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0045http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1200%2FJCO.2006.09.0274&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=17443000&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-34248218014&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0050http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1038%2Fclpt.2011.122&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=21775983&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-80052028980&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0055http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.ejca.2011.03.028&cf=abstract&site=ejc-sitehttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.ejca.2011.03.028&cf=fulltext&site=ejc-site
-
8/18/2019 The Role of White Cell Count and c
26/39
o | Full Text PDF
o | PubMed
o | Scopus (162)
12. Proctor, M.J. Optimization of the systemic inflammation-based Glasgow prognostic score: a Glasgow
inflammation outcome study. Cancer, in press.
1'. Motomura, T., Shirabe, K., Mano, Y., Muto, J., Toshima, T., Umemoto, Y. et al.Neutrophil–lymphocyteratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory
microenvironment. Journal of Hepatology. 2013; 58: 58–64
o View in Article
o | PubMed
o | Scopus (77)
1(. Kantola, T., Klintrup, K., Vayrynen, J.P., Vornanen, J., Bloigu, R., Karhu, T. et al.Stage-dependent
alterations of the serum cytokine pattern in colorectal carcinoma.British Journal of
Cancer. 2012; 107:1729–1736
o View in Article
o | CrossRef
o | PubMed
o | Scopus (39)
1*. Temel, J.S., Greer, J.A., Muzikansky, A., Gallagher, E.R., Admane, S., Jackson, V.A. et al.Early
palliative care for patients with metastatic non-small-cell lung cancer.New England Journal of
Medicine. 2010; 363: 733–742
o View in Article
o | CrossRef
o | PubMed
o | Scopus (1559)
16. Azab, B., Bhatt, V.R., Phookan, J., Murukutla, S., Kohn, N., Terjanian, T. et al.Usefulness of the
neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer
patients. Annals of Surgical Oncology. 2012; 19: 217–224
o View in Article
http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.ejca.2011.03.028&cf=pdf&site=ejc-sitehttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=4&doi=10.1016/j.critrevonc.2013.03.010&key=10.1016%2Fj.ejca.2011.03.028&cf=pdf&site=ejc-sitehttp://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=21724383&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=21724383&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-80755128486&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-80755128486&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0370http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0370http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_13_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=22925812&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_13_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=22925812&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_13_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-84871212252&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_13_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-84871212252&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0070http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0070http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_14_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1038%2Fbjc.2012.456&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_14_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1038%2Fbjc.2012.456&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_14_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=23059742&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_14_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=23059742&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_14_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-84869096388&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_14_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-84869096388&cf=http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0075http://www.croh-online.com/article/S1040-8428(13)00070-X/fulltext?mobileUi=0#back-bib0075http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_15_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1056%2FNEJMoa1000678&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_15_2&dbid=16&doi=10.1016/j.critrevonc.2013.03.010&key=10.1056%2FNEJMoa1000678&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_15_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=20818875&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_15_2&dbid=8&doi=10.1016/j.critrevonc.2013.03.010&key=20818875&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_15_2&dbid=137438953472&doi=10.1016/j.critrevonc.2013.03.010&key=2-s2.0-77955877759&cf=http://www.croh-online.com/servlet/linkout?suffix=e_1_5_1_2_15