Do 2-cm pancreatic tumors localize in the pancreas?Analysis of the greatest and smallest diametersof the autopsied pancreas

I nt r oduct i on

　Panc r e at i c c anc e r mor t al i t y has be e n i nc r e as i ng wor l dwi de

and i n Japan

. De s pi t e advanc e s i n di agnos t i c s and t he r ape ut i c s , panc r e at i c c anc e r pr ognos i s r e mai ns poor , wi t h an ove r al l 5- ye ar s ur vi val r at e of 6%, due i n par t t o di f f i c ul t i e s i n di agnos i ng c ar c i noma at an e ar l y s t age

. Pr e vi ous l y ,

we r e t r os pe c t i ve l y e val uat e d 8, 339 aut ops i e s pe r - f or me d at our hos pi t al and f ound t hat di s t ant me t as t as e s we r e pr e s e nt i n 27% of c as e s of oc c ul t panc r e at i c duc t al ade noc ar c i noma ( PDAC)

, s ugge s t - i ng t hat PDAC e xhi bi t s aggr e s s i ve be havi or e ve n at e ar l y s t age s .

　Loc al t umor gr owt h and t umor s i z e ar e t he ke y f ac t or s t hat de t e r mi ne t he pr ognos i s of pat i e nt s wi t h PDAC

. The r e f or e , we e val uat e d t umor s ac c or di ng

Do 2- cm pancr eat i c t umor s l ocal i z e i n t he pancr eas?

Anal ysi s of t he gr eat est and smal l est di amet er s of t he aut opsi ed pancr eas

Yoko Mat suda * , Toshi yuki I shi wat a ** , At suko Seki * , Kei suke Nonaka * , Junko Ai da ** , Kai yo Takubo ** , Wat ar u Ki mur a *** , Tomi o Ar ai *

**

* Depar t ment of Pat hol ogy, T ok yo Met r opol i t an Ger i at r i c Hos pi t al

** Res ear ch T eam f or Ger i at r i c Pat hol ogy, T ok yo Met r opol i t an I ns t i t ut e of Ger ont ol ogy

*** Depar t ment of Gas t r oent er ol ogi cal , Gener al , Br eas t and T hyr oi d Sur ger y, Yamagat a Uni v er s i t y Facul t y of Medi ci ne

（Accept ed Mar ch 25, 2016 ）

Backgr ound: Loc al t umor gr owt h and t umor s i z e ar e ke y f ac t or s t hat de t e r mi ne t he pr ognos i s of pat i e nt s wi t h panc r e at i c c anc e r s . I n t he pr e s e nt s t udy , we me as ur e d t he t he gr e at e s t and s mal l e s t di ame t e r s of t he panc r e as t o c l ar i f y t he l ar ge s t panc r e at i c duc t al ade noc ar c i nomas t hat c an be c onf i ne d t o t he panc r e as .

Mat er i al s and Met hods: Panc r e at i c t i s s ue s obt ai ne d f r om 10 aut ops i e d pat i e nt s we r e c ut i nt o 5- mm s e c t i ons ve r t i c al t o t he mai n panc r e at i c duc t . Eac h s l i c e was pr oc e s s e d f or mi c r os c opi c e xami nat i on and was c apt ur e d us i ng a vi r t ual s l i de s c anne r . We me as ur e d t he gr e at e s t di ame t e r of t he panc r e as i n e ac h s l i de .

Resul t s: The ave r age gr e at e s t di ame t e r s of t he panc r e at i c body and t ai l we r e l e s s t han 2 c m i n 2 c as e s f or t he panc r e at i c body and 5 c as e s f or t he panc r e at i c t ai l . Al l c as e s c ont ai ne d s l i de s f or whi c h t he gr e at e s t panc r e at i c di ame t e r me as ur e d l e s s t han 2 c m, wi t h 5 c as e s f or t he panc r e at i c he ad and body and 9 c as e s f or t he panc r e at i c t ai l . The ave r age s mal l e s t di ame t e r s of t he panc r e at i c he ad, body , and t ai l we r e l e s s t han 2 c m f or al l c as e s , and t he r e we r e 3 c as e s i n whi c h t he y we r e l e s s t han 1 c m.

Concl usi on: Our s t udy , whi c h e val uat e d t he e nt i r e panc r e at i c par e nc hyma f r om aut ops y t i s s ue s , r e ve al e d t hat t he panc r e as has many ar e as whe r e di ame t e r s ar e l e s s t han 2 c m, s ugge s t i ng t hat mos t 2- c m t umor s c annot be l i mi t e d t o t he panc r e as .

Key wor ds: panc r e as ; aut ops y; gr e at e s t di me ns i on; e ar l y c anc e r

ABSTRACT

t o t he Japane s e c l as s i f i c at i on of panc r e at i c c ar c i noma.

T1 t umor s ar e l i mi t e d t o t he panc r e as and me as ur e l e s s t han 2 c m at t he gr e at e s t di me ns i on. T2 t umor s ar e l i mi t e d t o t he panc r e as and me as ur e l ar ge r t han 2 c m at t he gr e at e s t di me ns i on. T3 t umor s e xt e nd be yond t he panc r e as but do not i nvol ve t he l ar ge ve s s e l s , whi l e T4 t umor s i nvol ve t he por t al ve i n, c e l i ac axi s , or t he s upe r i or me s e nt e r i c ar t e r y . T1 and T2 PDACs ar e e xpe c t e d t o have good pr ognos e s owi ng t o l i mi t e d panc r e at i c l oc al i z at i on

. Howe ve r , we of t e n s e e t hat s mal l PDACs e xpand be yond t he panc r e as and i nvol ve t he pe r i panc r e at i c adi pos e t i s s ue or duode num be c aus e t he panc r e as doe s not have a c aps ul e , and PDAC e as i l y i nvade s be yond t he panc r e as , e s pe c i al l y i n an at r ophi e d panc r e as . I n t he pr e s e nt s t udy , we me as ur e d t he gr e at e s t di me ns i on of

t he panc r e as t o c l ar i f y t he maxi mal s i z e of PDACs l i mi t e d t o t he panc r e as .

Mat er i al s and Met hods

Pat i e nt s

　Ti s s ue s we r e obt ai ne d f r om 10 aut ops y pat i e nt s who r ange d i n age f r om 42 t o 95 ye ar s ( f e mal e , 3;

mal e , 7) . Aut ops i e s we r e pe r f or me d at t he Tokyo

Me t r opol i t an Ge r i at r i c Hos pi t al be t we e n 2014 and

2015. Pat i e nt s wi t h i nvas i ve c ar c i noma and/ or

i nt r aduc t al papi l l ar y muc i nous ne opl as m ( I PMN)

t hat mi ght r e nde r panc r e at i c s i z e me as ur e me nt s

di f f i c ul t we r e e xc l ude d. Thi s s t udy was c onduc t e d i n

ac c or danc e wi t h t he pr i nc i pl e s e mbodi e d i n t he 2008

De c l ar at i on of He l s i nki , and i nf or me d wr i t t e n

Fi gur e 1. Gr os s e xami nat i on of t he panc r e as f r om an aut ops y c as e . The panc r e as was c ut i nt o 5- mm s e c t i ons

ve r t i c al l y ( bl ac k l i ne ) t o t he mai n panc r e at i c duc t ( c r os s s e c t i on) , and e ac h s l i c e was c ar e f ul l y e xami ne d be f or e

pr oc e s s i ng f or mi c r os c opi c e xami nat i on. The r e d l i ne i ndi c at e s t he panc r e as .

c ons e nt f or t he us e of t i s s ue s was obt ai ne d f r om t he be r e ave d f ami l i e s .

Pat hol ogi cal e xami nat i ons

　The panc r e as and t he at t ac he d duode num, i nc l udi ng t he papi l l a of Vat e r , we r e c ut i nt o 5- mm s e c t i ons ve r t i c al t o t he mai n panc r e at i c duc t . Af t e r gr os s e xami nat i on, e ac h s l i c e was pr oc e s s e d f or mi c r os c opi c e xami nat i on. A 3- μ m- t hi c k s e c t i on was c ut f r om e ac h par af f i n- e mbe dde d t i s s ue bl oc k, and t he s e c t i ons we r e s t ai ne d wi t h he mat oxyl i n and e os i n.

Al l s l i de s we r e c apt ur e d us i ng a vi r t ual s l i de s c anne r ( NanoZoome r 2. 0- RS, Hamamat s u phot oni c s K. K. , Hamamat s u, Japan) at × 200 magni f i c at i on. We me as ur e d t he gr e at e s t and s mal l e s t di ame t e r s of t he panc r e as i n e ac h s l i de ( Fi g. 2) .

Resul t s

　We me as ur e d t he gr e at e s t panc r e at i c di ame t e r s us i ng ve r t i c al panc r e at i c s e c t i ons . The ave r age gr e at e s t di ame t e r val ue s f or t he panc r e at i c he ad, body , and t ai l ar e s ummar i z e d i n Tabl e 1. I n al l c as e s , t he ave r age di ame t e r of t he panc r e at i c he ad was l ar ge r t han 2 c m, whi l e t he ave r age di ame t e r s of t he panc r e at i c body and t ai l we r e l e s s t han 2 c m i n 2 and 5 c as e s , r e s pe c t i ve l y . The s l i de numbe r s f or whi c h t he gr e at e s t panc r e at i c di ame t e r s we r e l e s s t han 2 c m ar e s ummar i z e d i n Tabl e 1. Among t he s e , we obs e r ve d 5 c as e s i nvol vi ng t he panc r e at i c he ad and body and 9 c as e s i nvol vi ng t he panc r e at i c t ai l .

T abl e 1. The gr e at e s t di ame t e r s of t he panc r e at i c t i s s ue s and t he s l i de numbe r s f or whi c h panc r e at i c di ame t e r s me as ur e d l e s s t han 2 c m

Numbe r of s l i de s f r om t i s s ue s wi t h di ame t e r s l e s s t han 2 c m The ave r age gr e at e s t di ame t e r

( c m) Se x

Age

Tai l Body

He ad Tai l

Body He ad

7/ 9 1/ 7

0/ 6 1. 64

2. 16 3. 48

M 88

0/ 4 1/ 3

0/ 3 1. 92

1. 75 4. 18

M 93

1/ 3 0/ 3

2/ 5 2. 08

2. 30 2. 57

M 61

2/ 4 3/ 6

1/ 5 1. 99

2. 07 3. 60

F 81

1/ 3 0/ 3

0/ 5 2. 25

2. 77 3. 06

F 95

3/ 8 5/ 8

1/ 7 1. 94

1. 94 3. 16

M 70

1/ 4 0/ 3

0/ 5 2. 31

2. 59 3. 11

F 78

1/ 2 1/ 4

1/ 5 2. 01

2. 36 3. 17

M 69

1/ 5 0/ 5

1/ 8 2. 23

2. 55 3. 89

M 42

3/ 3 0/ 1

0/ 2 0. 93

2. 29 3. 55

M 67

Fi gur e 2. Re pr e s e nt at i ve ve r t i c al i mage of t he panc r e at i c he ad. The bl ac k l i ne s i ndi c at e t he gr e at e s t di ame t e r

( 2. 43 c m) and t he s mal l e s t di ame t e r ( 1. 33 c m) .

　The ave r age s mal l e s t di ame t e r s of t he panc r e at i c he ad, body , and t ai l we r e l e s s t han 2 c m i n al l c as e s ( Tabl e 2) . I n t hr e e c as e s , t he ave r age s mal l e s t di ame t e r s we r e l e s s t han 1 c m.

Di scussi on

　I n t hi s s t udy , we e val uat e d t he e nt i r e panc r e as us i ng s e r i al s e c t i ons f r om 10 aut ops y s pe c i me ns . We f ound t hat t he r e ar e many ar e as f or whi c h t he gr e at e s t panc r e at i c di ame t e r i s l e s s t han 2 c m. I n addi t i on, t he ave r age s mal l e s t di ame t e r of t he panc r e as was l e s s t han 2 c m i n al l c as e s , whi l e i t was l e s s t han 1 c m i n 3 c as e s . The s e r e s ul t s i ndi c at e t hat as t he y gr ow, PDACs woul d not be l i mi t e d t o t he panc r e as , e ve n i f t he y me as ur e d l e s s t han 2 c m i n di ame t e r . Thi s al s o s ugge s t s t hat s mal l PDACs c an e as i l y i nvade pe r i panc r e at i c t i s s ue s . Mos t PDACs ar e c l i ni c al l y di s c ove r e d as T3 l e s i ons

. The r e f or e , we mi ght ne e d t o r e c ons i de r t he de f i ni t i on of T1 PDACs . Our dat a s ugge s t t hat t r ul y l oc al i z e d PDACs mus t me as ur e l e s s t han 1 c m.

　Ac c ur at e t umor s i z e and l oc at i on e val uat i on f or PDACs has be e n di f f i c ul t be c aus e i magi ng me t hods , i nc l udi ng CT, MRI , and ul t r as onogr aphy , c annot di s t i ngui s h be t we e n panc r e at i c t i s s ue and pe r i panc r e - at i c t i s s ue . The r e f or e , pat hol ogi c al e xami nat i on s ome t i me s f i nd c anc e r i nvas i on i nt o t he duode nal wal l and pe r i panc r e at i c adi pos e t i s s ue , e ve n f or c as e s pr e ope r at i ve l y di agnos e d as T1 or T2 l e s i ons .

　I nt e r e s t i ngl y , al l panc r e at i c t i s s ue s c ont ai ne d ar e as f or whi c h t he s i z e s we r e l e s s t han 2 c m. The

panc r e at i c ne c k and t ai l us ual l y had s mal l e r di ame t e r s t han t he he ad and body . The r e f or e , we ne e d t o e val uat e t umor s i z e s us i ng al l panc r e at i c s pe c i me ns t o obt ai n ac c ur at e pat hol ogi c al di agnos e s .

　Our s t udy has s e ve r al l i mi t at i ons . The ave r age pat i e nt age was 74. 4 ye ar s , whi c h i s ol de r t han t hat of t he ave r age pat i e nt wi t h PDAC. Mos t i mpor t ant l y , t umor s gr ow i n t hr e e - di me ns i onal s pac e s . The r e f or e , our t wo- di me ns i onal anal ys i s has l i mi t at i ons . We ne e d t o e val uat e t umor gr owt h t hr e e - di me ns i onal l y us i ng c omput e d t omogr aphy or magne t i c r e s onanc e i magi ng, but our anal ys i s us i ng pat hol ogi c al s pe c i me ns doe s pr ovi de an ac c ur at e s i z e f or panc r e at i c t i s s ue and di s t i ngui s he s i t f r om pe r i panc r e - at i c t i s s ue .

　I n s ummar y , our s t udy e val uat e d t he e nt i r e panc r e at i c par e nc hyma us i ng aut ops y s pe c i me ns and r e ve al e d t hat t he r e ar e panc r e at i c r e gi ons t hat me as ur e l e s s t han 2 c m i n di ame t e r . I de nt i f yi ng t he s e f e at ur e s may f ac i l i t at e ac c ur at e t umor s i z e , l oc at i on, and t umor s t age e val uat i on.

Acknowl edgement s

　The aut hor s t hank al l of t he t e c hni c al s t af f f r om t he De par t me nt of Pat hol ogy at Tokyo Me t r opol i t an Ge r i at r i c Hos pi t al f or t he i r t e c hni c al as s i s t anc e .

Ref er ences

1 . Si e ge l , R. , e t al . : Canc e r s t at i s t i c s , 2014. CA Canc e r J Cl i n, 2014; 64( 1) : 9- 29

T abl e 2. The s mal l e s t di ame t e r s of t he panc r e at i c t i s s ue s and t he s l i de numbe r s f or whi c h panc r e at i c di ame t e r s me as ur e d l e s s t han 2 c m

Numbe r of s l i de s f r om t i s s ue s wi t h di ame t e r s l e s s t han 2 c m The ave r age s mal l e s t di ame t e r

( c m) Se x

Age

Tai l Body

He ad Tai l

Body He ad

9/ 9 7/ 7

5/ 6 1. 08

1. 13 1. 24

M 88

4/ 4 3/ 3

3/ 3 0. 89

0. 96 1. 72

M 93

3/ 3 3/ 3

5/ 5 1. 14

1. 33 1. 34

M 61

4/ 4 6/ 6

4/ 5 1. 51

1. 40 1. 46

F 81

3/ 3 3/ 3

3/ 5 1. 13

1. 05 1. 71

F 95

8/ 8 8/ 8

6/ 7 0. 98

1. 00 1. 53

M 70

4/ 4 3/ 3

4/ 5 1. 02

1. 03 1. 73

F 78

2/ 2 4/ 4

2/ 5 1. 37

1. 12 1. 86

M 69

5/ 5 5/ 5

5/ 8 1. 16

1. 32 1. 60

M 42

3/ 3 1/ 1

2/ 2 0. 69

0. 95 0. 84

M

67

2 . Foundat i on f or Pr omot i on of Canc e r Re s e ar c h, Avai l abl e at : ht t p: / / ganj oho. j p/ dat a/ pr of e s s i onal / s t at i s t i c s / bac knumbe r / 2013/ c anc e r _s t at i s t i c s _2013. pdf Ac c e s s e d Apr i l 28, 2014

3 . Mat s uda, Y. , e t al . : Cl i ni c opat hol ogi c al Fe at ur e s of 15 Oc c ul t and 178 Cl i ni c al Panc r e at i c Duc t al Ade noc ar c i nomas i n 8339 Aut ops i e d El de r l y Pat i e nt s . Panc r e as , 2016; 45( 2) : 234- 240

4 . Hr uban, R. H. , e t al . : Tumour s of t he panc r e as , i n

WHO Cl as s i f i c at i on of Tumour s of t he Di ge s t i ve Sy s t e m , F . T. Bos man, e t al . , Edi t or s . 2010, I ARC: Lyon.

5 . Le wi s , R. , e t al . : A c ont e mpor ar y anal y s i s of s ur vi val f or r e s e c t e d panc r e at i c duc t al ade noc ar c i noma . HPB ( Oxf or d) , 2013; 15( 1) : 49- 60

6 . Har t wi g, W. , e t al . : Panc r e at i c c anc e r s ur ge r y i n t he

ne w mi l l e nni um: be t t e r pr e di c t i on of out c ome . Ann

Sur g, 2011; 254( 2) : 311- 319