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Copyright is owned by the Author of the thesis. Permission is given for a copy to be downloaded by an individual for the purpose of research and private study only. The thesis may not be reproduced elsewhere without the permission of the Author.

CARCINO!-IAS OF THE SMALL DiTESTINE

IN SEEEP

A Th8sis presented in partial fulfilment of the requireme�ts

for ·�he Degree of Doctor of Philosophy o.t Masse,y University.

Bruce Henry Simpscn

1971

A C K N 0 W L E D G E M E N T S

I wish to thank my supervisors for their hel� anQ encouragement

during this work. In particula�I thank Dr R.D. Jolly, for his

enthusiasm, interest and constructive discussions at all stages of the

investigations and preparation which have contributed to this thesis;

Dr M. C. Lc>.ncaster, for his interest and enthusiasm ,.,hich enabled this

work to be co��enced; Professor I. Hayman , for his assistance with the

analyses of the results of the epidemiological investigation; �tir D.

Cordes, for his interest throughout and f.:>!.' his comments on the draft

of this thesis; and Dr S. Jamieson, of the Department of Agriculturer

who together with M:r C.R. Ensor, my Controlling Officer at the time this

work was ccmmeltceU., enabled me to obtain time from other duties, and gave

me every encouragemer.t to complete this thesis.

The earlier investigatior..s of neoplasia in sheep by Ml"' IV. M. Webster

ciid much to sbmulate the intarest which :rade this project possible.

For this, and for his making available the detaile.:l. data he collected,

I wish to thanY: :Mr Hebster.

:My ap:pr�ciation is also extende;d to the staff of the histology

laboratory at Massey University (especially Mr D. Wa-rcl and 'Mrs J. Lang ),

for the preparation of histological material; the �taff of the electron

microscope 1.4ni t at the D. S. I.R. in Pa� merston North ( esp'3cic>.lly J.!essrs

A. Craig and n. Hopcroft ), for the preparation of material for

examination in the electron microscope and for printing the photographs

obtained fro._, that material; the staff of the computer unit at :rtassey

University (especially Miss N. Gordon and :r.1r T. Weber ) , for performing

statist ical analyses on the computer; I·ilr J. Austin of ?:!a:::sey University,

for printing the majority of photographs appearing in this thesis ; the

librarians at ]'.1assey University (especially Miss N. Green ), who obtained

the majority of references used in this thesi s from other librarie s ; and

Nrs V . Swan, for typing this thesis .

From the others \'lho assisted in various facets of this work, I

wish to mention the Livestock Instructors of the Department of Agriculture,

Palmerston North, who gave assistance in sheep handling and the colle ction

of bracken fern; li'J.r C . H. Van Kraayenoord and his staff of the N'ri.nistry

of Works , who provided grazing for, and assistance with the management of,

experimental shE:e:r; and the Management and Heat Inspection staffs at the

various Meat Export Wcrks visited, whose coop8ration made my task of

colle cting material and data from sheep slaughtered in those establishments

an easier one than it might othe��ise have been.

, Special thanks are due to the Central Districts Division of the

Cancer So ciety of New Zealand who provided financial ass:i.stance for t�is

work.

T A B L E 0 F C 0 N T E N T S

Page

LIST OF TABLES

LIST OF FIGURES

IN'rRODUCTION

CHAPTER I REVIEW OF LITERATUID� 1

NEOPLASIA D� SHEEP 1 S:1eep Pulmonary Adenomatosis 2 Neoplasia of the Olfactory Mucosa 5

Squamous Cell Carcinomas of the Exposed Skin 6 S�uamous Cell Carcinomas of the Wool Bearing Skin 6 Hepatic Neoplasms 1 Lymphosarcomas 8

Tumours of Cartilage 10

Carcinomas of the Bladder 10

Carcinomas of the Small Intestine 11

SOME COHPARATIVE ASP:!I:CTS OF THE OCCURRENCE OF

SivlALL INTESTINAL CARCINO!tli\S 1 3

Cattle 1 3

Dogs 1 4

Cats 15

Horses 15

Pigs 16

Goats 16

Non-domesticated Mammals 16 Laboratory animals 16

Birds 17

Humans 1 7

CHAPTER II : THE PATHOLOGY OF CARCINOfM.S ARISI�!G IN THE

SMALL INTESTINE OF SHEEl'

INTRODUCTION

1 9

1 9

The Pathology of Small Intestinal Carcinomas in Man 19

·rhe Pathology of Small Intestinal Carcinomas

in Sheep 20

The Pathology of Small Intestinal Carcinomas

in Other Domestic Species 23

The Histogenesis of Experimentally Induced

Carcinomas of the Small Intestine 24

:t>'IATERIALS AND IdE.'THODS 25

RESULTS 26

Gross Pathology of Small Intestinal Carcinomas 26

Histopathology of Small Intesti�al Carcinomas 30

Lll trastructure of Small Intestinal Carcinomas 34

DISCUSSION 37

mnn:ARY 45

CHAPTER III : AN INVESTIGATION OF THE EPIDEMIOLOGY OF

CARCDJOMAS OF 'rilli S.Mfl..LL INTESTINE IN

SHEEP

INTRODUCTION

MA'l'l!:RIALS AND METHODS

Collection and Evaluation of Data

Geographic Distribution of Carcinomas of the

Small Intestine

Correlation of Tumour Prevalence with Average

47

47

5.? 55

55

Stocking Densities in Areas 55 Effect of Environment on Prevalence of Small

Intestinal Carcinomas 57

Physiographic and Botanical Data Concerning

Farms Investigated

( i) Soil Types

( ii) Climate

( iii) Altitude and Latitude

(iv ) Plant Species

58

58

59

59

Managerial Factors

( i) Stock Ma.nagement

(ii) Animal Remedies and Agricultural

Chemicals Used

(iii) Supplementary food

59

59

60

60

Flock Disease History 60

Analysis of Data 60

RESULTS 6 1

Collection and Evaluation of Data 61

Geographic Distribution of Carcinomas of the

Small Intestine 62

Correlation of Prevalence of Carcinomas of the

Small Intestine vvi th Stock Density

The Effect of Znvironment on PrevaleDce of Small

Intestinal Carcinomas

(a) Differences betv;een Farms with High and

Lovl Prevalence o:l Small Intestinal

Carcinomas (b) Relationships Between Various Factors

and Prevalence of Small Intestinal

63

64

65

Carcinomas 67

Relationship Between Line Size and Prevalence

of Small Intestinal Carc::.r.oma 68

DISCUSSION 68

Geographic Distribution of Carcinomas of the

Small Intestine

The Effect of Environment on the Prevalence

of Small Intestinal Carcinomas

72

73

The Aetiological Significance of Factors Associated

with Variations in Prevalence of Carcinomas

of the Small Intestine

(a) Crested dogstail

(b) Potassic fertilisers

76

76

77

(c) Average annual rainfall

(d) Sheep stocking den3ity

(e) Length of time sheep \-Tere on the

property from \vhich they were sent

for slaughter

Factors Suggested of Aetiological Significance

by Previous Authors

78

79

80

81

(a) Phenothiazine 81

(b) Bracken fern (Pteridium aquilinum) 82

SUMMARY 84

CHAPTER IV CARCINOGENICITY OF CERTAIN CHEI,UCALS

ADMINISTT-3RED TO SHEEP 86

INTRODUCTION 86

Chemical Carcino�ens Previously Administered. to

Sheep 86

CarcinoGens Used in this experiment 87 Nethylcholanthrene 87 Benzpyrene 88

Urethane 88

U-methyl-N-nitrosoguanidine 89

MATERIALS AND METHODS 90

RESULTS 91

DISCUSSION 93

SUMr·1ARY 100

CHAPTER V THE CARCINOGENICITY OF BRACKEN FERN (Pteridium aquilnum va.r. esculentum) 101

INTRODUCTION 101

MATERIALS AND METHODS 103

Rats 103

Sheep ·103

Diet 104

RESULTS 104 Rats 1 04

Sheep 1 05

DISCUSSION

3UMMARY

CHAP'rER VI : AN ATTEMPT TO TRANSMIT OVHJE SMALL INTESTINAL

CARCINOMAS TO OTHEii SHEEP

INTRODUCTION

1•IA'rERIALS AND METHODS

RESULTS

DISCUSSION

SUMMARY

CHAPTER VII : GENERAL DISCUSSION

SUMftiARY

REFERENCES

1 05

1 09

1 1 0

1 1 0

1 1 1

1 1 2

1 1 3

1 2 1

1 22

1 30

1 33

Table

I

II

III

IV

V

VI

VII

VIII

IX

X

XI

XII

XIII

L I S T 0 F T ABLE S

The Prevalence of Tumours in Slaughtered

Animals

f·liscellaneous Neoplasms of Sheep Diagnosed

by Various Authors

The Numbers of Neopla.sms of Different Types

Diagnosed by Various Authors

Hepatic Tumours Diagnosed by Various Authors

The Number of Small Intestinal Carcinomas

Diagnosed in Series of Ovine Tumours

The Numbe�s of Small Intestinal Carcinomas

Diagnosed. in Series of Bo,'ine Tumours

Examined by Various Authors

The Numbers of Small Intestinal Carcinomas

Diagnosed in Series of Canine Neoplasms

The Number of Small Intestinal Carcinomas

Diagrwsed in Series of Feline Neoplasms

Proportion of Malignant Tumours of the Small

Intestine in Man \vhich are Carcinomas

Age and Sex Distribution of Human Patients

with Car·cinoma of the Small Intestine

Phe Number of Primary Lesions in Each of

Fifty Consecutive Sheep \ii th Carcinomas of

the Small Intestine

Counties Used in Calculations of Average

Stock Grazing Densities in Areas from

which Inspected Ewes Originated

Numbers of Ewes Examined and Small Intestinal

Carcinomas Found in Seven Geographic Areas

facing page

2

2

1

7

1 1

1 4

1 5

1 8

1 8

57

cf New Zealand During 1 967 and 1 968 62

Tables

XIV

XVI

XVII

XVIII

XIX

XX

XXI

XXII

XXIII

facirlg page

Carcinomas of the Small Intestine F'ound in

British Breed and "Fine Hool" Sheep Inspected

at South Canterbury Durin& 1 968 62

Carcinomas of the Small Intestine Found in

Sheep Identified as British Breed and "Fine

�vool" Sheep Inspected During 1 967 and 1 968 62

Carcinomas of the Small Intestine Found in

British Breed Sheep Inspected in Different

Districts of New Zealand During 1 967 and

1 968 62

X2

figuref: and Probabilities (p ) for

Differences Between Tumour L1cidences in

Tiritjsh Breed Sheep from Different Areas 62

Sheep and Beef Cattle StocL::ing Rates and

'l\�mour.� Prevalence in Areas from which � .. es

were Inspected

Analysis of Significance of the Assvciation

of Cattle and Sheep Stocking Rates with

'l\1mour Prevalence

Numbers of Ell'l'es Inspected From Indiv-idual

Sheep Vendors

Tabulations of Farm3 with High, and Low,

Prevalence of Carcinomas of the s�all

Intestine According to Knuwn Exposure to Various Physiographic, Botan1cal and

Managerial Factors

Cattle and Sheep Stodking Rates on High and

Low Tumour Prevalence Farms

Tabulations of Shee1: With, and Without,

Carcinomas of the Small Intestine According

to Known Exposure to Various Physiographic,

Botanical and Manc..gerial Factors

63

63

64

65

66

67

Table

x..xrv Prevalence (%) of Carcinomas of the Small

Intestine in Sheep Exposed, and not

Exposed to Factors with \vhich Statistically

Significant (p <. 05 ) Differences in

Prevalence were Associated

facing page

67

XXV Comparison of the Number of Significant

XXVI

XXVII

XXVIII

XXIX

XXX

XXXI

XXXII

Chi Squared Results in Table XXIII with

Number of Significant Results Expected

Due to Chance

Cross Tabulation of Data Pertaining to

Average Annual Rainfall and Presence or

Absence of Dogstail on the Property from

which Ewes Here Forwarded for S:!.aughter

Tumour Prevalence in Slaughtered �1es

For\varded by Vendors in Groups of Varying

Sizes

Prevalence of Tumours in Large and Small

Lines of E>ies ,.,here Lines of Both Over and

Under Fifty v1ere Inspected from the same

Vendor

The Prevalence of Carcinomas of the Small

Intestine in �.,res Forwarded f or Slaughter

67

68

68

68

in Lines of Various Sizes (Webster's data ) 71

Age of Control Sheep at Time of Death 91

The Effect of Treating Sheep with Intra-

peritoneal Injections of Methylcholanthrene 91

The Effect of Treating Sheep with Intra­

peritoneal Injections of Benzpyrene 91

Table

XXXIII

XXXIV

X:X:CVI

XXXVII

facing page

The Effect of Treating Sheep l'i'i th Intra­

peritoneal Injections of Urethane 91

The Effect of Treating Sheep with Intra-

peritoneal Injec·�ions of Ni trosoguanidine 91

The Effect of Treating Sheep with Intramural

Injections of Methylcholanthrene into the

Intestinal Wall 91

Surivival Times of Rats frorr. the Commencement

of Experimental Feeding

Numbers of Lambs of Each Sex Treated with

Various Tumour Homogenate Preparations

104

1 1 2

0 F FIGURES

Figure facing page

\

1 The anatomical distribution of primary

lesions of small intestinal carcinoma

in fifty consecutive affected sheep. 27 following page

2 A carcinoma of the: small intestine appearing

as a small white area on Lhe intestinal

serosa (A) but visible through the

serosa over a larger area (limits indicated

by large arrovlS). 26

3 A carcinoma of the small intestine (A)

extending as an annular band around

the intestine

4 The luminal surface of a small intestinal

carcinoma (C) raised above the surrounding

mucosa. (scale is in cm).

5 A carcinoma of the small intestine with

a single large polyp attached to the

mucosal portion uf th8 primary lesion

(scale is in cm).

6 1·1ul tiple polyps (P) developing from the

luminal surface of a primary carcinoma of

t�e small intestine (scale is in cm).

1 Dilatation of the small intectine proxim�l

to the primary lel::lion of a small intestinal

26

26

26

26

carcinoma (A). 26

8 White threads of lymphatic permeation (�P)

extending from a carcinomatous lesion on

the intestinal wall (I) to an affected

mesenteric lymph node (U:).

9 Secondary lesion of a small intestinal carcinoma

at the mesenteric attachment of the small

27

intestine (scaie is in cm). 27

Figure following page

1 0 Primary lesion (A) of a small intestinal

carcinoma with spread proxima�ly along

the intestinal serosa (SL) and with a

band of scirrhous tissue (S) extending

across the rnese;1tery to a mesenteric

lymph node (LN). (scale is in cm)

1 1 Part of small intestine proximal to primary

carcinomatous lesion vli th small nodules

(S) on serosal surface \.,ri th threads of lymphatic

permeation (LP) between the nodules and the

27

mesenteric attachment of' the small intestine. 27

1 2 Small secondary lesions (SL) of an

intestinal carcinoma, located on the wall

of the small intestine.

1 3 Bandc of scirrhous neoplastic lesions (SL)

e�t�nding lon�itudinally along the wall

of the small intestine.

1 4 Scirrhous tumour tissue (T ) ensheathing a

length of small i1�estine �roximal to the

primary lesion of an intestinal carcinoma

( A) •

1 5 Translucent lesion (Tr ) on the serosal surface

of the intestine proximal to the pr·imary

lesion of a carcinoma of the small intestine.

(scale is in cm ) .

1 6 Secondary lesions of a carcinoma of the ,'3mall

intest�ne forming white plaque (Pl) on the

27

27

28

28

parietal peritoneum. 28

1 7 Secondary lesions from a small intestinal

carc�noma involving the diaphr�m.

1 8 Portion of carcinoma of the small intestine

replacing the intestinal mucosa. The lesion consists, predominantly, of neoplastic cells

28

Figure follov-:ing page

(NC) , and the intact luminal surface is

lined by a single layer of cuboidal cells.

P.!1.S. X 1 50

1 9 Portion of carcinoma o f the small intestine

replacing the intestinal mucosa. In one

area none of the cells appear to be producing

mucus, while in another many of the neoplastic

29

ce lls contain mucus (�m) H & E. x 500 29

20 Neoplastic cells in the mucosal region of

small intestinal carcinoma. Tne nuclei

contain either one or two large nucleoli

(Nu ) . H & E. x 900.

2 1 Structures which appeared as large basophilic

intracytoplasmi c inclusionf' ( rr,c ) in H & E

stained paraffin sections. These proved

to be intracytoplasmic mi crocysts ( see

figures 24, 54, 60 and 6'1) H & E. x 900

22 Acinar arrangement (Ac ) of neoplastic cells

in that portion of a small intestinal

30

30

carcinoma replacing the mucoo�.. H & E. x 450 30

23 Acini , c�mposed of flattened neoplastic cells

( NO) , and containing numerous neutrophils.

H & E. x 650

24 Intracytoplasmic vacuoles ( MC) ¥ith both

contents and �argins staining with alcian

blue . (Mu = mucus in other neoplastic cells ) .

Alcian blue x 550

25 Submucosal portion of a carcinoma. -:>f the 'small

intestine with abundant collagenous stroma

30

30

( �) between the neoplastic cells (Ne) . H & E.x 30

400

26 Groups of neoplastic cells ( NO) within lymph

vessels ( LV) of the lamina propria of the

small intestine . H .& E. x 1 50 3 1

Figure following page

27 A plaque of neoplastic cells (Pl) protruding

into the lumen of a lymph vessel (LV)

immediately beneath the muscularis mucosa

(l.JM) near the primary lesion of a small

intestinal carcinoma. H & E. x 400

28 Neoplastic cells (NC) in the tunica

adventitia of a :::;ubmucosal blood vessel.

H & E. x 400

29 Neoplastic cells (Ne) in the thickened wall

of a blood vessel. H & s. x 150

30 Neoplastic cells containing mucus (Mu) within

a nerve in the wall of the small intestine

of a sheep with a carcinoma of the small

intestine. Alcian blue. x 350

31 Neoplast�c cells (Ne) penetrating from the

submucosal portion of a carcinoma of the

small intestine (SM) betHeen muscle bundles

31

31

31

31

of the internal muscular layer (H1) H & E.x 150 31

32 Aggregations of neoplastic ceEs (NC) between

the internal (IM) and external (Eitl) muscular

layers of the small intestine in the

vicinity of a primary small intestinal

carcinomatous lesion. H & E. x 150

.B A very small serosal lesion immediately

peripheral to the primary lesion of a

carcinoma of the small intest�ne. Neopiastic

cells (NC) are relatively numerous in the

31

collagenous stroma (s).H & E. x 150 31

34 Serosal lesion of carcinoma of the small

j ntestine showing that coll.aget: makes U.) a

large part of the lesion. van Gieson x 500. 31

Figure following page

35 Lymph ves�e l appearing as a large acinar

structure in a scirrhous serosal lesion.

Much of the lining of the lymph vessel

has been replaced by neop lastic cells (Ne).

There is a c lump of neop la stic cells in the

lumen (L) of the lymph vessel. H & E. x 150 32

36 Lymph vessel (LV) in a collagenou s lesion on

the diaphragm of a sheep with a carcinoma

of the small intestine. The lumen of the

lymph vessel contains a cord of neoplastic

cells (Ne). H & E. x 150 32

37 Acini of neoplastic cells (NC) in a serosal

lesion, aco,lt which the stroma is orientated

in a circular manner. H & E. x 150

38 Pyl�notic nuclear fragments lt-r) surrounded by

irr.mature fibrohlasts (F) in a serosal lesion

32

of a small intestinal carcinoma. H & E.x 650 32

39 Serosal lesion of a carcinoma of the small

intestine with collager.. (C) less abundant

in the immediate vicinity of neoplastic cells

(NC) than elsewhere. van Gieson x 100

40 Loose connective ti ssue which made up the

translucent lesions seen on the proximal

portions of the �mall intestinal wall of

some affected sheep. H & E. x 400

41 Neoplastic cells (Ne), some of which con�ain

mu cus (Mu), in the subcapsular sinus of a

32

32

mesenteric lymph node. P.A.S. x 400 32

42 Neoplastic cells (Ne) in the intermediate

sinuses of' a mesenh:ric lYI•'Ph l:.Jde. H & E.x 400 32

43 Acini of neoplastic cells part ly rep lacing the

normal tissue of a mesenteric lymph node in a

sheep affected by·carcinoma of the small

intestine. H & E. x 150 32

Figure following page

44 Section of a liver containing metastases of

a small intestinal carcinoma. Neoplastic

cells (NC) are radiating from the portal

areas (P) within liver sinusoids. H & E. x 150 32

45 Neoplastic cells , the nuclei of which contain ,

in one case , two nucleoli (Nu) and in another

an hypertFophied nucleolus (IDJ). x 151000 33

46 Myelin-like nuclear bodies (NB) in the nucleus

of a neoplastic ce!.l. The cytoplasm of the

cell contains distended rough endoplasmic

reticulum (RER) and a Golgi apparatus (G) .

X 221000

47 The nucleus of a neopla�tic cel l , the nuclear

33

membrane 0f which is deeply folded. x 101000 33

48 Interchromatin granules (IG) in the n�cleus of

a neoplastic cell . x 25,000

49 Neoplastic cells beneath the endothelium (E)

of a lymph vessel in the internal muscularis

(IM) of the intestinal wall. The rough

endoplasmic reticulum (RER) of the neoplastic

cells is distended . x 31000

50 Intracytop l.:l.smic mucous droplets (Mu) of

varying size and e lectron density in a group

of neoplastic cells. Collagen fibres (C)

are in close proximity to the neoplastic

cells. x 101000

51 The border of a neoplastic cell containing

mucous droplets (Mu) between which there· is

a rough endoplasmic reticulum (RER) and

mitochrondria (Mi). The surface of the cell

is invested with a basement me11brane (BM)

immediately adjacent to which are collagen

fibres (c ) . A fibrocyte (F) is aligned

parallel to the cell surface and only slightly

33

33

34

separated from it. x 15,000 34

Figure following page

52 Portions of the cytoplasm of two neoplastic

cells , one of which contains tonofibrils (T) ,

and between v:hich there are deGmosomes (D) .

X 25,000

53 A group of neoplastic ce lls , the borders of

which show deep folding and interdigitation.

Desmosomes (D) are present between tv10 cells.

The ba sement membrane (BM) surrounding the

34

cells is hypertroptied in one area (HEM) x 34 18, 000

54 A neopla stic ce ll , containing a large intra-

cytoplasmic vacuo le which is lined by micro­

vil li (MV) and contains an amorphous materia l

(Nu). The boundaries of thi s, and the adjoinjng,

cell are deeply folded and interdigitated. x

12,500

55 An acinu s of cells containing mucus (Mu) .

Nuclei (N) shovl variable polarity with respect

34

to the lumen of the acinus (L). x 3 , 500 34

56 An acim.1s of non mucus-producing cells. The

luminal surfaces of all cells in this section

give rise to large numbers of microvilli (MV). The areas of cytoplasm immed iately beneath

the microvilli are devoid of organel les. x

4, 000

57 An acinus of neoplastic cells, some of which

contain mucus (Mu) and some of which do not.

X 4, 000

58 The luminal border of cells in an acinus,

showing microvillu s (MV) formation and an

area of cytoplasm beneath the .::icrovilli

which is devoid of organe l les. x 9 , 000

34

34

34

Figure fol101.,ring page

59 The border of a neoplasti c cell, on which

there i s a discontinuou� basement membrane (BM) with cytoplasm (c) prot ruding through

the gap. Arrovrs indicate the positions at

which the basement membrane ends (N =

nucleus ) . x 48fooo 35

60 A large, intracytoplasmic vacuole (V) with

no microvil li (N = nucleus, arro1.,rs indicate

the cell membrane ) . x 12,000 35

61 An i ntracytoplasmi c vacuole i n a neoplastic

cell . Thr: vacuole is lined b;y microvilli

(�N) which have filaments (F) running along

their length and i nto the underlying cy�oplasrn.

The vacuole conte,ins a finely granular material

( Ji!U ) • X 1 6 r 000 3 5

62 Cuboidal epithelial cells l inine the intact

luminal rurface of a small intestinal carcinoma.

There are short mi crovilli (Wl) on the luminal

surface and two of the cells contain single

drop lets of mucus ( r.lu). x 9 , 000 35

63 A portion of a serosallesion in a sheep with

a �arcinoma of the small intestine . The

las�.on consists largely of fibrocytes (F)

and collagen fibras (c). x 3,000 35

64 A portion of a serosal lesion in a sheep with

a carcinoma of the small inte�tine. The

lesion consists, largely, of fibrocytes (F)

and collagen fibres (c). (N = nucleus ; HER =

rough endoplasmi c reticulum) . x 1 4,000

65 Mao of' New Zealand , showing lo ca � ions of Meat

�xport Works (+) at which viscera of slaughtered

ewes were inspected, and the approximate

boundaries of the.areas from which those Meat Export Works would obtain th� majority of

36

Figure facing page

their ewes.

66 The relationship oetween prevalence of

carcinoma8 of the small intestine in sheep

slaughtered in djffArent areas and the

average sheep stocking rate in representative

counties.

67 The locations of farms from which ewes -..;ere

55

63

inspected having been bred on tho se farms. 64

68 The locations of farms from which ewes were

inspected having been purchased by the vendor

at least four years previou sly.

69 �he locations of farms from which ewes were

inspected having been purchased by the vendor

less than four years previou sly.

70 The numbers of ewes inspe cted, and the percentage

of these ewe s with carcinomas of the small

intestine , from vendors who had owned the

64

64

ewes for whole of life or at least four years. 65

71 'f'18 locations of farms for\vc.rcling ewes with

72

hieh or low prevalence of carcinoma of the

small intestine , showing the rainfall status

of those farms and whether or not the vendors

reported crested dogstail was present on those

farms.

J. portion of the intestine and omentum of a

66 following page

sheep with an experimentally induc�d mesothelioma•

The peritoneal surfaces are covered by small nodules. 91

Figure follOi-fing page

73 Section of � nodu le of an experimentally

induced mesothelioma showing ce lls with

large , c l8ar nuc lei , abundont cytoplasm

and clearly defined cel l boundaries.

H & E. X 650

74 Surface of mesothe lioma showing a small

papilliform structure (P). H & E. x 350

75 Mesothelioma showing a single layer of cells

on the surface (s) and smal l grou.p s of cells

(G) beneath the surface of the lesion.

H & E., X 350

91

9 1

I N T R 0 D U C T I 0 N

Carcinomas of the small intestine were long considered uncommon

neoplasms i n all species. Ove� the last decade there has been a

growing a\vareness that, contrary to this belief, small intestinal

carcinomas are common in sheep, at least in New Zealand. Not only is

this high incidence of an otherwise rare neoplasm f>cientifically

intriguing, but it is also of potential economic importance both to

individual farmers <lnd to meat slaughtering firms. In addition, the

possibility of the existence, in the rural environment, of an

unrecognised carcino_c:en to whi0h man also might be susceptible adds

to the importance of this disease. These factors stimulated the

initiation of the present investigation into the patholo�� prevalence,

··epidemiology and aetiology of this neoplasm, results of which form the

basis of this thesis. Included also are reviews of the pertinent

literature concerning small intestinal carcinomas of other species,

including man, and of neoplasia of sheep in general. The results of

preliminary experiments to investigate the effect of known carcino�en�

on sheep are also reported.