carcinomas of the small intestine in sheep · intestine in man \vhich are carcinomas age and sex...
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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.