Colin Dale Flashcards
FAB classification
slide 12 of haem malignancies lecture
Disorders associated with ALL
- Down’s Syndrome
- Klinefelter’s Syndrome
- Fanconi’s anaemia
- Ataxia-Telangectasia
know all haem malignancy stuff in USMLE notebook
know all haem malignancy stuff in USMLE notebook
Infectious causes of NHL
- HTLV1 in adult T-cell leukaemia-lymphoma
- EBV in mature B-cell ALL and Burkitt’s lymphoma.`
ALL clinical characteristics
Nonspecific Symptoms
- Fatigue
- Anorexia / Weight Loss
- Fever / Infection
- Easy & excessive bruising
- Bleeding (nosebleeds and bleedings from gums)
- Dyspnoea
Bone /Joint pain
CNS involvement
morphological subtypes of ALL (FAB)
Subtype Morphology
Occurrence (%)
L1 - 75%
Small round blasts clumped chromatin
L2 - 20%
Pleomorphic larger blasts clefted nuclei, fine chromatin
L3 - 5%
Large blasts, nucleoli,
vacuolated cytoplasm
Peroxidase or sudan black - L1, L2 and L3 negative
Non specific esterase - L1, L2 , L3 all positive
Periodic acid Schiff - no reaction in any
B Lineage ALL MARKERS
B lineage accounts for 80% of ALL
Pro-B
CD19(+),Tdt(+),CD10(-),CyIg(-)
Common
CD19(+),Tdt(+),CD10(+),CyIg(-)
Pre-B
CD19(+),Tdt(+),CD10(+),CyIg(+),SmIg(-)
Mature-B
cD19(+),Tdt(+),CD10(±),CyIg(±),SmIg(+)
T lineage ALL marker
T lineage accounts for 20% of ALL
Pre-T
CD7(+), CD2(-), Tdt(+)
Mature-T
CD7(+), CD2(+), Tdt(+)
FavourabLe prognostic factors in ALL
- normal karyotype
-hyperdiploidy
>50 chromosomes
Poor prognostic factors in ALL
- t (8;14)
- t (4;11)
Very poor
9:22 BCR:ABL
High risk ALL
- Pre-T cell ALL
- Pro-B cell ALL
- Age > 35 years
- WBC >30,000 in B-ALL
>100,000 in T-ALL - No remission after 4 weeks of induction
therapy
Tx of ALL
Combination chemotherapy:
- Induction (4-8 weeks):
- Goals: restore normal haematopoiesis, induce a
complete remission rapidly
-4 or 5 drugs: vincristine, prednisone, anthracycline,
L-asparaginase, +/- cyclophosphamide
Tx of tumour lysis syndrome?
Allopurinol, aggressive hydration
Post remission in high and very high risk ALL
Allogeneic stem cell transplantation (SCT)
- Eradicates patient’s hematopoietic stem cells
- Replaced with those of an HLA-matched (Human Leucocyte Antigen) sibling donor or a matched unrelated donor
Survival rates in ALL
Children - 80%
Adults 30-40%
Recall that, embryologically, the colon is derived from both the mid-gut & hind gut. Where is the division and which arteries supply them?
Midgut extended to the proximal ⅔ of the transcending colon and the hind gut begins after this
Midgut supplied by SMA
Hindgut supplied by IMA
Retroperitoneal organs
Suprarenal glands (adrenal) Aorta (desc) Duodenum (2nd to 4th part) Pancreas (except tail) Ureters Colon (asc. and desc.) Kidneys Esophagus Rectum
Lymph drainage of the GI
lymph vessels – along arteries
lymph nodes - roots of the three
gut arteries in front of the aorta,
(inferior mesenteric, superior
mesenteric, coeliac nodes)
coeliac nodes => cisterna chyli
NOTE:
mucous membrane - ly mphoid follicles
Mesentery - paracolic nodes,
intermediate nodes.
Innervation of the foregut
(Coeliac plexus):
Sympathetic: Greater (T5-9) and
lesser (T10-11) splanchnic nerves
Parasympathetic: Vagus
Innervation of the midgut
(Superior Mesenteric Plexus):
Sympathetic: Coeliac and lesser
(T10-11) splanchnic nerves
Parasympathetic: Vagus
Innervation of the hindgut
(Inferior mesenteric and inferior
hypogastric plexuses):
Sympathetic: Intermesenteric
plexus, and lumbar sympathetic
trunk.
Parasympathetic: Pelvic Splanchnic
nerves (S2, S3, S4).
Features of the sympathetic fibres of the gut
- SEE NOTEBOOK
- Synapse in preaortic ganglia
- Travel along arterial supply
- Result in contriction of the gut and antagonise the PNS
Features of PNS
Vagus nerve follows arterial supply - see notebook
Pelvic splanchnic does not follow arterial supply as uniformly see notebook
Sensation of gut follow parasympathetic fibres
Pain afferents are proximal to mid sigmoid and follow sympathetic fibres
Fx of large colon
- Water absorption
2. Conversion of liquid chyme to solid stool/faeces
Extra features of the colon
Teniae coli from base of appendix to rectosigmoid junction
Haustra: sacculation of wall between the teniae
Features of the appendix
Blind intestinal diverticulum 6-10 cm
Contains lymphoid tissue
Mesoappendix
Usually retrocoecal
Features of the colon
Ascending -
- Secondarily retroperitoneal
- In 25% of people is has a short mesentery
- Right paracolic gutter
Transverse –
- intraperitoneal
- Attaches to the diaphragm through the
phrenicocolic ligament
Descending - - Secondarily retroperitoneal - In 33% of people is has a short mesentery especially in the iliac fossa - Left paracolic gutter
Sigmoid
- From the left iliac fossa to the S3 vertebra
- Rectosigmoid junction – termination of
teniae coli
Sigmoid mesocolon - inverted “V” shaped attachment - Posterior to the apex – left ureter and the division of the left common iliac artery
Where do the sigmoid and rectum differntiate
s3
Features of the rectum
RECTUM
- Primarily retroperitoneal and subperitoneal
- Peritoneal cover:
Superior third - anterior and lateral
Middle third - only anterior
Lower third - none
Continuous with sigmoid at S3
Ends near the tip of the coccyx just before the
anorectal flexure of the anal canal – where the gut
perforates the pelvic diaphragm (levator ani) - 80
degrees
Significance of the angle of the pelvic diaphragm
The angle at the pelvic diaphragm is maintained
by the puborectalis muscle and is an important
mechanism for maintaining continence
What is the dilated terminal part of the rectum called and what is its function
The dilated terminal part is called the ampulla
of the rectum – holds and accommodates faecal
material until defaecation
Pouches of the rectal area
In males, the reflection of peritoneum from the rectum to the posterior bladder wall forms the rectovesical pouch.
In females, the peritoneum reflects to the posterior vagina and cervix, forming the rectouterine pouch (pouch of Douglas)
Blood supply of the rectum
See notebook too
SUPERIOR RECTAL ARTERY (& VEIN)
- Continuation of Inferior Mesenteric – proximal part of
rectum
MIDDLE RECTAL ARTERIES (& VEIN)
- From anterior divisions of internal iliac – middle and
inferior part
INFERIOR RECTAL ARTERIES (& VEIN)
- From internal pudendal – anorectal junction and anal canal
Features of the anal canal
From the superior aspect of the pelvic diaphragm (puborectalis)
to the anus
2.5 – 3.5 cm long
Surrounded by the external and internal anal sphincters
Except during defecation, the anal canal is collapsed by the internal and external anal sphincters to prevent the passage of faecal material.
Features of the internal anal sphincter
Internal anal sphincter – surrounds the upper 2/3 of the anal canal. It is formed from a thickening of the involuntary circular smooth muscle in the bowel wall.
Contraction stimulated and maintained by sympathetic fibers (superior rectal and hypogastric plexuses)
Contraction inhibited by parasympathetic fibers
(pelvic splanchnic nerves)
Features of external anal sphincter
External anal sphincter – voluntary muscle that surrounds the lower 2/3 of the anal canal (and so overlaps with the internal sphincter). It blends superiorly with the puborectalis muscle of the pelvic floor.
- Attached anteriorly to perineal body and poster to
coccyx via the anococcygeal ligament
Superiorly it blends with the puborectalis muscle
Supplied by S4
What is at the junction of the internal and external sphincter and what are their functions
anorectal ring. It is formed by the fusion of the internal anal sphincter, external anal sphincter and puborectalis muscle, and is palpable on digital rectal examination.
What is the levator ani made up of
From closest to the anus to furthest away
Puborectalis, Pubococcygeus, Iliococcygeus
Coccygeus
Note: These muscles are contracted at normal times and their relaxation allows
urination and defaecation
Difference in the anal canal above and below the pectinate line
he anal valves collectively form an irregular circle – known as the pectinate line (or dentate line). This line divides the anal canal into upper and lower parts, which differ in both structure and neurovascular supply. This is a result of their different embryological origins:
Above the pectinate line – derived from the embryonic hindgut.
Below the pectinate line – derived from the ectoderm of the proctodeum.
Superior = columnar epithelium
Below = non keratinised stratified squamous epithelium (known as the anal pecten).
What prevents reflux of colonic contents into the terminal ileum?
ileocecal valve
What causes appendicitis? Why does it frequently become gangrenous?
Obstruction of the lumen of the appendix is the main cause of acute appendicitis. Faecolith (a hard mass of faecal matter), normal stool, or lymphoid hyperplasia are the main causes for obstruction. Faecolith alone causes simple appendicitis in 40%, gangrenous non-perforated appendicitis in 65%, and perforated appendicitis in 90% of cases.
Becomes gangrenous due to lack of blood supply
Signs and symptoms of appendicitis
- Constant mid-abdominal pain that later shifts to right lower quadrant. Usually worse on movement.
- Anorexia
- Classic sign is right lower quadrant abdominal tenderness (McBurney’s sign). There may be localized rebound tenderness, especially if the appendix is anterior. Compressing the left lower quadrant may also elicit pain in the right lower quadrant (Rovsing’s sign). Pain may also be elicited with the patient lying on their left side and slowly extending the right thigh to cause a stretch in the iliopsoas muscle (psoas sign) or by internal rotation of the flexed right thigh (obturator sign).
- Nausea, fever
- Diminished bowel sounds
- Tachycardia (especially in perforation
Characteristics and Fx of the small intestine
- Is divided anatomically into three regions:
Duodenum: 25 cm long
Jejunum: 2.5m long
Ileum: 3.5m long - Principal site of disgestion and absorption of food
What is the role of enterocytes
secrete enzymes
what are plicae circularis
Plicae circularis (circular folds): Permanent transverse folds of the intestinal surface.
Which surface are microvilli found
apical surface
Histological features of the duodenum
- Brunner’s glands in the submucosa (tubuloacinar mucous glands producing alkaline secretion, pH 8.8 to 9.3, that neutralises the acidic chime from the stomach)
- Villi are short and broad (leaflike)
- Surrounded by incomplete serosa
and extensive adventitia - Base of the crypts of Lieberkuhn may
contain Paneth cells
do tubular, villous or tubulovillous adenomas have hughest risk of becoming cancerous
villous
Histological features of jejunum
- Long finger like villi
- Well-developed lacteal in the core (central
lymphatic vessel) - No Brunner’s glands in submucosa
- Paneth cells are found in the crypts of
Lieberkuhn - Some Peyer’s patches in the lamina propria
Histological features of the ileum
- Peyer’s patches: lymphoid follicles
(nodules) in the mucosa and part of the
submucosa (GALT: gut-associated
lymphoid tissue) - Lack of Brunner’s glands
- Shorter finger-like villi
- Paneth cells at the base of Lieberkuhn’s
crypts
Components of the small intestinal villi
- Villi consists of a core of loose connective tissue covered by simple columnar epithelium.
- The lamina propria of the villus contains a central lymphatic
capillary called the lacteal. - Lieberkuhn’s crypts: intestinal simple tubular glands originate from
the muscularis mucosa, covered with simple columnar epithelium
that is continuous with the villi epithelium.
Fx goblet cells
mucus secretion
Fx of paneth cells
Secrete antimicrobial
substances. Easily identified by H&E
due to pink staining of the secreting
granules.
Fx of M cells (microfold cells)
modified
enterocytes that cover the lymphoid
Histological features of the large intestine
- Circular folds and villi are NOT present.
- It contains numerous straight tubular glands that extent through the
full thickness of the mucosa. - The mucosa is covered by simple columnar epithelium.
- The principal function of the large intestine is the reabsorption of water
and electrolytes and the elimination of undigested food. - The mucosa contains the same cell types (Goblet cells, enterocytes), as
the small intestine except Paneth cells that are absent in humans.
Histology of rectum
- Can be distinquished by the presence of transverse rectal folds.
- The mucosa is similar to the distal colon.
- Straight tubular glands with numerous goblet
cells
Histology of the anal canal
Divide into three zones:
Colorectal zone: simple columnar epithelium
Anal Transitional Zone: Transition between simple
columnar to stratified squamous epithelium.
Types of polyps
Sessile: No Stalk, Pedunculated: Stalked
Are polypscancerious
no
Types of adenommas
Tubular adenomas: Tubular glands
Villous adenomas: Vilous Projections
Tubulovillous adenoma: A mixture of the previous two
Histology of a polyp
serration of the luminal epithelial surface.
Delayed shedding of the epithelial cells leads to infolding and fission of the crypts
What are juvenile polyps
Juvenile polyps are hamartomatous lesions that consist of a lamina propria and dilated cystic glands rather than increased numbers of epithelial cells
What are peutz-jeghers polyps
hamartomatous lesion of glandular epithelium supported by smooth muscle cells that is contiguous with the muscularis mucosa
Features of tubular adenoma
the glands resemble normal colonic
tubules; these are often small and pedunculated, with low grade
dysplasia
Features of villous adenoma
sessile up to 10cm in diameter. Their histology is
characterized by villiform extensions of the mucosa, covered by
dysplastic and disordered columnar epithelium. All degrees of
dysplasia may be encountered.
Features of tubulovillous a
the glands resemble normal colonic
tubules but are thrown up into villous folds in many areas; these are
often large and may be sessile or pedunculated . Variable dysplasia.
Describe the adenoma carcinoma sequence
see slide 30 of colon cancer histology lecture
Tumour markers in the blood
- AFP : (hepatocellular Ca),
- Ca19.9 (pancreas),
- Ca125 - (ovary)
- CEA (colorectum –more often used in
follow-up)
Describe familial polyposis coli
- Germline mutation of APC gene
- Offered colectomy as soon as first adenomas appear
Describe TNM staging
T1: confined to submucosa
T2: confined to muscle
T3: through muscle into fat
T4: exposed on serosal surface or
invades adjacent organ/structure
N0: no nodes involved
N1: <4 nodes involved
N2: >4 nodes involved
M0/1: metastases -/+
Staging of cancer
Stage 0:
Tis N0 M0
~100% 5YS
Stage I:
T1/2 N0 M0
94% 5YS
Stage II:
T3/4 N0 M0
83% 5YS
Stage III:
Any T N1/2 M0
56% 5YS
Stage IV:
Any T Any N M1
27% 5YS
Dukes staging (not used practically)
A – Tumour infiltrating to muscularis propria • B – Tumour infiltrating through bowel wall • C – Tumour with lymph node involvement • ‘D’ – Distant Metastases
Tumour gradin
- Refers to how much the tumor
cells resemble normal cells of the same tissue type - G 1, 2, 3, and 4.
- Grade 1 tumors resemble normal cells, and tend to grow and multiply
slowly. Grade 1 tumors are generally considered the least aggressive in
behavior. - Grade 3 or Grade 4 tumors do not look like normal cells of the same type.
Grade 3 and 4 tumors tend to grow rapidly and spread faster than tumors
with a lower grade. There are different grading systems for each type of
cancer.
5YS Dukes
A = 85-90+%
B = 60-80%
C = 15-45%
Oncogene inheritence
usually autosomal dominant
TSG inheritance
usually autosomal recessive
Describe hypermethylation of CPG islands
repeated C-G-C-G-C-G- etc sequences found in many commonly
‘silenced’ tumour-related genes is often the way the 2nd
copy of a gene is ‘knocked out’, eg APC or RB-1
Featuresof growth factor oncogenes
Increased growth factor (autocrine
or paracrine effects) or abnormal growth factor production (eg c-sis
encodes FGF). Many other growth factor mutations are linked to tumours,
eg PDGF, EGF.
Features of cell-surface growth factor receptors
Increased growth factor receptor
expression or abnormal growth factor receptors (eg Her-2-neu gene
encodes EGFR – gene amplification due to mutation indicates that the
drug Herceptin will be clinically effective.)
Featrures of signal transduction oncogenes
Permanent activation of intracellular
signalling mechanisms cause continuous signal transduction (eg v-src
encodes a protein tyrosine kinase, c-ras encodes a
membrane-associated G-protein receptor). Ras gene point mutations are
the commonest oncogene mutations, eg colon, breast and lung cancers.
Features of nuclear protein oncogenes
Mutations of the messenger molecules which initiate
DNA transcription produce oncoproetins which continually stimulate cell
division. Translocation of c-myc to lie beside the Ig gene occurs in
Burkitt’s lymphoma (t8:14); amplification of myc is seen in breast and
lung cancer.
Resistance to apoptosis oncogene
(eg BCl-2 mutation prevents caspase
activation)
Featuresof TSG
gene mutations are
“recessive”, ie both alleles must be mutated).
TSGs that act on intermediate messengers
beta catenin acts in the cytoplasm, on
microtubules or cell-cell adhesion mechanisms
(APC acts at all these points).
TSGs affecting cell cycl
(The APC gene is a bit confusing, with bothdominant effects (AD inheritance in FAP) and a
TSG effect. This is probably due to effects on
both beta and gamma catenin .)
Featuresof p53, p21, p16-INK4:
P53 - a ‘caretaker gene’. P53
protein is produced if there is DNA damage. If DNA
repair is possible, p53 activates transcription of p21
protein. This inhibits CDKs, arresting the cell cycle
while DNA repair enzymes work. If repair is
impossible the cell is consigned to apoptotic death.
P53 mutation permits further mutations to occur.
Features of retinoblastoma gene
RB binds
transcription factor E2F, preventing it from driving
the cell cycle from G1 to S phase. Phosphorylation
of RB by CDK causes it to dissociate from E2F.
TFE2F activates DNA transcription genes, allowing
progression from G1 to S phase. P16-INK4 binds
CDK4/CyD, preventing phosphorylation of RB, thus
inhibiting progression.
Features of Cyclin kinases (eg CyB, D,E) and cyclin dependent kinases (eg CDK1,2,4))
suppressed by p53, p21 or p16, or
non-phosphorylated RB protein.
Features DNA mismatch repair enzymes,
eg MLH-1 and
MSH-2. MMR remove mismatched DNA segments
and install accurate replacements. These genes
protect against spontaneous replicative errors
during mitosis.
Microscopic features of malignancy
high N:C ratio
and their nuclei usually
show a variety of shapes
and much size variation.
Nuclear chromatin is coarse
in malignant tumours and
nucleoli are often prominent
and strange shapes.
Mitoses tend to be easily
visible on microscopy of
malignant tumours and are
often bizarre in shape.
definition of metaplasia
alteration of one mature
cell type for another
Are there precursors to cancer (ie can
we predict that a cancer will develop)?
Inherited mutations in key cancer-related
genes predispose to cancer development, eg:
- APC gene mutation (Ca colon)
- Mismatch repair (MMR) enzyme mutation (Lynch
syndrome /HNPCC) - BRCA-1 or 2 (Ca breast and elsewhere)
- RB-1 (retinoblastoma)
- NF-1 (neurofibromatosis, some sarcomas)
Where is squamous epithelium found
Covers skin, oropharynx, oesophagus,
anal canal, vagina, external auditory canal
- Benign and malignant tumours may arise
as a result of viral infection (eg HPV)
Definition of koilocytosis
term for warty
changes in the epithelium: spiky
nuclei and perinuclear haloes
Where is glandular epithelium found
-Covers entire GI tract from stomach to rectum Lines ducts and acini of glands Forms tubular structures, such as renal tubules
- Glandular tumours may arise at
‘inappropriate’ sites following
metaplasia, eg Barrett’s metaplasia in
gastro-oesophageal reflux disease
Where is urothelium (transitional epithelium)
Covers urothelial tract, ie renal pelvis,
ureter, bladder and urethra
Festures of tumours of renal parenchyma
Tumours of the renal parenchyma itself are a subtype of
adenocarcinoma, but because of their distinctive clear cells are
usually known as ‘clear cell carcinoma’
Germ cell tumours
Testicular tumours, eg:
Teratoma
Seminoma
Ovarian germ cell tumours, eg:
Teratoma
Dysgerminoma
which tumours do not spread
brain - BBBW
Which cells to GI stromal cell tumours arise from
Interstitial Cells of
Cajal – the pacemaker cells in the gut.
How do we predict GIST
Predicting their behaviour is made by assessing size and
mitotic activity and evidence of metastatic disease.
Tumours <2cm diameter are almost always benign.
tX OF gist
- surgical – the stomach is the commonest site and wedge resection is sufficient.
- Most inoperable GISTs respond well initially to Imatinib
(Glivec), a ‘designer drug’ which blocks TK receptors.
Mutational analysis is important in determining
What is transcoelomic spread
across peritoneal cavity
eg ovarian metastases from colorectal or gastric primary (krukenberg tumours)
Implanation spread of tumour
laparotomy wound or laparoscopic trocar ports.
Pre operative staging of colorectal cancer
Best estimate of the extent of disease at the time of diagnosis, based
on the results of the physical examination, colonoscopic biopsy, pre
op US, CT, MRI etc.
Tis tumour
Tis: (in situ). Tumour
involves only the mucosa.
Tx of T1- T2, N0, M0
Tumour is localized within the bowel
- Surgical Resection is usually adequate treatment
- No additional pre operative (neoadjuvant) or post-operative (adjuvant)
therapy (Chemo or radiotherapy) is necessary
Tx of T3, T4, N0
Any T with Nodal or M involvement
Tumour has breached the wall of the bowel
- Surgical Resection alone is inadequate treatment
- Additional pre operative (neoadjuvant) or post-operative (adjuvant) is
necessary
Types of bowel polyps
- Pseudopolyps – ( UC, crohns disease)
- Hyperplastic
- Hamartomatous - (Peutz Jeghers Syndrome) - malignant
- Adenomatous - (Familial Adenomatous Polyposis) - malignant
What does the risk of malignant transformation depend on?
- Number of polyps
- Their size (>2cm)
• The histological characteristics of
the polyp
• Tubular
• Villous
Defining high risk cancerous polyps
Positive resection margin
and / or
Poorly differentiated
and / or
Vascular or lymphatic invasion
Pros of surgical resection
- Certainty of local control
- Relevant lymph node clearance
- Accurate staging
Cons of surgical resection
• Morbidity and mortality of surgery
What are the symptoms of advanced disease
Abdominal distension
• Fatigue due to chronic anaemia
• Weight loss
• Sx of obstruction or perforation
Main diagnostic investigations
- Blood tests
- FBC, U&E , LFTS, Serum Proteins, INR
- Tumour markers
- CEA, CA 19-9
- Proctoscopy / Sigmoidoscopy (rigid / flexible)
- Barium enema
- Colonoscopy & definitive biopsy - GOLD STANDARD
Significance of CEA
• If elevated at time of diagnosis, may be a useful marker
of active disease
• Levels fall after surgery / adjuvant treatment
• Rising levels during follow-up may be the first sign of
recurrent disease
• Low levels at initial diagnosis may indicate high grade,
undifferentiated tumour with a poor prognosis
Staging investigations
Abdominal Ultrasound
CT Chest & Abdomen - GOLD STANDARD
Pelvic MRI
Endorectal Ultrasound
Use of CT in CRC
- Gold standard
• Accurately identifies
site of primary
• Detects invasion
into neighbouring
organs
Use of chest and abdominal CT
• Detects enlarged
lymph nodes
• Detects metastases
• Detects any
co-existent disease
Use of pelvic MRI
- eXTREMELY USEFUL
• Detailed images
of pelvic anatomy
• Accurate pre op
local staging of
rectal tumours
- Can determine size and shape and invasion of bowel wall
- nodal involvement
Use of endoanal unltrasound
• Position
• invasion of
bowel wall
• nodal involvement
Advantage of surgical resection
provides the most rapid relief of symptoms,
including those arising due to:
- Bleeding
- Obstruction
- perforation and
- fistulation into surrounding organs.
Use of combo of chemo and surgery
locally
advanced lesions (those that have penetrated the
muscular wall of the bowel) will benefit from adjuvant
chemotherapy and in the case of rectal tumours,
neoadjuvant chemoradiotherapy
Tx options
• Surgery only
• Surgery+ Adjuvant (post op) chemotherapy
(colonic tumours)
Neoadjuvant (pre-op) chemo /radiotherapy + Surgery
(rectal tumours)
Preparation for surgery
• ? neoadjuvant treatment
- On basis of pre-op staging – locally advanced rectal tumours
• Informed consent
• Preparation for stoma, counselling (if applicable)
- Low rectal cancers where sphincters cannot be saved
• Cross match blood
• Bowel preparation
- improves wound infection
- minimises septic consequences of anastomotic leak
• Antibiotic prophylaxis
- Cefuroxime / Metronidazole
- improves wound infection
• Thrombo-embolism prophylaxis
Bowel prep
2 days pre-op : Low fibre diet
I day pre-op : Cathartics (Kleen Prep, SennaPlus), Enemas
Principles of recetion
- Any surgical resection
requires 5 cm clearance
for colonic lesions
- 1 cm distal clearance of rectal lesions is adequate if mesorectum resected.(Total mesorectal excision) - if involves sphincter within 1cm you need to remove them
- Radial margin or circumferential resection margin (CRM) should be histopathologically free of tumour - This applies especially for rectal tumours – the CRM must be >1mm for a curative resection.
- For a segmental colectomy lymph node resection should be performed to the origin of the feeding vessel on the SMA or IMA
- En Bloc resection of
adherent tumours
should be performed
ie, removal of portion of
adherent neighbouring
organ in continuity with
resected bowel.
Benefit of adjuvant chemo
- T1 T2 N0 – No benefit
- T3-4, N0 – 2-5% absolute benefit
- T3-4, N1-3 – 5-10% absolute benefit
Poor prognostic factors for colon cancer
- T4 tumours
- Poorly differentiated
- Venous invasion
- Mucinous adenocarcinomas
Where to rectal recurrences tend to occur
Initial recurrences tend to be local
rather than distant, whereas in
colonic cancer initial recurrence is
usually to distant organs
- local recurrences are extremely difficult to treat
What has improved local recurrence
total mesorectal excision (entire mesorectal compartment including the rectum, surrounding mesorectal fat, perirectal lymph nodes and its envelope, i.e. the mesorectal fascia is completely removed.)
Types of rectal excision
- LOW ANTERIOR RESECTION
-
When is low anterior resecetion indication
• Low anastomosis
(usually <5 cm from anus)
• Preop radiotherapy
• Technically difficult anastomosis
What needsto be done with a low anatamoses
Diverting (defunctioning) stoma:
• diverts the faecal stream from the anastomosis
• protects it in the immediate postoperative period.
Usually closed 8-12 weeks later, after contrast or endoscopic study
demonstrating anastomotic integrity
Use of neoadjuvant Tx in rectal cancer
Proven to be of value in tumours that have breached the
muscular wall of the rectum T3,4, N0, T1T2 N+ as
indicated by pre-operative staging MRI
• Reduced toxicity as compared to post op (adjuvant)
treatment
Role of neo adjuvant therapy
• Reduces local recurrence rates (RXT alone)
- Convincing & large evidence base
• Shrinks locally advanced tumours (RXT & chemo)
- Facilitates ‘curative resection’ with clear margins
• Increases chance of sphincter preservation
- Controversial, not evidence based
• Definitive treatment in its own right
- In patients unfit for surgery
Indication for ABDOMINOPERINEAL RESECTION OF THE RECTUM
• Indicated only for very distal rectal tumours involving
sphincter or for advanced squamous cell tumours of the anus.
• Attempted anastomosis would result in poor function or
inadequate tumour clearance.
Method of abdominoperineal resection
• Recto-sigmoid, & anal sphincter complex excised and perineal
opening closed
• Permanent left iliac fossa stoma
• APR has increased local recurrence rates and poorer survival
than anterior resection.
Indication for local resection of rectal tumours
•Poor risk patients
•Benign polyps
•T1 N0 M0 tumours
Well / moderately well differentiated
Indication for transanal resection
Suitable for lesions which have their
upper margins lying within 5 cm from the
anal verge.
Can be done under epidural / spinal
Access to the lesion is by dilating the
anus by means of anal retractors, and
applying traction on the lesion.
Benign polyps (TVA’s) - submucosal excision
For T1 cancers - full thickness excision of the rectal wall, which is closed
with sutures.
Difference between open and laproscopic methods of surgery
no difference in
- overall survival
- disease-free survival
- and local and distant recurrence
Pros of laproscopic colorectal surgery
- Shorter hospital stay
- Quicker return to normal activities
- Avoidance of incisional hernias
• Fewer intra-abdominal adhesions
• Equivalent surgical resection
margins and lymph node retrieval
rates
• Probably no oncological
disadvantage
Complications of colorectal surgery
General: • Post op pneumonia • Deep venous thrombosis • Pulmonary embolus • Myocardial infarction
Specific: • Wound infection • Anastomotic leakage • Visceral injury (spleen, ureter) • Incisional hernias • Abdominal adhesions • Urinary / sexual dysfunction • Defaecatory disturbances • Local recurrence
Common emergency presentation of colorectal cancer
• Obstruction
clinical picture of small or large bowel obstruction
• Perforation
Peritonitis / paracolic abscess
- Fistulation
- Bleeding
Presentation of obstruction
Colicky abdominal pain Abdominal distension Constipation Nausea, Vomiting PR Bleeding, anaemia
Presentation of perforation
Faecal Peritonitis / localized abscess
Generalized abdominal pain
Localized mass (abscess)
Abdominal guarding, rigidity
Abdominal distension due to ileus
Fever, shock
Diagnostic investigations in emergency presentation
- Plain Chest / Abdominal Xrays
- Contrast studies
- CT Scanning
- Allows identification of site
- Stages the cancer
Use of CT in colorectal emergency
- Confirms diagnosis
- Identifies the site of obstruction
- Identifies the underlying cause
- Stages malignant disease (detects metastases)
- Detects perforation
- Detects any co-existent disease
Pre operative preparation
- Resuscitation
- O2 & fluids
- Fluid loss may be considerable ( >5 litres)
- Correct electrolyte abnormalities
- Correct anaemia
- Commence broad spectrum antibiotics
- main concern is that there is no bowel preparation
-This is less of a problem with right sided large bowel tumours
since an emergency right sided resection leaves no faecally
loaded large bowel proximal to the ileocolic anastomosis.
Options for left sided obstructed lesions
Defunction with proximal stoma - 1st stage of a 3 stage procedure
Hartmann’s procedure
Resection (+/- on-table lavage) and primary anastomosis
Subtotal colectomy
Use of Defunctioning proximal colostomy
- Very sick patient
- Inexperienced operator
- 1st stage of a 3 stage procedure
use of subtotal colectomy
• Multiple (synchronous) cancers
• Grossly dilated, ischaemic proximal
bowel
MAKE SURE YOU LOOK AT KECTURE SLIDES PICTURES OF THESE SURGIES
Outcome of elective vs emergency surgery
Elective Surgery
Mortality: 0.9 - 6%
Morbidity: 5 -15%
Emergency Surgery Mortality: 5 - 20% Morbidity: 10 - 50% Stoma rate: 41% (only 60% reversed)
Follow up of colorectal cancer
• Three monthly for first 1-2 years, then six monthly
and discharge after 5 years.
• 3-6 monthly CEA.
• 6m -Yearly CT / MRI for first three years.
• Colonoscopy – within six months (or Pre-op),
thereafter 5 yearly.
- Very rare for metastasis to occur after 5 years
Treatment of local recurrence
- Curative - Salvage surgery
- Sacrectomy,
- Pelvic exenteration
• Palliative
– Radiotherapy
- Chemotherapy
Tx of anal carcinoma
- Usually chemo/radiotherapyis sufficient
• Surgery only for:
• Tumours that fail to respond to radiotherapy
• Large tumours causing gastrointestinal obstruction
• Small anal margin tumours without sphincter
involvement
Phases of wound healing
- INFLAMMATORY PHASE
- PROLIFERATIVE PHASE
- REMODELLING PHASE
Describe the inflammatory phase of wound healing
I. INFLAMMATORY PHASE (Immediate to 2-5 days) • A. Haemostasis • Vasoconstriction • Platelet aggregation • Thromboplastin forms clot
- B. Inflammation
- Vasodilation
- PMN and Macrophage migration – Phagocytosis of debris
Describe the proliferative phase
II. PROLIFERATIVE PHASE ( 2 days to 3 weeks)
• A) Granulation
• Fibroblasts lay bed of collagen
• Fills defect and produces new capillaries (angiogenesis)
• B) Contraction
• Myofibroblasts pull wound edges together to reduce defect
• D) Epithelialization
• Replication by mitosis & migration of epithelial cells
Describe remodelling phase
III. REMODELLING PHASE ( 3 weeks to 2 years)
• Type II collagen replaced by Type I collagen which increases
tensile strength to wounds
• Blood vessels that are no longer needed are removed
by apoptosis
• Scar tissue is only 80 percent as strong as original tissue
Categories of wound healing
Primary wound healing (Healing by first intention)
• Occurs within hours of repairing by approximation
• eg suturing the edges of a full thickness surgical wound.
• Minimal scarring
Delayed primary healing
• If wound edges are not approximated immediately.eg
contaminated wounds
• Wound may be sutured 4-5th day. Scarring inevitable
Secondary healing (Healing by secondary intention)
• Full thickness wound allowed to heal without surgical
intervention
• More intense inflammatory response, pronounced wound
contracture
What must you always consider in an older patient presenting with appendicitis?
Cancer and diverticulitis (usually on the left instead of the right)
What can appendicitis be confused with in children and teenagers?
Mesenteric adentitis
To what does the transverse meso-colon attach? At which vertebral level? Branches of which artery does it contain?
Transverse mesocolon is the broad fold of peritoneum connecting the transverse colon to the posterior wall of the abdominal cavity.
Fuses with greater omentum to form gastrocolic ligament
Contains middle colic vessels, nerves and lymphatics
Embryologically, which structure does it fuse with? Therefore, how many layers constitute this structure?
Posterior wall of lesser sac - 4 layers
During which commonly performed surgical procedure is the transverse colon at risk of being injured?
Laproscopy
What is the white line of toldt
Lateral reflection of posterior parietal peritoneum of abdomen over the mesentery of the ascending and descending colon.
What is the ‘marginal artery of Drummond’? Clinical significance?
an artery that connects the inferior mesenteric arterywith the superior mesenteric artery. It is sometimes absent, as an anatomical variant.
Describe the lymphatic drainage of the colon and what is its clinical significance?
The lymphatic drainage of the ascending and transverse colon is into the superior mesenteric nodes. The descending colon and sigmoid drain into the inferior mesenteric nodes
What are ‘appendices epiploicae’?
a.k.a omental appendices - small pouches of the peritoneum filled with fat and situated along the colon, but are absent in the rectum.
Which parts of the colon are commonly used for ‘stoma’ formation?
Transverse and sigmoid
What are the ‘rectal valves’ (of Houston)?
lateral flexures of the rectum
What is ‘Denonvillier’s fascia’? Into which structure does it insert, inferiorly?
is a membranous partition at the lowest part of the rectovesical pouch. It separates the prostate and urinary bladder from the rectum. It consists of a single fibromuscular structure with several layers that are fused together and covering the seminal vesicles
What is the mesorectum and what is its surgical significance
Fatty tissue surrounding the rectum - Needs to be removed in rectal cancer to prevent metastasis
Why is the rectum not affected by diverticular disease?
Does not have omental bursae
What is the venous drainage of the rectum and what is the clinical significance of this
In the settin gof rectal cancer
IMA and SMA drain to the portal vein - metastasis to the liver
Pudendal drains to the IVC metastasis to the lung
Innervation of the rectum
See notebook
What is the lymphatic drainage of the rectum
pararectal lymph nodes, which drain into the inferior mesenteric nodes.
Additionally, the lymph from the lower aspect of the rectum drains directly into the internal iliac lymph nodes.
What constitutes the ‘internal anal sphincter?
Thickening of the circular smooth muscle layer. COntinuation of SM of the rectum
What is the inter-sphincteric groove and what marks this level?
a.k.a. hiltons white line - marks separation between the smooth and skeletal muscle
Describe the molecular pathogenesis of adenocarcinoma
SEE DISEASE LOB
- Must do this is an official lob
Histopathology of colon polyps
Must do see Despina lecture
Advice on wound care
- Paracetamol for pain - avoid aspirin, brufen or voltarol as this can prolong bleeding
- Rest and avoid strain
- Look for signs of infection
- Keep the dressing clean and dry for 48 hours avoiding baths and showers.
5.Avoid dirty water in baths and swimming
pools while the stitches are in place
What to do if a wound bleeds?
Very occasionally the wound may bleed. Do not remove the dressing but apply
continuous pressure with a clean handkerchief or towel for 15 minutes. Slowly
release pressure and if the wound is still bleeding re-apply firm pressure for
another 15 minutes.
What to do after stitches are removed
After
the stitches are removed ensure the wound is secured with steristrips for 1
week on the face or 6-8 weeks on the body or limbs. Avoid strenuous exercise
that will put tension on the wound for another 4-6 of weeks depending on the
site of surgery.
Long term management of wound?
massage the scar with vaseline or moisturiser for about 1
minute, 3 times a day for a year. This will help soften the scar and improve the
cosmetic result
Signs of wound infection?
Become more swollen Is hot or painful to touch or child is experiencing increasing pain Oozes pus or smells or change in discharge colour Bleeds Your child develops a fever and generally feels unwell
NICE guidelines for follow up after curative CRC surgery
- Clinic visits every 4-6 weeks
- a minimum of two CTs of the chest, abdomen, and pelvis in the first 3 years
- regular serum carcinoembryonic antigen tests (at least every 6 months in the first 3 years)
- Surveillance colonoscopy at 1 year after initial treatment. If this investigation is normal consider further colonoscopic follow‑up after 5 years, and thereafter as determined by cancer networks.
Principles of radiation
Generally normal cells have excellent repair
mechanisms but cancer cells are have diminished
ability to repair the damages and hence continue to
produce cells with the damage.
These cells, which have the damaged DNA, will either
die or reproduce slowly
Limitations of radiotherapy
Tumours outgrow their blood supply and
tissues become relatively hypoxic.
The more hypoxic the tumour is the greater the
resistance to radiotherapy.
Fixation of oxygen plays a very important role
in causing permanent damage to the DNA.
Indication for radiotherapy
Line of excision includes mesorectum
Side effects of radiotherapy
Acute:
- damage to epithelial surfaces of the skin, mouth, pharynx
and bowel mucosa cause soreness, diarrhoea and nausea.
Oedema and erythema:
swelling of the soft tissues is encountered during
radiotherapy. Red rashes are seen in the area of treatment.
The patient is given steroids to reduce swelling
Infertility
Fibrosis and skin problems: inflammation, desquamation,
hyperpigmentation, pruritus
Hair loss: radiotherapy to the head and neck region causes
permanent hair loss
Dryness: Dry mouth (xerostomia) and dry eyes (xerophthalmia)
Secondary malignancies: are seen in a small minority of patients,
generally >15 years after they have received a curative course of
radiation treatment.
Fetal damage is seen in case of pregnant woman
Radiotherapy lowers the immunity status of the patient and increases
the susceptibility of infection.
MOA of bevacizumab
Bevacizumab
Anti v-EGF antibody
Targets
neovascularization of
solid tumours
Survival benefit in
metastatic colon and
breast cancer
causing regression of existing microvasculature
within 24 hours of VEGF inhibition: loss of lumen patency,
cessation of blood flow in some vessels, endothelial cell
apoptosis
Role of cetuximab in colon cancer
EGFR over-expressed
in colon cancer
Monoclonal antibody
binds to EGFR
Clinical responses and
improved survival seen
in chemo-refractory
metastatic colon cancer
