Rectum

Question 1

Anatomically, rectal cancer is defined as a lesion straddling or inferior to?

An alternative definition based on distance?

Answer 1

Rectal cancer is defined as lesion straddling or inferior to peritoneal reflection (landmark is middle transverse fold at ~11 cm from anal verge)

OR lesion within 12 cm of verge.

If lesion is completely above this , treat as colon cancer

BUT trials have used up to 16 cm from verge.

Question 2

Where is the peritoneal reflection:

What is the standard anatomical superior boundary of the rectum:

Answer 2

At approximately 11cm from the verge. The anterior peritoneal reflection separates the intra- and extraperitoneal portions of the rectum and is a well-defined anatomic landmark at laparotomy.

Anatomically, the rectum becomes sigmoid above the pelvic inlet: Where pelvic cavity becomes false pelvis (line from sacral prom to sup edge of pubic symph on sagittal imaging).

Question 3

Basic epidemiology of rectal cancer:

Answer 3

Median age 70’s
Increased in M > F
Increasing incidence in younger patients
NZ has one of highest rates of diagnosis and death in the Western World

Question 4

Describe the mesorectal fascia:

Answer 4

The mesorectal fascia is a layer of connective tissue enclosing the perirectal fat that surrounds the rectum.
Important in rectal cancer staging, as it forms the circumferential resection margin for the non-peritonealised portion of the rectum.

Boundaries: extends from the beginning of the rectum to levator ani

Contents: perirectal fat, containing the superior rectal artery and branches, superior rectal vein and tributaries, and lymph nodes and vessels

Question 5

Rectal cancer risk factors:

Answer 5

Increasing age (median age 70)
Male gender
Inflammatory bowel disease
Dietery: high fat, low fibre, red meat
Alcohol and tabacco
Family history (1.8x risk CRC if one relative with)
Genetics syndrome: Eg FAP, HNPCC

Question 6

Lymphatic drainage of the rectum

Answer 6

1) At the dentate line, may drain to inguinal nodes, or more superiorly via EPIrectal nodes to the internal iliac nodes.
2) Inferior 1/3rd and middle 1/3rd drain to internal iliac nodes.
3) Superior third of rectum:peri-rectal, presacral, sigmoidal, and inferior mesenteric nodes

Question 7

Patterns of metastatic spread for rectal cancer:

Answer 7

Inferior 1/3rd can bypass the portal system, Liver is most common site of metastatic disease via portal venous system.

Increased propensity for metastasis to lungs for rectal cancer (lower rectum drains to internal iliac veins and then to IVC)

Question 8

Describe the rectal cancer T stages (T1 to T4):

Answer 8

T1: Invades mucosa only
T2: Involves muscularis but does not breach it.
T3: Extends beyond muscularis into meso/perocolic fat,
T4: Invades adjacent organs

Question 9

Adenocarcinoma make up what % of rectal cancers?

Prognostic and non-prognostic histological features of rectal adenocarcinomas:

Answer 9

More than 90% of rectal cancers are adenocarcinomas.

T stage: mucosa only (T1), involves muscularis (T2, beyond muscularis (T3), adjacent organs (T4)

Differentiation (well, mod, poor, undif) = gland formation (well =95%, undiff <55%)

Nuclear grade not used at present.

Approximately 15% to 20% of adenocarcinomas have colloid (extracellular mucin); Was thought no pronostic significance - but cancer genome atlas suggests worse.

Tumors with signet ring (intracellular mucin) compose 1% to 2% of adenocarcinomas and have worse prognosis.

Question 10

Less common rectal cancer types:

Answer 10

Other histologies: small cell, carcinoid, leiomyosarcoma, lymphoma

Question 11

Grading of quality and completeness of the mesorectum in a total mesorectal excision:

Answer 11

Complete,
Nearly complete
Incomplete

Question 12

Tumor regression score after neoadjuvant therapy for rectal cancer

Answer 12

Modified Ryan scheme for tumor regression score (only performed on primary tumor):

0 (complete response): no viable cancer cells
1 (near complete response): single cells or rare small groups of cancer cells
2 (partial response): evident tumor regression but more than single cells or rare small groups of cancer cells
3 (poor or no response): extensive residual cancer with no evident tumor regression

Question 13

What is unusual about the nodal staging grades for colorectal cancer?

Answer 13

Node negative disease can get an N1 score if subserosa, mesentery or nonperitonealized pericolic or perirectal / mesorectal tissues.

This is N1c = no nodes but tumour deposits as above.

Question 14

Patient with colon cancer has been found to have 2 positive regional lymph nodes and 1 tumor deposit in the subserosa. What is the correct pN staging?

A) N1b, metastases in 2 - 3 regional lymph nodes
B) N1c, tumor deposits in the subserosa, mesentery or nonperitonealized pericolic or perirectal / mesorectal tissues
C)N2a, metastases in 4 or more regional lymph nodes

Answer 14

N1b, metastases in 2 - 3 regional lymph nodes. N1c is used only if there are no lymph node metastases. The number of tumor deposits is NOT added to the number of positive lymph nodes if positive lymph nodes exist.

Question 15

What is N2 colorectal cancer:

Answer 15

N2: metastasis in 4 or more regional lymph nodes
N2a: metastasis in 4 - 6 regional lymph nodes
N2b: metastasis in 7 or more regional lymph nodes

Question 16

Stage III rectal cancer is

Answer 16

Node positive or tumour deposits in in the subserosa, mesentery or nonperitonealized pericolic or perirectal / mesorectal tissues. No mets

Stage 4 is mets.

Question 17

Genetic pathways for colorectal cancer:

Most important prognostic factor?

Answer 17

Typically arises through chromosomal instability pathway (70 - 80%) or microsatellite instability pathway (10 - 15%). Also (more modern) is the serrated (BRAF) pathway.

Stage is most important prognostic factor.

Question 18

What are:
APC
KRAS
SMAD
BRAF

Answer 18

APC - tumour supressor gene. Active APC helps arrange cells for orderly anaphase, inhibits DNA replication by interacting directly with DNA.

KRAS - encodes K-Ras protein in RAS/MAPK (Ras Raf Mek ERK) EGFR proliferation signal pathway

SMAD2 and 4 - TGF-Beta tumour suppressor signal proteins to regulate DNA replication

Ras->BRAF->MEK-ERK-> normal growth.
E.g BRAF V600E then amplification of EGFR signal.

Question 19

General steps of colorectal cancer oncogenesis:

The most common genetic pathway?
Link it to the above steps

Answer 19

(1) Initiation (normal mucosa) ->
(2) promotion (early adenoma/polyp) -> (3) Progression (late adenoma)->
(4) Cancer (carinoma) and Metastasis.

1) APC tumor suppressor inactivation (Mphase transition more likely)
2) KRAS mutation - increased EGFR signal
3) SMAD loss - increased DNA replication (Loss of TGF signal)
4) TP53 mutaion/loss

Question 20

2 Key genetic syndromes that increase colorectal cancer risk? Which is most common?
The most common rare syndrome (ie. 3rd most common)?

Answer 20

Lynch (HNPCC) and familial adenomatous polyposis (FAP). Lynch is most common at about 5% of CRCs. FAP 1%.

Peutz-Jeghers syndrome (PJS) is very rare, but 3rd most common cause.

Question 21

Natural history of FAP

Answer 21

In the most common type of FAP (FAP classic), 100s or 1000s of polyps develop in the colon and rectum, often starting at ages 10-12 years.

Cancer usually develops in 1 or more polyps as early as age 20. By 40, most patients require prophylactic colectomy.

FAP also have an increased risk for cancers of the stomach, small intestines, pancreas, liver, and some other organs.

Question 22

4 sub-types of FAP (which is most common?):

Answer 22

Classic FAP (most common): >100 polyps

Attenuated FAP or AFAP: pts have fewer polyps (<100), and colorectal cancer tends to occur at a later age (40s-50s).

Gardner syndrome: causes non-cancer tumors of the skin, soft tissue, and bones.

Turcot syndrome: higher risk of many adenomatous polyps and CRC. People with Turcot syndrome who have the APC gene are also at risk of medulloblastoma.

Question 23

The key 2 steps in the microsatelite instability pathway:

Answer 23

MSI:
MMR mutation/MLH1 methylation -> BRAF mutation.