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3 / 3 Question 1-3 of 29

Theme: Breast conditions

A. Mondors disease

B. Duct ectasia

C. Periductal mastitis

D. Lactational breast abscess

E. Fibroadenoma

F. Breast cyst

G. Intraductal papilloma

H. Atypical ductal hyperplasia

I. Radial scar

1. A 20 year old lady presents with a mobile lump in the upper outer aspect of her right breast. On examination she

has a firm mobile mass in the upper outer quadrant of her right breast.

Fibroadenoma

Fibroadenomas account for 60% of discrete breast lesions in the 18-25 year age group. They are mobile lesions.

Core biopsy should be performed in lesions measuring more than 4cm in diameter.

2. A 55 year old women presents with nipple discharge. On examination she has a slit like retraction of the nipple

in the centre of this area is a small amount of cheese like material. No discrete mass lesion is palpable in the

underlying breast.

Duct ectasia

Duct ectasia is a common alteration in the breast that occurs with ageing. As the ducts shorten and dilate a

degree of symmetrical slit like retraction occurs. A small amount of cheese like discharge may occur.

3. A 48 year old lady presents with discomfort in the right breast. On examination she has a discrete soft fluctuant

area in the upper outer quadrant of her right breast. A mammogram is performed and a "halo sign" is seen by

the radiologist.

Breast cyst

Lesions such as breast cysts compress the underlying fat and produce a radiolucent area (halo sign). If

symptomatic these cysts should be aspirated.

Question 4 of 29

A 45 year old male has alcoholic cirrhosis and decompensated liver failure, which of the following clotting factors is least

likely to be affected?

A. Factor V

B. Factor VII

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C. Factor IX

D. Factor VIII

E. Factor XI

Factor VIII is synthesised in the endothelial cells of the liver rather than the liver itself and therefore is less prone to the

effects of hepatic dysfunction.

Question 5 of 29

Which of the nerves listed below is responsible for the innervation of the lateral aspect of flexor digitorum profundus?

A. Ulnar nerve

B. Anterior interosseous nerve

C. Radial nerve

D. Median nerve

E. Posterior interosseous nerve

The anterior interosseous nerve is a branch of the median nerve and is responsible for innervation of the lateral aspect

of the flexor digitorum profundus.

Question 6 of 29

A 43 year old lady undergoes a live donor related renal transplant. Over the next few years it is noted that her renal

function progressively deteriorates. What is the most likely underlying explanation?

A. Type I hypersensitivity reaction

B. Type III hypersensitivity reaction

C. Type II hypersensitivity reaction

D. Type IV hypersensitivity reaction

E. None of the above

Chronic rejection of renal transplants is mediated via T lymphocytes and is therefore a type IV hypersensitivity reaction.

This process can be mitigated by immunosupression.

Question 7 of 29

Which of the following structures separates the subclavian artery and vein?

A. Digastric muscle

B. Prevertebral fascia

C. Anterior scalene muscle

D. Middle scalene muscle

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E. Omohyoid

The anterior scalene muscle is an important anatomical landmark and separates the subclavian vein (anterior) from the

subclavian artery (posterior).

Scalene muscles

The 3 paired muscles are:

• Scalenus anterior: Elevate 1st rib and laterally flex the neck to same side

• Scalenus medius: Same action as scalenus anterior

• Scalenus posterior: Elevate 2nd rib and tilt neck to opposite side

Innervation Spinal nerves C4-6

Origin Transverse processes C2 to C7

Insertion First and second ribs

Important

relations

• The brachial plexus and subclavian artery pass between the anterior and middle scalenes

through a space called the scalene hiatus/fissure.

• The subclavian vein and phrenic nerve pass anteriorly to the anterior scalene as it crosses

over the first rib.

Thoracic outlet syndrome

The scalenes are at risk of adhering to the fascia surrounding the brachial plexus or shortening causing compression of

the brachial plexus when it passes between the clavicle and 1st rib causing thoracic outlet syndrome.

1 / 3 Question 8-10 of 29

Theme: Management of testicular disorders

A. Fine needle aspiration cytology

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B. Excision biopsy

C. Orchidectomy via an inguinal approach

D. Lords procedure

E. Orchidectomy via a scrotal approach

F. Division of patent processus vaginalis via an inguinal approach

G. Division of patent processus vaginalis via a scrotal approach

H. Fowler Stephens procedure

I. Immediate scrotal exploration

J. Conservative management

8. An 85 year old man is diagnosed as having prostate cancer and is considered suitable for hormonal ablation.

However, he does not want the repeated injections of GnRH analogues.

Orchidectomy via a scrotal approach

At one time bilateral orchidectomy was performed routinely when prostate cancer was diagnosed

(sometimes under the same anaesthetic). A combination of modern agents (GnRH analogues) and better

consent processes have made this almost obsolete. Where required a scrotal approach should be used.

9. A 33 year old man presents with a painless lump in his left testes. USS and blood tests are suspicious for

teratoma.

Orchidectomy via an inguinal approach

Oncological orchidectomy is routinely performed via an inguinal approach to avoid contamination of another

lymphatic field.

10. A 4 year old boy is brought to the clinic by his mother. He has a swelling in his right hemiscrotum. On

examination is transilluminates brilliantly.

Division of patent processus vaginalis via an inguinal approach

Ligation of the patent processus vaginalis is performed via an inguinal approach. There is no indication for

scrotal surgery for hydrocele in young children.

Testicular disorders

Testicular cancer

Testicular cancer is the most common malignancy in men aged 20-30 years. Around 95% of cases of testicular cancer

are germ-cell tumours. Germ cell tumours may essentially be divided into:

Tumour type Key features Tumour markers Pathology

Seminoma • Commonest subtype

(50%)

• Average age at

diagnosis = 40

• Even advanced

� AFP usually normal

� HCG elevated in 10%

seminomas

� Lactate

dehydrogenase; elevated

in 10-20% seminomas

Sheet like lobular patterns of

cells with substantial fibrous

component. Fibrous septa

contain lymphocytic inclusions

and granulomas may be seen.

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disease associated

with 5 year survival of

73%

(but also in many other

conditions)

Non seminomatous germ

cell tumours (42%)

• Teratoma

• Yolk sac tumour

• Choriocarcinoma

• Mixed germ cell

tumours (10%)

� Younger age at

presentation =20-30 years

� Advanced disease carries

worse prognosis (48% at 5

years)

� Retroperitoneal lymph node

dissection may be needed for

residual disease after

chemotherapy

� AFP elevated in up to

70% of cases

� HCG elevated in up to

40% of cases

� Other markers rarely

helpful

Heterogenous texture with

occasional ectopic tissue such

as hair

Risk factors for testicular cancer

• Cryptorchidism

• Infertility

• Family history

• Klinefelter's syndrome

• Mumps orchitis

Features

• A painless lump is the most common presenting symptom

• Pain may also be present in a minority of men

• Other possible features include hydrocele, gynaecomastia

Diagnosis

• Ultrasound is first-line

• CT scanning of the chest/ abdomen and pelvis is used for staging

• Tumour markers (see above) should be measured

Management

• Orchidectomy (Inguinal approach)

• Chemotherapy and radiotherapy may be given depending on staging

• Abdominal lesions >1cm following chemotherapy may require retroperitoneal lymph node dissection.

Prognosis is generally excellent

• 5 year survival for seminomas is around 95% if Stage I

• 5 year survival for teratomas is around 85% if Stage I

Benign disease

Epididymo-orchitis

Acute epididymitis is an acute inflammation of the epididymis, often involving the testis and usually caused by bacterial

infection.

• Infection spreads from the urethra or bladder. In men <35 years, gonorrhoea or chlamydia are the usual

infections.

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• Amiodarone is a recognised non infective cause of epididymitis, which resolves on stopping the drug.

• Tenderness is usually confined to the epididymis, which may facilitate differentiating it from torsion where pain

usually affects the entire testis.

Testicular torsion

• Twist of the spermatic cord resulting in testicular ischaemia and necrosis.

• Most common in males aged between 10 and 30 (peak incidence 13-15 years)

• Pain is usually severe and of sudden onset.

• Cremasteric reflex is lost and elevation of the testis does not ease the pain.

• Treatment is with surgical exploration. If a torted testis is identified then both testis should be fixed as the

condition of bell clapper testis is often bilateral.

Hydrocele

• Presents as a mass that transilluminates, usually possible to "get above" it on examination

• In younger men it should be investigated with USS to exclude tumour

• In children it may occur as a result of a patent processus vaginalis

• Treatment in adults is with a Lords or Jabouley procedure

• Treatment in children is with trans inguinal ligation of PPV

2 / 3 Question 11-13 of 29

Theme: Oesophgeal disease

A. Schatzki ring

B. Plummer Vinson syndrome

C. Squamous cell carcinoma

D. Barretts oesophagus

E. Pharyngeal pouch

F. Adenocarcinoma

G. Leiomyoma

H. Oesophageal rupture

I. Diffuse oesophageal spasm

J. Hiatus hernia

11. A 56 year old man who drinks heavily is found collapsed by friends at his house. He was out drinking the

previous night and following this was noted to have vomited repeatedly so his friends brought him home.

Oesophageal rupture

Spontaneous rupture of the oesophagus may occur following an episode of vomiting. The subsequent

mediastinitis can produce severe sepsis and death if not treated promptly. Adequate drainage of sepsis and

early surgery are the cornerstones of management.

12. A 43 year old man has been troubled with dysphagia for many years. He is known to have achalasia and has

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had numerous dilatations. Over the past 6 weeks his dysphagia has worsened. At endoscopy a friable mass

is noted in the oesophagus.

Squamous cell carcinoma

The risk of squamous cell carcinoma of the oesophagus is increased in people with achalasia. The condition

often presents late and has a poor prognosis.

13. A 73 year old lady is troubled by episodic swallowing difficulty and halitosis. An upper GI endoscopy is

attempted and abandoned due to difficulty in achieving intubation.

Pharyngeal pouch

Pharyngeal pouches occur when a defect occurs in killians dehiscence. Difficulty in intubation is a well

recognised consequence and care must be taken to take the correct track during OGD to avoid perforation.

Most cases are now treated with endoscopic stapling.

Oesophageal disease

Disorder Features

Mallory-Weiss Tear Usually history of antecedent vomiting. This is then followed by the vomiting of a small amount

of blood. There is usually little in the way of systemic disturbance or prior symptoms.

Hiatus hernia of

gastric cardia

Often longstanding history of dyspepsia, patients are often overweight. Uncomplicated hiatus

hernias should not be associated with dysphagia or haematemesis.

Oesophageal rupture Complete disruption of the oesophageal wall in absence of per-existing pathology. Left postero-

lateral oesophageal is commonest site (2-3cm from OG junction). Suspect in patients with

severe chest pain without cardiac diagnosis and signs suggestive of pneumonia without

convincing history, where there is history of vomiting. Erect CXR shows infiltrate or effusion in

90% of cases(1).

Squamous cell

carcinoma of the

oesophagus

History of progressive dysphagia. Often signs of weight loss. Usually little or no history of

previous GORD type symptoms.

Adenocarcinoma of

the oesophagus

Progressive dysphagia, may have previous symptoms of GORD or Barretts oesophagus.

Peptic stricture Longer history of dysphagia, often not progressive. Usually symptoms of GORD. Often lack

systemic features seen with malignancy

Dysmotility disorder May have dysphagia that is episodic and non progressive. Retrosternal pain may accompany

the episodes.

Diagnosis

Most of the differential diagnoses listed above can be accurately categorised by upper GI endoscopy (usually most

patients). Where this fails to demonstrate a mechanical stricture the use of pH and manometry studies together with

radiological contrast swallows will facilitate the diagnosis.

Question 14 of 29

A 73 year old man develops disseminated intravascular coagulation following an abdominal aortic aneurysm repair. He

receives an infusion of cryoprecipitate. What is the major constituent of this infusion?

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A. Factor VIII

B. Factor IX

C. Protein C

D. Protein S

E. Factor V

Cryoprecipitate

• Blood product made from plasma

• Usually transfused as 6 unit pool

• Indications include massive haemorrhage and uncontrolled bleeding due to haemophilia

Composition

Agent Quantity

Factor VIII 100IU

Fibrinogen 250mg

von Willebrand factor Variable

Factor XIII Variable

Question 15 of 29

A 63 year old man is commenced on an infusion of packed red cells following a total hip replacement. Which of the

following adverse events is most likely?

A. ABO mismatching

B. Immune mediated intolerance of rhesus incompatible blood

C. Pyrexia

D. Jaundice

E. Graft versus host disease

Mild pyrexia during blood transfusion is the most common event and commonly occurs during transfusion.

Blood transfusion reactions

Immune mediated Non immune mediated

Pyrexia Hypocalcaemia

Alloimmunization CCF

Thrombocytopaenia Infections

Transfusion associated lung injury Hyperkalaemia

Graft vs Host disease

Urticaria

Acute or delayed haemolysis

ABO incompatibility

Rhesus incompatibility

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Notes:

GVHD: lymphocyte proliferation causing organ failure

Transfusion associated lung injury: neutrophil mediated allergic pulmonary oedema

ABO and Rhesus incompatibility: causes acute haemolytic transfusion reaction leading to agglutination and haemolysis

Question 16 of 29

A 45 year old women with breast cancer is started on a chemotherapy regime containing epirubicin. What is the primary

mode of action of this drug?

A. Intercalation of DNA

B. Antimetabolite

C. Monoclonal antibody to epidermal growth factor

D. Inhibition of DNA gyrase

E. Inhibition of topoisomerase 1

Class Example Mode of action

Antimetabolites 5 FU S Phase specific drug, mimics uracil and is incorporated into RNA

Anthracyclines* Doxorubicin Inhibits DNA and RNA synthesis by intercalating base pairs

Topoisomerase

inhibitors**

Etoposide Inhibits topoisomerase II, prevents efficient DNA coiling

Platinum Cisplatin Crosslinks DNA, this then distorts molecule and induces apoptosis (similar

to alkylating agents)

Alkylating agent Cyclophosphamide Phosphoramide mustard forms DNA crosslinks and then cell death

Taxanes Docetaxal Disrupts microtubule formation

*=Main adverse effect cardiotoxicity

**=Irinotecan is a similar drug which works by inhibition of topoisomerase I

Breast cancer treatment

Treatment Indication

Endocrine therapy • Oestrogen receptor positive tumours

• Downstaging primary lesions

• Definitive treatment in old, infirm patients

Irradiation • Wide local excision

• Large lesion, high grade or marked vascular invasion following mastectomy

Chemotherapy • Downstaging advanced lesions to facilitate breast conserving surgery

• Patients with grade 3 lesions or axillary nodal disease

Endocrine agents

Tamoxifen is used and works as a partial oestrogen receptor agonist. It will typically block activity at the breast. It does,

however, stimulate the receptors at other sites and it is this that accounts for its association with endometrial cancer. In

post menopausal women the process of aromatisation accounts for most oestrogen production. Therefore in this group

aromatase inhibitors are the preferred agents. Women who are perimenopausal start on tamoxifen and switch at 3

10

years.

Chemotherapy

The FEC regime is most commonly used (Fluorouracil, epirubicin and cyclophosphamide). This was found to be superior

to the older CMF regime. The Taxanes are commonly used in high risk patients and in this setting a regime of docetaxal,

doxorubicin and cyclophosphamide may be used. The anthracycline class drugs have marked cardiotoxicity (a property

that they share with trastuzumab) and this can limit their use.

Question 17 of 29

What is the commonest type of fistula in ano?

A. Trans-sphincteric

B. Supra levator

C. Complex supra levator

D. Intersphincteric

E. Suprasphincteric

Intersphincteric fistulas are the commonest type and lie between internal and external fistulas. These are the classical

type of fistula and will have an internal opening near the anal verge and obey Goodsalls rule. Primary fistulotomy in this

situation usually poses little risk to continence.

Anal fistula

Fistula in ano is the most common form of ano rectal sepsis. Fistulae will have both an internal opening and external

opening, these will be connected by tract(s). Complexity arises because of the potential for multiple entry and exit sites,

together with multiple tracts. Fistulae are classified into four main groups according to anatomical location and the

degree of sphincter involvement. Simple uncomplicated fistulae are low and do not involve more than 30% of the

external sphincter. Complex fistulae involve the sphincter, have multiple branches or are non cryptoglandular in origin[1]

Assessment

Examination of the perineum for signs of trauma, external openings or the stigmata of IBD is important. Digital rectal

examination may reveal the cord linking the internal and external openings. At the same time the integrity of the

sphincter mechanism can be assessed. Low, uncomplicated fistulas may not require any further assessment, other

groups will usually require more detailed investigation. For the fistula, the use of endo-anal USS with instillation of

hydrogen peroxide into the fistula tract may be helpful. Ano-rectal MRI scanning is also a useful tool, it is sensitive and

specific for the identification of fistula anatomy, branching tracts and identifying occult sphincter involvement[2].

Identification of the internal opening

Fistulas with an external opening less than 3cm from the anal verge will typically obey Goodsalls rule (see below).

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Therapies

Seton suture

A seton is a piece of material that is passed through the fistula between the internal and external openings that allows

the drainage of sepsis. This is important as undrained septic foci may drain along the path of least resistance, which

may result in the development of accessory tracts and openings. Their main use is in treating complex fistula. Two types

of seton are recognised, simple and cutting. Simple setons lie within the fistula tract and encourage both drainage and

fibrosis. A cutting seton is inserted and the skin incised. The suture is tightened and re-tightened at regular intervals.

This may convert a high fistula to a low fistula. Since the tissue will scar surrounding the fistula it is hoped that this

technique will minimise incontinence[3]. Unfortunately, a large retrospective review of the literature related to the use of

cutting setons has found that they are associated with a 12% long term incontinence rate [4]

Fistulotomy

Low fistulas, that are simple should be treated by fistulotomy once the acute sepsis has been controlled. Fistulotomy

(where safe) provides the highest healing rates [5]. Because fistulotomy is regarded as having a high cure rate, there are

some who prefer to use this technique with more extensive sphincter involvement. In these patients the fistulotomy is

performed as for a low fistula. However, the muscle that is encountered is then divided and reconstructed with an

overlapping sphincter repair. A price is paid in terms of incontinence with this technique and up to 12.5% of patients who

were continent pre-operatively will have issues relating to continence post procedure[6]. The same group also

randomised between fistulotomy and sphincter reconstruction and ano-rectal advancement flaps for the treatment of

complex cryptoglandular fistulas and reported similar outcomes in terms of recurrence (>90%) and disturbances to

continence (20%)[7].

Other authors have found adverse outcomes following fistulotomy in patients who have undergone previous surgery, are

of female gender or who have high internal openings [8], in these patients careful assessment of pre-operative sphincter

function should be considered mandatory prior to fistulotomy.

Anal fistula plugs and fibrin glue

The desire to avoid injury to the sphincter complex has led to surgeons using both fibrin glue and plugs to try and

improve fistula healing. Meticulous preparation of the tract and prior use of a draining seton is likely to improve chances

of success.

The use of anal fistula plugs in high transphincteric fistula of cryptoglandular origin is to be discouraged because of the

high incidence of non response in patients treated with such devices [9]In most patients septic complications are the

reasons for failure [10]. Fibrin glue is a popular option for the treatment of fistula. There is variability of reported healing

rates In some cases initial success rates of up to 50% healing at six months are reported (in patients with complex

cryptogenic fistula). Of these successes 25% suffer a long term recurrence of fistula [11]. There are, however, no

obvious cases of damage to the sphincter complex and the use of the devices does not appear to adversely impact on

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subsequent surgical options.

Ano-rectal advancement flaps

This procedure is primarily directed at high fistulae, and is considered attractive as a sphincter saving operation. The

procedure is performed either with the patient in the prone jack knife position or in lithotomy (depending upon the site of

the fistula). The dissection is commenced in the sub mucosal plane (which may be infiltrated with dilute adrenaline

solution to ease dissection). The dissection is continued into healthy proximal tissue. This is brought down and sutured

over the defect.

Follow up of patients with cryptoglandular fistulas treated with advancement flaps shows a success in up to 80%

patients[12-14]. With most recurrences occurring in the first 6 months following surgery[12]. Continence was affected in

some patients, with up to 10% describing major continence issues post operatively.

Ligation of the intersphincteric tract procedure

In this procedure an incision is made in the intersphincteric groove and the fistula tract dissected out in this plane and

divided. A greater than 90% cure rate within 4 weeks was initially reported[15]. Others have subsequently performed

similar studies on larger numbers of patients with similar success rates.

Fistulotomy at the time of abscess drainage?

A Cochrane review conducted in 2010 suggests that primary fistulotomy for low, uncomplicated fistula in ano may be

safe and associated with better outcomes in relation to long term chronic sepsis[16]. However, there is a danger that

such surgery performed by non specialists may result in a higher complication rate and therefore the traditional teaching

is that primary treatment of acute sepsis is incision and drainage only. All agree that high/ complex fistulae should never

be subject to primary fistulotomy in the acute setting.

Question 18 of 29

A 42 year old man undergoes a vasectomy at the surgical clinic. He is reviewed at the request of his general practitioner.

On examination he has a small rounded nodule adjacent to the vas. What is the most likely underlying diagnosis?

A. Haematoma

B. Sperm granuloma

C. Varicocele

D. Hydrocele

E. Epididymal cyst

Sperm granulomas are a common sequelae of vasectomy and are smooth round lumps adherant to the vas. They may

be safely left alone.

Vasectomy

Vasectomy is a commonly performed technique for achieving permanent sterilisation. It has a failure rate of 1 in 2000

and is conveniently performed under local anaesthesia.

Reversal success rates are approximately 55% if performed within 10 years of the procedure. For the purposes of

counseling the procedure should be deemed permanent.

Procedure

Small bilateral incisions and formal dissection of the vas is the standard technique. A technique involving the use of

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haemostats for skin puncture is used in the "no scalpel"

technique. It is not necessary to routinely send the vas for histology.

Controversies

Be wary of performing the procedure in childless, single men under age 30.

Risks

Following the procedure between 12 and 52% of men reported chronic scrotal pain. Of which 5.2% sought help.

Haematomas and sperm granulomas may also occur.

Follow up

Viable sperm may persist following surgery. Clearance should not be granted until a negative sperm sample is available.

This is usually taken after 12-16 weeks post procedure (and preferably after 24 ejaculates). Recanalisation may occur in

0.04% of cases.In a small minority of men, non-motile sperm persist after vasectomy. In such cases, "special clearance"

to stop contraception may be given when less than 10,000 non-motile sperm/mL are found in a fresh specimen

examined at least 7 months after vasectomy.

The risks of STI's are unchanged.

Question 19 of 29

A 23 year old man presents with blunt abdominal trauma and a splenic bleed is suspected. He is commenced on an

infusion of tranexamic acid. Which of the following best describes its mechanism of action?

A. Inhibition of plasmin

B. Inhibition of thrombin

C. Inhibition of factor II

D. Inhibition of factor Xa

E. Activation of factor VIII

Tranexamic acid inhibits plasmin and this prevents fibrin degradation.

Tranexamic acid

Tranexamic acid is a synthetic derivative of lysine. Its primary mode of action is as a fibrinolytic that competitively inhibits

the conversion of plasminogen to plasmin. Plasmin degrades fibrin and therefore rendering plasmin inactive slows this

process.

The role of tranexamic acid in trauma was investigated in the CRASH 2 trial and has been shown to be of benefit in

bleeding trauma when administered in the first 3 hours.

Question 20 of 29

Infusion with which of the following blood products is most likely to result in an urticarial reaction?

A. Packed red cells

B. Fresh frozen plasma

C. Platelets

D. Cryoprecipitate

E. Factor VIII concentrate

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Question 21 of 29

A 34 year old male donates a unit of blood. It is stored at 4 oC. After 72 hours which of the following clotting factors will

be most affected?

A. Factor V

B. Factor II

C. Factor VII

D. Factor IX

E. Factor XI

Factors V and VIII are sensitive to temperature which is the reason why FFP is frozen soon after collection.

Question 22 of 29

A 43 year old man is diagnosed as having a malignancy of the right adrenal gland. The decision is made to resect this

via an open anterior approach. Which of the following will be most useful during the surgery?

A. Division of the coronary ligaments of the liver

B. Mobilisation of the colonic hepatic flexure

C. Division of the right renal vein

D. Division of the ligament of Trietz

E. Division of the right colic artery

Mobilisation of the hepatic flexure and right colon are standard steps in open adrenal surgery from an anterior approach.

Mobilisation of the liver is seldom required.

Question 23 of 29

How many compartments are there in the lower leg?

A. 2

B. 1

C. 3

D. 5

E. 4

The deep compartment of the lower leg has both superficial and deep posterior layers, together with the anterior and

lateral compartments this allows for four compartments. Decompression of the deep posterior compartment during

fasciotomy may be overlooked with significant sequelae.

Question 24 of 29

A 73 year old lady sustains a distal radius fracture and this is manipulated using a Biers block with prilocaine as the local

15

anaesthetic agent. During the procedure the occlusion cuff deflates and the patient becomes progressively cyanosed.

What is the treatment of choice?

A. Intravenous calcium gluconate

B. Exchange transfusion

C. Intravenous methylene blue

D. Intravenous sodium thiosulphate

E. Intravenous gelofusine

Prilocaine is a recognised cause of methaemoglobinaemia, this is characterised by the development of cyanosis and

dyspnoea. This disorder occurs because of the change haemoglobin to a ferric subtype rather than ferrous (Fe2+

). This

type of change shifts the oxygen dissociation curve to the left and tissue hypoxia occurs. Methylene blue will revert the

haemoglobin to the ferrous type and reverse this effect.

Question 25 of 29

With which of the following blood products is iatrogenic septicaemia with a gram positive organism most likely?

A. Cryoprecipitate

B. Platelets

C. Packed red cells

D. Factor VIII concentrate

E. Factor IX concentrate

Platelets are stored at room temperature and must be used soon after collection. This places them at increased risk of

culturing gram positive organisms. Iatrogenic infection with gram negative organisms is more likely with packed red cells

as these are stored at 4 degrees.

Infections with blood products of this nature are both rare.

Question 26 of 29

A 34 year old man is diagnosed with an aggressive caecal adenocarcinoma. His sister died from the same disease at 38

years of age. His mother died from endometrial cancer at the age of 41. What is the most likely underlying abnormality?

A. Familial adenopolypomatosis coli

B. Gardeners syndrome

C. Microsatellite instability of DNA repair genes

D. Deletion of chromosome 6

E. MYH gene mutation

Lynch sydrome which is characterised by aggressive right sided colonic malignancy and endometrial cancer is caused

by microsatellite instability of DNA repair genes.

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Genetics of colorectal cancer

The lifetime risk of colorectal cancer in the UK population is 5%. Up to 5% of newly diagnosed bowel cancers will be in

those individuals who have a high genetically acquired risk of bowel cancer. Cancers arising in the low-moderate genetic

risk group comprise approximately 30% of newly diagnosed bowel cancer.

Genetics of inherited colorectal cancer syndromes

Syndrome Features Genes implicated

FAP More than 100 adenomatous polyps affecting the colon and rectum.

Duodenal and fundic glandular polyps

APC (over 90%)

Gardner syndrome As FAP but with desmoid tumours and mandibular osteomas APC

Turcots syndrome Polyposis and colonic tumours and CNS tumours APC +MLH1 and PMS2

HNPCC Colorectal cancer without extensive polyposis. Endometrial cancer, renal

and CNS

MSH2, MLH1, PMS2

and GTBP

Peutz-Jeghers

syndrome

Hamartomatous polyps in GI tract and increased risk of GI malignancy LKB1 andSTK11 (in up

to 70%)

Cowden disease Multiple hamartomas (see below) PTEN (85%)

MYH associated

polyposis

Autosomal recessive, multiple adenomatous polyps in GI tract, those in

colon having somatic KRAS mutations

MYH

FAP

Autosomal dominant condition, affects 1 in 12,000. Accounts for 0.5% of all CRCs. Lifetime incidence of colorectal

cancer in untreated FAP =100%. Up to 25% cases are caused by de-novo germ line mutations and show no prior family

history. The APC tumour suppressor gene is affected in most cases.

APC in non inherited colorectal cancer

Up to 80% of sporadic colorectal cancers will have somatic mutations that inactivate APC[1]. Both alleles are usually

affected. Although the APC protein more than likely has multiple critical cellular functions, the best-established role for

APC in the cancer process is as a major binding partner and regulator of the β- catenin protein in the so-called canonical

or β- catenin dependent Wnt signaling pathway.

HNPCC

HNPCC cancers differ from conventional tumours in a number of respects. In the colon the tumours are more likely to be

right sided, histologically they are more likely to be mucinous and have dense lymphocytic infiltrates. To be diagnosed

as having HNPCC individuals must show typically HNPCC tumours in at least three individuals, (one of whom must be a

first degree relative to the other two). In at least two successive generations. At least one cancer must be diagnosed

under the age of 50. FAP must be excluded and tumours should be verified by pathological identification (Amsterdam

criteria). The genetic changes in HNPCC stem primarily from microsatellite instability affecting DNA mismatch repair

genes. In HNPCC the mismatch repair genes most commonly implicated include; MSH2 and MLH1 and these occur in

up to 70% of people with HNPCC. The finding of microsatellite instability is unusual in sporadic colorectal cancers.

Approximately 60% of individuals who fulfill the Amsterdam criteria will not be found to have evidence of mismatch repair

gene defects on genetic testing. The risk of developing colorectal cancer in those who do not have demonstrated

mutation of the mis match repair genes is increased if they fulfill the Amsterdam criteria, but not the the extent that it is

increased in those who fulfill the criteria AND have evidence of mis match repair gene defects.

KRAS Mutations

The RAS family of small G proteins act as molecular switches downstream of growth factor receptors. KRAS and the

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other two members of the family; HRAS and NRAS, are the site of mutation in approximately 40% of colorectal cancers.

When adenomas are examined the proportion of adenomas less than 1cm showing KRAS mutations was only 10%

which contrasts with 50% in those lesions greater than 1cm.

p53 mutations

The p53 protein functions as a key transcriptional regulator of genes that encode proteins with functions in cell-cycle

checkpoints at the G1/S and G2/M boundaries, in promoting apoptosis, and in restricting angiogenesis . As such,

selection for p53 defects at the adenoma-carcinoma transition may reflect the fact that stresses on tumor cells activate

cell-cycle arrest, apoptotic, and antiangiogenic pathways in cells with wild-type p53 function. Many colonic tumours will

demonstrate changes in the p53 gene that may facilitate tumour progression through from adenoma to carcinoma.

Cowden syndrome

Also known as multiple hamartoma syndrome. Rare autosomal dominant condition with incidence of 1 in 200,000.. It is

characterised by multiple mucocutaneous lesions, trichilemmomas, oral papillomas and acral keratosis. Most often

diagnosed in third decade of life. Breast carcinoma may occur in up to 50% of patients and conditions such as fibrocystic

disease of the breast may occur in 75% of women. Thyroid disease occurs in 75% and may include malignancy.

Endoscopic screening will identify disease in up to 85% although the small bowel is rarely involved. There is a 15-20%

risk of developing colorectal cancer and regular colonoscopic screening from age 45 is recommended.

Terminology

Oncogene Oncogenes are genes which have the potential to induce cellular proliferation and avoid apoptosis.

Oncogene mutations are general gain of function and are therefore dominant. Increased expression of

oncogenes are found in most tumours

Tumour

suppressor

gene

These genes generally inhibit cellular proliferation or induce apoptosis. Mutations in tumour

suppressor genes are generally loss of function mutations, and are therefore recessive. Mutations in

both tumour suppressor gene alleles allow cells to proliferate without restraint

0 / 3 Question 27-29 of 29

Theme: Levels of evidence

A. I

B. II

C. III

D. IV

E. V

27. One of the senior surgeons in the hospital advises as to the best management of Merkel cell tumours of the

skin in which she has a special interest.

V

Personal expert opinion qualifies for level V evidence.

28. A group of surgeons review a meta-analysis of a series of randomised controlled trials on the Cochrane

database and decide that one type of hip replacement is superior to another.

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I

A meta- analysis of more than one well designed trials will typically represent level I evidence. It does, of

course, depend on how well the trials were conducted and reported.

29. A group of surgeons are trying to decide which type of mesh to use for incisional hernia repair. Their

assimilated evidence includes two case series and one randomised controlled trial.

II

Data which includes at least one RCT will usually qualify for level II evidence.

Levels of evidence

The level of evidence refers to the study design used by investigators to minimise bias.

Level of

evidence

Source

I Evidence obtained from systematic review of all relevant randomised controlled trials

II Evidence derived from at least one properly designed randomised controlled trial

III Evidence derived from well designed pseudo-randomised controlled trials (e.g. alternate allocation) or

historical controls

IV Evidence derived from case series or case reports

V Panel or expert opinion