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Flashcards in MRCS Part B Microbiology & Pathology Deck (66)
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1

What is Clostridium difficile? What factors allow Clostridium difficile to cause symptoms? How does it spread so readily? What is a spore? How do you treat C.diff?

C.diff is a gram POSITIVE, spore forming ROD - facultative anaerobe. Causes symptoms by production of exotoxins - such as enterotoxin (C.diff toxin A) and cytotoxin (C.diff toxin B) that attack the walls of the bowel leading to local inflammation and diarrhoea.. The spores are highly resistant and readily transferred, able to survive in conditions other bacteria would not be able to withstand. A SPORE is a minute, one-celled, reproductive unit capable of giving rise to a new individual without sexual fusion. 1st line agent is oral metronidazole, for those who do not respond/are severely unwell the 2nd line agent is vancomycin. Fidaxomicin is a new agent that can also be tried.

2

A 73 year old man is admitted with diarrhoea and is found to have Clostridium difficile colitis. He is treated with oral metronidazole for 10 days. You are the surgical registrar who has been called to review him. On examination he has some right sided abdominal tenderness but his abdomen is soft. He has a recent plain film.

How would you manage him?

This man is likely to have failed medical management and has developed toxic megacolon. The correct treatment is therefore resuscitation, laparotomy and sub total colectomy and end ileostomy formation. Continued attempted antibiotic treatment is highly unlikely to improve the situation rapidly and avert spontaneous perforation.

 

Clostridium difficile is a Gram positive rod often encountered in hospital practice. In the UK it can be found in 3% of normal adults and up to 66% of babies. It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis. 

Risk factors

Broad spectrum antibiotics

Use of PPI and H2 receptor antagonists

Contacted with persons infected with c.difficile


Features

Diarrhoea

Abdominal pain

A raised white blood cell count is characteristic

If severe, toxic megacolon may develop


Diagnosis is made by detecting Clostridium difficile toxin (CDT) in the stool

Management

First-line therapy is oral metronidazole for 10-14 days

If severe, or not responding to metronidazole, then oral vancomycin may be used

Patients who do not respond to vancomycin may respond to oral fidaxomicin

Patients with severe and unremitting colitis should be considered for colectomy

3

What is a surgical site infection? What is the commonest organism responsible for surgical site infections? What factors help to minimise the risk of surgical site infections?

A surgical site infection is the colonisation of a recent surgical wound with pathogenic bacteria that causes local and/ or systemic symptoms and local wound complications. It is important to have a clear appreciation of what constitutes a wound infection because unit outcomes are now widely reported and both over and under diagnosis can have adverse outcomes.

Staphylococcus aureus is the most common organism causing surgical site infections. 

Factors Minimising Risk of SSInfections:

  • Not shaving the wound 
  • Healthcare professionals adhering to good practice by changing clothes, washing hands and wearing gloves as appropriate
  • Timely administration of perioperative antibiotics and continuing doses in those patients for whom it is justified
  • Chlorhexidine skin preparation
  • Avoid incise drapes, if necessary then use iodophor impregnated drapes
  • A recent trial (Rossini) suggests that wound protectors do not reduce the risk of surgical site infections.

 

Surgical site infections may occur following a breach in tissue surfaces and allow normal commensals and other pathogens to initiate infection. They are a major cause of morbidity and mortality.

Surgical site infections (SSI) comprise up to 20% of all healthcare associated infections and at least 5% of patients undergoing surgery will develop an SSI as a result.

In many cases the organisms are derived from the patient's own body. Measures that may increase the risk of SSI include:

Shaving the wound using a razor (disposable clipper preferred)

Using a non iodine impregnated incise drape if one is deemed to be necessary

Tissue hypoxia

Delayed administration of prophylactic antibiotics in tourniquet surgery


Preoperatively

Don't remove body hair routinely

If hair needs removal, use electrical clippers with single use head (razors increase infection risk)

Antibiotic prophylaxis if:

- placement of prosthesis or valve
- clean-contaminated surgery
- contaminated surgery

Use local formulary

Aim to give single dose IV antibiotic on anaesthesia

If a tourniquet is to be used, give prophylactic antibiotics earlier


Intraoperatively

Prepare the skin with alcoholic chlorhexidine (Lowest incidence of SSI)

Cover surgical site with dressing

A recent meta analysis has confirmed that administration of supplementary oxygen does not reduce the risk of wound infection. In contrast to previous individual RCT's(1)

Wound edge protectors do not appear to confer benefit (2)


Post operatively
Tissue viability advice for management of surgical wounds healing by secondary intention

Use of diathermy for skin incisions
In the NICE guidelines the use of diathermy for skin incisions is not advocated(3). Several randomised controlled trials have been undertaken and demonstrated no increase in risk of SSI when diathermy is used(4). 

References
1. Brar M et al.. Perioperative supplemental oxygen in colorectal patients: a meta analysis. J Surg Res 2011 (166): 227 -235. 
2. Pinkney T et al. Impact of wound edge protection devices on surgical site infection after laparotomy: impact of a multicentre randomised controlled trial (ROSSINI Trial). BMJ 2013 (347):10.
3. http://www.nice.org.uk/CG74
4. Ahmad N and Ahmed A. Meta-analysis of the effectiveness of surgical scalpel or diathermy in making abdominal skin incisions. Ann Surg 2011, 253(1):8-13.

 

4

A 45 year old man is admitted profoundly septic and on examination, is found to have a small wound on his right foot. There is relative anaesthesia of the surrounding skin which appears slightly pale. What is the most likely diagnosis? What is the immediate management of this condition? What is the usual cause? What are the main risk factors? What is meant by the term "Fournier gangrene" and how is it managed?

A combination of altered tissue perfusion, sepsis and cutaneous anaesthesia is suggestive of necrotizing fasciitis.

Management is Immediate administration of broad spectrum intravenous antibiotics together with radical surgical debridement. Most cases are polymicrobial with mixed infection consisting of anaerobes and gram negative aerobic organisms. The classical "flesh eating" variant is monomicrobial infection with group A haemolytic streptococcal organisms.

 

Main risk factors for nec fasc: DM, Immunosuppression, PVD

 

Fournier gangrene is a localised form of necrotizing fasciitis that affects the scrotal area and it is managed with radical debridement. The subsequent defects pose considerable reconstructive challenges.

 

Although it may resemble synergistic bacterial gangrene, necrotizing fasciitis is a much more acute and highly toxic infection, causing widespread necrosis and undermining of surrounding tissues. Fournier gangrene is a localised form of necrotizing fasciitis that is localised to the scrotal area. A variety of microbial causes are recognised and three sub groups are recognised; 

 

Type I: Polymicrobial - Mixed anaerobic and gram negative aerobic organisms

Type II: Monomicrobial - Group A haemolytic streptococcal infection

Type III: Gas gangrene - Clostridium perfringens


A major risk factor for infection is underlying disease with poor tissue perfusion from peripheral vascular disease. Immunosupression and diabetes are also major risk factors. Diabetes poses a particular risk because is can result in impaired neutrophil function, poor healing following minor injury and localised tissue hypoperfusion as a result of microvascular disease. 

In many cases there is an underlying injury. This can sometimes be trivial and not readily recalled by the patient. Patients are often profoundly toxic. The overlying skin may not appear overtly abnormal. However, there may be palpable crepitus and the sensation of the overlying skin can be altered as cutaneous nerves are disrupted. 

The initial management is surgical with urgent, wide, radical debridement. The wounds are left open and patients are returned to theatre at 24 hour intervals until no further debridement is required. Negative pressure wound management systems (VAC dressings) have transformed the management of this patient group. Once a healthy wound bed is established, skin grafting is often required. Broad spectrum intravenous antibiotics are administered from the outset and may be adjusted according to microbiological culture of debrided tissue.

5

What type of organism is streptococcus pyogenes? What types of infection are linked to streptococcus pyogenes infection?

Strep pyogenes is a gram positive cocci, Lancefield Group A. These can be categorised as being invasive or non invasive. Invasive infections include; necrotising fasciitis, toxic shock syndrome and puerperal fever. Non invasive infections include pharyngitis, erysipelas and impetigo.

 

Streptococcus pyogenes:

Gram positive cocci Lancefield group A streptococci 

Causes suppurative infections in the respiratory tract and skin 

Virulence factors- adhesion to host cells by interaction between bacterial F protein and human fibronectin, cell surface M proteins allow organism to resist polymorphonuclear leucocytes. Some stains possess a capsule Streptolysins O and S produced by some strains, may play a role in development of rheumatic fever. Pyogenic exotoxins, responsible for many immune effects such as toxic shock. Hyaluronidase production, facilitates spread of infection. Streptokinase, facilitates fibrin breakdown and bacterial spread Infections 

Non invasive disease; includes pharyngitis which may be complicated by the development of scarlet fever. Also causes impetigo and erysipelas

Invasive infection; these include necrotising fasciitis , toxic shock syndrome and puerperal fever. These may occur in previously healthy individuals 

Non suppurative sequlae : rheumatic fever and glomerulonephritis

6

Which of the virulence factors possessed by streptococcus pyogenes are implicated in invasive infections? What systemic complications of non invasive streptococcal disease are you familiar with?

The production of streptolysins, hyaluronidase and streptokinase all break down tissue planes and fibrin and accounts for the spreading and invasive nature of some infections. Pyogenic exotoxins account for many of the features seen in toxic shock syndrome.

 

Systemic complications of non-invasive strep: These include scarlet fever, rheumatic fever and glomerulonephritis. Rheumatic fever is an autoimmune mediate event whereas glomerulonephritis is mediated by immune complex deposition.

 

Streptococcus pyogenes:

Gram positive cocci Lancefield group A streptococci 

Causes suppurative infections in the respiratory tract and skin 

Virulence factors- adhesion to host cells by interaction between bacterial F protein and human fibronectin, cell surface M proteins allow organism to resist polymorphonuclear leucocytes. Some stains possess a capsule Streptolysins O and S produced by some strains, may play a role in development of rheumatic fever. Pyogenic exotoxins, responsible for many immune effects such as toxic shock. Hyaluronidase production, facilitates spread of infection. Streptokinase, facilitates fibrin breakdown and bacterial spread Infections 

Non invasive disease; includes pharyngitis which may be complicated by the development of scarlet fever. Also causes impetigo and erysipelas

Invasive infection; these include necrotising fasciitis , toxic shock syndrome and puerperal fever. These may occur in previously healthy individuals 

Non suppurative sequlae : rheumatic fever and glomerulonephritis

7

What is the difference between cleaning and sterilisation of instruments? What is the reason behind cleaning instruments prior to sterilisation? How are the majority of surgical instruments sterilised?

The process of cleaning instruments refers to the systematic removal of foreign material and visible debris from a device. Sterilisation involves the removal of all viable micro-organisms from a device. Disinfection involves the reduction in the number of viable micro-organisms from a surface, but does not remove them all.

The process of sterilisation does not, in itself, involve the removal of debris from the surface of an instrument. If a device is not cleaned prior to sterilisation then there will still be proteinaceous material and other debris present on the surface following use. Apart from being aesthetically displeasing this can impair the function of the instrument and may introduce foreign material, albeit denatured, into a new wound.

Sterilisation: The usual practice is to autoclave them. This involves placing clean instruments into a specialised unit that delivers high pressure and temperature steam into a closed unit. A median treatment time of three minutes at 134 degrees oC is the usual strategy.

 

Surgical equipment has to be cleaned and sterilised prior to use. The extent to which these processes will be required varies according to the type of equipment and the purpose for which it will be used. In general, the three processes are relevant; cleaning, disinfection and sterilisation.

Cleaning refers to removal of physical debris.

Disinfection refers to reduction in numbers of viable organisms.

Sterilisation is removal of all organisms and spores.

Autoclaving: Air removed and high pressure steam used (usually 134 oC for 3 minutes)Most reusable surgical equipment, must be physically cleaned prior to autoclaving, unsuitable for fragile items

Glutaraldehyde solution (2%): Colourless oily liquid, directly cytocidal and virucidal even at low temperaturesSpecifically used for endoscopes and some laparoscopic items, staff can rapidly develop allergy to this substance which has limited its more widespread use

Ethylene oxide: 3% mixture of gas with carbon dioxide usedUsed for packaged materials that cannot be heated, the gas is explosive and environmentally toxic, it is used mainly in the industrial setting

Gamma irradiation: Gamma rays emitted from radioactive substance such as cobalt 60 or caesium 137Suitable for batch treatment of relatively thermostable items, typically an industrial process

8

What is the Bowie-Dick test and how does it relate to autoclaves? Name all the known prion diseases? What precautions must be taken when undertaking surgery or an invasive procedure on a patient with a known or suspected prion disease?

During autoclaving the usual practice is to create a vacuum at the beginning and the end of each sterilisation cycle. The Bowie-Dick test consists of a unit containing indicator strips that change colour when the autoclave cycle, including the vacuum phases is working correctly. These units are placed into an autoclave and a cycle is run. The unit and its indicators are then checked at the conclusion of the cycle. It provides a warning of device malfunction.

 

Known prion diseases: Kuru, Creutzfeldt-Jacob Disease, variant Creutzfeldt-Jacob Disease, fatal familial insomnia and Gerstmann-straussler-scheinker-syndrome (GSS).

 

All patients irrespective of known or suspected prion disease: Single use devices must be used for lumber punctures and surgery relating to the eye, tonsils, brain or spinal cord.

For known and suspected cases of CJD for all types of surgery: it is important that the Infection Prevention & Control Team and Hospital Sterilising and Disinfection Unit Manager are informed by clinicians of all suspected or known patients with CJD, so that disposable instruments can be used for all surgery on those patients (wherever possible). All non-disposable instruments on such patients must be quarantined (suspected cases) or destroyed (known cases).

 

Surgical equipment has to be cleaned and sterilised prior to use. The extent to which these processes will be required varies according to the type of equipment and the purpose for which it will be used. In general, the three processes are relevant; cleaning, disinfection and sterilisation.

Cleaning refers to removal of physical debris.

Disinfection refers to reduction in numbers of viable organisms.

Sterilisation is removal of all organisms and spores.

Autoclaving: Air removed and high pressure steam used (usually 134 oC for 3 minutes)Most reusable surgical equipment, must be physically cleaned prior to autoclaving, unsuitable for fragile items

Glutaraldehyde solution (2%): Colourless oily liquid, directly cytocidal and virucidal even at low temperaturesSpecifically used for endoscopes and some laparoscopic items, staff can rapidly develop allergy to this substance which has limited its more widespread use

Ethylene oxide: 3% mixture of gas with carbon dioxide usedUsed for packaged materials that cannot be heated, the gas is explosive and environmentally toxic, it is used mainly in the industrial setting

Gamma irradiation: Gamma rays emitted from radioactive substance such as cobalt 60 or caesium 137Suitable for batch treatment of relatively thermostable items, typically an industrial process

9

What is tetanus? What are the features, present in a wound, that increase the risk of tetanus? How is it prevented? How would you manage a high risk tetanus prone wound in a non immunised patient? How would you manage a clean wound in a person who was fully immunised against tetanus more than ten years ago?

Tetanus is a condition characterised by generalised muscular spasms that occur as a result of the infection of a wound with the spore producing Clostridium tetani. The organism produces a neurotoxin (tetanospasmin) that is transported to the CNS and inhibits the release of inhibitory neurotransmitter molecules that results in unopposed neuronal motor discharge.

 

Wound risk factors: Heavy contamination with soil or faeces, Devitalised tissue, Infected or old neglected wounds, Puncture wounds

Tetanus is prevented by wound managment and immunisation  programmes.

High risk non-immunised wound Debride and clean wound. Administer human anti tetanus immunoglobulin and start an immunisation course of tetanus toxoid

Clean wound, immunised >10years ago: wound care and tetanus toxoid booster.

 

Tetanus is an acute and often fatal disease which is relatively rare in the Western world because of immunisation programmes and ready access to healthcare. It is caused by the organism Clostridium tetani which is commonly found in soil and animal faeces. The tetanus bacillus is a straight slender gram positive rod. A fully developed terminal spore gives the organism its classical drumstick appearance. It is an obligate anaerobe, the spores are highly resistant to adverse conditions. Clostridium tetani produces a number of toxins. However, the organisms neurotoxin (tetanospasmin) is the main pathogenic product. The toxin diffuses to the relevant level of the spinal cord to produce local tetanus and then affects the entire CNS. Infection to the key aspects of the CNS is via retrograde axonal transport. Once the entire toxin molecule is internalised into the presynaptic cells it affects the membrane of the synaptic vesicles and prevents the release of the neurotransmitter γ aminobutyric acid. Motor neurones are thus left under no inhibitory control and undergo sustained excitatory discharge causing the classical motor spasms of tetanus. The incubation period is usually 4-14 days. Management of established tetanus consists of providing full supportive care in the ITU as autonomic disturbance and cardiac arrhythmias are common. Penicillin, metronidazole and human tetanus immunoglobulin should be administered. Any wounds should be debrided. Tetanus immunisation programme The standard active immunisation programme consists of 3 IM doses of 0.5ml of tetanus toxoid given at monthly intervals from 2 months of age. Booster doses are given at 4 and 14 years of age. Immunisation following injury depends upon the immunisation status of the patient. 

The following features render a wound at high risk of tetanus: 
Heavy contamination with soil or faeces 
Devitalised tissue Infection or old neglected wounds 
Puncture wounds 

DOH guidance 

Immunisation statusClean woundTetanus prone wound

Full course or less than 10 yearsNilGive tetanus toxoid booster

Full course but more than 10 years agoGive tetanus toxoid booster (may be omitted if full five doses given at correct intervals)Give tetanus toxoid booster and human (may be omitted if full five doses given at correct intervals) anti tetanus immunoglobulin

Not immunised or unknownStart tetanus toxoid courseStart tetanus toxoid course and give human anti tetanus immunoglobulin

 

10

What is the difference between a community acquired infection and a nosocomial infection? What factors increase the risk of nosocomial infections? What is meant by the term ventilator acquired pneumonia? What aetiological factors contribute to the development of ventilator associated pneumonia?

Community acquired infections are those which originate in the community. These are, therefore, either present on admission or occur more than 10 days following discharge from hospital. They typically are not related to and surgical site or indwelling device inserted during that hospital admission, or in the case of prostheses, up to 1 year following implantation. The causative agent will usually be one that is present in the community and be sensitive to standard community based interventions. Nosocomial infections are those which are acquired in hospital or within 10 days following discharge. They are typically caused by different pathogens to community infections and have differing antimicrobial sensitivities.

 

Risk increased by: High patient occupancy levels
Poor infection control practice
Excessive use of indwelling devices or delayed removal of such devices
Failure to use infection control bundles, where these exist
Poor equipment handling (increasing risks of contamination)

 

It is defined as a pneumonia that occurs 48 hours after commencement of invasive ventilation or within 24 hours of extubation. 

Aetiological factors contributing to VAP: Bacterial overgrowth of the oropharynx and stomach
Impaired mucociliary clearance and coughing
Impaired glottis closure with pooling of secretions above endotracheal tubes
Microaspiration or oropharyngeal contents

 

Healthcare associated infections
As many as 1 in 10 patients may have a healthcare associated infection (HCAI) at any one time. Up to 5000 deaths occur in the UK each year as a result of HCAI. 
A number of different terms are used to describe infections that occur in hospitalised patients:

Nosocomial: Acquired as a result of admission to a healthcare facility
Infection not present on admission, commencing 48 hours following admission, or up to 10 days following discharge
Surgical site infections are those which occur up to 30 days following a procedure (1 year if prosthesis used)

HCAI: Used to describe situations of increased infection risk with pathogens found in hospitals
Affected by antibiotic policy
Vary according to site, illness, devices, concomitant therapy


Types of HCAI
UTIs are the most common, septicaemia has the highest mortality.

Bacterial:
UTI- device related
Pneumonia- use of ventilators
Surgical site infections
Bloodstream infections- use of central venous catheters
Clostridium difficle colitis

Viruses:
Gastroenteritis
Respiratory tract infections
Hepatitis B and C/ HIV
Prion disease

Reducing risk

Preoperative MRSA screening and decontamination if colonised
Hair removal with clippers
Correct antimicrobial prophylaxis (dose, drug, time)
Normoglycaemia
Normothermia

11

What diseases are associated with Helicobacter Pylori infection? What type of organism is H.pylori? How is a H pylori infection diagnosed? How is infection treated? 

Associated with H.pylori infection: Peptic ulcers, Gastric cancer, MALT lymphoma

H. pylori is a gram negative, slightly curved rod, it is microaerophilic.

Diagnosis H pylori: Culture (difficult, slow, but accurate), Microscopy (accurate but invasive), Serology (difficult to establish eradication), Biopsy rapid urease tests (Clo, invasive but quick)

 

Infection is treated with triple therapy: Abx, PPI

 

Infection with Helicobacter Pylori is implicated in many cases of duodenal ulceration and up to 60% of patients with gastric ulceration. 

It is a gram negative, helical shaped rod with microaerophillic requirements. It has the ability to produce a urease enzyme that will hydrolyse urea resulting in the production of ammonia. The effect of ammonia on antral G cells is to cause release of gastrin via a negative feedback loop. 

Once infection is established the organism releases enzymes that disrupt the gastric mucous layer. Certain subtypes release cytotoxins cag A and vac A gene products. The organism incites a classical chronic inflammatory process of the gastric epithelium. This accounts for the development of gastric ulcers. The mildly increased acidity may induce a process of duodenal gastric metaplasia. Whilst duodenal mucosa cannot be colonised by H-Pylori, mucosa that has undergone metaplastic change to the gastric epithelial type may be colonised by H- Pylori with subsequent inflammation and development of duodenitis and ulcers.

In patients who are colonized, there is a 10-20% risk of peptic ulcer, 1-2% risk gastric cancer and <1% risk MALT lymphoma.

12

You have just performed a radical orchidectomy for a suspected testicular cancer. Outline the steps involved in the pathological processing of this specimen such that the pathologist may be in a position to issue a histopathology report.

 

The specimen should be placed in a contained of adequate size and covered with saline/ formalin combination. The specimen should be clearly labeled with patient details and a request card completed with adequate clinical information. It should be transported to the hospital pathology department and the tissue allowed to fix prior to being cut by a pathologist. 
Sites of interest will then be processed and impregnated with wax before being embedded and cut using a microtome. A number of basic (H&E) and advanced (immunohistochemistry) stains will be applied to multiple sections to allow the pathologist to assess the tumour and provide useful prognostic information.

13

What would be the best method for assessing whether a peritoneal nodule encountered during the trial dissection phase of a Whipples procedure contained metastatic cancer or not?

In this situation a rapid diagnosis is required. If the nodule is indeed metastatic cancer then it represents peritoneal disease and attempts to proceed with definitive resection aborted. The surgeon should telephone the pathology department and warn then that a frozen section is about to be requested. The tissue should be taken immediately to the department, cut into small pieces and then frozen in liquid nitrogen. It is then cut into thin sections using a cryostat and stained. The pathologist can then view the specimen and attempt to determine whether there are cancer cells present or not.

 

Principles of pathological specimen processing


Surgeons frequently submit human tissues for histological assessment. In some cases the intention is to confirm a know or suspected diagnosis. At other times the diagnosis may have been elusive and only by direct analysis of tissue cellular composition and architecture can it be achieved. 

Histological assessment of tissue involves processing it such that it can be visible microscopically. There are two main methods for achieving this, the first involves frozen sections and the second, paraffin embedded ones.

Frozen sections are usually performed when tissue microscopy is required urgently, such as intra operatively. The tissue is cut up and then snap frozen using liquid nitrogen and cut into thin sections using a cryostat microtome. The thin tissue sections thus obtained are placed onto a glass microscope slide and stained with haematoxyllin and eosin. The advantage of the technique is speed. The main disadvantages of the technique are that it is very labour intensive and the quality of the sections obtained does not equate with those that are obtained following formalin fixation and wax embedding. On occasion the specimen quality may be so poor that a pathologist cannot make a robust diagnosis. 

The other method of specimen preparation for histology involves formalin fixation of the tissue specimen. Formalin cross links collagen fibres and maintains the structural and cellular integrity of tissues that facilitates subsequent analysis. This process takes between 24 and 72 hours depending upon the size of the tissue sample.Once fixed, the tissue is cut up by a pathologist into small blocks that represent regions of interest. These blocks are processed by impregnating the tissues with wax. They are eventually embedded in wax and cut into thin sections using a microtome. They can be stained with a number of different tissue stains. The advantage of this technique is that it provides specimens that are long lasting and require little special storage precautions. The main disadvantage is the time taken to prepare the tissues. Even in an efficient laboratory a turnaround time of less than 48-72 hours for small specimens would be unusual. 

There are some special histological immunohistochemistry tests that are impeded by the tissue fixation process with formalin. Renal biopsies and lymph nodes are two tissue types for which it is often best to check with the laboratory first. Particularly if there is any intention to submit part of a lymph node for culture.

14

What are the key differences between histology and cytology?

 

Histology allows determination of cell types in relation to their surrounding structures. This usually requires pieces of tissue for analysis. Cytology is concerned with analysis of individual cells. Whilst this may convey important clinical information, there are some situations where it is not possible to determine with certainty whether a pathology is present or not. This is well demonstrated by follicular lesions of the thyroid, where it is impossible to state whether cancer is present without histological assessment of the capsule.

 

Principles of pathological specimen processing


Surgeons frequently submit human tissues for histological assessment. In some cases the intention is to confirm a know or suspected diagnosis. At other times the diagnosis may have been elusive and only by direct analysis of tissue cellular composition and architecture can it be achieved. 

Histological assessment of tissue involves processing it such that it can be visible microscopically. There are two main methods for achieving this, the first involves frozen sections and the second, paraffin embedded ones.

Frozen sections are usually performed when tissue microscopy is required urgently, such as intra operatively. The tissue is cut up and then snap frozen using liquid nitrogen and cut into thin sections using a cryostat microtome. The thin tissue sections thus obtained are placed onto a glass microscope slide and stained with haematoxyllin and eosin. The advantage of the technique is speed. The main disadvantages of the technique are that it is very labour intensive and the quality of the sections obtained does not equate with those that are obtained following formalin fixation and wax embedding. On occasion the specimen quality may be so poor that a pathologist cannot make a robust diagnosis. 

The other method of specimen preparation for histology involves formalin fixation of the tissue specimen. Formalin cross links collagen fibres and maintains the structural and cellular integrity of tissues that facilitates subsequent analysis. This process takes between 24 and 72 hours depending upon the size of the tissue sample.Once fixed, the tissue is cut up by a pathologist into small blocks that represent regions of interest. These blocks are processed by impregnating the tissues with wax. They are eventually embedded in wax and cut into thin sections using a microtome. They can be stained with a number of different tissue stains. The advantage of this technique is that it provides specimens that are long lasting and require little special storage precautions. The main disadvantage is the time taken to prepare the tissues. Even in an efficient laboratory a turnaround time of less than 48-72 hours for small specimens would be unusual. 

There are some special histological immunohistochemistry tests that are impeded by the tissue fixation process with formalin. Renal biopsies and lymph nodes are two tissue types for which it is often best to check with the laboratory first. Particularly if there is any intention to submit part of a lymph node for culture.

15

What are the main features of the acute inflammatory process?What is an abscess? Why do abscesses form? What is an empyema?

The key features of acute inflammation are vasodilatation, formation of a protein rich exudate and the accumulation of neutrophil polymorphs at the site. The process concludes by resolution, abscess formation or progression to chronic inflammation.

 

An abscess is a collection of tissue flid and white cells within a contained space

 

Abscesses: usually arise because there is a significant microbial load at a specific anatomical site. This in turn results in the accumulation of a significant quantity of neutrophil polymorphs. Tissue fluid will extravasate into the site. The centre of abscesses is usually hypoxic and this can impede oxygen free radical dependent killing mechanisms and cellular phagocytic functions. This therefore impedes clearance of pus. Finally, there needs to be confinement of this process. This typically occurs as a result of anatomical factors such as the presence of skin or connective tissue which anatomically confines the process.

 

Empyema:  collection of pus within a hollow viscus

 

Inflammation is the reaction of the tissue elements to injury. Vascular changes occur, resulting in the generation of a protein rich exudate. So long as the injury does not totally destroy the existing tissue architecture, the episode may resolve with restoration of original tissue architecture.

Vascular changes: Vasodilation occurs and persists throughout the inflammatory phase. Inflammatory cells exit the circulation at the site of injury. The equilibrium that balances Starlings forces within capillary beds is disrupted and a protein rich exudate will form as the vessel walls also become more permeable to proteins.

The high fibrinogen content of the fluid may form a fibrin clot. This has several important immunomodulatory functions.


Sequelae:

Resolution: Typically occurs with minimal initial injury. Stimulus removed and normal tissue architecture results

Organisation: Delayed removal of exudate, Tissues undergo organisation and usually fibrosis

Suppuration: Typically formation of an abscess or an empyema. Sequestration of large quantities of dead neutrophils

Progression to chronic inflammation: Coupled inflammatory and reparative activities. Usually occurs when initial infection or suppuration has been inadequately managed


Causes

Infections e.g. Viruses, exotoxins or endotoxins released by bacteria

Chemical agents 

Physical agents e.g. Trauma

Hypersensitivity reactions 

Tissue necrosis


Presence of neutrophil polymorphs is a histological diagnostic feature of acute inflammation

16

What is amyloid? What types of amyloidosis are you familiar with? What organs are most commonly affected by amyloidosis? How is it diagnosed? How is it treated?

Amyloid: extracellular protein deposit which is insoluble. It is usually linked to a deposition of a specific fibrillar protein.

Both AA and AL types of amyloidosis are well described. AL is the most common type and related to conditions such as myeloma. AA amyloidosis is typically associated with chronic inflammatory states.

The heart and kidneys are the most common sites. However, amyloidosis is a multisystem disorder.

By biopsy of an affected organ. Histologically, the insoluble proteinaceous deposit will cause the birefringence of polarised light. 

There is no specific treatment for amylosis per se, treatment is directed at the underlying cause.

 

Amyloid is an extracellular protein deposit which is insoluble. These deposits disrupt normal tissue structure and if excessive may affect function. All types of amyloid consist of a major fibrillar protein that defines the type of amyloid (approximately 90%) plus various minor components.

Amyloid is classified with the prefix A (for amyloid) and the suffix depending upon the fibrillary protein present. The main clinical types are AA and AL amyloidosis. Systemic AA amyloidosis is a long-term complication of several chronic inflammatory disorders - e.g. rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, malignancies and conditions predisposing to recurrent infections. AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin light chains (most commonly of lambda isotype). Most patients have evidence of isolated monoclonal gammopathy or asymptomatic myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. AL type amyloidosis is the most common variant. The kidney and heart are two of the most commonly affected sites. Diagnosis is based on surgical biopsy and characteristic histological features which consist birefringence under polarised light. Immunohistochemistry is used to delineate the subtype. Treatment is usually targeted at the underlying cause.

17

What is meant by the term "metaplasia"? Describe the metaplastic processes involved in the development of Barrett's oesophagus.

What process may complicate Barrett's oesophagus that can result in the development of oesophageal cancer?

 

Metaplasia : transformation of one type of specialised epithelium to another, usually in response to a external stimulus.

Barrett's oeosphagus is characterised by long standing gastro-oesophageal reflux. This results in recurrent oesophagitis. Eventually, the squamous epithelium that lines the oesophageal lumen becomes replaced by goblet cells that are usually found in the stomach.

Dysplasia may complicate Barrett's oesophagus and can result in the development of oesophageal cancer

18

What is the main concern when severe dysplasia is identified in a segment of Barrett's oesophagus? What treatments are available for Barrett's oesophagus complicated by severe dysplasia? How is Barrett's oeosphagus without dysplasia managed?

The main concern is that a foci of invasive cancer has already developed and been missed through sampling error.

The treatment depends upon the fitness of the patient and patient wishes. Treatment options include photodynamic therapy, laser ablation and segmental resection.

Barrett's without dysplasia:  managed with long term proton pump inhibitor therapy. Endoscopic surveillance is also required.

 

Barretts oesophagus is a condition characterised by the metaplastic transformation of squamous oesophageal epithelium to columnar gastric type epithelium. Three types of this metaplastic process are recognised; intestinal (high risk), cardiac and fundic. The latter two categories may cause difficulties in diagnosis. The most concrete diagnosis can be made when endoscopic features of Barretts oesophagus are present together with a deep biopsy that demonstrates not just goblet cell metaplasia but also oesophageal glands. 

Barrett's can be sub divided into short (<3cm) and long (>3cm). The length of the affected segment correlates strongly with the chances of identifying metaplasia. The overall prevalence of Barrett's oesophagus is difficult to determine but may be in the region of 1 in 20 and is identified in up to 12% of those undergoing endoscopy for reflux. 

A proportion of patients with metaplasia will progress to dysplasia and for this reason individuals identified as having Barrett's should undergo endoscopic surveillance (every 2-5 years). Biopsies should be quadrantic and taken at 2-3cm intervals. Biopsies need to be adequate. Where mass lesions are present consideration should be given to endoscopic sub mucosal resection. Up to 40% of patients will be upstaged from high grade dysplasia to invasive malignancy with such techniques.

Treatment

Long term proton pump inhibitor

Consider pH and manometry studies in younger patients who may prefer to consider an anti reflux procedure

Regular endoscopic monitoring (more frequently if moderate dysplasia). With quadrantic biopsies every 2-3 cm

If severe dysplasia be very wary of small foci of cancer

 

19

What are the key pathological features of Crohns disease? What is the commonest extra intestinal complication of Crohns disease and why does it occur? Why do people with Crohns disease develop diarrhoea? What skin lesions are typically associated with Crohns disease?

It is a chronic inflammatory condition affecting the gastrointestinal tract. Focal inflammatory inflammation occurs in a non confluent fashion with a patchy distribution. Whilst the terminal ileum is the commonest site, any site can be affected. Macroscopically, the inflammation is transmural and typically heals by fibrosis, which accounts for the stricturing that occurs. On internal inspection, the transmural inflammation appears as cobblestones on the mucosa. Histologically, there are stigmata of chronic inflammation, particularly with the presence of granulomas.

 

Diarrhoea in Crohns may be multifactorial since actual inflammation of the colon is not common. Causes therefore include the following:

Bile salt diarrhoea secondary to terminal ileal disease

Entero-colic fistula

Short bowel due to multiple resections

Bacterial overgrowth

The commonest extra intestinal complication of Crohns disease is the development of gallstones. This is seen in up to 30% of cases. The pathogenesis of this relates to the high degree of terminal ileal involvement with Crohn's disease. Following resection or even healing with extensive fibrosis, there is an impairment of bile salt recycling, which then results in salt imbalance within bile and gallstone deposition.

The causes of diarrhoea in patients with Crohns disease are multifactorial. The inflammatory activity in the acute phase results in secretion of mucous into the bowel lumen and increased fluid volume that makes for a more watery stool. In addition, terminal ileal disease, results in bile salt malabsorption that can result in bile salt diarrhoea. Patients who have undergone extensive resections or even those with loss of absorptive surface area due to extensive disease have a mal absorptive state that is characterised by diarrhoea. Finally, some patients develop entero-colic fistulas that result in small bowel content entering the distal colon and presenting a fluid load that is then not absorbed.

 

Skin lesions: Erythema nodosum, an acute nodular erythematous eruption usually affecting the legs is sometimes seen. So too is pyoderma gangrenosum, which is a painful ulcerated lesion that can occur anywhere in the body but not infrequently occurs in close proximity to any stomas that may be constructed. It is challenging to treat.

20

A 38 year old male with long standing terminal ileal Crohns disease has recurrent episodes of small bowel obstruction. He has been investigated with colonoscopy which demonstrated a normal colon (but the ICV could not be entered) and MRI enteroclysis which demonstrates a 7cm terminal ileal stricture. What is the best treatment option? When performing a laparotomy for a patient with Crohns disease what external features of the affected segment are often present?

Long standing strictures like this are often fibrotic and seldom respond to medical management. The best management therefore involves optimising his nutritional state and once this is achieved proceed to surgery. The usual option here would be an ileocaecal resection. 7cm would be slightly too long for a stricturoplasty. In the event that he is smoker he should be given every encouragement to stop since smoking significantly increases his risk of recurrent disease. 

Features of external segment on laparotomy: It may be obviously inflamed and the bowel is often thick walled and may feel fibrotic. It is the friable, fatty mesentery that is usually one of the most striking and surgically challenging features.

 

Surgical interventions in Crohns disease
The commonest disease pattern in Crohns is stricturing terminal ileal disease and this often culminates in an ileocaecal resection. Other procedures performed include segmental small bowel resections and stricturoplasty. Colonic involvement in patients with Crohns is not common and, where found, distribution is often segmental. However, despite this distribution segmental resections of the colon in patients with Crohns disease are generally not advocated because the recurrence rate in the remaining colon is extremely high. As a result, the standard options of colonic surgery in Crohns patients are generally; sub total colectomy, panproctocolectomy and staged sub total colectomy and proctectomy. Restorative procedures such as ileoanal pouch have no role in therapy.
Crohns disease is notorious for the developmental of intestinal fistulae; these may form between the rectum and skin (peri anal) or the small bowel and skin. Fistulation between loops of bowel may also occur and result in bacterial overgrowth and malabsorption. Management of enterocutaneous fistulae involves controlling sepsis, optimising nutrition, imaging the disease and planning definitive surgical management.

 

Extraintestinal manifestations of Crohns

Related to disease extent: Aphthous ulcers (10%), Erythema nodosum (5-10%), Pyoderma gangrenosum (0.5%), Acute arthropathy (6-12%), Ocular complications (up to 10%)

 

Unrelated to disease extent

Sacroiliiitis (10-15%), Ankylosing spondylitis (1-2%), Primary sclerosing cholangitis (Rare), Gallstones (up to 30%), Renal calculi (up to 10%)

 

 

Crohn's disease: Mouth to anus. Macroscopic changes: Cobblestone appearance, apthoid ulceration. Depth of disease: Transmural inflammation. Distribution pattern: Patchy. Histological features: Granulomas (non caseating epithelioid cell aggregates with Langhans' giant cells)

Ulcerative colitis: Distribution: Rectum and colon. Macroscopic changes: Contact bleeding. Depth of disease: Superficial inflammation. Distribution pattern: Continuous. Histological features: Crypt abscesses, Inflammatory cells in the lamina propria

21

A 73 year old man presents with the knee pain and the following x-ray is obtained. What are the main abnormalities? What is the most likely diagnosis? Describe the main features of this condition.

This is an x-ray of the knee and the following abnormalities are demonstrated:
Joint space narrowing
Osteophyte formation
Increased subchondral bone density
Bone cyst formation

In keeping with OA of the knee

Osteoarthritis is a degenerative condition affecting synovial joints. It may be primary, where there is no overt antecedent cause, or secondary where there is an underlying reason (such as deformity or trauma). It is characterised by the destruction of hyaline cartilage in the early phases and then progressive destruction of the underlying cortical bone. In contrast to rheumatoid disease, there is a minimal inflammatory response and almost no systemic disturbance.

Diagnosis: It is largely a clinical diagnosis, a good history, compatible clinical examination and supportive plain films are usually supportive. In most cases, more specialised imaging is unnecessary. Blood testing for inflammatory markers is generally used to exclude rheumatoid disease.

 

Osteoarthritis is a very common degenerative joint disorder that arises as a result of hyaline cartilage destruction in synovial joints. The commonest presentation is with pain in the affected joint which is worse on movement. Osteoarthritis typically affects weight bearing joints and is less common in those that are not subjected to mechanical loads. In some cases there is a history of antecendant trauma. Where this is the case, the condition is termed secondary. More rarely, there is not and the condition occurs without an obvious primary cause, and is then termed primary.Osteoarthritis of the hands usually falls into this primary category.

Pain in osteoarthritis
Pain, the main presenting symptom of osteoarthritis, is presumed to arise from a combination of mechanisms, including the following:

Osteophytic periosteal elevation
Vascular congestion of subchondral bone, leading to increased intraosseous pressure
Synovitis with activation of synovial membrane nociceptors
Fatigue in muscles that cross the joint
Overall joint contracture
Joint effusion and stretching of the joint capsule
Torn menisci
Inflammation of periarticular bursae
Periarticular muscle spasm
Psychological factors
Crepitus (a rough or crunchy sensation)
Central pain sensitization

Investigation
Plain x-rays often demonstrate classical features in weight bearing joints including, loss of joint space, sub chondral bone sclerosis and bone cyst formation.

Laboratory investigations are of limited value and where they are undertaken are usually normal. Indeed, raised inflammatory markers are strongly suggestive of an alternative diagnosis. 

Management
Early cases respond to simple analgesia and physiotherapy. Once established, the only realistic definitive treatment option is arthroplasty or arthrodesis.

22

What are the cells of origin of carcinoid tumours? What is the most common site of carcinoid tumours? What are the typical luminal macroscopic features of carcinoid tumours ?

Carcinoid tumours are derived from neuroendocrine cells. The vast majority of tumours are identified within the appendix. They are most common in the terminal ileum, appendix and caecum. More rarely, they may be found in other sites such as the rectum and bronchi.

 

Luminal macroscopic features of carcinoid of sites such as the rectum: They typically appear as a mass lesion with normal overlying gastrointestinal mucosa and fell firm and smooth. This is because the neuroendocine cells from which they are derived as located beneath the mucosal layer. Invasion of the mucosal layer to form a classical exophytic growth is a late feature.

 

Carcinoid tumours secrete serotonin. They originate in neuroendocrine cells mainly in the intestine (midgut-distal ileum/appendix), but can occur in the rectum, bronchi. Hormonal symptoms mainly occur when disease spreads outside the bowel


Clinical features

Onset: insidious over many years

Flushing face, Palpitations, Pulmonary valve stenosis and tricuspid regurgitation causing dyspnoea, Asthma, Severe diarrhoea (secretory, persists despite fasting)


Investigation: 5-HIAA in a 24-hour urine collection, Somatostatin receptor scintigraphy, CT scan, Blood testing for chromogranin A


Treatment: Octreotide, Surgical removal

23

Following a routine appendicectomy a patients pathology report states that a 1.5cm carcinoid tumour of the appendix tip is identified. How should this be managed?

It is important to establish that the tumour was completely removed and the case and histology images should be reviewed in an MDT meeting. However, the incidence of metastatic or recurrent disease in patients with such a small lesion is too low to justify any further interventions. Generally speaking further resectional surgery (right hemicolectomy) is reserved for those patients with tumours greater than 2cm in diameter or with involved margins.

 

Carcinoid tumours secrete serotonin. They originate in neuroendocrine cells mainly in the intestine (midgut-distal ileum/appendix), but can occur in the rectum, bronchi. Hormonal symptoms mainly occur when disease spreads outside the bowel


Clinical features

Onset: insidious over many years

Flushing face, Palpitations, Pulmonary valve stenosis and tricuspid regurgitation causing dyspnoea, Asthma, Severe diarrhoea (secretory, persists despite fasting)


Investigation: 5-HIAA in a 24-hour urine collection, Somatostatin receptor scintigraphy, CT scan, Blood testing for chromogranin A


Treatment: Octreotide, Surgical removal

24

What is carcinoid syndrome? What medical therapy is most useful for managing the symptoms of patients with carcinoid syndrome?

This occurs in the presence of metastatic disease where the vasoactive peptides that tumours produce enter the systemic circulation. The symptoms comprise flushing, diarrhoea, bronchoconstriction and heart failure. The cardiac complications arise primarily of fibrosis of the endocardium with constriction of the tricuspid and pulmonary valves.

Administration of octreotide is the usual practice. A longer acting version, lanreotide, is also commonly used. It is a somatostatin analogue. It therefore suppresses the release of some of the hormones implicated in carcinoid syndrome.

 

Carcinoid tumours secrete serotonin. They originate in neuroendocrine cells mainly in the intestine (midgut-distal ileum/appendix), but can occur in the rectum, bronchi. Hormonal symptoms mainly occur when disease spreads outside the bowel


Clinical features

Onset: insidious over many years

Flushing face, Palpitations, Pulmonary valve stenosis and tricuspid regurgitation causing dyspnoea, Asthma, Severe diarrhoea (secretory, persists despite fasting)


Investigation: 5-HIAA in a 24-hour urine collection, Somatostatin receptor scintigraphy, CT scan, Blood testing for chromogranin A


Treatment: Octreotide, Surgical removal

25

During a laparotomy for abdominal pain and intermittent small bowel obstruction the following lesion is identified. How would you manage it?

There is evidence of a lesion compressing the small bowel and there is a separate nodule visible on the small bowel mesentery. I would perform a full staging laparotomy and even if metastatic disease were present, I would usually manage this situation by performing a small bowel resection and primary anastomosis. Even where metastatic disease is present, resection of such lesions can relieve obstructive symptoms and produce good palliation. This case was subsequently demonstrated to be carcinoid tumour of the small bowel.

 

Carcinoid tumours secrete serotonin. They originate in neuroendocrine cells mainly in the intestine (midgut-distal ileum/appendix), but can occur in the rectum, bronchi. Hormonal symptoms mainly occur when disease spreads outside the bowel


Clinical features

Onset: insidious over many years

Flushing face, Palpitations, Pulmonary valve stenosis and tricuspid regurgitation causing dyspnoea, Asthma, Severe diarrhoea (secretory, persists despite fasting)


Investigation: 5-HIAA in a 24-hour urine collection, Somatostatin receptor scintigraphy, CT scan, Blood testing for chromogranin A


Treatment: Octreotide, Surgical removal

26

What are the typical macroscopic appearances of a gastro intestinal stromal tumour? Where are most gastrointestinal tumours located? From which cells do they originate? What are the main principles followed in treating GIST's?

They typically appear as a smooth exophytic mass. More advanced lesions may develop mucosal ulceration and bleeding.

Around 70% of GIST's are located in the stomach.

They originate from the interstitial pacemaker cells of Cajal.

Surgical resection is the main treatment modality. However, radical resection is not required as diffuse sub mucosal infiltration is not commonly found. Generally, margins of 2cm are considered potentially curative. It is therefore rare for radical gastrectomy (most lesions are gastric) to be necessary.

 

GIST's are not common tumours (10 per million) and originate primarily from the interstitial pacemaker cells (of Cajal). Up to 70% occur in the stomach, the remainder occurring in the small intestine (20%) and the colon and rectum (5%). Up to 95% are solitary lesions and most are sporadic. The vast majority express CD117 which is a transmembrane tyrosine kinase receptor and in these there is a mutation of the c-KIT gene. 

The goal of surgery is resection of the tumour with a 1-2cm margin of normal tissue. As a result extensive resections are not required. Unfortunately there is a high local recurrence rate, the risk of which is related to site, incomplete resections and high mitotic count. Salvage surgery for recurrent disease is associated with a median survival of 15 months. 

The prognosis in high risk patients is greatly improved through the use of imatinib, which in the ACOSOG trial (imatinib vs placebo) improved relapse rates from 17% to 2%.
In the UK it is advocated by NICE for use in patients with metastatic disease or locally unresectable disease.

27

How would you characterise sarcomas? How do sarcomas and carcinomas differ?

Sarcomas a tumours that originate primarily from mesenchymal tissues. Their origins are thus typically tissues such as adipocytes, chondrocytes and bone. Apart from their tissue of origin, they are also described according to the degree of differentiation present.

 

Apart from the cells of origin, the main differences relate to incidence and prevelence, sarcomas being considerably less common. The patient demographic, most sarcoma patients are young. The biology of the tumour, sarcomas are more commonly associated with haematogenous metastasis than carcinomas.

 

Sarcomas = Malignant tumours of mesenchymal origin


Types  - May be either bone or soft tissue in origin. 
Bone sarcoma include: Osteosarcoma, Ewings sarcoma (although non bony sites recognised), Chondrosarcoma - originate from Chondrocytes


Soft tissue sarcoma are a far more heterogeneous group and include: Liposarcoma-adipocytes, Rhabdomyosarcoma-striated muscle, Leiomyosarcoma-smooth muscle, Synovial sarcomas- close to joints (cell of origin not known but not synovium) 


Malignant fibrous histiocytoma is a sarcoma that may arise in both soft tissue and bone.

Features
Certain features of a mass or swelling should raise suspicion for a sarcoma these include:

Large >5cm soft tissue mass

Deep tissue location or intra muscular location

Rapid growth

Painful lump


Assessment
Imaging of suspicious masses should utilise a combination of MRI, CT and USS. Blind biopsy should not be performed prior to imaging and where required should be done in such a way that the biopsy tract can be subsequently included in any resection.

Ewings sarcoma: Commoner in males, Incidence of 0.3 / 1, 000, 000, Onset typically between 10 and 20 years of age, Location by femoral diaphysis is commonest site, Histologically it is a small round tumour. Blood borne metastasis is common and chemotherapy is often combined with surgery


Osteosarcoma: Mesenchymal cells with osteoblastic differentiation, 20% of all primary bone tumours, Incidence of 5 per 1,000,000, Peak age 15-30, commoner in males, Limb preserving surgery may be possible and many patients will receive chemotherapy


Liposarcoma: Malignancy of adipocytes, Rare, approximately 2.5 per 1,000,000. They are the second most common soft tissue sarcoma, Typically located in deep locations such as retroperitoneum, Affect older age group usually >40 years of age. May be well differentiated and thus slow growing although may undergo de-differentiation and disease progression. Many tumours will have a pseudocapsule that can misleadingly allow surgeons to feel that they can 'shell out' these lesions. In reality, tumour may invade at the edge of the pseudocapsule and result in local recurrence if this strategy is adopted. Usually resistant to radiotherapy, although this is often used in a palliative setting


Malignant Fibrous Histiocytoma: Tumour with large number of histiocytes. Most common sarcoma in adults. Also described as undifferentiated pleomorphic sarcoma NOS (i.e. Cell of origin is not known). Four major subtypes are recognised: storiform-pleomorphic (70% cases), myxoid (less aggressive), giant cell and inflammatory. Treatment is usually with surgical resection and adjuvant radiotherapy as this reduces the likelihood of local recurrence

28

Clinically, what key features would make you suspicious that a soft tissue mass lesion was a sarcoma rather than a benign entity? If you were concerned that an extremity lesion was a sarcoma how should it be assessed?

An extremity lesion is more likely to be a sarcoma if the following criteria are present:

Mass >5cm

Deep location

Fixation to adjacent tissues

Rapid or progressive growth pattern

It should be imaged, typically with USS and CT/ MRI.
If there is diagnostic uncertainty, then consideration may be given to performing a tissue biopsy. However, this should not be undertaken lightly since these lesions have a considerable propensity for local recurrence and therefore in the event that a lesion proves to be a sarcoma, the biopsy track will need to be excised en bloc with the tumour.

 

Sarcomas = Malignant tumours of mesenchymal origin


Types  - May be either bone or soft tissue in origin. 
Bone sarcoma include: Osteosarcoma, Ewings sarcoma (although non bony sites recognised), Chondrosarcoma - originate from Chondrocytes


Soft tissue sarcoma are a far more heterogeneous group and include: Liposarcoma-adipocytes, Rhabdomyosarcoma-striated muscle, Leiomyosarcoma-smooth muscle, Synovial sarcomas- close to joints (cell of origin not known but not synovium) 


Malignant fibrous histiocytoma is a sarcoma that may arise in both soft tissue and bone.

Features
Certain features of a mass or swelling should raise suspicion for a sarcoma these include:

Large >5cm soft tissue mass

Deep tissue location or intra muscular location

Rapid growth

Painful lump


Assessment
Imaging of suspicious masses should utilise a combination of MRI, CT and USS. Blind biopsy should not be performed prior to imaging and where required should be done in such a way that the biopsy tract can be subsequently included in any resection.

Ewings sarcoma: Commoner in males, Incidence of 0.3 / 1, 000, 000, Onset typically between 10 and 20 years of age, Location by femoral diaphysis is commonest site, Histologically it is a small round tumour. Blood borne metastasis is common and chemotherapy is often combined with surgery


Osteosarcoma: Mesenchymal cells with osteoblastic differentiation, 20% of all primary bone tumours, Incidence of 5 per 1,000,000, Peak age 15-30, commoner in males, Limb preserving surgery may be possible and many patients will receive chemotherapy


Liposarcoma: Malignancy of adipocytes, Rare, approximately 2.5 per 1,000,000. They are the second most common soft tissue sarcoma, Typically located in deep locations such as retroperitoneum, Affect older age group usually >40 years of age. May be well differentiated and thus slow growing although may undergo de-differentiation and disease progression. Many tumours will have a pseudocapsule that can misleadingly allow surgeons to feel that they can 'shell out' these lesions. In reality, tumour may invade at the edge of the pseudocapsule and result in local recurrence if this strategy is adopted. Usually resistant to radiotherapy, although this is often used in a palliative setting


Malignant Fibrous Histiocytoma: Tumour with large number of histiocytes. Most common sarcoma in adults. Also described as undifferentiated pleomorphic sarcoma NOS (i.e. Cell of origin is not known). Four major subtypes are recognised: storiform-pleomorphic (70% cases), myxoid (less aggressive), giant cell and inflammatory. Treatment is usually with surgical resection and adjuvant radiotherapy as this reduces the likelihood of local recurrence

29

What causes of gastritis are you familiar with? How would you investigate and manage a case of suspected gastritis?

There are many causes of gastritis. These can be classified as being autoimmune, infective, chemical and haemodynamic. Autoimmune gastritis occurs as a result of autoantibodies to parietal cells together with local inflammation culminating in destruction of parietal cells, loss of gastric acid, intrinsic factor and vitamin B12 malabosorption. Infection with helicobacter pylori causes gastritis both as a direct result of colonisation and because it subsequently increases gastric acid production. Chemical causes of gastritis include the direct effects of injestion of substances such as toxic agents or alcohol. It also includes those patients with bile reflux who subsequently develop gastric inflammation. Finally, critically unwell patients can develop gastric mucosal hypoperfusion and subsequently develop stress ulceration through a complex interplay of loss of gastric mucous and elevated gastrin levels.

 

The main investigation for suspected gastritis is an upper GI endoscopy together with gastric biopsies. Conditions such as H-Pylori infection can be readily diagnosed using bedside testing at endoscopy. Management of most patients involves administration of proton pump inhibitors, with the subsequent achlorhydria, mucosal healing will occur. Management of cases such as pernicious anaemia involves management of the complications (with the need for B12 and folate supplementation).

 

Type A: Autoimmune, Circulating antibodies to parietal cells, causes reduction in cell mass and hypochlorhydria. Loss of parietal cells = loss of intrinsic factor = B12 malabsorption. Absence of antral involvement. Hypochlorhydria causes elevated gastrin levels- stimulating enterochromaffin cells and adenomas may form

Type B: Antral gastritis. Associated with infection with helicobacter pylori infection. Intestinal metaplasia may occur in stomach and require surveillance endoscopy. Peptic ulceration may occur

Reflux gastritis: Bile refluxes into stomach, either post surgical or due to failure of pyloric function. Histologically, evidence of chronic inflammation, and foveolar hyperplasia. May respond to therapy with prokinetics

Erosive gastritis: Agents disrupt the gastric mucosal barrier. Most commonly due to NSAIDs and alcohol. With NSAIDs the effects occur secondary to COX 1 inhibition

Stress ulceration: This occurs as a result of mucosal ischaemia during hypotension or hypovolaemia. The stomach is the most sensitive organ in the GI tract to ischaemia following hypovolaemia. Diffuse ulceration may occur. Prophylaxis with acid lowering therapy and sucralfate may minimise complications

Menetriers disease: Gross hypertrophy of the gastric mucosal folds, excessive mucous production and hypochlorhydria. Pre malignant condition

30

What non immune system mediated complications may occur as a result of the transfusion of several units of packed red cells?

The non immune mediated complications of transfusion of whole blood include fluid overload and pulmonary oedema, transmission of blood borne viruses, electrolyte disturbance including hyperkalaemia and hypocalcaemia.

 

Blood transfusion reactions


Acute transfusion reactions present as adverse signs or symptoms during or within 24 hours of a blood transfusion. The most frequent reactions are fever, chills, pruritus, or urticaria, which typically resolve promptly without specific treatment or complications. Other signs occurring in temporal relationship with a blood transfusion, such as severe dyspnoea, pyrexia, or loss of consciousness may be the first indication of a more severe potentially fatal reaction.
The causes of adverse reactions are multi-factorial. Immune mediated reactions, some of the most feared, occur as a result of component mismatch, the commonest cause of which is clerical error. More common, non immune mediated, complications may occur as a result of product contamination, this may be bacterial or viral. 
Transfusion related lung injury is well recognised and there are two proposed mechanisms which underpin this. One involves the sequestration of primed neutrophils within the recipient pulmonary capillary bed. The other proposed mechanism suggests that HLA mismatches between donor neutrophils and recipient lung tissue is to blame.

Immune mediated: Pyrexia, Alloimmunization, Thrombocytopaenia, Transfusion associated lung injury, Graft vs Host disease, Urticaria, Acute or delayed haemolysis, ABO incompatibility, Rhesus incompatibility

Non immune mediated: Hypocalcaemia, CCF, Infections, Hyperkalaemia