Colitides including IBD, Diverticulitis, Consequences of Messing with the GI tract

Question 1

Describe the Hinchey Classification System and its utility.

Answer 1

The Hinchey classification was originally published in 1978 as a four-stage system describing the intra- operative findings of complicated diverticulitis as a means of prognostication.

The advent and widespread uptake of high quality CT scans in recent years have seen this classification system modified to incorporate radiologic findings with the intention of now allowing clinicians to use images to guide treatment, particularly with respect to early discrimination of those who will require surgery and those amenable to less invasive management.​

Ia - Confined pericolic inflammation or phlegmon

Ib - Pericolic or mesocolic abscess

II - Pelvic, distant intra-abdominal, or retroperitoneal abscess

III - Generalized purulent peritonitis

IV - Generalized faecal peritonitis

(Distinguishing Stage III from Stage IV can be challenging radiologically and often remains an intra-operative diagnosis)

Question 2

Provide an overview of typical antibiotic usage in acute diverticulitis.

Answer 2

Antibiotics have long been considered the cornerstone of managing diverticulitis.

First line intravenous therapy generally includes a second or third generation cephalosporin (cefuroxime or ceftriaxone respectively) in addition to metronidazole. Alternate options include ‘triple’ therapy with amoxicillin, gentamicin, and metronidazole which provide similar cover to the above but with amoxicillin specifically covering Enterococcus species; or piperacillin-tazobactam where cases of multidrug resistance are suspected.

Amoxicillin-clavulanate is an appropriate oral antibiotic choice as it offers moderate Gram-negative cover and has activity against anaerobes.

Question 3

What is the state of evidence surrounding usage of antibiotics in acute diverticulitis?

Answer 3

A clear body of evidence has emerged supporting the use of symptomatic treatment without antibiotics in CT-proven uncomplicated diverticulitis.

The AVOD study from 2012 was a multicentre RCT that first showed that inpatient treatment without antibiotics had no significant bearing on complications (such as abscess or perforation) or length of stay in CT-proven uncomplicated diverticulitis. Subsequent cohort studies confirmed this.

A well designed placebo-controlled double-blinded randomised trial from Australasia was published in 2020 (Juang et al) and confirmed no difference between antibiotic and placebo arms with respect to length of stay, adverse events, or readmission in Hinchey 1a patients.

Question 4

Could diverticulitis be managed in the community?

What criteria would need to be satisfied?

Answer 4

Results from the 2014 DIVER trial showed that patients with uncomplicated diverticulitis treated with oral antibiotics as an outpatient (after an initial intravenous dose on presentation) had no difference in treatment failure or short-term quality of life compared with those who were admitted and placed on intravenous antibiotics. There was however a significant fiscal difference between the arms.

Criteria were devised for those who might by suitably managed on oral antibiotics as an outpatient and included patients with

• CT-proven uncomplicated disease
• Adequate social support
• No immunocompromise, severe pain, or sepsis.

Question 5

Describe the key considerations relating to the use of percutaneous drainage of diverticular abscesses.

Exapand on these.

Answer 5

• Clinical state of the patient
  
  • Patients with peritonitis or those demanding definitive source control due to physiological deterioration must be considered for laparotomy and Hartmann’s.
• Size of abscess
  
  • Close to 100% of abscesses <3cm in size are effectively treated with antibiotics alone.
  • Abscesses larger than this are incrementally less likely to resolve with antibiotics alone and become increasingly amenable to drainage.
  • The ‘cut-off’ size used for consideration of percutaneous drainage in stable patients at our institution is >4cm
• Location of abscess
  
  • Abscesses are generally amenable to drainage via a transabdominal or transgluteal approach, although transrectal and transvaginal have been described.
  • The transabdominal approach is favoured as it causes the least patient discomfort.
  • Presence of overlying viscera or underlying neurovascular structures may render the interventional approach unsafe

Question 6

What is the complication rate of percutaneous drainage of diverticular abscesses?

Answer 6

A recent large systematic review including 8,766 patients showed the procedure-related complication rate of percutaneous drainage was 2.5% – primarily related to small bowel injury requiring surgery or formation of enterocutaneous fistula – with a pooled average of 15.5% of patients required re-siting or further drain placement.

Question 7

What are the indications for surgery in acute diverticulitis?

Answer 7

Indications for surgery in acute diverticulitis include

• Sepsis not responsive to basic resuscitative measures
• Generalised peritonism
• Hinchey III-IV disease
• Hinchey Ia-II disease unsuitable for or refractory to non-operative management.

Threshold for surgical intervention should be lower in those with significant immunocompromise including elderly patients, transplant recipients or those on medications such as long-term steroids, biologics, immunomodulators or chemotherapy.

Question 8

What is the evidence of primary anastomosis (PRA) versus non-restorative resection (NRR) in emergency surgery for acute diverticulitis?

Answer 8

A 2020 meta-analysis of the 4 RCTs in this area (including the LADIES and DIVERTI trials) demonstrated that for the initial procedure morbidity did not differ between primary anastomosis and Hartmanns groups but there was a significantly higher risk of intra-abdominal collection following NRR (3.3% in PRA vs 11.3% in NRR; p<0.01).

The rate and morbidity of reversal of diverting ileostomy were respectively significantly higher and lower than for end colostomy.

It is worth noting that three of the four RCTs utilised on-table colonic lavage prior to construction of the primary anastomosis; the impact of colonic lavage on outcome is unclear particularly as two of the trials routinely performed defunctioning loop ileostomy with the third at the discretion of the surgeon.

This data makes a compelling argument for anterior resection and diverting ileostomy in lieu of end colostomy as the preferred operation for perforated diverticulitis.

Question 9

Summarise the evidence for laparoscopic lavage in Hinchey III acute diveriticulitis.

Include the outcomes reported by the SCANDIV, LOLA, and DILALA trials.

Provide a summary statement balancing out the pros and cons.

Answer 9

Three RCTs have since been published investigating laparoscopic lavage vs sigmoid resection in Hinchey III diverticulitis. The lavage technique varied between these trials in terms of volume of irrigation, drain placement, and drain number; similarly, the trials were designed to assess varying primary outcomes.

• SCANDIV (2015): post-op complications (CD>III) at 90 days
• LOLA (2015): morbidity and mortality at 12 months
• DILALA(2016): re-operation rate at 24 months

The SCANDIV trial showed an equivalent rate of severe post-operative complications between arms but noted an increased risk of deep surgical site infection (32% vs 13%, p<0.01) and surgical re-intervention (27% vs 10%, p=0.01) in the laparoscopic lavage group.

The LOLA trial showed no difference in morbidity and mortality at 12 months but was terminated early because of increased adverse events in the lavage arm (39% vs 19%, p=0.04) including abscess formation requiring drainage (20% vs 7%, p<0.01) and need for surgical re-intervention (20% vs 7%; p=n.s.).

The DILALA trial showing no difference in re- operation rate within 30 days, but fewer operations in the lavage group at 24 months and it was concluded that lavage is preferable to resection.

“Proponents of laparoscopic lavage in Hinchey III disease draw attention to the possibility of avoiding the morbidity associated with acute resection and reducing the chance of stoma formation. The merits of these outcomes must be balanced by the trifecta of re-intervention, recurrence, and malignancy.”

Question 10

Explain the utility of colonoscopy following acute diverticulitis, both complicated and uncomplicated.

Answer 10

A meta-analysis published last year found that out-patient colonoscopy performed 6-8 weeks after an episode of diverticulitis yielded a colorectal cancer detection rate of 2.1% and ‘advanced neoplasia’ rate of 6.9%. Subgroup analyses subsequently showed the prevalence of colorectal cancer following complicated disease was 8.3% compared to 0.5% in uncomplicated disease.

There is hence a clear body of evidence supporting the use of follow-up colonoscopy after complicated diverticulitis.

Recommendations regarding colonoscopy after uncomplicated disease are however mixed – SAGES advocates for it, EAES against it, with no clear recommendation from ASCRS or the NHMRC. Cancer detection rates in uncomplicated disease mirror that of an average risk population and while a case may be made for the use of colonoscopy as an ‘opportunistic’ screening tool, it is our unit’spolicy to not routinely offer it but to advise patients within the screening age to enrol in the NBCSP.

Question 11

Describe the natural history following an attack of acute diverticulitis.

Answer 11

The natural history following an acute flare of diverticulitis is important in guiding further management and can generally be stratified into one of four groups:

1. Asymptomatic (the majority ~66%)
2. Recurrent acute diverticulitis
3. Smouldering diverticulitis (or “symptomatic uncomplicated diverticular disease”)
4. Complicated sequelae of disease.

Question 12

Explain your approach to definitive management of complicated diverticulitis.

Answer 12

Definitive management of those who initially present with Hinchey Ib-II complicated diverticulitis is controversial. The current ASCRS guidelines advocate resection as “patients who present with a diverticular abscess experience recurrences at a substantial rate”.

This assertion is supported by a large observational study which found a recurrence rate of 60% after non-operatively managed diverticular abscess, but is at odds with a larger but quite heterogeneous systematic review that described recurrence rate at 28.5%.

It would therefore seem prudent to have a lower threshold for resection in those who present with complicated disease, without it being an absolute indication.

Question 13

Discuss preventative measures against diverticulitis and the current evidence base for these.

Answer 13

• Recommendation of high-fibre diets as a secondary preventative measure in acute diverticulitis are based on low-quality data and data by inference, but represent a low-risk intervention.
• There has been considerable interest in the use of 5-ASA to prevent recurrent diverticulitis by treating a possible underlying chronic inflammatory component. A recent Cochrane review meta-analysed data across seven randomised trials and found no significant reduction in the rate of recurrent flares in those on 5-ASA vs control (31.3% vs 29.8%; p=0.11)
• There may be an evolving role for probiotics such as Lactobacillus casei or Bifidobacter species in combination with 5-ASA, but at present its routine use is not recommended.

Question 14

Define Crohn’s disease.

Answer 14

Crohn’s disease is a disease characterised by relapsing and remitting, discontinuous transmural inflammation, which affects the gastrointestinal tract (GIT) anywhere from mouth to anus.

Question 15

What is the pathogenesis of Crohn’s disease?

Answer 15

The current hypothesis is that it arises from inappropriate activation of the mucosal immune system in response to commensal bacteria in a genetically susceptible host.

Question 16

How can Crohn’s “recurrence” be defined?

Desribe the rates of recurrence in each category.

Answer 16

• Endoscopic recurrence
  
  • ​​Defined using the Rutgeerts’ score
  • Occurs in 30 – 90% of patients at the neoterminal ileum within 12 months of surgery and almost universally by 5 years.
• Clinical recurrence
  
  • Defined using the Crohn’s Disease Activity Index (CDAI)
  • Occurs in 20 – 40% of patients within 12 months of surgery and 35 – 50% of patients by 5 years.
• Surgical recurrence
  
  • Defined as postoperative CD requiring resection
  • Occurs in approximately 25% of patients by 5 years and 35% of patients by 10 years.

Question 17

What is a Rutgeert’s score?

How is it calculated?

Answer 17

A Rutgeert’s score is an endoscopic grading system of Crohn’s recurrence at the neoterminal ileum at 6 months post-surgery.

i0 = No lesions

i1 = ≤ 5 aphthous ulcers

i2 = > 5 aphthous ulcers with normal intervening mucosa or patchy areas of larger lesions or lesions confined to the ileocolic anastomosis

i3 = diffuse apthous ileitis and diffusely inflamed mucosa

i4 = diffuse ileal inflammation with large ulcers, nodules, or stenosis.

Question 18

What risk factors are associated with CD recurrence following surgery?

Answer 18

• Smoking
• More than two surgeries
• Penetrating disease phenotype

​

• Extensive SB disease (>50cm)
• Perianal disease
• Short interval between diagnosis and surgery
• Young age at diagnosis

Question 19

What is the Crohn’s Disease Activity Index?

What is the utility of this index?

Answer 19

The Crohn’s Disease Activity Index or CDAI is a research tool used to quantify the symptoms of patients with Crohn’s disease. The index consists of eight factors, each summed after adjustment with a weighting factor.

While it is an impractical tool clinically, it is useful in research studies done on medications used to treat Crohn’s disease.

Question 20

Describe the distribution of Crohn’s disease along the GI tract.

What proportion of patients have perianal disease?

Answer 20

• 50% have ileocolic disease
• 30% have isolated SB disease
• 20% have isolated colonic disease
• A minority (<10%) of Crohn’s patients will have:
  
  • Isolated upper GI disease
  • Exclusive perianal disease
  • Extra-intestinal manifestations.
• Around 25% of patients have perianal disease.

Question 21

Describe the Montreal Classification of Crohn’s Disease.

Answer 21

Age + Location + Behaviour with Perianal modifier

• A1 = 16 years of age or younger
• A2 = 17-40 years of age
• A3 = Older than 40 year of age
• L1 = Ileal only
• L2 = Colonic only
• L3 = Ileocolic
• L4 = Isolated upper disease
• B1 = Non-penetrating, non-stricturing
• B2 = Stricturing
• B3 = Penetrating

p = perianal disease modifier (present, not present)

Question 22

What proportion of CD patients undergo surgery?

What are the non-emergent indications for surgery in CD?

How is failure of steroid therapy defined?

Answer 22

33 – 47% of patients proceed to surgery due to treatment failure.

1. Persistent or worsening symptoms despite correct treatment
2. Onset of unacceptable drug-related complications/intolerance when there is no other efficacious medical alternative
3. Steroid–dependence
4. Onset of disease related complications that compromise a patient’s quality of life (QOL)

Patients who fail to achieve complete clinical response within 8 – 12 weeks are considered treatment failures, while inability to wean off CS within 3 – 6 months is also considered failure.

Question 23

Describe the impact of anti-IBD medications on post-operative outcomes.

Answer 23

Pre-operative anti-IBD therapy can be divided into 5 categories, two of which have a substantial impact on post operative outcomes:

1. Corticosteroids (e.g Hydrocortisone)
   
   • 1.7x OR total infectious complications
2. Anti-TNF (e.g. Infliximab)
   
   • 1.6 x OR total infectious complications
   • Mixed evidence, some say no effect.
3. Immunomodulators (e.g. Azathioprine)
   
   • No significant effect
4. Anti-integrin (e.g. Vedolizumab)
   
   • No significant effect
   • BUT, significant increase in superficial SSI and ileus
5. 5-ASAs (e.g. Sulphasalazine)
   
   • No significant effect

Question 24

What are the techniques of stricturoplasty in Crohn’s strictures?

Briefly describe how they are performed.

Answer 24

1. Heineke-Mikulicz
   
   • Open longitudinally, close transversely
2. Finney’s type
   
   • (Long) Stricture made into a U-bend then U-bend incision opened on anterior surface; back wall closed then front wall closed
3. Jaboulay
   
   • (Short) Stricture made into a U-bend then bypassing side to side anastomosis created in two layers
4. Michellasi
   
   • (Long) Stricture divided at midpoint; proximal aspect advanced to lay side-by-side and common channel created in two layers; need to spatulate ends.
5. Poggioli - Described two techniques!!
   
   • Ileocolic stricture mobilised with right colon then strictured ileum opened and interfaced with linear incision in the ascending colon (1997)
   • Modified Michellasi where the advancement and side-to-side ileum is secured onto healthy colon (1998).

Question 25

Describe the pathophysiology of fistulating Crohn's disease. Cite therapeutic targets in your answer.

Answer 25

Our understanding of the pathophysiology of Crohn’s disease-associated fistulas is not complete. Two mechanisms seem to have a major role: 1. Epithelial-to-mesenchymal transition (EMT) 2. Matrix remodelling enzymes (MMPs) EMT: * In EMT, differentiated epithelial cells transform to mesenchymal-type cells and **acquire the ability to migrate** and penetrate adjacent tissues. * This process is essential in embryogenesis, organ development and would healing, and has also been documented to occur in tumour growth and metastasis. * Known inducers of EMT include transforming growth factor (TGF)β and **TNF (hence Infliximab!)** * EMT might also be involved in the pathogenesis of fistula-associated neoplasia. MMP: * Matrix metalloproteinases (MMPs) can degrade virtually all components of the extracellular matrix. * **Increased MMP activity has been found in experimental and human IBD.** Biologic therapy forms a mainstay of IBD treatment and understanding the role of tumour necrosis factor in the formation of fistulae may help explain some of biolgic therapy’s efficacy. MMP inhibitors have found success in preventing fistulae in IBD, but only in animal models.

Question 26

What is the role of the mesentery in Crohn's disease? Should it be excised or should it remain?

Answer 26

The role of the mesentery in Crohns disease remains unclear. The mesentery contains inflammatory cells, nerves and blood vessels which are thought to play a role in Crohns disease. Coffey et al examined the role of mesenterectomy and showed lower recurrence rates after ileocolic resection with mesenterectomy than conventional sparing of the mesentery- **2.9% compared to 40%.** However, this was a retrospective study that compared **pre 2010 conventional resections with post 2010 mesenterectomy** that may be confounded by **_advances in medical therapy_**. The verdict for mesenterectomy is yet to be determined.

Question 27

What is the association between appendicectomy and IBD? Discuss both Ulcerative Colitis and Crohn's Disease.

Answer 27

* **Initial** epidemiological studies appeared to show the appendicectomy was "protective" against UC. * The **largest epidemiological trial to date** (Taiwanese, 2021) including just under 500,000 patients, showed that appendicectomy **actually increased the OR of both** UC (2.2x) and CD (3.5x) compared to non-appendicectomy patients. * In patients **who already have UC** there is weak evidence suggesting that appendicectomy after diagnosis is associated with reduced need for colectomy and reduced disease severity (case-series only). * In patients with CD, there **appears to be a correlative relationship where CD has a higher incidence** of diagnosis in the appendicectomy cohort, though it is felt that this is **likely diagnostic bias as the correlation is weaker towards null the longer the interval** between appendicectomy and diagnosis.

Question 28

How is the appendix histologically different to the caecum? What is thought to be its function?

Answer 28

The appendix contains substantial lymphoid tissue and the mucosa and submucosa of the lamina propria are histologically distinct from the caecum. The presence of **B and T lymphoid cells creates a lymphoid pulp** that aids immunologic function by **_increasing lymphoid products including IgA, and operating as part of the gut-associated lymphoid tissue system._** The appendix serves as a **microbial reservoir of the intestinal commensal microbiome**, which facilitates reinoculation of the proximal large bowel and terminal ileum.

Question 29

Describe Trulove and Witt's criteria

Answer 29

From 1955! Mild disease was defined as 4 or fewer bowel motions a day with "no more than small amounts of macroscopic blood in stools"; no fever; no tachycardia; anemia not severe; and ESR not increased more than 30mm/hr. Severe disease was defined as 6 or more motions a day with macroscopic blood in stools; fever (on at least 2 days out of 4); tachycardia (more than 90 beats/min); anemia; and "ESR much increased" (\>30 mm). Moderately severe was defined as intermediate between severe and mild.

Question 30

What is the criteria for diagnosis of Acute Severe Ulcerative Colitis?

Answer 30

≥6 bloody bowel motions per day and **any one of the following:** * HR \>90 * Temp \>37.8 * Hb \<105 * CRP \>30 (ESR \>30) (According to the British Society of GE Guidelines)

Question 31

Describe your Day-0 work-up of Acute Severe Ulcerative Colitis

Answer 31

* Senior colorectal/gastroenterology review * Baseline bloodwork * Stool specimen sent for micro esp *C diff* * Sigmoidoscopy within 24 hours including CMV biopsies * Concurrent CMV need Ganciclovir * CT if there are concerns of complications * Commence IV Hydrocortisone without delay * Commence VTEP without delay

Question 32

Describe the Mayo Scoring System in UC. Describe its utility. How is remission defined?

Answer 32

The Mayo Score for Ulcerative Colitis was originally devised in 1987 for a clinical trial for pH dependent 5-ASA (Asacol) at the Mayo Clinic. Comprised of 4 parameters, each is scored 0, 1, 2, or 3: * **stool frequency** 0 = normal 1 = 1-2 more than normal 2 = 3-4 more than normal 3 = \>4 more than normal * **rectal bleeding** 0 = none 1 = less than half blood 2 = more than half blood 3 = all blood * **endoscopic findings** 0 = normal 1 = mild; erythema, mildly friable 2 = moderate; erosions, marked erythema 3 = severe; spontaneous bleeding, ulceration * **physician’s global assessment** 0 = normal 1 = mild 2 = moderate 3 = severe The Mayo score is used in research to compare response to therapies. Response to therapy is defined differently in each trial, but most use a decrease of 3 or more points. **Remission is often defined as a total score of 2 or less with all individual categories ≤1**. Occasionally, remission is defined stringently as a score of 0.

Question 33

# Define steroid-refractory Acute Severe Ulcerative Colitis. How common is it?

Answer 33

**31% to 35%** of ASUC is steroid refractory, commonly defined as active **_disease that remains despite 3-5 days’ worth of treatment._**

Question 34

How do you decide if a patient with Acute Severe Ulcerative Colitis is failing medical treatment?

Answer 34

The Oxford Criteria has been used to assess liklihood of colectomy in historical (1996) series, when salvage therapy was not as widely available; * More than 8 bowel motions per day * Between 3-8 bowel motions per day + CRP \>45 * ***_Presence of either of these impart an 85% chance of colectomy. Contemporary data is 35%..._*** At **Day-3** post steroid therapy, the patient must be assessed by a colorectal surgeon and if colectomy is not immediately indicated, **salvage Infliximab or Cyclosporin should be commenced**. Daily surgical review continues and if there has been improvement by **Day-6 then colectomy is highly likely and delaying increases mortality** (triples by day-11).

Question 35

What is Cyclosporin? How does it work? How effective is it in the setting of Acute Severe Ulcerative Colitis?

Answer 35

Cyclosporin is a fungally derived **Calcineurin inhibitor.** Calcineurin is phosphatase that controls **transcription of IL-2**, a key T-cell modulator. Cyclosporine has been shown to be **effective in ~60-80%** of patients with UC failing intravenous corticosteroids

Question 36

What is Infliximab? How does it work? How effective is it in salvaging Acute Severe Ulcerative Colitis?

Answer 36

Infliximab is a **chimeric monoclonal antibody against TNF-α** It neutralises the effect of TNF-α on T-cells It has similar efficacy to Cyclosporin with **salvage rates of 60-80% within 7 days**.

Question 37

How is Infliximab administered? What is the dose? What is "accelerated dosing"?

Answer 37

Infliximab is administered as an IV infusion over around 2 hours, usually given at week-0, week-2, and week-6. 5mg/kg though some centres advocate for 10mg/kg Accelerated dosing is typically defined as * Two doses of 5 mg/kg with **second dose ≤ 7 days after the first** or * **10 mg/kg** for the first dose with **another dose within 2 weeks**. The evidence base is mixed for accelerated dosing and high-quality RCTs are needed.

Question 38

What do you do with the rectal stump at the time of a sub-total colectomy for Severe Acute Ulcerative Colitis? Justify this.

Answer 38

* Leaving the rectal stump intra-peritoneal is associated with the highest mortality rate and pelvic-sepsis-complication rate of the three aproaches. It also makes subsequent surgery more technically challenging. * Whether or not to mature a mucous fistula depends on the patient and their disease. If the rectosigmoid is grossly abnormal (and the staple line therefore questionable) I will mature a mucous fistula in the LIF. * If the staple line appears healthy, I will place the staple line in a subcutaneous position, again in the LIF. * Placement in the LIF avoids potential issues with future pregnancy, and if the staple line blows the LIF is easier to address with an appliance then the SP area.

Question 39

Outline the complications associated with ileoanal pouch formation. How do you define pouch failure?

Answer 39

* **Surgical and mechanical complications** * Anastomotic leak * 5-10% * Pelvic sepsis * 25% * Pouch fistula * \<2% * Pouch sinus * 3-8% * *Afferent limb syndrome* * *Volvulus* * *Pouch septum* * *Portal vein thrombus* * **Inflammatory complications** * Pouchitis * 50% at some point * 15% chronic * Crohn's disease * 10-20% eventually diagnosed with CD * High pouch failure rate * Cuffitis * **Functional complications** * Infertility and sexual dysfunction * Probably higher than appreciated * **10-20% baseline increases to 20-60% post IPAA.** * Irritable pouch syndrome * Paradoxical contraction * Pouch failure; cumulative of above ~20% at 30 years * Defined as acute within 12 months * Defined as failure if poor functional symptoms lead to excision of the pouch and permanent ostomy.

Question 40

What is the evidence for sub-total colectomy in favour of segmental colectomy in the setting of Crohn's colitis?

Answer 40

_Meta-analysis from 2006 by Heriot's group:_ * **No difference in overall or surgical recurrence rate** * **SC patients recur ~4 years earlier** than IRA * Better outcomes with **_IRA for two or more colonic segments_**.

Question 41

What is rate of fistula resolution on biologic therapy in Crohn's disease? What study is this based on and what was the study's approach to Setons?

Answer 41

**40-50% of patients who have disease responsive to the initial 0, 2, and 6 week Infliximab, will have durable fistula resolution.** This is over double what is achieved by placebo. The 2004 ACCENT trial demonstrated this. All Seton's had to be **removed by week 2** in the study protocol.

Question 42

What is the impact of Crohn's disease on fistula-in-ano repair techniques?

Answer 42

MAF = down to 60% LIFT = down to 50-60%

Question 43

What type of bacteria is *Clostridium difficile*? Describe the pathophysiology of *C difficile* infection

Answer 43

* C diff is a gram positive, spore-forming, anaerobic bacteria that are commensal in 1-3% in the community and up to 10% of hospitalised or nursing home patients. * There are three phases to *C diff* infection: 1. **_Microbial suppression_** * Typical antibiotics include Cephalosporins, Clindamycin, Carbapenams, and Ciprofloxacin 2. **_Collateral damage_** * Subsequent **germination of C diff spores and endotoxin production** leads to inflammatory changes and diarrhoea 3. **_Window of vulnerability_** * A window exists between commencement of *C diff* ABx and re-growth of the normal flora; in this window re-calcitrant diarrhoea may occur due to ongoing ***C diff* endotoxins being released by C diff spores.**

Question 44

How is *C diff* diagnosed?

Answer 44

C.diff is diagnosed via glutymate dehydrogenase (GDH) or real time Polymerase Chain Reaction (PCR) with positive screens being followed up by ELISA assays for endotoxin A and B. GDH results are available within a number of hours compared to toxin assays which can take up to 24hours.

Question 45

What are the 4 sub-types of E coli affecting the bowel? What is the treatment?

Answer 45

1. Enteroinvasive 2. Enteropathogenic 3. Enterotoxigenic - most common form of traveller's diarrhoea 4. Enterohaemorrhagic Treatment is supportive as ABx simply increase the risk of HUS and TTP, especially in enterohaemorrhagic sub-types.

Question 46

Which bacterial colitides require anti-bacterial treatment? Why should antibiotics be avoided in E. coli disease?

Answer 46

* Shigella - YES (Ceftriaxone) * Camplyobacter - Maybe (Cipro) * Salmonlella - No * Yersinia - No but it is notifiable Antibiotic use in E. coli is associated with increased HUS and TTP development, esepcially in enterohaemorrhagic sub-types.

Question 47

What is Segmental Colitis Associated with Diverticulosis? How prevalent is it? What age group does it affect? What distinguishes SCAD from UC? How can it be treated?

Answer 47

Diverticular colitis, also known as segmental colitis associated with diverticulosis, is a **colonic inflammatory disorder on the spectrum of inflammatory bowel disease** (IBD). The disease consists of **macroscopic and microscopic inflammation affecting inter-diverticular mucosa**, sparing peri-diverticular mucosa, with inflammation confined to the **descending and sigmoid colon**. Prevalence at **endoscopy is ~1%** Mean presentation is in the **7th decade of life.** **Cryptoarchitecture is preserved in SCAD.** **Treatment is with oral 5-ASAs.**

Question 48

What is the pathophysiology of diversion colitis?

Answer 48

This is incompletely understood. A number of contentious and contradictory hypotheses have been put forward: 1. **Bacterial over-growth theory** * Studies have shown _reduced_ pathogenic and fermenting anaerobic colonies 2. **Excess NO theory** * Nitrate reducing bacteria increased in diverted colons * NO is protective in low concentrations but toxic in high * Unproven with mixed studies 3. **SCFA-related ischaemia theory** * SCFA found to be low in diverted colons * Loss of SCFA increases arteriolar resistance with ischaemic features

Question 49

What is eosinophilic colitis? What are the sub-types? What is the treatment?

Answer 49

Eosinophilic colitis is a rare form of colitis exhibiting a bimodal distribution in neonates and late adolescence. The cause is unknown, though family history if often present as is a history of atopy. * Mucosal-predominant type; most common; diarrhoea, malabsorption * Muscular predominant-type; atypical presentations e.g. intussusception * Serosal-predominant type: rarest but best prognosis. Treated with dietary modifications to avoid allergen.

Question 50

What are the two types of microscopic colitis? What is found on endoscopic examination? How do they differ histologically? How is it treated?

Answer 50

**_Lymphocytic and Collagenous_** Typified by **normal findings in the context of a relapsing/remitting course of IBS-like symptoms**. May have patchy erythema, hyperaemic mucosa, and loss of vascular patterns. Lymphocytic: * **Intraepithelial lymphocytosis** with minimal crypt distortion Collagenous: * Sub-epithelial **collagenous band** Treated with **Budesonide 6mg PO OD**

Question 51

What is immunomodulator associated colitis?

Answer 51

Immunomodulator associated colitis, or Immune-Check-Point-Inhibitor (ICPI) Associated Colitis, describes a type of iatrogenically induced autoimmmune colitis, typically seen after the 2nd or 3rd doses of ICPIs. Their exact mechanism of action relating to enterocolitis remains elusive, however CTLA-4 blockade suppresses the body’s CTLA-4 mediated protection against autoimmunity. It is therefore responsible for the diverse profile of autoimmune side effects.

Question 52

Summarise the evidence base regarding anastomotic leak and mechnical bowel preparation with or without antibiotics.

Answer 52

The evidence base for MBP is _largely derived from retrospective registry data prone to bias_ and duplication of patient data. A recent meta-analysis of nearly 70,000 patients showed MBP + OAB reduced the risk of AL significantly (0R 0.62), **however when limited to randomised trials (which accounted for only 9% of included patients) there was no significant difference.** Similar conclusions were reached by a network meta-analysis limited to randomised trials. Overall, **_current evidence would suggest MBP + OAB provides a reduction in risk of surgical site infection, however the effect on the rate of AL remains contentious and should be interpreted with caution._** 2019 ASCRS Guidelines recommend use of MBP + OAB prior to elective colorectal resection.

Question 53

What is the risk of mortality following anastomotic leak? What are the estimated leak rates for small bowel anastomoses and rectal anastomoses?

Answer 53

7-14% SB anastomosis AL rate = 1-2% Rectal anastomosis AL rate = 11% *(systematic review of over 25,000 patients with anastomoses)*

Question 54

What is the impact of Anastomotic Leak on post operative function? What is the effect of Anastomotic Leak on oncological outcome?

Answer 54

* 25% of stomas created due to AL will never be closed * Those that have continuity restored suffer worse functional outcomes with **increased frequency, urgency, and incomplete evacuation**. Stricturing may also be present. * Patients with AL suffer delay to chemotherapy * Data regarding impact on LR, DFS, and OS are hetergogenous in study-type and results. * Whilst it has been suggested that AL is associated with an OR of 1.5-2 for LR and distant failure, **local (Australian) database research has not confirmed this, and well designed propensity matched studies suggest there is no effect.**

Question 55

What are the risk factors for Anastomotic Leak?

Answer 55

**_Modifiable Patient Related Factors_** * Obesity (OR ~3) * Medications * Corticosteroids (OR ~2) * Anticoagulant therapy (OR ~2) * Anti-mitotic and anti-angiogenic medications * Smoking * Alcohol intake over 21 units per week * Malnutrition/hypoalbuminaemia **_Non-modifiable Patient Related Factors_** * Gender (male; OR 1.5) * Age has no impact unless AL occurs (age predicts mortality) **_Treatment Related Factors:_** * Bowel preparation * Cyclical popularity; MPB with PO ABx lowers leak on large retrospective registry data (not with RCTs). * Intra-operative soiling * Intra-operative blood loss * Blood transfusion * Perfusional testing with ICG probably good * Air leak testing also associated with lower leak rates *Things that are discussed often but are NOT risk factors:* * *IMA ligation and SF mobilisation no effect* * *Configuration and technique of anastomosis* * *No difference except for Cochrane review showing stapled better in right hemicolectomy.*

Question 56

What is the mean number of VAC changes required in endosponge salvage of an anastomotic leak? What was the average duration of therapy?

Answer 56

11 VAC changes 34 days.

Question 57

Describe what constitutes a healthy biome. How does a "pathobiome" lead to anastomotic leak?

Answer 57

* The microbiota is predominated by two bacterial phyla - Bacteroidetes and Firmicutes, which include the genera *Clostridium*, *Peptostreptococcus*, *Bifidobacterium* and *Bacteroides.* * These prevent expansion of **facultative aerobes such as enterococcus** * **​***Enterococcus faecalis* ​ * Certain bacteria such as *Enterococcus*, *Pseudomonas* and *Escherichia,* usually under-represented in the biome, have been postulated to be key microbial organisms responsible for the **upregulation of MMPs** due to cellular disruption and **genotypic switching**, which can result in an anastomotic leak.

Question 58

Describe the physiology underlying wound healing, with particular regard to anastomoses.

Answer 58

1. Reactive phase * Activation of complement * Infiltration by **phagocytes** * Scaffold formed by **fibrotic cap** * Days 1-4 2. Regenerative phase * **Fibroblast** migration * **Collagen** synthesis * **Angiogenesis** with re-epithelialisation * Days 4-14 3. Remodelling phase * Ongoing fibroblast activity * **MMPs remodel the collagen matrix** * **Wound contraction via PDGF** and IL-1

Question 59

What are the functions of the gut microbiome?

Answer 59

1. **Metabolism** * Bile salts - conversion of primary bile acids to cholate * SCFA - bacteria ferment fibre to butyrate and proprionate * Vitamins - water soluble B vitamins e.g. Niacin/Cobalamin 2. **Immunomodulation** * Regulate development of APCs and CD4+ T-cells 3. **Mucosal barrier function** * Metabolites from the biome enhance goblet cell mucus production * Mice without biome have no mucous production

Question 60

Describe some of the specific activity of the "healthy biome" species that may alter risk of anastomotic leak

Answer 60

* **Butyrate**, mainly produced by _***Firmicutes* phylum**_, enhances mucosal barrier function and mucosal immunity. * Administration of butyrate in enemas increases the bursting strength of rat anastmoses. * **Acetate**, mainly produced by anaerobes like ***_Bifidobacterium_***, is thought to have a defensive role against *E coli.*

Question 61

What are the proposed mechanisms by which an altered gut biome may lead to colorectal cancer?

Answer 61

The gut biome and their metabolic prooducts **can both provide protection from and susceptability to the development** of colorectal cancer. Protection from: * A significantly lower abundance of **SCFAs** and SCFA-producing bacteria have been demonstrated in CRC, i.e. ***Bifidobacterium*** **and its SCFAs protect against bowel cancer.** Susceptability to: * *Enterococcus faecalis* and *Bacteroides fragilis* produce enterotoxin **fragylisin and ROS, which cause increased infammation, oxidative DNA damage**, and epithelial barrier damage, directly harming gut cells leading to chronic inflammation and CRC development. * Epidemiological data shows a relationship with CRC and early childhood antibiotics!

Question 62

How is IBS diagnosed?

Answer 62

Rome IV criteria for IBS: *Recurrent abdominal pain on average at least 1 day/week in the last 3 months, associated with two or more of the following:* * Related to defaecation * Associated with a change in frequency of stool * Associated with a change in character of stool

Question 63

What is the evidence for dysbiosis in IBS patients? Cite specific pathophysiological species.

Answer 63

The evidence for dysbiosis is provided by **consistent variation of the microbiota** of individuals diagnosed with IBS compared to normal controls. **Lactobacilli and Bifidobacteria** levels are greatly reduced in patients diagnosed with IBS. Severity of IBS has also been suggested to be related to absence of **Methanobacteriales**, a microbe responsible for removing excess hydrogen by converting it to methane. Methane is associated with reduced transit time, as well as having anti-inflammatory effects.

Question 64

What are probiotics? Which microbes are most commonly associated with probiotics?

Answer 64

Probiotics are defined by the World Health Organisation to be ***“live microorganisms that when administered in adequate amounts, confer a health benefit to the host”***. * Lactobacilli * Bifidobacterium * E. coli Nissle 1917 **Faecal transplants** may also be considered polymicrobial probiotics.

Question 65

What are prebiotics?

Answer 65

Prebiotics are “ingredients in food such as fibers and oligosaccharides that induce the growth or activity of beneficial microorganisms”. Common examples include: * Human milk oligosacharides * Fructans * Inulin

Question 66

In what areas of colorectal surgery is there good evidence for the use of Probiotics/Prebiotics?

Answer 66

1. Probiotic use in patients undergoing chemotherapy * RCTs showing reduced **chemotherapy-related diarrhoea** 2. Probiotic use in patients with IBD * Cochrane review of 14 RCTs suggesting **possible improved induction of remission** 3. Probiotic use in patients with IBS * RCTS showing **reduced pain and symptom severity** scores

Question 67

How do you classify GI fistulas? What proportion of fistulas are iatrogenic? What is the rate of spontaneous closure?

Answer 67

Anatomically and by output. Low output = Less than 200ml per day Moderate output = 200-500 ml per day High output = \>500ml per day Up to 75-85% are iatrogenic. Most studies report spontaneous closure rates of between 20-30%.

Question 68

Describe factors that reduce liklihood of fistula closure.

Answer 68

Foreign bodies Radiation Epithelialisation of the tract Inflammation/Sepsis Neoplasia Distal obstruction Short tract

Question 69

Describe the aetiology of enterocutaneous fistulas

Answer 69

(also FRIENDS) Foreign bodies (mesh) Radiation IBD Enterotomies Neoplasia Diverticular disease Sepsis

Question 70

Describe the medications used to reduce output in high output ECF.

Answer 70

1. **Anti-cathartics** * Loperamide up to 40mg per day * Codeine up to 240mg per day 2. **Somatostatin analogues** * Octreotide (hlaf life 2-3 hours) should be trialed for 3 days prior to continuation * Systematic reviews suggest no effect on spontaneous closure rate but do suggest a reduction in time to closure. 3. **Anti-secretories** * PPI and Histamine antagonists reduce acidity

Question 71

How is intestinal failure classified?

Answer 71

The functional classification of intestinal failure is based on **onset**, **metabolic derangement**, and **expected outcome criteria** * Type 1 * Acute, self-limiting * Less than 28 days * Prolonged post operative ileus * Type 2 * Acute, prolonged * 28 days to months * Metabolically unstable patients * Type 3 * Chronic * Months to years * Metbolically stable patients

Question 72

Define and explain intestinal adaptation.

Answer 72

Intestinal adaptation refers to ***structural and functional changes that lead to enhanced fluid and nutrient digestion and absorption in the remaining intestine.*** Adaptation occurs structurally and functionally. Structural adaptation: * Increased diameter * Increased length * Increased mucosal mass with deeper crypts and taller villi Functional adaptation: * Increased gut hormone activity * Slowed intestinal transit * Hyperphagia * Altered biome

Question 73

What are the discrete phases of short-bowel-syndrome? What are the key components in managing each phase?

Answer 73

1. Acute, hyper-secretory phase * First 3 months * Fluid management the main issue with significant electrolye losses and hypergastrinaemia 2. Adaptation phase * 3 months to 2 years * Aim to promote enteral nutrition * Consider medications to enhance adaptation (Teduglutide) 3. Persisting intestinal failure phase * Beyond 2 years * Long term PN is the mainstay * Consider surgical interventions to improve enteral route * Minimise complications of PN

Question 74

What are the drawbacks of somatostatin (and its analogues)?

Answer 74

* Cost * Rapid development of tolerance * Gallstones * Painful subcutaneous injections

Question 75

What medications are available for intestinal adaptation in SBS patients?

Answer 75

1. Teduglutide * GLP-2 analogue * Enhances functional and structural adaptation * Can be used (in Aus) after one year of PN-dependance 2. Somatotropin * Recombinant human growth hormone * Conflicting data

Question 76

Provide an overview of the complications associated with Short Bowel Syndrome and PN Why do these occur?

Answer 76

* **Complications related to long-term IV-access** * Acute * Pneumothorax * AVM * Bleeding * Chronic * Line sepsis * VTE * Embolism from line thrombus * **Complications related to long-term metabolic changes** * Cholelithiasis * Interrupted bile salt metabolism * Nephrolithiasis * Dehydration, absorption of oxalate instead of bile salts * Metabolic bone disease * Calcium and Vitamin-D deficiency * Intestinal Failure Associated Liver Disease * Unclear pathophysiology, ranges from mild to fulminant * Small Intestinal Bacterial Overgrowth * Mechanical and adaptive (e.g. lactobacillus) * D-lactic Acidosis * Severe neurological symptoms following CHO meal * Too much glucose and starch to colon.

Question 77

Describe the surgical procedures that have been used to slow intestinal transit.

Answer 77

1. Reversed intestinal segment 2. Intestinal valve 3. Colonic interposition graft

Question 78

Describe the surgical procedures used to increase functional bowel length in SBS

Answer 78

1. Serial transverse enteroplasty (STEP) procedure * Segmental stapled ingress into lumen to create staggered length 2. Longitudinal intestinal lengthening and tailoring (LILT) procedure * aka Bianchi procedure * Autologous intestinal reconstruction 3. Excisional tapering enteroplasty * Revision of a dilated small bowel side-to-side anastomosis * Creation of end-to-end tapered anastomosis

Question 79

What are the 10-year survival rates for intestinal transplant and home TPN?

Answer 79

Intestinal Transplant = 50% Home TPN = 50-85%

Question 80

Describe the 3 anatomically classified groups in Short Bowel Syndrome

Answer 80

Group 1 * End-jejunostomy with no colon in continuity. * CIF is usually observed usually with small bowel less than 1 metre. * This groups carries the worst prognosis and occurs in more than 1/3 of cases. Group 2 * Jejunocolic anastomosis with no ileo-cecal valve (ICV) and a part of the colon in continuity. * CIF is generally observed if \<50cm of small bowel remains with all the colon in place. * A greater length of small bowel is required where there is less colon. Group 3 * Jejuno-ileocolic anastomosis with both the ileo-caecal valve (ICV) and the entire colon in continuity. * This is the best case for which only 30-50cm of small bowel is enough to avoid CIF . This group has the best prognosis. * These patients often appear well following their resection except for diarrhoea/steatorrhoea, but loose weight in the following months and become severely undernourished.

Question 81

What are the specific roles of the terminal ileum nutritionally?

Answer 81

* Bile salt (re)absorption * Fat soluble vitamin absorption * B12 vitamin absorption

Question 82

# Define LARS How is it diagnosed?

Answer 82

Low Anterior Resection Syndrome is defined as ***disordered bowel function after rectal resection leading to a detriment in quality of life.*** The diagnosis of LARS requires a patient who has undergone low anterior resection to **develops at least one (of eight) symptoms, and at least one (of eight) consequences.** 1. Variable, unpredictable bowel function 2. Altered stool consistency 3. Increased stool frequency 4. Repeated painful stools 5. Emptying difficulties 6. Urgency 7. Incontinence 8. Soiling 1. Toilet dependance 2. Preoccupation with bowel function 3. Dissatisfaction with bowels 4. Strategies and compromise 5. Impact on emotional and mental wellbeing 6. Impact on social and daily activities 7. Impact on relationship and intimacy 8. Impact on roles, committments, and responsibilites.

Question 83

What is the prevalence of LARS?

Answer 83

Major LARS (defined by score of 30-42) had a prevalence of 41% after low anterior resection. Minor LARS (score of 21-29) was found in 24%.

Question 84

How is LARS scored? What score constitutes minor/major LARS?

Answer 84

The LARS scoring system comprises of five questions: 1. **Do you ever have occasions when you cannot control flatus** * 0 = No, never * 4 = Yes, less than once/week * 7 = Yes, more than once/week 2. **Do you ever have any accidental leakage of liquid stool?** * 0 = No, never * 4 = Yes, less than once/week * 7 = Yes, more than once/week 3. **How often do you open your bowels?** * 4 = \>7/ 24 hours * 2 = 4-7/24 hours * 0 = 1-3/24 hours * 5 = Less than once/24 hours 4. **Do you ever have to open your bowels again within one hour of the last bowel opening ?** * 0 = Never * 9 = Yes, less than once per week * 11 = Yes, at least once per week 5. **Do you ever have such a strong urge to open your bowels that you have to rush to the toilet?** * 0 = Never * 11 = Yes, less than once per week * 16 = Yes, at least once per week. Score 0-20 = No LARS, 21-29 = Minor LARS, 30-42 = Major LARS

Question 85

Provide an overview of the multi-factorial pathophysiology of LARS

Answer 85

**_Direct structural causes_** * Damage to the anal sphincter * ~20% have some form of injury on EAUS * Damage to the hiatal ligament and conjoint longitudinal muscle * Reduces pelvic floor coordination * Loss of the specialised rectum * The sigmoid has no RAIR or recto-anal contractile reflex **_Neuroanatomical causes_** * Damage to the inferior hypogastric plexus * Mixed sympathetic, parasympathetic, and afferent fibres * Denervation of the left colon * Loss of sympathetic tone, with increased motility * High tie of the IMA leading to neo-rectal spasticity * Double the loss of "propagating contraction waves" * Loss of the "rectosigmoid brake" * No more retrograde propagation

Question 86

What are the risk factors for LARS?

Answer 86

1. Neoadjuvant therapy 2. Rectal remnant height \<4cm 3. DLI \> 6 months 4. Anastomotic leak

Question 87

Provide an overview of LARS management

Answer 87

* Dietary management * Avoid caffeine, spicy food, citrus etc. * Psyllium Husk * Medications * Loperamide to slow transit and increase anal tone * Consider Serotonin antagonists e.g Ramosetron * Pelvic floor exercises * No harm, good for incontinence phenotype * Colonic irrigation * Peristeen has good data for improved frequency and QoL * Once started, cannot stop. i.e. quick rebound. * SNS * "Modification of ascending supraspinal control of defaecation" * Heterogenous meta-analysis showed good results * Surgery * End-game

Question 88

What are the pros and cons of the MSKCC-BFI score for LARS?

Answer 88

The MSKCC-Bowel Function Instrument is an 18-point questionnaire, asking patients to recall bowel function over a four-week time-frame. It is comprehensive and therefore time-consuming and less practical.

Question 89

Provide an overview of stoma complications

Answer 89

* Acute (within 30 days of formation) * Stoma retraction * Stoma necrosis * High stoma output in the post operative setting * Acute parastomal hernia +/- bowel obstruction * Delayed * Stomal prolapse * Stomal stenosis * Delayed PSH +/- bowel obstruction * Any at time * High stoma output * Dermatitis * Peristomal bleeding and granulation * Pychological impact of having a stoma

Question 90

How do you make St Mark's solution? Any alternatives?

Answer 90

20g sugar + 3.5g salt + 2.5g sodium bicarb + 1000ml water Any ORS; can use Powerade with one teapsoon of salt, halved and topped up with water. ~210mOsm. (normal Powerade is 390mOsm i.e too hypertonic)

Question 91

What are the risk factors for development of a Parastomal Hernia?

Answer 91

* Obesity * Female gender * Large aperture size * Older age * Trans-peritoneal stoma passage * Smoking * Diabetes * Malnutrition * Emergency surgery

Question 92

Describe the EHS Classification of Parastomal Hernia and its utility.

Answer 92

The most useful aspect of the classification system is not to predict whether surgery is required, but rather to provide a nomenclature around the entity of PSH, such that radiologists, surgeons, and researchers are speaking the same language.

Question 93

What is the role of imaging in investigation and management of Parastomal Hernias? Does CT over-estimate or under-estimate PSH?

Answer 93

The main role of cross sectional imaging is to provide additional information to **_guide operative planning_**; the presence of a concomitant midline hernia, the contents of the hernia, and the size of the hernia orifice may influence the operative approach. Cross sectional imaging should be used with consideration; some have suggested that CT over-estimates the presence of PSH by misinterpreting redundant bowel within the subcutaneous tissue as a PSH, others have claimed that significant PSH may be missed on a supine CT with the hernia contents reduced.

Question 94

Describe the Cleveland Clinic algorithm for management of a Parastomal Hernia

Answer 94

Question 95

What is the FODMAP diet? What is the evidence base for the FODMAP diet in colorectal surgery?

Answer 95

The low ****_f_**ermentable **_o_**ligo-, **_d_**i-, and **_m_**onosaccharide and **_p_**olyol** (FODMAP) diet has substantial evidence for efficacy in the management of symptoms of irritable bowel syndrome. There is low level evidence for its use in quiescent IBD and in faecal incontinence, though it is a low risk intervention.

Question 96

How are FODMAPs thought to affect gut function?

Answer 96

FODMAPs are short-chain carbohydrates with a small molecular size and a **high osmotic effect** that are poorly absorbed in the gastrointestinal tract. Consequently, a signifcant portion of the ingested FODMAPs reach the distal ileum and colon intact and are available to be used by the gut microbiota. These characteristics potentiate i**ncreasing fermentation by the gut microbiota with associated symptoms that include gas production, abdominal pain, bloating, cramping, distension and diarrhoea.**

Question 97

List unfavourable factors for spontaneous EC-fistula healing

Answer 97

F₂RIE₂N₂D₂S₂ * * Persistent **F**oreign body (e.g. mesh) & high **F**erritin (\>200ml/dL) * I**R**radiated tissue * **E**pithelialised track and long track (\>2cm) * **N**eoplasia and **N**on-surgical pathology (e.g. Crohn's) * **D**istal obstruction and **D**elayed referral to tertiary centre * **S**epsis and **S**ignificant output (\>500ml/24hrs)

Question 98

Why is ileostomy output alkaline despite gastric contents acidity?

Answer 98

After leaving the stomach, gastric acid is neutralised by alkaline pancreatic secretion. The expression of the Cl-/HCL- symporter increases along the small intestine, such that chyme is alkaline by the terminal ileum.

Question 99

In what clinical situations is CMV reactivated? What are the classic endoscopic features? How is it treated?

Answer 99

CMV infection is usually latent, but can be reactivated with immunosuppression (transplant, HIV, graft-versus-host etc.). Endoscopic features are varied, but include sub-epithelial haemorrhage, patchy inflammatory infiltrates, and occasionally ulcers. Biopsies can be taken for immunohistochemistry. Treatment is with retrovirals (Ganciclovir) and ideally stopping the immune-suppression.