Colitides including IBD, Diverticulitis, Consequences of Messing with the GI tract Flashcards
Describe the Hinchey Classification System and its utility.
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)
Provide an overview of typical antibiotic usage in acute diverticulitis.
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.
What is the state of evidence surrounding usage of antibiotics in acute diverticulitis?
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.
Could diverticulitis be managed in the community?
What criteria would need to be satisfied?
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.
Describe the key considerations relating to the use of percutaneous drainage of diverticular abscesses.
Exapand on these.
- 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
What is the complication rate of percutaneous drainage of diverticular abscesses?
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.
What are the indications for surgery in acute diverticulitis?
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.
What is the evidence of primary anastomosis (PRA) versus non-restorative resection (NRR) in emergency surgery for acute diverticulitis?
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.
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.
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.”
Explain the utility of colonoscopy following acute diverticulitis, both complicated and uncomplicated.
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.
Describe the natural history following an attack of acute diverticulitis.
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:
- Asymptomatic (the majority ~66%)
- Recurrent acute diverticulitis
- Smouldering diverticulitis (or “symptomatic uncomplicated diverticular disease”)
- Complicated sequelae of disease.
Explain your approach to definitive management of complicated diverticulitis.
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.
Discuss preventative measures against diverticulitis and the current evidence base for these.
- 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.
Define Crohn’s disease.
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.
What is the pathogenesis of Crohn’s disease?
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.
How can Crohn’s “recurrence” be defined?
Desribe the rates of recurrence in each category.
-
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.
What is a Rutgeert’s score?
How is it calculated?
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.
What risk factors are associated with CD recurrence following surgery?
- Smoking
- More than two surgeries
- Penetrating disease phenotype
- Extensive SB disease (>50cm)
- Perianal disease
- Short interval between diagnosis and surgery
- Young age at diagnosis
What is the Crohn’s Disease Activity Index?
What is the utility of this index?
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.
Describe the distribution of Crohn’s disease along the GI tract.
What proportion of patients have perianal disease?
- 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.
Describe the Montreal Classification of Crohn’s Disease.
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)
What proportion of CD patients undergo surgery?
What are the non-emergent indications for surgery in CD?
How is failure of steroid therapy defined?
33 – 47% of patients proceed to surgery due to treatment failure.
- Persistent or worsening symptoms despite correct treatment
- Onset of unacceptable drug-related complications/intolerance when there is no other efficacious medical alternative
- Steroid–dependence
- 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.
Describe the impact of anti-IBD medications on post-operative outcomes.
Pre-operative anti-IBD therapy can be divided into 5 categories, two of which have a substantial impact on post operative outcomes:
-
Corticosteroids (e.g Hydrocortisone)
- 1.7x OR total infectious complications
-
Anti-TNF (e.g. Infliximab)
- 1.6 x OR total infectious complications
- Mixed evidence, some say no effect.
- Immunomodulators (e.g. Azathioprine)
- No significant effect
- Anti-integrin (e.g. Vedolizumab)
- No significant effect
- BUT, significant increase in superficial SSI and ileus
- 5-ASAs (e.g. Sulphasalazine)
- No significant effect
What are the techniques of stricturoplasty in Crohn’s strictures?
Briefly describe how they are performed.
- Heineke-Mikulicz
- Open longitudinally, close transversely
- 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
- Jaboulay
- (Short) Stricture made into a U-bend then bypassing side to side anastomosis created in two layers
- 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.
- 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).
Describe the pathophysiology of fistulating Crohn’s disease.
Cite therapeutic targets in your answer.
Our understanding of the pathophysiology of Crohn’s disease-associated fistulas is not complete. Two mechanisms seem to have a major role:
- Epithelial-to-mesenchymal transition (EMT)
- 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.
What is the role of the mesentery in Crohn’s disease?
Should it be excised or should it remain?
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.
What is the association between appendicectomy and IBD?
Discuss both Ulcerative Colitis and Crohn’s Disease.
- 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.
How is the appendix histologically different to the caecum?
What is thought to be its function?
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.
Describe Trulove and Witt’s criteria
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.
What is the criteria for diagnosis of Acute Severe Ulcerative Colitis?
≥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)
Describe your Day-0 work-up of Acute Severe Ulcerative Colitis
- 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
Describe the Mayo Scoring System in UC.
Describe its utility.
How is remission defined?
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.
Define steroid-refractory Acute Severe Ulcerative Colitis.
How common is it?
31% to 35% of ASUC is steroid refractory, commonly defined as active disease that remains despite 3-5 days’ worth of treatment.
How do you decide if a patient with Acute Severe Ulcerative Colitis is failing medical treatment?
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).
What is Cyclosporin?
How does it work?
How effective is it in the setting of Acute Severe Ulcerative Colitis?
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
What is Infliximab?
How does it work?
How effective is it in salvaging Acute Severe Ulcerative Colitis?
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.
How is Infliximab administered?
What is the dose?
What is “accelerated dosing”?
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.
What do you do with the rectal stump at the time of a sub-total colectomy for Severe Acute Ulcerative Colitis?
Justify this.
- 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.
Outline the complications associated with ileoanal pouch formation.
How do you define pouch failure?
-
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
- Anastomotic leak
-
Inflammatory complications
- Pouchitis
- 50% at some point
- 15% chronic
- Crohn’s disease
- 10-20% eventually diagnosed with CD
- High pouch failure rate
- Cuffitis
- Pouchitis
-
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.
- Infertility and sexual dysfunction
Describe the surgical procedures that have been used to slow intestinal transit.
- Reversed intestinal segment
- Intestinal valve
- Colonic interposition graft
Describe the surgical procedures used to increase functional bowel length in SBS
- Serial transverse enteroplasty (STEP) procedure
- Segmental stapled ingress into lumen to create staggered length
- Longitudinal intestinal lengthening and tailoring (LILT) procedure
- aka Bianchi procedure
- Autologous intestinal reconstruction
- Excisional tapering enteroplasty
- Revision of a dilated small bowel side-to-side anastomosis
- Creation of end-to-end tapered anastomosis
Describe the EHS Classification of Parastomal Hernia and its utility.
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.
Describe the Cleveland Clinic algorithm for management of a Parastomal Hernia
