Ulcerative Colitis And Dysplasia Management

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Ulcerative Colitis And DysplasiaManagement

• César Yaghi, MD
• Service de Gastro-entérologie
• Hotel Dieu de France
• Université Saint Joseph

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Plan

• Introduction
• Incidence of colorectal cancer and dysplasia in
  IBD
• Risk factors for CRC
• Preventive treatments
• Screening for dysplasia and CRC
• Management of abnormal screening findings
• Conclusion

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INTRODUCTION

• Strategies for detecting colon cancer and/or
  dysplasia in patients with inflammatory bowel
  disease.
• REVIEWERS' CONCLUSIONS
• No clear evidence that surveillance colonoscopy
  prolongs survival in patients with extensive
  colitis.
• There is evidence that cancers tend to be
  detected at an earlier stage in patients who are
  undergoing surveillance and these patients have a
  correspondingly better prognosis but lead-time
  bias could contribute substantially to this
  apparent benefit.
• There is indirect evidence that surveillance is
  likely to be effective at reducing the risk of
  death from IBD-associated colorectal cancer
• Indirect evidence that it is acceptably
  cost-effective.

Mpofu C Cochrane Database Syst Rev.
2004(2)CD000279
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Plan

• Introduction
• Incidence of colorectal cancer and dysplasia in
  IBD
• Risk factors for CRC
• Preventive medical treatments
• Screening for dysplasia and CRC
• Management of abnormal screening findings
• Conclusion

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Incidence of Colorectal Cancer in Inflammatory
Bowel Disease

• Ulcerative colitis CRC Prevalence 3.7.
• The risk increased with duration of disease
• 2 incidence of cancer after 10 years
• 8 incidence after 20 years
• 18 incidence after 30 years of disease.
• 1/3 deaths related to ulcerative colitis.
• Eaden Aliment Pharmacol Ther. 2004 20
  424-30
• Similar risk for colorectal cancer in Crohn
  disease and in ulcerative colitis.
• 20-year cumulative incidences of CRC identical in
  extensive Crohn disease of the colon and equally
  extensive ulcerative colitis.
• Gillen Gut. 1994 351590-2
• In Crohn colitis, the relative risk 5.6,
  similar to ulcerative colitis.
• Ekbom Lancet. 1990 11336357-9

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Ekbom, et al NEJM, 1990
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PSC and Colon Cancer Risk
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Plan

• Introduction
• Incidence of colorectal cancer and dysplasia in
  IBD
• Risk factors for CRC
• Preventive treatments
• Screening for dysplasia and CRC
• Management of abnormal screening findings
• Conclusion

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Risk Factors for Colon Cancer in Ulcerative
Colitis and Crohns colitis
Importance
Risk Factor
Choi PM, et al. Gastroenterol Clin North Am
199524671-87. Eaden J. Am J Gastroenterol
2000952710-2719.
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Severity of inflammation is a risk factor for
colorectal neoplasia in ulcerative colitis

• the histological inflammation score (odds ratio,
  4.7 P lt 0.001).

Rutter et al Gastroenterology. 2004 126451
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Plan

• Introduction
• Incidence of colorectal cancer and dysplasia in
  IBD
• Risk factors for CRC
• Preventive treatments
• Screening for dysplasia and CRC
• Management of abnormal screening findings
• Conclusion

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Prevention of Colon Cancer in UC/CD

• Chemoprevention
• 5-ASA 1.2 gm once daily (Eaden, APT, 1999)
• Folic acid 1 mg daily (Lashner, Gastro, 1997)
• Ursodiol 300 mg bid (PSC) (Tung, Ann Int Med,
  2001)
• Insufficient evidence to modify screening and
  surveillance in UC patients who use these
  medications.
• Surgery (ileo-anal anastomosis)
• DALM, high grade dysplasia, ? low grade dysplasia

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5-aminosalicylate use and colorectal cancer risk
in inflammatory bowel disease

• 18,969 patients, of whom 100 patients had
  developed CRC during 5-ASA exposure. (76 patients
  had a history of ulcerative colitis ) .

Van Staa TP Gut. 2005 Jun 30 Epub ahead of print 
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Effect of 5-aminosalicylate use on colorectal
cancer and dysplasia risk

• Nine studies (3 cohort, 6 case-control)
• 1,932 subjects satisfied all inclusion criteria.
• 334 cases of CRC,
• 140 cases of dysplasia,
• Protective association between 5-aminosalicylates
  and CRC or a combined endpoint of CRC/dysplasia
  in patients with ulcerative colitis. Additional
  studies analyzing the effect of 5-ASA on risk of
  dysplasia are needed.

Velayos et al. Am J Gastroenterol. 2005
1001345-53.
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Surgical Prophylaxis

• It has been recommended by some experts to
  consider total proctocolectomy for patients with
  greater than 8 to 10 years of extensive disease.
• Total proctocolectomy is not without many
  potential complications, including pouch failure,
  increasing stool frequency, incontinence, and
  pouchitis.
• Patients with ileoanal pouch anastomosis still
  maintain a small potential risk for the
  development of colorectal cancer in the rectal
  cuff itself.

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Plan

• Introduction
• Incidence of colorectal cancer and dysplasia in
  IBD
• Risk factors for CRC
• Preventive treatments
• Screening for dysplasia and CRC
• Management of abnormal screening findings
• Conclusion

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Consensus Conference Colorectal Cancer Screening
and Surveillance in Inflammatory Bowel
DiseaseSteven H. Itzkowitz, and Daniel H.
Presentfor the Crohns and Colitis Foundation
ofAmerica Colon Cancer in IBD Study
GroupInflamm Bowel Dis Volume 11, Number 3,
March 2005
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Colorectal Cancer Screening and Surveillance in
Inflammatory Bowel Disease

• Duration of Disease
• screening colonoscopy 8 to 10 years after the
  onset of symptoms attributable to UC.
• The purpose
• reestablish disease extent
• look for evidence of dysplasia.
• Regular surveillance colonoscopy after a
  screening examination.
• Anatomic Extent
• Patients with UC classified into 1 of 3
  categories
• Extensive if there is evidence of UC proximal to
  the splenic flexure,
• Left-sided if UC is present in the descending
  colon up to, but not proximal to, the splenic
  flexure,
• Proctosigmoiditis if disease is limited to the
  rectum with or without sigmoid colon involvement
• The extent of involvement defined either at
  diagnosis or screening, whichever reveals more
  extensive involvement.
• Colonoscopy preferred to flexible sigmoidoscopy.

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Gross versus microscopic pancolitis and the
occurrence of neoplasia in ulcerative colitis.

• Thirty-six patients with colitis-related
  dysplasia/CRC were identified from colectomy
  specimen of whom 30 had slides available for
  review.
• Gross pancolitis was identified in 19 patients,
  though microscopic pancolitis was evident in all
  30 patients. Among the 11 patients with only
  distal gross colitis, 4/15 neoplastic lesions
  were proximal to the area of gross involvement.
• UC-related neoplasia can occur in areas of the
  colon not grossly involved with colitis, though
  it did not occur in any patients without
  microscopic pancolitis.

Mathy C Inflamm Bowel Dis. 2003 Nov9(6)351-5.
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Colorectal Cancer Screening and Surveillance in
Inflammatory Bowel Disease

• Primary Sclerosing Cholangitis
• not previously known to have IBD colonoscopy to
  determine the status.
• Biopsies from normal-appearing mucosa, for
  microscopic evidence of colitis
• If IBD demonstrated screening and subsequent
  surveillance since PSC onset.
• Age of Onset
• insufficient evidence to support starting
  screening and surveillance before 8 years of
  disease
• screening and surveillance based on other risk
  factors.

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Colorectal Cancer Screening and Surveillance in
Inflammatory Bowel Disease

• Positive Family History of CRC
• A positive family history of CRC is a risk factor
  for CRC in UC patients.
• Insufficient evidence to warrant altering either
  the initiation of surveillance or the interval
  between examinations based on this information.
• Obtain a detailed family history for intestinal
  and extraintestinal neoplasia and incorporate any
  evidence of heightened risk into the clinical
  decision making.
• Degree of Endoscopic and Histologic Activity
• Increased severity of inflammation, both
  endoscopically and histologically, Correlates
  with increased frequency of dysplasia.
• patients with longstanding quiescent colitis
  remain at risk for developing CRC.

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Timing of Screening Exams

• A screening colonoscopy should be performed in UC
• rule out colonic neoplasia (dysplasia or cancer)
  8 to 10 years after the onset of UC symptoms.
• Extent of disease should also be evaluated, with
  possible reclassification of extent if there is
  significant change.

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Timing of Surveillance Exams

• Patients with extensive colitis or left-sided
  colitis who have a negative screening colonoscopy
  should begin surveillance within 1 to 2 years.
• negative surveillance colonoscopy subsequent
  surveillance examinations should be performed
  every 1 to 2 years.
• With 2 negative examinations, the next
  surveillance examination may be performed in 1 to
  3 years until 20 years.
• gt20 years performing surveillance every 1 to 2
  years
• Patients with PSC surveillance yearly.
• Patients with other risk factors, such as
  positive family history of CRC, may require
  shorter surveillance intervals.
• Proctosigmoiditis should be managed according
  to standard CRC prevention

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Dysplasia arising in chronic ulcerative
colitisThe presence of nodular masses arising in
a mucosa affected by ulcerative colitis are
suspicious for malignancy.
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Colonoscopic Practice

• a minimum of 33 biopsies
• 4-quadrant biopsies every 10 cm
• Particularly in UC, consideration should be given
  to taking 4-quadrant biopsies every 5 cm in the
  lower sigmoid and rectum, because the frequency
  of CRC is higher in this region.

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The detection of colitis-associated colorectal
cancer during colonoscopy

• difficult because the dysplasia may be present in
  macroscopically normal mucosa
• only 20 to 50 of intraepithelial neoplasias can
  be detected by routine colonoscopy.
• Cancers in ulcerative colitis grow in a diffusely
  infiltrating pattern, also hindering the
  macroscopic diagnosis of dysplasia.

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Dysplasia associated lesion/mass.
Rutter, M D et al. Gut 200453256-260
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Dysplastic lesion highlighted by indigo carmine
dye spray.
Rutter, M D et al. Gut 200453256-260
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Role of chromoendoscopy for the detection of
intraepithelial neoplasia and colon cancer in
ulcerative colitis.

• The targeted biopsy protocol detects dysplasia in
  significantly more patients than the non-targeted
  protocol
• targeted biopsy protocol with pancolonic
  chromoendoscopy requires fewer biopsies
• better evaluation of degree and extent of colonic
  inflammation
• Using the modified pit pattern classification,
  both the sensitivity and specificity for
  differentiation between non-neoplastic and
  neoplastic lesions were 93.

Matsumoto T Am J Gastroenterol. 2003
Aug98(8)1827-33 Gut. 2004 Feb53(2)256-60 Kiess
lich R Gastroenterology. 2003 Apr124(4)880-8.
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Figure 1 Pit pattern classification according to
Kudo and colleagues.16. The typical crypt
architecture of types I-V are indicated (A). (B)
Examples of type I (left) and type IV (right)
lesions before and after chromoendoscopy.
Kiesslich, R et al. Gut 200453165-167
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Seven guidelines for chromoendoscopy in
ulcerative colitis
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Seven guidelines for chromoendoscopy in
ulcerative colitis
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Plan

• Introduction
• Incidence of colorectal cancer and dysplasia in
  IBD
• Risk factors for CRC
• Preventive treatments
• Screening for dysplasia and CRC
• Management of abnormal screening findings
• Conclusion

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Progression of flat low-grade dysplasia to
advanced neoplasia in patients with ulcerative
colitis

• The rate of neoplastic progression was 33 - 53
  at 5 years.

Ullman Am J Gastroenterol. 2002 Apr97(4)922-7
Ullman T Gastroenterology. 2003 Nov125(5)1311-9
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Management of Abnormal FindingsDefinition of
abnormal findings

• Any examination in which a single biopsy reveals
  mucosal changes interpreted as indefinite for
  dysplasia, low-grade dysplasia (LGD),
  high-grade dysplasia (HGD), or
  adenocarcinoma
• Biopsies
• Patients who have lt 33 biopsies / colonoscopy are
  more likely to have a missed diagnosis of
  neoplasia
• Should be confirmed by an experienced
  gastrointestinal pathologist.
• The decision for recommending colectomy should be
  considered in light of
• the quality of the preparation
• sufficient biopsies taken
• the presence of active inflammation that can
  occasionally make interpretation of the biopsies
  difficult.

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Recommended management strategies for abnormal
findings

• Indefinite for Dysplasia in Flat Mucosa
• If the diagnosis is confirmed, a follow-up
  surveillance examination should be performed
  within 3 to 6 months.
• LGD in Flat Mucosa
• Progression from LGD to HGD or CRC 50-55
• Unrecognized synchronous CRC 20
• Unifocal or Multifocal flat LGD prophylactic
  total proctocolectomy.
• If operative strategy deferred or the patient
  elects to continue with surveillance, repeat
  examination within 3-6 months
• Repeat exams
• extensive biopsy protocol
• patients who elect to pursue a nonoperative
  strategy for LGD continued, more frequent exams
  (6 mo) is recommended to ensure that the
  diagnosis is correct.
• HGD in Flat Mucosa
• If confirmed, total proctocolectomy

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Raised Lesions (Polyps) with Dysplasia

• Polypectomy and biopsies of surrounding mucosa (4
  biopsies adjacent to the raised lesion and
  submitted separately)
• Negative for dysplasia, and no dysplasia
  elsewhere in the colon, follow-up examination
  should be performed within 6 months, with regular
  surveillance resumed if no dysplasia is found.
• Dysplasia present in the surrounding mucosa, or
  polypoid lesion nonresectable or does not
  resemble a typical adenoma (DALM), a high risk of
  associated synchronous CRC would justify
  recommending a complete proctocolectomy.
• Adenoma-like polyps in areas of the colon
  endoscopically and microscopically free of
  disease
• to be managed according to standard
  recommendations for postpolypectomy follow-up of
  sporadic adenomas

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Conclusion

• Screening recommendations
• Frequency
• Timing
• Identifying dysplasia
• Number of biopsies
• Chromoendoscopy
• Trained pathologist
• Appropriate management
• Surgical treatment
• Surveillance