TME - Auditing the Surgeon

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Dr Bryan F Warren

Consultant Gastrointestinal Pathologist, Honorary Senior Lecturer and Fellow of Linacre College Oxford.

M62 Course 2007

Cuthbert E Dukes Consultant Pathologist St Mark’s Hospital 1926-1956

The Dukes classification

Does TME and its careful pathological assessment help?

Treatment of rectal cancer: reduction of local recurrence after the introduction of tme-experience from one University Hospital. Bernardshaw SV et al Dig Surg 2006; 23:51-9. Oslo.

 139 non TME and 181 TME patients 1990 2000. TME introduced in 1994.

  LR at 1,3,5 years 7,15,17% non TME LR at 1,3,5 years 4,9,9% TME

Does TME and its careful pathological assessment help?

Nationwide quality assurance of rectal cancer treatment.

Wibe A et al. Colorectal Dis 2006;8:224-9. Norway.

 Risk of local recurrence in 1999 50% below that observed in 1994. Survival also improved.

Rectal cancer-How I do it

The specimen is received fresh, and inspected by me +/- surgeon +/- trainee pathologists and surgeons.

• • • I/we inspect: Mesorectal margin Close distal margin Tumour on peritoneal surface/mesorectal margin

Audit the surgeon, the preop radiology, the pathology!

Mesorectal margin and local recurrence in rectal cancer

Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision Lancet 1986;8514:996

     14/52 LRM + 12/14 local recurrence Specificity 92% Sensitivity 95% Positive predictive value 85%

How many slices for histology?

How many slices for histology?

Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision Lancet 1986;8514:996

Single slice chosen macroscopically: 6/52 (12%) LRM + On embedding and sectioning the whole tumour using large blocks: (10u H&E stained sections cut on a sledge microtome) 14/52 (27%) LRM +

How many slices for histology?

Ng IO, Luk IS, Yuen ST, Lau PW, Pritchett CJ, Ng M, Poon GP, Ho J. Surgical lateral clearance in resected rectal carcinomas. A multivariate analysis of clinicopathological features. Cancer 1993; 71(6): 1972-6 .

   80 rectal cancers 6/80 LRM+ (<1mm) in single slice seen macroscopically to have maximum tumour invasion 16 LRM + after processing the whole specimen  “Embedding and examining the whole tumour and mesorectum is the only reliable way of assessing LRM”!

(UK-manpower implications)

How many slices for histology?

Quirke P, Dixon MF. The prediction of local recurrence in rectal adenocarcinoma by histopathological examination. Int J Colorect Dis 1988;3:127-131.

Macroscopic inspection indicates the deepest areas of invasion to sample.

4-6 blocks is usually adequate.

“Lateral” margin – a predictor of local recurrence or prognosis?

Cawthorn SJ, Parums DV, Gibbs NM, A’Hern RP, Caffarey SM, Broughton CI, Marks CG. Extent of mesorectal spread and involvement of lateral resection margin as prognostic factors after surgery for rectal cancer. Lancet 1990;335(8697):1055-9.

  167 patients  Local recurrence in 13/168(8%) of which 12 had a clear (mean 5mm) LRM 11/168 were LRM + mean survival 18.7 months.

Lateral margin positivity did not correlate with local recurrence but did correlate with poor prognosis.

Adam IJ, Mohamdee MO, Martin IG, Scott NA, Finan PJ, Johnston D, Dixon MF, Quirke P. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet 1994; 344(8924):707-711.

190 patients CRM + in 25%(35/141) potentially curative resections CRM + in 36%(69/190) of all cases Local recurrence after potentially curative resection in 25% CRM+ independently influenced both local recurrence and survival Confirms the need to examine CRM carefully

Hall NR, Finan PJ, Al-Jaberi T, Tsang CS, Brown SR, Dixon MF, Quirke P. Circumferential margin involvement after mesorectal excision of rectal cancer with curative intent. Predictor of survival but not local recurrence? Dis Colon Rectum 1998;979-983.

218 patients 152 potentially curative resections.

      20 (13%) tumour within 1mm CRM 50% disease recurrence CRM+ at 41 months Local recurrence in 15% 24% disease recurrence CRM- at 41 months Local recurrence in 11%(p=0.38) Disease free survival (p=0.01) and mortality (p=0.005) were related to CRM+ Patients with an involved CRM may die of distant disease before local recurrence is apparent.

Birbeck KF, Macklin CP, Tiffin NJ, Parsons W, Dixon MF, Mapstone NP, Abbott CR, Scott NA, Finan PJ, Johnston D, Quirke P. Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery. Ann Surg 2002;235:449-457.

608 patients 1986-1997  586 clinical follow up available     105 (17.9%) developed local recurrence 165 CRM positive 38.2% local recurrence 421 CRM negative 10% local recurrence. CRM – had improved (75%) 5 year survival over CRM+ (29%) CRM+ immediate post surgical predictor of survival (CR07) Useful indicator of the quality of surgery-Audit

Pathologists’ assessment of the mesorectum macroscopically.

Nagtegaal ID, van de Velde CJ, van der Worp E, Kapiteijn E, Quirke P, van Krieken JH; Cooperative Clinical Investigators of the Dutch Colorectal Cancer Group. Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control. J Clin Oncol 2002; 20: 1714-5.

  180 patients 24% (43) incomplete mesorectum 36.1% local and distant recurrence vs 20.3% in the group with a complete mesorectum  Survival is predicted by proper assessment of the mesorectum, and judgement of the quality of TME.

Trials – CR07 quality of surgery

P Quirke et al

Quality of surgery - 1

 Poor surgery – irregular mesorectum with defects > 1 cm 2 or incision down to muscularis propria. Irregular CRM with little bulk and little clearance anteriorly

Quality of surgery - 2

 Sub-optimal – Moderate bulk of mesorectum but some irregularity. Moderate coning may be present distally P Quirke et al

Quality of surgery - 3

 Optimal surgery – Good bulk of mesorectum, smooth surface, good clearance anteriorly, no defects in mesorectum P Quirke et al

Relationship betw een pathological assessment and CRM positivity

80 70 60 50 40 30 20 10 0 Complete Nearly complete Incomplete < 1 mm 1.1-2mm 2.1-5mm 5.1-10mm >10mm

Distance to CRM

Kruskall Wallis test p<0.001

Summary

• • • • • The pathologist’s role in TME specimen assessment: To stage the tumour accurately To assess the surgical margins of the resected rectum accurately To assess the quality of the surgery To audit pathology and to help audit radiology To communicate effectively with the multidisciplinary team