Presentation on theme: "Aspects on the Role of the Pathologist in CRC"— Presentation transcript:
1Aspects on the Role of the Pathologist in CRC Najib Haboubi FRCS FRCP FRCPath D PathProfessor of Health Sciences, Liver and Gastrointestinal Pathology.University Hospital of South ManchesterUK
2Selected Topics Multi Disciplinary Meeting(MDT). Resection Margins (Long and Circumferential).Assessment after CRT for Rectal Cancer
3BackgroundIn UK (60m) there are 35,000 new cases and 16,000 deaths per annum.New patterns in some parts of the world.In India 6th commonest among female and 9th amongst male.
4Accurate Pathological Reporting Confirm diagnosis.Inform prognosis.Plan treatment of individual patients.Audit pathology services.Evaluate and audit the quality of other services like radiology, surgery and oncology.Collect accurate data for cancer registration and epidemiology.Facilitate high quality research.Plan service delivery.
5Multi Disciplinary Team (MDT) Colorectal SurgeonsRadiologists.Pathologists.Oncologists.Specialist Nurse.Hepatobiliary(Thoracic) SurgeonStoma Nurse.Clinical geneticist / counsellor.Social worker.Clinical trials coordinator or research nurse.GPDietician.Gastroenterlogist
8MDT Takes place at regular intervals Encourages a more efficient and team working atmosphere .Have a consensus approach to treatment according to agreed protocols.Quick and appropriate referral pattern.Audit surgical treatment.Audit pathology reports.
24ConclusionDoes not influence Oncological outcome
25Additions in the 2nd edition (1) Documentation type of procedure .For rectal cancer, it is expected to have more AP than APR .
26National Audit AR 1670 APR 746 Hartman’s 299 There is a trend of increase the AR over APR due to:Better preoperative treatmentBetter imaging modalities andBetter surgery . Good surgeons should be able to undertake AR for tumours above 5cm from anal verge.
27CurrentlyIncreasingly there are surgeons who practice restorative surgery for ‘ultra’ low rectal cancer: 3 cm
35Addition to the 2nd edition (2) Grading of surgical plane of resection in rectal cancer.The continuous feedback to surgeons may lead to improve quality of surgery.
36Macroscopic Evaluation of Rectal cancer Resection Specimens Clinical Significance of the Pathologist in Quality Control.2 years follow up.Iris Nagtegaal et alJ Clin Oncol 2002, 20:
37Macroscopic Grading of TME A (3) ( Good). Complete. Smooth, no coning, defect >5 mm and regular CRMC (1) ( Poor). Defects down to the Muscularis ,conning, no bulk and irregular CRMB(2) .Nearly complete. Defect present but Muscularis is not apparent(except at the insertion of LA) and irregular CRM.
39Results Grade A&B - good and acceptable C- Poor Local Recurrence 8.7% 15%Local recurrence and Distant Metastasis20.3%36.1%2 Year Survival90.5%76.9%
40Addition to the 2nd edition (3) Measurement of tumour beyond the muscularis propria recorded in mm.This is to:a/ facilitate audit of preoperative imaging of extramural spread as it is of importance in selecting patients of rectal cancer to choose a therapy arm .b/ It has a prognostic implication for rectal cancer.5mm or more is associated with adverse prognosis.
42Addition to the 2nd edition (4) Recording tumour involvement of the NPRM in colonic tumours (in addition to rectum) like the caecum. These patients may be selected for post operative adjuvant therapy.Bateman et al J Clin Path 2005 and Quirke et al 2006 J Path
43Addition to the 2nd edition (5) Recording serosal ( peritoneal surface) involvement.‘Tumour cells visible either on the peritoneal surface or free in the peritoneal cavity carry bad prognosis’
44Shepherd, Baxter and Love J. Clin. Path 1995 Influence of local peritoneal involvement on pelvic recurrence and prognosis in rectal cancer.Shepherd, Baxter and LoveJ. Clin. Path 1995
45Local Peritoneal Involvement Detected in 25.8% (54/209) of cases.Showed considerable prognostic disadvantage in curative and non curative cases.May be an important factor in local recurrence of upper rectal cancers.
46The Prognostic Importance of Peritoneal Involvement in Colonic Cancer: a Prospective Evaluation Shepherd et al Gastroenterology 1997Strong predictive value for local recurrence / persistent disease specially when there is mucinous differentiation.
47Additions in the 2nd edition (6) Recording of marked or complete tumour regression in patients with rectal cancer that have received adjuvant chemo / radiotherapy (CRT)
48Rectal cancer that have received adjuvant R/CRT. Tumour regression is associated with improved prognosis.
49Pathologist should record marked or CTR Rectal cancer that have received adjuvant R/CRT.Tumour regression is associated with improved prognosis.
54Three folds decrease in local recurrence. Short course preoperative radiotherapy interferes with the determination of pathological parameters in rectal cancer Iris Nagtegaal et al. J Path 2002,197: patients(706 TME alone, 598 TME+RT)No change in stage (No change in depth and although there is decrease in no. of LN retrieval but not in +ve lymph nodes)!!Three folds decrease in local recurrence.
55Long course CRT Improves staging (depth and LN status). Associated with c&pCTR
56Classifications of Regression Mandard : Cancer 1994,73; (1-5)Dworak : Int CRD 1997,12; (0-4)Wheeler : DCR 2002,45; (1-3)Ryan : Histopathol 2005,47;141.(1-3)PRINCIPLETumour Volume V Fibrosis.
57Discrepancy in Staging AuthorGradeBest Response (pCR)Worst ResponseMandard1-515Dworak0-44Wheeler1-33Ryan
58Ryan’s modification of Mandard’s 5 point system G1: No viable cancer cells (pCTR): Single cells or small groups of cancer cells.G2: Residual cancer cells outgrown by fibrosis.G3: Significant fibrosis outgrown by cancer cells.: No fibrosis with extensive residual cancer.
59Rayan et al Histopathology:2005,47:141-146. 60 patients G1, G2,G3. Pathological response following long-course neoadjuvant CRT for locally advanced rectal cancerRayan et al Histopathology:2005,47:60 patientsG1, G2,G3.none of the G1&2 (excellent and good) had local recurrence after mean 22 months.
68Operative Versus Non Operative Treatment for Stage 0 Distal Rectal Cancer Following Chaemoradiation Therapy Long-term Results Angelita Habr-Gama, et al Ann Surgery 2004
69Results26.8% of patients who received CRT developed complete clinical tumour response (observational group).Full thickness biopsy?The five-year overall and disease-free survival rates were 88% and 83% in Resection Group and 100% and 92% in Observation Group
70ConclusionStage 0 rectal cancer disease is associated with excellent long-term results irrespective of treatment strategy.Surgical resection may not lead to improved outcome in this situation and may be associated with high rates of temporary or definitive stoma construction and unnecessary morbidity and mortality rates.
71Complete Clinical response After Preoperative CRT in Rectal cancer Is Wait and See Policy Justified?Glynne-Jones et alDCR 2008Narrative Review of 246 studies
72ResultsThe end point of complete clinical response is inconsistently defined.Insufficiently robust.Partial concordance with pathological complete response.
73ConclusionThe rationale of ‘wait and see’ policy when complete clinical response status is achieved relies on retrospective observations which are insufficient to support such policy. EXCEPTIn patients who are recognised as unfit or refused surgery
74What do we do when there is cCR? There are at least one trial in UK and an audit in the North West Region.Registering ALL cases with cCR and cPR.Outcome?
83Acute radiation colitis in patients treated with short term preoperative radiotherapy for rectal cancerLeupin et al (Switzerland)Am J Surg. Path.2002
84Radiation colitis Long Course Short CourseSever mucosal inflammation.Prominent eosinophils.Crypt disarrayCrypt epithelial damage.Nuclear abnormalityApoptosis of crypt epithelium.Either clinically silent or quick recovery.Long CourseThese features are either absent or rarely detected.
85Haboubi, Rowland, and Schofield The Light and Electron Microscopic Features of Early and Late Radiation-Induced ProctitisHaboubi, Rowland, and SchofieldAm.J.of Gastro.1988
92How SC differs from LC in pathological and clinical parameters 78 patients(SC 65, LC13) Age (average 67 years)54 males and 25 femalesMean follow up 56 months(4-105)AR in 31 cases; APR in 47cases.
93Results 1 32 Responders (Ryan grade 1 and 2) 10(76%) of LC vs. 22(33%)SC.
94Results 2 7 patients had local recurrence (6SC,1LC) Regression did not correlate with local recurrence
95Result 3Regression did not correlate with overall survival
96Prognostic Significance of Tumour Regression After Preoperative CRT for RC Rodel et al .J Clin Oncol 2005,23:8688G 4 (Good) in 10.4% DFS 86%.G 2& DFS 75%G 0&1(Bad) >10% DFS 63%
97Result 4Overall mortality correlated with lymph node positivity (p=0.009)29% of responders were LN+ve versus 48% non responders
98Absence of LN in the resected specimen after Radical Surgery for Distal Rectal Cancer and Neoadjuvant CRT: What does it mean? Habr-Gama et al DCR 2008,51;32(11%) patients had no LN.5YDFS 74%171(61%) had ypNO YDFS 59%78(28%) had yp(N+) YDFS 30%