iban aldecoa ansorregui hospital clínic de barcelona ...€¦ · • colon carcinomas / adenomas...
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Iban Aldecoa Ansorregui
Hospital Clínic de Barcelona
Universitat de Barcelona
ialdecoa@clinic.cat
Tools for improving LN analysis
• Specimen tattooing:
o Greater LN yields
o LNS most prone to harbour metastases?
• Pooling:
o Higher feasibility
o Acceptable results?
Colonoscopy
Williams, J. G. et al. Color. Dis. 15, 1–38 (2013)
Dawson, K., et al. Arch. Surg. 145, 826–830 (2010)
Bartels, S. A. L., et al. Gastrointest. Endosc. 76, 793–800 (2012)
Dawson, K., et al. Arch. Surg. 145, 826–830 (2010)
Bartels, S. A. L., et al. Gastrointest. Endosc. 76, 793–800 (2012)
Feo, C. V et al. J. Negat. Results Biomed. 14, 9 (2015)
• Bartels et al 95 tattooed patients; 210 non-tattooed as controls
• Median LN tattooed 15 (IQR 10-20) vs. non tattooed 12 (9-16) (P=0,014)
• Multivariante analysis: tattoo, specimen location, pT and pN stage (P<0,05)
Endoscopic tattooing for LN retrieval
To determine the usefulness of preoperative tattooing
• Colonic lesions (colon carcinoma and preinvasive lesions)
• Correlation with OSNA LN staging
Aim
• Colon carcinomas / adenomas May'12-Dec-'13
• Inclusion criteria:
+ 18 years old IHC CK19 +
• pT1 polyps with risk factors
• Unresectable adenomas
• pT1-2 colon carcinoma
• Exclusion criteria:
pT3-4 Rectal T. Appendicular Ca
Synchronic t. CC in IBD Other malignant tumours
Formalin Stent Adipose tissue involvement
Sample
• Screening (FIT) + → Colonoscopy
• Tattoo (median 63 days):
1. Polyps ≥ 2 cm
2. Suspicious lesions (excluding cecum/rectal)
• Unresectable polyps
• Suspected invasive submucosal carcinoma
• Partially resected advanced adenomas (> 10 mm,
villous, high grade dysplasia)
Endoscopic evaluation and tattooing
Results
(...)
15.3 % (44/286) tattooed LN
7.3 % (28/386) non-tattoed LN
OR 3.1
OSNA +
Results
• OSNA + 42/71 (59,2%) → cut-off 100 c/μL
• TTL median: 1.350 c/μL
• pN0 cases: 1.275 c/μL
• Two pN+ cases: 560.000 y 41.160 c/μL
• OSNA result associated to:
• Tumour size (P=0,02)
• High grade (P<0,01)
OSNA Results
• Median 984 days
• 2 pN+ cases → chemotherapy
• 2 cases → metastases at 4 and 21 months f/u
• pT2N0, Right c., low grade, 25 y 30 mm
1. No tattooed OSNA assessed 14/18 LN TTL 47,760 c/μL
2. Tattooed OSNA assessed 10/20 LN TTL 0
OSNA Results
Conclusions
• Colonoscopic tattooing highly efficient LN procurement
• Tattooing helps:
1. Endoscopist and the surgeon localize the tumour
2. Pathology tool to:
o Harvest a higher amount of LN
o Find those LNs which might shelter tumour
• Expansion of presurgical endoscopic tattooing
o Benefit patient’s diagnosis and therapeutic management
HE section
Neoplastic foci
Tissue allocation bias (TAB)
2-5 µm
Primary tumor5 year survival (%)
N0 / N1 / N2
T1 97.4 / 87.6 / 68.7
T2 96.8 / 87.7 / 76.6
T3 87.5 / 68.7 / 47.3
T4 71.5 / 50.5 / 27.1
Gunderson et al., JCO 28: 264-271, 2010
LN status
Micromtx
ITC
Sloothaak, D. A. M. et al. Eur. J. Surg. Oncol. 40, 263–269 (2014)
Occult disease in LN
But,
How much tumor does a LN have?
How do we quantify it?
H&E (conventional method) OSNA
(molecular method)
OSNA in breast SLN
Predictors of additional axillary metastases
Peg, V. et al. Breast Cancer Res. Treat. 139, 87–93 (2013)
Espinosa-Bravo, M. et al. Eur. J. Surg. Oncol. 39, 766–773 (2013)
Feasibility
Aim
To propose a new economical and effective
method of molecular lymph node analysis
in colorectal cancer for routine practice
H&E
≤600 mg
OSNA
Lymph node Pooling
Samples
• Colon carcinomas / adenomas
• Inclusion criteria:
+ 18 years old IHC CK19 +
CC Adenoma
• Exclusion criteria:
Rectal T. Metastatic disease
CC in IBD FAP Other malignant tumours
Formalin Stent Adipose tissue involvement
Neoadjuvant CT
– 86 CC / 1.757 LN OSNA
– Prospective (Feb 2015 - Dec 2015)
Cohorts: Pooling
– 102 CC cases/1.461 LN OSNA
– Retrospective (June 2012 - Dec 2013). Validation set
– *Excl. criteria cN1, gross metastatic LN
Cohorts: Individual
Clinical parameter n (%) / median (IQR) p-value
OSNA pooling
cohort
OSNA individual
cohort
Grade <0.001
High 49 (57.0) 26 (25.5)
Low 37 (43.0) 76 (74.5)
Vascular invasion 0.045
No 65 (75.6) 91 (89.2)
Yes 21 (24.4) 11 (10.8)
Perineural invasion 0.013
No 76 (88.4) 98 (96.1)
Yes 10 (11.6) 4 (3.9)
pT 0.004
pT0 6 (7.0) 8 (7.8)
pTis 6 (7.0) 17 (16.7)
pT1 9 (10.4) 26 (25.6)
pT2 16 (18.6) 19 (18.6)
pT3 32 (37.2) 24 (23.5)
pT4a 17 (19.8) 8 (7.8)
Results
Results
• Time spared: 2-3 hours/case
Results: Concordance with HE
Pooling
cohort (%)
Individual
Cohort (%)
Sens (pN+ and OSNA+) 88,9 100
Spec (pN0 and OSNA-) 79,2 44,6
PPV 33,3 16,4
NPV 98,4 100
Concordance 80,2 50
Internal validation test
• 42 cases LN collected in 2–7 tubes
• Sens 83.3%; spec 93.3%; agreement of 90.5% (k = 0.756)
• Discordant cases
↓
low TTL values
Conclusions Pooling Study
• Pooling allows analyzing a high number of LN with
few molecular determinations per patient
• This approach grants a cost-effective means of
introducing LN molecular analysis of CRC into
pathology departments
• Warrants a more accurate LN pathological staging
• The OSNA in CC must overcome different challenges:
– Feasibility
– Submitting the whole LN
– Characterization: tumor and patient
– Correlation of different prognostic factors
Perspectives
Citology (CK19) HE
Touch-prep. Five LNs/slide
Thank you
• RT-LAMP with/without Indian ink at 1:100
Indian ink – OSNA interference test
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