40. Not the type of surgical treatment but neoadjuvant treatment influences overall survival in patients with gastro-oesophageal junction tumours in the Netherlands

S24 ABSTRACTS

No conflict of interest.

http://dx.doi.org/10.1016/j.ejso.2014.08.034

38. Intraoperative sentinel lymph node detection in gastric cancer

using near-infrared fluorescence imaging and indocyanine green

coupled to nanocolloid

Q. Tummers1, L. Boogerd1, W. Steur1, F. Verbeek1, M. Boonstra1,

H. Handgraaf1, C. Hoogstins1, C. van de Velde1, A. Vahrmeijer1,

H. Hartgrink1

1 Leiden University Medical Center, Afdeling Heelkunde K6-R, Leiden,

Netherlands

Background: The extent of lymph node dissection in gastric cancer is

subject of debate and the sentinel lymph node (SLN) procedure is being

widely investigated. A SLN procedure could avoid an unnecessary lym-

phadenectomy when no tumor positive lymph nodes (LNs) are present

and can assist in identifying potentially involved LNs that our outside

the standard resection specimen.

Near-infrared fluorescence (NIRF) imaging is an innovative technique

to visualise lymphatic channels and lymph nodes. Previous studies already

proved the use of indocyanine green (ICG) in SLN mapping in gastric can-

cer, but showed detection of many fluorescent LNs and an extensive lym-

phadenectomy was still needed. Binding ICG to a nanocolloid increases its

hydrodynamic diameter, which results in better retention in the SLN. The

aim of this study is to investigate feasibility of ICG coupled to nanocolloid

as a lymphatic tracer and to determine accuracy of the SLN procedure in

gastric cancer patients.

Methods: Twenty patients with gastric cancer, planned for a (partial)

gastrectomy, were included. Patients received 1.6ml ICG:nanocoll (0,1

mg Nanocoll and 0,05 mg ICG) subserosally in four quadrants around

the tumor. During surgery, lymphatic pathways and SLNs were visualized

using the Mini-Flare camera system. All hotspots detected within 15 mi-

nutes after injection were identified as SLN, other hotspots as 2nd tier no-

des. Patients underwent a standard-of-care (partial) gastrectomy. After

resection the specimen was inspected again using the camera system.

Marked hotspots were analysed separately for tumor status.

Results: Median age was 64 years (range: 30-86 yr). Three patients

were excluded during surgery because of distant metastases and one pa-

tient was excluded of further analysis due to technical failure of the injec-

tion. In 15/16 remaining patients, at least 1 SLN was detected by NIRF

(mean: 2.1 SLNs per patient). In 4/16 patients tumor positive LNs were

found. Accuracy of the technique was 87%, which decreased by T-stage

of the tumor (100%, 100%, 100%, 75%, 0% for respectively Tx, T1, T2,

T3, T4 tumors). Mean ratio of the fluorescence signal between SLN and

surrounding tissue was 4.6 (range 1.7-19.8). In 4 patients SLNs were found

which were located outside standard dissection margins.

Conclusion: The current study is the first which proves successful use

of ICG:nanocoll as a lymphatic tracer for SLN detection in gastric cancer

patients. Especially in gastric cancer with low T-stage the SLN procedure

can be used for predicting lymph node tumor status. Also, potential

involved LNs outside the standard lymph node dissection margins can

be identified by this technique.



39. A novel methylation biomarker for oesophageal adenocarcinoma

M. Dilworth1, A. Beggs1, R. Hejmadi2, D. Alderson1, G. Matthews3,

O. Tucker1

1 University Hospital Birmingham, Academic Department of Surgery,

Birmingham, United Kingdom2University Hospital Birmingham, Department of Cellular Pathology,

Birmingham, United Kingdom

3 University of Birmingham, School of Cancer Sciences, Birmingham,

United Kingdom

Background: Worldwide, oesophageal adenocarcinoma (OADC) is

increasing in incidence. The inflammatory environment in which OADC

develops in the lower oesophagus is likely to result in epigenetic rather

than genetic changes. As yet, no robust biomarker for OADC exists. We

present our analysis of the Tumour Cancer Genome Atlas (TCGA) methyl-

ation data for OADC and our validation experiments to produce a novel

biomarker.

Materials and methods: Methylation data was extracted from the

recently published TCGA database, and analysed using a Bayesian linear

regression method. Differences in methylation profiles were compared be-

tween normal oesophageal squamous tissue and OADC.

Identified markers of interest were analysed using bisulfite pyrose-

quencing in 24 matched tumour and normal formalin fixed oesophageal

resection specimens with 8 matched Barrett’s oesophagus samples. An

additional 9 internal and 7 external matched tumour and normal formalin

fixed OADC resection specimens were analysed separately as a validation

set (power calculation at 99% proposed n¼6 samples for second round

validation).

Results: Analysis of the TCGA dataset probes tagging TRIM15 were

significantly hypermethylated 33 times, which meant that TRIM15 was

significantly over-represented in the probe set, suggesting it is an important

biomarker differentiating the two tissues. The top rated probe cg09769113

reached high significance and was ranked number 2 in the list of signifi-

cantly differentially methylated genes (BF ¼ 27.97, p¼7.26x10-12).

We validated our findings on an in-house sample set consisting of 24

samples of oesophageal adenocarcinoma, 24 matched normal mucosa

and 8 samples of Barrett’s metaplasia (an intermediate pre-malignant

lesion in oesophageal cancer). We quantified methylation levels at

TRIM15 via bisulphite pyrosequencing of 6 CpG’s within +100bp of the

start of the CpG island associated with TRIM15. We found that there

were significant differences (p<0.001) between tumour and normal sam-

ples at all CpG’s, and significant differences between Barrett’s metaplasia

and normal tissue (p<0.001). Using metaplasia & cancer together,

compared to normal mucosa, methylation at TRIM15 had a C-statistic of

0.91 (95% CI 0.88-0.99) in discriminating malignant and pre-malignant le-

sions from normal mucosa in the oesophagus.

Conclusions: Our data suggest that TRIM15 may be a methylation

biomarker for OADC. Further investigation of the functional significance

of this methylation marker is ongoing.



40. Not the type of surgical treatment but neoadjuvant treatment

influences overall survival in patients with gastro-oesophageal

junction tumours in the Netherlands

M. Koeter1, L. Haverkamp2, K. Perry2, R.H. Verhoeven3,

V.E.P.P. Lemmens3, J.P. Ruurda2,M.D.P. Luyer1, R.VanHillegersberg2,

G.A.P. Nieuwenhuijzen1

1 Catharina Hospital, Surgery, Eindhoven, Netherlands2 University Medical Centre Utrecht, Surgery, Utrecht, Netherlands3 Netherlands Cancer Registry, Research, Eindhoven, Netherlands

Background: There may be two different therapeutic strategies for

patients with resectable gastro-esophageal junction (GEJ) tumours.

Either, they are treated as an esophageal tumour with neoadjvant chemo-

radiation and a subsequent esophagectomy or as a gastric tumour with

perioperative chemotherapy and a gastrectomy. According to the

TNM classification, GEJ tumours with the epicentre within 5cm of the

GEJ and extension into the esophagus should be staged according to

the esophageal classification. Whereas, GEJ tumours within 5 cm of

the junction without extension into the esophagus should be staged ac-

cording to the gastric classification. The objective of this study was to




ABSTRACTS S25

determine the patterns of care for resectable GEJ tumours in the

Netherlands and to compare oncological outcome with the different treat-

ment regimes.

Material and methods: All patients with resectable GEJ tumours (T1-

3, N0-1, M0) diagnosed between 2000-2011 that were treated with either

an esophagectomy or gastrectomy (n¼1277) were selected from the pop-

ulation based Netherlands Cancer Registry. Differences between patients

receiving an esophagectomy or a gastrectomy were compared using the

chi-square test. Unadjusted estimates of survival rates were made using

the Kaplan-Meier method. Overall multivariate survival was performed

with Cox regression analyses.

Results: Patients treated with an esophagectomy (n¼970) were

significantly younger than patients treated with a gastrectomy (n¼307)

64 vs. 67 years (p<0.001). Furthermore, patients treated with esophagec-

tomy received neoadjuvant chemoradiation more often. Kaplan-Meier

analysis showed no survival differences between patients treated with

an esophagectomy or with a 5-year survival of 31 vs. 34%, respectively

(p¼0.97). Kaplan-Meier analysis showed a significant 5 year survival dif-

ference (p <0.001) between esophagectomy with chemotherapy (39%),

esophagectomy with chemoradiation (38%), gastrectomy with chemo-

therapy (42%), gastrectomy with chemoradiation (40%), esophagectomy

alone (28%) and gastrectomy alone (30%). Multivariate analyses showed

that older patients (>70years) had a worse overall survival (OR 1.3

CI 1.1-1.5). Patients receiving neoadjuvant chemotherapy (OR 0.7 CI

0.6-0.8) or chemoradiation (OR 0.8 CI 0.6-1.0) had a significantly better

overall survival. Multivariate analysis showed no significant difference

between patients treated with an esophagectomy or gastectomy

(p¼0.744).

Conclusions: Type of surgery (esophagectomy or gastrectomy) did not

show any survival difference in the treatment of patients with a GEJ

tumour. Although this is a population based study with possible confound-

ing factors, the administration of neo-adjuvant treatment appeared to be

associated with an improved survival.



41. The influence of delaying surgery for esophageal adenocarcinoma

after neoadjuvant chemoradiotherapy on postoperative outcome

N. Kathiravetpillai1, M. Koeter1, M.J.C. Van der Sangen2,

G.J. Creemers3,H.J.T. Rutten1,M.D.P. Luyer1,G.A.P. Nieuwenhuijzen1

1 Catharina Hospital, General Surgery, Eindhoven, Netherlands2 Catharina Hospital, Radiation Oncology, Eindhoven, Netherlands3 Catharina Hospital, Medical Oncology, Eindhoven, Netherlands

Background: The preferred treatment for cT1-3,N0-3,M0 esophageal

carcinoma is neoadjuvant chemoradiotherapy (nCRT) followed by esoph-

agectomy. The literature reports that esophagectomy is preferably per-

formed within 3 to 8 weeks after nCRT. In practice, however, surgery is

often delayed because of the patient’s condition. A few studies have

described delaying surgery in patients with esophageal squamous cell car-

cinoma, but little is known about time to surgery (TTS) in patients with

esophageal adenocarcinoma (EADC). The aim of this study was to eval-

uate whether timing of surgery has an effect on peroperative and postoper-

ative course, long-term survival and pathologic response in patients who

were treated curatively for EADC.

Materials and methods: We retrospectively included patients from a

prospectively obtained database. Patients were treated for EADC (cT1-3,

N0-3, M0) between 2001 and 2013. Treatment consisted of nCRT followed

by esophagectomy. Patients were divided into a group in which TTS was 8

weeks or less and in a group in which TTS was more than 8 weeks.

Results: Of 179 included patients, 65 had a TTS of � 8 weeks and 114

a TTS > 8 weeks, the median TTS was 50 and 70 days respectively. The

groups did not differ in age, sex, clinical T stadium, tumor location, weight

loss on diagnosis and need for enteral tube feeding after nCRT. Patients

with TTS > 8 weeks had significantly higher ASA scores and more co-

morbidities. No difference was observed in peroperative complications,

hospital stay and ventilation time. There was a trend towards more anasto-

mosis-related complications (20.0% vs. 32.5%, p ¼ 0.074) and complica-

tions with Clavien Dindo score � IIIb (13.8% vs. 22.8%, p ¼ 0.146) in

patients with a TTS > 8 weeks. More re-interventions (16.8% vs. 29.8%,

p ¼ 0.056) took place in patients with a TTS > 8 weeks. Multivariate an-

alyses, however, showed no significant effect of TTS on anastomosis-

related complications (95%CI [0.21-1.07], p ¼ 0.07) or re-interventions

(95%CI [0.23-1.26], p ¼ 0.16). There was no difference in pathologic com-

plete response (pCR) (32.3% vs. 25.7%, p ¼ 0.358). Mean survival was

4.97 years in patients with a TTS � 8 weeks and 4.91 years in patients

with a TTS> 8 weeks (p¼ 0.850), 5 year survival was 37% in both groups.

Mean disease free survival was 5.77 and 5.51 years respectively (p ¼0.831).

Conclusion: Our study showed a trend toward more anastomosis-

related complications and re-interventions in patients with a TTS > 8

weeks, but multivariate analysis showed no significant effect of TTS.

Higher ASA scores and co-morbidities in patients with a longer TTS

may play a role in this observation. More research is needed to evaluate

the safety of a longer TTS.



42 . Op t im i s i n g an enhanc ed re cov e ry prog ramme fo r

oesophagectomy: A stepwise evolution

S. Wood1, G. Morris-Stiff2, K. Barton1, A. Hassn1

1 Princess of Wales Hospital, General Surgery, Bridgend, United Kingdom2Cleveland Clinic, General Surgery, OH, USA

Background: Enhanced recovery after surgery (ERAS) programmes

are designed to reduce complications whilst improving patient recovery

times and are established for several resectional procedures. Consensus

on an optimal oesophagectomy ERAS program does not exist and there

is significant variation in the clinical practice of its components. We

describe the experience and outcomes of an evolving ERAS program for

oesophagectomy.

Methods: A retrospective review was performed of a prospectively

created database for patients undergoing oesophagectomy for malignancy

over a four year period in a District General Hospital. Patient data was an-

alysed for type of procedure and ERAS interventions, post-operative com-

plications and clinical outcomes.

Results: During the four year period 57 oesophagectomies were per-

formed of which 53 were hybrid minimally invasive procedures, 2 totally

minimally invasive and 2 open resections. ERAS interventions and pro-

tocol changes were introduced incrementally over the study period

and included preoperative counselling, laparoscopic approach, minimis-

ing pleural drainage (number of chest drains and length of drainage),

early oral intake / nutrition, optimising analgesia delivery (intercostal

blocks, reduced use of epidural analgesia) and early mobilisation. Over-

all, there was one death (1.9% mortality rate), one anastomotic leak,

one chyle leak, one wound infection and one postoperative bleed, result-

ing in 2 reoperations (3.8%). Median length of stay was 8 days (range

3 e 40) with the most recent protocol expected length of stay being 4

days.

Conclusions: Our experience demonstrates that a stepwise introduction

of ERAS ‘type’ interventions is a safe and effective way of optimising re-

covery after oesophagectomy. In the absence of evidence-based guidelines

or recommendations this method allows continual evolution and improve-

ment of surgical management and outcomes for patients undergoing major

resectional surgery.






Documents

40. Not the type of surgical treatment but neoadjuvant treatment influences overall survival in patients with gastro-oesophageal junction tumours in the Netherlands