CME-CVL/D3 vs D2
LYMPHADENECTOMY in colon
cancer
Principles of resection of solid tumors
Surgery is the mainstay in CRC treatment
Resection of
• Primary tumor
• Draining regional lymph nodes
• Intervening lymphatics en-masse
Still holds good for colon cancer
Defining a standard template for radical
colectomy- A daunting task
Diverse variation of colonic morphology
size
vascular anatomy
Compounded with multiple sites of tumor location and morphology
Issues of radical colectomy?
Extent of Extent of
colectomy lymphadenectomy
Total Mesorectal Excision (TME)
A gold standard for mid and lower rectal cancer
Dr. Bill Heald- 1982
Plane of dissection in TME
Holy plane of Bill Heald
Under direct vision, sharp dissection of the
avascular plane between the mesorectum
and the surrounding parietal tissue.
Between the presacral fascia and
mesorectal fascia
Lower rates of local and distant recurrences, overall survival, cancer related deaths and a
higher rate of sphincter preservation
Complete Mesocolic Excision (CME)-
A derivative of Total Mesorectal Excision (TME)
Dr. Werner Hohenberger- CME- 2009
Components of CME
• Mobilization of the colon within the mesocolic plane
• Resection of an adequate length of bowel on either side of the primary tumour
• Central vascular ligation
1. Mobilization of the colon within the
mesocolic plane
Fascia in the abdomen
Visceral mesenteric fascia
(mesocolic fascia)
Avascular plane
Parietal fascia
(Gerota’s fascia/Waldeyers
fascia/ Dennonvillieur’s
fascia)
Sharp dissection of the visceral plane from the retroperitoneal plane avoiding any breach of the visceral
peritoneal fascia.
The specimen can be harvested as a package which contains the tumour providing arteries, the draining
vessels, the lymph nodes, and eventually other tumour deposits.
2. Extent of colectomy
How much colon is enough colon to remove?
What do the Japanese say?
The Japanese Society for Cancer of the Colon and Rectum (JSCCR) has
recently published a prospective, multicenter, cohort study aimed at defining the
extent of pericolic lymph node metastasis with respect to the primary tumor and the
primary feeding artery.
25 centres, 2996 patients, Stage 1-3 Colon cancer
The incidence of LN metastasis was highest in the primary tumour region (27.2%) and
decreased with increasing distance from the primary tumour.
There was no significant difference in the anatomical distribution of the positive pericolic
nodes between the proximal and distal sides (P = 0.41).
The incidence of metastasis in LNs located ≥7 cm from the primary tumour was <1% both
proximal and distal to the primary tumour.
Although the anatomical distribution of positive LNs was associated with the T stage, only 2
(0.1%) of 1443 patients with T3 tumours and 2 (0.4%) of 449 patients with T4a tumours had
positive pericolic nodes located >10 cm from the primary tumour.
Similarly, the incidence of patients with pericolic positive nodes located >5 cm from the
primary tumour was <1% in T1 tumours.
DISTANCE INCIDENCE OF LN METS
Primary tumor 27.2%
0-3cm 10.3%
3-5cm 4.3%
5-7cm 1.3%
7-10cm 1.1%
>10cm 0.1%
JSCCR recommends 10cm resection both proximal and distal to the primary tumor.
What do the Americans say?
American Society of Colon and Rectal Surgeons recommend a margin of 5–7 cm
on either side of the tumor.
The extent of resection of the colon should correspond to the lymphovascular drainage of the
colon cancer. Grade of recommendation: strong recommendation based on moderate-quality
evidence, 1B.
What do the Europeans say?
The Erlangen technique is generally more radical and usually includes removal
of the next vascular arcade beyond the 10-cm margin to ensure that no regional
pericolic nodes remain.
Right sided colon carcinoma– ileocolic, right colic and right branch of middle
colic artery are ligated.
Evidence in pipeline
An international prospective observational cohort study aiming to include 4000 patients
with stage 1-3 colon cancer.
Primary analysis- to identify the general principles of metastatic lymph node distribution in
terms of its relation to the location of the primary tumor and feeding arteries
Secondary analysis- to estimate prognostic outcomes according to bowel resection length
and central radicality
It is of the opinion that the results of the T-Rex study will further ratify the 10-cm margin
and establish it as a minimum standard of care (SOC) for radical colectomy.
3. Extent of central radicality
D1, D2 and D3- by JSCCR
D0- incomplete removal of pericolic lymph
nodes
D1- pericolic lymph nodes
D2- pericolic + intermediate lymph nodes
(includes the nodes upto but not
including the nodes at the root of the named
vascular pedicles)
D3- pericolic + intermediate + main lymph
nodes
(dissection lays bare the origin of the
vascular pedicles)
D3 removes the lymph nodes depending on the tumor location.
Method of assessment of quality
of specimen
A- distance from the tumor to the
high vascular tie
B- closest bowel wall to the high
vascular tie
C- length of the large bowel
D- area of mesentery
CME with CVL or D3 Lymphadenectomy- Are
we talking the same language?
•The literature has often used the terminologies D3 dissection and CME
interchangeably.
•Both have similar concept as regard mesocolic dissection plane.
•Both have equivalent distance from the high vascular tie to the bowel wall.
•CME procedure requires proximal vascular ligation, but does not specify
dissection at the origin of the feeding vessels.
•D3 removes the LNs depending on tumor location(main LN).
•CME technique is more radical because it includes removal of the nearby
vascular arcade beyond 10-cm margin. Hence, large area of mesentery is obtained
and longer bowel is resected.
Both produce good oncological specimen, further randomized studies are now required to assess the benefit of high
ligation and extended longitudinal resection in the context of pathologically quality-assured meso-colic plane
surgery.
CME with CVL / D3 lymphadenectomy
vs
D2 lymphadenectomy
Proposed benefits of CME CVL
Enhances the rate of complete removal of lymph nodes that may harbor the cancer
cells.
Stage migration
Greater lymph node ratio
Better prognostication
Improved survival
Greater the ration of negative to metastatic lymph node, better the prognosis.
CME vs Conventional resection
Long term outcome
In his initial paper, Hohenberger et al. demonstrated
• a decrease in the local recurrence from 6.5 to 3.6%
• an improvement in cancer-related survival from 82.1 to 89.1% with CME for right
colon cancer.
Long-term results from the same group showed a 10% reduction in local recurrence
at 5 years.
4 large centres in Denmark, 2008-2011, 364 CME and 1031 controls
R1 resection and stage 4 diseases excluded
Results- Improved overall 4yDFS[86% vs 76%, P=0.001]
Lower recurrence[11% vs 16%, P=0.028].
Multivariate analysis showed CME as a predictor of
survival for all patients (stage I-III)[P=0.0025].
31 studies: 26,640 patients (13,830 CME/D3 vs 12,810 conventional)
• Better 3, 5 year overall (p=0.016)
• Better 5 year disease free survival (p<0.001)
• No difference in perioperative complications
Quality of evidence regarding survival is low and RCT are required to strengthen
the evidence base.
29 studies were enrolled (2,592 patients)
CME and D3 had- more harvested lymph nodes.
Significant decrease in local recurrence
Significant improvement in 3 year and 5 year OS rates
Improving survival in patients with stage 2 and 3 disease
Conclusions- CME + D3 is a feasible surgical procedure that allows to obtain
specimens with higher quality oncological resection, without greater associated
morbidity, thus improving survival in patients with stage 2 and 3 right colon cancer.
CME – not without complications
CME vs Conventional resection
Short term outcome
RCT, Phase 3 trial
17 hospitals in China
455 CME, 500 D2
Intra operative vascular injury was significantly higher in CME group (3% vs
1%). But it generally seems to be safe and feasible with experienced surgeons.
Higher aspiration rate leading to severe respiratory failure and to higher mortality.
Patient selection for this procedure may therefore be crucial.
4 large centres in Denmark,
2008-2013
529 CME and 1701 controls
Higher intraoperative organs injury (9.1% vs 3.6%)
• Splenic injury (3.2% vs 1.2%)
• SMV injury (1.7% vs 0.2%)
Higher rates of sepsis with vasopressor requirement (6.6% vs 3.2%)
Higher postoperative respiratory failure (8.1% vs 3.4%)
Higher incidence of chyle leak (4% vs. 0%) probably related to the disruption of
small bowel lymphatics during dissection over the superior mesenteric vessels
Randomized control trials
Primary endpoints- operative time, intraoperative blood loss, other complications, conversion
rate, and anastomotic leak
Secondary endpoints - overall postoperative complications
Results- higher number of lymph nodes and larger surgical specimen
No difference in intraoperative blood loss, conversion rate, leakage, or other postoperative complications.
Conclusion- CME were a safe and feasible technique with improvement in lymph nodes
harvesting and length of surgical specimens with no increase of surgical intraoperative and
postoperative complications.
RCT, Phase 3 trial
17 hospitals in China
455 CME, 500 D2
Intra operative vascular injury was significantly higher in
CME group (3% vs 1%). But it generally seems to be safe
and feasible with experienced surgeons.
Issues?
1. The definition of the procedures used for Radical Right Colectomy (RRC) has
not been consistently used. Studies have been describing the technique used
with different names, e.g. “CME”, “CVL”, “D3” and their variants. Until this
question is solved, reliability of results presented and especially their
comparison and generalizability remain poor.
2. Quality of evidence regarding survival is low and more RCTs are required to
strengthen the evidence base.
3. It has been noted that most of the comparative studies do not report an
increased postoperative morbidity with CME.
Morbidity has to be characterized in a more objective manner but is not accessible
throughout all studies. There is no consistencies regarding morbidities.
Implementing complete mesocolic excision
for colon cancer – mission completed?
The surgical resection of colon cancer continues to lack international
standardization, unlike rectal cancer, for which TME is considered the optimum
operation.
From the evidence presented above a D2 dissection, i.e. until the root of the named
vascular pedicles is essential for all radical colon resections but whether or not the
SMA/SMV (for right colon lesions) and the aorta (for left colon lesions) needs to be
laid bare in every colectomy, as a routine SOC, remains unanswered.
Although the incidence of nodal positivity of the root nodes varies from 3 to 5%,
nodal mapping studies show that the incidence of root nodal positivity is associated
with the T stage of the primary tumor with a zero incidence in T1 tumors.
D3 lymphadenectomy for colon cancer definitely has a place in radical colectomy,
but further studies are needed to accurately identify the patient group in whom it is
beneficial.
Thank you