Review for 10.1186/1471-230X-12-24 (2012)

Reviewer's report
Title:Metachronous metastases- and survival-analysis show prognostic
importance of lymphadenectomy for colon carcinomas
Version: 2Date:16 December 2011
Reviewer: Karl Sondenaa
Reviewer's report:
The major issue in this study is if lymph nodes make mets. That may seem a bit
odd because mets kill patients, being the major disadvantage of cancer. If the
statistics show a discrepancy between mets and survival variables the authors
should offer an explanation under Discussion since the statsitical models are
fundamental in the explanation of the findings in this study. E.g. N-category and
UICC stage were not signiificant for survival, only mets. Most other studies would
report that TNM stage is a major prognostic factor for overall survival (OS). May
the influence of age and sex point to other explanations for poor outcome? OS
certainly has shortcomings when it comes to a proper understanding of factors
that are important for survival. Relative survival and cancer specific survival may
contribute to a better analysis.
The authors have found that N+ was important for mets (p. 12) but not survival
(p13), and in the last paragraph they conclude they conclude that a standard
dissection of lymph nodes can be defended until proven otherwise. Do they
mean then that distant mets are not important tfor survival or that other factors
than N+ are important to the metastastic process?
Several studies have considered if a radical lymph node dissection (high tie or
D3) is of benefit in TNM II patients. However, in stage III not only increased
survival is an aim but also reduction of local recurrence. At least in that respect it
makes sense in stage III patients. Several centers now adhere to the policy of
radical, complete mesocolic excision (dissection) (CME) and removal of apical
lymph nodes and they have reported improved results. A discussion of this would
therefore seem appropriate.
Rather than focus on number of lymph nodes that may depend on several
factors, and may be seen only as a surrogate measure of radicality, an emphasis
on the importance of CME is warranted.
Many things in medicine are hard to prove and there are believers and
non-believers. The authors should explain why they think it is important to
demonstrate that lymph nodes may be or not be the origin of distant mets. The
main problem is rather if removal of lymph nodes without mets have an impact on
the disease development. In this respect I think the discussuion is a bit skewed.
In my opinion mets occur early as an inherent capacity of the main tumour
although most with distant mets also have lymph node mets. To prove a
connection would perhaps need more indepth studies. What goes on in all stages
in the mesocolic lymph nodes in the draining area of tumours?
The so-called upstaging has not been proven as long as an adequate number of
lymph nodes are removed. In fact, many reports include at most 45% TNM III in
any cohort and on average 3-4 positive lymph nodes per specimen no matter
how hard they search for mets.
T should be called category, not stage.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
My own interest in the field of colon cancer is asociated with a research project of
the utility of CME and radical lymph node dissection, see below:
Sundlisæter E, Dicko A, Sakariassen PØ, Sondenaa K, Enger PØ, and Bjerkvig
R. Lymphangiogenesis in colorectal cancer - Prognostic and therapeutic aspects.
Review. Int J Cancer 2007; 121: 1401-1409.
Sundlisæter E, Røsland GV, Sakariassen PØ, Almaas B, Dicko A, Søndenaa K.
Elevated lymphatic vascular density is established prior to Stage II colorectal
cancers, and FGF-2 is down-regulated in tumour tissue. APMIS 2009; 117;
212-221.
Storli K, Lindboe CF, Kristoffersen C, Kleiven K, Søndenaa K. Lymph node
harvest in colon cancer specimens depend on tumour factors, patients and
doctors but foremost on specimen handling. APMIS 2011; 119 (2): 127-134.
Dicko A, Jacobsen H, Wang J, Storli K, Leh S, Thorsen F, Bjerkvig R, Søndenaa
K, Pedersen P-H, Gullberg D, Enger PØ. Orthotopic xenograft tumors
established from human colon cancer biopsies in GFP NOD/Scid mice mimic the
histopathological features of the patient tumors.
Storli K, Søndenaa K, Bukholm I, Nesvik I, Bru T Furnes B, Hjelmeland B,
Iversen K, Eide GE. Overall survival after resection for colon cancer in a national
cohort study was adversely affected by TNM stage, lymph node ratio, gender,
and old age. Int J Colorectal Dis 2011; 26: 1299-1307.
Storli K, Søndenaa K, Furnes B, Leh S, Nesvik I, Bru T, Gudlaugsson E,
Bukholm I, Norheim-Andersen S, Eide GE. Improved lymph node harvest from
resected colon cancer specimens did not cause up-staging from TNM stage II to
III. World J Surg 2011, 35(12): 2796-2803.