Review for 10.1186/s12876-020-01543-1 (2020)

Reviewer’s report
Title: 
Severe weight loss after minimally invasive oesophagectomy is associated
with poor 5-year survival in patients with oesophageal cancer
Version: 
1 
Date: 
01 Jul 2020
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
No - there are minor issues
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Not sure - I am not able to assess the statistics in this study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
* What is your overall impression of the study?
Satisfactory conduct and design (with limitations due to the retrospective
design), the reporting has some issues which I detail below.
* What have the authors done well?
A useful addition to a growing body of evidence that severe weight loss after
esophagectomy is a predictor for poor outcomes (survival).
* In what ways does it not meet best practice?
Minor: I think more needs to be made of similarities and differences between
existing studies. 
It is interesting that severe weight loss is emerging as an
important predictive factor of poor survival, regardless of type of
oesophagectomy. 
Major: retrospective study design 
- 
however, for a first report, this is not an
issue, as the limitations of the study have been described in the Discussion, but
this needs to be a addressed in future studies.
The reporting has several omissions and inconsistencies which should be
rectified.
REQUESTED REVISIONS: 
Objective acceptable?
No - minor issues which I think are due to inconsistencies and omissions in the
reporting, e.g., of the variables under investigation. 
Without clarity in the aims/objectives, it is unclear, on reading the paper in detail
whether weight loss is the only variable associated with poor survival after MIE.
This could be rectified by clearly stating the aims and objectives in the Methods.
E.g., "We wanted to determine whether severe weight loss after MIE was
associated with survival outcomes 
(state which, overall, disease free, progression
free) at 3- and 5-year post-operative follow up in patients with oesophageal
cancer, by collecting data from patients in our centre who underwent MIE. 
We
investigated the following variables (state which) using multivariate analysis."
Design acceptable?
No - there are minor issues. 
The study has been carried out to acceptable
standards, but it is retrospective in design and therefore prone to biases.
The outcomes and time points should be stated in the methods section--overall
survival, cancer-free survival, and progression-free survival, at 3 and 5 years.
The 
variables under investigation should also be listed in the Methods section (at
present only listed in the paragraph on propensity score matching).
Execution acceptable?
No - there are minor issues related to the retrospective design. 
Statistics acceptable?
Not sure - I am not able to assess the statistics in this study.
I have not commented on the statistics in detail as this is best left to medical
statisticians. The methods used (univariate and multivariate analysis) appear to
be appropriate. 
The variables under investigation should also be stated in the methods section--
age, sex, tumour location, and preoperative body weight. The numbers or
percentage of deep, tumour invasion (cT3-4) and the number of patients who
underwent preoperative therapy, feeding tube placement should be more clearly
stated in the text.
Interpretation acceptable?
No - minor issues.
Abstract: The data presented in the abstract (Hazard ratios) does not match the
data presented in the text of the results section (percentages). 
Please amend the
abstract and provide short descriptions of the results in the figures and tables in
the results section. 
Please ensure that the results sections and abstract are
consistent.
Methods: 
"patients were classified into the severe weight loss and moderate
weight loss groups." - on what basis was the classification made? What was the
cut-off point for each group? 17% is mentioned, but it is unclear what this refers
to.
Minor: There are minor issues relating to the discussion of the results in relation
to existing studies - I have detailed this elsewhere in my review. 
Major: I note that tumour invasion depth was a predictor of poor outcome in
univariate and multivariate analysis - this is not mentioned in the abstract or the
Discussion. This is a major omission and should be corrected in the manuscript. 
Additional: Three outcomes are investigated , overall survival; cancer-specific
survival; progression-free survival. 
However, only OS is described in any detail,
and this is an omission that should be corrected in the Results, Abstract, and
Discussion.
Results: 
Please provide short descriptions of the results in the tables and figures in the
results section text and ensure that the abstract is consistent with the results
section.
Propensity score matching 
- please provide a very short description of what this
is. 
I would have liked a slightly more detailed description in the Results section
on the baseline clinical characteristics of the patients in addition to the tables.
"The two groups were comparable in terms of age, sex, tumour location, tumour
invasion depth, lymph node metastasis, FT placement, preoperative body weight,
anastomotic leakage incidence, and frequency of recurrent laryngeal nerve
palsy." This information is not enough to fully describe comparability between
the two groups at baseline.
(I did not receive copies of the tables/figures with my manuscript so I cannot
comment on the figures or tables).
I would have liked to see more in the Results text about the outcomes at the 3-
and 5-year follow-up time points, it was difficult to determine which time point
each result related to.
Having these longer time points is a significant addition to the available
evidence, and the authors could add this detail to the title and abstract. Suggest
revised title: 
"Severe weight loss after minimally invasive oesophagectomy is
associated with poor survival in patients with oesophageal cancer at three and
five years".
Discussion: The findings of this study are not completely novel, as prognostic
impact of weight loss after oesophagectomy has been studied before. E.g., ref 28
D'Journo et al. 
This study has some novel aspects in that it concerns MIE rather
than transthoracic esophagectomy patients. However, I would have liked the
Discussion to compare and contrast the findings of this study with other studies,
to demonstrate what may be different about MIE compared with traditional
esophagectomy approaches and what the similarities are. 
From the evidence that
this author team presents, severe weight loss after esophagectomy by any route,
even minimally invasive, is a prognostic factor for poor outcome.
I also think that the data presented regarding overall survival rates in patients
with and without feeding tube placement is interesting. 
"No differences in the
overall survival (OS) rates were observed between the FT group (blue line) and
the no-FT group (red line)." This result has the potential to change clinical
management significantly, and this result could be highlighted in the Discussion
- as an area where further research needs to be done. 
The paragraph in the discussion on limitations is good; however; I would like a
short description of how future research could be conducted - prospective and
perhaps comparing two cohorts MIE and transthoracic approaches, for example,
to provide further information about whether the approach is important or
whether severe weight loss is a universal factor which would predict poor
outcome and could therefore be addressed early on during recovery for all
patients.
The authors state that "Hence, further optimisation of nutritional support and
postoperative exercise is required." - could they describe how clinical
management might be optimised in the meantime, until further evidence is
available?
This is an interesting paper; however, the reporting is inconsistent. 
The authors
have not really done justice to the work they have carried out, as 
a number of
findings are incompletely reported, such as the relationship of tumour invasion
depth to poor outcome.
The findings reported here elicit further questions 
- Is tumour invasion depth
always prognostic for severe weight loss after surgery? What is the 
relationship
between tumour invasion depth and severe weight loss - poor overall status in
the patient? Or is it truly an independent factor? If we can identify patients at risk
of severe weight loss at the outset, can they be provided with effective nutritional
support pre- and post-operatively?
It may not be possible to address these uncertainties, given the data (and word
count) that the authors have, but these questions do impact upon clinical
management. 
The Discussion could go some way in addressing these issues, if
only to state that we do not have sufficient evidence to answer this yet and how
future studies could provide specific data to help provide answers.
ADDITIONAL REQUESTS/SUGGESTIONS: 
Additional revisions
Suggest: After oesophagectomy, many patients have reduced [their] appetite and
oral intake, which leads to severe weight loss.
I prefer the use of 'organised' into groups rather than dividing patients. 
It is only a
small issue.
"In this study, we could not reveal that enteral nutrition via FT improved the
incidence of severe weight loss and the OS in patients after MIE." 
I suggest
'demonstrate' rather than 'reveal'.
MIE or MIO? 
If it is 'oesophagectomy' rather than 'esophagectomy'.
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No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
No
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
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