Review for 10.1186/s12876-018-0880-1 (2018)

Reviewer ’s report  
 
Title:  Feasibility of a 20 -gauge ProCore needle in EUS -guided subepithelial tumor sampling: a 
prospective multicenter study  
 
Version: 0 Date: 27 Aug 2018 
 
Reviewer:  Per Hede nstrom  
 
Reviewer’s report:  
 
Comments by the reviewer:  
 
Summary:  
 
The current manuscript is a prospective study investigating the sampling feasibility and the 
diagnostic yield of a 20 gauge endosonography -guided biopsy needle ( EUS -FNB) with a coiled 
sheath in the context of subepithelial lesions (SEL) > 2 cm. The study design is interventional 
but the study lacks a reference group for comparison. The primary study outcome was the 
diagnostic sufficiency. The secondary outcomes we re the technical and diagnostic failure rate 
and the complication rate.  The study was registered in the clinicaltrials.gov -database.   
 
Over an eight month period a total of 39 study participants were recruited and sampled whereof 
36 participants were inc luded in the final analysis. The authors report the EUS -FNB procedure to 
be feasible in all cases and diagnostic in 89% of the lesions. The technical failure rate and the 
complication rate are reported low. The authors conclude that the EUS -FNB 20 gauge sa mpling 
procedure is technically feasible and effective in the diagnosis of gastrointestinal subepithelial 
lesions > 2 cm.  
 
 
General comments:  
 
Even though there are a growing number of publications on EUS -FNB performed in 
subepithelial lesions, the study to pic is of interest and merits attention since SELs are considered 
difficult and challenging to diagnose by most endosonographers. Furthermore, there is a growing 
number of EUS -needles available on the market, which all should be subjected to scientific 
evaluation. There exists a publication with a retrospective design investigating the current 20 
gauge Procore FNB -needle (Antonini Endoscopic Ultrasound 2018) but to the best of this 
reviewer's knowledge no existing study has an identical prospective design.  
 
The manuscript is well written but should improve with some minor language editing. The 
different sections were understandable and the results were acceptably discussed with respect to 
the current literature. However, there are some issues and points that  need clarification and that 
may benefit from revision.  
 
 
Specific comments and questions:  
 
1: When reading the manunscript in its current form it is not evident if the conclusive 
immunostaining pattern of the lesions was required to classify the EUS -FNB sample as 
diagnostic. The authors need to be more precise and specific on this issue. In gene ral, a sample of 
a subepithelial lesions with the inconclusive immunostaining pattern cannot be considered as 
diagnostic. As an example GISTs and leiomyomas are not possible to differentiate from one 
another without the conclusive immunohistochemistry.  
 
2: Did the authors apply the STARD document designed for diagnostic studies? If so, please 
specifiy. If not, please argue why not.    
 
3: Exclusion criteria. Why where lesions < 2 cm excluded from the study? There are other 
studies that have included lesions  smaller than 2 cm and sampled such lesions with success. 
GISTs may originate from the muscularis mucosae layer. Where there any such lesions referred 
for EUS but excluded in the current study?  
 
4: Is it motivated to use the larger 20 gauge Procore -needle (potentially more difficult to 
maneuver in the duodenum) when the thinner 22 gauge Procore -needle can provide a similar 
diagnostic sensitivity? There is an existing publication (Hedenström et al Surgical Endoscopy 
2018) investigating the 22 gauge Procore -needle and reporting a diagnostic sensitivity in SELs of 
90 % with a low adverse event rate. The authors should consider to compare and discuss their 
results with respect to this study or any comparable prospective study.  
 
5: The method's paragraph "Histolo gical analysis" would benefit from some revision. It would be 
easier to the reader if the paragraph could be split into two. First part = procedures performed on -
site by the endosonographer and the endoscopy staff. Second part = procedures performed by the  
pathologist in the pathology department including the different immune -antibodies used.  
 
6: Regarding the reference standard (page 7, line 143), the authors state that "Otherwise, 
histopathological assessment of the FNB samples was deemed to be the gold s tandard." When an 
FNB -sample is positive for malignancy this approach may be acceptable, but it could be a bit 
problematic if the FNB -sample is negative for malignancy. In most scenarios You would expect 
a period of clinical follow -up to rule out obvious m alignancy. In the current study, was there any 
period of follow -up in the case of a negative FNB -sample and if so, how long?  
 
7: According to the methods section the primary outcome parameter is the "diagnostic 
sufficiency", which is not commonly used in the EUS -literature. Such a parameter might still be 
appropriate to use if the parameter is well defined. Nevertheless, the abstract, as it now stands, 
does not use the expression "diagnostic sufficiency" to present the results but instead says "EUS -
FNB was  diagnostic in 88.9 % of SETs". Most readers would interpret that as the diagnostic 
sensitivity or the diagnostic accuracy of EUS -FNB. Meanwhile, such an outcome parameter is 
lacking in the methods section, which is a little bit confusing. Likewise, the "t issue adequacy" is 
presented in the abstract but this expression is lacking among the outcome parameters. The 
authors need to clarify this matter and be consistent throughout the manuscript, also in the results 
section.  
Please also be consistent regarding  the secondary outcome parameters, use the expressions 
"technical/diagnostic failure rate and the adverse event rate" identically in the methods section 
and in the results section (page 9, line 191 -195).  
 
Yet two terms, "the diagnostic yield" and "the diagn ostic rate", are used to present and discuss 
the data (page 10, line 198/206 and page 11, line 232). The diagnostic yield and the diagnostic 
rate may be an appropriate terms to use when presenting study data but in the current manuscript 
it is unfortunate due to the use of several other outcome parameters. Please try to rephrase and 
use a minimum number of expressions to present the data.  
 
8: The statistical analysis. The first two phrases (page 8, line 157 -160) may contain a 
miscalculation? A dropout rate of 20 % in 38 patients (~8 patients) should result in 30 patients 
remaining and not in 32 patients remaining. Please check the numbers.  
 
9: Page 10, line 210: "Our findings suggest that the 20 -gauge 210 ProCore needle may yield 
optimal core tissue samples with fewer needle passes". Page 13, line 279 -281: "In conclusion, 
EUS -FNB using a 20G ProCore needle is a technically feasible, safe, and 280 effective modality 
for histopathologic diagnosis of gastrointestinal SETs larger than 2 cm, providing adequate 
tissues core with less needle passes".  
 
Regarding both phrases - Compared with what?  
 
10: Some data in the first part of the results section is identical to the data presented in Table 1 
and could therefore be remowed from the manuscript text.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn  adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is r ecommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, ei ther now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating  to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing inte rests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
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