Review for 10.1186/s12876-016-0518-0 (2016)

Reviewer ’s report  
 
Title: Malignant pancreatic serous cystic neoplasms: systematic review with a new case  
 
 
Version: 0 Date: 06 Mar 2016  
 
 
Reviewer: Kevin  El-Hayek  
 
Reviewer's report:  
 
This is a nice review and additional case in the literature describing the entity of malignant 
serous cystic neoplasms (SCNs). It would be helpful for the authors to address a few 
comments/questions as listed below. By addressing these critiques, I believe the ove rall merit of 
the manuscript will increase and it will be suitable for publication.  
 
1. Background: It would be helpful to list the generally accepted rates of malignant SCNs when 
taking into account all SCNs. Many authors have this at less than 1%, wherea s others have it 
from 1 -3%. (Khashab MA, Shin EJ, Amateau S, Canto MI, Hruban RH, Fishman EK, et al. 
Tumor size and location correlate with behavior of pancreatic serous cystic neoplasms. Am J  
Gastroenterol 2011;106:1521 -6. Malleo G, Bassi C, Rossini R, Ma nfredi R, Butturini G, 
Massignani M, et al. Growth pattern of serous cystic neoplasms  
of the pancreas: observational study with long -term magnetic resonance surveillance and 
recommendations for treatment. Gut 2012;61:746 -51. Galanis C, Zamani A, Cameron JL , 
Campbell KA, Lillemoe KD, Caparrelli D, et al. Resected serous cystic neoplasms of the 
pancreas: a review of 158 patients with recommendations for treatment. J Gastrointest Surg 
2007;11:820 -6.) 
 
2. Background: I also think it would be helpful to list the  overall incidence of SCNs in relation to 
pancreatic cystic neoplasms. Several authors note that roughly 10 -15% of all pancreatic cystic 
neoplasms are SCNs and 1 -2% of all these lesions are SCNs. (Horvath KD, Chabot JA. An 
aggressive resectional approach t o cystic neoplasms of the pancreas. Am J Surg 1999;178: 269 -
74.) 
 
3. Background: Finally, a note that the majority of these lesions can be safely observed without 
resection is probably warranted, especially taking into account large natural history studies  that 
have proved this in the literature. (El -Hayek KM, Brown N, O'Rourke C, Falk G, Morris -Stiff G, 
Walsh RM. Rate of growth of pancreatic serous cystadenoma as an indication for resection. 
Surgery. 2013 Oct;154(4):794 -800; discussion 800 -2.) My concern i s that readers might be 
confused that the entity of malignant SCNs is of significant concern and therefore adopt a 
potentially harmful stance that all SCNs should be resected to prevent the development of 
malignant SCNs. In fact, perioperative morbidity an d mortality remains high and the majority of 
pancreatic resections still occur in low volume centers where outcomes are not as favorable as 
they are in high volume centers.  
 
4. Background: For the comment "However, the WHO classification is still under deb ate as 
many studies have classified SCNs that invade surrounding organs as malignant SCNs even 
though there is no distant metastasis," please provide references to support this statement.  
 
5. Presentation of our case: I was a little curious why no endoscop ic ultrasound, fine needle 
aspiration was performed pre -operatively for this case. Also, I am interested in if there was a 
suspicion of SCN given the characteristic appearance on the CT?  
 
6. Presentation of our case: Can you provide the ultimate outcome for the patient? Were the liver 
lesions resected? Was any therapy offered and if so, what? What is the outcome at latest follow -
up, and what is that follow -up? 
 
7. Morphologic and radiograph ic features: In relation to the comment, "Regarding the malignant 
features, local invasion to the adjacent vessels, spleen, liver, adrenal glands, stomach, or colon 
can be detected on CT and/or MR images," I think you need to clarify this some more. In rea lity, 
the bigger these lesions get, the harder it is to tell if there is truly "local invasion" or if it is just a 
mass effect. Specifically, when looking at the listed cases, those with peripancreatic fat, lymph 
node, or vascular invasion, it would be int eresting to find out if these were truly invasions or just 
involved in the specimen or adherent.  
 
8. Treatment and outcome: I think the mortality data should be expanded upon. Of those who 
died with pancreatic neoplasm, was metastasis present? If so, thes e are true serous 
cystadenocarcinoma. I think it's important to highlight that in these cases almost as many patients 
died from the operation (2) as did from the actual disease (3). So, one might argue that surgery 
isn't a great option for these patients? Also, I think it's important to use these cases to come up 
with predictive factors for death. Does local invasion put someone at risk? If so, into which 
organs? I would look at the metastatic vs. local invasion groups carefully as they are fairly 
different  (hence the WHO classification). If the supposition is that these malignant SCNs are all 
similar, shouldn't one expect similar long term outcomes for both metastatic and those with local 
invasion?  
 
9. Discussion: Regarding the comment "Although the 2010 WH O criteria apply a strict definition 
of pancreatic serous cystadenocarcinoma as tumors with distant metastasis, we believe that local 
invasion should be included as a diagnostic criteria for malignant SCNs because most deaths are 
due to local invasion rath er than distant metastasis." I'm not sure this comment is fully supported 
by the manuscript, especially given that 2 patients died from the operation itself and 3 died of 
advanced disease. In fact, further examination of these 5 deaths showed that 4/5 had metastasis 
(3 of which died from disease and 1 of which died from the operation) and 1/5 died from the 
operation itself, without metastatic disease. One could argue that we need to do a better job 
selecting these patients because the operation itself has a  high mortality, as shown by review of 
these cases. Furthermore, a comment about where the majority of pancreatic resections occur (at 
low volume centers) should warn clinicians to start resecting these lesions out of fear of death 
from "malignant SCNs" si nce the overall mortality rate is low even for those with local invasion.  
 
10. Discussion: I would like to hear a discussion on the definition of local invasion and whether 
this really means anything, especially given the fair amount of subjectivity associ ated with it.  
 
11. Again, regarding the comment that "since the prognosis of malignant SCN of the pancreas is 
generally, good, we believe that an aggressive treatment, such as resection of primary tumors as 
well as metastatic disease, are beneficial for p atient survival," I don't think the authors 
adequately proved that from this review of the cases presented. I would not gloss over the high 
morbidity/mortality of pancreatic resections in this manuscript.  
 
12. Conclusions: I'm not sure that radiologists a re going to be the final participants in figuring 
out malignant nature of these tumors. Rather, I believe that a full panel of imaging, 
cytopathology, tumor growth rate, and biological activity will ultimately be important. Please 
comment on the other moda lities offered to determine the nature of the cyst (ie: cyst fluid 
analysis, tumor markers, etc).  
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 supporte d 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 spe cify 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:  
 
Acceptable  
 
Declaration of competing interests  
Please comp lete 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 t his 
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, either now or in the future?  
 
3. Do you hold or are you currently apply ing 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 interests' 
below.  If your reply is y es to any, please give details below.  
 
I declare that I have no competing interests  
 
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