Ferritin, Serum Iron and Hemoglobin as Acute Phase Reactants in Laparoscopic and Open Surgery of Cholecystectomy: An Observational Prospective Study

Round 1

Reviewer 1 Report

Dear authors

the manuscript is well organized and of relevant clinical significance.

The only limitation I see is the discrepancy between the dimensions of the two groups. I believe that would be beneficial an extension of the study aimed to increment the number of subjects of the open cholecystectomy group.

Author Response

We are very grateful for your evaluation.

You are right when you say the open group should be bigger. At the initial design of the study we thought we were going to collect 15-20 open cholecystectomies, but fortunately for the patients we only got these small amount, including converted surgeries.

The main reason for that discrepancy is open cholecystectomy is not very often. Nowadays we only make this procedure open when technically it is not possible to finish it laparoscopically or when the patient's hemodynamic situation guards against it. 

Because we are every day more capable laparoscopically, and conversions are few, during the 3 years of data collection we only got 8.

This is an observational study, non a randomized trial, and for that reason we cannot modify the inclusion criteria in each arm. It wouldn't be ethical to do an open procedure when it is well known that laparoscopy is superior in time of recovery, cost, complications, and as we are ratifying, the inflammation response.

Despite the small size of the open group, significant statistical differences are observed; though it shows its statistical power.

Author Response File: Author Response.docx

Reviewer 2 Report

The study investigates ferritin, serum iron and hemoglobin as acute phase reactants in laparoscopic and open surgery of cholecystectomy. The serious flaw of this study is that it is focuses on the changes of inflammatory markers before and after surgery. It is no wonder that markers of acute inflammation are altered after cholecystectomy, in a more severe way in open cholecystectomy than laparoscopic surgery. I think this study hardly provides the novelty and the data do not support grounded conclusions due to the limited number of patients undergoing open cholecystectomy. I have some comments.

1. GENERAL: Please use American English in the manuscript.

2. INTRODUCTION: At the beginning of your introduction, I think SIR is an abbreviation of systemic inflammatory response. Please correct.

3. METHODS: This study is a prospective study. Please provide the registration number of clinical trials.

4. METHODS: You included the patients with acute cholecystitis who were treated with antibiotics at least 6 weeks before the surgery. I cannot understand the inclusion criteria because acute cholecystitis often requires emergency surgery. Why did you use antibiotics for so long?

5. RESULTS: At the end of page 3, you stated that we also found a non-significant decrease between A1 and A2 of serum iron. (Figures 1 and 2). But there is no information about iron in Fig. 1 and 2.

6. RESULTS: In the middle of page 5, you stated that TNF decreased at 24 h in a non-significant fashion (Figures 1 and 2). However, there is no information about TNF in Fig. 1 and 2.

7. STUDY DESIGN: You had better modify the study design. It would be interesting to study the prognostic value of inflammatory markers as predictors of complications and mortality.

Author Response

We appreciate your assessment and we are sure that your contributions help improve the quality of work.

The design of the work is to assess the pathophysiological response to surgical aggression, and for this reason we have chosen your specialized journal on this subject.

1. We have corrected the terms in British English and it has been reviewed by a native speaker.
2. We have corrected SIR and its meaning.
3. The work has been approved by the Ethics Committee of the Canary Islands Health Service (CEIM). Our registration clinical trial number is 2016_01. It is a prospective observational study. Informed consents were signed by all patients.
4. The antibiotic treatment only lasted 7-10 days, then we waited 6 weeks to schedule the surgery. You are right when you say acute cholecystitis should be treated surgically when you diagnose it. Treating it with antibiotics and scheduling the surgery after inflammation goes down is an old-fashioned practice, but it is a therapeutic option. The idiosyncrasy of our hospital forces us to keep on doing it this way, even though everyday we operate more in the acute moment. When we designed the study, we decided to take these situation as an advantage, because there are not many non-oncological surgeries in which patients are in a basal situation (no inflammation, no malnutrition, no malignant disease, etc).
5. “(Figures 1 and 2)” was concerning all paragraph. I’ve changed it, so I hope it is cleared up.
6. “(Figures 1 and 2)” was concerning all paragraph. I’ve changed it, so I hope it is cleared up.
7. ​​We agree with you and have evaluated complications and mortality. At the beginning, we were expecting to see higher levels of inflammatory parameters when complications occurred, but we only had one pneumonia and two wound seromas after surgery. We did not find any correlation with the inflammatory parameters and for this reason we have not included it in the work. We had no mortality in our series. We add this data in the paper.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Thank you for submitting the revised manuscript. The manuscript has improved, but I have some comments.

1. MATRIALS AND METHODS

“The patients included were adults who had acute cholecystitis in the past, treated with antibiotic one week, at least 6 weeks before the elective surgery. Patients with acute cholecystitis, another concurrent infection, or a neoplasm at the time of the surgery or with no completed follow up were excluded” I think that the second sentence is misleading; it seems to exclude all patients with acute cholecystitis. Please modify the second sentence to convey the proper meaning.

2. STASTISCAL ANALYSIS: “…whereas Spearman’s rho was…” Please correct this.

3. RESULTS: In the main text, Fig. 2 comes before Fig. 1. Fig 1 must come before Fig.2.

4. TABLES: The title of table 2 is comparison between LC vs OC at postoperative day 1 (A2). But there are A1 and A2 instead of LC and OC at the first line of table 3. Please correct.

Author Response

Thank you for your quick and favorable answer.

1. I’ve added “acute cholecystitis at the time of the surgery” to clarify that point. You were right it might confuse the lector.
2. I’m sorry for this grammatical error. Now it is in capital letters.
3. The order of the figures have been changed, so it is at the text too.
4. I’m sorry about this oversight. Now you can see LC and OC at the first line of table 3 as it was mean to be.

Author Response File: Author Response.docx