New Challenges in Surgical Approaches for Colorectal Cancer during the COVID-19 Pandemic

Round 1

Reviewer 1 Report

Manuscript ID: applsci-1666669

Title: New challenges in surgical approaches for colorectal cancer during the

Covid-19 pandemic

Dear Dr. Dragos Serban

   This paper” New challenges in surgical approaches for colorectal cancer during the Covid-19 pandemic ” by Dr. Dragos Serban described the fact that Colorectal cancer surgery may be performed safely during the Covid-19 pandemic, with strict adherence to the Sars-Cov-2 prevention protocols.

This work was interesting. But there is, however, a key piece of information missing from the article that need to be in place before it undergoes publication.

Minor revision:

After operation during the Covid-19 pandemic, the mortality was high.

The discussion should be better concentrating on the procedures to improve.

Author Response

Dear Reviewer,

Thank you very much for your appreciation and recommendations. We added a paragraph in the Discussions section, focusing on the possible ways to improve the outcomes for these patients.

We also improved the statistical analysis and add multivariate analysis to identify the variable that could be associated with worse outcomes in the pandemic group. We do hope that in this revised version, you will find it suitable to be published.

Reviewer 2 Report

This is a research of Covd-19 pandemic impact on colorectal cancer surgery. The Covd-19 pandemic had a significant impact on various medical fields. It is a serious concern now.

However, it is difficult to accept the contents of this paper. There is too much negative impact on the medical care of the pandemic, and there are a lot of data which cannot be easily believed. I don't understand what the new challenge in the paper title refers to.

 

1. It is quite a surprise that it decreases by as much as 70% after the pandemic. The impact of the pandemic is likely, but is it flowing to other facilities that it decreases so much?
2. It is understandable that the ratio of obstructive colorectal cancer has increased, but the mortality rate is too high. Your hospital seems to be treating only oncological emergency after the pandemic. What is the ratio of stent treatment to obstructive colorectal cancer?
3. I am surprised at the ratio of postoperative mortality rates during the Covid-19 pandemic era. I understand that there are many high-risk patients, but the high mortality rate is an unbelievable number. What are the most common causes of death? Analysis of the cause of death is required.

Author Response

Dear reviewer,

We were also surprised to find such a negative outcome in colorectal cancer patients treated during the pandemic, and this is the reason for our research. We aimed to analyze the possible co-variables that may be addressed to improve outcomes, such as less extensive surgery in emergency, reserving ICU beds for oncological patients, and increasing efforts to improve the accessibility of non-emergent cases with colorectal cancer to therapy, despite the increased burden during peak Covid-19 pandemic waves.

We improved our paper as statistic analysis, and also in the discussion section. We do hope that in this revised version, you will find it suitable to be published.

The causes of this important decreased number of patients treated for colorectal cancer during the Covid-19 pandemic are, in our opinion, disruptions in screening programs, less addressability due to traffic restrictions among regions, lockdown, a decreased number of consultations per day on an ambulatory basis, and decreased available hospital beds due to strict antiCovid-19 regulations. On the other hand, many patients postponed their visits to the doctor or admission to the hospital due to fear of getting Covid-19. All these causes led to a decrease in non-emergent presentations for colorectal cancer. On the other hand, Covid-19 put an increased pressure on hospital resources, due to the high number of ICU and non-ICU beds that were allocated for treating Covid-19 patients. We were confronted with a lack of ICU logistics and specifically trained personnel, so this also reflected in the outcomes of the challenging cases that underwent surgery in an emergency. Most of the public chronic and emergency care hospitals were equally affected by the Covid-19 pandemic in our city, and there is no available data that patient flow was diverted to other facilities, except for a limited number of patients that were addressed to private hospitals.

• It is understandable that the ratio of obstructive colorectal cancer has increased, but the mortality rate is too high. Your hospital seems to be treating only oncological emergencies after the pandemic. What is the ratio of stent treatment to obstructive colorectal cancer?

We do not use colonic stenting in emergency for obstructive colorectal cancer

• I am surprised at the ratio of postoperative mortality rates during the Covid-19 pandemic era. I understand that there are many high-risk patients, but a high mortality rate is an unbelievable number. What are the most common causes of death? Analysis of the cause of death is required.

The causes of death are presented in Table 2. Moreover, a Logistic Regression model was developed to identify the variables that may be correlated with adverse outcome.

The most frequent cause of death was septic shock, both in pandemic and in non-pandemic groups. The increased incidence of septic shock may be explained by the high number of cases admitted in emergency for bowel obstruction, with bacterial dissemination by colonic diastatic translocation and surgery on an insufficient prepared colon, as well as limited ICU resources for these patients.

Reviewer 3 Report

The manuscript presents a new challenge in surgical approaches during Covid-19 pandemic for colorectal cancer. The motivation for the work and all the decisions taken are well-supported by the literature. The structure of the manuscript is standard, easy to follow. However, I have some issues that I would like to see clarified. 

 

1. Statistical analysis
2. a) The statistical methods' section should have more information, particularly regarding multivariable regression and the criteria used.

 

2. Table 1
3. a) All tables should be self-explanatory. It would be useful to have information about which test was used (e.g. as a footnote).
4. b) Always use the same precision when presenting the results, namely, give p-values ​​always with the same number of decimal places (usually 3).
5. c) There are several results from this table that I can't understand, for example

- Emergency presentation, % don't add up to 100%.

            - Co-morbidities: can't patients have more than one comorbidity? If yes, shouldn't a p-value be presented for each one?

            - Histopathological findings- what is the p-value concerning?

1. d) why are there variables that have no associated p-value?

 

2. Table 2
3. a) All tables should be self-explanatory. It would be useful to have information about which test was used (e.g. as a footnote).
4. b) Always use the same precision when presenting the results, namely, give p-values ​​always with the same number of decimal places (usually 3).
5. c) For the variable Type of surgery and cause of death a chi-square test was applied (I hope so). This test has some assumptions that need to be fulfilled. Have they been verified?
6. d) The summary measures used to describe each variable should always be indicated;
7. e) The hospital LOS variable usually has a non-normal distribution, however the mean was used to describe it. Was the distribution of the variables verified?

 

A multivariable model should be developed  for quality of care. You cannot say that there was a decline without adjusting for confounders that may exist.

Author Response

Dear Reviewer,

Thank you very much for your time and effort to review our work! We have revised the manuscript according to all your recommendations, as presented below:

Statistical analysis

1. a) The statistical methods' section should have more information, particularly regarding multivariable regression and the criteria used.

 Response: we added more information regrading the statistical analysis used in this research.

1. Table 1
2. a) All tables should be self-explanatory. It would be useful to have information about which test was used (e.g. as a footnote).

Response: We added the required information in the Footnote of the tables.

1. b) Always use the same precision when presenting the results, namely, give p-values ​​always with the same number of decimal places (usually 3).

Response: We have corrected.

1. c) There are several results from this table that I can't understand, for example

- Emergency presentation, % don't add up to 100%.

Responses: Emergency presentation: percentages are of total number of cases for each period (44 out of 118 is 37.3% and 25 out of 36 is 69%). The causes for emergency presentation are presented below (obstruction, perforation, hemorrhage)

            - Co-morbidities: can't patients have more than one comorbidity? If yes, shouldn't a p-value be presented for each one?

Response. Thank you for the observation. This is correct. We have corrected and used the appropriate statistical test are a p-value was provided for each comorbidity. Moreover, the number of comorbidities per patient was evaluated in the 2 study groups.

            - Histopathological findings- what is the p-value concerning?

Response. We analyzed the distribution of the histopathological forms in the 2 groups, and we found that during the pandemic the mucinous adenocarcinoma were more frequent, while in the non-pandemic  group the conventional adenocarcinoma was encountered more frequent.

1. d) why are there variables that have no associated p-value?

Response:  We have corrected the missing values. When the differences in distribution was found irrelevant in one category ( TNM stage), the p-value was not further calculated for every variable in the same category

1. Table 2
2. a) All tables should be self-explanatory. It would be useful to have information about which test was used (e.g. as a footnote).

Response: We added the required information in the Footnote of the tables.

1. b) Always use the same precision when presenting the results, namely, give p-values ​​always with the same number of decimal places (usually 3).

Response: We have corrected

1. c) For the variable Type of surgery and cause of death a chi-square test was applied (I hope so). This test has some assumptions that need to be fulfilled. Have they been verified?

Response: We have not used chi-square test, instead we used the Fisher Exact test for N*2-Table, N>2 and Fisher’s Exact Test for 2*2-Table.

1. d) The summary measures used to describe each variable should always be indicated;

Response: we have corrected

1. e) The hospital LOS variable usually has a non-normal distribution, however the mean was used to describe it. Was the distribution of the variables verified?

Response: In tabel 2 we put the mean value+/- standard deviation, but the comparison of this variable in the 2 study groups was assessed using the non-parametric Mann-Whitney U-test for comparison of distributions. We did not compare the mean values of the 2 groups.

A multivariable model should be developed for quality of care. You cannot say that there was a decline without adjusting for confounders that may exist.

Response: we developed a multivariate analysis of the variables that correlates better with adverse outcomes, in terms of death and septic shock. We added a paragraph in the discussion section regrading the possible confounders and the procedures that may improve outcomes.

We hope, in this revised version, you will find the paper suitable to be published.

Reviewer 4 Report

It is an interesting study on surgical approach for colorectal cancer during the Covid-19 pandemic.

The study included relatively small number of patients, however shows significant differences between patients treated before and during pandemics.

There some minor comments

There are some typographical errors.

Table 1 is slightly out of order especially section on histopathologic findings.

Author Response

Dear Reviewer,

Thank you very much for the appreciation and the recommendations to improve our paper!

We have revised the English and corrected the typographical errors.

 We have rearranged the Table 1 and 2.

We improved our paper as a statistical analysis, and also in the discussion section. We do hope that in this revised version, you will find it suitable to be published.

Round 2

Reviewer 2 Report

The opinion about stenting therapy for obstructive colorectal cancer should be required in the discussion.

Author Response

Dear reviewer,

Thank you very much for your suggestion. We added a paragraph regarding the colonic stenting in emergency for obstructive colonic cancer and revised our references accordingly.

We consider this procedure as a strong alternative to reduce morbidity and mortality in emergency and we have initiated the necessary formalities so we can be able to implement this in our future clinical practice.

 

Reviewer 3 Report

Thank you for the effort in trying to answer my questions. I still have a question that I would like to clarify

You have included in the results the results of 2 multivariable models. However, I can't figure out which results they are showing. For example, for the model/score

d(pandemic/non-pandemic)= 1.542*bowelocclusion01+2.887*septicshock01+constant what is 1.542? Is it the Odds Ratio? Is it the coefficient of the regression? The same question arises for the others coefficient  as well as the other "score"  presented. The regression results can be presented in a table without the need to transform them into a score. You can do this, but you need to be careful that you are doing it the right way.

Author Response

Dear reviewer,

Thank you for your time and effort in reviewing our work. Indeed, the regression model was meant to calculate the odd ratio, and it is not exactly a score, but more a formula that can be better described and understood by the tables.

So, as you recommended, we provided the tables, commented upon the results, and removed the 2 equations from the main text.

We hope that you will find our work appropriate to be published in this revised version.

Kind regards,

Associate Prof. Dr. Dragos Serban

 

Round 3

Reviewer 3 Report

The authors answered all my questions and changed the article accordingly. Thank you very much.