Tumor-Bowel Fistula as a Rare Form of Recurrent Ovarian Cancer—Imaging and Treatment: Preliminary Report

Round 1

Reviewer 1 Report

This study wanted to determine whether CT or MRI was more effective in diagnosing tumour bowel fistula as a rare form of ovarian cancer relapse. 8 patients were used for this study.

This was an interesting study which yielded some interesting results, however some more information could be provided for some results. For table 4, do numbers 1-8 refer to each patient? If so, a column should be provided to indicate this. In addition, an abbreviation list will be nice to include so the reader can follow the paper easily.

Author Response

Manuscript ID

curroncol-2047539

 

Response to Reviewer 1

 

Thank you very much for your review, also for the helpful comments and suggestions. We modified the text accordingly.

 

In response to the question about table 4, we explain that each row of the table corresponds to a different patient. Therefore, as suggested, we added a column called "patient's number".

 

In response to a note regarding the list of abbreviations in the text, in the instructions for authors, it is specified that: abbreviations should be defined the first time they appear in each of three sections: the abstract, the main text, the first figure or the table.

That's why we didn't include a separate list explaining the abbreviations.

We have now checked and corrected the text and abbreviations in accordance with the publisher's instructions.

 

Thanks again for your review,

 

Laretta Grabowska-Derlatka and co-authors

Reviewer 2 Report

Dear Colleagues,

The topic of the article is with significant implications for medical practice. For example, studying the possibilities of imaging diagnosis and treatment of tumour-bowel fistula as a rare form of epithelial ovarian cancer is essential for improving the prognosis and mortality due to this pathology. Therefore, the topic is relevant and exciting to the journal field.

The article is presented as a pilot study but presents only 8 cases. Therefore, it does not meet the criteria of a pilot study. Thus, the recommendation is to reorganize it as case series, and in the future, when there will be more cases, a pilot study can be done.

From the article, it appears that: The aim of this pilot study was to evaluate the value of imaging techniques (CT and MRI) in the diagnosis of a tumor-bowel fistula as a rare form of epithelial ovarian cancer (EOC) relapse. In addition, we also performed an initial assessment of the effectiveness of treating this form of relapse.

The conclusion at the end of the summary is: In the case of relapsed EOC in patients with clinical symptoms in the form of a fistula, CT should not be the only diagnostic method, as MRI is a superior method for diagnosing fistulas. Bowel resection with simultaneous anastomosis is a good and safe solution for these patients. However, an appropriate qualification for surgery is essential. As you proposed, more pertinent conclusions can be drawn related to the value of the imaging techniques and the effectiveness of the treatment.

No conclusions are introduced at the end of the work.

Much emphasis is placed on the parameters of the devices used. I would have liked to see concretely for each patient what preoperative treatment was performed, some details related to staging and other medical data that could be significant for the evolution of each case. By reorganizing the data into case series, you can introduce these aspects.

In the Instructions for authors, it is specified that: Abbreviations should be defined the first time they appear in each of three sections: the abstract, the main text, the first figure or the table. Therefore, please verify and correct these aspects in the article.

The main text in Line 80 is written ... the study included 8 patients aged 37-78 years ... In table 1, the age is between 37-67.

Due to the small number of cases, you cannot generalize the results, but you can present them as hypotheses that can be verified later through a more extensive study.

The literature reviews are insightful and informative.

I congratulate all the authors for their efforts.

Author Response

Manuscript ID

curroncol-2047539

 

Response to Reviewer 2

 

Thank you very much for your review and for your helpful comments and suggestions. We modified the text accordingly.

 

Reply to note 1

Thank you for acknowledging that the topic of the article has important implications for clinical practice.

Of course, we agree with reviewer 2 that the strict criteria of the pilot study were not met. It seems to us that this is not a classic case study either. Therefore, we propose the form of a preliminary report. This is a form that may precede a pilot study.

 

Reply to note 2

The conclusion mentioned by the Reviewer ends the abstract. Of course, it is very general. According to the reviewer's opinion, we propose to extend it as follows:

In patients with suspected EOC recurrence with clinically suspected fistula, CT scan is not sufficient. In CT, the presence of a fistula is suspected based on indirect symptoms. MRI, as a method with much greater tissue resolution, confirms the diagnosis. In addition, MRI can identify the point of the tumor/bowel junction. This is especially true with a large infiltration covering several intestinal parts.

Bowel resection with simultaneous anastomosis is a good and safe solution for these patients. However, appropriate qualification for the procedure is necessary, which will allow for surgery without residual macroscopic disease (R0 surgery).

Due to the small number of cases, our results cannot be generalized. We treat them as a hypothesis that can be verified in a larger study.

We have added the listed conclusions at the end of the article.

 

Reply to note 3

The same CT and MRI method was used in all patients.

In our group, all patients completed first-line treatment with complete remission. The operation was the first stage of treatment. Considering the possibility of extensive surgery consisting in resection of the intestine, preoperative and postoperative parenteral nutrition was used in each patient. We have added this information in the material and methods section. Adjuvant treatment included chemotherapy and/or PARP inhibitors as described in the text.

If the Reviewer is of the opinion that information on first-line treatment is needed for each patient, we suggest adding such information in the supplementary material section. If necessary, we will prepare data in the form of a table.

 

Reply to note 4

We have now checked and corrected the text and abbreviations in accordance with the publisher's instructions.

 

Reply to note 5

We apologize for the typo. Should be 37-87 years old.

 

Reply to note 6

Of course, as stated by Reviewer 2, our results cannot be generalized due to the small number of cases. We treat them as a hypothesis that can be verified in a larger study. We have added this note in the conclusion section.

 

Thanks again for your review,

 

Laretta Grabowska-Derlatka and co-authors

Reviewer 3 Report

In general, I would suggest modifying the title of the manuscript and its overall structure into a pictorial essay article, with a main focus on illustrating the CT and MRI appearance of tumor-bowel fistulas in patients with recurrent ovarian cancer along with their surgical correlation and follow-up. The very small patient sample (N=8) can be justified by the rarity of this finding and is good enough for a pictorial essay, but it prevents drawing broader conclusions such as that presented (rather hastily, I would say) at the end of the Discussion, i.e. that tumor-bowel fistulas in patients with recurrent OC are associated with a poor prognosis.

 

Additional, more specific comments:

-Methods (CT imaging technique). Was slice thickness 1.25mm or 2.5mm? Was tube current fixed or modulated? Which molecule of contrast material was used and at which flow rate? Please modify "atrial" into "arterial".

-Results. Fluid fistulas should be hyperintense on T2-weighted images, whereas gas-containing ones should be hypo/anintense on all sequences. In view of this, please explain why most fistulas appeared as hypointense on T2wi.

-As mentoned above, I suggest avoiding concluding that tumor-bowel fistulas are associated with a poor prognosis, because there may be several confounding factors, such as the large size of the recurrent tumor (median 89mm!). To hypothesize this, one should compare PFS and OS of patients with fistulas with similar patients without them - this would require much larger numbers and is much likely beyond the scope of the study.

-Figure 1. Generally ok. I also see a gas bubble lateral to the ileal loops - did the patient also have intestinal perforation?

-Figure 2. In this figure one can just see that the tumor had a large contact area with the bowel - although this may increase the apriori likelihood that there may be a fistula, it is not a sign of fistula itself.

Author Response

Manuscript ID

curroncol-2047539

 

Response to Reviewer 3

 

Thank you very much for your review and for the helpful comments and suggestions. We modified the text accordingly.

 

 

Reply to note 1

Of course, we agree with the reviewer that the article describes a small number of patients, thus propose to consider the article as a Preliminary Report. The form of the Pictorial Essay seems interesting, but we're afraid that this form is not being published in Current Oncology.

 

We agree that the final conclusions were too far-reaching (just too brave for such a narrow material). Therefore at the end we have emphasised that it is only a hypothesis and a probable further-research catalyst.

 

In our department, in case of suspecting a recurrence of the ovarian cancer, we perform a CT test in the arterial and parenchymal phase. The thickness of layers in the arterial phase is 1,25 and 2,5 in the parenchymal. Of course, we also do the post-processing. I corrected the data in the table, adding the layer thicknesses. The intravenous low-osmolality iodinated contrast (Iodixanolum) Visipaque 320 mgI/ml had been injected with the automatic syringe with the velocity of 4ml/s. This data has been added to the “material and method” chapter.

 

The tube current was being modulated.

 

Fig. 1 Thank you (we can sense an experienced radiological eye here!), we had similar susception there. However, the intestinal perforation has not been confirmed during the surgery. The gas bubble was probably the result of a fistula, caused by infiltration.

 

Fig. 2 Thank you. I agree with the thesis that we suggest the presence of the fistula based on a CT examination. Especially when the tumor has such a large adherence area. Therefore we complete the examination with an MRI. I agree that fistulas should be hyperintense on T2-weighted images. The fistula channel, with the tumor, contains air, so only the channel’s borders are hyperintense.

 

Round 2

Reviewer 2 Report

The authors answered punctually to the observations and made the recommended changes. Finally, the work is ready to be published.

Reviewer 3 Report

Thank you.

I suggest improving the language of the entire manuscript, ideally with the aid of a professional English-speaking medical writer or editing service. Some typos are still present, e.g., 'atrial' instead of 'arterial' at line 107; "Magnetiv" instead of "Magnetic" at line 119; "Enlargen" for "Erlangen" at line 120.