3510276665392290_comment Reviewer's report Title: Medical and surgical treatment of haemorrhoids and anal fissure in Crohn's disease. Version: 3 Date: 10 April 2011 Reviewer: Gabriele Böhm Reviewer's report: Major Compulsory Revisions: Dear Authors, 1. Please, get a native speaker to correct the paper. The language has been checked. 2. The aim of the study or hypothesis is not clearly explained. Do you want to prove that treatment of haemorrhoids or fissure in ano have a higher surgical complication rate in patients with Crohn’s disease (CD)? Compared to what other group of patients? The groups are not clearly defined. From the article it seems that all patients suffered from CD. You seem to compare healing in active and dormant CD-groups. But this is not clearly outlined. And why do you not compare it to a matched patient group without any Crohn’s disease. With the database you mention, this is probably easily done. What did you expect to see in this particular CD group of patients compared to a general mixed patient population? And what do you want to prove regarding treatment options or decisions? The aim of the study is explained in the last sentence of the section Background and in the introductive part of the Discussion. We don’t want primarily to prove that surgery is associated to higher complication rate in CD patients with haemorrhoids or anal fissure. This report is an analysis with a global overview on the medical treatment and possible surgical options in a particular category of subjects affected by CD, considering that the scientific literature on this topic is very scant, with just few reports in many years and in absence of any published randomized clinical trial. This is the reason why we did not insert a control group to compare just the complication rate in the operative groups, beyond the purpose of the study. In the study are included patients with diagnosis of haemorrhoids or anal fissure, all suffering from CD. They are divided in two main groups, according with the anal pathology, discussed in different sections. Then, in each group, we analyzed the outcomes comparing patients with or without established diagnosis of CD when they arrived at our attention for the first time, and discussing the incidence of surgical complications in these two subgroups. This was made to understand if the knowledge of the presence of CD influenced the choice of the main treatment. We did not operate patients with active CD, but only those in a remission state (explained at page 5-fifth paragraph and at page 7-fourth paragraph). This organization of the study is explained in the section Methods (page 4, fifth paragraph). Regarding treatment options or decisions, with this clinical research we don’t want to give definitive guidelines about medical and surgical therapy of these patients, but we want to outline our experience, maybe comparing with future prospective randomized trial. In the Conclusion of the paper we added that future unbiased studies are needed. 3. Ad: Conclusion: ‘try to avoid surgery unless it is quiet Crohn’s disease’: on what evidence can you make this recommendation? We added in the paper, explaining better our conclusion, that only patients with a remission state, with CDAI < 150, underwent surgical treatment. From this point of view we consider that is better to avoid surgery in presence of an active disease. From the presented tables I notice a high surgical complication rate in one of the groups. The Table 1 did not report the incidence of surgical complications. Anyway in this series we observed a higher rate of complications, and we discussed about that in the paper. Again, if you want to show that surgical complications are higher in CD, I would rather compare results to a matched patient group without CD. One can then subdivide the CD group according to the degree of CD activity and compare dormant CD (no clinical signs of perianal CD) with theresults of theother groups. This may give a clear recommendation for the treating physician when and how to approach haemorrhoids or fissure in ano in CD. A flow chart is appreciated. We explained above the reason why we did not create a control group, and that only patients with a remission of the pathology underwent the surgical treatment. 4. Page 3, second and third paragraph: state references for all statements mentioned We added references. Is the incidence of fissures or haemorrhoids higher in Crohn’s disease compared to the general population? And if so, is it in active or dormant perianal Crohn’s? And are we talking of a typical fissure in ano e.g. 6 o’clock position/idiopathic type? This information is reported in the paper: regarding haemorrhoids at page 8, first paragraph; regarding anal fissure at page 9-10, first, second and third paragraph. 5. Page3, paragraph 6: state, why you searched your database, what precisely did you expect to clarify by this? We explained the type of the study, specifically that is a retrospective analysis of our prospective data, with the aim to investigate symptoms, medical and surgical treatment and outcomes of CD patients with haemorrhoids or fissure in ano. 6. Page 4 Statistical analysis: You mention two groups for the first time. Define your comparative group more detailed. Did these patients have underlying diseases that may affect the healing? See also 2. of this review. The legend for table 1 is not clarifying the two groups, which are now presented as ‘before and after CD diagnosis’. Talking about two groups, do you really mean the same patients before and after they were diagnosed with Crohn’s Disease? You really have to clarify this most important point. I would also recommend to present a table describing and grading their Crohn’s Disease. Replying at the point 2, we gave a detailed definition of the two groups. We explained that they are not the same patients, but we analyzed the outcomes comparing patients with or without established diagnosis of CD when they arrived at our attention for the first time. Considering this point of view, we think that the legend of the Table 1 is clear. Moreover, we stated that all the patients had a remission of the CD in case of surgery. 7. Ad Results: What is your normal approach to haemorrhoids according to their degree? First and second degree haemorrhoids can be approached conservatively, the latter with rubber band ligation. What do you do with third degree haemorrhoids? What is your approach accordingly in CD? We approach first degree haemorrhoids with medical therapy; second degree with medical therapy and rubber band ligation. In the presence of third degree haemorrhoids we do stapled haemorrhoidopexy if there is a prolapse associated; otherwise we do conventional haemorrhoidectomy. Our approach in CD patients is explained in the paper, section Results and Discussion. Describe for fissure in ano accordingly. I would recommend to separately compare results of BOTOX and sphincterotomy patients. It may show an advantage of BOTOX therapy, but this has to be proven. The first line therapy after diagnosis of anal fissure is medical, with topic application of either calcium channels blockers or GTN 0.4% for 8 weeks. In case of failure of this treatment Botox + fissurectomy or Lateral internal sphincterotomy is indicated, mainly according to manometric findings, chronicity of the fissure, patient preference. As reported in the paper, in subjects with definitive diagnosis of CD at the time of surgery, we did only Botox injection, with fissurectomy only in two cases because of the presence of highly fibrotic edges (page 6 – third paragraph; page 7 – second paragraph; page 11 – third paragraph). In the section Results – Anal fissure and in the Table 3 we put separately the results of Botox and LIS in the two subgroups of patients, explaining also the different complications. In the Discussion we highlighted the usefulness of the Botox, avoiding the section of the sphincter, with a remark also in the Conclusion. Certainly in the future, with bigger numbers, could be possible specifically to analyze the exact role of Botox therapy in anal fissure. Try to be more precise with the key points, expand here, and shorten the general information. What is the time to complete healing in the different groups? Present results more clearly in text and tables. We précised better the key points and expanded the sections related to the study. We added in the paper the time to complete healing. 8. Ad Discussion: Too long. The first two pages appear more like a review of literature. Shorten and discuss only the investigated points. The first part of the Discussion has the objective of give a status of the art about the topic of the article, and needs also to compare and discuss our results with the available literature. Anyway as you suggested we removed several sentences. Discretionary Revisions 9. Haemorrhoids and fissure are two distinct pathologies. Why do you want to present them both in one paper? Especially with the fissure being potentially Crohn’s related I would focus on the haemorrhoids and maybe skip the fissure part completely. Our aim is to publish in the future, with a bigger number of patients, the results about haemorrhoids and anal fissure separately, in order to better underline what can be the best approach of these pathologies in CD patients. However at present, considering the scant literature data, we want to give our contribution to the scientific community about the integrated treatment of perianal disease other than fistulae in subjects suffering from CD; our opinion is that with this paper some considerations can be made. Level of interest: An article whose findings are important to those with closely related research interests Quality of written English: Not suitable for publication unless extensively edited Statistical review: No, the manuscript does not need to be seen by a statistician. Declaration of competing interests: 'I declare that I have no competing interests'