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Sir,
I read your article with interest. It is indeed a novel idea for the treatment of fistula-in-ano, which on the surface would appear to simplify the management of what can be a very complex and difficult clinical condition. However, I have several comments and queries about the published article.
The article does not appear to be accurate with the anatomical location of the fistula; there is no mention of location in relation to the dentate line. The differentiation between high and low fistulas may be critical in the success (as it is in conventional forms of management) of fibrin sealant in the treatment of fistula-in-ano. I also suspect that the reason for the 100% success rate in healing of subcutaneous fistulae following injection of the sealant may be due to these fistulae being low and relatively superficial. I would be interested to know the anatomical location of the intersphinteric and transphincteric fistulae in relation to the dentate line and how this correlates with healing after injection of fibrin sealant. Is it possible that the transphincteric and intersphinteric fistulae that did not heal were high ones?
In your article you hypothesise that a reason for the failure of transphincteric fistulae to heal may have been due to the anal sphincter squeezing out the glue from the fistula tract. In order to substantiate this, it would be interesting to know the resting sphincteric pressure in patients having injection of sealant for intersphinteric/transphincteric fistulae. Is it possible that these fistulas may not have received the full complement of fibrin glue to fill the tract? Could treatment failure in certain types of fistula be operator dependent? The article does not state how many clinicians were involved in applying the fibrin glue, whether they (if more than one) received formal training in the application of the glue to fistulae and how success in filling the fistula track was assessed. These, in my opinion, are all very important factors that contribute to success of an interventional treatment.
MRI has been used to assess success of treatment in addition to the clinical evidence of healing. The interpretation of signal intensity within the fistula tract on MRI is very subjective and may consequently be observer dependent. It may have been of more value to actually quantify the signal intensity produced by injection of contrast medium. This has been performed in other clinical disorders, such as Crohn’s disease whereby disease activity (defined here as the degree of inflammation) has been analysed.1,2 It would be interesting to know the recurrence rate following healing of fistulae by this method in comparison to traditional management, such as seton and/or surgery. Are recurrence rates following successful treatment lower than or equal to current treatment methods of fistula-in-ano?
Associated medical conditions that may influence healing rates and recurrence (e.g. Crohn’s disease, diabetes mellitus) are not mentioned for the patient group in your article. For example, it is known that Crohn’s disease can present with complex anal fistulas that may also recur.3 Is it possible that some of your patients had Crohn’s disease and that is why treatment with fibrin sealant was unsuccessful?
This study has a patient recruitment of 10 people, a rather small number. It is, therefore; essentially an observational study and one could argue about its significance.
Yours sincerely,
Dr Singh-Ranger
Academic Department of Surgery, The Royal Free and
University College Hospitals, 67-73 Riding House Street,
London
1. Madsen SM, Thomsen HS, Munkholm S, Dorph S, Schlichting P. Active Crohn’s Disease and Ulcerative
Colitis Evaluated by Low-Field Magnetic Resonance
Imaging. Scand J Gastroenterol 1998, 33: 1193-2002
2. Schunk K et al. Hydro-MRI in Crohn’s Disease. Appraisal of Disease Activity. Investigative Radiology
2000, 35: 431-7
3. Forbes A. Inflammatory Bowel Disease. London: Arnold, 2001
Dear Dr Singh-Ranger,
Thank you for your comments and inquiries. All of our patients in the study had a low type of fistula-in-ano. The latter is defined by the level of the internal opening (below the anorectal ring), and their anatomical location and course of the fistula tract was delineated by MRI.
The reason for the failure of the transphincteric fistulae to heal, as a result of the activity of the sphincter muscles squeezing out the fibrin glue, is the hypothesis that we made after we analyzed our results. Since transphincteric fistula may pass through both the external and internal anal sphincter, measuring both the resting and voluntary contraction sphincter activity may help to verify our hypothesis; 85% of resting anal pressure is a result of internal sphincter activity1 and voluntary contraction provides an assessment of external sphincter and puborectalis activity.2
The method of injecting the fibrin sealant was designed to fill-up the whole fistula tract, as far as possible, and decrease operator dependant resin. Before the injection of the sealant, we inserted gauze into the patient’s rectum and excessive sealant had been seen in the gauze. In addition, we inject the sealant until overflow of the sealant at the external opening is noted. In this study, the first two authors performed the injection of fibrin glue.
The basic assumption of MRI being helpful to assess for the response to treatment is that a healing or healed fistula should be of decreased signal on STIR and contrast-enhanced T1 images. In order to facilitate the assessment for signal change on the follow-up MRI, the parameters of the examination, the grey scale setting as well as filming order are set to the same levels in the study. Only one radiologist, who performed all the MRI examinations, was responsible for the assessment. In fact, some of the cases have also been supplemented by measurement of the grey scale value at the workstation. This grey scale value should be correlated to signal intensity and is the most readily available measurement in the workstation. It is a practical way to assess the signal intensity in a service department without strong support from physicists for mathematical calculation. In our study, however, we demonstrated variable signal change to such a degree that it was obvious with qualitative assessment in some of the patients, with both successful and failed treatment. With further grey scale value measurement, more subtle change was further evaluated and confirmed.
It is agreed that it should be desirable to quantify the signal intensity. The objective measurement of the T1 and T2 relaxation time is one of the methods to do it but it involves sophisticated calculations that were not readily available in our department. A more readily available measurement is the grey scale value that could be obtained in the imaging workstation. This measurement should be correlated to the signal intensity. In order to take the variable noise level into consideration, a more refined modification of measurement of signal ratio to either internal (muscle) or external (phantom) reference would be a less error prone method of signal intensity assessment. In fact, this signal ratio assessment (with reference to adjacent muscle) was adopted to confirm our qualitative assessment in some of the patients with minimal or subtle signal change.
For non-Crohn’s disease the treatment of simple intersphincteric fistula by fistulotomy has a 95% success rate.3 However, variable recurrent rate was noted in the treatment of high type fistula-in-ano in the literature. Recurrent rates of 3.7% to 42% for high type fistula-in-ano by cutting seton, and 43% with persistent fistula treated by initial drainage seton and then by definitive surgery have been documented.3 Two to 32% recurrent rate has been described for those treated with anorectal advancement flaps. Patients with Crohn's disease complicated with fistula-in-ano have higher recurrent rates after treatment. It seems that fistulotomy for low type fistula-in-ano has a higher success rate compared with our group of patients. None of our patients had Crohn’s disease and none of them had a high type fistula-in-ano. We fully agree with you that the number of patient in our study is rather small. Randomised control trials are needed to compare different treatment modalities in order to reach a more meaningful conclusion.
Yours sincerely
K.M. Chan
Department of Surgery, Princess Margaret Hospital, 2-10
Princess Margaret Hospital Road, Lai Chi Kok, Kowloon,
Hong Kong
1. Frenckner B and Von Euler C 1975. Influence of
pudendal block on the function of anal sphincter. Gut
1975, 16: 482-489
2. Duthie HL and Watts JM, 1965. Contribution of the
external anal sphincter to the pressure zone in the anal
canal. Gut 6: 64-68
3. Surgery of the anus, rectum & colon. Micheal RB
Keighley & Norman S Williams
Sir,
We read with interest the recent article concerning the Dundee protocol for investigation of haematuria using an innovative approach of performing flexible cystoscopy first and using the cystoscopy findings, age and the presence of frank haematuria to define which further imaging of the upper tract to use.1
We are also interested in the imaging of the upper urinary tract, mindful of the fact that we should be limiting the amount of medical radiation to which our patients are exposed.2,3 Whilst the protocol outlined in the article would decrease the number of intravenous urograms (IVUs) performed nationally this benefit has to be balanced against the risk of missing urothelial malignancies in the renal pelvis or ureter.1
Our specific interest in the protocol is that upper tract tumours may have been overlooked on ultrasound in patients under 50 years of age who presented with microscopic haematuria as in the study no tumours were discovered in this subgroup of patients.
By utilising the British Association of Urological Surgeons (BAUS) Section of Oncology Data-base for 1999 to examine new cancer registrations, we are able to show that though these cancers are not common they do exist, with 14 patients under the age of 50 years having upper tract transitional cell carcinomas (TCCs) and 225 bladder TCCs.
To help to answer this concern, could the authors please confirm that all 10 patients with upper tract TCC presented with frank haematuria and state how many were under the age of 50 years? This is important because if any upper tract cancers were discovered in this younger age group it would enhance the validity of the protocol as it would then demonstrate a capability to identify upper tract TCCs in a younger age group, though importantly not by ultrasound but by intravenous urography. However, if all the 10 patients under 50 years of age with frank haematuria were found to have malignancies in their bladder then it supports the possibility that a number of TCCs in the upper tract may have been overlooked by the protocol.
Yours sincerely
J.S.A. Green, M. Winkler and D.C. Hanbury
Department of Urology, The Lister Hospital, Coreys Mill
Lane, Stevenage, Herts, UK
1. Alishahi S, Byrne D, Goodman CM, Baxby K.Haematuria investigation based on a standard protocol:
emphasis on the diagnosis of malignancy. J R Coll Surg
Edinb 47:1:422-427
2. Andrews SJ, Brooks PT, Hanbury DC, King CM, Prendergast CM, Bousted GB, McNicholas TA.
Ultrasonography and abdominal radiography versus
intravenous urography in investigation of urinary tract infection in men: prospective incident cohort study. BMJ
2002, 324:454-6
3. European Union Treaty EURATOM 97/43 effected May 2000
Sir,
I read with interest this informative study, "Haematuria investigation based on a standard protocol: emphasis on the diagnosis of urological malignancy". It demonstrates a malignancy incidence of 11.6% (121/1046), in haematuria patients who deserve the given emphasis. Urinary stones were also detected in 4.9% (51) and renal cysts in of 3.7% (37), leaving 80% of the haematuria patients as undiagnosed, of whom about a third had frank haematuria and 45% had associated urinary symptoms. Urinary tract infection (UTI) may take the incidence of explainable haematuria to about 25% - even when specific infections are considered. Thus, 75% have undiagnosed haematuria on a ‘standard protocol’, using not only ultrasonography (US) and intravenous urography (IVU) but also ancillary imaging. Such figures are clinically and statistically important. The advice to discharge, ignore or refer them to nephrology was based on the lack of demonstrable organic pathology. My experience suggests that many demonstrable anomalies and pathologies do indeed exist but are overlooked on a ‘standard protocol’.
Haematuria patients with ‘no abnormalities at all’ on ‘standard protocol’ of supine imaging reveal multiple anomalies on using “upright imaging protocol”, comparing supine with upright IVU films, and and retrograde pyelography (RGP). Overlooked features and complications of symptomatic nephroptosis (SN) become demonstrable.1,2 However, upright imaging is currently not done, and anomalies are impossible to detect otherwise, because SN was disparaged half a century ago.3
Segregating painful haematuria patients identifies a group who fit the definition of the loin pain haematuria syndrome (LPHS) using a ‘standard protocol’. The link between SN and LPHS has been overlooked until recently.1,2 The anomalies demonstrable on the “upright protocol” do not only explain the pathoaetiology of LPHS but also other renal idiopathic disorders, at an early stage of reversible neuro-ischaemic complications of SN long before the irreversible reno-vascular damage of LPHS occur.1,3
This view is based on nine years prospective study of 190 SN patients who presented with episodes of flank pain and the multiple associated splanchnic symptoms (MASS) of SN, who had repeatedly normal ‘‘standard protocol’s.1,2 Upright protocol” demonstratedd SN of >2 vertebrae in all patients, of whom 18.9% were complicated into LPHS and who also had normal ancillary imaging, when supine. The causes of renal pain were heterogeneous with intermittent and irreversible stages of pelvi-uretric junction kink obstruction and neuro-ischaemia of renal pedicle stretch/torsion. Cases of LPHS complicating SN demonstrated pyelocalyctaisis on RGP. Medulla papillary erosion communicating vascular and collecting systems, and intra-renal extra-vasation of contrast medium localised the upper calyx as the site of haematuria in early LPHS. Extensive renal damage may extend to affect the medulla of the mobile right kidney, and may affect the normally situated left kidney via sympathetic nephroplegia.1
Such evidence indicates that IVU should remain the “gold standard” investigation for haematuria, loin pain and UTI. Although, US may seem the most versatile imaging to use in SN, its usefulness was limited because on upright posture the ptosed kidney, was obstructed by bowel gas anteriorly and iliac bone posteriorly. Ancillary machines are also limited as imaging is not feasible on upright posture. “Upright imaging protocol” does not only demonstrate the newly discovered patho-aetiology of LPHS but may also explain nephrology disorders and atrophy, currently considered idiopathic. Reconsideration of the recommendations to discard IVU and of disparaged SN is justifiable.
N. Ghanem
King Khalid Hospital, P.O. Box 1120, Najran, Kingdom of
Saudi Arabia
1. Ghanem AN. Features and complications of
nephroptosis causing the loin pain and haematuria syndrome: A
preliminary report. Saudi Med. J. 2002; 23 (2): 197-205
2. Ghanem AN. “Disparaged” Nephroptosis. Urology 2000; 56: 183-4
3. Ghanem AN. Early experience of intra-ureteric capsaicin
infusion in loin pain haematuria syndrome. BJU Int.
2000; 86: 911-914
Sir,
We thank Green, Winkler and Hanbury for their comments on the above paper and the questions they posed. Of the ten patients who had upper tract TCC, seven presented with frank haematuria and three with microscopic haematuria. All these patients were 50 years of age or older (median 69; range 50-79 years).
To arrive at the protocol used in this study we previously analysed 614 patients presenting to us with haematuria. This has been published previously.1 In this study all patients of 40 years or older had both an IVU and ultrasound to investigate their upper tracts. No patient between 40 to 50 years with microscopic haematuria had an upper tract TCC. Indeed no patient under 50 with microscopic haematuria had a malignant diagnosis. We, therefore, changed our protocol to carrying out an IVU in those patients who were 50 years and older.
We also thank Dr. Ghanem for his interesting and thought-provoking comments.
Yours sincerely
S. Alishahi*, D.J. Byrne#, K. Baxby# and C. Goodman#
*Department of Surgery and #Department of Urology,
Ninewells Hospital and Medical School, University of Dundee
Scotland, Dundee, UK
1. Sultana SR, Goodman CM, Byrne DJ, Baxby K. Microscopic haematuria: urological investigation using a standard protocol. Br J Urol 1996, 78: 691-698