Review for 10.1186/1471-230X-10-128 (2010)

Reviewer's report
Title:Vesicocutaneous fistula formation during treatment with sunitinib malate:
Case report
Version: 2Date:24 August 2010
Reviewer: Axel Bex
Reviewer's report:
The authors provide an interesting case of vesicocutaneous fistula formation in a
patient with GIST following treatment with surgery, imatinib and then sunitinib.
Major compulsory revisions:
In my view it is equally interesting that the patient developed an
intestinocutaneous fistula in the previous surgical wound 2 years after initial
surgery and imatinib treatment which was then supplemented by 5-FU. Late
anastomotic leakages have been described in treatment with bevacizumab and
to my knowledge to a far lesser extent with inhibiting molecules. However, in the
end it will be very difficult to distinguish in this particular case, if the inhibitory
molecules were the basis for both the fistula formation in the intestine and
bladder or simply a progressive tumor that became necrotic. On page 7, first
lines the authors describe that an abdominal mass involved the abdominal wall,
urinary bladder wall, bowel, mesentery and peritoneum. Was the
intestinocutaneous fistula not simply caused by progression of peritoneal
metastasis ? In the case of the vesicocutaneous fistula the tumour mass
obviously decreased, but still we should be careful with the conclusion provided
on page 8, last line of the results, that 'the clinical course indicated that sunitinib
had played a role in the development of the vesicocutaneous fistula'. Again, it
may be that a tumour necrosis in itself independent from sunitinib treatment may
have caused the fistula. After draining the bladder with a catheter, the fistula
resolved, which may be reason for the success, more so than the withdrawal of
sunitinib.
All we can conclude is that the fistula formation may be associated with sunitinib,
but the conclusion in the abstract that sunitinib might encourage the development
of vesicocutaneous fistulas is far too general and dangerous. The same applies
for the statement in the abstract conclusion, that clinicians should be aware of
the possible complication of urinary fistula formation during sunitinb
administration. We have to bear in mind that this is a special case with prior
surgery, large intraperitoneal tumour deposits that may by themselves have
infiltrated and destroyed organ layers. It is possible, that sunitinib has
accelerated or supported fistula formation, but only an association with this
particular disease stage can be concluded. The authors need to change their
conclusions, otherwise it would imply that sunitinib may cause these fistulas in
patients without tumour involvement of these organs. I have never heard of a
case developing spontaneous vesicocutaneous fistula formation in an otherwise
healthy bladder while under sunitinib. This is, however, what the current
conclusion in the abstract suggests. I suggest to state:'This is the first description
of a vesicocutaneous fistula formation in a patient with extensive peritoneal
extravesical tumour deposits from recurrent GIST while under sunitinib treatment.
Clinicians should be aware of enterocutaneous or vesicocutaneous fistula
formation in patients with intraperitoneal GIST metastasis during treatment with
inhibitory molecules" The latter statement also refers to imatinib. The sentence in
the results that sunitinib encourages fistula formation should be removed or
changed to 'sunitinib may be associated with the formation of the
vesicocutaneous fistula in that particular patient'
Again, in Discussion, page 9, first lines. These findings do not necessarily
indicate that sunitinib contributed to the fistula formation, it may be necrosis and
healing due to catheter drainage. It is too little evidence. If at all, sunitinib was
associated with fistula formation. The conclusion in the main manuscript is much
more neutral and acceptable.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have received honoraria for consultancy for Pfizer, GSK, Bayer and Novartis