(page number not for citation purposes)Journal of Medical Case Reports [622853]

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(page number not for citation purposes)Journal of Medical Case Reports
Open Access Case report
Six years survival on imatinib wi th no disease progression after
diagnosis of metastatic duodenal gastrointestinal stromal tumour:
A case report
Sayantan Bhattacharya*1, Amit Kumar Choudhury2, Srinivasan Ravi2,
John Morrissey3 and George Mathew1
Address: 1Department of General Surgery, George Eliot Hospital, College Street, Nuneaton, Warwickshire CV10 7DJ, UK, 2Department of General
Surgery, Victoria Hospital, Wh inney Heys Road, Bl ackpool, Lancashire FY3 8NR, UK and 3Institute of Clinical Sciences, Warwick Medical School,
Coventry CV4 7AL, UK
Email: Sayantan Bhattacharya* – rxsayantan@rediffmai l.com; Amit Kumar Choudhu ry – [anonimizat];
Srinivasan Ravi – Mr.ravi@bfwhosp itals.nhs.uk; John Morrissey – jmor [anonimizat]; Ge orge Mathew – [anonimizat]
* Corresponding author
Abstract
Introduction: A duodenal Gastrointestinal Stromal Tumo ur (GIST) is a rare finding and until
recently advanced disease had a poor prognosis. A PubMed search reveal ed no reports of more
than five years survival of inoperable GIST on chemotherapy with WHO performance status zero.
Case Presentation: A 68 year old female was diagnosed with unresectable GIST in the
duodenum with metastasis to liver, pancre as and omentum in November 2001. She was
commenced on imatinib mesylate (Glivec) chemothe rapy. This case report was prepared from the
medical records and radiology reports. She had good tolerance with stable di sease. After six years
her CT scan showed no disease progressio n and her WHO performance status was zero.
Conclusion: This report supports the view that imatinib is a safe and effective drug in controlling
disease progression in advanced metastatic GIST and plays an important role in improving the
patient's quality of life.
Introduction
A duodenal tumour, especially a gastrointestinal stromal
tumour (GIST), is a rare finding and until recentlyadvanced disease had a poor prognosis. A PubMed searchrevealed only a few reports of prolongation of the lives ofpatients with advanced duodenal GIST by treatment withimatinib. The maximum length of follow up was 29
months [1] from diagnosis. A recent study suggested that
the prognosis for unresectable and/or metastatic GIST ispoor with few if any patients surviving more than fiveyears [2].Case Presentation
A previously fit and well, 68-year-old female presented inNovember 2001 with recent onset of epigastric discom-fort, significant loss of appetite and melaena. She had alsolost 5 kilos in weight over a three-week period. Over theprevious few weeks, she was mostly confined to bed, asshe was extremely lethargic.
Upper gastrointestinal endoscopy (Figure 1c) revealed a
pre-ampullary tumour in the second part of the duode-num. Histology confirmed the tumour to be a GIST withPublished: 18 April 2008
Journal of Medical Case Reports 2008, 2:110 doi:10.1186/1752-1947-2-110Received: 11 July 2007
Accepted: 18 April 2008
This article is available from: http:// www.jmedicalcasereports.com/content/2/1/110
© 2008 Bhattacharya et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/2.0 ),
which permits unrestricted use, distribution, and reproduction in any medium, provided the orig inal work is properly cited.

Journal of Medical Case Reports 2008, 2:110 http://www.jmedicalcase reports.com/c ontent/2/1/110
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(page number not for citation purposes)more than 10 mitotic activities per 50 high power fields
(HPF) (Figure 1a). The tumour was found to be positivefor a deletion mutation in exon-11 (of the c-KIT exon)
(Figure 1b). Computerised tomography (CT) of the abdo-
men showed multiple metastatic deposits in the liver (Fig-ure 2a). At laparotomy the tumour was found to involvethe liver, pancreas and omentum. A hard lump in the rightparacolic gutter was inseparable from the right kidney.Owing to the extensive nature of the disease the abdomenwas closed without any resection.
Oncology assessment recorded a WHO performance sta-
tus of three (see Additional file 1). She was commencedon Imatinib Mesylate (Glivec) 400 mg once daily. By Sep-tember 2002 her WHO performance status was zero. Shehad mild nausea but her appetite was normal and she had
no urinary or bowel symptoms. Full blood counts and
renal function tests were normal. Her liver function testswere abnormal even before treatment, probably a result ofhepatic metastases, and this persisted.After 28 months of treatment she developed minor side
effects including infrequent diarrhoea and watery painfuleyes. Her regime was modified to four weeks on treatmentwith an off period for the next two weeks and thisimproved her symptoms. The daily dose remained at 400
mg. At her most recent review in December 2007 she
remained symptomatically well. She was mobile and hadno difficulties in performing her daily activities. She wasfollowed up with a CT scan (Figure 2b and 2c) but sherefused any further endoscopic investigations.
Discussion
GIST is a rare form of sarcoma arising either from theinterstitial cells of cajal (ICCs) or from less differentiatedstem cells. The ICCs are located in the muscle layer of thegastrointestinal tract. GIST can occur anywhere butmainly affects the stomach (60%), jejunum and ileum(30%), duodenum (4–5%), rectum (4%), colon and
appendix (1–2%) and oesophagus (<1%) [3]. Rarely
extra-gastrointestinal GIST occurs in the vicinity of thestomach or intestines [3]. The overall incidence has beenestimated at 10–20 per million.CT scan imagesFigure 2
CT scan images . a: at diagnosis (November 2001) b and c :
at the last follow up (in December 2007).
Microscopy and Endoscopy pictures at diagnosis in Novem-ber 2001Figure 1
Microscopy and Endoscopy pictures at diagnosis in
November 2001 . a: shows pictures of H and E staining, b:
KIT positive staining c: Endoscopic findings.

Journal of Medical Case Reports 2008, 2:110 http://www.jmedicalcase reports.com/c ontent/2/1/110
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(page number not for citation purposes)There has been extensive study of GIST to determine
whether tumour size, mitotic activity and genetic charac-
teristics predict disease progression. GISTs more than 5cm in size, independent of mitotic rate, have a moderaterisk for metastases, and all tumours with less than 5mitoses per 50 HPFs have a high risk for metastases. Miet-tinen and Lasota reasoned that when data are analysed by
regression models tumour size may appear to show
greater predictive value because mitotic count reaches a'saturation point' when counts exceed 10 per 50 HPFs [3].
Bearzi et al [4] reviewed 158 cases of GIST. Only 12% of
patients with a mitotic count over 10 per 50 HPFs
remained disease-free after surgery, and all patients with a
mitotic count over 20 per 50 HPFs experienced recurrence.They argued that if the combination of size and mitoticcount place a tumour in the high-risk category, then themitotic count might be the more indicative variable.
Recent papers suggest a mutation found in a GIST may
predict its likelihood of recurrence. Emile et al [5] and
Martin et al [6] identified specific mutations within c-KITexon 11 which were associated with metastasis and poorprognosis. Several papers have found that patients withdeletions in exon-11 rather than substitutions or duplica-tions have a greater probability of recurrence or metastasis
than other GIST patients [7,8].
If these results are confirmed and expanded they could
provide a rationale for identifying patients who needcloser monitoring or perhaps adjuvant chemotherapypost-surgery to prevent recurrence rather than after the
appearance of metastasis in line with guidance by the UK
National Institute of Clinical Excellence (NICE; see Addi-tional file 2).
Cell proliferation in a GIST is a result of the activation of
growth factor receptors. KIT and platelet derived growth
factor receptor alpha (PDGFRA) tyrosine kinases [9] are
normally present on the ICCs. When the genes of thesereceptor cells are mutated activation take place withoutstimulation by the respective ligands (constitutive activa-tion). This causes tumour growth.
Imatinib Mesylate (Glivec) is the first effective treatment
for GIST. Imatinib binds to the intracellular activation
pockets of the KIT and PDGFRA receptors in their inactiveposition, blocking their binding to ATP and preventinggrowth signals being sent, which stops disease progres-sion. Drug response is related to the type of mutation ofthe c-KIT exon. Patients with the more common exon-11
mutation are most sensitive to imatinib [10] whereas
patients with the exon-9-mutation, mostly found in thosewith small intestinal GIST, are the least sensitive [11].The most commonly reported side effects of imatinib are
nausea, diarrhoea, periorbital oedema, muscle cramps,
fatigue, rash and headache. The most common seriousadverse events are unspecified haemorrhage and neutro-penia, each occurring in approximately 5% of patients(see Section 4.1.9 in [2]).
In our patient, imatinib was extremely effective in control-
ling the disease process. This was most likely a result of thetype of mutation (exon-11) that was present in thistumour. The WHO performance status at diagnosis wasthree. Since September 2002, her WHO performance sta-tus has remained at zero. She had suffered from minor
side effects of the drug like diarrhoea and watery painful
eyes. She was reviewed in the oncology clinic and thechange of regime to four weeks on and two weeks off thedrug relieved these side effects.
Conclusion
There have been articles published on the effectiveness of
imatinib but very few have shown a six-year disease-con-
trolled survival with a good quality of life when extensivespread of the disease was apparent at diagnosis. NICE [2]guidance (see Additional file 2) suggests imatinib shouldonly be used in patients with established metastases,unresectable disease or residual disease following surgery.
The effectiveness of this drug is dependent on the type of
mutation of the c-KIT exon. Knowledge of this mutationwould thus help in assessing the prognosis of treatment.We believe our report supports the view that imatinib is asafe and effective drug in controlling disease progressionin advanced metastatic GIST and plays an important role
in improving the patient's quality of life.
List of abbreviations
GIST: Gastrointestinal Stromal Tumour, ICC: Interstitial
Cells of Cajal, WHO: World Health Organization, HPF:High Power Field, ATP: Adenine Triphosphate
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
SB and AKC were actively involved in the follow-up of thepatient, obtained the consent from the patient and pre-
pared the final version of manuscript. SR was the consult-
ant colorectal and GI surgeon under whom the concernedpatient was admitted and managed. He has importantcontributions in preparation of the final version of themanuscript. JM and GM had separately revised the finalversion of the manuscript before the last submission and
had important contribution to the discussion section of
the manuscript. All the authors have read and approvedthe final version of the manuscript.

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(page number not for citation purposes)Consent
Written informed consent was obtained from the patient
for publication of this case report. A copy of the writtenconsent is available for review by the Editor-in-Chief ofthis journal.
Additional material
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Additional file 1
WHO scale for assessing the performanc e status of the patient. The table
describes the WHO performance status in patients.Click here for file[http://www.biomedcentral.com /content/supplementary/1752-
1947-2-110-S1.jpeg]
Additional file 2
NICE guidelines on Imatinib therap y in GIST. The table describes the
NICE guidelines for using Imatin ib mesylate in GIST patients.
Click here for file
[http://www.biomedcentral.com /content/supplementary/1752-
1947-2-110-S2.jpeg]