Department of Gastrointestinal Surgery, Lancashire Teaching Hospital NHS, Foundation Trust, Preston Road, Chorley, Lancashire, PR7 1PP, UK
Abstract
Background
Surgical resection has remained the mainstay of treatment of GIST with a 5-year-survival of 28–35%. Tyrosine kinase inhibitor (Imatinib) has revolutionised the treatment of these tumours. The current research is directed towards expanding the role of this drug in the treatment of GIST. We present our experience of managing GIST in this institute.
Methods
This is a case note study of patients identified from a prospectively kept database from January 2000 to August 2007.
Results
16 patients were diagnosed with GIST. The median age was 66 years (range 46 to 82) and the male to female ratio was 9:7. Eleven patients underwent surgery, 9 of which had R0 resection (2 laparoscopic, 1 converted to open), one had an open biopsy and one had a debulking procedure. 3 patients were inoperable and 2 were found to be unfit for surgery. Five patients received Imatinib (2 postoperatively). The risk assessment based on morphological criteria showed that 4 patients had low, 4 had intermediate and 8 had high malignant potential. The median follow up was for 12 months (range 3–72); 2 patients died of unrelated causes at 6 and 9 months after diagnosis.
Conclusion
Most GISTs can be managed effectively using existing protocols. However currently there is no evidence based guidance available on the management of GIST in the following situations-role of debulking surgery, the follow up of benign tumours not requiring surgical resection and role of laparoscopic surgery. Further research is needed to answer these questions.
Background
Gastrointestinal stromal tumours (GIST) represent a subgroup of mesenchymal tumours, which were traditionally known as leiomyomas or leiomyosarcomas and have traditionally been treated by surgery. The results of a simple surgical resection with clear margins were comparable to those of a radical resection
In spite of these developments the role of surgery itself has remained unchanged. We present our experience of 16 cases managed in this institute since introduction of Imatinib.
Methods
A case note study of all the patients diagnosed with GIST from January 2000 to August 2007 was carried out. Cases were identified from a prospectively kept database in the unit.
Results
16 patients were diagnosed with GIST during the study period. The demographics, presentation, histology, management and follow up of these patients are summarised in Table
Summary of patients with GIST
Patient
Age, Gender
Site
Presentation
Maximum diameter (mm)
CD117 & CD34
Mitosis per HPF
Operation
Imatinib
Follow up (months)
Risk
1
66, F
Stomach
Mass
70
Positive
10/50
Wedge resection
No
5, SD
High
2
82, M
stomach
GI bleed
60
Positive
2/50
Wedge resection
No
12, SD
Inter
3
60, M
Stomach
GI bleed
75
Positive
2/50
Lap to open Wedge resection
No
12, SD
Inter
4
72, M
Stomach
Pain and distension
110
Positive
300/50
Debulking
Yes
22, SD
High
5
51, M
Stomach
Mass
14.5
Positive
None seen
Inoperable*
Yes
3, PD
High
6
61, F
?Stomach/?extra-gasttrointestinal
Mass and distension
260
Positive
8/50
Excision and total hysterectomy
Yes
45, SD
High
7
72, M
Stomach
Mass
90
Positive
17/50
Inoperable**
Yes
6, Died of MI
High
8
68, F
Stomach
GI bleed
70
Positive
4/50
Lap. wedge resection
No
24, SD
Inter
9
70, F
Oesophagus
Dysphagia
20
N/A
N/A
Not fit
No
29, SD
N/A
10
46, F
Stomach
GI bleed
70
Positive
10/50
Distal gastrectomy
No
3 < SD
High
11
77, F
Stomach
GI bleed
80
Positive
34/50
Distal gastrectomy
No
9, Died
High
12
47, M
Stomach
GI bleed
50
Not done
Not done
Wedge resection
No
72, SD
N/A
13
60, M
Duodenum
Incidental
13
N/A
N/A
Not fit
No
14, SD
N/A
14
74, F
Stomach
GI bleed
40
Positive
2/50
Lap. wedge resection
No
9, SD
Low
15
57, M
Duodenum
Cholangitis
40
Positive Negative
None
Duodenectomy
No
62, SD
Low
16
76, M
Stomach
GI bleed
65
Negative
2/50
No
Yes
7, SD
Inter
N/A: No histological diagnosis available
*: Metastatic disease
**: locally advanced
SD: static disease at last follow up.
PD: progressive disease at last follow up.
Patient 6 was operated by Gynaecologist for fibroids and intraoperatively surgeons were called to remove a large irregular mass adherent to the greater curvature of the stomach and infiltrating the omentum. There was no evidence of peritoneal or liver metastasis. The mass was removed completely which proved to be GIST on histology with possible extra-gastrointestinal or gastric in origin.
Patients 9 and 13 had GIST in the oesophagus and the second part of the duodenum respectively. Due to their associated co-morbidities they were deemed unfit for major resectional surgery. In both the cases endoscopic biopsies were insufficient to give the histological diagnosis, but EUS (endoscopic ultrasound) findings were consistent with the diagnosis of GIST. They were both followed up by yearly EUS examinations.
Patient 16 had significant iscaemic heart disease and could not withstand staging laparoscopy and hence the operation is deferred till cardiac status improves.
Discussion
This cohort of patients showed a significant variation in presentation and wide range of disease stages at presentation. Most of these patients could be managed effectively with surgery and/or Imatinib using current protocols. Imatinib was used in patients with unresectable or metastatic disease according to the NICE guidelines
Our experience suggests that current guidelines are clear for the management of unresectable and metastatic GIST; however surgeons are faced with management dilemmas in the following situations.
• Small GIST
Small GISTs are often diagnosed radiologically as an incidental finding (patient 13 in our series). They are labelled as "benign" purely on the basis of their size and radiological appearance. These tumours, particularly those located in the oesophagus or the duodenum, are difficult to biopsy and in the absence of histological diagnosis there is a potential risk of keeping a malignant GIST under observation or exposing benign GIST to unnecessary surgery. This unnecessary surgery could mean a pancreaticoduodenectomy in such a patient or an oesophagectomy in patient 9, if deemed fit for operation. Currently there is no guidance available on the rationale of regular follow up or of the use of Imatinib in these patients. There are few reported series of endoscopic enucleation of these tumours
Many patients with a small GIST and requiring regular follow up do not get reported leading to a lack of data regarding long-term survival. There is a need for a central database of these cases to improve reporting and long-term follow-up.
• Debulking surgery
At the other end of the spectrum are locally advanced tumours (such as patient 4 in our series). This patient clearly benefited from "debulking" surgery followed by Imatinib. He underwent debulking surgery due to pressure symptoms even in the presence of peritoneal metastasis. This approach, which would have been seen as "unconventional" then, proved to be beneficial to the patient. This supports the current view of using Imatinib with cytoreductive surgery for synchronous metastasis
The role of surgery may need redefining in such patients.
• Adjuvant therapy with Imatinib
There are reports showing benefits of adjuvant Imatinib in GIST of high malignant potential
• Laparoscopic surgery
The change in nomenclature from leiomyosarcoma to GIST and the advent of Imatinib has changed the general perception of these tumours to be of benign nature, and there is an increasing trend towards laparoscopic treatment
Due to limited number of patients we have not applied any statistics to the data but tried to highlight the grey areas in the management of these patients.
Conclusion
We feel that future surgical trials need to be directed towards
• Long-term follow up of small GIST located in areas that are not readily accesible and diagnosed soley on
• Defining the role of debulking surgery, with or without down staging of disease.
Laparoscopic surgery should be considered only if it is not compromising the principles of cancer surgery.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
Mr Stylianides helped in acquisition of data and preparation of the first draft. Mr Date was responsible for conception of idea, overall preparation and revision of the manuscript. Mr Mughal, Mr Pursnani and Mr Ward were responsible for management of the patient and revising the manuscript critically for important intellectual content. All authors read and approved the final manuscript.