Gastrointestinal stromal tumours

BACKGROUND: Gastrointestinal stromal tumours (GISTs), previously classified as benign or malignant smooth muscle tumours, are the most common mesenchymal tumours of the gastrointestinal tract. GISTs express a growth factor receptor with tyrosine kinase activity, termed KIT. Mutations of KIT are common in malignant GISTs and lead to constitutional activation of tyrosine kinase function, which causes cellular proliferation and resistance to apoptosis. GISTs are notoriously unresponsive to chemotherapy and, until the recent introduction of the KIT inhibitor imatinib, there has been no effective therapy for advanced, metastatic disease. METHODS: A Medline literature search was preformed to locate all articles relating to gastrointestinal tumours, GISTs, KIT and imatinib. RESULTS AND CONCLUSIONS: The 5-year survival rate after complete resection of GISTs is approximately 50 per cent. The median duration of survival for patients with a metastatic GIST is approximately 20 months, and 9-12 months for patients with local recurrence. Phase II trials have investigated the effect of imatinib on irresectable or metastatic GISTs. In these trials more than 50 per cent of patients responded to imatinib within a few months and approximately 12 per cent had disease progression. Uptake of [(18)F]fluoro-2-deoxy-D-glucose demonstrated by positron emission tomography has been found to be reduced after starting imatinib. The potential for cure and the optimal length of treatment is currently unknown. Imatinib is the first effective systemic therapy for metastatic and locally irresectable GISTs. Large multi-institutional clinical trials to investigate the efficacy of imatinib as adjuvant or neoadjuvant therapy for GISTs are now required.     

Gastrointestinal stromal tumours

Aim-Background

The aim of this study is to present our experience in surgery of GIS tumours Gastrointestinal stromal tumours (GISTs) represent a unique category of neoplasms in patients that exhibit long term survival. Sixty percent of GISTs present in the stomach, 30% in the small intestine, 5% in the colon and rectum and 5% in the oesophagus. Twenty five percent of the patients are diagnosed with metastases when being evaluated for the first time, due to the silent course of the disease. Computed tomography (CT) is the best imaging modality for tumours > 5 cm, while endoscopic ultrasound (EUS) is ideal for tumours < 2 cm. Recent research has also proved PET scan, either alone or combined with CT, as a useful adjunct to the diagnosis and planning of a therapeutic plan. Fifty percent of the patients may be cured with R0 excision, without the need for adjuvant therapy. Neoadjuvant therapy with imatinib is frequently employed in metastasized, large or relapsed tumours. Imatinib is also employed as adjuvant therapy in tumours that exhibit specific characteristics concerning its size, location and the number of mitoses.

Methods

A series of 8 cases of patients with GISTs that were treated in our department is presented in this article, as well as a brief review of the relevant literature.

Results

None of our patients presented with metastatic disease, while R0 excision was possible in every one of them. All tumours were positive for CD117, while 7 out of 8 patients presented with tumours positive for the expression of CD34. Adjuvant therapy was administered to 5 out of 8 patients (62%). All the treated patients remain alive and under oncologic follow-up, except for one patient who passed away due a myocardial infarction.

Conclusion

GISTs are infrequent tumors that due to their unique characteristics deserve special consideration and attention. Specific intraoperative details are important for the treatment of the patients and prognosis. An individualized approach is recommended and a multidisciplinary team consisting of radiologists, oncologists and surgeons should care for these patients.     

Gastrointestinal stromal tumours: Our experience

Background  

Gastrointestinal stromal tumours (GIST) are histologically heterogenous group of mesenchymal tumours arising in gastrointestinal tract (GIT), though they represent only 0.2% of all GI tumours. The advent of effective chemotherapy for GIST has altered but not diminished the role of surgery which remains the standard therapy for all resectable non-metastatic tumours.     

Gastrointestinal stromal tumours of the oesophagus

A rare case of gastrointestinal stromal tumour (GIST) of the oesophagus is presented. Pathological features with a review of the treatment options and the literature are presented.     

Prognostic factors influencing surgical management and outcome of gastrointestinal stromal tumours

BACKGROUND: The purpose of this study was to review surgical experience with gastrointestinal stromal tumours (GISTs) at a single tertiary university hospital, and to identify morphological and genetic prognostic markers of tumour progression. METHODS: Forty-eight GISTs from 39 patients were reviewed retrospectively. The prognostic significance of DNA copy number changes, measured by comparative genomic hybridization (CGH), and morphological markers in low-risk and high-risk tumours were investigated. RESULTS: Significantly more patients died from disease after incomplete tumour resection than after complete primary resection (P = 0.020). Tumour size of 5 cm or greater, mitotic count of 2 or more, and proliferative activity greater than 10 per cent were significantly associated with a shorter recurrence-free survival (P = 0.020, P = 0.001 and P = 0.002 respectively). Patients with low-risk tumours had a significantly better outcome than those with high-risk GISTs, both in terms of overall and recurrence-free survival (P < or = 0.001). CGH performed on 16 tumours revealed fewer DNA sequence copy number changes in low-risk than in high-risk GISTs. Non-progressive GISTs contained significantly fewer genetic alterations than recurrent or metastatic tumours (P < 0.001). Only tumours with more than five changes showed disease progression. CONCLUSION: Complete surgical resection is the most important means of cure for GISTs. DNA copy number changes are related to the behaviour of these tumours and may serve as additional prognostic markers.     

Gastrointestinal stromal tumours of the stomach: personal experience

Gastrointestinal stromal tumours are a relatively new nosological entity with an increasing incidence. CD117 positivity at immunohistochemical analysis is mandatory to distinguish them from other mesenchymal tumours. A gastric localisation is observed in more than 70% of cases. In the present paper 11 primary gastrointestinal stromal tumours of the stomach operated during the last decade at our institution were retrospectively reviewed. Hospital files and histological slides of 11 patients with gastrointestinal stromal tumours of the stomach undergoing surgical resection at our institution over the period from 1993 to 2003 were reviewed retrospectively. The variables analysed were: morphological and immuno-histochemical characteristics of the tumours, demographic data, type of surgical treatment and postoperative course. Long-term survival was evaluated on the basis of clinical and/or telephone follow-up in all patients. Immunohistochemical analysis for CD11 7 proved positive in all patients. The size of the tumours ranged from 3 to 23 cm: tumour size was > 5 cm and > 10 cm in 8 and 3 patients, respectively. Nodal involvement was detected in one patient and another had liver metastases. Surgical treatment consisted of wedge resection in 3 cases, distal subtotal gastrectomy in 4 and total gastrectomy in 4. In 2 patients surgical excision was extended to other organs. No postoperative mortality or major postoperative complications were observed. Nine patients were still alive at follow-up; 1 patient died as a result of a neoplastic relapse (38 months) and 1 died of other causes (48 months). The median survival was 42 months. Gastrointestinal stromal tumours are characterised by slow growth and therefore clinical signs are delayed. For that reason large tumours are often observed at the time of diagnosis. Surgical resection is the only potential curative treatment; but the risk of recurrence (local or at distance) remains high.     

Gastrointestinal stromal tumours and acute haemorrhage: description of four cases

Gastrointestinal stromal tumours are uncommon neoplasias arising from stromal tissue of the intestinal wall. Discovery of the protooncogene c-kit and the presence of the CD117 protein on the neoplastic cells of the majority of gastrointestinal stromal tumours may suggest their possible origin from Cajal cells. The clinical symptoms of gastrointestinal stromal tumours are related to tumour size and are generally aspecific: acute or chronic bleeding, abdominal pain and palpable mass are some of the most common signs. Digestive endoscopy or US-endoscopy for gastroduodenal tumours, ultrasonography and CT scans are the procedures of choice in the evaluation of the location, size, invasion of adjacent organs and metastases. Surgery is the only curative therapy for gastrointestinal stromal tumours. Chemotherapy or radiotherapy are of no use for metastatic disease, but good results are obtained with ST1571 in advanced disease. In the absence of metastases, it is quite difficult to distinguish between benign and malignant lesions. The most important prognostic factors are number of mitoses and tumour size. We report here on 4 consecutive cases of gastrointestinal tumours, 2 gastric and 2 duodenal, which presented with acute gastrointestinal bleeding.     

Gastrointestinal stromal tumours: a broad spectrum of clinical presentations

Gastrointestinal stromal tumours, though rare, are the most common mesenchymal neoplasms affecting the gastrointestinal tract. The most frequent sites of origin are the stomach and the small bowel, but they can occur anywhere in the gastrointestinal tract. Mesenteric and retroperitoneal forms have been described. The Authors present their personal experience with the treatment of gastrointestinal stromal tumours, with particular reference to the broad spectrum of clinical presentations and to the consequent therapeutic implications. We report on a retrospective analysis of the clinical presentations and courses, surgical management and pathological features of 27 patients with such tumours treated in our institution from 1993 to 2005. The variables analysed were the morphological and clinical characteristics of the tumours, demographic data, type of surgical treatment and postoperative course. Long-term survival was evaluated on the basis of clinical and/or telephonic follow-up in all patients. One tumour was located in the oesophagus, 14 in the gastric area, 7 in the small bowel, 2 in the colon-rectum, and 3 in the peritoneum. All patients studied received radical surgical treatment. In 7 patients surgical resection was extended to other organs. No postoperative mortality or major postoperative complications were observed. Twenty-two patients are still alive at follow-up. Three patients died as a result of neoplastic relapse and 2 of other causes. The median survival was 36 months. The actuarial 3- and 5-year survival rates were 89.7% and 67.8%, respectively. Our experience indicates that the site of origin of gastrointestinal stromal tumours with their broad spectrum of clinical presentations may influence both the therapeutic choice (neoadjuvant utilisation of imatinib mesylate) and the surgical treatment (wedge resection vs enlarged operations).     

Gastrointestinal stromal tumours: a case report and review of the literature

Gastrointestinal stromal tumours are a heterogeneous group of neoplasms of the digestive apparatus characterised by a complex histogenesis and lines of differentiation that make it difficult to predict their biological behaviour. Expression of the c-kit receptor in about 99% of gastrointestinal stromal tumours suggests they may originate from a common mesenchymal element with a variable possibility of phenotypical differentiation. The Authors report a case of small bowel gastrointestinal stromal tumour referred to them for severe bleeding and treated surgically. They then go on to analyse the diagnostic and therapeutic problems that such tumours entail. Surgery is currently the only therapeutic option capable of improving survival in patients with gastrointestinal stromal tumours. Further studies are needed to assess the efficacy of laparoscopy and new chemotherapeutic agents.     

Gastro-intestinal stromal tumours (GISTs): prognostic and therapeutic features

The prognostic factors may be different evaluated. The biological behaviour is only hypothetical, according to the duration of symptomatology, the site and size of the tumour, the presence of hemorrhagic or necrotic areas, the cytological modifications and, above all, the number of mytosis: 5 mytosis x 50 HPF are considered significant for malignancy. In last thirty years we have reported 40 GISTs, mostly gastric. All of them have been operated on with simple enucleation or organ resection. In the benign GISTs (26 pts) we have reported early mortality only in 5 cases; in the borderline forms (6 pts), in 4 rapidly evolving cases, the tumour had > 5 cm in size and the mytosis were > 5 x 50 HPF. Also in the malignant GISTs we have noted a good correlation between survival and clinical and histopathological findings. As well in this experience the biological behaviour of GISTs is difficult in interpretation. Anyway the dimensions, the genetic modifications and the number of mytosis are considered good indicators for malignancy. We have always indicated a surgical treatment, enlarged according to the invasion of adjacent organs.     

Surgical management of gastrointestinal stromal tumours

Background:

Over the past decade, gastrointestinal stromal tumours (GISTs) have served as a model for the application of tyrosine kinase inhibitors in the treatment of solid neoplasms. Operative and medical management of GISTs is rapidly evolving, but current guidelines appear restricted to basic non‐organ‐specific recommendations.

Methods:

A PubMed search was made of the English literature from 1998 to 2008 for references containing the terms ‘gastrointestinal stromal tumours’ and ‘surgery’. This paper reviews the various operative strategies so far reported for GISTs within the digestive tract.

Results:

Many original procedures tailored to the specific characteristics of these rare sarcomas have been reported. GISTs exhibit distinct features, in particular an absence of metastases within locoregional lymph nodes. Operations requiring extended lymph node dissection, typically designed for adenocarcinomas, such as gastrectomy with extended lymph node dissection, Whipple's procedure and total mesorectum excision, are inappropriate for treating GISTs originating from the stomach, duodenum and rectum respectively.

Conclusion:

GISTs allow the possibility of performing oncologically adequate but limited (wedge; segmental) resections. Such surgery can be carried out in a variety of ways, such as open, laparoscopic, trans‐sacral or endoscopic. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Primary gastrointestinal sarcomas: analysis of prognostic factors and results of surgical management

BACKGROUND: This study was done to review the clinical presentation, surgical management, and prognostic factors for primary gastrointestinal sarcomas. METHODS: We reviewed medical records of 55 patients who were treated for primary gastrointestinal sarcomas from 1981 through 1996. Mean follow-up time was 32 months. RESULTS: Clinical findings included gastrointestinal bleeding (51%), palpable mass (36%), and abdominal pain (33%). The stomach was the most common site of disease (53%), followed by the small intestine (33%). Tumors were high grade in 76% of patients and low-grade in 24% of patients. Complete resection of all gross disease was accomplished in 35 patients (64%), incomplete resection in 17 patients (31%), and biopsy only in 3 patients (5%). Adjacent organ resection was required in 19 patients (35%). Overall actuarial survival was 22% (median survival, 32 months). Unfavorable prognostic factors were incomplete resection, high-grade histologic features, and tumor size of 5 cm or more (P<.05). En bloc resection of contiguous organs did not adversely effect survival. In patients with complete resections, tumor grade was the most important prognostic factor (median survival, 55 months vs 19 months for low-grade vs high-grade tumors; P<.05). CONCLUSIONS: Aggressive surgical resection, including en bloc resection of locally advanced tumors, appears warranted. Despite complete resections, patients with high-grade tumors remain at risk for recurrence.     

Primary sclerosing cholangitis: surgical options, prognostic variables and outcome

The natural history of primary sclerosing cholangitis (PSC) is poorly defined and its management remains controversial. Forty-eight symptomatic patients (median age 39 years, range 8-67 years; 30 male) with PSC were reviewed retrospectively. Thirty patients had inflammatory bowel disease. Four patients (8 per cent) developed or had an associated malignancy. Twenty-one (44 per cent) died; overall 5 year actuarial survival was 30 per cent. Twenty-three patients had 27 non-transplant related biliary operations (16 patients specifically for PSC) of whom 12 died. Serum bilirubin was the only parameter to improve after biliary surgery. Seventeen patients (35 per cent) underwent orthotopic liver transplantation (OLT) of whom nine are currently alive (1 year projected survival of 55 per cent). Previous biliary surgery correlated with a poor outcome (P less than 0.0001) after OLT. Being male, presence of cirrhosis, duration of symptomatic disease (greater than 3 years) and a serum bilirubin level greater than 100 mumol/l at presentation, were independently associated with a poor outcome (P less than 0.05). These data provide evidence that PSC is a progressive disease and conventional surgical options have little influence on the outcome. Previous biliary surgery adversely affects outcome following OLT. For progressive liver disease, liver transplantation should be considered the treatment of choice.     

Gastrointestinal stromal tumors: analysis of clinical and pathologic factors

Gastrointestinal mesenchymal tumors have been classified as benign (leiomyoma) or malignant (leiomyosarcomas). More recently, these tumors have been termed gastrointestinal stromal tumors (GISTs). GISTs have a highly variable clinical course. This review analyzes the clinical presentation, pathologic examination, and long-term follow-up of patients with GIST. A retrospective analysis of the clinical course of patients with GIST at a single institution from 1986 to 1998 was performed. Nineteen patients with GIST (12 gastric, two duodenal, three jejunal, and two rectal) were treated. The most common clinical presentation was gastrointestinal bleed. CT scans, contrast studies, and endoscopy were used to identify a tumor mass. Diagnosis of GIST was made in only two patients preoperatively. Tumor size ranged from 0.8 to 23 cm. Histology of the tumors was variable. All patients underwent surgical resection with curative intent. Follow-up ranged from 2 to 55 months. There were two perioperative deaths. Local recurrence occurred in one patient. GISTs are uncommon. Preoperative diagnosis can be difficult, and often the diagnosis is made at the time of surgery. With complete resection of the tumor the clinical course is favorable with very few local recurrences. Therefore complete resection of the tumor is recommended.     

Aggressive fibromatosis--impact of prognostic variables on management

OBJECTIVE: To determine the impact of prognostic variables on local control in patients with aggressive fibromatosis treated with or without radiation. MATERIALS AND METHODS: Forty-two patients presenting to the combined sarcoma clinic at Johannesburg Hospital with aggressive fibromatosis from 1990 to 2003 were analysed retrospectively. There were 14 males and 28 females. The lesions involved the head and neck in 6 cases (14%), the thorax in 6 (14%), the extremities in 19 (45%) and the abdomen in 11 (26%). Thirty-seven patients (88%) presented to the clinic for the first time, whereas 5 (12%) had recurrent disease at presentation. Fifteen patients (36%) underwent excision only, 15 (36%) had excision followed by postoperative radiation, 8 (19%) had biopsy only, and 4 (9%) had radiation only. The median dose of radiation was 60 Gy (range 9 - 70 Gy). RESULTS: One patient had local failure following excision and postoperative radiation therapy. The local control was 100% for surgery alone and 86% for surgery followed by postoperative radiation at > or = 24 months. On univariate analysis, age, sex, positive margins, primary or recurrent presentation, site of involvement and initial treatment did not affect local control significantly. Eight of 19 patients (42%) receiving radiation developed severe moist desquamation following treatment, and all these patients had doses of 60 Gy or more. CONCLUSION: Surgery with or without radiation therapy gave excellent local control. The addition of radiation therapy to surgery as well as other known prognostic parameters did not impact on local control. The morbidity of radiation treatment is considerable, as noted in this series, and adjuvant radiation therapy should therefore be considered only in situations where the risk of recurrence and the morbidity of re-excision are high.     

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目的 探讨胃肠道间质瘤的临床表现、诊断、治疗和预后。方法 回顾性分析1999年4月至2002年7月收治的15例胃肠道间质瘤的临床和病理资料。结果 主要临床表现为腹部不适(7／15)、消化道出血(6／15)。病变部位为胃13例，十二指肠l例，小肠1例。14例行手术治疗。15例镜下均见梭形细胞，其中良性9例，交界性4例，恶性l例，胃癌伴良性间质瘤l例。免疫组化CDll7( )73％，CD34( )73％，SMA(-)73％，S—100(-)67％。随访率100％，病人均存活。结论 内镜和影像学检查是发现胃肠道间质瘤病变的主要手段，术前确诊仍较困难，手术切除是病理确诊和治疗的主要方法。     

Renal tumours with cavo-atrial extension: surgical management and outcome

Surgery is the most effective treatment for the management of patients with renal cell carcinoma (RCC) and involvement of inferior vena cava (IVC). Data were accrued for 68 consecutive patients, who underwent surgical resection for RCC with IVC extension and required cardiothoracic surgical input from May 1993 to May 2005. The mean age of patients was 60.7 years (range 25-84, S.D. 11.6 years), 49 of these were males. The majority required application of vascular clamp at the junction of IVC with right atrium (RA), however, 21 patients required cardiopulmonary bypass (CPB) (29-193 min, mean 131 min). Hypothermic circulatory arrest (HCA) (12-42 min, mean 26 min) was used in 17 patients. The 30-day mortality was 6% (four patients) with no death in the elective CPB group. At a mean follow-up of 31 months, the overall two- and five-year survival rates were 50% and 37%, respectively. Cox regression revealed presence of metastasis (Odds ratio (OR) 3.1, 95% CI 1.2-8.2) and age >70 years (OR 2.9, 95% CI 1.3-6.3) adversely affected the long-term outcome. The management of RCC with IVC involvement is evolving for this complex group of patients. A multidisciplinary approach in selected patients is associated with good short- and long-term results.