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Gastrointestinal stromal tumors (GIST) of the stomach: retrospective experience with surgical resection at the National Cancer Institute
Abstract
Gastric GISTs account for more than half of all gastrointestinal stromal tumors and represent less than 5% of all gastric tumors. The peak age for harboring GIST of the stomach is around 60 years and a slight male preponderance is reported. These tumors are identified by expression of CD117 or CD34 antigen. Symptoms at presentation usually include bleeding, abdominal pain or abdominal mass. Endoscopically, they typically appear as a submucosal mass with or without ulceration and on CT scans an extragastric mass is usually seen. Complete surgical resection provides the only chance for cure, with only 1-2 cm free margins needed. However, local recurrence and/or metastases supervene in almost half the patients treated with surgery alone, even when no gross residual is left. Thereby imatinib mesylate was advocated as an adjuvant to surgery, which appears to have improved disease-free and overall survival.
The aim of this work was to assess clinico-pathological features of gastrointestinal stromal tumors (GIST) of the stomach and to appraise the results of treatment by surgery in patients treated at the National Cancer Institute (NCI) of Cairo between January 2002 and December 2007.
Nineteen patients with histologically and immuno-histochemically proven GIST of the stomach were treated by surgery at the NCI during the 6-year study period. Preoperative assessment included detailed history, clinical examination, full laboratory tests, endoscopy, abdominal ultrasound and CT. General medical assessment included chest X-ray, ECG and echocardiography.
The patients' age ranged from 26 to 77 years with a median of 51 years. Obvious male/female preponderance was noticed (68.4% to 31.6%). Tumors were located at the upper 1/3 in 42.1%, at the middle 1/3 in 31.6% and at the lower 1/3 in 26.3%. The most common clinical presentation was related to bleeding (hematemesis, melena or anaemia) and was seen in 63.2%. No tumors were labeled as very low or low risk while there were 52.6% intermediate risk and 47.4% high risk. Wedge resection was carried out in 15.8%, partial gastrectomy in 37.8%, total gastrectomy in 5.2%, extended gastric resection in 21.1% and only biopsy in 5.2%. Lymphadenectomy was carried out in 5/19 patients to reveal negative lymph nodes in all five. Complications occurred in 73.7% of patients and only 1 case of early postoperative mortality was recorded. Two patients were lost to follow-up. The remaining 16 patients were followed-up for a period ranging from 6-34 months with a mean of 19.5+/-5.6 months and they were all alive by the end of the study, 10 were free of disease and 6 showed disease recurrence.
Gastric GIST can present with vague and non specific clinical picture. Therefore, thorough clinical and radiological evaluation and preoperative endoscopy and biopsy are essential to reach the diagnosis and to assess the risk for metastasis. The clinical outcome of these tumors is influenced by completeness of tumor extirpation while avoiding tumor rupture, and by the tumor malignant potential. Accordingly for tumors with adverse factors, multimodal therapy with adjuvant imatinib or one of its successors should be considered in order to improve overall and disease-free survival.
... Although the potentially curative treatment for GISTs is surgical resection, their management has been revolutionized by the approval of imatinib as an adjuvant and neoadjuvant therapy [3][4][5]. Few studies have been made on GIST in Africa and to the best of our knowledge, no case series has been published in Benin [6,7]. Tumors are often diagnosed at a later stage in Africa [8,9]. ...
... Similar trends were seen in other African series. Only 19 cases of gastric GIST were identified in Cairo, Egypt, over a 6-year period at the National Cancer Institute; and 10 cases of GIST (all localizations included) over a 8-year period at the main hospital of Dakar, Senegal [6,7]. The median age at diagnosis was 52 years. ...
... The median age at diagnosis was 52 years. Similar data are reported by other series from Africa [6,7]. The median age in the western series seems higher than ours, ranging from 65,8 to 69 years [12][13][14]. ...
Background
GISTs are rare tumors but the most frequent mesenchymal tumors of the digestive tract. Diagnosis and treatment are challenging in low-income countries due to relatively poor access to immunohistochemistry and targeted therapy. In Africa, there are few studies about it. Imatinib, an oral targeted therapy, has been available in Benin since 2010 and free since 2016. This study describes the diagnosis and therapeutic management of GIST in Cotonou, Benin.
Methods
This is a descriptive cross-sectional study, with retrospective data collection over a 10-year period from 2010 to 2020, focused on patients with histological confirmed gastro-intestinal stromal tumor (GIST). Cases were identified using the registry database and the archival files of the Hubert Koutoukou Maga National University Hospital of Cotonou (CNHU-HKM).
Results
Fifteen GISTs were identified during the study period. The median age was 52 and the sex ratio was 2:1 (10 males and 5 females). The most frequent symptom was abdominal pain (n = 12). Delay in care seeking after onset of symptoms ranged from 24 h to 15 years. The most common site for GISTs was the stomach (n = 8). The median tumor size was 11 cm and the majority (n=10) was metastatic or locally advanced at the time of diagnosis. The tumors were often spindle-shaped at histology (n = 13) and the majority expressed KIT (n = 14). Most of the tumors (n = 12) were at high risk of recurrence according to the Joensuu scoring system. The availability of imatinib has improved the outcome of GIST with response in all cases it was used in neoadjuvant setting (n = 7).
Conclusion
GISTs are rare tumors and preferentially affect the stomach in Cotonou). Most of the tumors were large, unresectable at the time of diagnosis and at high risk of recurrence. Access to imatinib has revolutionized the management of those tumors in our country.
... All of those indicate that effective postoperative pain control after an ESD procedure is important for patients' short-term outcomes and long-term treatment compliance. In clinical practice, however, both anesthesiologists and clinicians are often reluctant to use painkillers such as opioid drugs due to the concern that these drugs may mask some postoperative complications of ESD, such as perforation, hemorrhage, and others [6,7]. In the available literature, thus, there have only been a few studies regarding postoperative pain management after ESD [8][9][10]; further studies are needed to obtain the appropriate and effective methods of pain control after ESD. ...
... The VAS score "0" was defined as no pain and "10" was defined as pain beyond imagination. According to the VAS scores, the severity of postoperative pain was classed into mild (0-3), moderate (4)(5)(6), and severe (7)(8)(9)(10). If the VAS pain score was ≥4 or the patient needed additional analgesia, 1 mg of intravenous morphine was administered. ...
Background:
Postoperative pain is one of the most common complications after gastric endoscopic submucosal dissection (ESD); however, there have been only a few studies assessing the efficacy of interventions on postoperative pain after gastric ESD. This prospective randomized controlled trial was designed to assess the effect of intraoperative dexmedetomidine (DEX) on postoperative pain after gastric ESD.
Materials and methods:
A total of 60 patients undergoing elective gastric ESD under general anesthesia were randomly divided into the DEX group receiving DEX with a loading dose of 1 μg/kg, followed by a maintenance dose of 0.6 μg/kg/h until 30 min before the end of the endoscopic procedure, and the control group receiving normal saline. The primary outcome was the visual analog scale (VAS) score of postoperative pain. Secondary outcomes were the dosage of morphine for postoperative pain control, hemodynamic changes during the observable period, the occurrence of adverse events, lengths of postanesthesia care unit (PACU) and hospital stays, and patient satisfaction.
Results:
The incidence of postoperative moderate to severe pain was 27% and 53% in the DEX and control groups, respectively, with a significant difference. Compared to the control group, VAS pain scores at 1 h, 2 h, and 4 h postoperatively, the dosage of morphine in the PACU, and the total dosage of morphine within 24 h postoperatively were significantly decreased in the DEX group. Both incidences of hypotension and use of ephedrine in the DEX group were significantly decreased during surgery, but they were significantly increased in the postoperative period. Postoperative nausea and vomiting scores were decreased in the DEX group; however, the length of PACU stay, patient satisfaction, and duration of hospital stay were not significantly different between groups.
Conclusion:
Intraoperative DEX can significantly decrease postoperative pain level, with a slightly reduced dosage of morphine and a decreased severity of postoperative nausea and vomiting after gastric ESD.
... Metastasis during initial presentation or after resection more commonly involve the liver and peritoneal surfaces due to GISTs tendency for local invasion [9,10]. Rarely lymph nodal involvement has been reported [11], but routine lymphadenectomy is not recommended [12]. Up to 30% of GISTs have poor prognostic factors including size >5 cm, lobulated contour, heterogeneous enhancement, presence of mesenteric fat infiltration, ulceration, regional lymphadenopathy or an exophytic growth pattern on CT [13]. ...
... GISTs occurring in the duodenum and remainder of the small bowel can also demonstrate any growth pattern but are commonly exophytic, possibly explained by slow growth and often delayed presentations (Figs. 6,7,8,9,10,11,12,13). Calcifications are uncommon but can occasionally be present within larger GISTs (Figs. 7, 11). ...
Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, are a relatively recently described entity. Most exhibit a mutated tyrosine kinase receptor gene and in some capacity are treated by tyrosine kinase inhibitors. GISTs can occur across the age spectrum but are more common in patients older than 40 years. They exhibit a wide range of clinical presentations and imaging characteristics. All patterns of enhancement on contrast enhanced computed tomography (CECT) can be seen with GISTs, including hypoenhancing, isoenhancing, and hyperenhancing tumors. They can be large or small, endoluminal or exophytic. Clinical presentations include asymptomatic patients, nonspecific symptoms, obstruction, and bleeding. Bleeding can take the form of slow, intraluminal GI bleeding or massive intraperitoneal bleeding secondary to rupture and can be seen regardless of the enhancement pattern. Some can cavitate, ulcerate, rupture or cause fistulae. The radiologist’s knowledge of the variety of combinations of presentations can narrow the differential diagnosis and ultimately lead to faster diagnosis and treatment.
... The completeness of surgical resection is a major prognostic factor [6]. But some authors suggested size of the tumor is more important than completeness of surgery [7]. After complete tumor removal, recurrence is not so rare, peritoneal surface and liver parenchymas are common metastasis sites. ...
... Naguib et al. in a report on 19 patients with gastric GIST had performed lymph node dissection for 5 cases. The reason for dissection was gross lymph node enlargement and none of nodes were involved [1,7]. ...
The Gastrointestinal Stromal Tumor (GIST) is a rare mesenchymal tumor of gastrointestinal (GI) tract. This tumor has tendency to liver metastasis and peritoneal recurrence, however; the primarily lymph node involvement or metastasis is rare. Here we reported a 17-years-old girl with multifocal gastric GIST and multiple lymph node involvement at presentation and recurrence in celiac lymph nodes. We also review some case reports on lymph node metastasis in GIST.
... This seemingly paradoxical phenomenon could also be explained by the low metastatic rate of lymph nodes for this disease. A C B D cell positive (12). Similarly, our supplemental analysis showed that over 90% of the dissected lymph nodes were cancer cell negative. ...
Background:
Current clinical practice suggests lymphadenectomy for gastrointestinal stromal tumor (GIST) patients with enlarged lymph nodes, but little is known about the influence of lymphadenectomy on long-term survival.
Methods:
This population-based study consisted of 3,819 non-metastatic GIST patients diagnosed between January 1st, 2001, to December 31st, 2015, from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier methods and Cox proportion regression models were used to compare differences in overall survival (OS) and cancer-specific survival (CSS) between the lymphadenectomy group and non-lymphadenectomy group.
Results:
Among the 3,819 GIST patients, 1,202 received lymphadenectomy and 2,617 did not receive lymphadenectomy. Lymphadenectomy was associated with poor OS (adjusted HR =1.25, 95% CI: 1.06-1.47) and CSS (adjusted HR =1.32, 95% CI: 1.07-1.64) in GIST patients. This was especially evident in GIST patients with a tumor size less than 2 cm (OS, HR =1.91, 95% CI: 0.79-4.60 and CSS, HR =6.37, 95% CI: 1.85-21.90), who were more than 40 years old (OS, HR =1.28, 95% CI: 1.08-1.51 and CSS, HR =1.36, 95% CI: 1.09-1.70), and with a stomach tumor (OS, HR =1.39, 95% CI: 1.12-1.72 and CSS, HR =1.77, 95% CI: 1.33-2.35).
Conclusions:
In conclusion, contrary to what was previously presumed, lymphadenectomy was associated with an increased and not a decreased risk of mortality in GIST patients.
... In our patient, lesion resection was facilitated by using a double stapler with simultaneous anastomosis, and intestinal resection was the minimum required to guarantee a negative margin. Lymphadenectomy is not required for clinically negative lymph nodes, as their involvement is very rare 1,6,7,10 . Laparoscopic approach is not recommended in patients with large tumors because of the risk of causing tumor capsule rupture 7 . ...
Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest mesenchymal tumors of the gastrointestinal tract (GIT). GISTs can affect any segment of the GIT, but the usual location is the stomach, followed by the small intestine. Surgical resection of the tumor is the gold standard treatment for localized GISTs, and in patients with inoperable and metastatic disease, imatinib mesylate is the standard treatment. Pathological diagnosis is based on morphology and immunohistochemical findings. We report the case of a 55-year-old man with jejunal GIST presenting with endophytic and exophytic growth, located in the proximal jejunum. He had history of melena, anemia and one episode of enterorrhagia, and was treated with surgical resection of the lesion.
Keywords: Gastrointestinal stromal tumor; gastrointestinal neoplasms
... Furthermore, adjuvant therapy with imatinib mesylate is indicated for specific cases, such as tumor measuring more than 5 cm, more than 5 mitoses per 50 HPF, malignancy behavior, recurrence or when there is no possibility of resection 10 . With regard to the surgical technique, resection with a margin of 1-2 cm is usually recommended, although microscopic margins that are negative for tumor cells are sufficient for complete and curative resection 11 . During surgery, when removing the surgical specimen, caution should be taken in order not to cause tumor capsule rupture. ...
Gastrointestinal stromal tumors (GISTs) are the most common non-epithelial tumors of the gastrointestinal tract1. The most usual location is the stomach, followed by the small intestine, where it may cause digestive bleeding and anemia6. Surgical resection of the tumor is the gold standard treatment, and definitive diagnosis is based on immunohistochemical analysis of the surgical specimen8. We report the case of a 53-year-old man with gastric GIST presenting with endophytic and exophytic growth, located at the posterior wall of the stomach, in the antrum-body transitional zone, treated with gastric sleeve.Keywords: Gastrointestinal stromal tumors; gastrointestinal neoplasms; gastric sleeve; diagnosis; prognosis; treatment
... The mainstay of treatment for primary GIST is surgical resection, whenever possible. The overall 5 year survival rate for resectable GISTs has been shown to range from 46% to 78.5% [23,24]. However, predicting the recurrence rate of primary resectable GISTs has been very challenging. ...
... Tüm sindirim sistemi boyunca saptanabilmekle beraber en sık midede ortaya çıkar (3). Tüm gastrointestinal sistem tümörlerinin %1'inden azını, tüm mide tümörlerinin ise yaklaşık %5'ten az bir kısmını oluşturmaktadır (7). GİST'ler, KIT tirozin kinaz reseptörü içermeleri ile de diğer gastrointestinal mezenkimal tümörlerden ayrılan spesifik bir tümör grubu oluşturmaktadır. ...
... GI tract is the most common location contributing to more than 80% of GISTS. 50-70% of GI tract GISTS are located in stomach [5]. In GI tract these arise from the layer muscularis propria [6]. ...
Gastrointestinal tumors are rarest of the gastrointestinal tumors. They arise from interstitial cells of Cajal. Objective: To review the current diagnosis and management of gastrointestinal tumors. Material and methods: Pubmed was searched for ‘gastrointestinal tumors’ and relevant studies used for this review. Conclusion: GISTs are one of the rarest tumors of GI tract. They are more common in middle aged males. Diagnosis involves radiology, histopathology and immunohistochemistry. Treatment is surgical and chemotherapy.
... The well-documented, generally benign behavior and the high prevalence of early gastric GIST in the elderly argue for a conservative management. Particularly in older patients, it is important to consider not only the hospital morbidity but also the low but not negligible perioperative mortality, which may amount to 1% or higher according to the published literature [27,28] . There are no clinical studies that have demonstrated any advantage (in quality-of-life or in survival) of surgery over endoscopic surveillance in patients with early (< 1 cm) gastric GIST [6] . ...
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract. Approximately two thirds of clinically manifest tumors occur in the stomach, nearly one third in the small bowel, and the rest in the colorectal region with a few cases in the esophagus. GIST originate within the smooth muscle layer in the wall of the tubular gastrointestinal tract and grow mostly toward the serosa, far less often toward the mucosa. In the latter case, ulceration may develop and can cause gastrointestinal bleeding as the cardinal symptom. However, most GIST of the stomach are asymptomatic. They are increasingly detected incidentally as small intramural or submucosal tumors during endoscopy and particularly during endoscopic ultrasound. Epidemiological and molecular genetic findings suggest that early asymptomatic GIST of the stomach (< 1 cm) show self-limiting tumorigenesis. Thus, early (< 1 cm) asymptomatic gastric GIST (synonym: micro-GIST) are found in 20%-30% of the elderly. The mostly elderly people with early gastric GIST have an excellent GIST-specific prognosis. Patients with early GIST of the stomach can therefore be managed by endoscopic surveillance.
... A lymphadenectomy is not imperative because GIST rarely metastasize to the lymph nodes. [22][23][24][25] Diagnosis were confirmed by two pathologists who placed the tumors in risk categories using Fletcher's system. 3 If the margin of the tumor specimen was microscopically positive, showing tumor cells in the frozen section, then extensive resection was indicated. For all patients, antibiotics were administrated the day prior to the operation. ...
To compare the efficacy of laparoscopically assisted and open resections in treatment of small bowel stromal tumors (SBST).
A retrospective study of 85 patients who underwent curative resections for SBST (38 by laparoscopically assisted procedures and 47 by open procedures) was performed.
There were no differences between open and laparoscopically assisted approaches in terms of patients' age, gender, presenting symptoms, histological risk or extent of resection (P > 0.05). The median tumor size for laparoscopically assisted resections was 4.0 cm (range 1.2-7.0 cm), which was the same as that for the open resections (range 2.0-10.0 cm). There were fewer complications in the laparoscopic group than those in the open resection group (7.9% vs 17.0%), but no significant difference was observed (P > 0.05). The 2-year survival of the two patient groups was almost the same (86.8% vs 89.4%). Laparoscopically assisted procedures required on average 22.5 min less of operating time (87.5 min vs 110.0 min, P = 0.006), 1.0 day less of bowel recovery time (3.0 days vs 4.0 days, P = 0.001) and 5.0 days less in hospital stay (8.0 days vs 13.0 days, P < 0.001).
Laparoscopically assisted resection of SBST is a safe alternative to open resection.
... Primary GISTs, as in the case here, have the potential for curative treatment with surgical resection. Overall 5-year survival rates for resectable GISTs have been shown to range from 46% to 78.5%; however, predicting the recurrence rate of primary resectable GISTs has been very challenging [17,18]. The survival rates from the reported gall bladder GISTs are mixed with only short-term followup noted in some of the cases. ...
Gastrointestinal stromal tumors (GISTs) compose the largest category of well-recognized nonepithelial neoplasms of the gastrointestinal tract (GI). GISTs of the gallbladder are extremely rare tumors. Only four malignant, two benign and one GIST-like tumor of the gall bladder have ever been described. The four malignant GISTs were all positive for CD 117 antigen (c-kit). We present for the first time a malignant gastrointestinal stromal tumor of the gallbladder, immunoreactive for platelet-derived growth factor receptor alpha (PDGFRA) and negative for CD 117 antigen (c-KIT).
A 65-year-old man presented to our hospital with a chief complaint of epigastric discomfort. Upper gastrointestinal endoscopy showed a submucosal tumor at the esophagogastric junction. Histopathological examination was positive for c-kit and CD34, and he was diagnosed with a gastric gastrointestinal stromal tumor (GIST). Computed tomography showed several swollen lymph nodes with a diameter of 3-5 mm in #1 and #2. Intraoperatively, lymph node #2 was sampled for a rapid pathological diagnosis, and metastasis was detected. Laparoscopic proximal gastrectomy with D1+ lymph node dissection was performed. Postoperative pathological examination showed a GIST, 30 mm in diameter, and one lymph node metastasis in #2. In general, gastric GISTs are treated with partial resection only, and lymph node dissection is not performed. However, it is necessary to recognize that there are rare cases of lymph node-positive GISTs, and this case is reported along with a review of the literature.
The chapter gives an overview of different mesenchymal lesions occurring in the gastrointestinal tract. After going through this chapter, the reader would be competent enough for the following things:
Background: GISTs are rare tumors but the most frequent mesenchymal tumors of the digestive tract. Diagnosis and treatment are challenging in low-income countries due to relatively poor access to immunohistochemistry and targeted therapy. In Africa there are few studies about it. This study described the diagnosis and therapeutic management of GIST in Cotonou, Benin.
Methods: This was a descriptive cross-sectional study, with retrospective data collection over a 10-year period from 2010 to 2020, focused on patients with histological confirmed gastro-intestinal stromal tumor (GIST). Data analysis was performed with Epidata Analysis software version 3.0.0.1.
Results: Fifteen GISTs were identified during the study period. The median age was 52 and the sex ratio was 2. The most frequent symptom was abdominal pain (n = 12). Delay in care seeking after onset of symptoms ranged from 24 hours to 15 years. The most common site for GISTs was the stomach (n = 8). The median tumor size was 11 cm and the majority (n=10) was metastatic or locally advanced at the time of diagnosis. The tumors were often spindle-shaped at histology (n = 13) and the majority expressed KIT (n = 14). Most of the tumors (n = 12) were at high risk of recurrence according to the Joensuu scoring system. The availability of imatinib have improved the outcome of GIST with response in all cases it was used in neoadjuvant setting (n = 7).
Conclusion: GISTs are rare tumors and preferentially affect the stomach in Cotonou. Most of the tumors were large, unresectable at the time of diagnosis and at high risk of recurrence. Access to imatinib has revolutionized the management of those tumors in our country.
Background: Gastrointestinal stromal tumors are some of the most common mesenchymal tumors of the gut. The aim of this study is to asses the clinical manifestation and treatment of gastric GISTs. Methodology: We performed a retrospective 5-year multicenter study conducted on a prospective collected database, which includes all the patients diagnosed with GIST in which surgery was performed. We selected all the pateients with gastric GISTs and we analyzed the clinical manifestation, treatment and prognostic factors. Results: There were 42 patients with GISTs of which the gastric GISTs were encountered in 23 cases (54.76%). There were 7 laparoscopic resections and 16 open surgery resections. Pathological examination showed that many of the patients were in group 6a and 6b (30.43%). CD117 was positive in 91.3% of cases. Regarding postoperative morbidity, there were 4 cases of pulmonary complications, 3 cases of surgical site infection and one postoperative hemorrhage. Conclusions: In our experience surgery for gastric GIST must be performed by a highly trained team, the keyset for a improved survival is the multidisciplinary approach that includes an accurate diagnosis, prognostic risk stratification and accurate treatment.
Discovery of the molecular pathogenesis of Gastrointestinal stromal tumors led to the development of targeted therapies, revolutionizing their treatment. However, surgery is still the mainstay of GIST therapy and the only chance for cure.
Here we present a single institutional consecutive case series of 159 GIST patients.
A total of 159 GIST-patients who underwent resection between 1994 and 2011 were reviewed for clinicopathohistological data, informations on surgical and medical therapy and further follow up, outcome and survival data.
Laparoscopic (25.2%) and open (71.1%) GIST surgery achieved complete resection rates of 97.5% and 85.2%, whereas 44.4% of incomplete and 6.6% of complete resected patients died from GIST. Compared to open surgery laparoscopy significantely reduced duration of operation (183.4 vs. 130.6 min), length of hospitalization (16.1 vs. 8.3 d) and morbidity (23% vs. 7.5%). Mean survival time was 3.7±2.7 years (R0: 5.1 a and R1: 2.6 a) and the mean overall survival was 4.5±3.8 years.
Complete surgical resection is the primary goal and laparoscopy can be performed safely in a subset of GIST-patients with potential perioperative advantages. Although not proven by the present study the authors assume that multimodal GIST-treatment, as performed in reference-centers, is required for advanced or high risk disease. Our data suggest the potential for minimally invasive GIST resection to achieving comparable oncological outcomes as after open surgery while providing low morbidity rates.
Background/aims:
Gastrointestinal stromal tumors (GISTs) have fairly recently been identified as a new type of tumor, thanks to advances in immunohistochemistry. Aim of our work was to investigate and describe GISTs in our hospital in a 10-year period.
Methodology:
Records of patients treated for GIST were analyzed and data describing demographics, comorbidities, primary tumor site, initial symptoms, immunohistochemical characteristics, method of detection and grade of malignancy were shown for each patient.
Results:
A total of 31 patients were analyzed. There was 54.8% of women and 46.7% of men with GIST. The mean age was 61.9±12.8 years. Predominant symptoms and signs were abdominal pain and anemia, bloody stool or melena, even though a significant portion of patients did not have any, or only mild symptoms. Stomach was the most frequent location of the tumor. CD117 was positive in all but two biopsy specimens.
Conclusions:
We observed approximately the same incidence of GISTs as in other published data. However, we reported less asymptomatic cases at the time of diagnosis. Also, we reported more women diagnosed with GIST in our population. Even though many tumors were diagnosed by other methods, immunohistochemistry remains the definitive diagnostic method.
As compared with Eastern countries, the incidence of gastrointestinal diseases caused by the ingestion of nematode eggs is very low in Europe, in spite of the fact that the consumption of raw fish has increased in these countries as well in recent years. The authors present here, a rare case of gastrointestinal bleeding due to Anisakis simplex. This is a very uncommon clinical presentation which rise several problems in diagnosis and management.
A gastric tumor was pointed out in 43-year-old woman as a result of a medical check-up. We performed partial gastrectomy based on a preoperative diagnosis of a gastrointestinal stromal tumor (GIST). However, as intraoperative frozen section histological examination showed lymph node metastasis, we performed a total gastrectomy simlilar to cases of gastric cancer with lymph node dissection. Postoperative histological examination showed that the tumor was positive for c-kit immunohistochemically, and consisted of spindle cells. We made a diagnosis of GIST of the stomach with lymph node metastasis. Lymph node metastasis in a case of GIST is rare, and has a poor prognosis. We report a case of a rare gastrointestinal stromal tumor with lymph node metastasis, followed up for 7 years with no evidence of recurrence after radical surgery with lymph node dissection.
Gastrointestinale Stromatumoren (GIST) sind eine jüngst definierte, das Protoonkogen c-kit (CD117) exprimierende, abdominale Sarkomentität. Der Primärtumor weist regelhaft keine Lymphknoten metastasen auf. Die R0-Resektion des Primär tumors mit tumorfreien Rändern ohne ausgedehnte Lymphadenektomie ist Ziel der Primärtherapie lokal begrenzter Tumoren. Patienten, die zur Resektion eines GIST einer multiviszeralen Operation bedürfen, erleiden rasch ein Tumorrezidiv. Die metastatische Tumor-ausbreitung erfolgt vorwiegend peritoneal und hepatisch. Bei Tumoren im metastasierten Stadium oder bei fortgeschrittenen Primärtumoren, die nicht sicher einer R0-Resektion unterzogen werden können, ist eine Behandlung mit dem Tyrosinkinase-In-hibitor Imatinib-mesylat (Glivec) indiziert und zugelassen. Eine systemische Chemotherapie oder Strahlentherapie muss derzeit als unwirksam angesehen werden.
Bei der Indikationsstellung zur Tumorresektion unter neo- 18 adjuvanten Gesichtspunkten ist die Durchführung einer FDG-PET hilfreich, um auf die Therapie ansprechende Tumoren ohne Größenregredienz von solchen abzugrenzen, die weiterhin progredient sind. Patienten mit inoperablem oder lokal fortgeschrittenem GIST, die unter Imatinib eine Tumorremission erzielen, sollen im Hinblick auf eine Resektion des Residual tumors evaluiert werden. In Einzelfällen kann es sinnvoll sein, solitäre, progrediente Metastasen, die auf eine Therapie mit Imatinib nicht mehr ansprechen, auch bei Vorhandensein weiterer Metastasen zu resezieren.
In Abhängigkeit von der Tumorgröße und der Mitosezahl lassen sich GIST-Tumoren in vier Risikoklassen einteilen. Eine adjuvante systemische Therapie mit Imatinib kommt für Patienten mit intermediärem und hohem Risiko für Fernmetastasen innerhalb von Studien in Betracht.
Lymph node (LN) metastasis of gastrointestinal stromal tumors (GIST) is unusual. Unlike gastric adenocarcinomas, routine lymphadenectomy is not recommended unless there is no suspicion for LN metastasis. Herein, we report a case of GIST of the stomach with LN metastasis treated with distal gastrectomy with perigastric LN dissection followed by adjuvant imatinib therapy.
A 32-year-old female presented with anemia. Diagnostic investigations including thoracoabdominopelvic computed tomography (CT) scan and gastroscopy revealed a 8 cm gastric antral submucosal tumor without any metastasis. Enlarged periantral LNs were detected during laparotomy and patient underwent distal gastrectomy with en bloc perigastric LN dissection. Pathologic investigation revealed antral stromal tumor with high mitotic and Ki-67 index. Lymph node metastasis was observed in 7 of 12 resected perigastirc nodes. Immunohistochemically, tumor cells were positive for CD117. She was diagnosed as high grade gastric GIST due to the presence of LN metastasis, large tumor size and unfavorable histopathologic features thus underwent adjuvant imatinib treatment (400 mg, daily). No recurrence or metastasis has been detected during a 12-month of postoperative follow-up.
Surgery remains the mainstay of treatment in patients with localized, resectable GISTs. Although lymphatic metastasis rarely occurs in patients with GIST, LN dissection should be considered for patients with any suspicion of nodal metastasis. Adjuvant imatinib treatment is recommended according to the well defined prognostic factors.
The authors report a case of a 29-year-old male patient with a severe lower gastrointestinal hemorrhage in whom a successful laparoscopic diagnosis and resection (assisted) of an ileal gastrointestinal stromal tumor (GIST) was performed. Laparoscopy can be very useful in the diagnosis and treatment of selected cases of lower gastrointestinal bleeding.
As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GIST), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and thedevelop-ment of novel and effective therapy for GISTs using thereceptor tyrosine kinase in hibitor STI-571, these tumors have become the focus of considerable attention among pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a sourceof confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health (NIH) convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity indiagnosis and a proposed scheme for estimating metastatic riskin these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term benign for any GIST, at least at the present time.
Background: Malignant gastrointestinal stromal tumors (GISTs), previously termed leiomyosarcomas or epithelioid leiomyosarcomas, are known to show wide variability in their malignancy. We evaluated the clinicopathological features of a large number of primary malignant gastric GISTs to clarify which features were independent prognostic factors. Methods: Clinicopathologic features (age, sex, tumor location, mode of growth and size, surgical method, ulceration, cell type, nuclear atypia, cellularity, mitotic index, growth pattern, necrosis, hemorrhage, direct tumor invasion, peripheral lymphoid cuffing, expression of α-smooth muscle actin [α-SMA], desmin, caldesmon, vimentin, CD34, c-kit protein and S-100 protein, and MIB-1 index) were evaluated by multivariate analysis in 140 patients with resected primary malignant gastric GISTs to identify independent prognostic factors. Results: Univariate analysis showed that each of the following factors had a significant deleterious influence on prognosis: male sex, tumor size 10 cm or more, presence of ulceration, an epithelioid cell component, severe nuclear atypia, high cellularity, a mitotic index of more than 10, an exogastric or invasive growth pattern, necrosis, hemorrhage, direct tumor invasion of surrounding tissue, negative caldesmon immunoreactivity, positive S-100 protein immunoreactivity, and a MIB-1 antigen labeling index of more than 10%. Multivariate analysis showed that male sex, tumor size 10 cm or more, presence of an epithelioid cell component, and a mitotic index of more than 10 were statistically significant indicators of a poor prognosis ( P = 0.013, 0.001, 0.014, and P = 0.009, 0.001, 0.043, and Conclusion: Male sex, tumor size 10 cm or more, and cell proliferation as estimated by the mitotic index or MIB-1 index are independent indicators of a poor prognosis in primary malignant gastric GIST.
Gastrointestinal stromal tumors (GIST) are infrequent and diagnosis and prognosis could be troublesome. We present short and long term results of surgical resection for GIST at the Department of Surgery, University of Insubria, during a period of 17 years.
All patients' data, tumor characteristics, surgical procedure and survival data were analyzed retrospectively. Tumors were divided in risk classes using the classification proposed by Fletcher, based on tumor size and number of mitosis.
Between 1987 and 2004, 25 patients underwent surgical resection for GIST. Stomach was the most common site of localization. Complete resection was achieved in 88% cases, while in 12% radical resection was not possible. The mean tumor size was 9.2 cm (1.2-30 cm): <5 cm diameter in 14/25 cases (56%), 5-10 cm in 5/25 (20%) and >10 cm in 6/25 (24%). Mitotic count was <10/50 HPF in 68% (17/25) and >10/50 in 32% (8/25). Using Fletcher's classification, tumors were divided in very low (11/25, 44%), low (4/25, 16%), intermediate (6/25, 24%) and high-risk (4/25, 16%) groups. The 5-year overall survival was 65% and 34% respectively with a statistically significant difference between tumors <5 cm and >10 cm in diameter and between complete and incomplete resection. High-risk tumors had a significantly shorter survival than low or very low risk.
Our experience confirms that GIST's are uncommon and aggressive cancers. The prognosis is strictly related to tumor size and number of mitosis. Although significant advances on new chemotherapeutic regimes have been made, to date, only radical surgery offers the chance of long-term survival.
Clinical and pathologic data from 51 patients with primary sarcomas of the gastrointestinal tract treated from 1951 through 1984 were reviewed to determine clinical presentation, histologic features, treatment, and prognostic factors. The most common signs and symptoms were abdominal pain (62%), gastrointestinal bleeding (40%), and/or abdominal mass (38%). The primary site was stomach in 50%, small bowel in 30%, colorectum in 15%, and esophagus in 5%. Virtually all the sarcomas were leiomyosarcomas. Distribution was uniform among the three histologic grades; although 88% of Grade 1 tumors could be completely excised, only 35% of Grade 3 tumors could be completely resected. The 5-year survival rate was 75% for Grade 1 tumors, 16% for Grade 2 tumors, and 28% for Grade 3 tumors (p = 0.0013, Grade 1 vs. 2 and 3). Thirty of the 51 patients (59%) had curative resection with an operative morbidity rate of 24% and an operative mortality rate of 12%; at 5 years the disease-free survival rate was 58% and the overall survival rate was 63% (48% at 10 years). Eleven patients (42%) had recurrent disease develop at a median interval of 2 years after complete tumor excision. Twenty-one patients (41%) had partial excision or biopsy only of their tumors with an operative morbidity rate of 28%, operative mortality rate of 8%, and median survival of only 9 months. Overall, patients whose tumors were confined to the site of origin had a 58% 5-year survival rate compared with 20% for those whose tumors had invaded adjacent organs (p less than 0.05). If the tumor was less than 10 cm in size, the 5-year survival rate was 78%, significantly better than the 38% for tumors greater than 10 cm (p = 0.03). These data suggest that histologic grade, local invasiveness, size, and extent of resection are the most important prognostic factors for patients with primary gastrointestinal sarcomas. Patients who have resection of all gross tumor, especially if it is well differentiated and localized, have a good prognosis.
One hundred ninety-one patients with gastrointestinal leiomyosarcomas were analyzed to determine the prevalence in patterns of failure and the factors predicting those at higher risk of relapse at specific sites. Of 100 assessable patients who died of disease, 89% were found to have peritoneal tumor, 78% had liver metastases, and 32% had extraabdominal metastases. Of 132 patients (69%) with initial complete resection of the primary tumor, only 10% (n = 13) remained free of disease as of the last follow-up. The median interval to recurrence was 18 months; 60% of all recurrences occurred within 2 years after surgery. Half of these patients (n = 61) had metastases (predominantly in the liver) as the initial recurrence. Factors significantly associated with improved survival after relapse were initial disease-free interval of 18 months or more, recurrences either isolated to the peritoneal cavity or within the liver, or complete resection of peritoneal recurrences or liver metastases. In contrast, those patients with recurrences at multiple sites or unresectable disease had significantly shorter survival times. The presence of extraabdominal metastases also heralded an equally poor outcome. In conclusion, a multi-modality approach is necessary to improve outcome from this disease because the liver and peritoneal cavity represent predominant sites of failure. Complete resection of isolated peritoneal or hepatic metastases improves survival and should be attempted when feasible. Cancer 1992; 69:1334-1341.
The appropriate surgical therapeutic options for either localized or more advanced disease in patients with gastrointestinal leiomyosarcomas remain unclear. A staging classification for this disease has not been adopted nor risk factors identifying patients at risk for recurrence defined. To address these issues, this study evaluated the influence of various clinicopathologic variables on overall and disease-free survival. In an univariate analysis of overall survival involving 191 patients, the Cox proportional hazards model identified four factors that were associated with a significantly better outcome: complete resection without tumor rupture (p less than 0.001), localized lesions (p less than 0.001), low grade of tumor (p = 0.02), and tumors smaller than 5 cm (p = 0.03). When interactive effects of these factors were taken into account, however, type of resection of the tumor was selected as the only significant prognostic factor in a multivariate analysis. Complete resection without tumor rupture improved overall survival of patients with localized disease (median, 46 months) as well as those with contiguous organ invasion (median, 36 months) or peritoneal implants (median, 36 months). In contrast, patients with incomplete resections survived for a median of 21 months. Patients with tumor rupture, despite removal of all gross disease, behaved similarly to those with incomplete resections; median survival was only 17 months. For disease-free survival, important determinants selected from a multivariate analysis were tumor rupture (p = 0.002), contiguous organ invasion (p = 0.02) and high tumor grade (p = 0.02). A staging classification incorporating these prognostic factors of significance was evaluated using a TGM system: T1 (less than 5 cm), T2 (greater than or equal to 5 cm), T3 (contiguous organ invasion or peritoneal implants), T4 (tumor rupture); G: G1 (low grade), G2 (high grade); M: M0 (no metastases), M1 (metastases present). The corresponding 5-year overall survivals for stages I, II, III, IVA, and IVB were 75%, 52%, 28%, 12%, and 7%. Disease-free survival at 2 years after surgery was 89%, 57%, and 47% for stages I, II, and III, respectively. In conclusion, surgery remains the primary modality of treatment for patients with gastrointestinal leiomyosarcomas, and complete resection of all disease without tumor rupture, even of locally advanced disease, improves overall and disease-free survival. A staging classification appears feasible and is recommended to determine outcome in patients with leiomyosarcomas arising from the gastrointestinal tract.
To analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively.
A GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of treatment because adjuvant therapy is unproven.
Two hundred patients with malignant GIST were admitted and treated at Memorial Hospital during the past 16 years. Patient, tumor, and treatment variables were analyzed to identify patterns of tumor recurrence and factors that predict survival.
Of the 200 patients, 46% had primary disease without metastasis, 47% had metastasis, and 7% had isolated local recurrence. In patients with primary disease who underwent complete resection of gross disease (n = 80), the 5-year actuarial survival rate was 54%, and survival was predicted by tumor size but not microscopic margins of resection. Recurrence of disease after resection was predominantly intraabdominal and involved the original tumor site, peritoneum, and liver.
GISTs are uncommon sarcomas. Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection. Tumor recurrence tends to be intraabdominal. Investigational protocols are indicated to reduce the rate of recurrence after resection and to improve the outcome for patients with GIST.
Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors.
A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998.
Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months.
Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival.
Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival.
Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor prognosis, with decreased survival, and increased local and/or distant recurrence.
Gastrointestinal stromal tumor (GIST) has emerged in the past year as a prototypical neoplasm that responds to therapy directed against a single target molecule-the KIT receptor tyrosine kinase protein. Although GIST seldom responds to conventional chemotherapeutic agents, early experience with the tyrosine kinase inhibitor, STI-571 (Gleevec; Novartis, Basel, Switzerland), has been extremely encouraging. Early results have appeared in a recent case report in the New England Journal of Medicine (April 5, 2001),(1) and in early clinical trials from the United States and Europe that were reported at the plenary session of the American Society of Clinical Oncology in San Francisco on May 14, 2001. STI-571 is one of the earliest examples of a nontoxic chemotherapeutic agent (an agent whose anti-cancer activity is not predicated on a cytotoxic mechanism). STI-571 has already shown clinical value in BCR-ABL-positive leukemias. Early clinical results in GIST are so encouraging that oncologists may soon be wrestling with the opportunity of referring every patient with malignant GIST into clinical trials with STI-571. To ensure appropriate treatment, pathologists need to understand the biology and treatment of this tumor and to have standard methods and criteria for providing diagnosis (GIST or not GIST) and consistent prognostic classification (high risk of metastasis or low risk of metastasis).
Gastrointestinal stromal tumors (GISTs) are unique neoplasms that occur throughout the gastrointestinal tract, mesentery, omentum, and retroperitoneum. They are the most common mesenchymal neoplasm of the gastrointestinal tract and are defined by their expression of KIT (CD117), a tyrosine kinase growth factor receptor. The expression of KIT is important to distinguish GISTs from other mesenchymal neoplasms such as leiomyomas, leiomyosarcomas, schwannomas, and neurofibromas and to determine the appropriateness of KIT-inhibitor therapy. The series described herein was accumulated over 2 years and includes 64 pathologically proved GISTs (28 gastric, 27 small intestinal, six anorectal, one colonic, one esophageal, and one from the small bowel mesentery). Radiologic features of GISTs vary depending on tumor size and organ of origin. Since most GISTs arise within the muscularis propria of the stomach or intestinal wall, they most commonly have an exophytic growth pattern and manifest as dominant masses outside the organ of origin. Dominant intramural and intraluminal masses are less common radiologic manifestations. GISTs occurring in the gastrointestinal tract and mesentery characteristically have hemorrhage, necrosis, or cyst formation that appears as focal areas of low attenuation on computed tomographic images. Although the radiologic features of GISTs are often distinct from those of epithelial tumors, criteria to separate GISTs radiologically from other nonepithelial tumors have not yet been fully developed.
Myogenic neoplasms of the stomach are the most common submucosal mass. Their natural history is indeterminate, and surgical resection is advised regardless of size. These lesions have typically required open resection, but a variety of laparoscopic techniques have been described. We report results of endoscopically guided, laparoscopic intragastric resection. Fourteen lesions have been excised in 13 patients in the last 3.5 years. There were eight women and five men with a mean age of 57 years (range 34-72). All patients were asymptomatic, and no lesions had mucosal ulceration. Eight lesions were located at the gastroesophageal junction, two each at the incisura and posterior body, and one each in the fundus and anterior wall of the corpus. All lesions were predominantly intraluminal, and three were transmural. The diagnosis of a myogenic lesion was confirmed by endoscopic ultrasound in eight patients. The laparoscopic/endoscopic technique included two or three, 2 or 5 mm intragastric trocars; endoscopic suture passage and specimen removal; and laparoscopic intragastric suture repair of the gastric defect. The mean operative time was 186 minutes. The mean size of the resected specimens was 3.8 cm (range 1.5-7.0). There was no mitotic activity on histopathology, and all were considered pathologically benign. The median length of stay was 3.8 days (range 3-8). There was no mortality or operative morbidity. At a mean follow-up of 16.2 months (range 1-32) there has been no local recurrences. A combined laparoscopic/endoscopic intragastric resection is most appropriate for intraluminal, benign-appearing submucosal lesions of the proximal stomach.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. These tumors span a wide clinical spectrum from benign to malignant and have long been recognized for their nearly absolute resistance to chemotherapy and radiation treatment. We reviewed the worldwide experience on GIST diagnosis, prognosis and treatment and describe our own series. PubMed was searched for references using the terms gastrointestinal stromal tumor, GIST and gastrointestinal sarcoma. Recent reports were given emphasis because GIST is a novel clinical entity and older published work on gastrointestinal sarcomas might be contaminated with other histologic tumor types. At present, surgery is the standard treatment for primary resectable GIST. To increase the activity of conventional chemotherapeutic agents, locoregional therapies are being implemented in the clinical setting. A major breakthrough is the development of a new class of anticancer agents targeting tumor-specific molecular abnormalities. Preliminary results on administration of imatinib mesylate, a signal transduction inhibitor, are particularly encouraging, showing potent activity of this drug against metastatic GIST. Molecular targeting of the critical pathogenetic mechanism underlying GIST might not only revolutionize the strategy to treat locally advanced and metastatic GIST but also improve disease control after macroscopically radical surgery.
Many different laparoscopic approaches to resection of gastric stromal tumor have been described in the literature. We reviewed our experience of laparoscopic approaches to surgical resection of gastric stromal tumors seven in six consecutive patients. The tumor locations were the gastric cardia (n = 2), gastroesophageal junction (n = 1), gastric fundus (n = 2), and gastric antrum (n = 2). Laparoscopic localization of endoluminal tumors included intraoperative endoscopy, laparoscopic ultrasound, and laparoscopic palpation. There were five males with a mean age of 57 years. Laparoscopic approaches to resection were laparoscopic wedge resection (n = 4) for tumors in the gastric fundus and antrum, laparoscopic enucleation (n = 2) for tumors in the gastric cardia, and transgastric endoluminal resection (n = 1) for a tumor located at the gastroesophageal junction. There was no conversion to laparotomy. The mean operative time was 143 +/- 54 minutes and mean blood loss was 57 +/- 27 mL. None of the patients required intensive care stay. The mean length of hospital stay was 3 days. There were no major or minor complications and no mortality. Surgical pathology demonstrated gastric stromal tumor with less than 2/50 mitosis per high power field in all seven specimens. Tumor size ranged from 2.8 cm to 7.1 cm in greatest diameter. There has been no tumor recurrence with a mean follow-up of 9 months. Laparoscopic resection of benign gastric stromal tumor is safe and feasible. The laparoscopic approaches to surgical resection should be tailored based on the location and characteristics of the tumor.
Gastrointestinal stromal tumours (GISTs) are currently defined as mesenchymal tumours of the gastrointestinal tract that express KIT receptor tyrosine kinase. However, a small subgroup of tumours that fulfil the clinical and morphological criteria for GISTs lack KIT expression. So far, the biological features of these tumours have rarely been addressed. The present study describes seven gastrointestinal stromal neoplasms that presented clinicopathological features typical of GISTs but showed absence of CD117 expression as detected by immunohistochemistry. The tumours originated from the stomach (n = 5), duodenum (n = 1), and colon (n = 1), showing histologically either predominantly epithelioid (n = 3), mixed spindled and epithelioid (n = 2), or anaplastic/spindle cell (n = 2) type features. CD34 and alpha-smooth muscle actin (alpha-SMA) positivity was present in four and three tumours, respectively. Chromosomal analysis was performed in two cases, both showing losses of chromosomes 14, 22, and 1p, which is the characteristic feature of GISTs. Dual-colour interphase fluorescence in situ hybridization (FISH) analysis, utilizing chromosome 1p-, 14-, and 22-specific probes, revealed a similar cytogenetic profile in the remaining five tumour specimens. Mutational analysis of exons 9, 11, 13, and 17 of KIT, and exons 12 and 18 of PDGFRA was performed in all cases by denaturing high-pressure liquid chromatography (DHPLC) pre-screening, followed by direct sequencing. None of the tumours showed KIT mutant isoforms. Three tumours harboured PDGFRA exon 18 activating mutations; two were Asp --> Val(842) missense substitutions and one was a DIM842-844 amino acid deletion. KIT and PKC theta (protein activated in interstitial cells of Cajal and GISTs) expression was determined by western immunoblotting of the total cell lysates from three tumour biopsies. None of these three tumours expressed KIT, while all specimens showed expression of PKC theta protein. These findings indicate that there is a subgroup of KIT-negative GISTs that exhibit the same morphological, cytogenetic, and molecular features as KIT-positive tumours. While intragenic PDGFRA activating mutations are present in some of these tumours, the oncogenic events underlying the pathogenesis of the others remain unknown.
The current definitive treatment for gastrointestinal stromal tumor (GIST) of the stomach is complete resection. GIST has a highly variable clinical course, and recurrent disease sometimes develops despite curative treatment. Although several known risk factors for recurrence exist, adequate treatment strategies are lacking. This study evaluated factors associated with relapse after curative treatment. Sixty patients with gastric GIST were identified from a hospital disease registry database. Clinicopathologic characteristics of these patients were reviewed and the Cox proportional hazards regression analysis was used to identify recurrent risk factors. With a median follow-up of 60 months (range 5-286 months), recurrence occurred in eight (13%) patients, three of whom underwent resection of the recurrent disease and are alive to date. Univariate analysis demonstrated that invasion of the adjacent organs (p = 0.0005), tumor size (p = 0.0046), and expression of proliferative markers [MIB-1 proliferative index (PI) > or = 10%] (p = 0.0001) were significant risk factors for recurrence. Multivariate analysis with these three factors as variables revealed that only MIB-1 PI was a significant independent risk factor for recurrence (p = 0.0051). In conclusion, surgical resection may be indicated whenever a recurrent GIST is considered resectable. A high MIB-1 PI was identified as an independent indicator of risk for recurrent disease following curative surgery.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm arising in the stomach. These tumors were previously classified as smooth muscle tumors, but in recent years it has become clear that they are clinically, pathologically, and molecularly distinct from other tumors and are much more common than previously appreciated. Historically, patients with primary localized or advanced GIST have been managed surgically, as there was no proven role of other treatment modalities such as radiation or chemotherapy. However, the field of GIST was revolutionized with the 1998 discovery that the vast majority of these tumors have oncogenic gain-of-function mutations of the KIT receptor tyrosine kinase. Follow-up studies have confirmed that KIT is both a useful diagnostic marker and an excellent therapeutic target. Imatinib, an inhibitor of KIT kinase activity, is now the standard front-line therapy for patients with advanced GIST. In this review, we discuss pathological and molecular features of gastric GISTs and review the historic and current roles of surgery in the treatment of patients with primary or metastatic GIST. The importance of a multi-disciplinary approach using both surgery and imatinib therapy is emphasized.
Gastrointestinal stroma tumors (GIST), an abdominal stroma entity, are characterized by a gain-in-function mutation in the c-kit proto-oncogen (CD117). Initial treatment should aim at complete removal of the primary tumor (R0 resection), which almost never develops lymphatic metastases. Distant metastatic spread mainly involves the peritoneal cavity and the liver. In patients with metastatic disease, treatment with the tyrosine kinase inhibitor imatinib mesylate is indicated and very effective. Systemic chemotherapy and external beam radiation must be considered ineffective. Patients requiring multivisceral resection for primary tumor removal quickly develop tumor recurrence and could benefit from preoperative treatment with imatinib. To assess the response to treatment, 18F-FDG positron emission tomography or gadolinium-enhanced magnetic resonance imaging have proven helpful, as the conventional criteria of tumor shrinkage according to WHO standards are rarely met. Primary tumors are classified into four risk categories according to size and mitotic activity. The possible advantages of adjuvant treatment are currently under investigation through international randomized trials. Patients who develop extensive remission of metastatic disease should be evaluated individually for resection of the tumor remnants. Even the resection of single progressive lesions (newly developed mutations) should be considered in carefully selected patients if the remaining tumor can be controlled by continued imatinib treatment.
This review describes the pathologic and epidemiologic features of gastrointestinal stromal tumor (GIST) as well as the contemporary management of this tumor. The integration of surgery and treatment with targeted molecular agents in the treatment of GIST is highlighted.
GIST is the most common mesenchymal tumor of the gastrointestinal tract. Its cellular origin from the interstitial cell of Cajal and distinctness from smooth muscles tumors were only recently appreciated. The discovery of the centrality of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST.
We conducted a review of the English literature on GIST. The pathology, epidemiology, diagnosis, and treatment of this tumor are summarized with particular emphasis on recent developments in the field.
GIST is a rare tumor that usually arises from the stomach or small intestine. It is characterized by immunohistochemical staining for KIT. Treatment of primary localized tumors is surgical. The benefit of adjuvant treatment with the KIT tyrosine kinase inhibitor imatinib is the subject of investigation. The treatment of unresectable, recurrent, or metastatic GIST is primarily imatinib treatment. The integration of surgery or ablative modalities is often employed, particularly when all disease is amenable to gross resection or destruction, or when GIST becomes resistant to imatinib. Newer tyrosine kinase inhibitors, such as sunitinib are the subject of ongoing investigation.
The treatment paradigm for GIST has required the integration of surgery and molecular therapy and this will likely serve as a paradigm for the treatment of other solid tumors as targeted agents are developed.
Gastro-intestinal stromal tumours are uncommon malignancies of the gastro-intestinal tract, accounting for only 0.2% of all gastro-intestinal malignancies, but are the most common of abdominal sarcomas. Classically, they have been considered amenable only to early stage surgical intervention. Recent advances in targeted cancer therapies have led to the development of effective non-surgical treatment options. This article discusses the epidemiology and physiopathology of, as well as treatment options available for, this uncommon disease.
Because gastric GISTs show variable clinical behavior, we reviewed our experience with primary gastric GISTs after surgical treatment and imatinib mesylate treatment for advanced disease.
Between December 1995 and December 2005, 111 patients who underwent surgical treatment for primary gastric GISTs were enrolled in this study. Patients were grouped according to the risk assessment classification, and clinicopathological features, tumor recurrence and patient survival were assessed.
One patient was included in the very low risk group, 35 in the low risk group, 31 in the intermediate risk group and 44 in the high-risk group. All patients with very low, low and intermediate risk GISTs and 70% of patients with high risk GISTs underwent R0 resection. While there was no recurrence or metastasis in patients with very low, low and intermediate risk GISTs, 23% of those with high risk GISTs showed a distant metastasis at diagnosis and 35% of these patients had a recurrence after R0 resection. The overall 5-year survival rate of the high risk patients was 77.1%. Nineteen patients received imatinib mesylate therapy due to an incomplete resection or recurrence; 7 with no measurable lesion at the CT scan by a local tumor control showed no tumor progression after imatinib mesylate therapy, however, 12 patients with measurable lesions showed variable clinical courses after treatment. The overall 5-year survival rate of 19 patients with imatinib mesylate treatment was 80.0%.
The clinical outcome of the very low, low and intermediate risk gastric GISTs was excellent, while high risk gastric GISTs had a high rate of recurrence and therefore a less favorable outcome. A complete resection is the most important treatment for cure; however imatinib mesylate treatment may improve the clinical outcome of the patients with metastatic or recurrent gastric GISTs.
Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) is safe and effective.
Retrospective medical record review.
Tertiary referral center.
Patients undergoing laparoscopic resection of gastric GISTs from April 1, 2000, to April 1, 2006.
Demographic data, diagnostic workup, operative technique, tumor characteristics, morbidity, mortality, and follow-up.
Thirty-three patients underwent attempted laparoscopic resection of gastric GISTs, with 31 operations completed laparoscopically. The mean patient age was 68 years (age range, 35-86 years). The female to male ratio was 18:15. Sixteen patients (49%) were asymptomatic, and their tumors were found incidentally. Of 24 patients (73%) who underwent preoperative endoscopic ultrasonography, the results of fine-needle aspiration verified the diagnosis in 13 patients (54%). The mean operative time was 124 minutes (range, 30-253 minutes). A combined endoscopic-laparoscopic approach was used in 11 patients (33%). The mean tumor size was 3.9 cm (range, 0.5-10.5 cm). Two patients (6%) underwent conversion to an open procedure. The median hospital stay duration was 3 days. The mean follow-up was 13 months (range, 3-64 months). There were no local recurrences. Three patients (9%) experienced complications, including 1 wound infection and 2 episodes of upper gastrointestinal tract bleeding. There were no mortalities.
Although technically demanding, the laparoscopic approach to gastric GISTs is safe and effective, resulting in a short hospital stay duration and low morbidity.
Laparoscopic gastric gastrointestinal stromal tumor resection: The mayo clinic experience
- Kl Huguet
- Rm Rush
- Jr
- Dj Tessier
- Rt Schlinkert
- Ra Hinder
Huguet KL, Rush RM Jr, Tessier DJ, Schlinkert RT,
Hinder RA, et al. Laparoscopic gastric gastrointestinal
stromal tumor resection: The mayo clinic experience.
Arch Surg. 2008 Jun, 143 (6): 587-90.