Clinicopathological features, risk profile assessment, and the surgical outcome of gastrointestinal stromal tumors in Lagos, Nigeria.

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs originate from the interstitial cells of Cajal and are most commonly found in the stomach. Most available reports on GISTs in the Sub-Sahara Africa were in case reports and case series. Aim: To report our local experience and challenges in the management of GISTs in 33 patients in Lagos, Nigeria. Methodology: This is a descriptive study of adult patients of 16 years and above managed for GISTs at the Lagos University Teaching Hospital and some Lagos private hospital facilities between January 2015 and March 2021. Information on the patients' demographic characteristics, clinicopathological features, surgery performed, and postoperative complications were retrieved from the hospital's medical records for analysis. Data analysis was carried out using IBM SPSS Statistics for Windows, Version 23.0., Armonk, NY, USA: IBM Corp. Results: Thirty-three patients comprising 19 males and 14 females with a male: female ratio of 1.4:1 were included in the study. The mean age at presentation was 52.5 years. Abdominal pain (69.7%) and anemic symptoms (45.4%) were the principal modes of presentation. Abdominal computed tomography (CT) scan revealed stomach as the primary source of GISTs in 75.8% of patients. Forty-five percent of the patients had CT features of local organ invasion and 27.2% had features of metastasis. Surgical resection was feasible in 28 (84.8%) patients. Postoperative mortality was recorded in two patients with recurrent GISTs. Histological cell types were spindle cell (57.6%), mixed spindle and epithelioid (24.2%), and epithelioid (18.2%). Joensuu high-risk tumors (64. 3%) were the most prevalent in our series. Conclusion: Advanced-stage disease and features of anemia were hallmarks of GISTs among patients in this series. Surgical resection of GIST may be possible in some cases of advanced disease. Spindle cell types and high-risk GISTs were the most common pathological varieties in our patients.

Résumé Contexte: Les tumeurs stromales gastro-intestinales (GIST) sont les tumeurs mésenchymateuses les plus courantes du tractus gastro-intestinal. Les GIST proviennent des cellules interstitielles de Cajal et se trouvent le plus souvent dans l'estomac. La plupart des rapports disponibles sur les GIST en Afrique subsaharienne étaient des rapports de cas et des séries de cas. Objectif: rendre compte de notre expérience locale et des défis dans la gestion des GIST chez 33 patients à Lagos, au Nigeria. Méthodologie: Il s'agit d'une étude descriptive de patients adultes de 16 ans et plus pris en charge pour des GIST à l'hôpital universitaire de Lagos et dans certains établissements hospitaliers privés de Lagos entre janvier 2015 et mars 2021. Informations sur les caractéristiques démographiques des patients, les caractéristiques clinicopathologiques, la chirurgie effectuée, et les complications postopératoires ont été extraites des dossiers médicaux de l'hôpital pour analyse. L'analyse des données a été effectuée à l'aide d'IBM SPSS Statistics pour Windows, version 23.0., Armonk, NY, États-Unis: IBM Corp. l'étude. L'âge moyen à la présentation était de 52,5 ans. Les douleurs abdominales (69,7 %) et les symptômes anémiques (45,4 %) étaient les principaux modes de présentation. La tomodensitométrie abdominale (TDM) a révélé que l'estomac était la principale source de GIST chez 75,8 % des patients. Quarante-cinq pour cent des patients présentaient des caractéristiques CT d'invasion d'organes locaux et 27,2 % présentaient des caractéristiques de métastases. La résection chirurgicale était réalisable chez 28 (84,8 %) patients. La mortalité postopératoire a été enregistrée chez deux patients avec des GIST récurrents. Les types de cellules histologiques étaient les cellules fusiformes (57,6 %), les cellules mixtes fusiformes et épithélioïdes (24,2 %) et les épithélioïdes (18,2 %). Les tumeurs à haut risque de Joensuu (64,3 %) étaient les plus répandues dans notre série. Conclusion: La maladie à un stade avancé et les caractéristiques de l'anémie étaient les caractéristiques des GIST chez les patients de cette série. La résection chirurgicale des GIST peut être possible dans certains cas de maladie avancée. Les types de cellules fusiformes et les GIST à haut risque étaient les variétés pathologiques les plus fréquentes chez nos patients. Mots clés: Bilan, tumeurs stromales gastro-intestinales, pathologie, risque, gestes chirurgicaux.

A proposed risk assessment score for gastrointestinal stromal tumors based on evaluation of 19,030 cases from the National Cancer Database.

BACKGROUND: Standard risk assessment algorithms for gastrointestinal stromal tumor (GIST) are based on anatomic and histopathological variables with arbitrarily defined subcategories. Our goal was to improve risk assessment for GIST through retrospective analysis of patient data. METHODS: The National Cancer Database (NCDB) was queried for patients with GIST; the final cohort consisted of 19,030 cases. Main outcomes were metastasis at presentation and overall survival. A test dataset was used to reevaluate risk stratification parameters in multivariate regression models. A novel risk assessment system was applied to the validation dataset and compared to other currently used risk assessment schemes. RESULTS: Analysis of observed prevalence of metastases at presentation suggested 7 cm and mitotic rates > 10 per 5 mm2 as optimal threshold values. A proposed risk stratification score showed statistical superiority compared to the National Comprehensive Cancer Network, American Joint Committee on Cancer, and modified National Institute of Health classifications in predicting probability of presentation with metastasis at diagnosis and 4-year overall survival after accounting for important covariables including patient age and comorbidities, year of diagnosis, and surgical/systemic therapeutic regimen. CONCLUSIONS: Reexamination of prognostic factors for GIST demonstrated that current threshold values for tumor size and mitotic rate are suboptimal. A risk stratification score based on revised categorization of these factors outperformed currently used risk assessment algorithms.

[Real world study and its application in gastrointestinal stromal tumor].

Gastrointestinal stromal tumor (GIST) is a relatively rare type of gastrointestinal tract tumors. Thus, it is difficult to perform randomized controlled trials (RCTs) of GIST in a single center, which are often plagued by a small number of participants. Real world study (RWS) is a complement to the evidence derived from traditional RCT. Emerging sources of real world data offer enormous opportunity for deeper understanding of why treatments work (or not) and for whom. Evidence generated from RWD can help clarify best use of treatments for individuals and populations, and care value. Thus, RWS of GIST has attracted much attention. RWS helps us better understand the diagnosis, treatment, prognosis and outcome prediction of GIST in clinical practice. GIST is often misdiagnosed as other tumor. A diagnostic test provides evidence on how well a test correctly identifies or rules out GIST. Therapeutic research aims to evaluate the effectiveness and/or safety of a therapy for GIST. Prognostic research aims to forecast the likely outcome of GIST, explore the factors affecting the outcome, and analyze quality of life. Predictive research aims to quantify the probability of identification or health outcome of GIST based on a set of predictors. Pharmacoeconomic data in real world can evaluate the cost-effectiveness of medicinal products for GISTs and serve as a guidance tool for optimal healthcare resource allocation. Attaching importance to data sourse and data quality, strenthening communicate with a qualified statistician, and the implementation of a standardized process are necessary for performing a high-quality RWS.

The cost-saving effect of centralized histological reviews with soft tissue and visceral sarcomas, GIST, and desmoid tumors: The experiences of the pathologists of the French Sarcoma Group.

OBJECTIVE: This study examined the types of discordance occurring in the diagnosis of soft tissue and visceral sarcomas, gastrointestinal stromal tumors (GIST), and desmoid tumors, as well as the economic impact of diagnostic discrepancies. METHODS: We carried out a retrospective, multicenter analysis using prospectively implemented databases performed on a cohort of patients within the French RRePS network in 2010. Diagnoses were deemed to be discordant based on the 2013 World Health Organization (WHO) classification. Predictive factors of discordant diagnoses were explored. A decision tree was used to assess the expected costs of two strategies of disease management: one based on revised diagnoses after centralized histological review (option 1), the other on diagnoses without centralized review (option 2). Both were defined based on the patient and the disease characteristics, according to national or international guidelines. The time horizon was 12 months and the perspective of the French National Health Insurance (NHI) was retained. Costs were expressed in Euros for 2013. Sensitivity analyses were performed using low and high scenarios that included ± 20% estimates for cost. RESULTS: A total of 2,425 patients were included. Three hundred forty-one patients (14%) had received discordant diagnoses. These discordances were determined to mainly be benign tumors diagnosed as sarcomas (n = 124), or non-sarcoma malignant tumors diagnosed as sarcomas (n = 77). The probability of discordance was higher for a final diagnosis of desmoid tumors when compared to liposarcomas (odds ratio = 5.1; 95%CI [2.6-10.4]). The expected costs per patient for the base-case analysis (low- and high-case scenarios) amounted to €8,791 (€7,033 and €10,549, respectively) for option 1 and €8,904 (€7,057 and €10,750, respectively) for option 2. CONCLUSIONS: Our findings highlight misdiagnoses of sarcomas, which were found to most often be confused with benign tumors. Centralized histological reviews are likely to provide cost-savings for the French NHI.

Overcoming Cost Implications of Mutational Analysis in Patients with Gastrointestinal Stromal Tumors: A Pragmatic Approach.

BACKGROUND: Genetic analysis of tissue derived from patients with advanced gastrointestinal stromal tumors (GISTs) is not uniformly applied on a national and international level, even though mutational data can provide clinically relevant prognostic and predictive information, especially in patients qualifying for treatment with expensive targeted agents. METHODS: The current article describes the rationale for genetic testing of GIST tissue, looks at financial implications associated with such analysis and speculates on potential cost savings introduced by routine mutational testing and tailored use of tyrosine kinase inhibitors based on genotyping. This work is based on a hypothetical analysis of epidemiological data, drug costs, reimbursement criteria and market research figures. RESULTS: The cost burden for routine genotyping of important genes in GISTs, especially in patients at high risk for relapse after primary surgery and in advanced, inoperable metastatic disease, is relatively low. The early identification of GISTs with primary resistance mutations should be the basis for personalized GIST treatment and reimbursement of drugs. As illustrated by Belgian figures, the exclusive use of a drug such as imatinib in patients who are likely to benefit from the agent based on genetic information can lead to significant cost savings, which outweigh the costs for testing. CONCLUSIONS: Mutational analysis of GIST should be considered early in all patients at risk for relapse after curative surgery and in the case of advanced, inoperable, metastatic disease. The costs for the actual genotyping should not be used as an argument against profiling of the tumor. The adjuvant and palliative systemic treatment of GISTs should be personalized based on the genotype and other known prognostic and predictive factors. Reimbursement criteria for essential agents such as imatinib should be adapted accordingly.

Comparison of performance of various tumor response criteria in assessment of sunitinib activity in advanced gastrointestinal stromal tumors.

PURPOSE: To compare the performance of various tumor response criteria (TRC) in the assessment of patients with advanced gastrointestinal stromal tumor (GIST) treated with sunitinib after failure of imatinib. METHODS: Sixty-two participants with advanced GIST in two clinical trials received oral sunitinib after prior failure of imatinib (median duration 24 weeks; interquartile range 14-56) and were followed with contrast-enhanced computed tomography at baseline and thereafter at median intervals of 6 weeks (IRQ 6-9). Tumor response was prospectively determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.0, and retrospectively reassessed for comparison using RECIST 1.1, Choi criteria, and modified Choi (mChoi) criteria using the original target lesions. For mChoi criteria, progressive disease was defined as 20% increase in sum of the longest dimension, similar to RECIST 1.1. Clinical benefit rate (CBR; complete response, partial response, or stable disease ≥12 weeks) and progression-free survival were compared between various TRCs using kappa statistics. RESULTS: While partial response as the best response was more frequent by Choi and mChoi criteria (50% each) than RECIST 1.1 (15%) and RECIST 1.0 (13%), CBR was similar between various TRCs (overall CBR 60%-77%, 77%-94% agreement between all TRC pairs). Time to best response was shorter for Choi and mChoi criteria (median 11 weeks each) compared to RECIST 1.1 and RECIST 1.0 (median 25 and 24 weeks, respectively). PFS was similar for RECIST 1.1, RECIST 1.0, and mChoi (median 35 weeks each), and shortest for Choi criteria (median 23 weeks). CONCLUSIONS: CBR was similar among the various TRCs, although Choi criteria led to earlier determination of disease progression. Therefore, RECIST 1.1 and mChoi criteria may be preferred for response assessment in patients with advanced GIST.

Assessment of early response to imatinib 800 mg after 400 mg progression by ¹8F-fluorodeoxyglucose PET in patients with metastatic gastrointestinal stromal tumors.

INTRODUCTION: Imatinib is the standard first-line therapy for advanced gastrointestinal stromal tumor. (18)F-fluorodeoxyglucose PET computed tomography (FDG PET/CT) shows a faster response than computed tomography in nonpretreated patients. PATIENTS & METHODS: After disease progression on imatinib 400 mg, 16 patients were exposed to 800 mg. Tumor response was evaluated by FDG PET/CT on days 7 and 37. Primary objective was to correlate early metabolic response (EMR) with progression-free survival (PFS). RESULTS: EMR by FDG PET/CT scan was not predictive of PFS. Median PFS in these patients was 3 months. Overall survival was influenced by gastric primary site (p = 0.05). CONCLUSION: The assessment of EMR by FDG PET/CT in patients with advanced gastrointestinal stromal tumor exposed to imatinib 800 mg was not predictive of PFS or overall survival.

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

Practical aspects of risk assessment in gastrointestinal stromal tumors.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract, which are characterized in the majority of cases by activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). The introduction of tyrosine kinase inhibitors has revolutionized the management of patients with metastatic GIST. However, complete surgical resection remains the mainstay of management for those with localized disease. Recently, three large trials have confirmed the benefit of adjuvant imatinib therapy in patients who were at high risk of recurrence following complete resection. In this setting, it is critical that oncologists understand the various GIST risk assessment criteria and be able to apply these methods to accurately assess the risk of recurrence and the need for adjuvant imatinib therapy. PURPOSE: The aim of this review is to outline the risk stratification systems currently available to oncologists who are treating patients with GIST, so they can be optimally applied for clinical decision-making.

Impact of introduction of laparoscopic surgery on management of unresolved intra-abdominal malignancies in a West African hospital.

BACKGROUND: Intra-abdominal malignancies often pose diagnostic problems to surgeons in resource-challenged centers such as ours due to limitations in modern imaging and other facilities. This prompted the adoption of laparoscopy in our hospital as an adjunctive tool in diagnosing these conditions. METHOD: Pre- and per-operative data of consecutive cases of clinically unresolved advanced intra-abdominal tumors subjected to laparoscopy from January 2009 through June 2013 were reviewed. Anatomic diagnosis and tissue biopsies were carried out during the procedures. RESULTS: Of the 152 patients seen with intra-abdominal tumors, 74 (48.7 %) had advanced conditions that could not be resolved clinically. Of these, 33 (44.6 %) were able to afford and had computed tomography (CT), scan while the remaining (N = 41; 55.4 %) less endowed only had an ultrasound scan. This cohort underwent laparoscopic evaluation, and biopsies confirmed the following: 27 (36.5 %) metastatic adenocarcinomas, 12 (16.2 %) primary hepatic malignancies, 11 (14.9 %) cases each of lymphomas and colonic adenocarcinomas, 4 (5.4 %) gastrointestinal stromal tumors, 3 (4.1 %) pancreatic carcinomas, 2 (2.7 %) cases each of carcinoid tumors and abdominal tuberculosis, and one case each of schistosomiasis and HIV-related Kaposi's sarcoma. Additionally, 26 (35.1 %) had ascites, while 29 (39.1 %) had peritoneal surface malignancies. With local adaptations and improvisations, laparoscopy was cheaper than an abdominal CT scan in our setting, with the additional benefit of obtaining tissue diagnosis to institute treatment. CONCLUSION: Although laparoscopy is commonly used for staging intra-abdominal tumors, we found it useful in complementing clinical diagnosis and attaining histopathological confirmation in a setting where access to and funding of modern imaging is limited.

Gastrointestinal stromal tumors: risk assessment and adjuvant therapy.

Adjuvant imatinib prolongs recurrence-free survival and probably overall survival of patients who have undergone surgery for gastrointestinal stromal tumor (GIST). Estimation of the risk of recurrence with a prognostication tool and tumor mutation analysis is essential before imatinib initiation, because approximately 60% of patients with GIST with operable tumor are cured by surgery alone and some mutated tyrosine kinases are insensitive to imatinib. Adjuvant imatinib is usually administered for 3 years at the dose of 400 mg once daily. Early detection of tumors that recur despite adjuvant therapy with longitudinal imaging of the abdomen is likely beneficial.

Diffusion-weighted magnetic resonance imaging in metastatic gastrointestinal stromal tumor (GIST): a pilot study on the assessment of treatment response in comparison with 18F-FDG PET/CT.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (MRI) is increasingly being used for assessing the treatment succes in oncology, but the real clinical value needs to evaluated by comparison with other, already established, metabolic imaging techniques. PURPOSE: To prospectively evaluate the clinical potential of diffusion-weighted MRI with apparent diffusion coefficient (ADC) mapping for gastrointestinal stromal tumor (GIST) response to targeted therapy compared with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). MATERIAL AND METHODS: Eight patients (mean age, 56 ± 11 years) known to have metastatic GIST underwent 18F-FDG PET/CT and MRI (T1Gd, DWI [b = 50,300,600], ADC mapping) simultaneously, before and after change in targeted therapy. MR and PET/CT examinations were first analyzed blindly. Second, PET/CT images were co-registered with T1Gd-MR images for lesion detection. Only 18F-FDG avid lesions were considered. Maximum standardized uptake value (SUVmax) and the corresponding minimum ADCmin were measured for the six largest lesions per patient, if any, on baseline and follow-up examinations. The relationship between changes in SUVmax and ADCmin was analyzed (Spearman's correlation). RESULTS: Twenty-four metastases (12 hepatic, 12 extra-hepatic) were compared on PET/CT and MR images. SUVmax decreased from 7.7 ± 8.1 g/mL to 5.5 ± 5.4 g/mL (P = 0.20), while ADCmin increased from 1.2 ± 0.3 × 10(-3)mm(2)/s to 1.5 ± 0.3 × 10(-3)mm(2)/s (P = 0.0002). There was a significant association between changes in SUVmax and ADCmin (rho = - 0.62, P = 0.0014), but not between changes in lesions size (P = 0.40). CONCLUSION: Changes in ADCmin correlated with the response of 18F-FDG avid GIST to targeted therapy. Thus, diffusion-weighted MRI may represent a radiation-free alternative for follow-up treatment for metastatic GIST patients.

Response assessment in gastrointestinal stromal tumor.

Imatinib is standard first-line treatment for patients with advanced gastrointestinal stromal tumor (GIST). Initial responses are not always accompanied by reductions in tumor size; consequently, other parameters should be considered in response assessments. Conventional size-based criteria such as Response Evaluation Criteria in Solid Tumors (RECIST) may underestimate responses to imatinib and have poor predictive value for outcome. Imatinib-responding tumors demonstrate decreased metabolic activity on positron emission tomography within the first weeks of treatment, often showing reduced density and greater homogeneity on computed tomography (CT) scans regardless of initial changes in tumor size. New criteria, based on reductions in tumor size or in tumor density on CT, seem more sensitive and specific for detecting early responses to imatinib, and more predictive of time to tumor progression and disease-specific survival. Compared with conventional size-based criteria, new CT-based criteria may potentially offer improved response assessment and be predictive of outcome in GIST. However, such emerging criteria should be further explored and validated in large, multicenter trials with imatinib and other kinase inhibitors in GIST and in other solid tumors.

[GIST: Imaging diagnosis, staging, and response assessment]. / Bildgebende Diagnostik bei GIST.

Diagnosis of gastrointestinal stromal tumors (GIST), which are located in the stomach or colon, is a domain of endoscopy. For midgut GIST is contrast-enhanced multidetector-CT the standard imaging technique. With the development of enteroclysis - MDCT better distension of the small bowel can be achieved to find even small tumors in the bowel wall. For staging of GIST is contrast-enhanced MDCT of the abdomen (and chest) recommended, unless PET/CT is widely available. Contrast-enhanced MRI is used for local staging of rectal tumors and as a problem-solving tool in patients with equivocal lesions at CT of the liver. In chemotherapy-responders, metastases may undergo necrosis and liquefaction with shrinkage. Therefore the RECIST criteria have been found to be unreliable to assess tumor response. The modified CT response criteria of Choi et al. have been developed and validated for more accurate assessment of chemotherapy. If available, is FDG-PET/CT the modality of choice for the follow-up of GIST patients at risk of metastases.

High-grade soft-tissue sarcomas: tumor response assessment--pilot study to assess the correlation between radiologic and pathologic response by using RECIST and Choi criteria.

PURPOSE: To compare radiologic response as defined according to both Response Evaluation Criteria in Solid Tumors (RECIST) and the new Choi criteria recently proposed for gastrointestinal stromal tumors with pathologic response in high-grade soft-tissue sarcomas (STSs) treated with preoperative chemotherapy and radiation therapy. MATERIALS AND METHODS: The institutional ethical committee approved the trial in which patients were enrolled. Signed informed consent was obtained. Thirty-seven patients (21 men, 16 women; mean age, 44.2 years) enrolled in a collaborative randomized trial on preoperative chemotherapy and radiation therapy in localized high-risk STS at a single institution were selected for this retrospective analysis. Tumor response to preoperative treatment was assessed by using both RECIST and Choi criteria at computed tomography (CT) and was adapted to be used at magnetic resonance (MR) imaging. Pathologic response was assessed as either good or very good. Sensitivity, specificity, and predictive value of RECIST and Choi criteria were calculated with pathologic response as the reference standard and were reported with 95% confidence intervals. RESULTS: For 28 patients without synovial sarcomas, sensitivity of RECIST versus adapted Choi criteria was 32.0% versus 88.0% for good response and 41.2% versus 82.4% for very good response, respectively; specificity for pathologic response was 100% versus 100% for not a good response and 90.9% versus 27.3% for not a very good response, respectively. In synovial sarcoma, the nontreatment-related neoplastic cystic component of the tumor was a major obstacle for both RECIST and Choi criteria. CONCLUSION: In STS treated with chemotherapy and radiation therapy, tumor size may be insufficient to render actual tumor response. Tumor attenuation at CT or tumor contrast material enhancement at MR imaging may complement tumor size, thus making Choi criteria more predictive of pathologic response.

Imaging of gastrointestinal stromal tumors and assessment of benefit from systemic therapy.

While gastrointestinal stromal tumors have been increasingly recognized with the prolonged survival and highly effective new targeted treatments, the role of imaging has become important not only for diagnosing and staging the tumors, but also for monitoring the effects of treatment and surveillance. Computed tomography is the imaging modality of choice for these purposes. Fluorine-18 fluorodeoxyglucose positron emission tomography is primarily used in problem solving when there are inconsistencies between CT and clinical findings or inconclusive CT images. The roles of MRI and ultrasound are also described.

Early response assessment in gastrointestinal stromal tumors with FDG PET scan 24 hours after a single dose of imatinib.

Gastrointestinal stromal tumors (GIST), rare mesenchymal tumors of the gastrointestinal tract, are gaining the interest of researchers because of the impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate. FDG PET is now routinely used to assess treatment response in cases of GIST because this has proven to give metabolic information, which demonstrates response earlier than anatomic imaging modalities. A 50-year-old man presented with abdominal pain and the CT scan showed a large lobulated heterogeneously enhancing mass in the abdomen. Fine needle aspiration cytology (FNAC) confirmed GIST with strong immunoreactivity to C-Kit protein. A baseline FDG PET done before initiation of therapy showed intense nonhomogenous FDG uptake in the mass (standard uptake value maximum, SUVmax of 13.45). A whole body FDG PET, repeated 24 hours after a single dose of imatinib mesylate 400 mg, showed a significant reduction in FDG uptake with a SUVmax of 4.26.

Microfluidic deletion/insertion analysis for rapid screening of KIT and PDGFRA mutations in CD117-positive gastrointestinal stromal tumors: diagnostic applications and report of a new KIT mutation.

Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KIT and PDGFRA genes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Because most GIST mutations are deletions/insertions, we used a microfluidic apparatus to detect these size variations in polymerase chain reaction-amplified DNA. This approach, termed microfluidic deletion/insertion analysis (MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded CD117-positive GISTs (60%), comprising 25 deletions and five insertions. Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions, including two 3-bp alterations. Sequencing of all 20 MIDIA-negative samples also showed highly consistent results with MIDIA because 10 cases were wild type and eight displayed a single base substitution in which detection by MIDIA was not expected. Sequencing also revealed a 3-bp deletion undetected by MIDIA, thus establishing the resolution limit of MIDIA at deletions/insertions >or=3 bp. Denaturing high-pressure liquid chromatography analysis confirmed all mutations detected by MIDIA and sequencing. We pro-pose MIDIA as the first step in mutational screening of GIST because it allowed the detection of 75% of mutated cases (94% of deletions/insertions) in less than 30 minutes after polymerase chain reaction amplification and at a lower cost compared with denaturing high-pressure liquid chromatography and sequencing, which might then be used only for MIDIA-negative cases.

The outcome assessment of double-balloon enteroscopy for diagnosing and managing patients with obscure gastrointestinal bleeding.

Diagnosing and treating patients with obscure gastrointestinal bleeding is clinically challenging. Most lesions responsible for the origin of obscure gastrointestinal bleeding are located in the small bowel. Double-balloon enteroscopy is a novel method for exploring the small intestine and has significant therapeutic potential. This study evaluated the value of double-balloon enteroscopy in diagnosing and managing obscure gastrointestinal bleeding. From October 2003 to January 2006, a total of 20 patients (6 men, 14 women; mean age, 55.2 years old) with obscure gastrointestinal bleeding (18 obscure overt bleeding, 2 obscure occult bleeding) were investigated by double-balloon enteroscopy. A total of 29 procedures (15 via oral approach and 14 via rectal approach) were performed. The diagnostic yield, endoscopic therapeutic procedures, complications, and outcome were then assessed. Small bowel lesions potentially responsible for the bleeding were identified in 15 (75%) of 20 patients, including 9 angiodysplasias, 2 gastrointestinal stromal tumors (GISTs), 2 ulcers, 1 jejunal granulation polyp, and 1 Peutz-Jeghers polyposis. Endoscopic treatments including heater probe coagulation, polypectomy, and endoscopic mucosal resection were performed in 11 patients. Two patients with GISTs received surgical intervention. Two patients with angiodysplasias that endoscopic treatment failed underwent laparoscopic resections following tattooing. There were no complications and the procedures were tolerated well. Among the 15 patients who had a lesion identified with subsequent treatment, rebleeding occurred in 3 (20%) patients with angiodysplasias. Of the five patients in whom no definite lesion was detected, rebleeding developed in four (80%). For patients with an identified lesion that was further treated, the rebleeding rate was lower than for those with "persistent" obscure gastrointestinal bleeding (P=0.031). We conclude that double-balloon enteroscopy offers a safe and effective method for diagnosing and managing patients with obscure gastrointestinal bleeding.