LECTURES

Online course on Gastrointestinal Stromal Tumours (GIST)

Nikolaos Memos, MD, Ph.D.: Surgical challenges of GIST tumors

Gastrointestinal Stroma Tumours are rare mesenchymal neoplasms that are mainly located at the gastrointestinal tract. Most commonly involve the stomach, with second most common location the small bowel but they are also seen at the esophagus, rectum, duodenum etc. The treatment cornstone of GIST is surgical removal with negative margins (R0 resection). GISTs are diagnosed as soft tissue tumour either as incidental finding in imaging scans or as the cause of GI symptoms such as early satiety, bloating, ileus or GI bleeding. Prognosis of GIST depends on the size of the tumour that ranges from couple of cm to >10 cms, the mitotic index and the GI location. In addition, the risk of tumour rupture either spontaneously or iatrogenically is independent malprognostic factor. The surgical challenges for the GISTs mainly involve the location of the tumour and the extend of the resection. Large tumours located at the stomach, the duodenum or at the rectum may require multivisceral resection increasing mortality and morbitity. In the imatinib era, the neoadjuvant treatment and the advances in the surgical techniques, the R0 resections can now be more applicable. However, the response seen following treatment in mainly partial, making the multivisceral resection still the main treatment modality for curing the patient. In the present lecture we will discuss the challenges that a surgical oncologist faces when asked to operate at the GIST tumours in the post imatinib area. In addition, we will discuss the input of minimally invasive surgical techniques for the treatment of GIST.

Jose Duran Moreno, MD, MSc.: Targeted therapy for GIST

Gastrointestinal Stroma Tumours are rare mesenchymal neoplasms that are mainly located at the gastrointestinal tract. Carcinogenesis of GISTs is driven in about 85% of cases by a punctual mutation of gene c-kit or pdgfra. This knowledge permitted the successful development of several therapies that, targeting these mutations, improve the survival and quality of life of patients with unresectable GIST, turning this tumor into the pioneer and paradigm of targeted therapy in solid tumors. In the present lecture we will discuss the achievements, limitations and challenges of target therapy in GIST.

George Agrogiannis, MD, MSc., Histopathologist

George Agrogiannis, Histopathologist, Assoc. Professor,1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens.

GASTROINTESTINAL STROMAL TUMOURS: Histology and genetics.

GISTs are the most common clinically significant mesenchymal neoplasm of the GI tract. Population-based studies estimate the annual incidence at 10 cases per million. They are found along the entire length of the digestive tract but are most common in the stomach. No etiologic factors related to GIST have been identified and although the vast majority of GISTs occur as sporadic tumors with somatic mutations, GISTs also occur rarely in various tumor syndromes. The lesions vary in their cellularity, ranging from low, to intermediate, to high. Regarding the immunoreactivity in gastrointestinal stromal tumors, cytoplasmic pattern for KIT B, dot-like or membranous pattern are all common. For DOG1 expression, the membranous staining pattern is typical. Understanding underlying mutations in GISTs is critical for the diagnosis and patient care and these are tumors with quite well defined molecular alterations which reflects to the targeted therapy. Imatinib is the mostly used drug agent for the therapy of GISTs. Four different regions of KIT, namely exon 9, exon 11, exon 13, and exon 17, are most often mutated in sporadic GISTs. Exon 18, exon 12, and exon 14 are the 3 PDGFRA regions that are mutated in GISTs. Fifteen (15) percent of the tumors do not harbor either the KIT or PDGFRA mutations and they are designated as Wild Type GISTs, while a small subset harbors SDH mutations. A subset of GISTs lack mutations in the KIT/PDGFRA or RAS pathways and yet retain an intact SDH complex. It was proposed that these tumors could be designated as quadruple wild- type (WT) GIST. GISTs demonstrate diverse clinical profiles in that they can arise in any part of the GI tract and can present as tumors ranging from incidental microscopic tumors to those that follow a malignant and life – threatening course by metastasis. This diversity is also reflected in the oncogenic events that lead to their development.