Eduardo Linhares

Atualização em GIST

Gastrointestinal stromal tumor (GIST) has been recently the subject of considerable clinical and experimental interest. This focus is based on insights gained during the past years concerning its identification as a distinct clinical entity and the advances in knowledge about the diagnosis and management. Historically, surgery has been considered the most effective treatment in spite of its limitations. Others therapeutic approaches have been tryng without success, until the introduction of imatinib. This drug provided hopeful results in the treatment of this neoplasia. The idea that imatinib could improve surgical outcome have led to some clinical trials with the hope that this association (imatinib & surgery) could achieve good results.

Major hepatectomy for isolated metastases from gastric adenocarcinoma

BACKGROUND Liver metastases from gastric adenocarcinoma denote a poor prognosis. Most gastric metastases will be diffuse, and for these chemotherapy remains the only useful treatment modality. The treatment of isolated liver metastases is still unclear. The Japanese literature has reported good results with surgical resection, but Western series were unable to achieve the same results. We report our results with resection of liver metastases from gastric cancer in nine patients. METHODS A retrospective analysis was undertaken to determine the results of the surgical treatment of hepatic metastases from gastric carcinoma over the last five decades. Only nine patients underwent such treatment. Variables analysed were age, gender, the primary tumour, the type of liver operation performed, the time of occurrence of liver metastasis, the morbidity and mortality and the overall survival. Follow-up was complete. RESULTS There were eight patients with gastric carcinoma staged as T3 and one as T4 (UICC-97). All patients had positive lymph nodes. The hepatic procedure performed was a hemihepatectomy in eight patients and a left lateral segmentectomy in one patient. Right hepatectomy was performed in six cases. There were four patients with synchronous liver metastasis: three involved the right liver and the other involved segments II/III. All were treated by one-step surgery. The five metachronous metastases involved the right liver in three patients (accounting for half of the right hepatectomies), while the other two underwent left hepatectomies. There was a high postoperative mortality rate (33%, 3/9), two of the deaths occurring in the first decade of the study (1956, 1966) secondary to hepatic insufficiency and one from sepsis. One patient died suddenly without recurrence after 3 months. The other five died with evidence of disease at between 2 and 11 months. DISCUSSION Despite some anecdotal reports of treatment with chemotherapy, either systemic or intrahepatic, the more consistent results for the treatment of patients with hepatic metastases from gastric adenocarcinoma come from the Japanese literature with the use of radical surgery. Unfortunately, Western series, including our own, do not achieve the same results. At the present time, in view of these results, we are performing less aggressive treatment such as radio-frequency ablation.

Involvement of signaling molecules in the prediction of response to imatinib treatment in metastatic GIST patients.

Imatinib therapy has undoubtedly contributed to the treatment of metastatic gastrointestinal stromal (GIST) tumors that were previously untreatable. However, disease progression during treatment with tyrosine kinase inhibitors remains an issue in clinical practice not fully explained by KIT and PDGFRA mutation status. We investigated the role of three important signaling molecules (insulin-like growth factor 1 receptor [IGF1R], protein kinase C-θ [PKCθ], and Raf kinase inhibitor protein [RKIP]) that have been implicated in GIST pathogenesis as potential biomarkers for prediction of response to imatinib treatment. We retrospectively reviewed 76 patients with metastatic GIST submitted to imatinib treatment between 2002 and 2007, and analyzed 63 of them. Insulin-like growth factor 1, total PKCθ, phosphorylated PKCθ, and RKIP immunohistochemical expression were correlated with objective response to imatinib treatment and progression-free and overall survival. Median follow-up was 31.2 mo (95% confidence interval, 26.3-36.1 mo). There was a statistically significant association between IGF1R expression and type of response to imatinib treatment (P = 0.05)-that is, higher IGF1R expression was related to lower objective response. However, IGF1R higher expression did not affect progression-free and overall survival. Insulin-like growth factor 1, but not PKCθ and RKIP, emerges as a potential biomarker for prediction of response to imatinib treatment in metastatic GISTs. Validation studies are warranted.

Tumor estromal gastrointestinal: análise de 146 casos do centro de referência do Instituto Nacional do Câncer - INCA

OBJECTIVE: To evaluate the treatment of GIST in INCA. METHODS: We conducted a retrospective analysis of all cases of GIST treated at INCA in the period from 1997 to 2009. RESULTS: We analyzed 146 patients with a mean age of 44.5 years and female predominance. The main symptom was abdominal pain. We observed the occurrence of a second primary tumor in 22% of cases and 92% of the immunohistochemistry exams were positive for CD117. The most frequent location was in the stomach and the high-risk group was predominant. Surgery was considered R0 (extensive) in 70% of the cases and the main sites of metastases were liver and peritoneum. Overall survival in two and five years was, respectively, 86% and 59%. There was a significant difference between overall survival (p = 0.29) of the high-risk group versus the other. CONCLUSION: Our patients presented mainly in the form of high-risk disease, with obvious impact on survival. The use of imatinib improved survival of patients with recurrent and metastatic disease. We should study its use in the setting of adjuvant and neoadjuvant therapy to improve results of the high risk group. The creation of reference centers is a need for the study of rare diseases.

Aspectos tomográficos do tumor estromal gastrintestinal de origem gástrica: estudo de 14 casos

OBJECTIVE: The purpose of this study was to describe the tomographic findings of gastric gastrointestinal stromal tumor. MATERIALS AND METHODS: Fourteen patients with histopathologically and immunohistochemically confirmed gastric gastrointestinal stromal tumors, who had already been submitted to computed tomography scans before the treatment, were evaluated in the period between January 1999 and December 2006. The following tomographic variables were analyzed: lesion topography, size/dimensions, homogeneity, contour, margins, morphology, pattern and intravenous contrast-enhancement intensity, growth pattern, invasion of adjacent organs, presence of ulceration, fistula, calcifications, mesenteric fat infiltration, lymphadenomegaly and presence of distant metastasis. RESULTS: Tumors were found in the body (57.1%) or in the gastric fundus (42.9%), with sizes ranging between 6.0 cm and 23.0 cm (mean, 11.5 cm). Predominantly extraluminal growth was observed in 57.1% of cases and intra/extraluminal in 35.7%. Subtle contrast-enhancement was observed in 50%, moderate in 50%, and heterogeneous in 64.3% of cases. Additionally, central hypodensity was observed in 64.3%, invasion of adjacent organs in 42.9%, and hepatic metastasis in 7.2% of cases. CONCLUSION: In the present study, the majority of tumors were found in the gastric body, with an average size of 11.5 cm, presenting with central hypodensity, heterogeneous contrast-enhancement and predominantly extraluminal growth.

Fatores prognósticos clínicos e anatomopatológicos dos tumores estromais gastrointestinais (gist) de origem gástrica

BACKGROUND: This study wants to identify clinical and pathologic prognostic factors of resected gastric gastrointestinal stromal tumors (GIST). METHODS: Twenty-nine patients with c-Kit positive gastric GIST who underwent surgical resection at the Brazilian National Cancer Institute (INCA) between 1983 and 2004 were reviewed retrospectively. Prognostic significance of clinical and pathological variables was investigated. The endpoints were overall survival and disease free survival. RESULTS: Median follow-up was 35 months. Five-year estimate survival rate was 53%. Univariate analysis for overall survival identified size 13.5 cm (p=0.01) and recurrence (p=0.03) as prognostic factors. Size 13.5 cm and recurrence were independent factors (p=0.01 and p=0.03 respectively) in multivariate analysis. Univariate analysis for disease free survival identified size 13.5 cm (p=0.04) and grade (p=0.04) as prognostic factors but only size 13.5 cm was an independent factor in multivariate analysis. CONCLUSION: Size 13.5 cm and recurrence were identified as independent prognostic factors for overall survival. Only size 13.5 cm was an independent prognostic factor for disease free survival.

O papel atual do cirurgião no tratamento do GIST

Recent progress in gastrointestinal stromal tumors (GIST) treatment were responsible for changing GISTs natural history. Knowlegde acquirement of molecular mechanism-based systemic therapy gave rise to the development of targeted antineoplastic drugs capable of reaching outcomes that had never been reached before. The introduction of imatinib in the clinical practice not only changed GISTs patients survival but also shifted paradigms. However, besides all these new advances and the improved results with imatinib, the surgeon still plays a pivotal role in the management of the primary GIST tumor and even in the metastatic setting.

Transanal minimally invasive surgery for total mesorectal excision (ETM) through transanal approach (TaETM) with robotic and Transanal Endoscopic Operations (TEO) combined access: step by step surgery

Rational In the treatment of colorectal cancer, from 1982 Heald proposed standardization of the total mesorectal excision, with a significant reduction in the recurrence rate. But the treatment of lower rectal lesions is still a challenge. Aim To describe the association of robotic low anterior resection- TATA (Transanal Abdominal Transanal Resection), with transanal access using Transanal Endoscopic Operations - TEO in the treatment of lower rectal cancer. Method The TATA performs robotic abdominal approach and the TEO performs the perineal approach, developing total mesorectal excision (TME) transanally (TaETM). Result The TaETM technique was applied in a woman with rectal adenocarcinoma 5 cm from the anal verge that had been submitted to chemoradiation. The procedure was performed with satisfatory operative time and favorable oncological outcome (grade 3 mesorectal excision). Conclusion This is a promising minimally invasive procedure in the armamentarium of rectal cancer treatment, specially in challenging scenarios such as narrow pelvis, obesity and very low rectal tumors.