- Email: [email protected]
Tu1153 Clinical and Prognostic Features of Rectal Neuroendocrine Tumors
AGA Abstracts
is a valuable tool in evaluation of the small bowel tumor. The DBE with biopsy of suspected lesion has very high histological diagnostic yield and commonly proceeded by abnormal imaging studies. The capsule endoscopy prior to DBE was sensitive to suspect presence of small bowel tumor in approximately 92% of the cases. Indications and findings of DBE during which small bowel tumors were discovered (total n = 88 procedures)
Tu1154 Tu1153
HsTRAIL/Apo2L-Induced Apoptosis in Enteropathy-Associated T-Cell Lymphoma Marijn Radersma, Laura R. de Baaij, Nathalie J. Hijmering, Chris J. Meijer, Chris J. Mulder, Saskia A. Cillessen
Clinical and Prognostic Features of Rectal Neuroendocrine Tumors Brett M. Weinstock, Michelle K. Kim, Noam Harpaz, Steven H. Itzkowitz, Richard R. Warner
EATL is an intestinal tumor of aberrant intraepithelial T-lymphocytes (IELs) and may be preceded by refractory celiac disease type II (RCD II). Current therapies include surgery, chemotherapy and autologous and/or allogeneic stem cell transplantation. Despite these therapies, the overall outcome of EATL is very poor with 1- and 5-year survival rates in the range of 31-39% and 8-20%, respectively. Therefore, new therapeutic options are needed. Human soluble tumor necrosis factor-related apoptosis-inducing ligand, hsTRAIL/Apo2L, a member of the TNF family, has proven to selectively kill tumor cells via an alternative, death-receptor mediated apoptosis pathway. In this present study we evaluated if hsTRAIL/ Apo2L induces apoptosis in both isolated lymphoma cells of EATL biopsies and isolated cells of RCD II biopsies. hsTRAIL/Apo2L induced apoptosis in isolated EATL lymphoma cells. RCD II cells were less sensitive to hsTRAIL/Apo2L compared to EATL cells. EATL cells demonstrated high expression of TRAIL receptors R1 and R2 and almost no expression of R3 and R4, whereas RCDII cells showed little expression of TRAIL receptor R1 and R2. hsTRAIL/Apo2L-induced apoptosis in EATL cells was caspase-9 dependent, but unexpectedly only low to moderate caspase-8 involvement could be detected. RT-MLPA analysis on EATL samples confirmed this observation by showing increased levels of c-Flip in EATL cells, which suggests a blockage in the extrinsic apoptosis pathway. In conclusion, our study showed that hsTRAIL/Apo2L induces apoptosis in EATL cells, mainly through the intrinsic apoptosis pathway. Therefore, hsTRAIL/Apo2L may be a new therapeutic option for EATL patients.
Background: Rectal neuroendocrine tumors (NETs) are among the most common neuroendocrine tumors. At The Mount Sinai Hospital, we have a large population of patients with neuroendocrine tumors with known outcomes. Aims: The primary aim was to identify predictors of survival. The secondary aim was to identify characteristics associated with the presence of metastatic disease. Methods: From existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation, we identified 141 patients with rectal NETs seen at the Mount Sinai Hospital between 1972 and 2011. A comprehensive database with demographic, clinical, pathologic, staging, and outcome data was constructed. Tumors were staged from pathology reports based on tumor size, depth of invasion, presence of nodal involvement, and presence of metastases. Statistical analysis was performed using SPSS. 2-sided t tests and chi-square analysis were performed. Kaplan Meier survival curves were constructed; the log rank test was used to identify differences in survival. Results: The average age was 53.1 years (range 12-87); 43% were males. Average tumor size was 0.65 cm (range, 0-5.3). Tumors < 1.0 cm accounted for 82.4%, 7.6% were between 1.0 and 2.0cm, 9.9% were > 2.0cm. Most tumors (75.9%) were staged T1aN0M0. Stage 1-4 tumors accounted for 83%, 3.5%, 3.5% and 9.9% respectively. The majority (70.9%) of the NETs were incidental findings. NETs were treated by endoscopy (65.1%), transanal resection (13.5%) or by surgical resection (18.4%). Kaplan Meier curves showed an overall 5-year survival rate of 84.4% (Figure 1). The average known survival to date was 7.43 years (range, 0.8-34.7 years). Both incidental presentation and early tumor stage were predictive of survival (p=0.001, Figure 1). Comparing metastatic vs nonmetastatic tumors, tumor size was a predictor of metastases, with metastatic tumors having an average size of 2.2 cm and non-metastatic tumors 0.5 cm (p=0.013). Patients with metastatic tumors were more likely to present with symptoms. Only 35.7% presented as incidental findings, 74.8% with non-metastatic tumors presented incidentally (p= 0.013). Endoscopically treated tumors accounted for 63.0% of patients with non-metastatic NETs, vs 28.6% with metastatic tumors (p=0.019). Conclusion: In this retrospective study, patients with rectal NETs typically had small tumors (<1.0 cm) with low stage (T1aN0M0) and were treated endoscopically. Factors predicting favorable outcomes included incidental detection and early stage. There were clear survival differences between stages. Those with metastatic tumors were more likely to have large symptomatic tumors, treated with a more extensive surgical approach. Prospective studies are needed to further refine the treatment algorithm of endoscopic resection, transanal resection, and surgical approaches.
AGA Abstracts
Tu1155 The Extension of Mucosal Lesions, Helicobacter pylori Infection Status and API2-MALT1 Positivity are Associated With the Therapeutic Response for Gastric MALT Lymphoma Sawako Okada, Hidekazu Suzuki, Juntaro Matsuzaki, Hitoshi Tsugawa, Seiichiro Fukuhara, Kenro Hirata, Toshihiro Nishizawa, Toshifumi Hibi Background. Gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) accounts for 20-40% of extranodal lymphoma. Helicobacter pylori (H. pylori) is known as a causative role in the onset and t(11;18)(q21;q21)/API2-MALT1 is reported to be associated with non-responsiveness of H. pylori eradication. However, whether other factors influenced the outcome of the disease is not clear. The present study is designed to evaluate the possible relationship between the course of gastric MALT lymphoma, endoscopic findings, H. pylori infection, and the presence of API2-MALT1 in retrospective study.Method. All the patients who had attended a hospital for treatment of gastric MALT lymphoma in Keio University Hospital from July 2007 to November 2011 were enrolled. The H. pyloristatus was determined by histology, culture, 13C urea breath test, and/ or serology. The location of lesions was classified into two groups: "focal type" is defined as a lesion located on one area of the three portions of stomach, which are the upper third (proximal), middle third, and lower third (distal). "Diffuse type" is defined as a lesion located on more than 2 areas. We examined the difference between the patients with complete histological response (ChR) and non-responders using χ2 test.Result. A total of 61 patients with gastric MALT lymphoma (22 men, 61.5±5.2 years; 39 women, 61.8±3.7 years) was examined. Their clinical stage of Ann-Arbor classification were stage I (n=60) and II (n=1). During the follow-up periods ranging from 0.1 to 15.0 years (mean; 4.6±7.8 years), 9 patients were subjected to “watch and wait” strategy and 52 were treated by H. pylori eradication (n=42), chemotherapy after eradication (n=4), chemotherapy alone (n=4), radiotherapy (n=1) or endoscopic resection (n=1). ChR was achieved in 43 patients (72.9%) by “watch and wait” (n=5), eradication (n=32), chemotherapy after eradication (n=2), chemotherapy alone (n=2), radiotherapy (n=1) and endoscopic resection (n=1). 16 patients (27.1%) did not respond to treatments; “watch and wait” (n=4), eradication (n=8), chemotherapy after eradication (n=2), chemotherapy alone (n=2). 8 of 30 patients with ChR (26.7%) had diffuse type lesions, whereas 9 of 16 non-responders (56.3 %) showed diffuse lesions (p= 0.025). The prevalence of H. pylori infection was higher in ChR patients (n=32/40, 80.0%) than in non-responders (n=7/16, 43.8%) (p=0.012). The prevalence of API2-MALT1 was lower in ChR patients (n=2/17, 11.8%) than in non-responders (n=9/13, 69.2%) (p= 0.002).Conclusion. Patients with gastric MALT lymphoma who were infected with H. pylori had good response to treatments. On the other hand, patients with diffuse type lesions and API2-MALT1 had a refractory course of the disease. These factors would be useful to predict the outcome of the treatment for gastric MALT lymphoma.
S-760
is a valuable tool in evaluation of the small bowel tumor. The DBE with biopsy of suspected lesion has very high histological diagnostic yield and commonly proceeded by abnormal imaging studies. The capsule endoscopy prior to DBE was sensitive to suspect presence of small bowel tumor in approximately 92% of the cases. Indications and findings of DBE during which small bowel tumors were discovered (total n = 88 procedures)
Tu1154 Tu1153
HsTRAIL/Apo2L-Induced Apoptosis in Enteropathy-Associated T-Cell Lymphoma Marijn Radersma, Laura R. de Baaij, Nathalie J. Hijmering, Chris J. Meijer, Chris J. Mulder, Saskia A. Cillessen
Clinical and Prognostic Features of Rectal Neuroendocrine Tumors Brett M. Weinstock, Michelle K. Kim, Noam Harpaz, Steven H. Itzkowitz, Richard R. Warner
EATL is an intestinal tumor of aberrant intraepithelial T-lymphocytes (IELs) and may be preceded by refractory celiac disease type II (RCD II). Current therapies include surgery, chemotherapy and autologous and/or allogeneic stem cell transplantation. Despite these therapies, the overall outcome of EATL is very poor with 1- and 5-year survival rates in the range of 31-39% and 8-20%, respectively. Therefore, new therapeutic options are needed. Human soluble tumor necrosis factor-related apoptosis-inducing ligand, hsTRAIL/Apo2L, a member of the TNF family, has proven to selectively kill tumor cells via an alternative, death-receptor mediated apoptosis pathway. In this present study we evaluated if hsTRAIL/ Apo2L induces apoptosis in both isolated lymphoma cells of EATL biopsies and isolated cells of RCD II biopsies. hsTRAIL/Apo2L induced apoptosis in isolated EATL lymphoma cells. RCD II cells were less sensitive to hsTRAIL/Apo2L compared to EATL cells. EATL cells demonstrated high expression of TRAIL receptors R1 and R2 and almost no expression of R3 and R4, whereas RCDII cells showed little expression of TRAIL receptor R1 and R2. hsTRAIL/Apo2L-induced apoptosis in EATL cells was caspase-9 dependent, but unexpectedly only low to moderate caspase-8 involvement could be detected. RT-MLPA analysis on EATL samples confirmed this observation by showing increased levels of c-Flip in EATL cells, which suggests a blockage in the extrinsic apoptosis pathway. In conclusion, our study showed that hsTRAIL/Apo2L induces apoptosis in EATL cells, mainly through the intrinsic apoptosis pathway. Therefore, hsTRAIL/Apo2L may be a new therapeutic option for EATL patients.
Background: Rectal neuroendocrine tumors (NETs) are among the most common neuroendocrine tumors. At The Mount Sinai Hospital, we have a large population of patients with neuroendocrine tumors with known outcomes. Aims: The primary aim was to identify predictors of survival. The secondary aim was to identify characteristics associated with the presence of metastatic disease. Methods: From existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation, we identified 141 patients with rectal NETs seen at the Mount Sinai Hospital between 1972 and 2011. A comprehensive database with demographic, clinical, pathologic, staging, and outcome data was constructed. Tumors were staged from pathology reports based on tumor size, depth of invasion, presence of nodal involvement, and presence of metastases. Statistical analysis was performed using SPSS. 2-sided t tests and chi-square analysis were performed. Kaplan Meier survival curves were constructed; the log rank test was used to identify differences in survival. Results: The average age was 53.1 years (range 12-87); 43% were males. Average tumor size was 0.65 cm (range, 0-5.3). Tumors < 1.0 cm accounted for 82.4%, 7.6% were between 1.0 and 2.0cm, 9.9% were > 2.0cm. Most tumors (75.9%) were staged T1aN0M0. Stage 1-4 tumors accounted for 83%, 3.5%, 3.5% and 9.9% respectively. The majority (70.9%) of the NETs were incidental findings. NETs were treated by endoscopy (65.1%), transanal resection (13.5%) or by surgical resection (18.4%). Kaplan Meier curves showed an overall 5-year survival rate of 84.4% (Figure 1). The average known survival to date was 7.43 years (range, 0.8-34.7 years). Both incidental presentation and early tumor stage were predictive of survival (p=0.001, Figure 1). Comparing metastatic vs nonmetastatic tumors, tumor size was a predictor of metastases, with metastatic tumors having an average size of 2.2 cm and non-metastatic tumors 0.5 cm (p=0.013). Patients with metastatic tumors were more likely to present with symptoms. Only 35.7% presented as incidental findings, 74.8% with non-metastatic tumors presented incidentally (p= 0.013). Endoscopically treated tumors accounted for 63.0% of patients with non-metastatic NETs, vs 28.6% with metastatic tumors (p=0.019). Conclusion: In this retrospective study, patients with rectal NETs typically had small tumors (<1.0 cm) with low stage (T1aN0M0) and were treated endoscopically. Factors predicting favorable outcomes included incidental detection and early stage. There were clear survival differences between stages. Those with metastatic tumors were more likely to have large symptomatic tumors, treated with a more extensive surgical approach. Prospective studies are needed to further refine the treatment algorithm of endoscopic resection, transanal resection, and surgical approaches.
AGA Abstracts
Tu1155 The Extension of Mucosal Lesions, Helicobacter pylori Infection Status and API2-MALT1 Positivity are Associated With the Therapeutic Response for Gastric MALT Lymphoma Sawako Okada, Hidekazu Suzuki, Juntaro Matsuzaki, Hitoshi Tsugawa, Seiichiro Fukuhara, Kenro Hirata, Toshihiro Nishizawa, Toshifumi Hibi Background. Gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) accounts for 20-40% of extranodal lymphoma. Helicobacter pylori (H. pylori) is known as a causative role in the onset and t(11;18)(q21;q21)/API2-MALT1 is reported to be associated with non-responsiveness of H. pylori eradication. However, whether other factors influenced the outcome of the disease is not clear. The present study is designed to evaluate the possible relationship between the course of gastric MALT lymphoma, endoscopic findings, H. pylori infection, and the presence of API2-MALT1 in retrospective study.Method. All the patients who had attended a hospital for treatment of gastric MALT lymphoma in Keio University Hospital from July 2007 to November 2011 were enrolled. The H. pyloristatus was determined by histology, culture, 13C urea breath test, and/ or serology. The location of lesions was classified into two groups: "focal type" is defined as a lesion located on one area of the three portions of stomach, which are the upper third (proximal), middle third, and lower third (distal). "Diffuse type" is defined as a lesion located on more than 2 areas. We examined the difference between the patients with complete histological response (ChR) and non-responders using χ2 test.Result. A total of 61 patients with gastric MALT lymphoma (22 men, 61.5±5.2 years; 39 women, 61.8±3.7 years) was examined. Their clinical stage of Ann-Arbor classification were stage I (n=60) and II (n=1). During the follow-up periods ranging from 0.1 to 15.0 years (mean; 4.6±7.8 years), 9 patients were subjected to “watch and wait” strategy and 52 were treated by H. pylori eradication (n=42), chemotherapy after eradication (n=4), chemotherapy alone (n=4), radiotherapy (n=1) or endoscopic resection (n=1). ChR was achieved in 43 patients (72.9%) by “watch and wait” (n=5), eradication (n=32), chemotherapy after eradication (n=2), chemotherapy alone (n=2), radiotherapy (n=1) and endoscopic resection (n=1). 16 patients (27.1%) did not respond to treatments; “watch and wait” (n=4), eradication (n=8), chemotherapy after eradication (n=2), chemotherapy alone (n=2). 8 of 30 patients with ChR (26.7%) had diffuse type lesions, whereas 9 of 16 non-responders (56.3 %) showed diffuse lesions (p= 0.025). The prevalence of H. pylori infection was higher in ChR patients (n=32/40, 80.0%) than in non-responders (n=7/16, 43.8%) (p=0.012). The prevalence of API2-MALT1 was lower in ChR patients (n=2/17, 11.8%) than in non-responders (n=9/13, 69.2%) (p= 0.002).Conclusion. Patients with gastric MALT lymphoma who were infected with H. pylori had good response to treatments. On the other hand, patients with diffuse type lesions and API2-MALT1 had a refractory course of the disease. These factors would be useful to predict the outcome of the treatment for gastric MALT lymphoma.
S-760