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Clinical Outcomes of Endoscopic Resection for Rectal Neuroendocrine Tumors
AGA Abstracts
the induction of H. pylori-specific immune responses in the host, the infection is unable to be cleared. It is widely accepted that H. pylori can manipulate host defence mechanisms to persist in the host, utilising virulence factors to limit detection and avoid eradication by regulating innate and adaptive immune responses. The many therapeutic vaccines against H. pylori that have failed in human trials illustrates a significant need to better understand the host immune response to H. pylori. The recent success of a prophylactic vaccine is encouraging. Improving the understanding of immune responses to H. pylori in humans will lead to better vaccines and anti-infective strategies to combat the infection, particularly in high risk individuals. Therefore, we set out to study acute host responses in humans by challenging volunteers with H. pylori strains of different genotypes. Methods Thirty six H. pylori sero-negative individuals with normal endoscopic findings were enrolled into the trial. 30 subjects were infected with 5 genetically-diverse H. pylori strains, and the remaining six were given placebo. Biopsy, serology, breath test and culture results were obtained from all subjects at 2 and 12 weeks post-challenge. Symptoms were recorded using diary cards. Subjects received standard antibiotic treatment after 12 weeks to eradicate the infection. Bacterial load, antibody levels and tissue inflammation were assessed. Results Overall, 27 of 30 subjects challenged with H. pylori achieved infection as demonstrated by histology and culture test. At 2 weeks, 24/30 subjects were infected with H. pylori with no difference in infection rates between the groups (Figure 1a). After 12 weeks, 19 subjects were infected (Figure 1b). Eight subjects spontaneously cleared the infection, which was associated with a specific H. pylori genotype. All infected subjects seroconverted with good antibody responses. Active inflammation was present in 29/30 subjects. A mild to moderate level of inflammation was associated with H. pylori infection. Inflammatory patterns differed among the groups. Conclusions Challenge of human subjects with diverse H. pylori strains achieved similar levels of colonisation that were either persistent or spontaneously cleared. Infection resulted in active gastritis and seroconversion. Different inflammatory patterns were associated with specific strains of H. pylori and one strain induced little inflammation. This study provides valuable insight into strain-specific induction of H. pylori immune responses in relation to spontaneous clearance of the infection.
obstruction and ischemia. The classification of NETs using both the WHO histological grading system and the American Joint Committee on cancer staging (AJCC) has been well validated in gastroenteropancreatic neuroendocrine neoplasms in terms of prognosis. In a published survival analysis of a large cohort of patients with SINETs from our centre the median survival was 10.7 years, but studies evaluating predictors of survival in the subgroup of SINETs with desmoplasia are lacking. Methods: A total of 147 patients with small bowel neuroendocrine tumours associated with mesenteric desmoplasia who were followed-up in our centre from 2001 to 2013 were included in this retrospective study. Data collected included patient demographics (age, sex, smoking history), tumour characteristics (tumour grade, extent of liver and extrahepatic metastases), clinical (presenting symptoms at diagnosis, performance status, number of comorbidities, presence of secondary malignancies and carcinoid heart disease, surgical resection of primary, medical therapies during follow-up) and biochemical data (chromogranin A, urine 5-HIAA). Data were measured at the time of initial diagnosis. These parameters were analysed by univariate (UVA) and multivariate analysis (MVA) (table 1) as predictive factors of overall survival. Results: The mean and median overall survival for this group were 7.4 and 6.8 years respectively (Figure 1). On UVA age>65, volume of liver metastases >50% of liver parenchyma, carcinoid heart disease, chromogranin A levels>10 times upper limit of normal (ULN) and urine 5-HIAA levels >5 times ULN were associated with a worse survival, whereas primary resection (but not bypass surgery) was associated with a better outcome. MVA of statistically significant factors on UVA demonstrated that only age>65 and urine 5-HIAA>10 times ULN remained statistically significant as negative predictors of survival, whereas primary resection showed a trend as a predictive factor of better outcome, although it did not quite reach the level of statistical significance (Cox hazard ratio=0.54, p=0.09). Conclusions: Our data suggest that age>65 and urine 5-HIAA levels>10 times ULN at diagnosis are predictive of a worse outcome in patients with SINET and desmoplasia. Patients with SINET and desmoplasia have worse overall survival than SINET and no desmoplasia. Primary resection showed a trend as a predictor of better survival and this finding should be evaluated further in adequately powered prospective trials. Multivariate analysis of predictors of survival in SINETs associated with desmoplasia (*indicates statistical significance)
Figure 1. Colonisation rates of 5 H. pylori strains in human subjects 2 and 12 weeks after infection.
Mo1151 CLINICAL OUTCOMES OF ENDOSCOPIC RESECTION FOR RECTAL NEUROENDOCRINE TUMORS Jihye Kim, Jaeyoung Chun, Jee Hyun Kim, Jooyoung Lee, Youn Su Park, Jong Pil Im, Joo Sung Kim Background/Aims: The incidence of rectal neuroendocrine tumors (NETs) is rapidly increasing because of the frequent use of endoscopic screening for colorectal cancers. However, the clinical outcomes of endoscopic resection for rectal NETs are still unclear. The aim of this study was to assess the histologically complete resection (H-CR) rate and recurrence after the endoscopic resection for rectal NETs. Methods: A retrospective analysis was performed in the patients who underwent endoscopic resection of rectal NETs between January 2002 and March 2015 at Seoul National University Hospital. Primary outcomes were H-CR and recurrence rates after the endoscopic resection. H-CR was defined as free of tumor invasion in the lateral and deep margins of resected specimens. Secondary outcomes were additive treatment for histologically incomplete resection, procedure-related complications, and disease-related deaths. Results: Among 298 patients, 243 (87%) were treated with injectionassisted endoscopic mucosal resection (EMR), 23 (8%) with EMR using a dual-channel endoscope, 21 (7%) with endoscopic submucosal dissection (ESD), and 11 (4%) with EMR after precutting. The median tumor size was 6.4 (range, 1-20) mm in diameter and all lesions were confined to the submucosal layer. The en-bloc resection rate was 99% and all patients achieved endoscopically complete resection. The H-CR rates were 74%, 73%, 72% and 52% for injection-assisted EMR, EMR using a dual-channel endoscope, EMR after precutting and ESD, respectively. Multivariate analysis showed that H-CR was associated with tumor size regardless of endoscopic treatment modalities (p=0.001). Of the 298 patients, 198 patients (66%) underwent at least one endoscopic follow-up. Five out of the 198 patients (2%) with endoscopic follow-up had tumor recurrence with a median of 18 months (range 2-98). There was 1 case of disease-related death occurred 156 months after the endoscopic treatment because of bone marrow failure as a result of tumor metastasis. Conclusions: Although the en-bloc resection rate was 99% in rectal NETs, H-CR rates were 72-74% for various EMR procedures. H-CR may be associated with tumor size regardless of endoscopic treatment modalities.
Mo1152 PREDICTORS OF SURVIVAL IN PATIENTS WITH SMALL BOWEL NEUROENDOCRINE TUMOURS ASSOCIATED WITH MESENTERIC DESMOPLASIA Faidon-Marios Laskaratos, Leonidas Diamantopoulos, Martin Walker, Mohamed Khalifa, Henry Walton, Apostolos Koffas, George Demetriou, Christos Toumpanakis, Martyn Caplin, Dalvinder Mandair
Kaplan-Meier curve of overall survival in patients with small bowel neuroendocrine tumours associated with mesenteric desmoplasia
Background: Small intestinal neuroendocrine tumours (SINETs) represent 30-50% of small bowel neoplasms and their incidence is rising. They are often associated with a desmoplastic reaction in the mesentery, which can lead to gastrointestinal complications, including bowel
AGA Abstracts
S-668
the induction of H. pylori-specific immune responses in the host, the infection is unable to be cleared. It is widely accepted that H. pylori can manipulate host defence mechanisms to persist in the host, utilising virulence factors to limit detection and avoid eradication by regulating innate and adaptive immune responses. The many therapeutic vaccines against H. pylori that have failed in human trials illustrates a significant need to better understand the host immune response to H. pylori. The recent success of a prophylactic vaccine is encouraging. Improving the understanding of immune responses to H. pylori in humans will lead to better vaccines and anti-infective strategies to combat the infection, particularly in high risk individuals. Therefore, we set out to study acute host responses in humans by challenging volunteers with H. pylori strains of different genotypes. Methods Thirty six H. pylori sero-negative individuals with normal endoscopic findings were enrolled into the trial. 30 subjects were infected with 5 genetically-diverse H. pylori strains, and the remaining six were given placebo. Biopsy, serology, breath test and culture results were obtained from all subjects at 2 and 12 weeks post-challenge. Symptoms were recorded using diary cards. Subjects received standard antibiotic treatment after 12 weeks to eradicate the infection. Bacterial load, antibody levels and tissue inflammation were assessed. Results Overall, 27 of 30 subjects challenged with H. pylori achieved infection as demonstrated by histology and culture test. At 2 weeks, 24/30 subjects were infected with H. pylori with no difference in infection rates between the groups (Figure 1a). After 12 weeks, 19 subjects were infected (Figure 1b). Eight subjects spontaneously cleared the infection, which was associated with a specific H. pylori genotype. All infected subjects seroconverted with good antibody responses. Active inflammation was present in 29/30 subjects. A mild to moderate level of inflammation was associated with H. pylori infection. Inflammatory patterns differed among the groups. Conclusions Challenge of human subjects with diverse H. pylori strains achieved similar levels of colonisation that were either persistent or spontaneously cleared. Infection resulted in active gastritis and seroconversion. Different inflammatory patterns were associated with specific strains of H. pylori and one strain induced little inflammation. This study provides valuable insight into strain-specific induction of H. pylori immune responses in relation to spontaneous clearance of the infection.
obstruction and ischemia. The classification of NETs using both the WHO histological grading system and the American Joint Committee on cancer staging (AJCC) has been well validated in gastroenteropancreatic neuroendocrine neoplasms in terms of prognosis. In a published survival analysis of a large cohort of patients with SINETs from our centre the median survival was 10.7 years, but studies evaluating predictors of survival in the subgroup of SINETs with desmoplasia are lacking. Methods: A total of 147 patients with small bowel neuroendocrine tumours associated with mesenteric desmoplasia who were followed-up in our centre from 2001 to 2013 were included in this retrospective study. Data collected included patient demographics (age, sex, smoking history), tumour characteristics (tumour grade, extent of liver and extrahepatic metastases), clinical (presenting symptoms at diagnosis, performance status, number of comorbidities, presence of secondary malignancies and carcinoid heart disease, surgical resection of primary, medical therapies during follow-up) and biochemical data (chromogranin A, urine 5-HIAA). Data were measured at the time of initial diagnosis. These parameters were analysed by univariate (UVA) and multivariate analysis (MVA) (table 1) as predictive factors of overall survival. Results: The mean and median overall survival for this group were 7.4 and 6.8 years respectively (Figure 1). On UVA age>65, volume of liver metastases >50% of liver parenchyma, carcinoid heart disease, chromogranin A levels>10 times upper limit of normal (ULN) and urine 5-HIAA levels >5 times ULN were associated with a worse survival, whereas primary resection (but not bypass surgery) was associated with a better outcome. MVA of statistically significant factors on UVA demonstrated that only age>65 and urine 5-HIAA>10 times ULN remained statistically significant as negative predictors of survival, whereas primary resection showed a trend as a predictive factor of better outcome, although it did not quite reach the level of statistical significance (Cox hazard ratio=0.54, p=0.09). Conclusions: Our data suggest that age>65 and urine 5-HIAA levels>10 times ULN at diagnosis are predictive of a worse outcome in patients with SINET and desmoplasia. Patients with SINET and desmoplasia have worse overall survival than SINET and no desmoplasia. Primary resection showed a trend as a predictor of better survival and this finding should be evaluated further in adequately powered prospective trials. Multivariate analysis of predictors of survival in SINETs associated with desmoplasia (*indicates statistical significance)
Figure 1. Colonisation rates of 5 H. pylori strains in human subjects 2 and 12 weeks after infection.
Mo1151 CLINICAL OUTCOMES OF ENDOSCOPIC RESECTION FOR RECTAL NEUROENDOCRINE TUMORS Jihye Kim, Jaeyoung Chun, Jee Hyun Kim, Jooyoung Lee, Youn Su Park, Jong Pil Im, Joo Sung Kim Background/Aims: The incidence of rectal neuroendocrine tumors (NETs) is rapidly increasing because of the frequent use of endoscopic screening for colorectal cancers. However, the clinical outcomes of endoscopic resection for rectal NETs are still unclear. The aim of this study was to assess the histologically complete resection (H-CR) rate and recurrence after the endoscopic resection for rectal NETs. Methods: A retrospective analysis was performed in the patients who underwent endoscopic resection of rectal NETs between January 2002 and March 2015 at Seoul National University Hospital. Primary outcomes were H-CR and recurrence rates after the endoscopic resection. H-CR was defined as free of tumor invasion in the lateral and deep margins of resected specimens. Secondary outcomes were additive treatment for histologically incomplete resection, procedure-related complications, and disease-related deaths. Results: Among 298 patients, 243 (87%) were treated with injectionassisted endoscopic mucosal resection (EMR), 23 (8%) with EMR using a dual-channel endoscope, 21 (7%) with endoscopic submucosal dissection (ESD), and 11 (4%) with EMR after precutting. The median tumor size was 6.4 (range, 1-20) mm in diameter and all lesions were confined to the submucosal layer. The en-bloc resection rate was 99% and all patients achieved endoscopically complete resection. The H-CR rates were 74%, 73%, 72% and 52% for injection-assisted EMR, EMR using a dual-channel endoscope, EMR after precutting and ESD, respectively. Multivariate analysis showed that H-CR was associated with tumor size regardless of endoscopic treatment modalities (p=0.001). Of the 298 patients, 198 patients (66%) underwent at least one endoscopic follow-up. Five out of the 198 patients (2%) with endoscopic follow-up had tumor recurrence with a median of 18 months (range 2-98). There was 1 case of disease-related death occurred 156 months after the endoscopic treatment because of bone marrow failure as a result of tumor metastasis. Conclusions: Although the en-bloc resection rate was 99% in rectal NETs, H-CR rates were 72-74% for various EMR procedures. H-CR may be associated with tumor size regardless of endoscopic treatment modalities.
Mo1152 PREDICTORS OF SURVIVAL IN PATIENTS WITH SMALL BOWEL NEUROENDOCRINE TUMOURS ASSOCIATED WITH MESENTERIC DESMOPLASIA Faidon-Marios Laskaratos, Leonidas Diamantopoulos, Martin Walker, Mohamed Khalifa, Henry Walton, Apostolos Koffas, George Demetriou, Christos Toumpanakis, Martyn Caplin, Dalvinder Mandair
Kaplan-Meier curve of overall survival in patients with small bowel neuroendocrine tumours associated with mesenteric desmoplasia
Background: Small intestinal neuroendocrine tumours (SINETs) represent 30-50% of small bowel neoplasms and their incidence is rising. They are often associated with a desmoplastic reaction in the mesentery, which can lead to gastrointestinal complications, including bowel
AGA Abstracts
S-668