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P.1.65: KIR AND HLA COMBINATIONS IN AUTOIMMUNE GASTRITIS AND GASTRIC CANCER SUSCEPTIBILITY
S170
Abstracts of the XVII National Congress of Digestive Diseases / Digestive and Liver Disease 43S (2011) S115–S264
P.1.64 RISK STRATIFICATION USING OCTREOTIDE TEST FOR PATIENTS WITH GASTRO-ENTERO-PANCREATIC NEUROENDOCRINE TUMORS: RESULTS OF PROSPECTIVE VALIDATION OF THE TEST S. Massironi 1 , M.P. Spampatti 2 , R.E. Rossi ∗ ,2 , D. Conte 2 , C. Ciafardini 2 , M. Peracchi 2 1 Fondazione Irccs Ca’ Granda Ospedale Maggiore Policlinico Milano, Milano, Italy; 2 Dipartimento di Scienze Mediche, Università degli Studi di Milano, Milan, Milano, Italy
Background and aim: Selection criteria for treatment with somatostatin analogs (SSAs) of gastroenteropancreatic neuroendocrine tumors (GEPNETs) are presence of somatostatin receptors, a positive Octreoscan® or a >50% hormone level decrease after octreotide s.c. injection (octreotide test) (OT). Recently, we demonstrated that a plasma CgA decrement >30% in response to OT is a simple selection criterion that could also predict the clinical response to SSAs. In this study we evaluated prognostic value of OT in a prospective cohort of patients. Material and methods: From January 2008 to June 2010 we prospectively evaluated 44 consecutive newly diagnosed GEP-NET patients, receiving octreotide 200 μg s.c., with plasma CgA determination at 0, 3 and 6 hours. Long-term SSA treatment was then given by monitoring clinical outcome. Results: In all patients, CgA levels decreased, after OT, from 54 (9.3-3021) to 23 (4.3-2386) U/L (nadir, P=0.02). In the group of 36 patients responsive to OT, treated for at least six months, a successfully objective response occurred in 21 patients (58%), in eight patients (22%) disease remained stable and in seven patients (20%) disease progressed. In the remaining eight unresponsive cases, with CgA decrement <30%, chronic treatment with long-acting SSAs was unsatisfactory with disease progression in six patients (75%), disease stabilization in one and an objective response in only one patient. Basal plasma CgA levels were significantly higher in patients with functioning than nonfunctioning tumors [median (range): 153.4 (12.4-3021) vs 37.85 (9.3-1502) U/L, P<0.001] and in those with than without metastases [148 (14.8-3021) vs 39.3 (9.3-330) U/L, P<0.001]. CgA levels significantly correlated with WHO classification, clinical TNM staging and Ki-67 proliferative index. Conclusions: In GEP-NETs, plasma CgA is a reliable marker and its decrease >30% after OT confirm to have a relevant prognostic meaning allowing it to identify the subgroup of patients most likely to be responsive to chronic SSAs.
P.1.65 KIR AND HLA COMBINATIONS IN AUTOIMMUNE GASTRITIS AND GASTRIC CANCER SUSCEPTIBILITY V. De Re ∗ , L. Caggiari, M. De Zorzi, V. Canzonieri, S. Maiero, R. Cannizzaro Centro di Riferimento Oncologico, Irccs - National Cancer Institute, Aviano (PN), Italy Background and aim: Gastric carcinogenesis is a multi-step and multifactorial process facilitated by the interaction of several factors, including host immunogenetic constitution. Killer immunoglobulin like receptor (KIR) are activating or inhibitory receptors which after recognizing of human leucocyte antigen (HLA) class I molecules could lead to either triggering or blocking of NK-cell activity, and consequently innate and adaptive host immune response. In previous studies, specific KIR/HLA combinations were found involved in early control of several infections as well as in elimination of transformed tumour cells. KIR gene variations could be discriminative in predicting the risk of precancerous autoimmune gastritis (AG) and/or progression towards gastric cancer (GC). The aim of the present study was to characterize KIR/HLA gene combinations in AG and GC. Material and methods: For the study, 71 patients with autoimmune gastritis (21) or gastric cancer (50) were included. DNA was extracted from peripheral blood and genotyped for KIR, KIR2DL5A/B, KIR2DS4del/ful variants and HLA-class I at high resolution by sequence based typing and software analysis. The results were compared with prevalence of HLA/KIR frequency and haplotype from 69 blood donors (BD).
Results: A significant difference was found in KIR2DL5 and KIR3DS1 frequencies. KIR2DL5A 19% in AG compared to 46.0% in GC (p=0.04), KIR3DS1 19% vs 48.0% (p=0.03). Functional analysis of KIR/HLA combination showed that the frequencies of KIR2DS1/C2 was significantly decreased in AG (0.0%) vs GC (28.0%, p=0.007) and also vs BD (33.3%, p= 0.001). In GC group, KIR2DL3/C1 and KIR3DL1/Bw4-T80 were both significantly increased compared with BD (86.0% vs 62.3%, p=0.006; 38.0% vs 13.0%, p=0.04). The differences were associated with a specific reduction in homozygous C2 (10.0% GC vs 29.0% BD, p=0.01) and in a highest prevalence in Bw4-T80 variant (40.0% vs 21.7%, p=0.04). Conclusions: In conclusion, although our data are preliminary, we showed different frequencies of KIR/HLA combinations in GA and in CG suggesting they could be considered as possible risk factors for GC malignancies. Analysis from an enlarge series of patients are in course.
P.1.66 SAFETY AND EFFECTIVENESS OF TREATMENT WITH SORAFENIB IN ELDERLY CIRRHOTIC PATIENTS AFFECTED BY ADVANCED HEPATOCELLULAR CARCINOMA T. Raffaella, A. Galeota Lanza, F. Lampasi, M. De Luca, M.T. Tartaglione, R. Pacilio, G.G. Di Costanzo ∗ Cardarelli Hospital, Naples, Italy Background and aim: Hepatocellular carcinoma (HCC) is a common cancer worldwide and the risk of its occurrence increases with age. Sorafenib is the first drug approved for the treatment of patients with advanced HCC, but there is a lack of detailed data on how older patients with liver disease tolerate this drug. Elderly patients may be at higher risk for toxicity due to slower metabolism and comorbid conditions. Therefore, the aim of this analysis was to explore the safety of sorafenib use in older patients with advanced HCC. Material and methods: This was an observational study of outcomes in patients aged <70 years (Group A) or =70 years (Group B). From October 2008 to October 2010, 101 patients were treated with sorafenib 800mg/day until progression or unacceptable toxicities. Response was analyzed according to the modified RECIST criteria and AEs were monthly recorded according to the “common toxicity criteria” (scored 0-4). Time to progression (TTP) and overall survival (OS) were evaluated by Kaplan-Meier method. Results: Sixty-six patients were in Group A (median age 63 years, range 42-69; males 58) and 35 patients in Group B (median age 75 years, range 70-84; males 24). Ninety-four percent of patients in both groups had AEs and no difference in type fo AEs was observed between groups. Permanent drug discontinuation due to AEs was required in 21% of group A patients and in 29% of group B (p=.20). Partial tumor response or stable disease was observed in 36% of cases in group A and in 42% in group B. TTP was 6 months (range 4-8) in group A and 11 months (range 4-18) in group B (p=.86). OS was 8 months (range 5-11) in group A and 15 months (range 5-25) in group B (p=.30). Conclusions: Sorafenib use in elderly patients resulted safe. In our experience, occurrence and type of AEs was similar between older and younger patients. Tumor control resulted slightly better in older than in younger patients, but the difference was not statistically significant.
P.1.67 LOW DIAGNOSTIC YIELD OF URGENT COLONOSCOPY (UC) WITHOUT PREPARATION IN PATIENTS WITH LOWER GI BLEEDING (LGB) G. Manes ∗ , S. Ardizzone, G. Maconi, P. Molteni, S. Pallotta, E. Bareggi Ospedale Sacco, Endoscopia, Milano, Italy Background and aim: UC is effective for LGB with a diagnostic yield of 5090%. Although recommended most studies report data of UC without previous colon preparation. Without cleansing UC is likely to be inaccurate and several other procedures are needed to achieve diagnosis. In the present study we analyze accuracy of UC in a series of consecutive patients presenting with LGB.
Abstracts of the XVII National Congress of Digestive Diseases / Digestive and Liver Disease 43S (2011) S115–S264
P.1.64 RISK STRATIFICATION USING OCTREOTIDE TEST FOR PATIENTS WITH GASTRO-ENTERO-PANCREATIC NEUROENDOCRINE TUMORS: RESULTS OF PROSPECTIVE VALIDATION OF THE TEST S. Massironi 1 , M.P. Spampatti 2 , R.E. Rossi ∗ ,2 , D. Conte 2 , C. Ciafardini 2 , M. Peracchi 2 1 Fondazione Irccs Ca’ Granda Ospedale Maggiore Policlinico Milano, Milano, Italy; 2 Dipartimento di Scienze Mediche, Università degli Studi di Milano, Milan, Milano, Italy
Background and aim: Selection criteria for treatment with somatostatin analogs (SSAs) of gastroenteropancreatic neuroendocrine tumors (GEPNETs) are presence of somatostatin receptors, a positive Octreoscan® or a >50% hormone level decrease after octreotide s.c. injection (octreotide test) (OT). Recently, we demonstrated that a plasma CgA decrement >30% in response to OT is a simple selection criterion that could also predict the clinical response to SSAs. In this study we evaluated prognostic value of OT in a prospective cohort of patients. Material and methods: From January 2008 to June 2010 we prospectively evaluated 44 consecutive newly diagnosed GEP-NET patients, receiving octreotide 200 μg s.c., with plasma CgA determination at 0, 3 and 6 hours. Long-term SSA treatment was then given by monitoring clinical outcome. Results: In all patients, CgA levels decreased, after OT, from 54 (9.3-3021) to 23 (4.3-2386) U/L (nadir, P=0.02). In the group of 36 patients responsive to OT, treated for at least six months, a successfully objective response occurred in 21 patients (58%), in eight patients (22%) disease remained stable and in seven patients (20%) disease progressed. In the remaining eight unresponsive cases, with CgA decrement <30%, chronic treatment with long-acting SSAs was unsatisfactory with disease progression in six patients (75%), disease stabilization in one and an objective response in only one patient. Basal plasma CgA levels were significantly higher in patients with functioning than nonfunctioning tumors [median (range): 153.4 (12.4-3021) vs 37.85 (9.3-1502) U/L, P<0.001] and in those with than without metastases [148 (14.8-3021) vs 39.3 (9.3-330) U/L, P<0.001]. CgA levels significantly correlated with WHO classification, clinical TNM staging and Ki-67 proliferative index. Conclusions: In GEP-NETs, plasma CgA is a reliable marker and its decrease >30% after OT confirm to have a relevant prognostic meaning allowing it to identify the subgroup of patients most likely to be responsive to chronic SSAs.
P.1.65 KIR AND HLA COMBINATIONS IN AUTOIMMUNE GASTRITIS AND GASTRIC CANCER SUSCEPTIBILITY V. De Re ∗ , L. Caggiari, M. De Zorzi, V. Canzonieri, S. Maiero, R. Cannizzaro Centro di Riferimento Oncologico, Irccs - National Cancer Institute, Aviano (PN), Italy Background and aim: Gastric carcinogenesis is a multi-step and multifactorial process facilitated by the interaction of several factors, including host immunogenetic constitution. Killer immunoglobulin like receptor (KIR) are activating or inhibitory receptors which after recognizing of human leucocyte antigen (HLA) class I molecules could lead to either triggering or blocking of NK-cell activity, and consequently innate and adaptive host immune response. In previous studies, specific KIR/HLA combinations were found involved in early control of several infections as well as in elimination of transformed tumour cells. KIR gene variations could be discriminative in predicting the risk of precancerous autoimmune gastritis (AG) and/or progression towards gastric cancer (GC). The aim of the present study was to characterize KIR/HLA gene combinations in AG and GC. Material and methods: For the study, 71 patients with autoimmune gastritis (21) or gastric cancer (50) were included. DNA was extracted from peripheral blood and genotyped for KIR, KIR2DL5A/B, KIR2DS4del/ful variants and HLA-class I at high resolution by sequence based typing and software analysis. The results were compared with prevalence of HLA/KIR frequency and haplotype from 69 blood donors (BD).
Results: A significant difference was found in KIR2DL5 and KIR3DS1 frequencies. KIR2DL5A 19% in AG compared to 46.0% in GC (p=0.04), KIR3DS1 19% vs 48.0% (p=0.03). Functional analysis of KIR/HLA combination showed that the frequencies of KIR2DS1/C2 was significantly decreased in AG (0.0%) vs GC (28.0%, p=0.007) and also vs BD (33.3%, p= 0.001). In GC group, KIR2DL3/C1 and KIR3DL1/Bw4-T80 were both significantly increased compared with BD (86.0% vs 62.3%, p=0.006; 38.0% vs 13.0%, p=0.04). The differences were associated with a specific reduction in homozygous C2 (10.0% GC vs 29.0% BD, p=0.01) and in a highest prevalence in Bw4-T80 variant (40.0% vs 21.7%, p=0.04). Conclusions: In conclusion, although our data are preliminary, we showed different frequencies of KIR/HLA combinations in GA and in CG suggesting they could be considered as possible risk factors for GC malignancies. Analysis from an enlarge series of patients are in course.
P.1.66 SAFETY AND EFFECTIVENESS OF TREATMENT WITH SORAFENIB IN ELDERLY CIRRHOTIC PATIENTS AFFECTED BY ADVANCED HEPATOCELLULAR CARCINOMA T. Raffaella, A. Galeota Lanza, F. Lampasi, M. De Luca, M.T. Tartaglione, R. Pacilio, G.G. Di Costanzo ∗ Cardarelli Hospital, Naples, Italy Background and aim: Hepatocellular carcinoma (HCC) is a common cancer worldwide and the risk of its occurrence increases with age. Sorafenib is the first drug approved for the treatment of patients with advanced HCC, but there is a lack of detailed data on how older patients with liver disease tolerate this drug. Elderly patients may be at higher risk for toxicity due to slower metabolism and comorbid conditions. Therefore, the aim of this analysis was to explore the safety of sorafenib use in older patients with advanced HCC. Material and methods: This was an observational study of outcomes in patients aged <70 years (Group A) or =70 years (Group B). From October 2008 to October 2010, 101 patients were treated with sorafenib 800mg/day until progression or unacceptable toxicities. Response was analyzed according to the modified RECIST criteria and AEs were monthly recorded according to the “common toxicity criteria” (scored 0-4). Time to progression (TTP) and overall survival (OS) were evaluated by Kaplan-Meier method. Results: Sixty-six patients were in Group A (median age 63 years, range 42-69; males 58) and 35 patients in Group B (median age 75 years, range 70-84; males 24). Ninety-four percent of patients in both groups had AEs and no difference in type fo AEs was observed between groups. Permanent drug discontinuation due to AEs was required in 21% of group A patients and in 29% of group B (p=.20). Partial tumor response or stable disease was observed in 36% of cases in group A and in 42% in group B. TTP was 6 months (range 4-8) in group A and 11 months (range 4-18) in group B (p=.86). OS was 8 months (range 5-11) in group A and 15 months (range 5-25) in group B (p=.30). Conclusions: Sorafenib use in elderly patients resulted safe. In our experience, occurrence and type of AEs was similar between older and younger patients. Tumor control resulted slightly better in older than in younger patients, but the difference was not statistically significant.
P.1.67 LOW DIAGNOSTIC YIELD OF URGENT COLONOSCOPY (UC) WITHOUT PREPARATION IN PATIENTS WITH LOWER GI BLEEDING (LGB) G. Manes ∗ , S. Ardizzone, G. Maconi, P. Molteni, S. Pallotta, E. Bareggi Ospedale Sacco, Endoscopia, Milano, Italy Background and aim: UC is effective for LGB with a diagnostic yield of 5090%. Although recommended most studies report data of UC without previous colon preparation. Without cleansing UC is likely to be inaccurate and several other procedures are needed to achieve diagnosis. In the present study we analyze accuracy of UC in a series of consecutive patients presenting with LGB.