M. Cravo

Body Composition as a Prognostic Factor of Neoadjuvant Chemotherapy Toxicity and Outcome in Patients with Locally Advanced Gastric Cancer

Purpose Neoadjuvant chemotherapy has been shown to improve survival in locally advanced gastric cancer, but it is associated with significant toxicity. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher chemotherapy toxicity and morbi-mortality. The aim of this study was to assess the prevalence of sarcopenia/sarcopenic obesity in patients with gastric cancer, as well as its association with chemotherapy toxicity and long-term outcomes. Materials and Methods A retrospective analysis was performed using an academic cancer center patient cohort diagnosed with locally advanced gastric cancer between January 2012 and December 2014 and treated with neoadjuvant chemotherapy. We analyzed body composition (skeletal muscle and visceral fat index) in axial computed tomography images. Results A total of 48 patients met the inclusion criteria. The mean age was 68±10 years, and 33 patients (69%) were men. Dose-limiting toxicity was observed in 22 patients (46%), and treatment was terminated early owing to toxicity in 17 patients (35%). Median follow-up was 17 months. Sarcopenia and sarcopenic obesity were found at diagnosis in 23% and 10% of patients, respectively. We observed an association between termination of chemotherapy and both sarcopenia (P=0.069) and sarcopenic obesity (P=0.004). On multivariate analysis, the odds of treatment termination were higher in patients with sarcopenia (odds ratio=4.23; P=0.050). Patients with sarcopenic obesity showed lower overall survival (median survival of 6 months [95% confidence interval {CI}=3.9–8.5] vs. 25 months [95% CI=20.2–38.2]; log-rank test P=0.000). Conclusions Sarcopenia and sarcopenic obesity were associated with early termination of neoadjuvant chemotherapy in patients with gastric cancer; additionally, sarcopenic obesity was associated with poor survival.

Clinical and genetic factors predicting response to therapy in patients with Crohn’s disease

Aim To identify clinical and/or genetic predictors of response to several therapies in Crohn’s disease (CD) patients. Methods We included 242 patients with CD (133 females) aged (mean ± standard deviation) 39 ± 12 years and a disease duration of 12 ± 8 years. The single-nucleotide polymorphisms (SNPs) studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9 C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with real-time PCR with Taqman probes. Results Older patients responded better to 5-aminosalicylic acid (5-ASA) and to azathioprine (OR 1.07, p = 0.003 and OR 1.03, p = 0.01, respectively) while younger ones responded better to biologicals (OR 0.95, p = 0.06). Previous surgery negatively influenced response to 5-ASA compounds (OR 0.25, p = 0.05), but favoured response to azathioprine (OR 2.1, p = 0.04). In respect to genetic predictors, we observed that heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids (OR 2.51, p = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine (OR 0.23, p = 0.03 and OR 0.08, p = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine (OR 2.38, p = 0.01), while carriers of ABCB1 G2677T/A SNP, as well as responding better to azathioprine (OR 1.89, p = 0.07), had a lower chance of responding to biologicals (OR 0.31, p = 0.07), which became significant after adjusting for gender (OR 0.75, p = 0.005). Conclusions In the present study, we were able to identify a number of clinical and genetic predictors of response to several therapies which may become of potential utility in clinical practice. These are preliminary results that need to be replicated in future pharmacogenomic studies.

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease:

Background Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. Aim The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Methods Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. Results The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Conclusions Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

Handgrip Dynamometry and Patient-Generated Subjective Global Assessment in Patients with Nonresectable Lung Cancer

ABSTRACT Introduction: Undernutrition is frequently associated with advanced lung cancer. Accurate nutritional assessment tools are important to provide the proper nutritional therapy. Handgrip dynamometry has already been used in these patients, and the findings suggest that it is a good indicator of nutritional status. Aims: The aim of this study was to evaluate the association between nutritional status and handgrip strength (HGS) in patients with nonresectable lung cancer. Methods: Cross-sectional study involving thirty-seven subjects with nonresectable lung cancer. Nutritional status was obtained using Patient Generated Subjective Global Assessment (PG-SGA), and muscle function was evaluated by HGS using a Jamar® handgrip dynamometer on the nondominant hand. The results of both methods were compared and correlated. Results: According to PG-SGA, 73% (n = 27) of the patients were moderately undernourished, and 8% (n = 3) were severely undernourished. In total, 81% (n = 30) were undernourished. HGS was below the 50th percentile in 57% of the patients (n = 21). We found a significant association between nutritional status according to PG-SGA and HGS (P = 0.026, CI = 95%). Conclusions: Handgrip dynamometry can be a useful tool to evaluate the functional and nutritional status. It can be included in lung cancer patients evaluation, along with other nutritional assessment tools.

MON-LB013: Handgrip Dynamometry and Patient-Generated Subjective Global Assessment in Patients With Non-Resectable Lung Cancer

with hormone-receptor+ BCs, since excess fat tissue in postmenopausal women results in higher blood estrogen concentrations. While endocrine-treatment with aromatase inhibitors has markedly improved BC outcomes, there is evidence that obese women may not fully benefit from these agents. This longitudinal study aimed to evaluate changes in weight/body composition in BC pts on hormone-therapy (HT). Methods: 23 pts were enrolled (15 on tamoxifen, 7 on letrozole). Anthropometrics and body composition were assessed in the beginning of the HT and 3 months (3 mo) later. Results: At baseline, 30% of women were obese (BMI 30 kg/m2) and 48% were overweight (25 30 kg/m2), while the remainder had regular BMI (19 25 kg/m2); 3 mo later, the prevalence of obesity decreased to 9%, while overweight was present in 35% of pts. However, taking into acount the body composition at both timepoints, all women had excess fat mass index (FMI). Nevertheless, at baseline, 64% of pts had an adequate fat free mass index (FFMI), though this prevalence reduced to 54% 3 mo later (3 kg/m2). When we compared the differences of tamoxifen vs letrozole, 37% on tamoxifen gained a mean of 1.5 kg vs 40% on letrozole that showed an increase of 1.8 kg in weight. Mean values of weight loss were 2.8 kg and 0.6 kg, respectively. FFMI decreased more in women on letrozole (2.6 kg/m2 vs 2.0 kg/m2). No women on tamoxifen increased FFMI vs 40% of those on letrozole, who increased 2.6 kg/m2. In 67% of pts, FMI was higher in the second timepoint and the remainder maintained the initial values. Conclusion: The prevalence of overweight/obesity was significant, as the prevalence of excess body fat, which increased in the majority of pts after 3 mo. FFMI decreased mainly in women on tamoxifen. These results need to be made aware to clinicians due to clinical/prognostic implications.

SUN-LB028: Effect of Bread Containing High Level of Resistant Starch on Glucose and Insulin Responses

Resistant starch (RS) is defined as the sum of starch and products of starch degradation not absorbed in the small intestine of healthy individuals. RS appears to confer considerable health benefits related of inflammatory bowel disease and bowel cancer, reduction of postprandial glycaemia/insulinemia, improvement of insulin sensitivity and fat oxidation, increase satiety as well as play a prebiotic role.

P100 Vitamin D in patients with Crohn's disease

Conclusions: In contrast to previous non European reports culture of colonoscopic biopsy specimens is an highly SENS/SPEC to differentiate GITB from other ileo-cecal inflammations. Different methodological details, in sampling and processing, and the presence of exITB may have some influence on the results. Higher theoretical contamination chance with in house nested PCR may increase false (+) rate.

PP114-MON: Vitamin D in Patients with Crohn’s Disease

Rationale: Systemic sclerosis is a rare chronic autoimmune disease, characterized by fibrosis and inflammation and associated with a physical impairment and higher mortality. We assessed prevalence of sarcopenia and the impact of muscle strength and quality of life. Methods: Body composition was assessed with bioelectrical impedance analysis. Fat free mass was determined with algorithm suggested by Kyle et al and corrected for height. (FFMI, kg/m2). Values below 17.4 kg/m2 in men and <15 kg/m2 in women were considered indicative of sarcopenia. Maximal grip strength was measured with Jamar Dynamometer, and maximal knee extension strength with Digimax Dynamometer. Quality of Life was assessed with the validated SF 36. C-reactive protein was measured immunometric assay. Results: 107 patients were recruited (97 female, 59.3±14 years old, BMI 24.3±5 kg/m2). 41 (38.3%) patients were sarcopenic. Patients with sarcopenia did not differ from nonsarcopenic patients with regard to age, number of affected organs, comorbidities or treatment, but they exhibited significantly lower grip and knee strength, BMI (21.0±1.9 vs. 26.5±5.3, p < 0.0001) and CRP (7.7±12.9 vs. 2.8±3.6; p < 0.009). FFM correlated significantly with grip and knee extension strength (r = 0.64 and r = 0.37, p < 0.0001). There were no differences in quality of life.

P484 Identification of clinical and genetic predictors of response to therapy in patients with ulcerative colitis (UC)

P484 Identification of clinical and genetic predictors of response to therapy in patients with ulcerative colitis (UC) P. Ferreira1 *, P. Sousa2, P. Moura Santos2, P. Ministro3, J. de Deus4, L. Tavares2, P. Peixe5, J. Velosa2, M. Brito1, M. Cravo6. 1Escola Superior de Tecnologia da Saude de Lisboa, Lisboa, Portugal, 2Hospital Santa Maria, Lisboa, Portugal, 3Hospital S. Teotonio, Viseu, Portugal, 4Hospital Fernando Fonseca, Lisboa, Portugal, 5Hospital Egas Moniz, Lisboa, Portugal, 6Hospital Beatriz Ângelo, Loures, Portugal

Brief Case ReportsColonic cancer in a 34-yr-old woman: should it prompt microsatellite instability studies and mismatch repair gene testing?

It remains debatable whether young patients with colorectal tumors should undergo genetic testing with the aim of identifying new hereditary nonpolyposis colorectal cancer families. We describe a case of a young woman with colon cancer with no clinical criteria of hereditary nonpolyposis colorectal cancer, whose genetic analysis showed that the tumor displayed microsatellite instability, and in whom a truncated protein in hMSH2 gene was found, which was also present in two at-risk relatives.