Body composition and Crohn's disease behavior: Is adiposity the main game changer?

OBJECTIVE: We investigated the association between body composition upon diagnosis and complicated phenotypes and time until surgery in patients with Crohn's disease (CD). METHODS: We conducted a retrospective cohort study including patients with CD who had a computed tomography enterography or a magnetic resonance enterography performed ≤6 mo of diagnosis. Skeletal muscle and visceral and subcutaneous adipose tissue cross-sectional areas were determined with computed tomography or magnetic resonance images at the third lumbar vertebral level, processed with the sliceOmatic (TomoVison, Magog, QC, Canada) and ABACS plugin. RESULTS: We included 63 patients: 33 (52%) men, median age 35 y. Disease location (L) and behavior (B) according to the Montreal classification were L1 (ileal disease) = 28 (44%), L2 (colonic disease) = 13 (21%), L3(ileocolonic disease) = 18 (28%), L1 + L4 (ileal and isolated upper disease) = 1 (2%), L3 + L4 (ileocolonic and isolated upper disease) = 3 (5%), B1 (non-stricturing) = 39 (62%), B2 (stricturing) = 11 (17%), and B3 (penetrating)= 13 (21%); 20 (32%) patients had perianal disease. Visceral obesity was present in 12 (19%) patients and was associated with higher age of CD onset (median 60 versus 34 y; P = 0.002) and complicated disease behavior (B2 and B3) (66.7% versus 31.7%; P = 0.021). After adjusting for age and perianal disease, total adipose tissue was associated with a 4% increase in the odds of complicated behavior per 10 cm2 of total adipose tissue (odds ratio [OR] = 1.004; 95% confidence interval [CI], 1.00-1.008; P = 0.043). Median follow-up time was 3.35 y, during which 15 (24%) of patients underwent abdominal surgery. Visceral obesity was associated with 5.10-times higher risk of abdominal surgery (95% CI, 1.52-17.09; P = 0.008); after adjusting for disease behavior, visceral obesity maintained a near-significant association with a 2.90-times higher risk of surgery (95% CI, 0.83-10.08; P = 0.09). CONCLUSION: Total fat was associated with complicated disease phenotype and visceral obesity, with higher risk of abdominal surgery and shorter time until surgery.

EBV and MSI Status in Gastric Cancer: Does It Matter?

We investigated the impactof microsatellite instability (MSI) and Epstein-Barr virus (EBV) status in gastric cancer (GC), regarding response to perioperative chemotherapy (POPChT), overall survival (OS), and progression-free survival (PFS). We included 137 cases of operated GC, 51 of which were submitted to POPChT. MSI status was determined by multiplex PCR and EBV status by EBV-encoded RNA in situ hybridization. Thirty-seven (27%) cases presented as MSI-high, and seven (5.1%) were EBV+. Concerning tumor regression after POPChT, no differences were observed between the molecular subtypes, but females were more likely to respond (p = 0.062). No significant differences were found in OS or PFS between different subtypes. In multivariate analysis, age (HR 1.02, IC 95% 1.002-1.056, p = 0.033) and positive lymph nodes (HR 1.82, IC 95% 1.034-3.211, p = 0.038) were the only prognostic factors for OS. However, females with MSI-high tumors treated with POPChT demonstrated a significantly increased OS compared to females with MSS tumors (p = 0.031). In conclusion, we found a high proportion of MSI-high cases. MSI and EBV status did not influence OS or PFS either in patients submitted to POPChT or surgery alone. However, superior survival of females with MSI-high tumors suggests that sex disparities and molecular classification may influence treatment options in GC.

Potential of miR-21 to Predict Incomplete Response to Chemoradiotherapy in Rectal Adenocarcinoma.

Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear. Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes. Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre- and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade-TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3). Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03-1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04). Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).

Preoperative enteral nutrition in adults with complicated Crohn's disease: Effect on disease outcomes and gut microbiota.

OBJECTIVES: The use of exclusive enteral nutrition (EEN) in patients with Crohn's disease (CD) before surgical resection can reduce disease activity and improve nutritional status. The mechanism of EEN action is unclear, but it might involve modulation of the intestinal microbiota. The aim of this study was to evaluate the effects (namely changes in gut microbiota) of preoperative EEN in adults with complicated CD referred to surgery. METHODS: This was a prospective study of adult patients with CD referred to surgery. Patients with body mass index <18.5 kg/m2, weight loss >10 %, serum albumin <3 g/dL, or a combination of some or all three, received EEN for ≥2 wk. The effects of EEN on clinical (Harvey-Bradshaw Index [HBI]) and laboratory markers (C-reactive protein [CRP], serum albumin, and fecal calprotectin) and fecal microbiota were analyzed after EEN (before surgery) and 6 mo later. We used 16 S rRNA gene sequencing to determine changes in the fecal microbiota. RESULTS: Fifteen patients were included, of whom 60% were men with a mean age of 45.4 ± 19.1 y. Of those, 10 received EEN. The median duration of preoperative EEN was 41.5 d (15-70 d). During EEN, there was a significant reduction in mean HBI (8.7 ± 1.9 versus 4.1 ± 2.4; P = 0.001) and CRP (11.7 ± 10.3 versus 0.8 ± 0.8 mg/dL; P = 0.008) and an increase in serum albumin (3.1 ± 0.6 versus 4 ± 0.6 g/dL; P = 0.022). Two patients did not require surgery after EEN. The overall microbial composition changed after EEN (Permutational analysis of variance test, P = 0.046) and there was a significant reduction in α diversity (8 ± 2.3 versus 5.2 ± 1.5; P = 0.023). EEN significantly changed the relative abundance of 11 taxonomic operational units (OTUs). At the family level, we found this was mainly due to the decrease in the Enterobacteriaceae family (7 OTUs). Six months after surgery, α diversity was not different from that before or after EEN; at this time point 6 OTUs were significantly different, mainly due to the decrease of Clostridiales order (3 OTUs). The incidence of postoperative complications and hospital length of stay were similar in EEN and immediate surgery groups, as well as clinical and endoscopic recurrence rates 6 mo after surgery. CONCLUSIONS: Preoperative EEN improved disease activity and nutritional status in patients with CD referred to surgery. Despite being malnourished, patients given EEN did not have increased postoperative complications compared with well-nourished patients. During EEN, overall microbiota composition changed and α diversity decreased. EEN did not influence postoperative recurrence and gut microbiota 6 mo after surgery.

Body Composition Influences Post-Operative Complications and 90-Day and Overall Survival in Pancreatic Surgery Patients.

INTRODUCTION: Pancreatic surgery still carries a high morbidity and mortality even in specialized centers. The aim of this study was to evaluate the influence of patients' body composition on postoperative complications and survival after pancreatic surgery. METHODS: This was a retrospective study on patients undergoing pancreatic surgery between March 2012 and December 2017. Demographics, clinical data, and postoperative complications classified according to Clavien-Dindo were recorded. Body composition was assessed using routine diagnostic or staging computed tomography (CT). Multiple Cox proportional hazards models were adjusted. RESULTS: Ninety patients were included, 55% were male, and the mean age was 68 ± 10.9 years. Of these 90, 92% had a total pancreatectomy or pancreaticoduodenectomy, 7% a distal pancreatectomy, and 1% a pancreaticoduodenectomy with multi-visceral resection; 84% had malignant disease. The incidence of major complications was 27.8% and the 90-day mortality was 8.8%. The ratio of visceral fat area/skeletal muscle area (VFA:SMA) was associated with an increased risk of complications (OR 2.24, 95% CI 1.14-4.87, p = 0.03) and 90-day survival (HR 2.13, 95% CI 1.13-4.01, p = 0.019). On simple analysis, shorter overall survival (OS) was observed in patients aged ≥70 years (p = 0.0009), with postoperative complications ≥IIIb (p = 0.01), an increased VFA:SMA (p = 0.007), and decreased muscle radiation attenuation (p = 1.6 × 10-5). In an OS model adjusted for age, disease malignancy, postoperative complications, and body composition parameters, muscle radiation attenuation remained significantly associated with survival (HR 0.94, 95% CI 0.90-0.98, p = 0.0016). A model which included only body composition variables had a discrimination ability (C-statistic 0.76) superior to a model which comprised conventional clinical variables (C-statistic 0.68). CONCLUSION: Body composition is a major determinant of postoperative complications and survival in pancreatic surgery patients.

INTRODUÇÃO: A cirurgia pancreática continua associada a uma elevada morbimortalidade mesmo em centros de referência. O objetivo do presente estudo foi avaliar a influência da composição corporal nas complicações e sobrevivência após cirurgia pancreática. MÉTODOS: Estudo retrospetivo em doentes submetidos a cirurgia pancreática entre Março 2012 e Dezembro 2017. Foram registadas variáveis demográficas, clínicas, complicações pós-cirúrgicas classificadas de acordo com a classificação de a classificação de Clavien Dindo. A composição corporal foi avaliada utilizando imagens de Tomografia Axial Computorizada (TAC) realizada no diagnóstico. Modelos de riscos porporcionais de Cox foram ajustados. RESULTADOS: Incluídos 90 doentes, 55% homens e média de idade de 68 ± 10.9 anos; 92% submetidos a pancreatectomia/pancreatoduodenectomia, 7% pancreatectomia distai e 1% pancreatoduodenectomia com ressecção multivisceral; 84% tinham doença maligna. A incidência de complicações major foi de 27.8% e a mortalidade aos 90 dias de 8.8%. O rácio da Área de Gordura Visceral (AGV) / Área de Tecido Muscular Esquelético (ATME) associou-se a um risco acrescido de complicações (OR 2.24, 95% Cl 1.14­4.87, p = 0.03) e de morte aos 90 dias (HR 2.13, 95% Cl 1.13­4.01, p = 0.019). Observámos uma sobrevivência global mais baixa em doentes com idade ≥70 anos (p = 0.0009), com complicações ≥IIIb (p = 0.01), com AGV/ ATME aumentada e atenuação muscular diminuída (p = 1.6 × 10−5). A atenuação muscular ajustada para a idade, malignidade, complicações, manteve-se associada à sobrevivência global (HR 0.94, IC 95% 0.90­0.98, p = 0.0016). Um modelo que inclua apenas variáveis de composição corporal mostrou uma capacidade discriminatória (C-statistic 0.76) superior a um modelo convencional com variáveis clínicas (C-statistic 0.68). CONCLUSÃO: A composição corporal é um determinante major de complicações pós-cirúrgicas e de sobrevivência de doentes submetidos a cirurgia pancreática.

Dietary patterns and their relationships to sarcopenia in Portuguese patients with gastrointestinal cancer: An exploratory study.

OBJECTIVES: The purpose of this exploratory study was to identify the main dietary patterns of a Portuguese population of patients with gastrointestinal cancer and to analyze their association with sarcopenia. METHODS: This was a prospective study with a consecutive sample of 100 patients with gastrointestinal cancer enrolled at diagnosis. Dietary intake was assessed with a semiquantitative Food Frequency Questionnaire, and dietary patterns were obtained with principal component analysis. Nutritional assessment was done using the Patient-Generated Subjective Global Assessment, and body composition was evaluated with anthropometric measures and computed tomography image processing obtained at the third lumbar vertebrae. Sex and body mass index specific cutoffs were used to define sarcopenia. RESULTS: Four major patterns were identified: high-fat dairy products, fried snacks, and processed meat diet; legumes, vegetables, and fruit diet; fat and fish diet; and alcohol, cereal, and animal protein diet. On simple logistic regression, the occurrence of sarcopenia in participants in the second tertile (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.10-0.83; P = 0.02) and third tertile (OR 0.24; 95% CI 0.08-0.69; P = 0.01) of adherence to the high-fat and fish diet was reduced compared with the first tertile. On multiple logistic regression, the second tertile (OR 0.38, 95% CI 0.11-1.19; P = 0.10) of the fat and fish dietary pattern maintained a trend toward a reduction of the odds of sarcopenia compared with the first tertile, independently of calorie intake, age, disease location, and stage. CONCLUSIONS: The fat and fish dietary pattern was associated with lower odds of sarcopenia in this population of patients with gastrointestinal cancer.

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.

Lower skeletal muscle attenuation and high visceral fat index are associated with complicated disease in patients with Crohn's disease: An exploratory study.

BACKGROUND AND AIMS: The prognostic value of body composition analysis in patients with Crohn's disease (CD) is poorly explored. The aims of the present study were to assess fat and skeletal muscle compartments including muscle radiation attenuation (MA) in patients with CD, and to analyze its predictive value to identify complicated phenotypes. METHODS: Seventy one patients with CD who have had an abdominal CT within one month of clinical, laboratory, and endoscopic evaluation were included. Skeletal muscle area (SMA) and index (SMI), visceral fat area (VFA) and index (VFI), subcutaneous fat area (SFA), and mean MA were measured using appropriate software. Sarcopenia, as defined by Martin's criteria was assessed. Montreal classification was used to characterize disease phenotype. RESULTS: Mean MA was lower in patients >40 years (p = 0.001), L2 (p = 0.09) and stricturing/penetrating disease (p = 0.03) whereas SMA and SMI were significantly lower in patients with positive C-reactive protein and previous hospital admissions (p < 0.01). On multivariate analysis, higher MA was protective against the complicated disease phenotype (stricturing/penetrating disease and/or previous surgeries) (OR 0.81; p = 0.002) whereas a high visceral fat index increased such risk (OR 26.1; p = 0.02). A ROC curve showed a 82.4% sensibility, 90.3% specificity, 17.6% positive predictive value, 9.7% negative predictive value and an area under the curve (AUC) of 0.91 for body composition analysis to predict complicated disease. CONCLUSIONS: A lower muscle attenuation and a high visceral fat index seem to be associated with more severe phenotypes in patients with CD.

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.

IL23R polymorphisms influence phenotype and response to therapy in patients with ulcerative colitis.

OBJECTIVE: We aimed to identify the clinical and genetic [IL23 receptor (IL23R) single nucleotide polymorphisms (SNPs)] predictors of response to therapy in patients with ulcerative colitis. PATIENTS AND METHODS: A total of 174 patients with ulcerative colitis, 99 women and 75 men, were included. The mean age of the patients was 47±15 years and the mean disease duration was 11±9 years. The number of patients classified as responders (R) or nonresponders (NR) to several therapies was as follows: 110 R and 53 NR to mesalazine (5-ASA), 28 R and 20 NR to azathioprine (AZT), 18 R and 7 NR to infliximab. Clinical and demographic variables were recorded. A total of four SNPs were studied: IL23R G1142A, C2370A, G43045A, and G9T. Genotyping was performed by real-time PCR using Taqman probes. RESULTS: Older patients were more prone to respond to 5-ASA (P=0.004), whereas those with pancolitis were less likely to respond to such therapies (P=0.002). Patients with extraintestinal manifestations (EIMs) were less likely to respond to 5-ASA (P=0.001), AZT (P=0.03), and corticosteroids (P=0.06). Carriers of the mutant allele for IL23R SNPs had a significantly higher probability of developing EIMs (P<0.05), a higher probability of being refractory to 5-ASA (P<0.03), but a higher likelihood of responding to AZT (P=0.05). A significant synergism was observed between IL23R C2370A and EIMs with respect to nonresponse to 5-ASA (P=0.03). CONCLUSION: Besides extent of disease and age at disease onset, the presence of EIMs may be a marker of refractoriness to 5-ASA, corticosteroids, and AZT. IL23R SNPs are associated both with EIMs and with nonresponse to 5-ASA and corticosteroids.

[High dose chemotherapy with autologous stem-cell support in germ cell tumors: The Instituto Português de Oncologia de Lisboa Francisco Gentil Series]. / Quimioterapia de alta dose com suporte hematopoiético autólogo em tumores de células germinativas Experiência do Instituto Português de Oncologia de Lisboa Francisco Gentil.

BACKGROUND: High dose chemotherapy with autologous stem cell transplantation (HDCT-ASCT) has been administered to patients with high-risk germ cell tumours (GCT). The role of this treatment for GCT still remains unclear, including the identification of subgroups more likely to benefit from such strategy. METHODS: A retrospective review was conducted of all male patients with gonadal and extra gonadal GCT treated with HDCT-ASCT between 1996 and 2008 at the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG). RESULTS: Twenty patients were treated with HDCT-ASCT, 17 with primary testicular tumours, two mediastinal and one retroperitoneal GCT. According to the International Germ Cell Cancer Consensus Group (IGCCCG) classification, at diagnosis three patients had good risk, four intermediate, eight poor but for the patients left the risk group could not be ascertained. In eight patients HDCT-ASCT was used upfront, after induction with first-line conventional chemotherapy, and in the remaining 12 for relapsed GCT. One patient had platinum-resistant and another platinum-refractory disease. Only two patients had Beyer score > 2. All but one patient were treated with ICE (Ifosfamide, Carboplatin, Etoposide). Six patients underwent a second HDCT-ASCT course. The 5-year overall survival and progression free survival were respectively 53% and 44%; both patients with mediastinal GCT are long term survivors. CONCLUSION: Randomized studies to date have failed to indicate a survival advantage for HDCT-ASCT in GCT. This series is small and heterogeneous which prevents us from drawing conclusions regarding the benefit of this treatment for GCT. However, we could confirm the lack of benefit of HDCT-ASCT for platinum-resistant GCT and to question the absolute contraindication to this therapeutic modality in mediastinal GCT. HDCT-ASCT should therefore be performed exclusively in experienced centers and, preferably, in the setting of clinical trials.

Dietary intake adequacy and cognitive function in free-living active elderly: a cross-sectional and short-term prospective study.

BACKGROUND & AIMS: Adequate dietary intake might prevent cognitive decline among ageing subjects; hence, the relationships between dietary intake and cognitive function in a sample of non-institutionalized active elderly were assessed. METHODS: Total 187 subjects aged over 65. Dietary intake was assessed using a three-day record and cognitive function using the mini-mental state examination (MMSE). After 8.5+/-3.5 months of follow-up, cognitive function was re-assessed in 110 subjects. RESULTS: A considerable portion of the subjects presented a low intake of several key nutrients. At baseline, no differences were found between subjects with normal or low MMSE score regarding all dietary parameters. At follow-up, 63 subjects (57%) showed a mild improvement of their MMSE score; their consumption of calcium and of n-3 fatty acids was higher (p<0.01 and p<0.03, respectively) than subjects without improvement. Similarly, multivariate logistic regression showed subjects whose consumption of calcium was above the dietary reference intake had a significantly higher odds ratio (OR) of improving their MMSE (OR=5.41; 95% CI: 1.44-20.29), whereas no effect was found for n-3 fatty acids (OR=2.48; 95% CI: 0.46-13.36). CONCLUSION: Increased calcium consumption is related to improved cognitive function; the exact effect of n-3 fatty acids intake remains to be assessed.