Small bowel carcinomas in celiac or Crohn's disease: Distinctive histophenotypic, molecular and histogenetic patterns

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (β-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage- and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear β-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat β-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and/or pancreatobiliary-type) mucosa, often through dysplastic polypoid growths of metaplastic phenotype. In conclusion, despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn's disease-associated small bowel carcinomas differ substantially in histological structure, phenotype, microsatellite instability/tumor-infiltrating lymphocyte status, Wnt pathway activation, mucosal precursor lesions and prognosis

Development of a technology for the production of snacks based on blackcurrant berries (Ribes nigrum)

Interest in the consumption of berries is largely due to the content of biologically active substances in them and their importance as dietary antioxidants. Polyphenolic compounds found in blackcurrant berries are known as agents that act prophylactically and therapeutically on the human body. The following were determined: total content of phenolic substances, flavonoids, anti-radical activity according to the DPPH method, restoring power according to the FRAP method, anthocyanins, organoleptic characteristics, dietary fiber content, vitamin C content for feedstock, semi-finished products (blackcurrant berries, blackcurrant puree, two types freeze-dried snacks from blackcurrant berries). According to the results of the study, it was found that the freeze-dried berry (snacks of two types of freeze-drying) showed good results: 42.05 mmol Fe2 +/1 kg (snacks with a structure-forming agent, 5% pectin), 38.6 mmol Fe2 +/1 kg ( snacks) restoring power according to the FRAP method, 47.1 Ec 50 mg/ml (snacks), 79.4 Ec 50 mg/ml (snacks with a builder, pectin 5%) anti-radical activity according to the DPPH method, 766 mg HA/100 g ( snacks), 835 mg HA/100 g (snacks with a builder, pectin 5%) total phenolic content, 374 mg K/100 g (snacks), 392 mg K/100 g (snacks with by a touring agent, 5% pectin) total flavonoid content, 166.07 mg CG/100 g (snacks), 174.21 mg CG/100 g (snacks with a structuring agent, 5% pectin) anthocyanins content, 50.1% (snacks), 66.9% (snacks with a builder, pectin 5%) vitamin C content, 76.8% (snacks), 90% (snacks with a builder, pectin 5%) dietary fiber, 1.92% (snacks), 2.13 % (snacks with a builder, pectin 5%) – titratable acidity. Thus, we can conclude that vacuum drying provides samples with good physicochemical properties and is better than a dried sample

Study of organoleptic and physico-chemical parameters of snacks based on mountain ash (Aronia melnocarpa)

The objects of study were chokeberry berries, mashed chokeberry berries, snacks sublimated from chokeberry, and snacks sublimated from chokeberry with the addition of 5% pectin. Organoleptic indicators, soluble solids, sugars, titratable acidity, content of vitamin C, dietary fiber, total phenolic content, flavonoids, anthocyanins, anti-radical activity by DPPH method, restoring ability by FRAP method were determined for the studied samples. Determination of the total content of flavonoids, anthocyanins and phenolic substances, as well as the restoring activity of the studied samples as indicators characterizing the antioxidant activity of the compounds, showed the positive effect of grinding as mechanical processing and freeze-drying as heat treatment on the antioxidant properties of chokeberry. As a result of determining the content of dietary fiber, soluble solids, sugars and titratable acidity, antiradical properties in the studied samples, an increase in the values of these indicators by 3-6 times in the process of freeze-drying was revealed, which shows the feasibility of using this type of heat treatment in the production of functional products based on chokeberry. Determination of the vitamin C content in the test samples allows us to conclude that the freeze-drying has a negative effect on the vitamin C content in aronia. A methodology for organoleptic evaluation of a new type of freeze-dried snacks based on mashed chokeberry is developed. It has been established that a new kind of snacks has high organoleptic characteristics, which makes their production a promising direction

CLINICAL COURSE OF SEVERE COLITIS: A COMPARISON BETWEEN CROHN'S DISEASE AND ULCERATIVE COLITIS.

Few data are available about the clinical course of severe colonic Crohn's disease (CD). The aim of this study is to desrcibe the clinical course of severe Crohn's colitis in a patients cohort with isolated colonic or ileo-colonic CD and to compare it with the clinical course of patients with severe ulcerative colitis (UC). Thirthy-four patients with severe Crohn's colitis were prospectively identified in our cohort of 593 consecutive hospitalized patients through evaluation of the Crohn's Disease Activity Index score and the Harvey-Bradshaw Index. One undred sixty-nine patients with severe ulcerative colitis were prospectively identified in our cohort of 449 consecutive hospitalized patients through evaluation of the Lichtiger score and the Truelove-Witts score. We evaluated the following data/aspects: response to steroids, response to biologies, colectomy rate in acute, colectomy rate during follow-up, megacolon and cytomegalovirus infection rate. We did not find significant differences in the response to stertoids and to biologies, in the percentage of cytomegalovirus infection and of megacolon, while the rate of colectomy in acute turned out be greater in patients with severe Crohn's colitis compared to patients with severe UC, and this difference appeared to be limit of statistical significance (chi-squared 3.31,p=0.069, OR 0.39); the differenc between the colectomy rates at the end of the follow-up also not significant. In the whole population, by univariate analysis, according to the luinear regression model a young age at diagnosis is associated with a higher overall colectomy rate (p=0.024) and a higher elective colectomy rate (p=0.022), but not with a higher acute colectomy rate, and an elevated ESR is correlated with a higher overall colectomy rate (p = 0.014) and a higher acute colectomy rate (p = 0.032), but not with a higher elective colectomy rate. This correlation was significant on multivariate analysis. The overall rate of colectomy in the cohort of patients with severe Crohn\u2019s colitis was greater than that of the cohort of patients with severe UC, but this figure is not supported by a different clinical response to steroid therapy or rescue therapy with biologics. The clinical course of severe Crohn\u2019s colitis requires to be clarified by prospective studies that include a larger number of patients in this subgroup of disease

Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas

Background: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. Patients and Methods: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability. Results: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status. Conclusions: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy

Small bowel carcinomas in coeliac or Crohn's disease: Clinico-pathological, molecular, and prognostic features. A study from the small bowel cancer Italian consortium

Background and Aims: An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. Methods: A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. Results: CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancerspecific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI-which was the result of MLH1 promoter methylation in all but one cases-and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications. Conclusions: In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy