Crohn's disease (CD) and Ulcerative colitis (UC) are grouped as Inflammatory Bowel Diseases (IBD). The IBD is associated to a multifaceted interplay between immunologic, microbial, genetic, and environmental factors. Nowadays, the gut microbiota (GM) dysbiosis has been indicated as a cause in the IBD development, affecting the impaired cross-talk between GM and immune cells. Moreover, recent studies have uncovered a crucial role for bacterial post-biotics (metabolites) in the orchestration of the host immune response, as they could be messengers between the GM and the immune system. In addition, transgenic mouse models showed that SCFAs (Short Chain Fatty Acids) and Tryptophan (Trp) post-biotics play important immunomodulatory effects, regulating both innate and adaptive immune cell generation, their function and trafficking. Here, we present an overview on the main microbial post-biotics and their effects on the gut mucosa with specific emphasis on their relevance for IBD. Finally, we discuss the therapeutic potential of SCFA and Trp post-biotics on IBD through approaches based on the “immunonutrition,” defined as a modulation of the immune system provided by specific interventions that modify dietary nutrients.

Correlations between germline APC mutation sites and colorectal pathophenotypes, as evaluated by the direct count of adenomas at colectomy, were investigated analysing colectomy specimens from 29 FAP patients carrying one mis-sense (codon 208) and 14 frame-shift or non-sense APC mutations (codons 232, 367, 437, 623, 876, 995, 1061, 1068, 1075, 1112, 1114, 1309, 1324, 1556). The mis-sense mutation at codon 208 was associated with a relatively mild colorectal pathophenotype. The mutation at codon 367, subject to alternative splicing, was associated with attenuated FAP. The mutation at codon 1309 was associated with the profuse colorectal adenomatosis. For 13 mutations, predicted to result in null alleles or truncated APC proteins, we correlated density and distribution of colorectal adenomas with the predicted functional effects of the mutation. The most severe colorectal pathophenotype was significantly associated with the truncating mutation at codon 1309, which is located downstream to the I β-catenin binding domain but upstream II β-catenin-binding domain. Mutations between codons 867 and 1114, which affect the I β-catenin binding domain, as well as mutations occurring in exons 6 and 9, predicted to result in null alleles, were associated with a less severe colorectal pathophenotype. Overall, the highest number of adenomas was detected in the right colon, followed by the left colon, transverse colon sigma and rectum. However, the highest density of adenomas was observed in the left colon, followed by the right colon, sigma, transverse colon and rectum. Colorectal carcinomas, observed in only five patients, were all in the left colon. © 2000 Cancer Research Campaign

Functional results after anterior rectal resections are commonly considered satisfactory but variable percentages of postoperative incontinence are often reported. Continence was evaluated after 20 low anterior resections (LAR) and 13 high anterior resections (HAR) by means of clinical assessment, anorectal manometry, and evacuation proctography. Whereas all HAR patients had perfect continence, 10 patients (50 percent of the LAR group had occasional episodes of soiling from liquid feces, 5 patients (25 percent had frequent soiling or occasional incontinence for solid feces, and 1 patient (5 percent had frequent solid stool loss requiring surgical treatment. Anal canal resting pressure at 3 and 4 cm from the anal verge was significantly lower in the LAR group (P less than 0.02 and P less than 0.05, respectively) than in the HAR group. However, the maximum voluntary contraction did not differ between the two groups. Rectoanal inhibitory reflex was found to be present in 17 of the 20 patients with LAR and in all patients with HAR. The volume at which the anal sphincter is continuously inhibited was significantly reduced in the LAR group (P less than 0.001). Also, the conscious rectal sensibility volumes were found to be significantly reduced for threshold, constant, and maximum tolerated volume. Threshold volume for internal sphincter relaxation was lower than the threshold volume for rectal sensation in some patients with LAR. This could allow postoperative fecal soiling. Rectal compliance was decreased (P less than 0.001) in the LAR group. Evacuation proctography, performed in six LAR patients affected by major soiling or solid stool loss, revealed an abnormal obtuse anorectal angle and pathologic lowering of the perineum at rest and during defecation. The concomitance of internal and sphincter impairment, reduction in rectal compliance, and previous pelvis floor muscle damage are postulated as cause affecting continence in patients who underwent LAR.

Sulindac appears to influence the morphological appearance of polyps in FAP patients, inducing apparent regression. However, at a dose of 200 mg, it does not influence the progression of polyps toward a malignant pattern.

Background: A gold standard method for malnutrition diagnosis is still lacking in Inflammatory Bowel Disease (IBD). Objective: The aims of this study are to determine the prevalence of malnutrition in IBD patients according with recently published Global Leadership Initiative on Malnutrition (GLIM) criteria, to detect the factors contributing to the onset of malnutrition, and to evaluate the most accurate predictor of malnutrition risk within the available nutritional screening tools. Methods: Fifty-three consecutive adult IBD patients [38 Crohn’s disease (CD) and 15 ulcerative colitis (UC)] had been assessed preoperatively by a multidisciplinary IBD team before undergoing elective surgery. Several malnutrition risk tools were tested, such as NRS-2002, MUST, MST, MIRT, and SaskIBD-NR. The statistical association of independent GLIM variables with baseline characteristics of patients was explored as well as the concordance with the European Society for Clinical Nutrition and Metabolism (ESPEN 2015) and the screening tools. Results: Twenty-two IBD patients (42%) were malnourished according to GLIM criteria, of which 13 were CD (34%) and 9 UC (60%). The etiological criteria of inflammation and reduction of food intake were present in 51% and 19% of our patients, respectively. The prevalence of GLIM phenotypic criteria was 28%, 28% and 34% for BMI, Free Fat Mass Index (FFMI) and unintended weight loss (UWL), respectively. The presence of ileostomy was statistically associated with a higher prevalence of BMI (p = 0.030), FFMI (p = 0.030) and UWL (p = 0.002) values lower than the GLIM criteria cut-offs, while secondary surgery is associated with a decrease in FFMI (p = 0.017) and UWL (p = 0.041). The sensitivity of the tested nutritional screening tools, compared with the GLIM prevalence of malnutrition, was not satisfactory (between 50 and 82%). Conclusions: GLIM has a higher rate of malnutrition detection than ESPEN 2015, as malnutrition in IBD seems linked to inflammation and secondary malabsorption even without a reduction of food intake. The sensitivity of the screening tools is lower than the specificity when compared with GLIM criteria for malnutrition diagnosis.

Ileal pouch adenomas were common after restorative proctocolectomy. Patients >50 years of age and patients with >1000 colonic adenomas at the time of colectomy were more prone to ileal pouch adenomas. The development of malignancy in the terminal ileum can present a fast course and does not seem to follow the classic adenoma-carcinoma sequence.

Primary carcinoid tumors of the extrahepatic biliary tree are exceedingly rare, accounting for 0.2-2% of all digestive carcinoids. The authors in this study describe a case of biliary duct primary well-differentiated endocrine tumor in a 30-year-old man with symptoms of biliary obstruction and watery diarrhoea. Abdominal ultrasound showed a 2-cm solid lesion in the head of the pancreas, compressing the distal common bile duct. A computed tomography scan confirmed these findings, revealing the hypervascular pattern of the tumor. Gastrointestinal hormonal screening demonstrated an increase in plasma serotonin. The patient underwent standard pylorus-preserving pancreatoduodenectomy. Pathological examination showed a neuroendocrine tumor of the distal common bile duct measuring 1.8 cm in greatest dimension. The tumor cells were immunopositive for neuron-specific enolase (NSE), chromogranin A, synaptophysin, serotonin, and cytokeratin. Stains for gastrin and somatostatin were negative. Seven years later, the patient is well, with no evidence of disease. Given the site of these tumors and the difficulty in differentiating them from periampullary lesions, decisions as to the appropriate surgical approach may be problematic. After an exhaustive review of the literature, the authors conclude that pancreatoduodenectomy is the treatment of choice.

Background: Crohn’s disease (CD) is an idiopathic inflammatory bowel disease (IBD) in the pathogenesis of which both Th1 and Th17 lymphocytes have been described as being involved. The NK-associated molecule CD161 has recently been described as a marker of IL-17-producing lymphocytes. In this work we assessed the presence and the functional features of CD161 T helper lymphocytes infiltrating CD-associated perianal fistulas, both before and after inoculation of anti-TNF-α mAbs along the fistula. Methods: In a group of 9 CD patients with fistulizing perianal disease, we evaluated phenotypic and functional features of T cells recovered from the fistula, comparing them with peripheral blood (PB) T lymphocytes. Moreover, the effects anti-TNF-α mAbs injections along the fistula in terms of ability to reduce the inflammatory infiltrate and to determine fistula disappearance were assessed. Results: In CD patients with fistulizing disease there is an accumulation of CD161+ T helper lymphocytes, with higher frequencies of Th1, Th17 and Th17/Th1 cells in the fistula than in PB. Local anti-TNF-α administration is associated with fistula resolution in the majority of patients with disappearance of infiltrating T lymphocytes, without any systemic effect in circulating effector T cells. Conclusions: These findings suggest that CD4+CD161+ T cells with Th17, Th17/Th1 and Th1 phenotype accumulate in CD perianal fistulas, and indicate local anti-TNF-α mAbs administration along the fistula as a promising tool for the treatment of these patients.