• X-ray
• feces
• intestinal injury
• microRNA-375-3p
• serum

• fecal markers
• intestinal damage
• intestinal stem cells
• ionizing radiation
• mouse model

Background: Lactoferrin, an iron-binding glycoprotein, and calprotectin, a calcium binding protein, are sensitive markers of inflammation and their fecal levels increase during radiotherapy of prostate cancer patients. With this background, we analyzed mouthrinse calprotectin and lactoferrin levels of head- and neck-cancer patients before, during and after radiotherapy. Methods: Twenty cancer patients (mean age 55.85 ± 15.01, 80% male), who had been planned to undergo radiotherapy to the head and neck area, were included in this study. Mouthrinse samples were collected before radiotherapy, at the 3rd and 6th weeks of radiotherapy and 4 weeks after the radiotherapy. Mouthrinse samples were analyzed for calprotectin and lactoferrin using commercial ELISA kits. Results: Calprotectin levels increased significantly during radiotherapy (p = 0.022). Both markers, lactoferrin (p = 0.011) and calprotectin (p = 0.006), decreased significantly after the treatment. Conclusions: Present study results may suggest that the elevations in calprotectin and lactoferrin levels during radiotherapy reflect the increased and emerging inflammatory environment in the oral cavity, thus may increase the risk of periodontal disease initiation or progression.

Allogeneic hematopoietic stem cell transplantation (HCT) is an often curative intent treatment, however it is associated with significant gastrointestinal (GI) toxicity and treatment related mortality. Graft-versus-host disease is a significant contributor to transplant-related mortality. We performed a phase 2 trial of the somatostatin analog pasireotide to prevent gastrointestinal toxicity and GVHD after myeloablative allogeneic HCT.

Patients received 0.9mg pasireotide every 12 hours from the day prior to conditioning through day +4 after HCT (or a maximum of 14 days). The primary outcomes were grade 3–4 gastrointestinal toxicity through day 30 and acute GVHD. Secondary outcomes were chronic GVHD, overall survival and relapse free survival at one year. Stool and blood samples were collected from before and after HCT for analyses of stool microbiome, local inflammatory markers, and systemic inflammatory and metabolic markers. Results were compared with matched controls.

Twenty-six patients received pasireotide and were compared to 52 matched contemporaneous controls using a 1–2 match. Grade 3–4 GI toxicity occurred in 21 (81%) patients who received pasireotide and 35 (67%) controls (p = 0.33). Acute GVHD occurred in 15 (58%) patients in the pasireotide group and 28 (54%) controls (p = 0.94). Chronic GVHD occurred in 16 patients in the pasireotide group (64%) versus 22 patients in the control group (42%) (p = 0.12). Overall survival at 1 year in the pasireotide group was 63% (95% CI: 47%,86%) versus 82% (95% CI: 72%, 93%) in controls (log-rank p = 0.006). Relapse-free survival rate at one year was 40% (95% CI: 25%, 65%) in the pasireotide group versus 78% (95% CI: 68%, 91%) in controls (log-rank p = 0.002). After controlling for the effect of relevant covariates, patients in the pasireotide group had attenuated post-HCT loss of microbial diversity. Analysis of systemic inflammatory markers and metabolomics demonstrated feasibility of such analyses in patients undergoing allogeneic HCT. Baseline level and pre-to-post transplant changes in several inflammatory markers (including MIP1a, MIP1b, TNFa, IL8Pro, and IL6) correlated with likelihood of survival.

Pasireotide did not prevent gastrointestinal toxicity or acute GVHD compared to contemporaneous controls. Pasireotide was associated with numerically higher chronic GVHD and significantly decreased OS and RFS compared to contemporaneous controls. Pasireotide may provide a locally protective effect in the stool microbiome and in local inflammation as measured by stool calprotectin, stool beta-defensin, and stool diversity index.

• Adult
• Combined Modality Therapy
• Female
• Gastrointestinal Diseases/etiology
• Gastrointestinal Diseases/pathology
• Gastrointestinal Diseases/prevention & control
• Graft vs Host Disease/etiology
• Graft vs Host Disease/pathology
• Graft vs Host Disease/prevention & control
• Hematologic Neoplasms/pathology
• Hematologic Neoplasms/therapy
• Hematopoietic Stem Cell Transplantation/adverse effects
• Hematopoietic Stem Cell Transplantation/methods
• Hormones/therapeutic use
• Humans
• Male
• Middle Aged
• Somatostatin/analogs & derivatives
• Somatostatin/therapeutic use
• Transplantation Conditioning
• Transplantation, Homologous

• P01 CA023766 NCI NIH HHS
• R01 CA228308 NCI NIH HHS
• P30 CA008748 NCI NIH HHS
• K08 HL143189 NHLBI NIH HHS
• R01 HL123340 NHLBI NIH HHS
• Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center
• NHLBI NIH
• MSKCC Cancer Center
• Novartis

• Inflammatory bowel disease
• Prostate cancer
• Radiotherapy
• Rectum balloon implant

• 5-Aminosalicylic acid
• Fecal biomarkers
• Probiotics
• Radiation proctitis

Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder characterized by unspecific symptoms. In clinical practice it is crucial to distinguish between non-inflammatory functional problems and inflammatory, malignant or infectious diseases of the GI tract. Differentiation between these involves the use of clinical, radiological, endoscopic, histological and serological techniques, which are invasive, expensive, time-consuming and/or hindered by inaccuracies arising from subjective components. A range of faecal markers now appears to have the potential to greatly assist in the differentiation of inflammatory bowel disease (IBD) and IBS. Faecal markers of neutrophil influx into the mucosa are reliable indicators of intestinal inflammation and their role has been mainly studied in discriminating IBD from non-IBD conditions (including IBS) rather than organic from non-organic diseases. Phagocyte-specific proteins of the S100 family (S100A12, calprotectin) are amongst the most promising faecal biomarkers of inflammation. Faecal leukocyte degranulation markers (lactoferrin, polymorphonuclear elastase and myeloperoxidase) have also been suggested as diagnostic tools for the differentiation of IBD and IBS. More recently, additional proteins, including granins, defensins and matrix-metalloproteases, have been discussed as differential diagnostic markers in IBD and IBS. In this review, some of the most promising faecal markers, which have the potential to differentiate IBD and IBS and to advance diagnostic practices, will be discussed.

• S100A12
• Calprotectin
• Lactoferrin
• M2-pyruvate kinase
• Polymorphonuclear elastase
• Defensins
• Granins
• Irritable bowel syndrome

• Animals
• Biomarkers/analysis
• Diagnosis, Differential
• Feces/chemistry
• Humans
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/metabolism
• Irritable Bowel Syndrome/diagnosis
• Irritable Bowel Syndrome/metabolism
• Predictive Value of Tests
• Prognosis

• Abdominal Pain/etiology
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers/analysis
• Colonic Polyps/diagnosis
• Colonoscopy
• Colorectal Neoplasms/diagnosis
• Constipation/etiology
• Diarrhea/etiology
• Feces/chemistry
• Female
• Gastroenteritis/diagnosis
• Humans
• Leukocyte L1 Antigen Complex/analysis
• Male
• Middle Aged
• Outpatients
• Predictive Value of Tests
• Prospective Studies
• Young Adult

• Humans
• Neoplasms/radiotherapy
• Proctitis/etiology
• Proctitis/prevention & control
• Proctitis/therapy
• Radiation Injuries/etiology
• Radiation Injuries/prevention & control
• Radiation Injuries/therapy
• Radiotherapy/adverse effects

AIM: To investigate possibility and clinical application of fecal calprotectin in determining disease activity of ulcerative colitis (UC).

METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of calprotectin in feces obtained from 66 patients with UC and 20 controls. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), acid glycoprotein (AGP) were also measured and were compared with calprotectin in determining disease activity of UC. The disease activity of UC was also determined by the Sutherland criteria.

RESULTS: The fecal calprotectin concentration in the patients with active UC was significantly higher than that in the inactive UC and in the controls (402.16 ± 48.0 &mgr;g/g vs 35.93 ± 3.39 &mgr;g/g, 11.5 ± 3.42 &mgr;g/g, P < 0.01). The fecal calprotectin concentration in the inactive UC group was significantly higher than that in the control group (P < 0.05). A significant difference was also found in the patients with active UC of mild, moderate and severe degrees. The area under the curve of the receiver operating characteristics (AUC^ROC) was 0.975, 0.740, 0.692 and 0.737 for fecal calprotectin, CRP, ESR and AGP, respectively. There was a strong correlation between the fecal calprotectin concentration and the endoscopic gradings for UC (r = 0.866, P < 0.001).

CONCLUSION: Calprotectin in the patient’s feces can reflect the disease activity of UC and can be used as a rational fecal marker for intestinal inflammation in clinical practice. This kind of marker is relatively precise, simple and noninvasive when compared with other commonly-used markers such as CRP, ESR and AGP.

• Fecal calprotectin
• Disease activity
• Ulcerative colitis
• Enzyme-linked immunosorbent assay

• Aged
• Biomarkers/analysis
• Humans
• Intestinal Mucosa/pathology
• Male
• Middle Aged
• Pelvis/radiation effects
• Proctitis/diagnosis
• Proctitis/etiology
• Proctitis/pathology
• Prostatic Neoplasms/radiotherapy
• Radiation Injuries/diagnosis
• Radiation Injuries/pathology
• Rectum/pathology

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Colitis, Ulcerative/diagnosis
• Colonoscopy
• Crohn Disease/diagnosis
• Feces/chemistry
• Female
• Gastroenteritis/diagnosis
• Humans
• Inflammatory Bowel Diseases/diagnosis
• Lactoferrin/analysis
• Leukocyte L1 Antigen Complex/analysis
• Male
• Middle Aged
• Predictive Value of Tests
• Sensitivity and Specificity