Marathon pancreatitis: a case of acute pancreatitis caused by distance running.

Marathon running or other forms of strenuous exercise have been reported as a rare cause of acute pancreatitis. Theories as to the mechanism of acute pancreatitis include microvascular ischaemia due to dehydration or repetitive trauma to the pancreas. We report a case of a healthy woman in her 30s who developed abdominal pain, nausea and vomiting after a 32 km marathon training run. She was found to have elevated lipase and inflammation of the pancreatic tail with associated pericolic and pelvic free fluid on CT scan. Workup including abdominal ultrasound and magnetic resonance cholangiopancreatography (MRCP) did not reveal biliary or pancreatic duct pathology. She improved with conservative management. These findings support the hypothesis of exercise-induced pancreatitis from long-distance running.

Fluid resuscitation in acute pancreatitis.

PURPOSE OF REVIEW: The purpose of the review is to critically evaluate the evidence from the literature to establish the current perspective on fluid resuscitation (FR) in acute pancreatitis (AP). We will review the rationale, type of fluid, rate of administration, total volume, duration, monitoring, ideal outcomes to be studied in clinical trials and recommendations for future studies. RECENT FINDINGS: FR remains the key component of supportive therapy in AP. The paradigm has shifted from administration of aggressive fluid resuscitation towards more moderate FR strategies. Lactated Ringer's remains the preferred fluid for resuscitation. There remain critical gaps in knowledge regarding the end point(s) to indicate adequate resuscitation, and accurate assessments of fluid sequestration and intravascular volume deficit in AP. SUMMARY: There is insufficient evidence to state that goal-directed therapy, using any of the parameters to guide fluid administration, reduces the risk of persistent organ failure, infected pancreatic necrosis, or mortality in AP, as well as the most appropriate method for the same.

Characteristics of 30-Day All-Cause Hospital Readmissions Among Patients with Acute Pancreatitis and Substance Use.

BACKGROUND/OBJECTIVES: Previous studies on healthcare resource utilization and 30-day readmission risks among patients with acute pancreatitis (AP) have focused upon opioid and alcohol use. The data on other substance types are lacking. In this study we aim to estimate the 30-day readmission rates, predictors of readmission, impact of readmission on patient outcomes and resulting economic burden among patients with AP and substance use in the USA. METHODS: This was a retrospective cohort study, based upon data from 2017 National Readmission Database of adult patients with AP and substance use (alcohol in combination, opioid, cannabis, cocaine, sedatives, other stimulants, other hallucinogens, other psychoactive, inhalant and miscellaneous). We estimated the 30-day readmission rates and predictors of 30-day readmission. RESULTS: Among 25,795 eligible patients, most were male, belonged to the lower income quartile, resided in the urban facility and had a Charlson comorbidity score of 0 or 1. The use of a combination of substances was the most common in 17,265 (66.9%) patients followed by only opioids in 4691 (18.2%) patients and only marijuana in 3839 (14.9%) patients. A total of 14.6% patients were readmitted within 30 days after discharge for non-elective causes with the highest risk of readmission within the 1st week after discharge with 5.2% readmissions. Among top ten causes of readmission, most of the principal diagnosis were related to AP in 53.1%. Compared to index admission, readmitted patients had significantly higher rates of acute cardiac failure, shock, and higher in-hospital mortality rate. Overall, readmission attributed to an additional 17,801 days of hospitalization resulting in a total of $150 million in hospitalization charges and $36 million in hospitalization costs in 2017. On multivariate analysis, chronic pancreatitis, self-discharge against medical advice, treatment at the highest volume centers, higher Charlson comorbidity index, increasing length of stay and severe disease were associated with higher odds of readmission while female gender and private insurance were associated with lower odds. CONCLUSION: Readmission was associated with higher morbidity and in-hospital mortality among patients with AP and substance use and resulted in a significant monetary burden on the US healthcare system. Several factors identified in this study may be useful for categorizing patients at higher risk of readmission warranting special attention during discharge planning.

Provider Differences in Monitoring and Management of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) is a common cause of exocrine pancreatic insufficiency (EPI). Regular monitoring and treatment are recommended to decrease morbidity. This study evaluates whether provider type impacts EPI monitoring and management in CP. METHODS: Fecal elastase 1 (FE-1) testing and pancreatic enzyme replacement therapy (PERT) utilization were retrospectively compared between primary care providers (PCPs), gastroenterologists and pancreas specialists using pairwise comparisons. Multivariate analysis was conducted to study the association between adequate PERT and age, sex, race, insurance status, provider type, and etiology. RESULTS: Among 256 patients, FE-1 was measured in 115 (44.9%) and of 143 (55.9%) patients who received PERT, 100 (69.9%) received adequate dosage. Fecal elastase 1 testing was performed in 7/57 (12.3%) by PCP, 11/38 (28.9%) by gastroenterologists, and 97/161 (60.2%) by pancreas specialists (P < 0.0001). Adequate PERT was prescribed in 7/24 (29.2%) patients by PCPs, 11/20 (55.0%) by gastroenterologists, and 82/99 (82.8%) by pancreas specialists (P < 0.0001). On multivariate analysis, pancreas specialists were significantly more likely to prescribe adequate PERT compared with PCP (odds ratio, 11.3; 95% confidence interval, 3.3-38.2; P < 0.001). CONCLUSIONS: Many patients with CP receive inadequate surveillance and EPI treatment. Pancreas specialists are more likely to surveil and treat EPI adequately.

Nutrition and Acute Pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is characterized by severe abdominal pain, elevated pancreatic enzymes, and pancreatic changes on abdominal imaging. AP is, by nature, an inflammatory process that leads to protein catabolism and an increased metabolic rate, highlighting the strong need for early nutritional support in the initial management of the disease process. The goal of nutritional support in acute pancreatitis is to correct the negative nitrogen balance to reduce inflammation and improve outcomes. Many trials and multiple systemic reviews and meta-analyses have examined the best modality, timing, and composition of nutritional support for acute pancreatitis. Early enteral nutrition has emerged as an important aspect of the clinical management of AP. This narrative review aimed to provide an overview of the clinical management of nutrition in acute pancreatitis based on the currently available data.

Provider type influences adherence to lifestyle changes in chronic pancreatitis.

BACKGROUND: /Objectives: Alcohol and smoking cessation are recommended in chronic pancreatitis. The aim of this study is to measure the rates of alcohol and smoking cessation counselling among providers and adherence to recommendations. METHODS: Retrospective cohort study of chronic pancreatitis patients at a tertiary hospital. Provider types were defined as primary care (PCP), gastroenterologist, or pancreas specialist. Pairwise comparisons and multivariable analysis were conducted to assess the relation between provider type and smoking/alcohol cessation. RESULTS: Of 256 patients with chronic pancreatitis, 142 (55.5%) consumed alcohol and 130 (91.5%) were advised to stop. Alcohol cessation was advised to 88.9, 96.0 and 92.5% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively. Sixty-one patients (46.9%) were compliant with the recommendation: 31.3, 44.0 and 54.1% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, others nonsignificant). In multivariable analysis, patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation compared to those followed by PCP (OR = 4.31, CI 1.52-12.20, p = 0.006). Smoking cessation was advised to all the 127 current smokers (100%). Fifty-six (44.1%) were compliant with the recommendation: 24.1, 58.3 and 47.3% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, PCP vs. Gastroenterologist: p = 0.01, others nonsignificant). Multivariable analysis did not confirm this finding. CONCLUSIONS: The majority of providers counsel for alcohol/smoking cessation. Less than half the patients follow the recommendations. Patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation.

Does Provider Type Affect Bone Health Surveillance in Chronic Pancreatitis?

BACKGROUND: Bone density screening (DEXA) and vitamin D serum assay (Vit-D) are recommended in chronic pancreatitis, but adherence by providers is unknown. AIMS: Assess DEXA/Vit-D testing according to provider type. METHODS: A retrospective cohort study of chronic pancreatitis patients followed in a tertiary hospital (August 2017-2018) was conducted. Provider type was primary care (PCP), gastroenterologist, and pancreas specialist. Chi-square test and multivariable analysis were conducted to assess the relation between provider type and DEXA/Vit-D testing. Subset analyses were performed among patients with fecal elastase < 200 mcg/g. RESULTS: A total of 478 charts were reviewed, and 256 (53.6%) met diagnosis of chronic pancreatitis; 184 (71.9%) definite, 45 (17.6%) probable, and 27 (10.6%) borderline chronic pancreatitis. DEXA was tested in 112/256 (43%) patients; 16/57(28%) patients followed by PCP, 11/38 (28.9%) by gastroenterologists, and 85/161(52.2%) by pancreas specialists (p = 0.001). Vit-D was tested in 210/256 (82.0%) patients; 42/57(73.7%) followed by PCP, 29/38 (76.3%) by gastroenterologists, and 139/161(86.3%) by pancreas specialists (p = 0.06). Multivariate analysis assessing DEXA/Vit-D testing showed pancreas specialists were more likely to test compared to PCP (DEXA: OR 3.70, CI 1.77-7.74, p = 0.001. Vit-D: OR 3.24, CI 1.43-7.38, p = 0.005), but gastroenterologists were not. In patients with low fecal elastase, pancreas specialists were more likely to test DEXA (pancreas specialists: 62.1%, PCP: 40.0%, Gastroenterologists: 11.1%, p = 0.01) and all patients received Vit-D testing. CONCLUSIONS: Chronic pancreatitis patients often do not receive optimal preventive care. Pancreas specialists were more likely to perform DEXA and Vit-D testing compared to PCP and gastroenterologists. More physician education is needed.

Overview of Inositol and Inositol Phosphates on Chemoprevention of Colitis-Induced Carcinogenesis.

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn's disease. Importantly, patients with IBD have a significantly increased risk for the development of colorectal carcinoma. Dietary inositol and its phosphates, as well as phospholipid derivatives, are well known to benefit human health in diverse pathologies including cancer prevention. Inositol phosphates including InsP3, InsP6, and other pyrophosphates, play important roles in cellular metabolic and signal transduction pathways involved in the control of cell proliferation, differentiation, RNA export, DNA repair, energy transduction, ATP regeneration, and numerous others. In the review, we highlight the biologic function and health effects of inositol and its phosphates including the nature and sources of these molecules, potential nutritional deficiencies, their biologic metabolism and function, and finally, their role in the prevention of colitis-induced carcinogenesis.

Hypertriglyceridemia and acute pancreatitis.

Hypertriglyceridemia is the third most common cause of acute pancreatitis. It typically occurs in patients with an underlying disorder of lipoprotein metabolism and in the presence of a secondary condition such as uncontrolled diabetes, alcohol abuse, or medication use. The presentation of hypertriglyceridemia-induced pancreatitis is similar to that of acute pancreatitis due to other causes; however, patients with hypertriglyceridemia-induced pancreatitis are more likely to have severe disease courses and have a higher likelihood of persistent organ failure. The initial treatment of hypertriglyceridemia-induced pancreatitis is also similar to acute pancreatitis from other causes and consists of aggressive fluid resuscitation, pain control, and nutritional support. Hypertriglyceridemia is specifically treated with apheresis or insulin therapy when necessary. The prompt recognition of hypertriglyceridemia in the setting of acute pancreatitis is essential in both the initial and long-term management of this disease and are essential to prevent recurrent acute pancreatitis. The review seeks to highlight the etiology, pathogenesis, and clinical course of hypertriglyceridemia-induced acute pancreatitis.

Opiate Prescriptions at Discharge Are Not Associated with Early Readmissions in Acute Pancreatitis.

BACKGROUND: Early readmissions in acute pancreatitis (AP) are common. The impact of opiate prescriptions on readmissions is unknown. AIMS: To determine whether the prescription of opiates at hospital discharge and the dose prescribed are associated with early readmissions in AP. METHODS: Direct admissions from the Emergency Department (ED) for AP from September 1, 2013, to August 31, 2016 were identified. Opiate prescription was defined as a new prescription at discharge in an opiate-naïve patient. Early readmission was ED visit or hospitalization within 30 days for an AP-related reason. Multivariable logistic regression was performed, adjusted for age, Charlson Comorbidity Index, pancreatic necrosis, baseline opiate use, non-opiate analgesics, and pain score at discharge. RESULTS: A total of 318 AP patients were identified; the overall early readmission rate was 18%. One hundred and twenty-one (38%) were prescribed opiates at discharge, and 22% had an early readmission. One hundred and ninety-seven (62%) were not prescribed opiates, and 16% had an early readmission. Median opiate dose was 48 mg (24-h morphine equivalents). On multivariable analysis, neither the prescription of opiates (OR 1.2, 95% CI 0.6-2.4, p = 0.55) nor the dose of opiates (OR 0.99, 95% CI 0.99-1.00, p = 0.39) was associated with early readmission. In subset analysis of patients discharged with an opiate prescription, those on opiates at baseline were significantly more likely to have an early readmission (OR 4.19, 95% CI 1.04-16.94, p = 0.04). CONCLUSIONS: In AP patients, neither prescription of opiates at discharge nor prescribed dose was associated with early readmission. Patients on opiates at baseline discharged with an opiate prescription were more likely to have an early readmission.

Are Opioid-Naive Patients With Acute Pancreatitis Given Opioid Prescriptions at Discharge?

OBJECTIVES: Opioids are commonly used in the management of acute pancreatitis (AP). Inpatient opioid exposure is known to increase the risk of chronic opioid use after discharge. Prescription patterns for opioids at discharge for AP are unknown. METHODS: Medical records of adult AP patients who presented to the emergency department from September 1, 2013, to August 31, 2016, were reviewed. Opioid prescription at discharge was defined as a prescription for opioids in a patient who was opioid naive at admission. Multivariable logistic regression was performed to identify predictors of opioid prescription at discharge. RESULTS: A total of 259 opioid-naive AP patients were identified. Of these, 108 (41.6%) of 259 were discharged with an opioid prescription and 61 (56.5%) of 108 had discharge pain scores of 3 or lower. Two hundred twenty-two (85.7%) received opioids during admission and 105 (47.3%) of 222 were discharged with an opioid prescription. On multivariable analysis, predictors of discharge opioid prescription included inpatient use of opioids, female sex, and discharge pain score greater than 3. CONCLUSIONS: In opioid-naive AP patients, 41.6% were discharged from the hospital with a new prescription for opioids, even though a significant proportion had pain scores of 3 or lower. Guidelines are needed for opioid prescriptions at discharge for AP.

A clinical primer of the role of gut microbiome in health and disease.

Gut microbiome represents the total microbes present in the gastrointestinal tract including the genes they encode. These microbes primarily exist in a reciprocal state with the host contributing several important functions such as carbohydrates fermentation, vitamin biosynthesis and regulation of the immune system. The gut microbiome represents a dynamic organ, which responds to changes in the host, such as genetics and age, as well as environment such as diet and antibiotics. While these microbes can adapt to change, any disturbance in this host-microbe equilibrium has the potential to initiate a cascade of events leading to a disease phenotype. In this review we highlight the emerging role of gut microbiome in different gastrointestinal and systemic diseases, the role of current therapies and development of future therapies targeting the gut microbiome as a potential mode of treatment.

Sulindac inhibits pancreatic carcinogenesis in LSL-KrasG12D-LSL-Trp53R172H-Pdx-1-Cre mice via suppressing aldo-keto reductase family 1B10 (AKR1B10).

Sulindac has been identified as a competitive inhibitor of aldo-keto reductase 1B10 (AKR1B10), an enzyme that plays a key role in carcinogenesis. AKR1B10 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and exhibits lipid substrate specificity, especially for farnesyl and geranylgeranyl. There have been no studies though showing that the inhibition of PDAC by sulindac is via inhibition of AKR1B10, particularly the metabolism of farnesyl/geranylgeranyl and Kras protein prenylation. To determine the chemopreventive effects of sulindac on pancreatic carcinogenesis, 5-week-old LSL-Kras(G12D)-LSL-Trp53(R172H)-Pdx-1-Cre mice (Pan(kras/p53) mice) were fed an AIN93M diet with or without 200 p.p.m. sulindac (n = 20/group). Kaplan-Meier survival analysis showed that average animal survival in Pan(kras/p53) mice was 143.7 ± 8.8 days, and average survival with sulindac was increased to 168.0 ± 8.8 days (P < 0.005). Histopathological analyses revealed that 90% of mice developed PDAC, 10% with metastasis to the liver and lymph nodes. With sulindac, the incidence of PDAC was reduced to 56% (P < 0.01) and only one mouse had lymph node metastasis. Immunochemical analysis showed that sulindac significantly decreased Ki-67-labeled cell proliferation and markedly reduced the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Raf and mitogen-activated protein kinase kinase 1 and 2. In in vitro experiments with PDAC cells from Pan(kras/p53) mice, sulindac exhibited dose-dependent inhibition of AKR1B10 activity. By silencing AKR1B10 expression through small interfering RNA or by sulindac treatment, these in vitro models showed a reduction in Kras and human DNA-J homolog 2 protein prenylation, and downregulation of phosphorylated C-raf, ERK1/2 and MEK1/2 expression. Our results demonstrate that sulindac inhibits pancreatic carcinogenesis by the inhibition of Kras protein prenylation by targeting AKR1B10.

Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mice.

There are several studies supporting the role of HMG-CoA reductase inhibitors such as atorvastatin against carcinogenesis, in which inhibiting the generation of prenyl intermediates involved in protein prenylation plays the crucial role. Mutation of Kras gene is the most common genetic alteration in pancreatic cancer and the Ras protein requires prenylation for its membrane localization and activity. In the present study, the effectiveness of atorvastatin against pancreatic carcinogenesis and its effect on protein prenylation were determined using the LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mouse model (called Pankras/p53 mice). Five-week-old Pankras/p53 mice were fed either an AIN93M diet or a diet supplemented with 100 ppm atorvastatin. Kaplan-Meier survival analysis with Log-Rank test revealed a significant increase in survival in mice fed 100 ppm atorvastatin (171.9 ± 6.2 d) compared to the control mice (144.9 ± 8.4 d, P < 0.05). Histologic and immunohistochemical analysis showed that atorvastatin treatment resulted in a significant reduction in tumor volume and Ki-67-labeled cell proliferation. Mechanistic studies on primary pancreatic tumors and the cultured murine pancreatic carcinoma cells revealed that atorvastatin inhibited prenylation in several key proteins, including Kras protein and its activities, and similar effect was observed in pancreatic carcinoma cells treated with farnesyltransferase inhibitor R115777. Microarray assay on the global gene expression profile demonstrated that a total of 132 genes were significantly modulated by atorvastatin; and Waf1p21, cyp51A1, and soluble epoxide hydrolase were crucial atorvastatin-targeted genes which involve in inflammation and carcinogenesis. This study indicates that atorvastatin has the potential to serve as a chemopreventive agent against pancreatic carcinogenesis.

Soluble epoxide hydrolase gene deficiency or inhibition attenuates chronic active inflammatory bowel disease in IL-10(-/-) mice.

BACKGROUND: Soluble epoxide hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids (EETs) into their much less active dihydroxy derivatives dihydroxyeicosatrienoic acids. Thus, targeting sEH would be important for inflammation. AIMS: To determine whether knockout or inhibition of sEH would attenuate the development of inflammatory bowel disease (IBD) in a mouse model of IBD in IL-10(-/-) mice. METHODS: Either the small molecule sEH inhibitor trans/-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) or sEH knockout mice were used in combination with IL-10(-/-) mice. t-AUCB was administered to mice in drinking fluid. Extensive histopathologic, immunochemical, and biochemical analyses were performed to evaluate effect of sEH inhibition or deficiency on chronic active inflammation and related mechanism in the bowel. RESULTS: Compared to IL-10 (-/-) mice, sEH inhibition or sEH deficiency in IL-10(-/-) mice resulted in significantly lower incidence of active ulcer formation and transmural inflammation, along with a significant decrease in myeloperoxidase-labeled neutrophil infiltration in the inflamed bowel. The levels of IFN-γ, TNF-α, and MCP-1, as well VCAM-1 and NF-kB/IKK-α signals were significantly decreased as compared to control animals. Moreover, an eicosanoid profile analysis revealed a significant increase in the ratio of EETs/DHET and EpOME/DiOME, and a slightly down-regulation of inflammatory mediators LTB(4) and 5-HETE. CONCLUSION: These results indicate that sEH gene deficiency or inhibition reduces inflammatory activities in the IL-10 (-/-) mouse model of IBD, and that sEH inhibitor could be a highly potential in the treatment of IBD.

SRp38 regulates alternative splicing and is required for Ca(2+) handling in the embryonic heart.

SRp38 is an atypical SR protein splicing regulator. To define the functions of SRp38 in vivo, we generated SRp38 null mice. The majority of homozygous mutants survived only until E15.5 and displayed multiple cardiac defects. Evaluation of gene expression profiles in the SRp38(-/-) embryonic heart revealed a defect in processing of the pre-mRNA encoding cardiac triadin, a protein that functions in regulation of Ca(2+) release from the sarcoplasmic reticulum during excitation-contraction coupling. This defect resulted in significantly reduced levels of triadin, as well as those of the interacting protein calsequestrin 2. Purified SRp38 was shown to bind specifically to the regulated exon and to modulate triadin splicing in vitro. Extending these results, isolated SRp38(-/-) embryonic cardiomyocytes displayed defects in Ca(2+) handling compared with wild-type controls. Taken together, our results demonstrate that SRp38 regulates cardiac-specific alternative splicing of triadin pre-mRNA and, reflecting this, is essential for proper Ca(2+) handling during embryonic heart development.

Increased susceptibility of chronic ulcerative colitis-induced carcinoma development in DNA repair enzyme Ogg1 deficient mice.

Ogg1 DNA repair enzyme recognizes and excises oxidative stress-caused 8-hydroxyl-deoxyguanosine (8-OHdG) from GC base-pairs. Ogg1 knockout mice are phenotypically normal, but exhibit elevated levels of 8-OHdG in nuclear and mitochondrial DNA, as well as moderately elevated mutagenesis and spontaneous lung tumors and UV-induced skin tumors. To elucidate the mechanistic role of inflammation-caused oxidative stress in carcinogenesis, the development of chronic ulcerative colitis (UC)-induced carcinoma in Ogg1 knockout mice was studied using a dextran sulfate sodium (DSS)-induced UC model without the use of a carcinogen. Ogg1 (-/-), Ogg1 (+/-), and wild type C57BL/6 mice were subjected to long-term, cyclic DSS treatment to induce chronic UC and carcinogenesis. In wild type C57BL/6 control mice after 15 cycles of DSS treatment, colorectal adenocarcinoma incidence was 24.1% (7/29 mice), with a tumor volume of 27.9 +/- 5.2 mm(3). Ogg1 (-/-) mice showed significantly increased adenocarcinoma development in the colon with a tumor incidence of 57.1% (12 of 21 mice, P < 0.05) and a tumor volume of 35.1 +/- 6.1 mm(3). Ogg1 mice (+/-) also exhibited significantly increased tumor development in the colon with a tumor incidence of 50.0% (13/26 mice) and a tumor volume of 29.1 +/- 7.2 mm(3). Histopathologic analyses revealed that colorectal tumors were well-differentiated tubular adenocarcinomas or mucinous carcinoma and adjacent colonic mucosa showed mild to moderate chronic UC. Using immunohistochemical approaches, Ogg1 (-/-) and (+/-) mice exhibited similar numbers and staining intensities of macrophages in UC areas as seen in Ogg1 (+/+) mice, but markedly increased numbers and staining intensities of 8-OHdG positive inflammatory and epithelial cells. These results provide important evidence on the relationship between inflammation-caused oxidative stress, DNA repair enzyme Ogg1, and carcinogenesis.

Inhibition of chronic ulcerative colitis associated adenocarcinoma development in mice by inositol compounds.

Chronic inflammation is a well recognized risk factor for cancer and patients with long-standing ulcerative colitis (UC) are at an increased risk for colorectal carcinoma development. In order to prevent UC associated carcinogenesis, we tested the effects of inositol compounds (including inositol and hexaphosphate inositol) on UC-associated carcinogenesis in our novel mouse model. Female C57BL/6 mice were subjected to long-term, cyclic dextran sulfate sodium (DSS) treatment and fed a 2-fold iron-enriched diet. The inositol compounds were administered via the drinking fluid. In the DSS-plus-2-fold iron positive control group, colorectal adenocarcinoma incidence was 70.6% (24/34 mice) after 15 cycles of DSS treatment (1 DSS cycle=7 day DSS treatment period followed by a 10 day recovery period). Tumor multiplicity was 1.26+/-1.05 and tumor volume was 21.4+/-5.2 mm3. Adding 1% inositol, tumor incidence was statistically significantly reduced (42%, 9 of 21 mice with tumors), as was tumor multiplicity (0.5+/-0.7) and tumor volume (4.2+/-1.9 mm3). Administration of hexaphosphate inositol noticeably reduced tumor incidence (50%, 12 mice with tumors out of 24 total), tumor multiplicity (0.8+/-0.9) and tumor volume (12.3+/-4.1 mm3); however, the results were not statistically significant (P>0.05). Further mechanistic studies showed that the inhibition of UC-associated carcinogenesis by inositol compounds might relate to their function on the modulation of macrophage mediated inflammation, nitro-oxidative stress and cell proliferation in UC-associated carcinogenesis. This study indicates that inositol compounds may have the potential to serve as preventive agents for chronic inflammation-carcinogenesis.