The Association of Lactose Intolerance With Colon and Gastric Cancers: Friend or Foe?

BACKGROUND: Lactose intolerance (LI) appears usually in later ages when the lactase enzyme becomes deficient or absent in the small intestine. Conflicting results have been reported in the literature about the association of lactose intolerance with various gastrointestinal malignancies. Hence, our aim was to study the association between LI, colon cancer (CCa), and gastric cancer (GC) using a large database. METHODS: A cross-sectional study was performed using the National Inpatient Sample (NIS) database between 2004 and 2014. We identified adult patients (18-90 years) who were diagnosed with LI (study group) using appropriate International Classification of Diseases, Ninth Revision (ICD-9) codes. The control group comprised patients who did not have a diagnosis of LI. We identified the diagnosis of CCa and GC in both study and control groups using the ICD-9 codes. Univariable and multivariable logistic regression analyses were performed to assess the association between LI, CCa, and GC. RESULTS: The total population comprised 71,360,501 patients, of which 57,909 (0.08%) were diagnosed with LI. LI patients were older (62 vs 51 years) with more females (61.5% vs 60.1%) and less African American patients (11.8% vs 14.3%) (p <0.0001 for all). In addition, LI patients had more smoking (12.4% vs 12%) and obesity (15% vs 8.9%). On the other hand, patients in the LI group had less alcohol use (3.8% vs 4.2%) (p <0.0001). After adjusting for the age, gender, race, smoking, alcohol, obesity, and inflammatory bowel disease, the LI group had a slightly lower rate of CCa (OR 0 .974, 95%CI 0.906-1.048, p = 0.486) and a lower rate of GC (OR: 0.993, 95%CI 0.924-1.068, p =0.853); however, the results were not statistically significant. CONCLUSION: Patients with lactose intolerance may have a lower risk of colon and gastric cancer. However, these findings were not statistically significant. Further studies are needed to understand this association.

The Off-Label Use of a Lumen-Apposing Metal Stent (LAMS) for a Benign Colon Anastomotic Stricture Causing Recurrent Bowel Obstruction in a Patient with Keloids.

Anastomotic strictures are a known complication of colorectal surgery. Despite a wide range of medical devices that have been deployed for this complication, outcomes remain challenging. Lumen-apposing metal stents (LAMSs) have recently emerged as a potentially superior therapeutic option. We herein report a patient with a past medical history of pT3, N0 adenocarcinoma of the colon with anastomotic stricture recurrence who underwent successful placement of an LAMS. We suggest that patients with a predisposition for keloid formation or fibrosis-prone anastomotic wound healing should be considered for LAMS deployment early in the treatment course.

Association between Inflammatory Bowel Disease and Lactose Intolerance: Fact or Fiction.

Background/Aims: Inflammatory bowel disease (IBD) is a complex condition precipitated by genetic susceptibility and possibly a disturbed microbiome. The role of dairy foods in IBD is controversial. This study examined the association between lactose intolerance (LI) and IBD. Methods: Data on hospital admissions of all IBD adult patients were extracted from the National Inpatient Sample database between 2004 and 2014. The comorbidities and outcomes of interest were defined by querying all the diagnostic and procedural fields for the corresponding International Classification of Diseases 9th version (ICD-9) codes. Patients with IBD were defined as the "study group," and the patients who did not have IBD were defined as the "control group". LI was identified in both groups using the ICD-9 codes. Multivariate logistic regression was performed to examine the association between IBD and LI. Results: The total population was 71,342,237 patients, of which 598,129 (0.83%) had IBD. The IBD patients were younger (52 years vs. 57 years) and with fewer females (57.5% vs. 60.1%) (p<0.001 for all). After adjusting for the potential confounding factors, the IBD group had a significantly higher rate of LI (OR 2.71, 95% CI 2.55-2.88, p<0.001) compared to the non-IBD group. The findings were similar on the further stratification of IBD into Crohn's disease compared to the control group (OR 2.70, 95% CI 2.50-2.92, p<0.001) and ulcerative colitis compared to the control group (OR 2.71, 95% CI 2.46-2.98, p<0.001). Conclusions: IBD patients have a 2.7 times higher risk of LI. Screening for LI in this population is warranted to avoid confusing or overlapping symptomatology.

A multi-institution consensus on how to perform EUS-guided biliary drainage for malignant biliary obstruction.

BACKGROUND AND OBJECTIVES: EUS-guided biliary drainage (EUS-BD) was shown to be useful for malignant biliary obstruction (MBO). However, there is lack of consensus on how EUS-BD should be performed. METHODS: This was a worldwide multi-institutional survey among members of the International Society of EUS conducted in February 2018. The survey consisted of 10 questions related to the practice of EUS-BD. RESULTS: Forty-six endoscopists of them completed the survey. The majority of endoscopists felt that EUS-BD could replace percutaneous transhepatic biliary drainage after failure of ERCP. Among all EUS-BD methods, the rendezvous stenting technique should be the first choice. Self-expandable metal stents (SEMSs) were recommended by most endoscopists. For EUS-guided hepaticogastrostomy (HGS), superiority of partially-covered SEMS over fully-covered SEMS was not in agreement. 6-Fr cystotomes were recommended for fistula creation. During the HGS approach, longer SEMS (8 or 10 cm) was recommended. During the choledochoduodenostomy approach, 6-cm SEMS was recommended. During the intrahepatic (IH) approach, the IH segment 3 was recommended. CONCLUSION: This is the first worldwide survey on the practice of EUS-BD for MBO. There were wide variations in practice, and randomized studies are urgently needed to establish the best approach for the management of this condition.

Cyclic-GMP-Elevating Agents Suppress Polyposis in ApcMin mice by Targeting the Preneoplastic Epithelium.

The cGMP signaling axis has been implicated in the suppression of intestinal cancers, but the inhibitory mechanism and the extent to which this pathway can be targeted remains poorly understood. This study has tested the effect of cGMP-elevating agents on tumorigenesis in the ApcMin/+ mouse model of intestinal cancer. Treatment of ApcMin/+ mice with the receptor guanylyl-cyclase C (GCC) agonist linaclotide, or the phosphodiesterase-5 (PDE5) inhibitor sildenafil, significantly reduced the number of polyps per mouse (67% and 50%, respectively). Neither of the drugs affected mean polyp size, or the rates of apoptosis and proliferation. This was possibly due to increased PDE10 expression, as endogenous GCC ligands were not deficient in established polyps. These results indicated that the ability of these drugs to reduce polyp multiplicity was primarily due to an effect on nonneoplastic tissues. In support of this idea, ApcMin/+ mice exhibited reduced levels of endogenous GCC agonists in the nonneoplastic intestinal mucosa compared with wild-type animals, and this was associated with crypt hyperplasia and a loss of goblet cells. Administration of either sildenafil or linaclotide suppressed proliferation, and increased both goblet cell numbers and luminal apoptosis in the intestinal mucosa. Taken together, the results demonstrate that targeting cGMP with either PDE5 inhibitors or GCC agonists alters epithelial homeostasis in a manner that reduces neoplasia, and suggests that this could be a viable chemoprevention strategy for patients at high risk of developing colorectal cancer. Cancer Prev Res; 11(2); 81-92. ©2018 AACR.

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis.

OBJECTIVES: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN). METHODS: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence. RESULTS: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one. CONCLUSIONS: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

Sildenafil Suppresses Inflammation-Driven Colorectal Cancer in Mice.

Intestinal cyclic guanosine monophosphate (cGMP) signaling regulates epithelial homeostasis and has been implicated in the suppression of colitis and colon cancer. In this study, we investigated the cGMP-elevating ability of the phosphodiesterase-5 (PDE5) inhibitor sildenafil to prevent disease in the azoxymethane/dextran sulfate sodium (AOM/DSS) inflammation-driven colorectal cancer model. Treatment of mice with sildenafil activated cGMP signaling in the colon mucosa and protected against dextran-sulfate sodium (DSS)-induced barrier dysfunction. In mice treated with AOM/DSS, oral administration of sildenafil throughout the disease course reduced polyp multiplicity by 50% compared with untreated controls. Polyps that did form in sildenafil treated mice were less proliferative and more differentiated compared with polyps from untreated mice, but apoptosis was unaffected. Polyps in sildenafil treated mice were also less inflamed; they exhibited reduced myeloid-cell infiltration and reduced expression of iNOS, IFNγ, and IL6 compared with untreated controls. Most of the protection conferred by sildenafil was during the initiation stage of carcinogenesis (38% reduction in multiplicity). Administration of sildenafil during the later promotion stages did not affect multiplicity but had a similar effect on the polyp phenotype, including increased mucus production, and reduced proliferation and inflammation. In summary, the results demonstrate that oral administration of sildenafil suppresses polyp formation and inflammation in mice treated with AOM/DSS. This validation of PDE5 as a target highlights the potential therapeutic value of PDE5 inhibitors for the prevention of colitis-driven colon cancer in humans. Cancer Prev Res; 10(7); 377-88. ©2017 AACRSee related editorial by Piazza, p. 373.

Sildenafil normalizes bowel transit in preclinical models of constipation.

Guanylyl cyclase-C (GC-C) agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation. Oral administration of sildenafil caused increased cGMP levels in mouse intestinal epithelium demonstrating that blocking cGMP-breakdown is an alternative approach to increase cGMP in the gut. Both linaclotide and sildenafil reduced proliferation and increased differentiation in colon mucosa, indicating common target pathways. The homeostatic effects of cGMP required gut turnover since maximal effects were observed after 3 days of treatment. Neither linaclotide nor sildenafil treatment affected intestinal transit or water content of fecal pellets in healthy mice. To test the effectiveness of cGMP elevation in a functional motility disorder model, mice were treated with dextran sulfate sodium (DSS) to induce colitis and were allowed to recover for several weeks. The recovered animals exhibited slower transit, but increased fecal water content. An acute dose of sildenafil was able to normalize transit and fecal water content in the DSS-recovery animal model, and also in loperamide-induced constipation. The higher fecal water content in the recovered animals was due to a compromised epithelial barrier, which was normalized by sildenafil treatment. Taken together our results show that sildenafil can have similar effects as linaclotide on the intestine, and may have therapeutic benefit to patients with CIC, IBS-C, and post-infectious IBS.

cGMP Signaling Increases Antioxidant Gene Expression by Activating Forkhead Box O3A in the Colon Epithelium.

Signaling through cGMP has therapeutic potential in the colon, where it has been implicated in the suppression of colitis and colon cancer. In this study, we tested the ability of cGMP and type 2 cGMP-dependent protein kinase (PKG2) to activate forkhead box O (FoxO) in colon cancer cells and in the colon epithelium of mice. We show that activation of PKG2 in colon cancer cells inhibited cell proliferation, inhibited AKT, and activated FoxO. Treatment of colon explants with 8Br-cGMP also activated FoxO target gene expression at both RNA and protein levels, and reduced epithelial reduction-oxidation (redox) stress. FoxO3a was the most prominent isoform in the distal colon epithelium, with prominent luminal staining. FoxO3a levels were reduced in Prkg2-/- animals, and FoxO target genes were unaffected by 8Br-cGMP challenge in vitro. Treatment of mice with the phosphodiesterase-5 inhibitor vardenafil (Levitra) mobilized FoxO3a to the nucleus of luminal epithelial cells, which corresponded to increased FoxO target gene expression, reduced redox stress, and increased epithelial barrier integrity. Treatment of human colonic biopsy specimens with 8Br-cGMP also activated catalase and manganese superoxide dismutase expression, indicating that this pathway is conserved in humans. Taken together, these results identify a novel signaling pathway in the colon epithelium, where FoxO tumor suppressors could provide protection from redox stress. Moreover, this pathway is regulated by endogenous cGMP/PKG2 signaling, and can be targeted using phosphodiesterase-5 inhibitors.

Liver abscess and bacteremia caused by lactobacillus: role of probiotics? Case report and review of the literature.

BACKGROUND: Lactobacilli are non-spore forming, lactic acid producing, gram-positive rods. They are a part of the normal gastrointestinal and genitourinary microbiota and have rarely been reported to be the cause of infections. Lactobacilli species are considered non-pathogenic organisms and have been used as probiotics to prevent antibiotic associated diarrhea. There are sporadic reported cases of infections related to lactobacilli containing probiotics. CASE PRESENTATION: In this paper we discuss a case of an 82 year old female with liver abscess and bacteremia from lactobacillus after using probiotics containing lactobacilli in the course of her treatment of Clostridium difficile colitis. The Lactobacillus strain identification was not performed and therefore, both commensal microbiota and the probiotic product should be considered as possible sources of the strain. CONCLUSION: Lactobacilli can lead to bacteremia and liver abscesses in some susceptible persons and greater awareness of this potential side effect is warranted with the increasing use of probiotics containing lactobacilli.

Risk of Gastrointestinal Bleeding with Rivaroxaban: A Comparative Study with Warfarin.

Introduction. The risk of gastrointestinal (GI) bleeding with rivaroxaban has not been studied extensively. The aim of our study was to assess this risk in comparison to warfarin. Methods. We examined the medical records for patients who were started on rivaroxaban or warfarin from April 2011 to April 2013. Results. We identified 300 patients (147 on rivaroxaban versus 153 on warfarin). GI bleeding occurred in 4.8% patients with rivaroxaban when compared to 9.8% patients in warfarin group (p = 0.094). GI bleeding occurred in 8% with therapeutic doses of rivaroxaban (>10 mg/d) compared to 9.8% with warfarin (p = 0.65). Multivariate analysis showed that patients who were on rivaroxaban for ≤40 days had a higher incidence of GI bleeding than those who were on it for >40 days (OR = 2.8, p = 0.023). Concomitant use of dual antiplatelet agents was associated with increased risk of GI bleeding in the rivaroxaban group (OR = 7.4, p = 0.0378). Prior GI bleeding was also a risk factor for GI bleeding in rivaroxaban group (OR = 15.5). Conclusion. The incidence of GI bleeding was similar between rivaroxaban and warfarin. The risk factors for GI bleeding with rivaroxaban were the first 40 days of taking the drug, concomitant dual antiplatelet agents, and prior GI bleeding.

Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes.

Dyslipidemia associated with triglyceride-rich lipoproteins (TRLs) represents an important residual risk factor for cardiovascular and chronic kidney disease in patients with type 1 diabetes (T1D). Levels of growth hormone (GH) are elevated in T1D, which aggravates both hyperglycemia and dyslipidemia. The hypothalamic growth hormone-releasing hormone (GHRH) regulates the release of GH by the pituitary but also exerts separate actions on peripheral GHRH receptors, the functional role of which remains elusive in T1D. In a rat model of streptozotocin (STZ)-induced T1D, GHRH receptor expression was found to be up-regulated in the distal small intestine, a tissue involved in chylomicron synthesis. Treatment of T1D rats with a GHRH antagonist, MIA-602, at a dose that did not affect plasma GH levels, significantly reduced TRL, as well as markers of renal injury, and improved endothelial-dependent vasorelaxation. Glucagon-like peptide 1 (GLP-1) reduces hyperglucagonemia and postprandial TRL, the latter in part through a decreased synthesis of apolipoprotein B-48 (ApoB-48) by intestinal cells. Although plasma GLP-1 levels were elevated in diabetic animals, this was accompanied by increased rather than reduced glucagon levels, suggesting impaired GLP-1 signaling. Treatment with MIA-602 normalized GLP-1 and glucagon to control levels in T1D rats. MIA-602 also decreased secretion of ApoB-48 from rat intestinal epithelial cells in response to oleic acid stimulation in vitro, in part through a GLP-1-dependent mechanism. Our findings support the hypothesis that antagonizing the signaling of GHRH in T1D may improve GLP-1 function in the small intestine, which, in turn, diminishes TRL and reduces renal and vascular complications.

Comparison of Ischemic Colitis in the Young and the Elderly.

BACKGROUND: Ischemic colitis is traditionally known as a disease of the elderly; however, its recognition among the young recently has increased. The aim of this study was to illustrate the features of ischemic colitis in a younger population. METHODS: Medical records of patients with ischemic colitis from January 2007 to January 2013 were reviewed. The study was conducted in 2 hospitals, and the patients were divided into 2 groups: < 50 and ≥ 50 years old. RESULTS: A total of 118 patients with ischemic colitis were identified. Fifteen patients (12.7%) were < 50 years of age; 103 patients (87.3%) were ≥ 50 years old. While drugs and vasculitis­as a group­was the most common precipitating factor for ischemic colitis in the younger age group, constipation was the most common precipitating factor in the older age group. All patients in the younger group had rectal bleeding vs 70.9% in the older group (P = 0.009). History of coronary artery disease, dyslipidemia, and hypertension were higher in the older group. Length of hospital stay was shorter in the younger group (3.4 days) than the older group (7.2 days). CONCLUSION: In this study, 12.7% of the patients were under age 50. All patients in this "young" age group experienced rectal bleeding and their hospital stay was shorter.

Gastrointestinal bleeding with dabigatran, a comparative study with warfarin: a multicenter experience.

BACKGROUND/AIMS: The risk of gastrointestinal (GI) bleeding with dabigatran when compared to warfarin has been controversial in the literature. The aim of our study was to assess this risk with the use of dabigatran. METHODS: We examined the medical records of patients who were started on dabigatran or warfarin from October 2010 to October 2012. The study was conducted in two hospitals. RESULTS: A total of 417 patients were included (208 dabigatran vs. 209 warfarin). GI bleeding occurred in 10 patients (4.8%) in the dabigatran group compared to 21 patients (10.1%) in the warfarin group (p=0.0375). Multivariate analysis showed that patients who were on dabigatran for ≤ 100 days had a higher incidence of GI bleeding than those who were on it for >100 days (p=0.0007). The odds of GI bleeding in patients who were on dabigatran for ≤ 100 days was 8.2 times higher compared to those who were on the drug for >100 days. The incidence of GI bleeding in patients >65 years old was higher than in those <65 years old (p=0.0453, OR=3). History of previous GI bleeding was another risk factor for GI bleeding in the dabigatran group (p=0.036, OR=6.3). The lower GI tract was the most common site for GI bleeding in the dabigatran group (80.0% vs. 38.1%, p=0.014). CONCLUSIONS: The risk of GI bleeding was lower with dabigatran. The risk factors for GI bleeding with dabigatran were the first 100 days, age >65 years, and a history of previous GI bleeding.

Risk of gastrointestinal bleeding with dabigatran: a head-to-head comparative study with rivaroxaban.

INTRODUCTION: The risk of gastrointestinal (GI) bleeding of dabigatran and rivaroxaban is relatively unexplored. The aim of our study was to compare this risk in both drugs. METHODS: We examined the medical records of patients on either dabigatran or rivaroxaban from October 2010 to April 2013 in two hospitals. RESULTS: A total of 374 patients (147 rivaroxaban vs. 227 dabigatran) were identified. GI bleeding occurred in 5.3% in the dabigatran when compared to 4.8% in the rivaroxaban group (p = 0.8215). Multivariate analysis showed that the odds of GI bleeding while on dabigatran for ≤40 days when compared to ≥40 days was 8.3 (p < 0.0001). In the rivaroxaban group, patients who were on the drug for ≤40 days had a higher incidence of bleeding when compared to those >40 days (OR = 2.8, p = 0.023). Concomitant use of antiplatelets (single or dual) or non-steroidal anti-inflammatory drugs was not associated with increased bleeding in the dabigatran group; however, the use of dual antiplatelet agents with rivaroxaban was associated with an increased risk of GI bleeding (OR = 7.4, p = 0.0378). Prior GI bleeding had a higher risk of bleeding in the rivaroxaban group (OR = 15.5, p = 0.0002). CONCLUSION: Dabigatran was not associated with a higher incidence of GI bleeding. Both drugs had a higher bleeding risk in the first 40 days.

Ischemic colitis: A forgotten entity. Results of a retrospective study in 118 patients.

OBJECTIVE: The aim of our study was to document our 6-year experiences in identifying the clinical characteristics, laboratory findings, risk factors and the outcomes of patients with ischemic colitis (IC) in a community hospital setting. METHODS: The medical records of patients who were diagnosed with IC from 2007 to 2013 in two community hospitals were retrospectively reviewed. Their clinical characteristics, laboratory results, radiological, endoscopic and histological evidence, anatomic location of the lesion, comorbidities, concomitant use of drugs, and so on, were collected. RESULTS: A total of 118 patients with IC was identified, most were elderly individuals with a female predominance. The most common symptoms were abdominal pain, rectal bleeding and diarrhea. Hypertension, hyperlipidemia, coronary artery disease and diabetes mellitus were the most common comorbidities. Erythema, edema and erosions/ulcerations were the most common endoscopic findings. Left colon was the most affected location of lesion (84.8%), and there was one case of pancolitis. The descending colon was the most common affected segment, while rectum was the least affected segment. Severe IC occurred in 12.7% of the patients. Death within 30 days from the diagnosis of the disease occurred in 4.2%. CONCLUSIONS: IC is majorly occurred in elderly with a female predominance. Cardiovascular disease and its associated risk factors are the most common comorbidities. Left colon is the most affected location of the disease and the overall mortality rate was 4.2%. Physicians should make every effort to identify these patients, especially those with high risks.

Risk factors of recurrent ischemic colitis: a multicenter retrospective study.

BACKGROUND/AIMS: Recurrence of ischemic colitis (IC) has not been studied extensively. The aim of this study was to investigate the characteristics of recurrent IC in the community setting and to identify any risk factors. METHODS: We conducted a retrospective study in two community hospitals. Medical records of patients with IC from January 2007 to January 2013 were reviewed. Demographic details, clinical features, co- morbidities, concomitant use of medications,laboratory studies, imaging findings, endoscopic and histological features, surgery, hospital stay, and death within 30 days were collected. Patients were divided into two groups (recurrent IC group, non-recurrent IC group). RESULTS: A total of 118 patients with IC were identified. IC recurred in 10 patients (8.5%) during the study period. Half of the patients in the recurrent IC group were current smokers as compared to only 18.7% of patients in the non-recurrent group. In the recurrent IC group, 20.0% of patients never smoked as compared to 61.7% in the non-recurrent group (p=0.027).Abdominal aortic aneurysm (AAA) was more frequent in the recurrent IC group (40.0% vs. 4.7%; p=0.003). No differences in other clinical symptoms, CT scan findings, comorbidities, endoscopic features, or use of concomitant medications were observed between the two groups. The need for surgical intervention, blood transfusion, intensive care unit stay, mechanical ventilation,length of hospital stay, and anatomic location of affected segments did not differ between the two groups. CONCLUSIONS: IC recurred in 8.5% of patients during the six-year study period. Current smoking status and presence of AAA were identifying risk factors for recurrence of IC.

Lubiprostone induced ischemic colitis.

Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.