Obesity, obesities and gastrointestinal cancers.

Obesity has been recognized to be increasing globally and is designated a disease with adverse consequences requiring early detection and appropriate care. In addition to being related to metabolic syndrome disorders such as type 2 diabetes, hypertension, stroke, and premature coronary artery disease. Obesity is also etiologically linked to several cancers. The non-gastrointestinal cancers are breast, uterus, kidneys, ovaries, thyroid, meningioma, and thyroid. Gastrointestinal (GI) cancers are adenocarcinoma of the esophagus, liver, pancreas, gallbladder, and colorectal. The brighter side of the problem is that being overweight and obese and cigarette smoking are mostly preventable causes of cancers. Epidemiology and clinical studies have revealed that obesity is heterogeneous in clinical manifestations. In clinical practice, BMI is calculated by dividing a person's weight in kilograms by the square of the person's height in square meters (kg/m2). A BMI above 30 kg/m2 (defining obesity in many guidelines) is considered obesity. However, obesity is heterogeneous. There are subdivisions for obesity, and not all obesities are equally pathogenic. Adipose tissue, in particular, visceral adipose tissue (VAT), is endocrine and abdominal obesity (a surrogate for VAT) is evaluated by waist-hip measurements or just waist measures. Visceral Obesity, through several hormonal mechanisms, induces a low-grade chronic inflammatory state, insulin resistance, components of metabolic syndrome, and cancers. Metabolically obese, normal-weight (MONW) individuals in several Asian countries may have BMI below normal levels to diagnose obesity but suffer from many obesity-related complications. Conversely, some people have high BMI but are generally healthy with no features of metabolic syndrome. Many clinicians advise weight loss by dieting and exercise to metabolically healthy obese with large body habitus than to individuals with metabolic obesity but normal BMI. The GI cancers (esophagus, pancreas, gallbladder, liver, and colorectal) are individually discussed, emphasizing the incidence, possible pathogenesis, and preventive measures. From 2005 to 2014, most cancers associated with overweight and Obesity increased in the United States, while cancers related to other factors decreased. The standard recommendation is to offer or refer adults with a body mass index (BMI) of 30 or more to intensive, multicomponent behavioral interventions. However, the clinicians have to go beyond. They should critically evaluate BMI with due consideration for ethnicity, body habitus, and other factors that influence the type of obesity and obesity-related risks. In 2001, the Surgeon General's ``Call to Action to Prevent and Decrease Overweight and Obesity'' identified obesity as a critical public health priority for the United States. At government levels reducing obesity requires policy changes that improve the food and physical activity for all. However, implementing some policies with the most significant potential benefit to public health is politically tricky. The primary care physician, as well as subspecialists, should identify overweight and Obesity based on all the variable factors in the diagnosis. The medical community should address the prevention of overweight and Obesity as an essential part of medical care as much as vaccination in preventing infectious diseases at all levels- from childhood, to adolescence, and adults.

Malnutrition in obesity before and after bariatric surgery.

Bariatric surgeries are considered the only effective way of weight loss therapy in morbidly obese patients, i.e. body mass index ≥ 35. However, micronutrient deficiencies and malnutrition are common after most bariatric procedures and thus, pre- and postoperative nutritional assessment and corrections are advised. The present review is presented in an effort to describe in some detail about prevalence, and mechanisms of macro- and micronutrient deficiencies in obese and post-bariatric surgery individuals. We also aimed to summarize the data on screening and supplementation of macro- and micronutrients before and after bariatric surgeries.

Opioid Use Disorder Increases 30-Day Readmission Risk in Inflammatory Bowel Disease Hospitalizations: a Nationwide Matched Analysis.

BACKGROUND AND AIMS: The opioid epidemic has become increasingly concerning, with the ever-increasing prescribing of opioid medications in recent years, especially in inflammatory bowel disease [IBD] patients with chronic pain. We aimed to isolate the effect of opioid use disorder [OUD] on 30-day readmission risk after an IBD-related hospitalization. METHODS: We retrospectively extracted IBD-related adult hospitalizations and 30-day, any-cause, readmissions from the National Readmissions Database [period 2010-2014]. OUD and 30-day readmission trends were calculated. Conventional and exact-matched [EM] logistic regression and time-to-event analyses were conducted among patients who did not undergo surgery during the index hospitalization, to estimate the effect of OUD on 30-day readmission risk. RESULTS: In total, 487 728 cases were identified: 6633 [1.4%] had documented OUD And 308 845 patients [63.3%] had Crohn's disease. Mean age was 44.8 ± 0.1 years, and 54.3% were women. Overall, 30-day readmission rate was 19.4% [n = 94,546], being higher in OUD patients [32.6% vs 19.2%; p < 0.001]. OUD cases have been increasing [1.1% to 1.7%; p-trend < 0.001], while 30-day readmission rates were stable [p-trend = 0.191]. In time-to-event EM analysis, OUD patients were 47% more likely (hazard ratio 1.47; 95% confidence interval [CI]:1.28-1.69; p < 0.001) to be readmitted, on average being readmitted 32% earlier [time ratio 0.68; 95% CI: 0.59-0.78; p < 0.001]. CONCLUSION: OUD prevalence has been increasing in hospitalized IBD patients from 2010 to 2014. On average, one in five patients will be readmitted within 30 days, with up to one in three among the OUD subgroup. OUD is significantly associated with increased 30-day readmission risk in IBD patients and further measures relating to closer post-discharge outpatient follow-up and pain management should be considered to minimize 30-day readmission risk.

Opioid use disorder in admissions for acute exacerbations of chronic pancreatitis and 30-day readmission risk: A nationwide matched analysis.

BACKGROUND: The opioid epidemic in the United States has been on the rise. Acute exacerbations of chronic pancreatitis (AECP) patients are at higher risk for Opioid Use Disorder (OUD). Evidence on OUD's impact on healthcare utilization, especially hospital re-admissions is scarce. We measured the impact of OUD on 30-day readmissions, in patients admitted with AECP from 2010 to 2014. METHODS: This is a retrospective cohort study which included patients with concurrently documented CP and acute pancreatitis as first two diagnoses, from the National Readmissions Database (NRD). Pancreatic cancer patients and those who left against medical advice were excluded. We compared the 30-day readmission risk between OUD-vs.-non-OUD, while adjusting for other confounders, using multivariable exact-matched [(EM); 18 confounders; n = 28,389] and non-EM regression/time-to-event analyses. RESULTS: 189,585 patients were identified. 6589 (3.5%) had OUD. Mean age was 48.7 years and 57.5% were men. Length-of-stay (4.4 vs 3.9 days) and mean index hospitalization costs ($10,251 vs. $9174) were significantly higher in OUD-compared to non-OUD-patients (p < 0.001). The overall mean 30-day readmission rate was 27.3% (n = 51,806; 35.3% in OUD vs. 27.0% in non-OUD; p < 0.001). OUD patients were 25% more likely to be re-admitted during a 30-day period (EM-HR: 1.25; 95%CI: 1.16-1.36; p < 0.001), Majority of readmissions were pancreas-related (60%), especially AP. OUD cases' aggregate readmissions costs were $23.3 ± 1.5 million USD (n = 2289). CONCLUSION: OUD contributes significantly to increased readmission risk in patients with AECP, with significant downstream healthcare costs. Measures against OUD in these patients, such as alternative pain-control therapies, may potentially alleviate such increase in health-care resource utilization.

Hepatocellular carcinoma is leading in cancer-related disease burden among hospitalized baby boomers.

INTRODUCTION AND OBJECTIVES: Three fourths of chronic hepatitis C virus (HCV) infected adult patients in the United States (US) are born between 1945 and 1965, also known as baby boomers (BB). Prevalence of hepatocellular carcinoma (HCC) is raising in BB due to their advancing age and prolonged HCV infection. We evaluated inpatient hospitalization and mortality in BB associated with HCC. MATERIALS AND METHODS: It is a retrospective cohort study utilizing the Healthcare Utilization Project-National Inpatient Sample (HCUP-NIS) database. From 2003 to 2012, top five primary cancer related hospitalization and mortality among BB were studied. RESULTS: Among 48,733 hospitalizations related to HCC in HCUP-NIS database from 2003 to 2012, BB accounted for 49.6% (24,210) whereas non-BB 50.4% (24,523). Within BB cohort, the top five cancers with the highest proportion of hospitalizations were HCC (46%), prostate (43%), kidney (41%), pancreas (33%), and bladder (21%). From 2003 to 2012, the proportion of HCC related hospitalizations represented by BB almost doubled (33.5 to 57.8%) whereas there was one-third reduction (66.4 to 42.1%) among non-BB. Similarly, HCC-related inpatient mortality in BB decreased by 28% (6.1 to 2.7 per 100,000 hospitalization) but it remained unchanged in non-BB (11.1 to 10.6). HCC accounted for 2nd highest mortality (4960 total deaths) among hospitalized BB behind pancreatic cancer. HCC related to HCV was disproportionately higher in BB compared to non-BB (50.6% vs. 19%; P<0.001). CONCLUSION: HCC ranks number one among the top five cancers with highest proportion of inpatient burden. Future studies should focus on understanding the underlying reasons for this ominous trend.

Beyond O&P Times Three.

Although examination of the stool for ova and parasites times three (O&P ×3) is routinely performed in the United States (US) for the evaluation of persistent and/or chronic diarrhea, the result is almost always negative. This has contributed to the perception that parasitic diseases are nearly non-existent in the country unless there is a history of travel to an endemic area. The increasing number of immigrants from third-world countries, tourists, and students who present with symptoms of parasitic diseases are often misdiagnosed as having irritable bowel syndrome or inflammatory bowel disease. The consequences of such misdiagnosis need no explanation. However, certain parasitic diseases are endemic to the US and other developed nations and affect both immunocompetent and immunocompromised patients. Testing for parasitic diseases either with O&P or with other diagnostic tests, followed by the recommended treatment, is quite rewarding when appropriate. Most parasitic diseases are easily treatable and should not be confused with other chronic gastrointestinal (GI) disorders. In this review, we critically evaluate the symptomatology of luminal parasitic diseases, their differential diagnoses, appropriate diagnostic tests, and management.

Improved Outcomes Following Hepatocellular Carcinoma (HCC) Diagnosis in Patients Screened for HCC in a Large Academic Liver Center versus Patients Identified in the Community.

Background and Aims: Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer worldwide. Knowledge and adherence to HCC surveillance guidelines has been associated with earlier detection. We sought to evaluate characteristics and outcomes following HCC diagnosis in patients screened for HCC in a large academic liver center versus patients diagnosed and referred from the community. Methods: We reviewed the records of patients diagnosed with HCC in the liver center of an academic institution from January 1999 till December 2013. Patients were classified into two groups: patients followed in our hepatology clinic and patients with HCC recently referred to our center. Univariate analysis was performed using chi-squared test and multivariate analysis was performed using SPSS 22.0. Results: The records of 410 patients were reviewed, and included 77.3% of patients referred from the community and 22.7% of patients followed in our clinic. In the clinic group, 75.6% were identified with one nodule at initial diagnosis, compared to 65.6% in the referral group. Patients in the referral group were more likely to present with tumors ≥5 cm at diagnosis, with 28.7% compared to 5.4% in the clinic group (p < 0.0001). Patients referred from the community were also less likely to undergo transplant, with 32.2% as compared to 48.4% of the clinic group (p < 0.004). Conclusion: Patients with chronic liver disease managed in an academic liver center present in the early stage of HCC diagnosis and are more likely to meet the Milan criteria and undergo transplant. Early referral to a specialized transplant center, if feasible, where a multidisciplinary approach is utilized might be essential in the management of chronic liver disease.

Spectrum of Drug-induced Chronic Diarrhea.

The evaluation of a patient with chronic diarrhea can be quite frustrating, as it is expensive and involves multiple diagnostic studies. Moreover, identification of a drug as a cause of chronic diarrhea is a challenge in patients taking multiple medications. The disease may either be associated with intestinal mucosal changes, mimicking diseases such as celiac disease, or purely functional, with no histopathologic change. Drug-induced diarrhea may or may not be associated with malabsorption of nutrients, and a clinical improvement may occur within days of discontinuation of the drug, or may take longer when associated with mucosal injury. Diarrhea in diabetics, often attributed to poor management and lack of control, may be due to oral hypoglycaemic agents. Chemotherapy can result in diffuse or segmental colitis, whereas olmesartan and a few other medications infrequently induce a disease that mimics celiac disease, but is not associated with gluten intolerance. In short, increased awareness of a drug, as a cause for diarrhea and a clear understanding of the clinical manifestations will help clinicians to solve this challenging problem. This article aims to review drug-induced diarrhea to (a) understand known pathophysiological mechanisms; (b) assess the risk associated with frequently prescribed medications, and discuss the pathogenesis; and

Nonalcoholic Fatty Liver Disease and Mean Platelet Volume: A Systemic Review and Meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity, metabolic syndrome, and cardiovascular disease. Increased mean platelet volume (MPV), a marker of platelet activity, is associated with acute myocardial infarction, stroke, thrombosis, and increased mortality after myocardial infarction. The purpose of this study was to perform a meta-analysis to investigate the relationship between NAFLD and MPV. METHODOLOGY: A systematic search of MEDLINE (Ovid), PubMed, and CINAHL databases from 1950 to May 2014, complemented with manual review of references of published articles for studies comparing MPV in patients with and without NAFLD was done. Results were pooled using both fixed and random effects model. RESULTS: Our analysis from pooling of data from 8 observational studies including 1428 subjects (NAFLD=842 and non-NAFLD=586) showed that MPV was significantly higher in patients with NAFLD than those without. The standardized mean difference in MPV between NAFLD and controls was 0.457 (95% confidence interval: 0.348-0.565, P<0.001) using fixed and 0.612 (95% confidence interval: 0.286-0.938, P<0.001) using random effects model. CONCLUSIONS: This study suggests that MPV is significantly higher in patients with NAFLD, indicating the presence of increased platelet activity in such patients. Future research is needed to investigate whether this increased MPV is associated with increased cardiovascular disease in patients with NAFLD.

PANCREATITIS OR NOT?--Elevated lipase and amylase in ICU patients.

Elevation in serum levels of pancreatic enzymes (Hyperamylasemia and/or Hyperlipasemia) can occur in any Intensive Care Unit (ICU) patient either as a result of true acute pancreatitis (AP) or as a reflection of a non-pancreatic disease. Although most patients may not have clinical pancreatitis, identifying true acute pancreatitis in the ICU setting may be critical in the presence of associated co-morbid conditions of the disease for which the patient is being managed. With neither amylase nor lipase being specific for pancreatitis, it is important for the clinician to be aware of different causes of hyperamylasemia and hyperlipasemia, especially when clinical diagnosis of pancreatitis is unclear. This review will focus on understanding different non-pancreatic conditions where there is elevation of pancreatitis enzymes and to identify true acute pancreatitis in critically ill patients without typical symptoms.

Nonalcoholic fatty liver disease and carotid artery atherosclerosis in children and adults: a meta-analysis.

Observational studies suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased carotid intimal medial thickness (C-IMT) and carotid plaques in both children and adults. We carried out a meta-analysis to evaluate the relationship between NAFLD and carotid atherosclerosis measured as C-IMT and carotid plaque prevalence. Medline (Ovid), PubMed, Web of Science, and CINAHL databases were searched from 1946 to September 2014, complemented with a manual review of references of the published articles for studies that compared C-IMT or carotid plaque prevalence in adults and children. Results were pooled using both fixed and random effects models. Of the studies identified, 20 were suitable for testing the effect of NAFLD on C-IMT in adults, 13 for testing the effect of NAFLD on carotid plaque prevalence in adults, and five for testing the effect of NAFLD on C-IMT in the pediatric population. The pooled data from 20 studies (19,274 adult participants: NAFLD=8652, controls=10,622) showed significantly increased C-IMT in patients with NAFLD, compared with controls without NAFLD, according to both fixed [standardized mean difference (SMD)=0.251, 95% confidence interval (CI): 0.220-0.282, P<0.001] and random effects models (SMD=0.944, 95% CI: 0.728-1.160, P<0.001). NAFLD was also found to be associated with a higher carotid artery plaque prevalence when compared with controls, according to both fixed (OR=1.273, 95% CI=1.162-1.394, P<0.001) and random effects models (OR=1.769, 95% CI: 1.213-2.581, P=0.003), on pooling of 13 studies (14,445 adult participants: NAFLD=5399 and controls=9046). Analysis of pooled data from five studies in the pediatric population (1121 pediatric participants: NAFLD=312 and controls=809) also found NAFLD to be associated with significantly increased C-IMT according to fixed (SMD=0.995, 95% CI: 0.840-1.150, P<0.001) and random effects models (1.083, 95% CI: 0.457-1.709, P=0.001). NAFLD is associated with increased C-IMT in both children and adults, and with increased carotid plaque prevalence in adults. Individuals identified with carotid disease should be evaluated for NAFLD and vice versa.

Musculoskeletal manifestations in inflammatory bowel disease: a revisit in search of immunopathophysiological mechanisms.

Inflammatory bowel diseases are chronic inflammatory disorders of multiple organ systems, primarily involving the gut, with chronic relapsing and remitting course. Musculoskeletal involvement is the most common extraintestinal manifestation. Distinct cell-mediated and humoral immunopathophysiological mechanisms have been identified underlying gut and joint inflammation in patients with inflammatory bowel disease and arthritis. Genetic polymorphisms in genes coding for NOD2 and IL12/IL23 complex lead to impaired antigenic handling in the gut and local immune dysregulation. The gut-synovial axis hypothesis implicates both environmental and host factors acting as triggers to initiate inflammation in genetically predisposed individuals, leading to priming of Th1 and Th17 lymphocytes in the gut and subsequent homing to the synovial tissue. Similar to gut, antibody-dependent cell-mediated cytotoxicity and complement-mediated cell lysis may also contribute to the joint damage. Involvement of peripheral joints occurs in 2 distinct manners, one being oligoarticular asymmetric arthritis associated with active disease and the other being polyarticular symmetric involvement of small joints. The axial involvement may include asymptomatic sacroiliitis, inflammatory back pain, and ankylosing spondylitis, running an independent clinical course. Noninflammatory involvement of the musculoskeletal system may present as osteopenia, osteonecrosis, fibromyalgia, or myopathies, leading to significant impact on quality of life.

Secular trends of fibrocalculous pancreatic diabetes and diabetes secondary to alcoholic chronic pancreatitis at a tertiary care diabetes centre in South India.

CONTEXT: Data on prevalence and trends in diabetes secondary to chronic pancreatitis in developing countries is scarce. OBJECTIVE: To compare the secular trends in the prevalence of fibrocalculous pancreatic diabetes (FCPD) and diabetes secondary to alcoholic chronic pancreatitis (ACP) at a diabetes centre in south India. DESIGN: A retrospective analysis was done of all patients registered at Dr. Mohan's Diabetes Specialties Centre, Chennai, India between January 1991 and December 2010. PATIENTS: A total of 1,079 subjects with diabetes secondary to chronic pancreatitis were identified, of whom 47 were excluded because of difficulty in classification. MAIN OUTCOME MEASURE: The number of patients with FCPD and diabetes secondary to ACP were calculated as a percentage of the total number of diabetes patients seen at the centre during five year blocks. RESULTS: Of the total of 1,032 cases of diabetes secondary to chronic pancreatitis, FCPD comprised 898 (87%) and ACP 134 (13%). The prevalence of FCPD decreased from 1.6% during 1991-1995 to 0.2% during 2006-2010 (P<0.001). The prevalence of ACP remained constant at 0.1%. The age at diagnosis of FCPD increased (P=0.002) while that of ACP decreased (P=0.025) during the study period. There was a significant increase in BMI of FCPD P<0.001), but not of ACP (P=0.248) patients. CONCLUSIONS: At this centre, FCPD continues to be more common than ACP, but there is a decline in its frequency. The age at diagnosis of FCPD has increased, while that of ACP has decreased. The decline in FCPD probably reflects improved nutrition.

The complex exocrine-endocrine relationship and secondary diabetes in exocrine pancreatic disorders.

The pancreas is a dual organ with exocrine and endocrine functions. The interrelationship of the endocrine-exocrine parts of the pancreas is a complex one, but recent clinical and experimental studies have expanded our knowledge. Many disorders primarily of the exocrine pancreas, often solely in the clinical realm of gastroenterologists are associated with diabetes mellitus (DM). Although, the DM becoming disorders are often grouped with type 2 diabetes, the pathogenesis, clinical manifestations and management differ. We review here data on the association of exocrine-endocrine pancreas, the many hormones of the pancreas and their possible effects on the exocrine functions followed by data on the epidemiology, pathogenesis, and management of DM in chronic pancreatitis, cystic fibrosis, pancreatic cancer, and clinical states after pancreatic surgery.

Acute pancreatitis in pregnancy.

Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10,000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations influence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated with greater concerns as it deals with two lives rather than just one as in the non-pregnant population. The recent advances in clinical gastroenterology have improved the early diagnosis and effective management of biliary pancreatitis. Diagnostic studies such as endoscopic ultrasound, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography and therapeutic modalities that include endoscopic sphincterotomy, biliary stenting, common bile duct stone extraction and laparoscopic cholecystectomy are major milestones in gastroenterology. When properly managed AP in pregnancy does not carry a dismal prognosis as in the past.