Dispatches From The Guild Conference, Series #13

Routine Health Maintenance and Disease Prevention in Patients with Inflammatory Bowel Disease

June 2018 • Volume XLII, Issue 6
Sean Fine,Adam S. Cheifetz

Read Article

Disease prevention and health maintenance is crucial, however patients with inflammatory bowel disease (IBD) do not receive the same rate of preventative interventions as the general population. This article highlights recommendations regarding health maintenance issues in patients with IBD including vaccinations, screening for colorectal, skin and cervical cancers, screening for osteoporosis and guidance on smoking cessation.

Disease prevention and health maintenance is crucial, however patients with inflammatory bowel disease (IBD) do not receive the same rate of preventative interventions as the general population. Vaccine preventable illnesses affect patients with IBD at a higher rate secondary to chronic illness and immunosuppression, yet many patients with IBD go unvaccinated. A lack of awareness regarding the significance of vaccinations, poor insight about the safety, and ambiguity about the gastroenterologists’ role in providing vaccinations may be contributing factors to the lower vaccination rates. Since patients with IBD often identify their gastroenterologist as their primary care provider, gastroenterologists need to specifically define and help coordinate the unique needs of these patients with other healthcare providers. This article highlights recommendations regarding health maintenance issues in patients with IBD including vaccinations, screening for colorectal, skin and cervical cancers, screening for osteoporosis and guidance on smoking cessation.

Sean Fine, MD, MS, Director, Inflammatory Bowel Disease Center, Alpert Medical School, Brown University, East Providence, RI Adam S. Cheifetz, MD, Director, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Associate Professor of Medicine, Harvard Medical School. Boston, MA

INTRODUCTION

Inflammatory bowel disease is a chronic gastrointestinal disease that includes both ulcerative colitis (UC) and Crohn’s disease (CD). The course of these diseases is characterized by intermittent relapses. Agents used to manage more aggressive disease include corticosteroids, immunomodulators and biologic agents. It is now recognized that patients with IBD are at an increased risk for a number of different health issues that include infections, osteoporosis, depression, skin and colorectal cancers. The importance of health maintenance and prevention has emerged as a crucial objective in the overall delivery of care. Patients with IBD frequently have a strong relationship with their gastroenterologist and often turn to them for primary care needs and questions.1 However, data has shown that patients with IBD get less preventative and health maintenance care than non-IBD patients of the same age.2 This in part may be due to the fact that the gastroenterologists do not feel it is their job as the specialist, and the primary care physicians often feel uncomfortable managing these issues in patients who are often immunocompromised. It is therefore important for both the gastroenterologist and primary care physician to work closely together to ensure these preventive interventions are carried out properly.

Vaccinations

Though patients with IBD are at risk for infectious complications secondary to the disease and immunosuppression from medical therapy, they tend to be under vaccinated.3 The reasons for these low vaccination rates are likely multifactorial. Gastroenterologists have reported a lack of knowledge about the importance of vaccinations in this group of patients.4 Furthermore, gastroenterologist often do not have the vaccines available at their medical practice and feel it is the job of the primary care physician to administer vaccinations. Another barrier to vaccination often raised by patients is the concern of vaccines causing or exacerbating a flare. Fortunately, vaccines have not been shown to lead to flares in patients with underlying rheumatologic diseases or IBD.5,6 Patients with IBD who were given the influenza vaccine were not found to have an increased risk for disease flare within four weeks of its administration.7 Similarly, another study that included 43 patients with IBD on thiopurines did not observe any increase in disease severity attributable to vaccinations.8 Therefore, inactivated vaccinations should not be withheld from patients for the fear of causing a disease flare.

National guidelines for age appropriate vaccinations should be implemented for patients with IBD, with special considerations given to those who are on, or planning to initiate, immunosuppressive therapy. Luckily, most patients in the United States will have received routine childhood vaccinations. For patients who need to begin treatment with immunosuppressive therapy, delaying live vaccines in order to timely start treatment will be necessary.9

All patients with IBD, regardless of immunosuppression, should receive inactivated vaccines (Table 1). The level of immunosuppression will dictate which patients should receive live vaccines. Typically, the level of immunosuppression has been broken down into “low” and “high.” Patients on low-level immunosuppression can safely receive live vaccines while those on high-level should avoid live vaccines. “Low-level” immunosuppression is defined as patients receiving a daily dose of systemic corticosteroids for ≥14 (20mg/day equivalent and within three months of stopping), methotrexate ≤0.4 mg/kg/week and within three months of stopping, azathioprine ≤3.0 mg/kg/day, and 6-mercaptopurine ≤1.5mg/kg/day and within three months of stopping.10 Patients on the typical IBD doses of methotrexate and thiopurines fall into this category. The Infectious Disease Society of America guidelines consider all patients on anti-tumor necrosis factors (anti-TNF) to have high level immunosuppression and should not receive live vaccines. These guidelines were written prior to the availability of vedolizumab and ustekinumab, but avoidance of live vaccines should likely still apply to ustekinumab. And, given the gut selectivity of vedolizumab, oral live vaccines should probably be avoided.

Inactivated Vaccinations
Influenza Vaccination

Influenza infection may result in serious life threatening illness and therefore it is recommended that all immunosuppressed patients receive the vaccine.11 Patients with IBD are felt to be at an increased risk for infection regardless of immunosuppressive treatment.12 Currently it is recommended that the injectable forms of the influenza vaccines be given, not the live attenuated nasal spray.13 Yearly vaccination is required secondary to antigenic drift of the virus in order to best provide protection. It is of value to discuss the importance of receiving the influenza vaccination with all patients with IBD because even a partial, blunted response may provide some degree of protection.14,15

Pneumococcal Vaccination

Pneumococcal pneumonia is more prevalent in patients with IBD compared to age-matched controls16 and patients with IBD who are hospitalized secondary to pneumonia tend to have worse outcomes.17 Certain risk factors such as proton pump inhibitors, anti-TNFs, narcotics, and steroids appear to increase this risk. Recent guidelines recommend that all immunosuppressed patients with IBD receive immunization against pneumococcus, ideally prior to starting immunosuppression.18 The typical vaccination schedule is to receive a single dose of PCV13 (pneumococcal conjugate vaccine), followed by the PPSV23 (pneumococcal polysaccharide vaccine) 2-12 months later. If the patient has already received the PPSV23 vaccine, then the PCV13 vaccine should be given after one year. A booster PPSV23 should be given five years after the initial vaccine and then should be given again after the age of 65 years if more than five years has passed since the prior booster (Diagram 1).16

Hepatitis A Vaccination

The incidence of hepatitis A infection (HAV) in the United States has decreased by 95% since the vaccination became available in 1995.19 Currently, the HAV vaccine is part of the recommended series of childhood vaccines. However, there still remain many unvaccinated adults. Gastroenterologists should inquire about prior vaccination to HAV. If patients are unable to recall, they can be given the vaccine again as there are no known harms of receiving a second dose series of the vaccine. The vaccine is given in a two-part regimen at zero months followed by a second dose at six months. It is not recommended to perform post-vaccination testing as there is a high rate of vaccine response and not all testing methods are reliable for detecting low, but protective anti-HAV concentrations.20

Hepatitis B Vaccination

Hepatitis B virus (HBV) infection can cause both acute and chronic liver disease and have long-term health implications. Patients with IBD are at an increased risk for HBV infection secondary to immunosuppressive therapy, surgery and blood transfusions. Understanding the HBV immunologic status for patients with IBD is of particular importance given the implications and serious repercussions immunosuppressive therapy can have on HBV reactivation.21 Testing for HBV infection or prior exposure [hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb)] in all patients with IBD is encouraged, and certainly for those who will need treatment with biologic therapy.

If not already immune, vaccination for HBV is recommended ideally at the time of IBD diagnosis, during disease remission or before starting immunosuppressive therapy.22 There are currently two single antigen HBV vaccines (Engerix and Recombivax) and one combined vaccine (Twinrix, HBV and HAV) that are indicated for the adult population.23 The typical schedule in which the vaccination should be administered is a dose at 0, 1, and 6 months with the goal to achieve Hepatitis B surface ab >10IU/L. Accelerated vaccination protocols have been established for patients traveling to endemic areas who are at high risk for HBV exposure; these schedules can be applied to patients with IBD who are not immune to HBV prior to starting immunosuppressive therapy if needed. The protocol schedule gives the vaccine at day 0, 7, 21-30, and a booster at 12 months.24 Regardless of the regimen used, serologic titers should be checked one to two months after completion of the vaccination series. If no vaccine response is seen (Hepatitis B surface ab >10IU/L), then patients should receive an additional series of either double dose HBV vaccine or the combined HAV/HBV vaccine at 0, 1, and 6 months.

Tetanus, Diphtheria, and Pertussis Vaccination

There is a five part childhood vaccination series DTaP that provides protection against diphtheria, pertussis and tetanus and a Td booster is recommended every ten years thereafter.25 Recently there has been a rise in pertussis epidemics and it is now recommended that patients between the ages of 11-64 receive one Td booster substituted by Tdap. The timing of the Tdap vaccine in patients with IBD seems to be important. In a prospective study looking at post vaccination Tdap antibody titers, patients with IBD on immunomodulator monotherapy or combination immunomodulator/anti-tumor necrosis factor (TNF) alpha therapy had decreased response rates.26 Based on this observation, the ideal time to administer the Tdap booster in patients with IBD would be prior to the initiation of immunosuppressive therapy.

Meningococcal Vaccination

Meningococcal disease can lead to serious complications such as sepsis, limb ischemia, meningitis, and rarely death. There are two serogroup B meningococcal (MenB) inactivated vaccines currently available in the United States, MenB-FHbp and MenB-4C.27 All adolescents and young adults between the ages of 16-23 should receive the vaccination. As there is no current evidence that patients with IBD are at increased risk for meningococcal infection, patients should receive the vaccination according to the Advisory Committee on Immunization Practices (ACIP) guidelines.27 The MenB-FHP is currently approved for both a two-dose series (0 and 6 months) and a three-dose series (0, 1-2, 6 months) while the MenB-4c is given in a two-dose series (0 and 6 months). Persons considered being at highest risk should be given the three dose series as it likely provides better immunogenicity. Importantly, the same vaccine must be used for all doses and are not interchangeable.

Human Papilloma Virus Vaccination

Human papilloma virus (HPV) has been clearly linked to the development of cervical cancer. Female patients with IBD have been found to have an increased risk of abnormal Papanicolaou (Pap) smears linked to HPV 16 or 18 serotypes, which has been associated with immunosuppressive therapy.28 There are currently two licensed vaccines available in the United States against HPV that include protection against serotypes 16 and 18. Gardasil comes in a quadrivalent and 9-valent form. The 9-valent vaccination covers five additional serotypes that account for 15% of cervical cancers as well as HPV serotypes 6 and 11 that cause most anogenital warts.29 The additional coverage of the 9-valent vaccine is felt to mostly provide beneficial protection to women over men. Since patients with IBD are considered to be immunocompromised, the three-dose regimen of either vaccine should be administered at 0, 1-2 and 6 months to patients aged 9-26.

Live Vaccinations Measles, Mumps, Rubella Vaccination

Since the adaptation of universal vaccination protocols, the incidence of measles, mumps and rubella (MMR) has drastically decreased in incidence.30 The vaccination is a live vaccine and is given to children around the age of one in a two-part series. If a patient with IBD is not immune to MMR, then the vaccination can be safely administered to the patient as long as there is no plan to start high-level immunosuppressive therapy within 6 weeks or high-level therapy has been discontinued for at least three months.10

Varicella Zoster

Varicella Zoster virus (VZV) is a highly contagious infection that can lead to severe disseminated disease in immunocompromised patients. Corticosteroid use in combination with immunosuppressive agents appears to be a significant risk factor for infection.31 The majority of adults have immunity to VZV either through acquisition during childhood infection or vaccination. The VZV vaccine is a live attenuated vaccine. Given the high risk for complications, all patients with IBD should have their immunity to VZV assessed (documentation of two-dose regimen, history or varicella infection, or laboratory evidence of immunity). If the patient is not immune, a two-dose vaccination series should be initiated if there is no plan to start high-level immunosuppressive therapy within six weeks or high-level therapy has been discontinued for at least three months. For patients with IBD without immunity who are on high-level immunosuppressive therapy (and who cannot stop it without risk of flare) but are at increased risk for exposure to varicella, such as health-care workers or teachers, the risk of infection needs to be weighed against receiving the vaccination.32 There is some evidence available in small case series that administration of the VZV vaccine was safe in pediatric patients who were on either thiopurines or infliximab.33

Zoster/Shingles Vaccination

Varicella Zoster virus (VZV) persists as a latent infection in sensory nerve ganglia and can reactivate, especially in immunocompromised patients, causing Herpes zoster.34 About one in three people will develop zoster in the general population. The most common side effect is postherpetic neuralgia, however immunocompromised patients may suffer from disseminated infection that can be potentially fatal.35 In 2006, the live Zoster vaccine (Zostavax) was released and recommended by the Center for Disease Control (CDC) for patients 60 years or older. This live attenuated single-dose vaccine is at least 14 times the potency of the varicella vaccine. The CDC advises that administration of the vaccine to patients on “low-doses” of methotrexate, azathioprine or 6-mercaptopurine is safe. There is limited data to suggest the vaccine is safe for patients on anti-TNF therapy36, but the CDC does not recommend its use.

Recently, an inactivated vaccine consisting of varicella zoster protein in an adjuvant system (Shingrix) was FDA approved. It has remarkable efficacy in immunocompetent individuals, reducing the risk of developing zoster by 97%.37 This vaccine is indicated for patients 50 years or older as a two-dose regimen, at month 0 followed by a second dose at 2-6 months. Although this vaccine has not been directly tested in patients with IBD on immunosuppression, its safety and efficacy has been demonstrated in patients post renal transplant on immunosuppression as well as patients with either solid tumor or hematologic malignancies receiving chemotherapy.38,39

Screening and Surveillance of Cancer
Cervical Cancer Screening

Cervical dysplasia and cancer have been linked to the oncogenic properties of the HPV virus. Fortunately, the mortality rate has drastically decreased due to the implementation of mass screening with the Pap smear.40 Screening women with IBD is of particular importance as patients on immunosuppressive therapy have been shown to be at increased risk for cervical neoplasia, particularly in relationship to thiopurines.41 Unfortunately, despite these heightened risk, patients with IBD still seem to be under vaccinated for HPV42 and do not receive adequate cervical cancer screening.43 Patients with IBD who are on immunomodulator therapy should undergo yearly Pap Smears regardless if the patient has received the HPV vaccine.44 All patients with IBD who are on chronic immunosuppressive therapy should also be considered for yearly pap screening according to the American College of Obstetrics and Gynecology.45

Colorectal Cancer Screening and Dysplasia Surveillance

Patients with UC and colonic Crohn’s disease are at an increased risk of colon cancer that is two times the risk of the general population. Risk factors for development of colon cancer and dysplasia in patients with IBD include duration and extent of disease, family history of colon cancer, primary sclerosing cholangitis (PSC) and young age at disease onset.46 All patients with IBD should have a restaging (screening) colonoscopy eight years after disease onset as disease involvement may progress over time and proximal biopsies should exclude microscopic involvement in endoscopically normal appearing areas. The extent of the disease should be based either on endoscopic or microscopic involvement, whichever reveals more extensive disease.47 Patients with UC involving and proximal to the sigmoid colon and Crohn’s patients with more than a third of the colon involved should be placed in an endoscopic surveillance protocol. The presence of limited proctitis has not been proven to be a risk factor for the development of colorectal cancer.48 Ideally, surveillance should be undertaken when disease is in remission as active disease can hinder accurate interpretation of dysplasia.49

Current guidelines recommend colonoscopies every 1-3 years depending on risk factors and decided on a patient-to-patient basis. The patients at highest risk should undergo yearly surveillance colonoscopies (Table 2). For patients who are not in the high-risk group, lengthening the surveillance interval from one year can be considered if patients have endoscopically and histologically normal mucosa on two or more surveillance colonoscopies.46 The Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients (SCENIC) guidelines recommend chromoendoscopy over white-light endoscopy with random biopsies as the preferred method of surveillance in patients with IBD. Targeted biopsies or resection (if the lesion is felt to be endoscopically resectable) should be performed if a lesion is identified with chromoendoscopy. One may also consider two biopsies from each colonic segment for histologic staging.46 If chromoendoscopy is not available or the yield is reduced by significant inflammation, poor preparation or multiple pseuodpolyps, then random biopsies with targeted biopsies of any suspicious lesion should be undertaken.

Skin Cancer Screening

The awareness of the risk of skin cancer in patients with IBD has grown overtime. Non-melanoma skin cancer (NMSC) includes both squamous cell and basal cell carcinoma. The risk of acquiring NMSC is largely associated with thiopurine use (odds ratio of 4) and not IBD alone.50 There has been conflicting evidence in regards to the ongoing risk of NMSC once thiopurine use has stopped. A large French prospective cohort study demonstrated a pronounced increase in the incidence of NMSC in patients 50 or older with prior thiopurine exposure compared to controls.51 Contrary, a study on a large cohort of Veterans Affairs patients demonstrated that the incidence of NMSC reverted back to pre-exposure levels after the thiopurine was stopped regardless of the prior exposure duration.52

While NMSC appears to be strongly correlated to thiopurine use, patients with IBD have a significantly higher incidence of melanoma compared to the general population regardless of medical therapy.53 In addition, anti-TNF agents do appear to double the risk of melanoma.54,55 Given that there is an increased risk for melanoma in patients with IBD, routine counseling on the importance of decreased sun exposure, avoidance of tanning beds, use of protective sunscreen and clothing should be performed at office visits.

Our practices recommend referrals to dermatology for all of our IBD patients to undergo screening and in order to identify the particular risk and needs of continued surveillance according to individual risk factors based on our current understanding. Given the conflicting data of thiopurine use and risk for NMSC after cessation, it seems most reasonable to continue surveillance even after cessation in patients older that 50.

Osteoporosis and Osteopenia

Patients with IBD are at increased risk for bone mineral disorders including osteopenia and osteoporosis. The reported prevalence of osteoporosis in patients with IBD is estimated to be as high as 40% and more subtle degrees of decreased bone mineral density can be seen in 70% of patients with IBD.56 There are certain risk factors that lead to accelerated bone mineral loss. Patients with IBD who have one or more of the following risk factors should undergo screening with Dual-energy X-ray absorptiometry (DEXA): corticosteroid use more than three months or repeated use, history of low trauma-fracture, post-menopausal women, and males older than 50.57 Other risk factors to consider are chronic inflammation, active smoking, and malnutrition. If osteoporosis is found then referral to the patient’s PCP, endocrinologist or rheumatologist should be made for consideration of bisphosphonate therapy. Vitamin D levels should be checked at regular intervals and adequate calcium intake (1000mg/day) is recommended for all patients with IBD.58

Smoking

It is important to assess for tobacco use and provide cessation counseling to all patients with IBD given the overall health implications. Despite the observation that smoking may be protective against UC, practitioners should still encourage cessation, but caution the patient about the potential for flare. More importantly, Crohn’s patients should be advised that it is absolutely crucial to stop smoking. There is good evidence that patients with Crohn’s who smoke are at an increased risk of flare and smoking cessation lessens the risk.59 Furthermore, smoking is associated with increased steroid exposure, greater risk for surgery and increased risk of post-operative recurrence.60,61 There are a number of support systems that practitioners can refer patients to that include telephone based, mobile applications, and support group programs to help achieve cessation. Furthermore, medical therapy options that have been shown to be beneficial in smoking cessation include Nicotine replacement therapy, varenicline and bupropion.62

CONCLUSION

Inducing and maintaining remission for patients with IBD still remains the primary goal. However, the importance of health maintenance and prevention has emerged as a crucial objective in the overall delivery of care. Providers should take an active role in maintaining the wellness of patients and preventing any future adverse events. The role of the gastroenterologist should be as the principal physician closely managing the care with other health care professionals to ensure the patients are up to date with age appropriate vaccinations, cancer screening, screening for osteoporosis, and smoking cessation.

Download Tables, Images & References

A Case Report

Esophageal Dieulafoy Lesion – A Rare Cause of Upper Gastrointestinal Bleeding

May 2018 • Volume XLII, Issue 5
Tehseen Haider,Harish Guddati,Hilary Hertan

Read Article

Tehseen Haider, MD1 Harish Guddati, MD2 Hilary Hertan, MD, FACG2 1Department of Medicine, 2Department of Gastroenterology, Montefiore Medical Center, Wakefield Division, Bronx, NY

INTRODUCTION

Named after French surgeon Georges Dieulafoy, Dieulafoy lesions are uncommon but important causes of acute gastrointestinal (GI) bleeding which can be massive and life threatening.1 Dieulafoy lesions are known to occur anywhere in GI tract but are rarely reported in the esophagus and lower GI tract. Diagnosed endoscopically, they are amenable to treatment but pose a threat of rebleeding after the first intervention. We present a case of 91 year-old female with acute upper GI bleeding due to an esophageal Dieulafoy lesion.

Case Report

A 91 year-old African American woman presented with acute left upper extremity pain to emergency department (ED). She was taken to the operating room (OR) for acute limb ischemia. She experienced an episode of hematemesis in the post anesthesia care unit (PACU) with 300 ml of coffee ground aspirate in the nasogastric (NG) tube. She was transferred to intensive care unit (ICU) for hypovolemic shock and respiratory failure. Laboratory studies were significant for drop in hemoglobin from her baseline of 13.6 g/dL to 10.6 g/dL in 12 hours, indicating acute blood loss anemia. Emergent bedside esophagogastroduodenoscopy (EGD) showed coffee ground material in the stomach, necessitating lavage. A single, ectatic blood vessel with stigmata of recent bleeding was visualized in the lower third of the esophagus (Figure 1). The vessel was injected with four cc of 1:10,000 solution of epinephrine, and one hemostatic clip was placed to prevent recurrent bleeding (Figures 2 & 3). She was monitored in the ICU for recurrent bleeding, but she remained stable afterwards with no further rebleeding.

DISCUSSION

Dieulafoy lesions are a rare cause of acute nonvariceal GI bleeding, responsible for approximately 1.5% of acute upper GI bleeding.2 They can be associated with massive, life threatening bleeding. Initially reported in the stomach only, Dieulafoy lesion have been known to occur elsewhere in GI tract and extraintestinal locations. Most of these lesions, 75-90%, occur in the stomach, generally along the lesser curvature, within five cm of the gastro-esophageal junction. Rarely they can occur in small bowel (around 14-18%) and even more rarely in esophagus (roughly 8%)3,4,5

A Dieulafoy lesion is a congenital arteriovenous malformation which bleeds in arterial pulsatile fashion. Unlike normal arteries which go through narrowing of their caliber as they approach the mucosa, the Dieulafoy is a “caliber persistent artery” maintaining its caliber through the submucosa to the mucosa.4 The caliber of artery is in the range of 1-3 mm, which is approximately 10 times the normal caliber of mucosal capillaries. The mechanism of bleeding is erosion secondary to pulsations of the artery, rather than primary ulceration of mucosa. The mechanism and processes by which the artery maintains its caliber and tortuosity is largely unknown.3 Bleeding is mostly seen in men with comorbidities such as hypertension, cardiovascular disease, chronic kidney disease, diabetes mellitus or alcohol abuse.4 Endoscopy is the diagnostic modality of choice. On endoscopy, it appears as a stream of arterial blood emanating from mucosa. A nonbleeding Dieulafoy lesion appears as a raised nipple or visible vessel without an associated ulcer. The diagnosis rates for initial endoscopy range from 49% to 63%, and repeat endoscopy is often required (6%) due to intermittent bleeding.6 Repeat endoscopy timed as close as possible to a rebleeding event is crucial for the diagnosis. Endoscopic criteria for diagnosis of a Dieulafoy lesion has been established and includes (i) active arterial oozing/spurting from a small defect in the mucosa, (ii) visualization of a small vessel protruding from normal mucosa, (iii) fresh blood clot adherent to a defect of normal mucosa.7

Endoscopy is the mainstay of treatment. Multiple modalities can be utilized including mechanical therapy such as band ligation, hemoclip placement, thermocoagulation, cyanoacrylate injection, epinephrine or ethanolamine injection. Injection monotherapy has a high initial success rate, however there seems to be a high rate of rebleeding. In a retrospective analysis a rebleeding rate of 55% was reported with injection therapy. Combination therapy with injection followed by heater probe thermocoagulation is preferred. Doppler ultrasound can be used to confirm ablation of a Dieulafoy lesion by documenting the absence of blood flow following intervention.8 In view of unknown pathophysiology, there is little evidence to support acid suppression therapy to prevent rebleeding. If endoscopy fails, angiography is used as diagnostic intervention as in other causes of GI bleeding.9 Rebleeding is treated with repeat endoscopic hemostasis, angiographic embolization or surgical wedge resection of the lesion. The long-term rate of rebleeding is low once a Dieulafoy lesion is completely eradicated.

CONCLUSION

Dieulafoy lesions are one of the lesser known cause of massive upper GI bleeding with the stomach being the most common site. This condition can be encountered in any age group. Early endoscopy is essential to identify the source of bleeding and manage it appropriately. It is important to involve gastroenterology, critical care, interventional radiology and surgery in the management of these patients.

Download Tables, Images & References

Dispatches From The Guild Conference, Series #12

Inflammatory Bowel Disease in the Older Patient

May 2018 • Volume XLII, Issue 5
Sara Lewin,Uma Mahadevan

Read Article

Older patients with IBD require special attention due to comorbidity, polypharmacy, functional status, and increased risk of infection and malignancy compared to younger IBD patients. Medication interactions, prevention of infection and management of comorbidities may require closer monitoring to determine therapeutic response and to ensure adequate safety of medical therapy for IBD. In this article, we discuss the importance of developing a treatment strategy for older patients with IBD focused on restoration of normal bowel function and improved quality of life, avoidance of hospitalization and unnecessary surgery and minimizing long-term risk of therapies.

Sara Lewin, MD, Clinical Fellow, Division of Gastroenterology Uma Mahadevan, MD, Professor of Medicine, Division of Gastroenterology, University of California San Francisco, San Francisco, CA

INTRODUCTION

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic conditions characterized by inflammation of the gastrointestinal tract. The peak incidence of IBD occurs in the second to fourth decades of life.1 Although IBD is often thought of as a disease of the young, the incidence of IBD in older patients has been reported to be 10-15%. As the global population ages and the overall incidence of inflammatory bowel disease increases, the number of older patients who are diagnosed with IBD and the number of aging patients diagnosed with IBD when they were younger will increase considerably.1 With current estimates that 10-30% of patients with IBD are over the age of 60,3 the anticipated growth of older patients with IBD introduce distinct challenges and considerations in the care of this patient population.

Epidemiology and Pathophysiology

Older patients with IBD, also termed “elderly” or “geriatric,” typically defined as ≥60 years of age, comprise a heterogeneous group due to a wide range of medical co-morbidities and functional status. Older-onset ulcerative colitis is more common than older-onset Crohn’s disease, and older men have higher incidence rates of IBD than older women.4

Genetics and family history appear to have less influence on the development of older-onset IBD when compared to younger populations suggesting other factors at play.5 As the immune system ages, age-related T-cell impairment and decline in T-cell production can lead to a relative immunodeficiency. This immunodeficiency predisposes older patients to gastrointestinal infections, but immune dysregulation with advancing age also leads to the increased production of pro-inflammatory cytokines, which are implicated in the development of inflammatory diseases.6 In addition to immune dysregulation, current theories of IBD pathogenesis suggest that alterations in the intestinal microbiome may trigger the development of IBD.7 The composition of the intestinal microbiota also evolves with aging, with less overall diversity characterized by decrease in anaerobes, such as bifidobacteria, and increase in enterobacteria. These changes in the microbiota are hypothesized to be caused by changes in diet, mobility, intestinal motility, increased use of antibiotics associated with aging.8 Frailty is also associated with decreased microbiota diversity compared to non-frail older individuals.9

Clinical Presentation

Clinicians experience more difficulty diagnosing IBD in older patients, leading to misdiagnosis and delayed diagnosis. 60% of older patients with CD are initially misdiagnosed, compared to 15% of younger patients.10 The clinical presentation of IBD in older patients may be confused with infectious (such as Clostridium difficile), ischemic, radiation, non-steroidal anti-inflammatory drug-induced, or diverticular-associated enterocolitis.11 Older-onset IBD patients present with more subtle disease compared to younger adults. They more frequently present with isolated colonic inflammation (61.9% vs. 36.7% in younger adults) and less frequently present with small bowel involvement or upper gastrointestinal disease (38.1% vs. 63.3% in adults). 12 In CD, older patients are more likely to present with rectal bleeding without profound diarrhea, abdominal pain, fever, or weight loss.4 Additionally, older-onset CD patients more often have isolated colonic disease without penetrating disease, a phenotype similar to UC.3 In UC, older patients are more likely to present with left-sided colitis rather than ulcerative proctitis or pancolitis, and often have milder symptoms of abdominal pain and rectal bleeding than younger patients.12 Extraintestinal manifestations of IBD (e.g., arthritis, erythema nodosum, pyoderma gangrenosum, apthous stomatitis, uveitis) are less common in patients diagnosed with IBD at an older age.13 Progression of disease, such as extension of ulcerative proctitis to left-sided colitis, or the development of penetrating disease, is less common in older-onset IBD.13

Outcomes and Complications of IBD

Despite having milder disease and less progression, older patients with IBD are less likely to utilize IBD-specific outpatient care14 and more likely to be hospitalized for IBD.15 A study of IBD patients in a Swedish National Registry found that older patients with IBD are less likely to have IBD-specific outpatient healthcare and more likely to have IBD-related hospitalizations and intestinal surgeries.16 It has been hypothesized that increased hospitalizations and surgeries in older IBD patients may be related to reluctance to use corticosteroid-sparing immunomodulator and biologic medications in older patients due to other comorbid conditions and risk of complications.17 Older age is an independent risk factor for hospital mortality in IBD-related hospitalizations.20 Lastly, older patients who undergo surgery for IBD have longer post-operative length of hospital stay19 and may have increased post-operative mortality.20

Older patients with IBD are also at increased risk for serious infection regardless of treatment type,18 though use of immunosuppression, disease activity and use of narcotics also increase the risk of serious infection in older IBD patients. Due to immunosenescence, older patients with IBD are at increased risk for infection, including zoster infection.21 Immunization (with inactive vaccines for patients on immunosuppresive therapies) for influenza and pneumonia are recommended for all older patients with IBD. Zoster vaccination is also recommended for all individuals 60 and older. A new, inactive vaccine for herpes zoster (Shingrix, GlaxoSmithKline), with >90% reduction in shingles incidence, is now commerically available and is likely safe in immunosuppressed patients with IBD.22

Patients with IBD are at a two- to three-fold increased risk of developing a venous thromboembolism (VTE). This risk increases significantly with age; there is a 20% increased risk of a venous thromboembolism for each increased decade in age.23 There are no specific guidelines for VTE prevention in older IBD patients, though smoking cessation, weight reduction in obese patients, and mobilization in the hospital, at home, and during long-distance travel should be encouraged.24

The most well-recognized risk factors for the development of colorectal cancer in inflammatory bowel disease are duration and extent of disease.25 Based on these established risk factors, it is plausible that patients diagnosed with IBD at an older age would be at lower risk for IBD-associated colorectal cancer given shorter duration of disease and typically less extensive involvement. However, cohort studies from Hong Kong and the Netherlands have found that older-onset IBD is associated with a shorter time to the development of colon dysplasia and colorectal cancer.26,27 While this may represent sporadic disease, earlier colonoscopy for colon cancer surveillance than guidelines suggest (e.g., eight years after diagnosis) in elderly-onset IBD is advisable.

Management

The general approach to treatment in elderly-onset IBD is no different than in the younger IBD population. Treatment goals should focus on inducing and maintaining remission, preventing disease-related and treatment-related complications, and optimizing quality of life. The therapeutic choices may be more challenging in older IBD patients due to different disease phenotype, patient comorbidities, and concern for polypharmacy. Additionally, older patients with IBD are often excluded from clinical studies, particularly randomized control trials for IBD therapeutics. The paucity of efficacy and safety data specifically pertaining to older IBD patients, further complicates treatment decisions.

Mesalamine

5-aminosalicylic (5-ASA) agents are widely used for treatment of mild to moderate ulcerative colitis and may also be used for treatment of Crohn’s colitis.28 Over 80% of patients with IBD diagnosed after age 60 are treated with 5-ASA agents.4 5-ASA can be taken orally, with several formulations requiring dosing multiple times per day or with multiple pills for each dose.29 Topical 5-ASA therapies include suppositories, which can treat inflammation in the distal 10 cm of the rectum, and enemas, which can theoretically treat inflammation distal to the splenic flexure. In the older IBD patient, several factors can influence adherence to medical therapy. Cost of medications, concern for side effects, difficulties with pill size and number, difficulty with enema and suppository administration, and complex dosing schedules all can affect adherence to medical therapy.30

Although 5-ASA agents are generally considered to have an excellent safety profile, side effects and adverse reactions can occur. The most common adverse reactions include nausea and vomiting, headache, and rash. Nephrotoxicity, which is typically due to interstitial nephritis, is rare but clinically important, with a mean occurrence of 0.26% per patient-year. The incidence of nephrotoxicity appears to be idiosyncratic, as it has not been found to be related to formulation, dosing, or duration of 5-ASA therapy.31 As many older patients with IBD may have comorbid chronic kidney disease or risk factors for the development of renal insufficiency (e.g., diabetes mellitus, hypertension), renal function should be monitored closely before and during treatment.31

Corticosteroids

Corticosteroids are effective in establishing but not maintaining remission in moderate to severe IBD. Despite this, 30-40% of older IBD patients are on maintenance therapy with systemic corticosteroids.33,34 Long-term corticosteroid use is associated with many adverse effects, which are more frequent and severe in the geriatric population. Adverse effects include osteoporotic-related fractures, serious and opportunistic infections, altered mental status and delirium, precipitating or exacerbating diabetes mellitus and hypertension, and development of cataracts and glaucoma.35,36 Budesonide, a newer corticosteroid with formulations targeting both the small intestine and the colon, possesses some safety advantage to conventional corticosteroids, such as prednisone. Budesonide has extensive first-pass metabolism in the liver, leading to fewer systemic adverse effects and increased tolerability in patients. However, cost and lack of insurance coverage may limit use and corticosteroids may still be required for induction of remission in more severe disease activity.17

Immunomodulators: Thiopurines and Methotrexate

Some patients who are unable to achieve disease remission with oral mesalamine may be treated with thiopurine agents (such as azathioprine or 6-mercaptopurine) or methotrexate for maintenance therapy in IBD. In older patients with IBD, use of thiopurines and methotrexate is quite uncommon, (6% and 1%, respectively in one retrospective study33), potentially due to concern for adverse effects associated with these agents.

Use of thiopurines can lead to leukopenia and elevated liver enzymes, though testing for thiopurine methyltransferase genetics and/or enzyme activity prior to initiation of thiopurine therapy can help to identify those at highest risk for leukopenia.37 Acute pancreatitis is also associated with thiopurine use.38 Thiopurine use has been associated with increase risk of lymphoma, with a median age of onset of 60.39 Thiopurine use is also associated with an increased risk of non-melanoma skin cancer,40 with risk increasing with age.

Common side effects of methotrexate use include nausea, fatigue, stomatitis and rash. Rarely, hepatotoxicity can occur; liver enzymes should be monitored routinely. Methotrexate appears to be safe in older patients. Renal function, rather than advancing age itself, predicts development of toxicity, and should be taken into consideration when initiating and monitoring methotrexate therapy.41 Folic acid supplementation is recommended to prevent methotrexate-associated hepatic and gastrointestinal hepatotoxicity as well as associated folate deficiency.41

Biologic Therapies

Biologic agents, including tumor necrosis factor alpha (TNF-.), integrin and interleukin antagonists, are effective treatments for moderate to severe UC and CD. Although TNF-. agents have been in use for over a decade, use in the elderly IBD population is infrequent, possibly due to lack of safety data in this population or concern for side effects associated with these therapies.17

Anti-TNF agents may be less effective in older patients, as older IBD patients are more likely to be primary non-responders compared to younger IBD patients. Older IBD patients on anti-TNF therapy also have higher rates of IBD-associated hospitalizations, surgeries and serious infections compared to younger IBD patients.43

Anti-TNF use is associated with increased risk of serious infection that may be even higher in older patients with IBD and may lead to earlier discontinuation of anti-TNF compared to younger IBD patients.44 The increased risk of infection is most pronounced in combination therapy when anti-TNF and thiopurine agents are given concurrently. Live vaccines should not be given to patients on anti-TNF therapy and inactive vaccines may be less effective in patients receiving anti-TNF therapy. The combination of inadequate immune response and non-adherence to vaccination increases the risk of infection in the vulnerable older IBD patient population. Anti-TNF therapy has also been associated with worsening congestive heart failure, and is contraindicated in New York Heart Association Class III and IV heart failure,45 which is more likely to be a comorbid condition in older patients with IBD. There is also an increased risk of lymphoma with use of anti-TNF agents, particularly with combination therapy, and long-term combination therapy should be avoided in individuals 65 and older.17,39 The risk of both non-melanoma and melanoma skin cancers are increased in patients taking anti-TNF, and they should undergo regular dermatologic skin examinations.46

The administration of anti-TNF agents, which are given as an infusion (infliximab) or as a self-administered injection (adalimumab, certolizumab-pegol, golimumab), may provide logistical challenges for the older patient with IBD, who may have difficulty with transportation to infusion centers, with venous access, with self-administration of injectable agents due to poor dexterity and decreased visual acuity, and with adherence to a complex dosing schedule.47

Vedolizumab is a gut-selective monoclonal antibody that inhibits a4?7 integrin to block lymphocyte trafficking to the intestinal endothelium that is used for moderate to severe UC and CD. Vedolizumab has an excellent safety profile, with no increased risk of serious infection and low rates of malignancy in the general IBD population.48 The safety profile of vedolizumab in older patients with IBD, has not been extensively studied, though preliminary data suggests that vedolizumab is low risk for use in older patients with IBD,49 and may be a preferred treatment choice for moderate to severe IBD due to its low lymphoma and infection risk.

Ustekinumab

Ustekinumab is a monoclonal antibody against IL-12 and IL-23, initially approved for the use in psoriasis, but now is approved for use in moderate to severe CD. Clinical trials of ustekinumab in Crohn’s disease have also demonstrated an excellent safety profile with no increased risk of adverse events compared to placebo.50 There is a paucity of data regarding safety of ustekinumab in the older IBD population, but studies of ustekinumab use in older psoriasis patients have demonstrated favorable safety profile,51 and may also be a preferred treatment choice for older patients with Crohn’s disease.

Similar to anti-TNF agents, older patients with IBD on vedolizumab or ustekinumab may have difficulty with adherence to intravenous (IV) infusions and self-administered subcutaneous injections with complex dosing schedules. In general, immunosuppressive regimens should be minimized or avoided, if possible, in patients with multiple poorly controlled comorbidities, poor functional status, severe malnutrition, and cognitive decline. However, older IBD patients with minimal or well-controlled comorbidities with excellent cognitive, nutritional, and functional status are suitable candidates for immunosuppressive therapy if clinically indicated.

Drug-drug interactions

Older patients with IBD are prescribed an average of nine routine medications to manage their IBD and other comorbid conditions. Nearly one-third of medication regimens in older patients with IBD have major drug-drug interactions.34 (Table 1.) Careful review for drug-drug interactions with IBD medications should be considered prior to introducing a new medication. As 5-ASA agents are the most common medications used in older patients with IBD, drug-drug interactions with mesalamine agents are common, including with non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors, histamine blocker, and warfarin use. Corticosteroids have many drug-drug interactions, including increased risk of tendon rupture when taken with fluoroquinolones, and increased risk of hypokalemia when taken with thiazide and loop diuretics. Allopurinol and angiotensin-converting-enzyme (ACE) inhibitors use may increase myelotoxicity when given with thiopurines and thiopurines may decrease the anticoagulation effect of warfarin. NSAIDs, aspirin, thiazide diuretics, and penicillin may inhibit renal excretion of methotrexate, leading to increased risk of methotrexate toxicity. Antibiotics given as treatment for and management of complications of IBD, such as metronidazole, have an increased risk of neuropathy when given with statins, and ciprofloxacin has the potential to increase the anticoagulation effects of warfarin.52 Biologic therapies have not been associated with significant drug-drug interactions with other common medications.53

In order to minimize drug-drug interactions, all providers caring for older patients with IBD, including gastroenterologists and primary care providers, should review the patient’s medication regimen carefully. Factors to consider include determining if there is an appropriate indication for the drug, that is effective for its intended condition, and that the dosage and directions are correct and practical given the patient’s comorbidities and functional limitations. Other considerations include ensuring that there are no significant drug-drug interactions or drug-disease interactions, that the duration of therapy is acceptable, and that the cost of the patient’s medical regimen compared to alternatives of equal usefulness is minimized.

CONCLUSION

Older patients with IBD require special attention due to comorbidity, polypharmacy, functional status, and increased risk of infection and malignancy compared to younger IBD patients. Medication interactions, prevention of infection, and management of comorbidities may require closer monitoring to determine therapeutic response and to ensure adequate safety of medical therapy for IBD. Although the side effects and risks of corticosteroids are well-known, many older IBD patients are maintained on long-term corticosteroid use, which should be avoided in favor of other corticosteroid-sparing agents. A treatment strategy for older patients with IBD should be focused on restoration of normal bowel function and improved quality of life, avoiding hospitalization and unnecessary surgery, and minimizing long-term risk of therapies.

Download Tables, Images & References

Frontiers In Endoscopy, Series #43

Endoscopic Mucosal Resection (EMR)

May 2018 • Volume XLII, Issue 5
Constantine Melitas,Serge A. Sorser,Douglas G. Adler

Read Article

Removal of large colon polyps can put patients at risk for procedure complications and inadequate resection of the lesion. Endoscopic mucosal resection (EMR) is a well-described technique that is safe and predominantly used for removal of larger lesions (> 1cm) of the gastrointestinal tract, which are limited to the superficial layers such as the mucosa and submucosa. In this article, we discuss several EMR techniques, each with their own indications,risks, and benefits.

Constantine Melitas, MD, Gastroenterology and Hepatology Fellow, Michigan State University College of Human Medicine, Providence, Providence Park Hospitals, Southfield, MI Serge A. Sorser, MD, Clinical Assistant Professor, Gastroenterology and Hepatology, Michigan State University College of Human Medicine, Providence, Providence Park Hospitals, Southfield, MI Douglas G. Adler, MD, FACG, AGAF, FASGE, Division of Gastroenterology and Hepatology, Utah School of Medicine, Salt Lake City, UT

INTRODUCTION/BACKGROUND

Removal of large colon polyps can put patients at risk for procedure complications and inadequate resection of the lesion. Endoscopic mucosal resection (EMR) is a well-described technique that is safe and predominantly used for removal of larger lesions (> 1cm) of the gastrointestinal tract, which are limited to the superficial layers such as the mucosa and submucosa. EMR can be used to remove benign, premalignant, and early (T1N0) malignant lesions, which can prevent the need for surgical intervention. To perform EMR, patient selection is critical for optimal outcomes. Patients should be selected if concern for an invasive lesion is low, based on lesion size, and if polyp features are of low complication risk. Also, patients who do not meet these criteria but are poor surgical candidates may also benefit from EMR. There are several EMR techniques, each with their own indications, risks, and benefits. Lesions may either be taken out whole (i.e. en bloc) or by removing them in segments (i.e. piecemeal). It has been studied that lesions greater than 1.5 or 2 cm should be removed piecemeal to reduce the risk of perforation.1-5

Techniques

There are three main techniques for EMR: injection, cap, and band ligation. Underwater EMR is a more recent technique, which also is performed by some endoscopists.

Injection-assisted EMR is a technique that involves injection of a substance under the mucosa to separate the mucosa from the submucosa to allow for resection of the lesion without penetration into the deeper layers of the GI tract in an attempt to decrease the risk of perforation. This also allows for removal of lesions en bloc, depending on the size of the lesion. It is important to inject and lift the proximal side of the lesion first as if this is not done, the lesion may be distorted into a position that is away from the endoscope obstructing visualization and placing it in an unfavorable position for resection. Nonlifting of a lesion can be a predictor of deeper invasion and is not indicated for removal through EMR.1,6-8 However, nonlifting can also occur if the lesion has previously manipulated or intervened upon. If nonlifting is thought to be due to prior manipulation of the lesion, EMR may be attempted.9

After the lesion is adequately lifted, resection is then performed using a snare with electrocautery. (Figure 1) If the lesion size is not amenable to removal en bloc, it may be removed piecemeal by systematically beginning at one margin and working across the entire lesion. The endoscopist must take great care to ensure islets of residual tissue are not left as these may become difficult to remove. Prior to removal of each portion of the polyp, the portion to be ensnared should be lifted away from the mucosa to further help prevent injury to the muscularis propria. Resection should be continued until the muscularis propria has been exposed. Remnants of adenomatous tissue can be removed with conventional methods for polypectomy such as forceps or snares, however the remnant tissue may also be treated with argon plasma coagulation (APC), alternative forms of monopolar coagulation, or may be fulgrated.

The cap-assisted technique also begins with injection of a solution in the submucosal space similar to the injection-assisted technique. However, a cap is placed at the end of the endoscope to allow for suction of the entire lesion or portion of the lesion into the cap. An electrocautery device, such as a hot snare, is placed in position prior to the retraction of the lesion into the cap and is used to resect the retracted portion of the lesion. There are caps available, which include an electrocautery device, most commonly a snare, attached to them. This process is repeated until the lesion is fully resected. The caps that are available are plastic and are cylindrical in order to fit on the end of the endoscope similar to caps used for variceal band ligation.10

Ligation-assisted EMR is a technique that does not require an injection into the submucosal space. As in cap assisted, a cap is placed over the end of the endoscope. However, the cap used with this technique is equipped with band ligation. The lesion is retracted into the cap by the use of suction. A band is then deployed onto the lesion to ligate the portion to be resected. An electrocautery device is subsequently used to resect the ligated area.11,12 The EMR band ligator allows for passage of a snare through the working channel of the endoscope without removal of the band ligating cap. The cap is typically equipped with six bands. (Figure 2)

The underwater technique is performed by filling the GI tract with water, which theoretically allows the lesion to elevate itself or float. It has been hypothesized that this enables the lesion to separate itself from the deeper layers of the GI tract and therefore theoretically allow for resection with less risk of injury or perforation.13 This method however has been thought to have a decreased risk of seeding malignant cells into the deeper layers of the mucosa after resection. Furthermore, it has been postulated that this technique may also decrease the fibrosis formation at the resection area making recurrent lesions easier to manipulate.9 As fibrosis makes lifting a lesion much more difficult, the underwater technique has been found to be valuable and beneficial in treating lesions which have been previously manipulated.6,14-20

Injectable Solutions

Several solutions are available for injection into the submucosal space to help prevent injury to the deeper layers of the GI tract with EMR. Normal saline is the most commonly used solution, is readily available, and is inexpensive, however, it dissipates after only a few minutes. Dissipation of the lift can be managed with repeating the injection, which is a common occurrence, especially when removing large lesions. Solutions such as hyaluronic acid, hydroxypropyl methylcellulose, succinylated gelatin, glycerol, and fibrinogen containing solutions have all been found to last longer than normal saline.21-27 Hyaluronic acid is also inexpensive but is not readily available in the U.S. In several trials with which have compared hyaluronic acid to normal saline, it has been concluded that hyaluronic acid sustains a more effective lift. Hyaluronic acid has been found to be the solution that sustains a lift for the longest duration of all currently available solutions.28 Hydroxypropyl methylcellulose however is a readily available solution and has a good duration of lift but has been found to have a risk of tissue damage at the injection site.29,30 Succinylated gelatin is readily available and inexpensive but is mainly used for colonic lesions > 20 mm as it has been found to assist in removing lesions in piecemeal fashion.31

Other endoscopic tools and techniques are available to further assist the endoscopist to identify the lesion margins. Chromoendoscopy is one modality, which involves staining the colonic mucosa with a topical solution to help delineate the lesion in its entirety. Solutions that have been used include methylene blue, toluidine blue, Lugol’s solution, Congo red, phenol red, and indigo carmine. Another tool that can be used is narrow band imaging (NBI) which is a mode that most high definition endoscopes are now equipped with and which enhances the mucosal surface without the need for dyes. The wavelengths that make up white light have been found to have different penetration abilities. Blue light has been shown to penetrate only the superficial layers of the colon while red light penetrates into the deeper layers. NBI therefore uses blue light wavelengths to reveal the superficial vasculature of the mucosa, which helps identify the lesion easier.32 Along with these tools, other helpful solutions may be added to the solution used to lift the lesion to be resected. Epinephrine (1:100,000 – 1:200,000) is sometimes added to the solution to theoretically decrease the risk of post polypectomy bleeding by means of vasoconstriction of the feeding vessels. However, this has the potential side effects of epinephrine use, such as severe hypertension, tachycardia, arrhythmias, and intestinal ischemia, which are all rare complications but are well documented when epinephrine is absorbed systemically.33-36 Other very helpful additives to a solution are methylene blue and indigo carmine. These additives significantly assist in delineating the margins of the lesion as it stains the underlying mucosa blue without affecting the color of the lesion itself, highlighting the margins. This staining may also help identify the muscularis propria and therefore can help prevent perforation.37,38

Efficacy

In the esophagus, EMR can be used for removal of superficial malignancies as well as Barrett’s associated high-grade dysplasia and intramucosal carcinoma.39-41 For Barrett’s associated neoplasia, EMR may be used as a solitary modality to remove neoplastic lesions or may be used in conjunction with ablative techniques to remove large segments of Barrett’s. A recent study which evaluated the efficacy of complete resection of Barrett’s and its associated neoplasia through EMR, found that neoplasia with high risk characteristics, such as submucosal invasion, poor differentiation, lymphatic or vascular infiltration, was completely eradicated in 98.8% of patients.41 Recurrence rates in this study were found to be very low (1.4%) for both neoplastic and highly dysplastic lesions. Studies have compared cap-assisted and ligation-assisted techniques for removal of Barrett’s associated neoplasia and it has been shown that the ligation-assisted technique slightly decreases the time of the procedure, however both techniques were found to be equally efficacious and had similar rates of adverse events.42

Studies that have evaluated EMR with radiofrequency ablation for Barrett’s have shown remission of neoplasia and metaplasia in 90% of patients 5 years after treatment. In these prospective studies, EMR was first performed on the visible abnormalities and was followed up by circumferential radiofrequency ablation 4-6 weeks after the initial treatment.43

EMR can also be used to remove superficial squamous cell carcinoma (SCC) in the esophagus. Many studies have evaluated the efficacy of EMR on SCC, which have seen a recurrence rate of as low as 0.3% in lesions smaller than 20 mm.40

In the stomach, endoscopic submucosal dissection, or ESD, is most commonly used for gastric cancer as it has been found to be associated with lower recurrence rates when compared to EMR (0.7% vs 6.4% respectively), however, EMR and ESD for early gastric cancer have been found to have similar overall survival rates.44 Due to the lower recurrence rate, ESD is the preferred method for removal of gastric cancer, when available, as it also carries the benefit of histologic evaluation of the margins of the removed lesion 45 (ref 45). EMR does not have this benefit, especially when lesions are removed piecemeal. Gastric carcinoids that are less than 1 cm can also be resected with EMR, however ESD again is the preferred modality as it has also been shown to reduce local recurrence rates in this setting.46,47

Several non-ampullary lesions have been resected with EMR, however in the duodenum, the risk of bleeding and perforation are the highest due to its thin walls. There are several studies that have quoted success rates of up to 96% in removal of these lesions, however as previously mentioned, many of these studies have reported a higher risk of complications.48-51

The colon is largely the most common area of the gastrointestinal tract where EMR is used and is typically performed using the injection-assisted technique. One recent study has shown that local recurrence rates for removal of flat lesions are as low as 3% when removed en bloc but up to 20% when removed in piecemeal.52 After endoscopic retreatment of these areas, with APC, EMR, or both, recurrence rate was 21%, however eradication rate of 91.4% was eventually achieved with an average of 1.2 retreatment sessions. Another large study revealed a recurrence rate of 16% at 4 months and a 4% recurrence rate at 16 months.52 The majority of recurrences in these patients were managed endoscopically and through the results, a timeframe for follow-up colonoscopy after a lesion was removed via EMR was proposed. It was proposed that patients with lesions greater than 15 mm and removed piecemeal, should have colonoscopy repeated in 6-12 months to evaluate for recurrence.51,53 Interestingly, when injection-assisted EMR has been compared to under water EMR, it was found that recurrent lesions were removed significantly better by using the underwater technique (88.9% vs 31.8%).14 A prospective study with polyps ranging from 20 – 100 mm removed via en bloc or piecemeal had an overall recurrence rate of 4.2% after a mean of 30 months. Recurrence was most commonly seen in patients with polyps greater than 40 mm.18 However, in another recent study with a mean polyp size of 30mm, invasive adenocarcinoma was found in 6 polyps (3.4%), 5 of which were successfully treated with EMR.20

As previously mentioned, colonic lesions that do not lift with injection into the submucosal space should not be lifted as this likely indicates invasion into the deeper layers of the bowel wall.1,6-8 However, if a lesions’ inability to lift is thought to be due to fibrosis secondary to a previous intervention, it has been found that these lesions are amenable for removal via EMR.9

As in the esophagus, other techniques may be used as an adjunct to EMR for removal of colonic adenomatous lesions. Several other techniques have been used with EMR, such as biopsy forceps or snare to ablate or remove residual tissue. Interestingly, this adjunctive technique has been found to increase the risk of recurrent lesions.52

Adverse Events

The most common adverse events associated with EMR are bleeding, perforation, and strictures. The most common overall complication is bleeding. Clinically significant bleeding rates can be seen in 11-22% of cases with removal of colonic lesions greater than 20mm.17,54 About one third of these patients may need endoscopic intervention to establish hemostasis. Conventional endoscopic methods for hemostasis are used in this setting.54 Risk factors for clinically significant post-EMR bleeding include size of the lesion, Paris classification (0-IIa and Is), and tubulovillous or villous histology.17

Luckily, colonic perforation with EMR is rare and occurs in less than 1% of cases.1,6,18,55 Signs of injury to the muscularis propria include a whitish or grey central circular area surrounded by the blue staining of the submucosal layer (if a staining additive has been used). This is also known as the “target” sign.56 As with perforations in the colon through other methods, small defects may be controlled with the use of endoclips, however larger perforations often require surgical intervention.56-59

Bleeding secondary to gastric EMR can be seen in up to 11.5% of cases and is also managed through conventional hemostatic techniques.60,61,62 Bleeding rates in the duodenum have similar risk as in the stomach for lesions less than 3cm but have been reported in up to 58% of cases with larger lesions.49-63 The risk of perforation in the stomach is low (<1%) likely due to the increased thickness of the stomach wall.64 Few studies have been performed which have evaluated the risk of perforation in the duodenum and report a risk of less than 2%, however the risk is believed to be higher given the thin duodenal walls, therefore it is advised that EMR in the duodenum should be performed with caution.63

In the esophagus, adverse events are overall much lower than in the colon. Unlike the colon, the most common adverse effect in the esophagus is stenosis and can widely range between 6-88% of cases according to several studies.41,65,66-70 Strictures can occur after removal of large mucosal resections, circumferential resections, or resection of multiple lesions but can be treated similarly to strictures of any alternative etiology with esophageal dilation.41,67,70 Bleeding can also occur in the esophagus and has been observed in about 1.2% of patients.71-76 Perforation in the esophagus is also seen less often and has been reported as low as less than 0.5% in the setting of an experienced endoscopist who routinely uses EMR.41,60,66,76-83 In comparison to ESD, EMR has been associated with a significantly lower rate of perforation.40

CONCLUSION/SUMMARY

EMR is a very helpful and safe endoscopic technique for removal of larger premalignant and early-stage malignant lesions of the gastrointestinal tract. Prior to the consideration of EMR, it is critical that the lesion selection is appropriate. Close endoscopic evaluation to delineate lesion margins, size (>1 cm), and identification of lesion depth are imperative. EUS can be used, if needed, to stage the lesion and further identify the depth of mucosal involvement. Many endoscopists have found it helpful to lift the lesion with a staining solution or mark the periphery of the lesion with cautery such as argon plasma coagulation or with the tip of a hot snare to further define the lesion margins and extent to be resected. Adjunctive techniques may be used along with EMR to further remove or ablate residual tissue. Lesions greater than 1.5 or 2 cm should be removed piecemeal. However, close follow-up colonoscopy, especially if the lesion is removed piecemeal as this poses a higher risk for recurrence. The most common adverse event is bleeding and if the lesion is deemed to be high risk, preventative measures or conventional hemostatic methods should be taken if post-resection bleeding occurs. Endoscopists performing EMR should be knowledgeable and skilled in treating possible adverse events associated with EMR.

Download Tables, Images & References

A Case Report

Necrotizing Rash Associated with Autoimmune Hepatitis

April 2018 • Volume XLII, Issue 4
Lili Loni Barsky,Yaw A. Adjepong

Read Article

Background:
An unfamiliar skin eruption often prompts an immediate referral to dermatology, when more thorough evaluation may be warranted first. We describe a case where an unusual skin lesion was the first observed sign of an underlying gastrointestinal illness.

Clinical Case:
A previously well male presented with a burning skin rash.
Physical examination revealed multiple desquamating lesions. Serologic evaluation showed elevations in liver enzymes, international normalized ratio, antinuclear antibody, anti-smooth muscle antibody and gammaglobulin titers, thrombocytopenia and C4 hypocomplementemia. Skin biopsy revealed epidermal necrosis and diffuse lymphocytic infiltrate. Liver biopsy showed interface hepatitis. Upon initiation of steroids, the skin lesions and abnormal liver enzymes resolved.

Conclusion:
The clinical findings and response to steroids confirmed autoimmune hepatitis. This case highlights the importance and challenge the internist faces in distinguishing between primary dermatoses and cutaneous manifestations of gastrointestinal disease.

Lili Loni Barsky, MD Yaw A. Adjepong, MD, MPH, PhD Yale University/Bridgeport Hospital, Bridgeport, CT

Case Presentation

A49-year-old previously well male presented with a three-week history of multiple burning and peeling skin lesions. These lesions initially appeared on his right palm and fingers and subsequently spread diffusely. His review of systems was otherwise negative. The man denied any recent changes in soaps, lotions or detergents, trauma, known allergies, insect bites, heat or chemical exposure or sick contacts. He did not take any medications, vitamins or supplements. The patient immigrated to the United States from South America ten years ago but had not traveled since. He worked in construction but always wore gloves. He most recently engaged in sexual intercourse four years ago with one female partner, with intermittent condom use. He denied any history of sexually transmitted infection. He admitted to consuming two beers weekly for the past eight years as well as a remote history of marijuana use, but he denied use of tobacco or other recreational drugs.

On admission, the patient was afebrile and hemodynamically stable. His physical examination revealed multiple small, coalescing, desquamating, vesiculopustural lesions with surrounding erythema (Figure 1), in a scattered distribution on the bilateral palms, left elbow, scalp and bilateral ears. The mouth, groin and soles were spared. Nikolsky sign was negative.

Laboratory evaluation showed an elevated alanine aminotransferase of 100, aspartate aminotransferase of 571, alkaline phosphatase of 184, hyperbilirubinemia of 1.5, hypoalbuminemia of 2.7, increased international normalized ratio of 1.56 and thrombocytopenia of 18,000. He also had elevated antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA) titers of 1:320, hypergammaglobulinemia and C4 hypocomplementemia. Titers were negative for the viral hepatidites, rapid plasma reagin, human immunodeficiency virus, human T-cell lymphotropic virus, Babesia, Ehrlichia, double stranded deoxyribonucleic acid, Ro, cryoglobulins, porphyrins, glucose-6-phosphate dehydrogenase, rheumatoid factor, celiac panel and the anti-neutrophil cytoplasmic, cardiolipin, topoisomerase-1, histone and mitochondrial antibodies. The urine drug screen, gonorrhea screen and blood and skin cultures were negative. Skin biopsy revealed confluent epidermal necrosis with increased dermal mucin (Figure 2a) and diffuse perivascular and periadnexal lymphocytic infiltrate (Figure 2b), with no deposition on direct immunofluorescence (DIF). Liver biopsy demonstrated interface hepatitis. The patient was initiated on steroids, and his skin lesions and abnormal liver enzymes resolved after four months.

Case Discussion

The presence of elevated liver transaminases, ANA and ASMA titers and hypergammaglobulinemia in conjunction with liver biopsy finding of interface hepatitis and response to steroids all verify the diagnosis of autoimmune hepatitis (AIH).1 While other dermatological conditions may be considered, they do not embody the clinicopathologic characteristics of this patient’s skin lesions. While the skin’s histological findings could suggest Rowell’s syndrome,2 the positive ANA titer was the only major criterion for the condition fulfilled in this case. Also, the lack of deposition on DIF and atypical clinical appearance for any of the subtypes excluded cutaneous lupus erythematosus. Perivascular and periadnexal lymphocytic infiltration can also be observed in polymorphous light eruption (PLE), Jessner’s lymphocytic infiltration of the skin and reticular erythematosus mucinosis (REM).3 However, these differentials were excluded by the atypical clinical appearance, presence of mucin deposition and high ANA titer. The patient’s skin eruption was attributed to a cutaneous manifestation of his underlying AIH.

Case Conclusion

When faced with an unusual desquamative diffuse skin rash as described here, the primary care physician may rush to consult dermatology, when instead a more comprehensive systemic evaluation should be pursued. Such an abnormal skin finding can actually be the first indication of something systemic. This case highlights the importance and challenge presented to the primary care physician in distinguishing between primary dermatoses and cutaneous manifestations of gastrointestinal disease.

Download Tables, Images & References

A Special Article

Hepatitis C Screening Among Baby Boomers at Risk for Hepatitis B

April 2018 • Volume XLII, Issue 4
Rotimi R. Ayoola,Sebastian Larion,David Poppers,Renee Williams

Read Article

The Centers for Disease Control (CDC) recommends that baby boomers (adults born between 1945-1965) be screened for hepatitis C (HCV). Patients with HCV are at increased risk of co-infection with hepatitis B (HBV). In this article, we investigate HCV screening rates in a baby boomer cohort with chronic HBV or at high-risk for HBV infection from a large healthcare system.

Background and Aims: The Centers for Disease Control (CDC) recommends that baby boomers (adults born between 1945-1965) be screened for hepatitis C (HCV). Patients with HCV are at increased risk of co-infection with hepatitis B (HBV). We investigated HCV screening rates in a baby boomer cohort with chronic HBV or at high-risk for HBV infection from a large healthcare system.

Methods:
We conducted a retrospective cohort analysis of 792 baby boomers, evaluated at New York Langone (NYU) from 2012-2017 with chronic HBV or at high-risk for HBV infection. CDC guidelines were used to assess whether a patient was considered at high-risk for HBV infection. Medical history including hepatitis serology was extracted from electronic health records. Multiple logistic regression was used to identify clinical risk factors independently associated with HCV screening.

Results:
Among 792 patients, 419 (52.9%) were screened. Multivariate regression of factors significant (P< .05) on univariate analysis revealed that health insurance, end-stage renal disease (ESRD), chronic liver disease (CLD), diabetes mellitus (DM) and current alcohol use were each independently associated with HCV screening. The strongest predictors of HCV screening were ESRD (OR: 3.346; 95% CI: 1.688-6.634) and CLD (OR: 3.027; 95% CI: 2.102-4.359), while DM (OR: 0.680; 95% CI: 0.497-0.930) was associated with a decreased likelihood of prior screening.

Conclusion:
In a retrospective study of patients at NYU, the baby boomer cohort with chronic HBV or at high-risk for HBV infection are not being adequately screened for HCV. Improvement in HCV screening should be strongly encouraged by all healthcare systems.

Rotimi R. Ayoola, MD1 Sebastian Larion, MD2 David Poppers, MD3 Renee Williams, MD3 1Department of Medicine, New York University Langone Health, Brooklyn, NY 2Department of Medicine, Augusta University, Augusta, GA 3Department of Medicine, Division of Gastroenterology, New York University Langone Health, New York, NY

INTRODUCTION

Hepatitis C virus (HCV) is a major public health issue in the United States and worldwide. It is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC) and the most common indication for liver transplantation in the United States.1 From 2003 to 2010 an estimated 2.2-3.2 million Americans were chronically infected with HCV, with a high proportion of people unaware of their infection (estimates range from 45-85%).2,3 Studies show that 76% of people diagnosed with HCV infection in the United States are in the “baby boomer” cohort (those born between 1945 and 1965).

Given the strong incidence of HCV within this birth cohort, in 2012 the Centers for Disease Control and Prevention (CDC) recommended one- time testing for HCV in baby boomers without specific HCV risk factors.3,4 Application of current guidelines for risk-based screening would result in an estimated 25% of the US adult population being tested. 5 Initial evaluation should include a standard anti-HCV antibody serologic test, with a reactive result followed by a confirmatory nucleic acid test or polymerase chain reaction for HCV ribonucleic acid. One-time testing of baby boomers has been estimated to identify 800,000 infections, with subsequent treatment and management potentially avoiding up to 120,000 HCV-related deaths.6

Screening rates in this birth cohort in patients with chronic hepatitis B virus (HBV) or in those at high-risk for HBV infections have not been well documented. HCV and HBV patients share common risk factors (intravenous drug use, hemodialysis treatment and human immunodeficiency virus infection). About 2-10% of HCV-positive patients are found to be positive for HBV surface antigen, and 5-20% of patients with HBV are found to be anti-HCV positive.7-11 Per CDC criteria, all individuals in the birth cohort should be screened for HCV regardless of specific risk factors, yet a better understanding of screening rates in patients with chronic HBV or at high-risk for HBV infection is needed (Table 1). A greater awareness of HCV screening failures could potentially lead to improved screening rates, better HCV and HBV management practices and patient care.

In this study, we report HCV screening rates and independent clinical factors associated with screening adherence in a diverse birth cohort patient population with chronic HBV or at high- risk for HBV infection.

MATERIALS AND METHODS

A retrospective analysis was performed using electronic medical records (EMR) of patients presenting at New York Langone Health between 2012 and 2017 with chronic HBV or at high-risk for contracting HBV infection. Patients were considered at high-risk for contracting HBV infection if they had a medical comorbidity or activity that was classified as high-risk by CDC criteria (Table 1).4 Medical conditions were identified using ICD-10 classification and patients were randomly selected to be included in the study. Patients were excluded from the study if they were not born between 1945 and 1965 and did not have one of the documented risk factors for HBV infection or a history of chronic HBV infection.

Patient information was obtained from the EMR by individual chart review and entered into a password-protected, HIPPA-compliant and de-identified REDCap repository (Vanderbilt University, Nashville, TN). Patient demographics and clinical history were compared between a cohort of patients who were screened for HCV versus a cohort of patients who were not screened for HCV. Screening was considered to have been performed if HCV serology was listed in the EMR (either positive or negative for HCV antibody). Results are presented as frequencies or percentages, with categorical variables compared using chi- square and continuous variables compared using two-sided Student’s t-test or Mann-Whitney U test, as appropriate. Covariates found significant on univariate analysis were inputted into a multiple logistic regression with HCV serology listed as the binary dependent variable. The Hosmer- Lemeshow statistic was used to assess model calibration. Statistical analysis was performed using SigmaPlot v10.2 (Systat Software, San Jose, CA). The Institutional Review Board of New York University Langone Health approved this study.

RESULTS

A total of 1,100 high-risk patients were evaluated in the initial data set, of which 792 were born between 1945 and 1965 and included in the final study (Figure 1). Patient demographics for the entire study cohort are listed in Table 2, showing that most patients were older (mean age: 61.7 years), male (63.9%) and overweight (median BMI: 27.4 kg/ m2). The study population was socio-economically diverse with 51.9% of respondents reporting non- white ethnicity and 43.6% lacking private health insurance.

High-risk medical conditions for the study population are listed in Table 3. Diabetes mellitus (DM) (46.3%; median hemoglobin A1c: 6.4%; 25- 75th quartiles: 5.6-7.7%), chronic kidney disease (CKD) (43.7%) and high-risk sexual behavior (27.2%) were the most commonly reported comorbidities. End-stage liver disease (ESLD) was present in 12.9% of patients with 9.2% listed for liver transplant with median Model for End- Stage Liver Disease (MELD) score of 13 (25-75th quartiles: 9-21). A total of 37 (4.7%) patients died during the data collection period, including 13 (1.6%) from liver-related etiologies. Most patients (75.8%) had two or more high-risk conditions, while 39.6% had 3 or more conditions. Importantly, a history of intravenous drug use (2.8%) or alcoholic hepatitis (3.2%) was reported in only small subset of these patients. Other medical comorbidities are listed in Table 4. Cardiovascular risk factors such as hypertension (58.0%), hyperlipidemia (42.9%) and a history of tobacco use (40.2%) were highly prevalent in our patient population. Primary care physicians evaluated a total of 29.4% of patients at least annually, while a gastroenterologist evaluated 26.4% of patients at least yearly.

A total of 419 patients (52.9%) were screened for HCV while 373 patients (47.1%) were not screened. Univariate analysis revealed that patients who were screened for HCV more frequently had private health insurance (58.0% vs 54.7%; P=0.004; Table 2), history of intravenous drug use (4.1% vs 1.3%; P=0.035; Table 3) or were currently using alcohol (35.1% vs 25.0%; Table 4). Patients who were screened were more likely to have a significant liver history including chronic liver disease (CLD) (44.9% vs 22.0%; P<0.001; Table 4) or ESLD (18.4% vs 6.7%; P<0.001; Table 3). Patients with HCV screening also presented with a higher rate of renal pathology including CKD (50.4% vs 36.2%; P<0.001) and end-stage renal disease (ESRD) (44.9% vs 29.2%; P<0.001), and less frequently with DM (40.3% vs 53.1%; P<0.001; Table 3).

Multivariate regression of factors significant (P<0.05) on univariate analysis revealed that health insurance, ESRD, CLD, ESLD, DM and current alcohol use were each independently associated with HCV screening (Model 1; Table 5). The strongest predictors of HCV screening were ESRD (OR: 3.346; 95% CI: 1.688-6.634) and CLD (OR: 3.027; 95% CI: 2.102-4.359), while DM (OR: 0.680; 95% CI: 0.497-0.930) was associated with a decreased likelihood of prior screening. The Hosmer-Lemeshow statistic was not significant (P=.215), indicating that the regression fit the data. Using more restrictive modeling where only the most significant (P<0.01; Model 2) factors were inputted into the multivariate analysis, there was no appreciable change in the study findings, suggesting that intravenous drug use and alcoholic hepatitis do not change the likelihood of HCV screening.

In addition, patients who were not screened for HCV were less frequently vaccinated against hepatitis A (12.8% vs 76.1%; P<0.001) or HBV (6.3% vs 42.9%; P=0.009). These patients were less likely to utilize health care resources such as annual primary care evaluation (19.8% vs 38.0%; P<0.001), emergency department visits (26.0% vs 39.4%), or a gastroenterology specialist consultation (13.4% vs 38.0%; P<0.001). Listing for liver transplant was also less likely (5.1% vs 12.9%; P<0.001) in patients who were not screened for HCV, despite no difference in MELD score between groups (median: 13 vs 12: P=0.763). All-cause mortality (6.9% vs 2.1%; P=0.003) and liver-related mortality (2.6% vs 0.5%; P=0.042) were significantly increased in patients who were screened for HCV.

DISCUSSION

Despite CDC recommendations concerning practice management guidelines for HCV and HBV, baby boomers with chronic HBV or at high- risk for HBV infection are not being adequately screened for HCV. These patients are also less frequently vaccinated for other conditions such as hepatitis A or HBV, less likely to utilize primary care or specialty services and less likely to be listed for liver transplant.

Most individuals are unaware of their HCV and HBV infection status.12 This study retrospectively evaluated HCV screening patterns in a diverse, birth cohort in the New York area, which revealed a screening non-adherence rate (52.9%) more than twice that reported in a previous study.13 This study also identified socioeconomic risk factors such as insurance status that were independently associated with reduced HCV screening. These patients were also less likely to utilize health care resources such as primary care or gastroenterology subspecialist services. Patients who were not screened for HCV were also significantly less likely to be listed for liver transplant, despite no differences in MELD score between patient groups. Thus, socioeconomic factors can impair access to appropriate medical care, often resulting in non-adherence with HBV and HCV practice management guidelines and adverse patient outcomes. Larger studies with longer patient follow-up are needed in order to assess whether socioeconomic factors in the at- risk HBV birth cohort results in increased all-cause or liver-related mortality. Due to the 2012 CDC recommendations on HBV screening, the New York State legislation enacted a public health law in 2014 that requires all health care providers to offer HCV screening. Thus, hepatitis screening and virus detection are expected to improve.14,15

HBV and HCV co-infection is frequent due to shared risk factors and modes of transmission such as intravenous drug use. Previous studies have demonstrated that HBV/HCV co-infected patients carry a greater risk of advanced liver disease, cirrhosis and hepatocellular carcinoma in comparison to monoinfected patients.11,16 Early detection and treatment of HBV and HCV could potentially prevent progression of liver disease, decrease the need for liver transplantation and reduce the risk for overall liver disease-related morbidity and mortality.17,18 With only 52.9% of eligible patients appropriately screened for HCV, our study identifies a substantial potential area of improvement in practice management that could significantly improve patient care. However, increasing patient and clinician awareness of viral liver disease continues to pose challenges, which may be attributed to a number of factors in our diverse study population including lack of physician emphasis and knowledge regarding current screening recommendations, cultural barriers and socioeconomic elements constraining access to appropriate medical care.19

Few studies have focused on HBV and HCV screening and vaccination rates in at-risk HBV patients in the baby boomer cohort.

Viral hepatitis serology is frequently completed in order to properly manage chronic HBV infection. Despite the low rate of screening in our high-risk cohort, HCV screening is performed even less frequently in the general birth cohort. One 2004- 2008 study of the commercially-insured birth cohort population in New York estimated an HCV screening rate of 17.6%.20 Another study examining hospitalized patients reported that only 35% of eligible patient underwent HCV screening.15 Certainly, while the presence of chronic HBV or risk factors for HBV infection contribute to the differences in screening, it is important to note that screening rates for both the general and high-risk population remain low.

This study was subject to several limitations. Retrospective reviews of EMR data are limited by the ability to extract relevant data from the patient record. It is possible that patients were screened by outside providers or primary care facilities that were not accessible in the EMR, raising the possibility that true HCV screening rates are underestimated. Another possibility is that appropriate screening was indeed performed, but not accurately listed in the patient EMR. Although the CDC recommends one-time HCV screening in all individuals born between 1945- 1965 regardless of risk, clinical judgment and cognitive bias may often direct screening practices. Other potential biases include selection bias and errors in patient sampling. However, these biases are believed to be mitigated by the size of our sample population. Patients also may not know their complete medical history or choose not to divulge their behaviors to the attending physician, resulting in the underestimation of the high-risk patient population. For example, disclosure of past or current intravenous drug use is often not disclosed or under-reported. With recent reports of HCV infections tripling between 2010 and 2015, with highest rates among 20-29 year-old users of illicit substances, it is even more important to thoroughly review and document a patient’s medical history.4 Lastly, during the study one of the academic hospitals in our health system underwent a change in EMR and information on some patients could therefore not be obtained. One subject that remains to be explored is how to improve HCV screening awareness and specific barriers to screening.

CONCLUSION

This study reveals that HCV screening in patients in the birth cohort with chronic HBV or at high- risk for HBV infection remains low despite CDC practice recommendations. Due to the fact that HBV/HCV co-infection is not uncommon and may lead to more rapid progression to advanced liver disease compared to monoinfection, including HCC, it remains imperative to properly screen these individuals to allow for early recognition and management. Greater emphasis should be placed on increasing physician awareness of CDC guidelines advocating for one-time HCV screening of people born between 1945-1965, particularly those with chronic HBV or at high risk for infection. However, challenges remain to identify methods that improve physician adherence with these recommendations.

Download Tables, Images & References

Gastrointestinal Motility And Functional Bowel Disorders, Series #24

Upgrade Your Dysphagia Expertise – How to Diagnose Oculopharyngeal Muscular Dystrophy

April 2018 • Volume XLII, Issue 4
Alejandro Del Cerro Rondon,Majd Michael,Darine Kassar,Richard W. McCallum

Read Article

Oculopharyngeal muscular dystrophy (OPMD) is rare, adult-onset, familial muscular dystrophy, which has been mainly characterized clinically by progressive dysphagia and ptosis. In this article, we present our experience with three patients with OPMD and the challenges in the diagnosis and treatment.

Oculopharyngeal muscular dystrophy (OPMD) is rare, adult-onset, familial muscular dystrophy, which has been mainly characterized clinically by progressive dysphagia and ptosis. Dysphagia determines prognosis due to an increase in the risk of aspiration pneumonia and also poor nutrition. OPMD is suspected clinically in older adults with the combination of ptosis and dysphagia. A positive family history may be obtained. Impairments in cricopharyngeal relaxation and hypertonicity of the upper esophageal sphincter (UES) can be best documented through a modified barium swallow. Molecular genetic testing confirms the diagnosis. Treatment options include cricopharyngeal myotomy, cricopharyngeal dilatation and cricopharyngeal botulinum toxin injection. Dilatation of the upper esophageal sphincter by the gastroenterologist is a safe and effective procedure. It has the advantage that can be repeated over the years and complications are rare. Cricopharyngeal (UES) myotomy is the most common surgical intervention. Improvement is seen immediately after surgery, but high recurrence rates and the procedure itself leave the patient at risk for aspiration pneumonia. Botulinum toxin injection has limited literature support and unclear outcomes. We present our experience with three patients with OPMD and the challenges in the diagnosis and treatment.

Alejandro Del Cerro Rondon, MD, PGY-1 Internal Medicine Resident, Department of Internal Medicine Majd Michael, MD, PGY-3 Internal Medicine Resident, Department of Internal Medicine Darine Kassar, MD, Assistant Professor, Department of Neurology, Texas Tech University Richard W. McCallum, MD, FACP, FRACP (AUST), FACG, AGAF, Professor of Medicine and Founding Chair, Division of Gastroenterology, Director, Center for Neurogastroenterology and GI Motility, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX

CASE 1

A 71-year old female with past medical history of asthma, diabetes, hypertension, hypothyroidism, rheumatoid arthritis, obstructive sleep apnea, gastroesophageal reflux disease (GERD) and a surgical history significant for cardiac pacemaker was referred for progressive dysphagia over the past ten years. The dysphagia was initially to solids, worsening in the last three years and now is to both solids and liquids. The patient also noticed hoarseness. She developed bilateral ptosis four years ago, and at that time underwent blepharoplasty. The patient also reported difficulty climbing stairs.

On physical exam, the patient had bilateral ptosis with normal extraocular muscles movement, mild hoarseness and weakness of deltoid, supraspinatus and iliopsoas muscles bilaterally. The patient demonstrated a steady gait.

Initial evaluation for dysphagia utilizing a modified barium swallow study showed irregular filling in the piriform sinus esophageal stenosis at the C5-C6 level, cricopharyngeus hypertrophy and silent aspiration. Upper endoscopy revealed a normal esophagus, thrush in the oropharynx, non-bleeding gastric erythema and normal duodenum. High-resolution esophageal manometry documented decreased lower esophageal sphincter pressure with adequate relaxation. Findings of normal peristalsis in smooth muscle portion of the esophagus as well as striated muscle weakness were noted. Also, pharyngeal contractions and esophageal mobility at cervical level appeared reduced.

Laboratory workup results were negative for acetylcholine receptor antibodies, muscle-specific kinase (MuSK) antibodies, myeloperoxidase antibodies, and antineutrophil cytoplasmic antibodies (ANCA) profiles also came back negative.

Modified barium swallow showed a weak oropharyngeal phase of swallowing with significant pooling of contrast in the piriform sinuses and vallecula. Silent aspiration was also noted (Figure 1). The patient was referred to speech therapy, and, after a few sessions of exercise to improve swallowing, she continued to have aspirations that resulted in pneumonia.

The decision was made to dilate the upper esophageal sphincter to facilitate emptying and decrease aspiration risk. The dilation was performed utilizing a balloon through the scope to a maximum balloon size of 20 mm. Dilation was tolerated with no complications. However, her dysphagia did not improve so the decision was made to undergo a second esophagogastroduodenoscopy (EGD). This time a mild, benign-appearing, intrinsic stenosis was found in the upper third of the esophagus and was dilated utilizing a Savary dilator method over a guidewire with fluoroscopy monitoring with no resistance at 18, 19 and 20 mm. The dilation site was re-examined and showed mild improvement in luminal narrowing (Figures 2 and 3).

The patient reported improvement of the dysphagia after the second dilation and started a diet of pureed food. Genetic confirmatory testing for oculopharyngeal muscular dystrophy (OPMD) was ordered.

CASE 2

A 71-year-old woman with a past medical history of hypothyroidism and dyslipidemia experienced difficulty with swallowing starting at 40 years of age. Also, around same time noticed bilateral ptosis requiring blepharoplasty twice. She reported a family history of similar symptoms in her mother, maternal grandmother and three siblings. On physical exam, there was weakness in orbicularis oculi muscles bilaterally with limitation in extraocular muscles movements. Muscular strength of upper and lower extremities was adequate. The DNA test came back positive for 9 GCG repeat expansion in PABP2 gene confirming OPMD.

A modified barium swallow showed increased pooling in the vallecula, accumulation of contrast in the piriform sinus with penetration and aspiration of liquids. The patient started working with speech therapy weekly. Esophageal upper sphincter dilation was performed twice using a through the endoscope balloon technique with a minor improvement of the dysphagia.

CASE 3

A 70-year-old man with a past medical history of hypertension and hyperlipidemia presented to the clinic for evaluation of muscle weakness. He reported difficulties using the stairs for the last 10 years. Also, in the previous five years, he noticed a change in his voice and swallowing problems when eating solids. Multiple family members from his mother side have similar symptoms including his mother, three aunts, one uncle and a grandmother. On physical exam, weakness of the orbicularis oculi muscles was remarkable. Extraocular movements were intact. Proximal lower extremity muscle weakness was noted. A modified barium swallow showed a marked deficiency of the swallow mechanism with increased pooling in the vallecula and piriform sinus. Penetration and aspiration were present. DNA test was ordered and came back positive for 9 GCG repeat expansion in PABP2 gene confirming OPMD. The patient refused treatment for dysphagia and also percutaneous endoscopic gastrostomy (PEG) tube placement.

Discussion

Oculopharyngeal muscular dystrophy (OPMD) is rare, adult-onset, familial muscular dystrophy which has been mainly characterized clinically by progressive dysphagia and ptosis due to an involvement of the pharyngeal and palpebral musculature, respectively. E. W. Taylor first described it in 1915 emphasizing the unusual combination of ptosis and pharyngeal palsy in a family of French-Canadian descent. However, Taylor believed that the cause of this rare entity was a degeneration of vagus and glossopharyngeal nuclei. He called it progressive vagus-glossopharyngeal paralysis with ptosis. It was not until 1951 after the observations of Kiloh and Nevin of cases with similar symptoms but also had involvement of limb and trunk muscles suggesting the myopathic nature of the disease. In 1962, Victor et al. reported three cases in Jewish family from eastern Europe with a dominant mode of inheritance with clinical features of progressive dysphagia and ptosis in the late life and named the disease oculopharyngeal muscular dystrophy.1

Cases of patients with OMPD have been reported in numerous countries in all five continents. The most significant clusters of patients are in Quebec of French-Canadian origin,2 in Israel from Bukhara Jewish immigrants3 and in Hispanics living in New Mexico.4

The mean age of onset for ptosis is 48 years and for dysphagia is 50 years. Dysphagia determines prognosis due to an increase in the risk aspiration pneumonia and also poor nutrition. As the disease progresses, there are other signs like hoarseness, weakness of the tongue, facial muscles and proximal upper and lower extremities. Involvement of the central nervous system (CNS) also has been reported.5 Severe OPMD represents five to 10% of all cases and is characterized by symptoms before age 45 years and incapacitating proximal leg weakness before age 60 years.6

The mechanisms contributing to dysphagia in OPMD patients include reduced lingual pressure generation, impairments in cricopharyngeal relaxation and hypertonicity of the UES and incomplete laryngeal vestibule closure and subsequent airway compromise. Swallowing efficiency and safety are affected and is a significant determinant of prognosis due to an increase in the risk aspiration pneumonia and also poor nutrition. In the end stages of disease is recommended the use of PEG tubes to address both malnutrition and aspiration risks.7 Swallowing-related quality of life is moderately impacted characterized by prolonged mealtime durations and increased burden that contribute to social withdrawal and decrease enjoyment of meals in these patients.8

OPMD is suspected clinically with a combination of ptosis, defined as either vertical separation of at least one palpebral fissure measuring less than eight mm at rest or previous corrective surgery and dysphagia, characterized by a swallowing time greater than seven seconds when drinking 80 ml of ice-cold water. Modified barium swallow (MBS) using applesauce, cereal, liquids and videofluoroscopic swallowing study (VFSS) are essential to document aspiration and dysfunction of the pharyngeal muscles and upper esophageal sphincter (UES).6 Standard esophageal motility studies to analyzed upper esophageal sphincter function have not been rewarding or diagnostic.

Molecular genetic testing confirms the diagnosis with a detection of an expansion of a GCN trinucleotide repeat in the first exon of PABPN1 (previously named PABP2). Normal alleles contain 10 GCN 6 GCG trinucleotide repeats. Autosomal dominant alleles range in size from 12 to 17 GCN repeats. Patients with longer PABPN1 expansion and homozygotes are, on average, diagnosed at an earlier age, the disease is more severe and shows a faster progression.9

Autosomal recessive alleles comprise 11 GCN repeats and present later in life usually after the six decades.6,10,11

Muscle biopsy is only necessary if suspicion of the disease exists and there is a presence of two normal PABPN1 alleles. The biopsy of muscle shows in some patients with OPMD, intranuclear inclusions of tubular filaments that are 250 nm in length, dystrophic changes such as atrophic muscle fibers of different width, ragged red fibers, and rimmed vacuoles. Electromyography (EMG) is not specific or necessary for OPMD diagnosis and often shows signs of myopathic changes that could also be related to age. Serum creatine kinase (CK) concentrations are usually in range or twice the upper limit. CK level is not sensitive or specific for the diagnosis of OPMD.6

Differential Diagnosis

  • Facioscapulohumeral dystrophy (FSHD) symptoms usually begin in the 2nd decade, in contrast to OPMD that presents later in life. The muscular weakness has a different distribution than OPMD with facial, scapular, abdominal upper and lower extremities affected. Facial muscles weakness is milder compared to OPMD. Dysphagia is rare in this entity.12
  • Myotonic dystrophy presents with different genotypes and onset of presentation. There is a combination of proximal and distal weakness. Myotonia and muscle pain are cardinal symptoms, and both are absent in OPMD.13
  • Mitochondrial myopathies have variable clinical expression. Myopathy could be a major or a minor clinical feature depending on presentation. Muscles symptoms range from fatigue, myalgia and exercise intolerance. Other associated features are retinitis pigmentosa, ataxia. These are not present in OPMD patients. The inclusion body myositis found in mitochondrial myopathies are 15-18 nm filaments compared to 250 nm filaments in OPMD.14
  • Myasthenia Gravis usually presents with ptosis, diplopia and bulbar involvement as dysarthria, dysphagia, generalized weakness and positive test results for anti-AChR or anti-MuSK antibodies. These serologic markers are negative in patients with OPMD.15

Treatment

The treatment in OPMD patients is supportive in most cases. Avoiding secondary complications such as aspiration pneumonia, malnutrition and social withdrawal is the primary focus. Blepharoplasty is the treatment of choice for ptosis. Surgery is usually done for cosmetic reasons and is recommended when it affects vision in the central position of gaze and neck pain due to retroflexion of the neck.16,17 It has been hypothesized that this compensatory position also affects dysphagia in OPMD patients.18 Exposure keratitis is a known complication of this surgery.16

Cricopharyngeal (UES) myotomy is the most common surgical treatment for dysphagia. Clinical improvement is seen immediately after surgery, but long-term follow-up shows a decrease in success due to the progression of the myopathic process in the pharyngeal muscles, making early diagnosis and treatment necessary. This procedure also carries the increased risk of aspiration when gastroesophageal reflux occurs in the setting of weakened pharyngeal protection.19-21

Botulinum toxin injections for dysphagia are another alternative to treatment. Safety and efficacy of this intervention is dose-dependent, requires frequent retreatment and is expensive. Higher doses have led to worsening of the dysphagia and also dysphonia due to diffusion of neurotoxins in nearby muscles.24,25

Dilatation of the UES through an upper GI endoscope is a relatively safe, well-tolerated procedure that is usually performed as an outpatient and only requires moderate sedation. The Savary dilatation method is recommended where a guidewire is passed and dilatation with increasing sizes is performed under fluoroscopic monitoring. This procedure can be repeated throughout the years and complications are rare and include perforation or hemorrhage. This technique has a reasonable success rate in improving dysphagia, weight maintenance, prolongation of oral feedings and avoidance of necessity for PEG which is an option.22,23

Download Tables, Images & References

The Microbiome And Disease, Series #4

The Microbiome and the Heart

April 2018 • Volume XLII, Issue 4
Alon Steinberg,Sabine Hazan

Read Article

In this article, we discuss further understanding the gut microbiome along with its effect on metabolites and cardiovascular health. This understanding will give us opportunities to develop new test and therapeutic approaches to arteriosclerosis. In the future, stool transplantation with lean or low risk for cardiovascular disease microflora may be a way of treating patients who are susceptible to arteriosclerosis.

Alon Steinberg MD, Cardiology Associates Medical Group, Ventura Clinical Trials, expertcardiologist.com Sabine Hazan, MD, Gastroenterology/Hepatology/ Internal Medicine Physician, CEO, Ventura Clinical Trials, CEO, Malibu Specialty Center, Ventura, CA

Despite great focus and multiple treatments for coronary artery disease and its risk factors, the residual number of deaths is very large. Cardiovascular disease is the number one cause of death in the world.1 Our well-known risk factors for arteriosclerosis do not always explain the degree of cardiovascular disease development and risk of myocardial infarction and death. Researchers and physicians are looking to uncover novel reasons and risk factors in hopes to explain why patients develop arteriosclerosis and ruptured plaque. There has been an interest in inflammation including obesity and metabolic syndrome as contributing factors. As eloquently summarized in last issue of Practical Gastroenterology,2 the microbiome may contribute significantly to these risks.

Humans have a symbiotic relationship with our gut microflora. The gut microbiome helps metabolize fuels, aids with absorption and helps create important vitamins and amino acids. The microbiota breaks down toxins and is a barrier against invading bacteria. What we eat has a large impact on the development of heart disease. Can the study of the microbiome help us understand why we develop heart disease? Can we can work to manipulate the microbiome to prevent heart disease?

There appears to be lean and obese microbiota.3 In study with mice, lean and obese donors had their cecal microbes transplanted to germ-free recipients. Those mice colonized with obese microbiome developed obesity while those with lean donors remained lean. This documents that our microbiome can affect what we absorb and is a factor in our metabolism. This study also showed that this may be transmissible and changed.3 In a human study, stool transplant from lean donors to obese recipients with metabolic syndrome showed significant and persistent improvement in insulin sensitivity.4 This shows that changing gut microorganisms can alter mechanisms that can transform and improve metabolism. Further understanding hopefully with can lead to developing intestinal microbiota as a therapeutic agent to reduction of obesity, metabolic syndrome, inflammation and cardiovascular disease.

There is a saying that the best way to a man’s heart is through his stomach. But we now know that is not just what you eat but what your gut microbiome lets pass and creates. Metobolomic studies have now revealed effective routes linked to cardiovascular disease. Metabolites choline, TMAO, and betaine were shown to predict risk for cardiovascular disease in an independent large clinical cohort.5 These metabolites are linked to lecithin (or phoshaphatidylcholine) metabolism. Our Western diet is full of lecithin. Gut microbes use lecithin to create trimethylamine (TMA) which gets absorbed by the gut. While in blood circulation, the liver then converts TMA to TMAO.

Dietary supplementation with these metabolites in mice showed an upregulation of multiple macrophage scavenger receptors and creation of foam cells and arteriosclerosis. When these diet supplements were given to mice with gut free of flora, dietary metabolites were not created and thus did not promote arteriosclerosis.5 In a human study, suppression of intestinal microbiota with oral broad-spectrum antibiotics showed plasma levels of TMAO were markedly suppressed. TMAO rise reappeared after withdrawal of antibiotics.6

Further testing has been done with Trimethylamine N-oxide (TMAO). Increased levels of TMAO were associated with an increased risk of major adverse cardiovascular events6 and may be a stronger risk factor than LDL and C-reactive protein. A recent meta-analysis showed TMAO increased cardiovascular risk and mortality.7 This gut metabolite that has been associated with accelerated arteriosclerosis, enhanced platelet hyper-reactivity and thrombosis risk.8

One way to control TMAO levels is diet. Vegetarians, vegans and those on Mediterranean diet9 are associated with lower TMAO levels. TMAO decrease may explain the reduction in cardiovascular risk with the Mediterranean diet.

Another way to target TMAO is antibiotics. Prior antibiotic trials for prevention of coronary disease events have been disappointing. It is thought that a possible and intriguing risk factor for development of arteriosclerosis is inflammation due to infectious disease (e.g. chlamydia). Randomized trials with antibiotics in humans targeting certain bacteria have not shown to have a significant effect on cardiovascular outcomes and may cause increased risk.10 These trials were targeting specific organisms and not on adjusting the makeup of intestinal microbiota. The risks of microflora change (and QT prolongation) did not outweigh of the benefits. Future studies with antibiotics aiming at reducing TMAO may be in order but other therapeutic approaches may be better.

We need to further understand the gut microbiome better along with its effect on metabolites and cardiovascular health. This understanding will give us opportunities to develop new test and therapeutic approaches to arteriosclerosis. Medications can be developed against microbial enzymes creating dangerous metabolites like TMA and TMAO, blocking diet induced arteriosclerosis. Stool transplantation with lean or low risk for cardiovascular disease microflora may be a way in the future of treating patients who are susceptible to arteriosclerosis.

Download Tables, Images & References

Frontiers In Endoscopy, Series #42

Endoscopic Ultrasound-Guided Gallbladder Drainage

April 2018 • Volume XLII, Issue 4
Douglas G. Adler,Judith Staub

Read Article

Here we discuss EUS-GBD, an evolving technique that can be an alternative to PTGBD when treating acute or chronic cholecystitis in high-risk surgical patients, and also has promising results when used for long-term or definitive treatment.

Judith Staub, MD Douglas G. Adler, MD, FACG, AGAF, FASGE, Division of Gastroenterology and Hepatology, Utah School of Medicine, Salt Lake City, UT

CASE REPORT

An 81 year old man with metastatic pancreatic cancer, diabetes mellitus, and other comorbidities developed fever, right upper quadrant pain with a serum bilirubin of 9.8 mg/dL, an alkaline phosphatase of 770 U/L, and an AST of 110 U/L. His white blood count was 15,000/uL. CT scan showed findings consistent with a malignant biliary obstruction and acute cholecystitis. The gallbladder was enlarged and distended with a thickened wall and dense internal contents. General surgery evaluated the patient and felt that he was not a candidate for cholecystectomy. The therapeutic service was consulted to perform ERCP and to place a transmural gallbladder stent to decompress both the biliary tree and gallbladder in one procedure.

At ERCP, a malignant appearing stricture was seen in the mid common bile duct. This was stented with an 8x10mm uncovered metal biliary stent (Alimaxx-B, Merit Endotek, South Jordan, Utah) (Figure 1). After the ERCP, a linear echoendoscope was used to evaluate the gallbladder. The gallbladder had a thick wall, pericholecystic fluid, and dense fluctuant appearing contents (Figure 2). Using a freehand technique, an electrocautery- enhanced, 15mm wide x 10mm long lumen apposing metal stent (Axios, Boston Scientific, Natick, MA) was used to access the gallbladder in a transgastric manner (Figure 3). The stent was deployed without difficulty with one flange in the gallbladder and one in the stomach (Figure 4). There was copious drainage of purulent gallbladder contents and sludge into the stomach. The lumen of the stent was dilated with a 13.5mm esophageal dilation balloon to good effect (Figure 5). A 7Fr double pigtail stent was then placed across the stent with one pigtail in the gallbladder and one in the stomach (Figure 6). The patient tolerated the procedure well and there were no complications. The patient’s laboratory studies normalized and he had a rapid improvement in his clinical symptoms. The patient was discharged to hospice and passed away several months later without recurrence of biliary symptoms.

Overview and Efficacy of EUS Guided Gallbladder Drainage

Laparoscopic cholecystectomy is the definitive treatment of choice for acute cholecystitis. Patients who are poor surgical candidates or have severe sepsis at presentation often undergo percutaneous transhepatic gallbladder drainage (PTGBD) for second line primary therapy or as a bridge to surgery. However, hospital readmissions and adverse events associated with using external drainage catheters such as pneumothorax, peritonitis, bleeding and dislodgement are reported in up to 12% of cases. Endoscopic ultrasound- guided transmural gallbladder drainage (EUS- GBD) has emerged as a promising alternative that allows for minimally invasive, internal drainage of the gallbladder in the setting of acute and chronic cholecystitis in high-risk patients. Using EUS guidance, transmural stents can be placed via a transgastric or transduodenal approach.

Several studies have described the advantages of EUS-GBD over PTGBD, which include fewer adverse events, decreased cost, and fewer re-interventions. EUS-GBD has several other distinct advantages. For example, placement of lumen-apposing metal stents (LAMS) creates a portal between the gallbladder and the luminal GI tract that can allow, in some cases, for spontaneous passage of stones and further advanced endoscopic evaluation.5 Complete clearance of gallbadder stones with LAMS has been reported in up to 88% of patients. EUS-GBD has also been shown to be safe and effective in patients with coagulopathy or that require anticoagulation.

Several large studies have looked at outcomes for patients who have received EUS-GBD for acute cholecystitis and have had very positive results. Tyberg et al. performed a retrospective review comparing 42 patients who underwent EUS-GBD with 113 patients who underwent PTGBD. This study found similar technical success between the two (95.3 vs. 99%), but patients with EUS-GBD required fewer repeat procedures (9.5% vs. 27.7%) and had fewer hospital readmission (14.3% vs. 23.9%). Further, clinical success was higher EUS- GBD vs. PTGBD (95% vs. 86%).

Teoh et. al. performed a matched cohort study of 118 patients comparing EUS-GBD (59 patients) with PTGBD (59 patients).6 This study found similar rates of technical and clinical success, but, similar to the study by Tyberg et al., patients who underwent EUS-GBD had decreased hospital readmission rates (6.8% vs. 71.2% respectively) and no significant difference in 30-day adverse events. Critically, 95.2% of the readmissions were related to tube dislodgement in the PTGBD group. Finally, Dollhopfet et al. recently performed a multicenter retrospective review of 75 patients who underwent EUS-GBD for acute cholecystitis with a novel LAMS with an electrocautery enhanced delivery catheter (ECE-LAMs). The procedure had very high rates of clinical and technical success (98.7% and 95.9% respectively), with a rate of adverse events of 10.7%. This study also found that using the electrocauteryenhanced device led to significantly decreased stent deployment times. These studies demonstrate that EUS-GBD has similar efficacy to PTGBD, but fewer hospital readmissions and adverse events related to external tube dysfunction.

Adverse Events

Adverse events associated with EUS-GBD have been reported to occur in 6.3% to 32.2% for patients who have undergone the procedure for acute cholecystitis, but this rate has declined as endoscopic experience with the technique has grown.8,11 Immediate adverse events include bleeding, bile leak and stent migration. Stent migration can be both into the luminal GI tract and into the gallbladder, and is more common when plastic stents are used. Notably, the progression from plastic stents to SEMS and LAMS has reduced the incidence of stent migration and bile leak by anchoring the stent on the apposing organs of the newly created fistulous tract. However, procedure and stent related adverse events associated with LAMS use have been reported up to 13%, suggesting a high level of endoscopic expertise is pivotal.13 Delayed adverse events include abscess formation and recurrent cholecystitis.7 Interestingly, the rate of recurrent cholecystitis in EUS-GBD is about 4%, compared to up to 22% after 151 days from drain removal for PTGBD.11 The reduced rate of recurrent cholecystitis may be related to clearance of stones through the fistulous tract over time.8,11,13

Long Term Management

Several studies have performed long-term evaluation of SEMS or LAMS kept in place for up to 3 years.13 Reasons for foregoing stent removal in these studies include poor clinical condition, patient refusal, and tissue overgrowth. A recent study by Walter et al. in which patients had LAMS in place for up to 364 days found that 10% of patients studied had significant tissue overgrowth of their LAMS that precluded stent removal. However, no LAMS-related complications had occurred by long-term follow up. Choi et al. used partially covered SEMS with large bilateral flares (BONA-AL stent, Standard Sci Tech Inc., Seoul, Korea) and found that complete distal migration of the stent had occurred in 3.6% of patients at long-term follow up, but interestingly had no recurrence of cholecystitis occurred, suggesting full maturation of the cholecysto-enteric fistulous tract. These studies suggest that EUS-GBD may serve as not only an effective treatment for acute cholecystitis, but also definitive management in a select group of patients who remain poor surgical candidates over time due to malignancy or other significant medical comorbidities.

CONCLUSION

EUS-GBD is an evolving technique that can be an alternative to PTGBD when treating acute or chronic cholecystitis in high-risk surgical patients, and also has promising results when used for long- term or definitive treatment. Current research suggests that the two procedures appear to have similar technical and clinical efficacy, however it may not be valid to extrapolate this data to centers without high levels of endoscopic expertise.

Download Tables, Images & References

Dispatches From The Guild Conference, Series #11

How to Grade IBD Disease Activity in Your Daily Practice

April 2018 • Volume XLII, Issue 4
Trilokesh D. Kidambi,Fernando Velayos

Read Article

A clear understanding of disease activity can facilitate better care for IBD patients by addressing the impact of disease as well as risk of progression. The aim of this review is to discuss accessible measures of disease activity in IBD that can be used regularly in the office with the goal of facilitating consistent clinic care, use of a shared vocabulary for IBD activity and to provide an objective basis for treatment and assessment of treatment response.

Trilokesh D. Kidambi MD1 Fernando Velayos MD, MPH2 1Clinical Fellow Gastroenterology, Division of Gastroenterology, University of California San Francisco, San Francisco, CA 2Professor of Medicine, University of California; Regional Director-Kaiser Northern California Inflammatory Bowel Disease Program Division of Gastroenterology, Kaiser Permanente San Francisco, San Francisco, CA

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by immune dysregulation. Measurement of disease activity, which refers to the inflammatory burden and its impact on the patient at any one point in time, is a crucial step in the assessment of patients and factors into decision making regarding therapy. Categorizing disease activity into three domains – quality of life, clinical symptoms and endoscopic inflammation – can help the clinician follow disease activity using objective and standardized grading systems. This in turn can help assess response to treatment, which is increasingly important as the paradigm of management in IBD shifts to a “treat-to-target” approach. A clear understanding of disease activity can facilitate better care for IBD patients by addressing the impact of disease as well as risk of progression. The aim of this review is to discuss accessible measures of disease activity in IBD that can be used regularly in the office with the goal of facilitating consistent clinic care, use of a shared vocabulary for IBD activity and to provide an objective basis for treatment and assessment of treatment response.

INTRODUCTION

Inflammatory bowel disease (IBD), a progressive and chronic condition, is driven by immune dysregulation of the digestive tract which results in chronic inflammation and disease activity.1,2 A significant challenge is how to describe disease activity and severity in a way that is reproducible and actionable. An additional challenge is determining if disease activity and severity is best described using symptoms, colonoscopy findings, or impact of the disease on quality of life. The aim of this review is to discuss accessible measures of disease activity in IBD that can be used regularly in the office with the goal of facilitating consistent clinic care, use of a shared vocabulary for IBD activity and to provide an objective basis for treatment and assessment of treatment response.

Disease Activity Versus Severity in IBD

A fundamental, though often misunderstood, concept in the understanding of IBD disease scoring is the difference between disease activity and severity. Disease activity refers to a measure of the inflammatory burden and its impact at any one point in time and disease severity is a measure of the cumulative impact of the inflammatory burden over time.4 While disease activity and severity can be related, they are separate concepts that should not be used interchangeably. The focus of this article will be on disease scoring and tracking disease activity as it influences daily care by aiding in decisions for management and monitoring response to treatment.

Three Domains of Disease Activity A recent review divides disease activity into three domains: quality of life (QOL), clinical symptoms, and inflammation5 as shown in Table 1. Each domain has specific measures for ulcerative colitis (UC) and Crohn’s disease (CD). It is useful to think of these domains separately, though admittedly they overlap and are interrelated. However, considering them separately allows for a standardized approach to disease activity scoring.

Quality of Life

Quality of life (QOL) is a critical component of disease activity as it evaluates the patient’s social and emotional well-being, behavior and attitudes, and physical disease related symptoms and is the ultimate goal of therapy.5 Because many QOL measures are lengthy and cumbersome, we recommend only measures which are fast to complete, valid, reliable, and acceptable to patients. Measurement tools for QOL in IBD fall into three categories: psychological distress, disease adaptation and global QOL.

Measures of psychological distress are not IBD-specific and include the Patient Health Questionnaire-9 (PHQ-9) and the Hospital Anxiety and Depression Scale. The PHQ-9 was validated for diagnosing and monitoring major depressive disorder, but is easy to use in a clinical setting and given the high prevalence of comorbid depression in IBD6 is relevant. The Hospital Anxiety and Depression Scale was validated to screen for depression, anxiety and emotional distress in the outpatient setting utilizing just 14 questions and is commonly used, though never validated, in IBD-related research. A recent study confirmed prevalent depression and anxiety in IBD patients, but recognition of the symptoms by gastroenterologists was only fair.7 We believe routine use of a standardized measure will help in the identification of patients who would benefit from addressing their comorbid psychiatric conditions. to capture important changes that are difficult to otherwise to identify. The Brief Illness Perception Questionnaire is one such measure with nine items that has the added benefit of being positively associated with medication adherence8 and thus serves as a potential target to improve outcomes.

The Short Inflammatory Bowel Disease Questionnaire is an IBD-specific measure of global QOL that consists of 10 items that address bowel symptoms, emotional health, systemic symptoms and social function. It is easy to use, validated, reproducible and responsive and correlates well with longer IBD-specific questionnaires.9 It is subject to license so does require a fee to use.

Clinical Symptoms

In clinical practice, assessment of symptoms predominates patient encounters and thus it is crucial to objectively assess symptoms as they relate to disease activity to guide precision in decision making.10 There are over 20 indices of clinical symptoms in UC and CD, some of which are cumbersome to use in clinical practice and require complex calculations like the Crohn’s Disease Activity Index. We present the indices we have found to be straight-forward and easy to integrate into daily practice.

An important first step in clinical symptom assessment is determining disease extent in UC patients and the phenotype of CD patients as this helps understand the cause of symptoms or guide investigation into complications that may be driving the onset of new symptoms. The Montreal Classification is a simple tool that categorizes UC patients based on disease extent – E1 disease is limited to the rectum (proctitis), E2 disease is limited to the splenic flexure (left- sided) and E3 disease extends beyond the splenic flexure (extensive).11 Similarly, CD is categorized based on age of disease onset (A1: ≤ 16 years, A2: 17-40 years, A3 >40 years), location (L1: ileal, L2: colonic, L3: ileocolonic, L4: isolated upper gastrointestinal), and behavior (B1: non-stricturing, non-penetrating, B2: stricturing; B3: penetrating, +p if perianal disease present).

We recommend use of the Harvey Bradshaw Index (HBI) for symptom assessment in CD given it is simple to use and correlates well the complex Crohn’s Disease Activity Index, which has been an outcome measure in many of the studies of treatments for CD. The HBI has five variables and items are scored based on the previous making it easy to use as shown in Table 2. The major limitation is that perianal disease is a low contributor to the total score, which may underestimate the more severe phenotype. HBI scores greater than 16 are consistent with severe disease activity, whereas scores between 5-7 suggest mild activity and 8-16 suggest moderate activity. Response to therapy is defined by a reduction in the score by 3 points or more.5,12,13 As shown in Table 3, the Simple Clinical Colitis Activity Index (SCCAI) is an easy to use index for the assessment of clinical symptoms in UC. This can be filled out by patients without the need for lab values, endoscopy results or physician assessment, making it our preferred measurement tool for clinical symptoms in UC. It includes nocturnal bowel movements and urgency to defecate which are omitted in other indices, but, in our experience, are vitally important to patients. It is the best non-invasive index for validity, reliability, feasibility with the added benefit of being able to measure responsiveness, or change in disease activity.5,14 A score of two or less on the SCCAI indicates remission.

Inflammation

Inflammation is closely linked to progression of disease and therefore impacts severity of disease; it is one of the hallmarks of IBD disease activity and the gold-standard for measurement is endoscopy. Complementary measures of inflammation include histology (which is obtained via endoscopy), imaging (such as magnetic resonance and computed tomography imaging) and biomarkers (such as C-reactive protein and fecal calprotectin). Various endoscopic scoring symptoms exist and are specific for UC and CD, which will be the focus of this review.

We recommend use of either the UC Endoscopic Index of Severity15 (UCEIS) or the Mayo endoscopic sub-score to assess inflammation activity in UC. The UCEIS is the only validated endoscopic index in UC, is simple to use, and has high inter-observer reproducibility. The endoscopist grades the inflammation, without considering disease extent, based on the most severe area in three categories: vascular pattern, bleeding, and erosions and ulcers as shown in Table 4. While the UCEIS does not further classify the activity as mild, moderate, or severe, the target score for remission is one or less.3,5,16 An alternative endoscopic index for UC that is commonly utilized in clinical practice is the endoscopic sub-score of the Mayo index, which is simple to use but lacks strong inter-observer reliability and is not a validated measure of mucosal healing.3,5,16 Endoscopic activity is graded in each segment of the examined colon as normal (Mayo 0), mild (Mayo 1: erythema, mild friability and loss of vascular pattern), moderate (Mayo 2: presence of erosions and marked erythema, friability) and severe (Mayo 3: spontaneous bleeding and ulcers). Endoscopic remission corresponds to a Mayo 0 or 1. In our endoscopy unit, the Mayo endoscopic sub-score is widely used to grade disease activity to standardize assessment across physicians.

The gold-standard for the endoscopic assessment of disease activity in CD is the CD Endoscopic Index of Severity (CDEIS), which is reproducible, validated and used extensively in clinical trials.4,5,17 However, because it is cumbersome to use we don’t routinely measure it as part of clinical care in our practice. Instead, we recommend measurement of the Simple Endoscopic Score for CD (SES-CD), which is validated, correlates with the CDEIS and is easier to use, though admittedly still takes time. Each part of the colon as well as the ileum are graded on four categories (size of ulcers, ulcerated surface area, affected surface area and presence of narrowing) and the total score correlates with remission (0-2), mild (3-6), moderate (7-16), and severe (>16) as shown in Table 4. A response is defined by at least 50% reduction in the score.3,18 In post-operative CD patients, the Rutgeert’s post- operative endoscopic score is an important activity index because it correlates with risk of recurrence and thus helps inform decision-making regarding post-operative treatment of CD.19 The Rutgeert’s grade (i0-i4), as shown in Table 5, is based on the number and nature of ulcers at the neoterminal ileum and i0 and i1 grades are considered remission given the low risk of recurrence at five years.

Integrating Assessment of Disease Activity into Clinical Practice

Armed with an accurate, objective and reproducible assessment of disease activity in IBD, the clinician is able to understand the risks and benefits of continuing or changing therapies for their patients. Recently, an evidence-based expert consensus process was conducted to examine potential treatment targets in IBD with a focus on a “treat- to-target” clinical management strategy and the results of their discussions were published as the Selective Therapeutic Targets in IBD (STRIDE) recommendations.12 The rationale behind a “treat- to-target” approach is to focus on achieving remission and low disease activity; accordingly, physicians and patients should discuss the targets and work to achieve them within set time frames in order to improve outcomes (in all domains of disease activity, as previously described).

In UC, the STRIDE recommendation is to treat to a target of clinical symptomatic remission and patient reported outcomes as well as endoscopic remission (UCEIS ≤ 1 or Mayo endoscopy sub- score of ≤ 1). Clinical symptoms and QOL should be assessed at least every three months during active disease and endoscopic evaluation should be performed every three months until remission. For CD, similarly the target was clinical remission (defined by clinical symptoms and QOL indices) as well as endoscopic remission or resolution of inflammation objectively documented on cross- sectional imaging. As in UC, clinical symptoms of QOL should be assessed at least every 3 months, but endoscopic evaluation can be performed in 6-9 month intervals until resolution.

The Role of Disease Severity

The STRIDE recommendations did not specify treatment modalities and instead focused on treatment targets. Decisions on which treatment to choose in IBD is complex and requires an understanding of both disease activity as well as severity since an assessment of current and prior activity as well as prognostication for long-term complications factors into risk assessment of patients with low and high severity of disease.

CONCLUSION

The three domains of disease activity (quality of life, clinical symptoms, and inflammation) present an opportunity to capture activity longitudinally to help care for IBD patients. Using a standardized approach to measurement of disease activity allows objective assessment of response to treatment and standardizes practice and facilitates comparisons between endoscopies and treating physicians with the ultimate goal of providing better care for IBD patients by addressing not only impact of the disease but also the risk of progression.

Download Tables, Images & References

jojobethacklinkmarsbahisJojobet GirişcasibomJojobet GirişCasibomCasibomvaycasinoholiganbetcasibommarsbahis girişJojobettaraftarium24madridbet güncel girişmadridbet girişmadridbetGrandpashabet