Page 35 – Practical Gastro

INTRODUCTION

Urothelial carcinoma of the bladder (UBC) accounts for 90% of all primary bladder tumors. ¹ Although 75% of newly diagnosed UBCs are noninvasive, they have a high rate of recurrence despite treatment. ² Recurrence most often occurs locally in the bladder or remaining upper tract with <1% involving the colon. ³ We present a case report of a patient whose initial presentation of metastatic UBC to the rectum was bright red blood per rectum and acute anemia.

Case Report

An 85-year-old man, former smoker, with a history of stage IIIA (pT3aN0M0) urothelial carcinoma of the bladder status post radical cystectomy and ileal loop conduit eight years prior was admitted to the hospital for 3-4 days of progressive scrotal pain and swelling that had not responded to outpatient ketoconazole topical ointment. Physical examination revealed a swollen and erythematous scrotum, which was tender to palpation. Initial laboratory work-up was notable for normocytic anemia with hemoglobin 8.0 g/dL (normal 13.5- 16.0 g/dL), mean corpuscle volume 83 fL (normal 80-98 fL) without leukocytosis (white blood cell count 6.9 x 109 /L). His scrotal cellulitis was treated with piperacillin-tazobactam.

Over the course of two hospital days, he developed hematochezia and acute chronic anemia with a down-trending hemoglobin of 6.2 g/dL. Gastroenterology was consulted. His abdominal exam was soft, non-tender, and non-distended with blood noted on rectal exam. Flexible sigmoidoscopy revealed a large rectal ulcer (Figure 1) with oozing. Adjacent to the ulcer was impacted stool. A diffuse area of erythematous mucosa was also found in the rectum. Given the appearance of the ulcer and the adjacent impacted stool, a stercoral ulcer was the suspected source of the bleed. Biopsies of the ulcer bed and surrounding tissue revealed rectal mucosa with urothelial carcinoma with positive immunohistochemical staining of cytokeratin 7 (CK7) (Figure 2), keratin 20 (CK20), and GATA3. For the remainder of the patient’s hospital stay, his bleeding subsided and hemoglobin stabilized. Palliative immunotherapy was pursued per the patient’s and family’s requests but was not tolerated. Hospice services were requested for comfort care; he ultimately died six months later.

Discussion

Bladder cancer is the second most common genitourinary malignancy. In the United States, approximately 70,000 patients are newly diagnosed with bladder cancer annually. ⁴ Risk factors for bladder cancer include smoking and exposure to aromatic amines. 2 Urothelial bladder cancer (UBC), a subtype of bladder cancer, comprises 90% of all primary bladder cancers. ³ Approximately 75% of newly-diagnosed UBCs are noninvasive while the remaining 25% invade the muscular layers and require radical surgery or radiotherapy. ² Radical cystectomy is the current gold standard for muscle invasive UBC. ⁵ Common distal recurrence and metastasis sites are lungs, liver, and lymph nodes (nonpelvic). ⁶ However, local recurrence is more common in the bladder or remaining urinary tract. ³ The clinical presentation of recurrent UBC varies depending on the site of recurrence, most commonly with no symptoms, venous status, or localized pain. ⁷

Gastrointestinal tract involvement of metastatic UBC is rare. ³ Literature review has identified 34 reported cases, with 16 involving rectal metastases. 8 Five cases presented with hematochezia. ^3,8 Four cases of metastatic UBC involving the rectum occurred after radical cystectomy. 8 Recurrence of bladder cancer after radical cystectomy occurs in up to 40% of patients and has been attributed to potential occult metastasis and/or seeding during surgical intervention.⁵

Unique to this case was its endoscopic finding. Colonoscopy has confirmed metastases to rectum in three other cases. However, the tissues biopsied were of fixed masses or thickened rectal wall.⁸ In our case report, the tissue biopsied was a single ulcer. Because of the appearance of the ulcer, a stercoral ulcer was thought to be the source of the bleeding. This circumstance highlights the importance of obtaining biopsies from an ulcer bed during colonoscopy for histological examination in the appropriate clinical setting.

CONCLUSION

Gastrointestinal tract involvement of metastatic UBC is rare. In this case report, a patient presented with hematochezia, found to be secondary to metastatic UBC involving the rectum. An ulcer was identified on endoscopy, and initially was suspected to be secondary to a stercoral ulcer. Biopsies were taken and consistent with metastatic disease, highlighting the importance of obtaining biopsies from an ulcer bed.

References

^{Kaufman DS, Shipley WU, Feldman ASJTL. Bladder cancer. 2009;374(9685):239-49}
^{Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. 2013;63(2):234-41}
^{El Douaihy Y, Krzyzak M, Barakat I, Deeb LJAcrj. Recurrence of Urothelial Bladder Carcinoma in the Colon Presenting as Hematochezia. 2016;3(4)}
^{Ploeg M, Aben KK, Kiemeney LAJWjou. The present and future burden of urinary bladder cancer in the world. 2009;27(3):289-93}
^{Lotan Y, Gupta A, Shariat SF, et al. Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. 2005;23(27):6533-39}
^{Wallmeroth A, Wagner U, Moch H, Gasser TC, Sauter G, Mihatsch MJJUi. Patterns of metastasis in muscle-invasive bladder cancer (pT2–4): an autopsy study on 367 patients. 1999;62(2):69-75}
^{Cornu J-N, Neuzillet Y, Hervé J-M, Yonneau L, Botto H, Lebret TJWjou. Patterns of local recurrence after radical cystectomy in a contemporary series of patients with muscleinvasive bladder cancer. 2012;30(6):821-26}
^{Aneese AM, Manuballa V, Amin M, Cappell MSJWjoge. Bladder urothelial carcinoma extending to rectal mucosa and presenting with rectal bleeding. 2017;9(6):282}

FROM THE LITERATURE

Necrotizing Enterocoliltis:Is Care Getting Better?

Necrotizing enterocolitis (NEC) is a devastating intestinal condition typically associated with premature infants in neonatal intensive care units (NICUs). NEC is associated with both a high mortality rate as well as a high rate of neurodevelopmental disability (NDD).

As survival of premature infants increases, the risk of NEC also has increased, and the authors of this study looked at current outcomes of NEC in the medical literature. In particular, a review of the literature occurred using the PRISMA Statement (http:// www.prisma-statement.org/PRISMAStatement/ PRISMAStatement). PubMed also was searched for the following terms: “NEC,” “mortality,” “morbidity,” “neurodevelopmental outcome,” “outcomes”, and “intestinal failure.” Included articles had to be in English and had to be published after January 2010 with reported NEC outcomes (mortality) from international/national/regional/multi-center studies from high-income countries.

Initially, 1371 articles were included, but only 31 articles met the criteria of studying mortality that could be included in a meta-analysis. Mortality from NEC (Bell stage 2A or higher) was 23.5% (95% confidence interval 18.5% to 28.8%) with low birthweight and history of NEC surgery being risk factors. In particular, the mortality of infants less than 1000 grams who underwent surgery for NEC was 50.9% (95% confidence interval 38.1% to 63.5%). The meta-analysis demonstrated that mortality from NEC in premature infants ranged from 10% to 21%. Five studies meeting criteria for evaluating NDD in the setting of NEC, and severe NDD ranged between 24.8% and 59.5% although the definition of “severe” varied between studies. Finally, only three studies described the association between intestinal failure (defined as intestine loss preventing normal intestinal absorption and growth) and NEC with intestinal failure rates of 15.2% in all infants with NEC and 35.4% in infants with NEC requiring surgery.

This meta-analysis provides convincing evidence that NEC still is extremely problematic in NICUs, and further research is necessary to decrease associated morbidity and mortality. Further research should be aimed towards understanding potential associated genetic mechanisms involved in NEC as well as considering the possibility of new types of pre-/pro-/ symbiotic strains to reduce the complications of this devastating disease.

^{Jones I. and Hall N. Contemporary outcomes for infants with necrotizing enterocolitis – a systemic review. Journal of Pediatrics 2020; 220: 86-92.}

FROM THE LITERATURE

Collagenous Colitis Shares Genetic Risk with Other Immune-Mediated Diseases

An array-based, genetic association study was carried out in a cohort of patients with collagenous colitis (CC) and the common genetic basis was investigated between that and Crohn’s disease (CD), ulcerative colitis (UC), and celiac disease.

DNA from 804 CC formalin-fixed, paraffinembedded tissue samples were genotyped with Illumina Immunochip. Matching genotype data was carried out on control samples and CD, UC, and celiac cases were provided by the respective consortia.

A discovery association study followed by metaanalysis with an independent cohort, polygenic risk score calculation and cross-phenotype analyses were performed. Enrichment of regulatory expression, quantitative trait loci among the CC variants was assessed in hemopoietic and intestinal cells.

Three HLA alleles (HLA-B08:01, HLADRB103:01 and HLA-DQB1*02:01), related to the ancestral haplotype 8.1, were significantly associated with increased CC risk. An independent protective effect on HLADRB04; 01 was noted on CC risk. Polygenic risk score quantifying the risk across multiple susceptibility loci was strongly associated with CCI risk.

An enrichment of expression quantitative trait loci was detected among the CC susceptibility variants in various cell types. The cross-phenotype analysis identified a complex pattern of polygenic pleiotropy between CC and other immune-mediated diseases.

It was concluded in this largest genetic study of CC to date, with histologically confirmed diagnosis, this strongly implicated the HLA locus and proposed potential non-HLA mechanisms in disease pathogenesis. A shared genetic risk was also detected between CC, celiac disease, CD and UC, supporting clinical observations of comorbidity.

^{Stahl, E., Roda, G., Dobbyn, A., et al. “Collagenous Colitis is Associated with HLA Signature and Shares Genetic Risks with Other Immune-Mediated Diseases.” Gastroenterology 2020; Vol. 159, pp. 549-561.}

FROM THE LITERATURE

Peripheral Eosinophils and Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease associated with mucosal infiltration of the esophagus. EoE incidence appears to be increasing, especially in children, and repeat esophagogastroduodenoscopy (EGD) often is needed to confirm therapeutic response to EoE (typically topical mucosal steroid therapy or dietary changes directed at preventing allergic disease). Since clinical symptoms of EoE are not a good indicator of clinical response to therapy, one of the current goals in EoE research is to find non-invasive biomarkers to monitor disease activity. In that regard, the blood eosinophil count has the potential to be such a marker

The authors of this study performed a retrospective chart review of all pediatric patients (less than 18 years of age) diagnosed with EoE over a 7-year period. Patients with coexisting GI disease were excluded, and EoE was defined as an eosinophil count greater than or equal to 15 eosinophils per highpower field (HPF) in biopsies in any of 3 regions of the esophagus (lower, mid, upper). All patients in this group had been on a proton pump inhibitor for at least 4 weeks prior to EGD. The primary study endpoint was determination of a possible correlation between absolute peripheral eosinophil count and esophageal eosinophilic infiltration. The secondary study endpoint was to see if esophageal eosinophils correlated with biopsy findings of basilar hyperplasia, spongiosis, and the presence of neutrophils and lymphocytes.

A total of 57 patients with EoE, 91 EGDs, and 279 biopsy specimens were included in the study. The oldest patient in the study was 17.9 years while the youngest patient was 1.6 years. The age of participants ranged from 1.6 years to 17.9 years of age, and white study subjects comprised 80% of the study population. A total of 66 procedures (71%) had biopsies consistent with EoE while the other 29% had less than 15 eosinophils per HPF or had no disease noted on biopsies. A significant correlation was seen between absolute eosinophil counts in blood samples and highest esophageal counts in biopsy specimens (P=0.0009). There was a significant correlation between absolute eosinophil counts in patients with active EoE compared to patients with biopsies showing less than 15 eosinophils per HPF or no eosinophilic infiltration. An absolute eosinophil count less than 500 correlated well with patients with inactive disease although an absolute eosinophil count greater than 500 did not correlate well with active EoE. However, when using a logistic regression model for race, sex, weight, height, and body mass index (BMI), none of these factors correlated with absolute eosinophil counts in relation to EoE activity.

It was noted that 58.1% of patients with EoE had allergic rhinitis, 50.5% of patients had food allergies, 38% had asthma, 29 % had eczema, and 14% had all of these conditions together. The most common symptoms included odynophagia (6.5%), food impaction (7.5%), chest pain (11.8%), nausea (23.7%), gastroesophageal reflux symptoms (24.7%), emesis (24.7%), dysphagia (25.8%), and abdominal pain (33.3%). The most common endoscopic finding in patients with EoE included esophageal furrowing (43%). Basilar hyperplasia, spongiosis, and microabscesses were significantly more common in patients with EoE compared to patients with no EoE although the presence of lymphocytes and neutrophils in biopsies did not differ between groups.

Although absolute eosinophil count may be a marker for inactive EoE which has the potential to be used for disease response, this study showed that it was difficult to correlate such findings with worsening EoE. Basilar hyperplasia, spongiosis, and microabscesses (potential early markers of the development of fibrosis) did seem to correlate with EoE although infiltration of other cell types (neutrophils, lymphocytes) did not. The authors state that the patients with EoE in this study were all treated with swallowed budesonide, and we have no data on other interventions such as swallowed fluticasone or dietary therapy. It appears that absolute eosinophil count is not a good marker for following EoE activity over time.

^{Choudhury S., Kozielski R., Hua J., Wilding G., Baker S. Do histological features of eosinophilic esophagitis in children correlate with peripheral eosinophils? Journal of Pediatric Gastroenterology and Nutrition 2020; 70: 604-607.}

FELLOWS’ CORNER

A Case of Small Bowel Lipoma Presenting with Intussusception

Luisa Recinos,Chiranjeevi Gadiparthi,

Arkady Broder

CASE PRESENTATION

A 55-year-old female was referred to gastroenterology service with severe and intermittent epigastric abdominal pain of 2 weeks duration. She had unintentional weight loss of 15 lbs. The pain was not associated with food intake. She had no prior abdominal surgeries. Her medical history was significant for arterial hypertension and diabetes mellitus. Physical examination revealed normal vital signs and epigastric tenderness with no palpable mass.

A complete blood count and chemistry panel were normal. An upper endoscopy and colonoscopy revealed no apparent cause of her symptoms but were remarkable for mild gastritis, diverticulosis, and small hemorrhoids. A contrastenhanced CT scan of the abdomen and pelvis showed small bowel intussusception in the right lower quadrant in mid-ileum as shown in Figure 1. For better visualization of small bowel, CT enterography was done (Figure 2) which confirmed the intussusception. An anterograde single balloon enteroscopy was unsuccessful in reaching the site of the intussusception. Surgical resection was arranged.

QUESTIONS

What are the clinical manifestations of small bowel intussusception in adults?
What are the causes of small bowel intussusception?
What are the gastrointestinal manifestations of lipomas?
What is the radiological diagnosis?

What are the Clinical Manifestations of Small Bowel Intussusception in Adults?

Intussusception is the telescoping of a proximal segment of the intestine into an adjacent distal segment. In a retrospective study,¹ abdominal pain was the most frequently reported symptom (79%). The mean duration of acute pain was 4 hours, and 80% described an intermittent and cramping pain. Other described symptoms include vomiting and diarrhea. Bloody stool and a palpable mass are frequently seen in the pediatric population, however very uncommon in adults.

What are the Causes of Small Bowel Intussusception?

According to a recent meta-analysis,² the common causes of intussusception in adults include benign tumors, followed by malignant tumors and idiopathic causes. The most common malignancies in enteric intussusception were metastatic carcinoma, metastatic lymphoma, and gastrointestinal stromal tumor (GIST). Benign tumors that can cause enteric intussusception include hamartoma, hemangioma, polyp (inflammatory, Peutz-Jegher), lipoma, and neurofibroma. These small bowel tumors typically result in lead-point for intussusception as shown in our case.

Non-lead point intussusception has been associated with celiac disease and Crohn’s disease. Inflammation with wall thickening and decreased or dysrhythmic small-bowel motility have been the suggested underlying mechanisms of intussusception.^3,4

What are the Gastrointestinal Manifestations of Lipomas?

Lipomas are submucosal tumors that can grow in any part of the gastrointestinal tract and up to 20-25%⁵ are found in the small bowel. Most commonly lipomas are asymptomatic and found incidentally during endoscopic procedures. When symptomatic, they may have pseudopedicle that leads to intussusception. At times, they can ulcerate and cause anemia due to microscopic blood loss.

What is the Radiological Diagnosis?

The imaging modalities to assess intussusception include CT scan, ultrasound, and barium enema. The accuracy of the CT scan is varied widely, and has been reported to be 58-100%⁶ and is the preferred initial test of choice. Classic findings on CT scan include the target, bulls-eye, or sausageshaped lesions. When compared to a regular CT scan, CT enterography uses thinner sections and a large amount of low-density enteric contrast. CT enterography better depicts the small bowel wall and lumen making it a superior tool to assess small bowel neoplasms with a sensitivity of 84% and specificity of 96.9%.⁷

In our case, the CT scan of the abdomen showed small bowel intussusception involving a 12 cm segment within the right abdomen, with the characteristic sausage-shaped appearance (Figure 1). The CT enterography showed small bowel intussusception in the mid ileum and the lead point was a lipoma which measured 23 x 29 x 16 mm (Figure 2). The small bowel lipoma was not evident on the contrast-enhanced CT scan of the abdomen and single balloon enteroscopy.

References

^{Cochran AA, Higgins GL, 3rd, Strout TD. Intussusception in traditional pediatric, nontraditional pediatric, and adult patients. Am J Emerg Med. 2011;29(5):523-527.}
^{Hong KD, Kim J, Ji W, Wexner SD. Adult intussusception: a systematic review and meta-analysis. Tech Coloproctol. 2019;23(4):315-324.}
^{Gonda TA, Khan SU, Cheng J, Lewis SK, Rubin M, Green PH. Association of intussusception and celiac disease in adults. Dig Dis Sci. 2010;55(10):2899-2903.}
^{Lopez-Tomassetti Fernandez EM, Lorenzo Rocha N, Arteaga Gonzalez I, Carrillo Pallares A. Ileoileal intussusception as initial manifestation of Crohn’s disease. Mcgill J Med. 2006;9(1):34-37.}
^{Thompson WM. Imaging and findings of lipomas of the gastrointestinal tract. AJR Am J Roentgenol. 2005;184(4):1163-1171.}
^{Marsicovetere P, Ivatury SJ, White B, Holubar SD. Intestinal Intussusception: Etiology, Diagnosis, and Treatment. Clin Colon Rectal Surg. 2017;30(1):30-39.}
^{Ilangovan R, Burling D, George A, Gupta A, Marshall M, Taylor SA. CT enterography: review of technique and practical tips. Br J Radiol. 2012;85(1015):876-886.}

MEDICAL BULLETIN BOARD

Research Update: Icureceliac Patient Registry Leads to New Research Findings

With your generous support, we invest heavily in celiac disease research to accelerate diagnosis, the development of treatments, and a cure. One of our most important research investments over the last several years has been in iCureCeliac®, the nation’s leading celiac disease patient registry. Again and again, iCureCeliac® has helped researchers from around the world develop a greater understanding of celiac disease, leading to investment in promising interventions and therapeutics.

In October, researchers published three important studies about celiac disease that used the iCureCeliac® patient registry database as the data source. I am pleased to be able to share these studies with you.

The first study was published in the Journal of American Medical Association (JAMA) and is titled Prevalence of Dermatitis Herpetiformis Within the iCureCeliac Patient-Powered Research NetworkPatient Characteristics and Dietary Counseling. Results of the University of Pennsylvania study showed patients with dermatitis herpetiformis (DH) were less likely to recall receiving counseling on a gluten-free diet at the time of diagnosis when compared with patients with celiac disease but without DH. This is likely because only 20% of patients diagnosed with DH present with classic GI symptoms associated with celiac disease at the time of diagnosis. As well, most DH diagnoses are made by dermatologists who may lack appreciation of the need to offer counseling on the gluten-free diet. As a result, DH patients who fail to adopt a strict glutenfree diet within the first 5 years of diagnosis may have an increased risk of mortality from lymphoma in this period of time.

The second study, Disease burden and quality of life impacts in patients with celiac disease on a gluten-free diet: an analysis of the iCureCeliac registry, was presented as a poster at the United European Gastroenterology Week Virtual 2020 Congress, October 11-13, 2020 and at the American College of Gastroenterology 2020 Virtual Annual Scientific Meeting, October 23-28. Authored by researchers from Takeda Pharmaceuticals and the Celiac Disease Foundation, the study presents compelling evidence that, ‘despite gluten-free diet adherence, many patients with celiac disease still have symptoms that substantially impact their lives. This was seen for all patients but was most pronounced for those with higher symptom burden, highlighting the heterogeneity of celiac disease burden and need for further therapies beyond a gluten-free diet.’ Takeda currently has two celiac disease drugs in development, TAK-101, which is designed to promote immune intolerance, and TAK062, which works by enzymatically digesting gluten. Findings from iCureCeliac® continue to substantiate the need for treatment alternatives to a gluten-free diet.

Probiotics Use in Celiac Disease: Results from a National Survey, the third study, is also currently being presented at ACG 2020 Virtual and is an Outstanding Poster Presenter recipient. Led by Andrew Joelson, MD, Gastroenterology Fellow at the Celiac Disease Center at Columbia University, the study examined probiotic use in the Foundation’s iCureCeliac® patient registry population finding that about one-third of patients reported using probiotics to treat persistent symptoms. Patients on a gluten-free diet who were still experiencing symptoms were twice as likely to use probiotics as patients who reported controlled symptoms. This is the Celiac Disease Foundation’s fifth collaboration with Dr. Joelson and his team at Columbia University since 2017 with iCureCeliac® data demonstrating the serious burden of celiac disease.

As always, we thank you for your generous support that makes our work possible.

To Our Health
Marilyn G. Geller, Chief Executive
For the latest information on celiac disease and
COVID-19, view our Resource Center.
Celiac Disease Foundation
20350 Ventura Boulevard | Suite 240
Woodland Hills, California 91364
818.716.1513
info@celiac.org

MEDICAL BULLETIN BOARD

IBD Plexus®

Academic Request for Proposals

The Crohn’s & Colitis Foundation has released a request for proposals (RFP) for academic researchers to gain access to IBD patients’ biosamples and/or research-ready datasets housed within IBD Plexus®.

IBD Plexus was founded by the Foundation to advance science, accelerate progress toward precision medicine, and improve the care of patients living with IBD. This first-of-its kind, national-scale, cloud-based platform integrates clinical, patient reported, genetic, and other molecular data from diverse research study cohorts, real-world clinical care settings, and patients’ experiences. IBD Plexus provides academic and industry researchers with access to research-ready datasets and biosamples to more rapidly perform activities that promise to speed treatment development, optimize existing therapies through development of biomarkers and diagnostics, and improve health outcomes.

IBD Plexus unites clinicians, scientists, educators, industry partners, and patients to answer questions that are critically important to advance the field of IBD research. The Foundation seeks research proposals that would utilize IBD Plexus biosamples and/or data to facilitate efforts in four main areas: identification and/or validation of diagnostics/biomarkers, therapeutic development and optimization, disease management, and disease prevention.

This is a rolling solicitation. The Foundation will continue to accept responses to the RFP until all awards are distributed.

For more information visit: crohnscolitisfoundation.org/PlexusRFP

MEDICAL BULLETIN BOARD

Sebela Pharmaceuticals Receives Fda Approval for Sutab® Tablets for Colonoscopy Preparation

SUTAB® Tablets with Active Sulfate Ingredients Give Gastroenterologists a New, Safe, and Effective Alternative to Liquid Bowel Preparations

BRAINTREE, MA — Sebela Pharmaceuticals® announces that the U.S. Food and Drug Administration (FDA) approved SUTAB® (sodium sulfate, magnesium sulfate, and potassium chloride) tablets. SUTAB, a sulfate-based tablet preparation for colonoscopy, was developed and will be marketed by Braintree Laboratories, the makers of SUPREP® Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution—the market leader in branded colonoscopy preparations.¹ SUTAB gives patients and physicians an alternative to liquidbased colonoscopy preparations. Braintree, a leader in gastroenterology, is part of Sebela Pharmaceuticals.

Colonoscopy is the most common detection method for colorectal cancer, a leading cause of cancer-related deaths that can be managed more effectively through screening.² It is considered the gold standard of colorectal cancer screening methods for its ability to view the entire colon and both detect and remove polyps during the same procedure.^3,4 Nineteen million colonoscopies are performed in the U.S. every year.⁵ For those patients, particularly those who have had difficulty completing colonoscopy preparation in the past, SUTAB presents a welcome alternative to liquid bowel preparation.

“Successful bowel prep is critical for gastroenterologists to clearly see any polyps or abnormalities, yet the immense volume of liquid prep solutions can prevent patients from adequately completing their regimens. Tablets provide a welcome alternative for successful prep completion and visualization of the colon,” said Douglas K. Rex, M.D., Director of Endoscopy at Indiana University Hospital and Professor, Department of Medicine, Division of Gastroenterology and Hepatology, University of Indiana School of Medicine.

Alan Cooke, President and CEO of Sebela Pharmaceuticals, said “Gastroenterologists and their patients have repeatedly asked for a safe and efficacious tablet bowel prep. Now patients can benefit from SUTAB, thanks to Braintree’s innovative and dedicated team, who have worked tirelessly to develop this important product. SUTAB’s FDA approval underscores Braintree’s more than thirtyfive year commitment to gastroenterology.”

In two pivotal trials, 92% of patients achieved successful bowel cleansing with SUTAB6 and 92%- 95% of patients achieved successful cleansing in all segments of the colon, including the proximal colon.⁷ In one pivotal trial, 91% of patients rated SUTAB as very easy to tolerable to consume.⁷ Seventyeight percent said they would request SUTAB again for a future colonoscopy.⁷ Fifty-two percent of all SUTAB and MoviPrep®⁸ patients reported at least one selected gastrointestinal adverse reaction.⁶ More SUTAB patients reported experiencing nausea and vomiting than comparator, with ≤1% of these reports considered severe.⁶

“The approval of SUTAB provides a welcome relief for patients who struggle with the unpleasant taste issues commonly associated with other products for colonoscopy preparation,” said Jack A. Di Palma, M.D., Professor of Medicine and Fellowship Program Director of the Division of Gastroenterology at the University of South Alabama College of Medicine and Past-President of the American College of Gastroenterology. “And because SUTAB contains the active sulfate ingredients similar to SUPREP, gastroenterologists will already be familiar with its effects.”

SUTAB will be available by prescription to patients in the U.S. on January 1, 2021.

Important Safety Information

SUTAB® (sodium sulfate, magnesium sulfate, potassium chloride) tablets for oral use is an osmotic laxative indicated for cleansing of the colon in preparation for colonoscopy in adults. DOSAGE AND ADMINSTRATION: A low residue breakfast may be consumed. After breakfast, only clear liquids may be consumed until after the colonoscopy. Administration of two doses of SUTAB (24 tablets) are required for a complete preparation for colonoscopy. Twelve (12) tablets are equivalent to one dose. Water must be consumed with each dose of SUTAB and additional water must be consumed after each dose. Complete all SUTAB tablets and required water at least 2 hours before colonoscopy. CONTRAINDICATIONS: Use is contraindicated in the following conditions: gastrointestinal obstruction or ileus, bowel perforation, toxic colitis or toxic megacolon, gastric retention. WARNINGS AND PRECAUTIONS: Risk of fluid and electrolyte abnormalities: Encourage adequate hydration, assess concurrent medications and consider laboratory assessments prior to and after each use; Cardiac arrhythmias: Consider predose and postcolonoscopy ECGs in patients at increased risk; Seizures: Use caution in patients with a history of seizures and patients at increased risk of seizures, including medications that lower the seizure threshold; Patients with renal impairment or taking concomitant medications that affect renal function: Use caution, ensure adequate hydration and consider laboratory testing; Suspected GI obstruction or perforation: Rule out the diagnosis before administration. ADVERSE REACTIONS: Most common gastrointestinal adverse reactions are: nausea, abdominal distension, vomiting and upper abdominal pain. DRUG INTERACTIONS: Drugs that increase risk of fluid and electrolyte imbalance.6 See Full Prescribing Information and Medication Guide

About SUTAB®

Safety and effectiveness of SUTAB® in pediatric patients have not been established.⁶

About Sebela Pharmaceuticals®

Sebela Pharmaceuticals is a US-focused, growthoriented specialty pharmaceutical company developing and commercializing gastroenterology, women’s health, and dermatology prescription products. Braintree, a part of Sebela Pharmaceuticals, is a pioneer in gastroenterology therapy for bowel cleansing prior to colonoscopy having developed multiple innovative prescription bowel prep and constipation products including SUTAB®, SUPREP® Bowel Prep Kit, GoLYTELY® and NuLYTELY®. Our gastroenterology product line also includes Motofen®, Analpram HC® and recently approved Pizensy™ (indicated for chronic idiopathic constipation in adults). Sebela Pharmaceuticals has multiple further advances in bowel prep therapy in clinical development. Sebela Pharmaceuticals also has two next generation intra-uterine devices (IUDs) for contraception in development that hold the promise of a better patient experience in addition to excellent efficacy. Sebela Pharmaceuticals has offices in Roswell, GA; Braintree, MA; and Dublin, Ireland, has annual net sales of $200-250 million and has grown to over 300 employees through strategic acquisitions and organic growth.

References

IQVIA. National Prescription Audit Report. September 2020.
Doubeni CA, Corley DA, Quinn VP, et al. Effectiveness of screening colonoscopy in reducing the risk of death from right and left colon cancer: a large community-based study. Gut. 2018;67(2):291-298.
Niederreiter M, Niederreiter L, Schmiderer A, Tilg H, Djanani A. Colorectal cancer screening and prevention—pros and cons. Memo. 2019;12;239-243.
Stauffer CM, Pfeifer C. Colonoscopy. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 31, 2020. Accessed October 6, 2020.
iData Research. An Astounding 19 Million Colonoscopies Are Performed Annually in The United States. https://idataresearch. com/an-astounding-19-million-colonoscopies-are-performedannually-in-the-unitedstates/. August 8, 2018. Accessed October 22, 2020.
SUTAB® [package insert]. Braintree Laboratories, Inc., Braintree, MA: 2020.
Di Palma JA, Bhandari R, Cleveland M, et al. A safety and efficacy comparison of a new sulfate-based tablet bowel preparation versus a PEG and ascorbate comparator in adult subjects undergoing colonoscopy. Am J Gastroenterol. Published online November 6, 2020. doi: 10.14309/ ajg.0000000000001020
MoviPrep® (PEG-3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution) is a registered trademark of Velinor AG.

FROM THE PEDIATRIC LITERATURE

Serologic Markers for Celiac Disease in Young Children

October 2020 • Volume XLIV, Issue 10

Celiac disease (CD) is an autoimmune disease associated with small intestinal damage (villous atrophy and lymphocytic infiltration) in response to gluten ingestion. Although esophagogastroduodenoscopy (EGD) with duodenal biopsy is considered the “gold standard” test for confirming CD, the tissue transglutaminase IgA antibody titer (TTG IgA) is a highly sensitive and specific serum test for CD screening. National guidelines (such as from the Celiac Disease Foundation) do not recommend TTG IgA screening before 2 years of age because of concerns about testing sensitivity in that age group. The authors of this study tested this recommendation by reviewing medical records of children from 3 tertiary children’s hospitals in the United States. Two of the hospitals had retrospective records reviewed as far back as 20 years while the third hospital utilized a prospective database of children with villous atrophy diagnosed by EGD. All included patients were evaluated for diagnostic criteria for CD (including serologic markers of disease and duodenal biopsy findings), resolution of gastrointestinal symptoms on a gluten-free diet, and normalization of serologic markers for CD while on a gluten-free diet. Thus, patients with CD associated with positive serologic markers and positive duodenal biopsy findings were compared to a control group of children with duodenal biopsies consistent with CD but who had negative serologic findings and no gluten exposure or no response to a gluten-free diet.

A total of 150 children were included in the study for which 127 had CD and 23 belonged to the control group. The median age at time of duodenal biopsy was 18 months (range 3 – 24 months) with most children having a diagnosis of failure to thrive. Biopsies demonstrated intraepithelial lymphocytosis in 3% of children, partial villous atrophy in 45% of children, and total villous atrophy in 52% of children. Various CD serologic markers were ordered for these patients with TTG IgA being the most common test although other testing types included endomysium IgA, antigliadin IgA with / without IgG, and deamidated gliadin protein IgA with / without IgG. Of the 127 children with CD, 115 underwent TTG IgA testing for which 112 patients (97.5%) had elevated TTG IgA titers with the remaining 3 patients having positive TTG IgG titers. IgA deficiency was present in 5.5% of patients with CD although all such children had some type of positive IgG testing (such as TTG, anti-gliadin, or deamidated gliadin protein). Alternatively, 19 of the 23 children in the control group had TTG IgA testing performed, and all tests were negative. The remaining 4 children in the control group consisted of one patient with negative endomysium IgA testing and 3 children with no other serologic testing performed. When all patients with TTG IgA testing were compared, patients with CD were significantly older (19 months versus 15 months, P=0.001) and had a higher TTG IgA level (7.4 times the upper limit of normal versus 0.3 times the upper limit of normal, P<0.001).

This study, based on retrospective data, seems to indicate that TTG IgA testing may be an appropriate screen for CD in children younger than 2 years of age. The authors point out that IgG antibody testing may be indicated for those young patients with negative TTG IgA testing but with symptoms of CD.

^{Khan M, Silvester J, Sparks B, Hintze Z, Ediger T, Larson J, Hill I, Absah I. The utility of IgAbased serologic markers in diagnosing celiac disease in children 24 months of age or younger. Journal of Pediatrics 2020; 224: 158-161.}

MEDICAL BULLETIN BOARD

Compulink Readies EHR Coding Engine to Support E/M 2021 Changes

October 2020 • Volume XLIV, Issue 10

Company’s EHR will help providers identify best codes to bill for maximum reimbursement

Newbury Park, CA – Compulink Healthcare Solutions, the creator of Advantage SMART Practice®, the EHR and practice management system powered by artificial intelligence (AI), has announced it is readying its EHR coding engine to support the new 2021 Evaluation and Management (E/M) CPT codes. Slated to become effective on January 1, 2021, the E/M changes are major and will impact coding and billing for every office visit.

To support E/M 2021, the company’s EHR coding engine will utilize the new coding methodology and time spent guidelines to automatically identify the best code to bill for maximum reimbursement. For its eyecare clients, Advantage will also automatically evaluate three possible eyecare codes and suggest the code with highest level of reimbursement.

“The last time the E/M coding underwent this major a revision was in the 1990s. These changes will have a huge impact on workflow and payment eligibility for our clients,” said Link PRACTICAL GASTROENTEROLOGY Celebrating Over 44 Years of Service practicalgastro.com Wilson, CEO and product architect for Compulink. “We’ve consulted with industry coding experts to help ensure providers will get paid the maximum amount for their services, and that we’re ready by the January deadline.”

The company also announced it is offering a money back guarantee to have its products ready to support the 2021 E/M changes.

Compulink’s Advantage SMART Practice, all-in-one database solution includes a specialtyspecific EHR, practice management, inventory management, patient engagement, ASC, E-commerce, and Optical POS (for eyecare practices). The company also provides an expert revenue cycle management service for its clients. Advantage is 2015 ONC Certified for MIPS. Compulink is used by more than 25,000 providers in over 4,700 locations, 60 ASCs, and 19 universities and colleges.

About Compulink Healthcare Solutions

A leader in specialty specific, all-in-one EHR and Practice Management solutions for 35 years, Compulink’s Advantage SMART Practice uses artificial intelligence to improve clinical and financial results.