Page 40 – Practical Gastro

NAPLES, FL – The Bruce and Cynthia Sherman Charitable Foundation announced its annual call for nominations for the 2020 Sherman Prizes, recognizing exceptionally talented, dedicated individuals working tirelessly to improve outcomes for people with Crohn’s disease and ulcerative colitis, and advancing research that could lead to prevention, remission, and cures.

Established in 2016, the Sherman Prize program is the first of its kind, providing financial prizes and national recognition to individuals who exemplify excellence in Crohn’s disease and ulcerative colitis, also known as the inflammatory bowel diseases (IBDs).

“My wife Cynthia and I created the Sherman Prize to celebrate excellence in IBD and inspire greater advances so fewer families have to face the challenges of these diseases,” said Bruce Sherman, Founder of the Sherman Prize. “It’s been inspiring to see the innovative work being done by brilliant IBD professionals. We’re excited to begin our fifth year and we can’t wait to see who is nominated.”

To date, twelve IBD professionals, representing diverse specialties, have been honored through the Prize program. They include physician scientists, a pediatric IBD specialist, a colorectal surgeon, a psychiatrist specializing in IBD and a physician assistant. To learn more about the many ways they are making life better for people with IBD, watch their tribute films at ShermanPrize.org.

Nominations for the 2020 Prizes may be submitted at ShermanPrize.org into the summer. A final deadline will be announced later in the spring. The Prizes will be presented December 10 at the Advances in IBD (AIBD) conference in Orlando, Florida.

About the Sherman Prize Program

The Sherman Prize program honors out-of-the-box thinkers from a variety of professional disciplines who represent “Excellence in Crohn’s and Colitis” in their chosen endeavors, having dedicated their careers to the fight to overcome IBD.

Two $100,000 Sherman Prizes are awarded annually to IBD clinicians, surgeons, researchers and/or academics, recognizing exceptional and pioneering contributions that transform the care of people with IBD. This Prize honors visionaries who are driven to solve IBD’s most difficult challenges and whose work inspires future innovators.

A $25,000 Sherman Emerging Leader Prize is awarded to an IBD clinician, surgeon, researcher, academic, physician assistant, nursing professional, or public health advocate who, while early in his or her career, has contributed to an advancement and shows great promise for significant future contributions.

Sherman Prize honorees are selected by the Sherman Prize Board of Directors, with guidance from the Sherman Prize Selection Committee, chaired by Dr. Dermot P.B. McGovern, the Joshua L. and Lisa Z. Greer Endowed Chair in Inflammatory Bowel Disease Genetics at CedarsSinai. Joining him on the Selection Committee are Dr. Lee Denson, Cincinnati Children’s Hospital Medical Center; Dr. Mark Gerich, University of Colorado Crohn’s and Colitis Center; Dr. Sunanda Kane, Mayo Clinic; and Dr. Amy Lightner, Cleveland Clinic.

Full eligibility guidelines and guidance on how to submit a nomination may be found at: ShermanPrize.org

DISPATCHES FROM THE GUILD CONFERENCE, SERIES #28

Approach to a Patient with a Liver Lesion

Laura M. Kulik

The presence of a liver lesion undoubtedly causes significant stress and anxiety not only for the patient but also for health care providers. It is important to realize that most liver lesions can be accurately diagnosed utilizing distinguishing features on imaging, laboratory data and clinical history. In lesions that remain indeterminate, a biopsy of the lesion may be warranted. Reviewing older imaging studies can provide invaluable information regarding the stability of the lesion in question and need for additional evaluation.

Liver lesions in the setting of cirrhosis substantially alter the level of concern and clinical approach to testing. Aggregate data, including patient history, laboratory results (to calculate the the aspartate aminotransferase to platelet ratio index, or APRI), evidence of portal hypertension (pHTN) on imaging and physical signs suggestive of chronic liver disease should be used to assess patients individually.

Benign Hepatic Lesions

Hepatic hemangioma, focal nodular hyperplasia (FNH) and hepatic adenoma (HA) are the most common benign liver lesions. The European Association for the Study of the Liver (EASL) has comprehensive guidelines on the management of benign liver lesions.¹ When considering if surgical resection is warranted in a patient with a benign liver lesion, there are key questions to consider: 1. Has there been growth of the lesion? 2. Is the lesion atypical or the diagnosis in question? 3. Is the patient having symptoms that could be attributed to the lesion? Magnetic resonance imaging (MRI) is the recommended imaging modality to most accurately characterize suspected benign liver lesions.

Hepatic hemangioma, a blood filled cavity lined by a single layer of epithelial cells that derives its blood supply from the hepatic artery, is the most common benign liver lesion. Thought to be congenital, hemangiomas are more common in woman than men. In contradistinction to other common benign liver lesions, hemangiomas can be seen in cirrhosis, however with less frequency and often diminished in size. These lesions demonstrate avid T2 enhancement on MRI. When small, they may lack the classis features such as centripetal enhancement or a “filling” in, so they must be distinguished from a malignancy in cirrhosis, particularly intrahepatic cholangiocarcinoma (iCCA). Most hemangiomas are less than 5 cm; when greater than 10 cm they are known as a giant hemangioma and size does not correlate with symptoms. When imaging features are consistent with a typical hemangioma, follow up imaging is not required. If a confident diagnosis cannot be made with imaging, a liver biopsy is not contraindicated, however, there must be the presence of normal liver parenchyma between the capsule and the margin of the lesion to minimize complications. Those with symptoms related to a hemangioma or a gaint hemangioma should be evaluated in a multidisciplinary clinic.

Thought to occur as a result of a congenital anomaly as a result of a venous infarct, which leads to arterialization of the affected tissue, the next most common benign liver lesion is FNH. FNH is more common in females (90%), located in the right lobe and generally solitary (conditions that are associated with multiple FNHs include: Budd Chiari syndrome, obliterative portal venopathy, post treamtnet with oxaliplatin).² A vital feature that aids in distinguishing FNH from HA is the presence of bile ducts and kuffer cells in the former. Using a biliary agent, such as Eovist or Multihance, can help radio graphically differentiate FNH from HA. An MRI is nearly 100% specific for FNH. The hallmark radiographic sign of FNH is a central scar, which represents a corkscrew artery, however in small lesions this may not be present. In lesions less than 3 cm, a contrast enhanced ultrasound (US) may be more accurate. While there is no supporting evidence that FNH have any malignant potential, it can mimic a very rare malignancy, fibrolamellar carcinoma (approximately 200 cases per year reported worldwide) due to the presence of a calcified central scar seen in 55%. Similar to hemangioma, there is no direct correlation with symptoms and size, and resection is rarely needed.

Hepatic adenomas are the least common but most concerning (risk of bleeding and development of hepatocellular carcinoma (HCC) related to size) of the benign liver lesions. The exact incidence of HA is unknown but is 10 times less common than FNH. The classic risk factors have been use of estrogen and androgens. They are more common in females than males, 10:1, and are usually single. While the incidence of HA is declining related to oral contraceptive pill (OCP) use, it is rising due to obesity and the metabolic syndrome, often leading to multiple HA. For males, resection is recommended for HA regardless of size. In females, lifestyle changes (discontinuation of OCP and weight loss) are recommended, with repeat imaging in six months. If the lesion decreases to less than 5 cm, repeat MRI in one year is recommended. If the lesion remains greater than 5 cm, repeat imaging in an additional six months is recommended. If the lesion increases in size by 20% or more, resection is indicated.

The risk of bleeding is highest in adenomas that are larger than 5 cm and exophytic. Additional risk factors for hemorrhage include use of OCPs in the last six months, pregnancy, and the inflammatory subtype (described below). When hemorrhage does occur with HA, embolization by interventional radiology should be performed to control bleeding. Emergent resection is associated with higher mortality rates.

A sub-classification of HAs was initially described in 2006 and updated in 2017.³ Associated with obesity and alcohol use, the lowest risk of degeneration to HCC is in the subtype HNF (inactivated hepatocyte nuclear factor). On imaging there is diffuse steatosis within the lesion. The inflammatory HA carries the highest risk of bleeding and also has a risk of HCC. The highest risk of developing HCC is seen in the beta catenin activated HA.

Pregnancy is no longer considered a contraindication in females with HA larger than 5 cm. If it is larger than 5 cm or there is a history of prior bleeding, resection prior to pregnancy should be discussed. There is currently no evidence based- algorithm for the management of HA in pregnancy. US every 6-12 weeks to monitor for growth is recommended. If a lesion is noted to be growing, embolization can be performed. The highest risk of bleeding during pregnancy is in the third trimester and carries a high mortality rate.

Malignant Hepatic Lesions

When evaluating a lesion that is concerning for malignancy, determining the presence of underlying liver disease, specifically cirrhosis, is important as cirrhosis predisposes patients to HCC as well as iCCA. Other malignant lesions are unrelated to the presence of cirrhosis.

The most common primary liver cancer is HCC, with 80 – 90% of cases occurring in patients with cirrhosis. In 2016, data from the CDC showed a 43% increase in mortality in the United States during the period of 2000-2016. This is thought to be due to the rising incidence of HCC with fairly steady 10-year mortality rates due to HCC. HCC is the leading cause of mortality in patients with cirrhosis with an estimated 1/3 of patients developing HCC in their lifetime. The diagnosis of HCC with known cirrhosis can be made based on radiographic findings without the need for a pathologic confirmation with a biopsy. The presence of arterial enhancement with washout in the venous phase is diagnostic if HCC, regardless of the alpha-fetoprotein (AFP) level (normal in up to 30% of tumors). Arterial enhancement, due to increased hepatic artery blood flow related to angiogenesis, promotes tumor growth and spread.

The American Association for the Study of Liver Diseases (AASLD) recommends HCC surveillance in patients with cirrhosis, regardless of etiology, every six months with an US, with optional AFP level.⁴ Surveillance is not recommended in patients with Child Pugh C cirrhosis unless they are listed for transplant. The rationale is that mortality will be driven by decompensated cirrhosis and therapy for HCC, if found, is supportive in the presence of significantly impaired liver function. If a lesion on US is detected to be greater than 1 cm, contrast enhanced imaging with computed tomography (CT) or MRI is used to make a diagnosis of HCC.

The liver imaging reporting and data system (LIRADS) was developed by the American College of Radiology with the goal of standardizing the reporting of liver lesions in patients at risk for HCC. There are 5 categories ranging from definitely benign (LI-RADS 1) to definitely malignant (LIRADS 5). A LI-RADS 5 lesion is subdivided based on size: 5A is ≥ 1 cm & < 2 cm and 5B is ≥ 2 cm & ≤ 5 cm. For both of these, a diagnosis of HCC requires the presence of non-rim arterial phase hyperenhancement (APHE) and non-peripheral washout and/or 50% increase or more in size in six months.⁵ The probability of HCC being present is shown based on the respective LI-RADS category (Table 1).

Liver transplant (LT) provides the best chance for long term overall survival by removing not only the carcinoma but also the cirrhotic liver. Unfortunately, there remains a shortage of organs to allow transplant in all that are listed. Additionally, patients with HCC tend to have preserved liver function and thus a low model for end-stage liver disease (MELD) score. In order to overcome a disadvantage in patients with HCC and a low MELD score, patients with HCC are given a “boost”, or MELD upgrade. While a lesion 1 cm or larger can be diagnosed as HCC based on characteristics seen on contrast enhanced imaging, unless a lesion is a 5A, there is not an MELD HCC upgrade. Once a lesion is 2 cm (T2 lesion), an HCC MELD upgrade is awarded. The prioritization for HCC meeting T2 criteria has evolved since the inception of the MELD allocation system with a lowering in prioritization for HCC with each reiteration in order to make access to an organ more equitable between patients with HCC and those without cancer who are listed with their biological MELD. Currently patients are given an increase in MELD score after a six month waiting period to ensure that the tumor does not harbor aggressive biological behavior that would become more obvious after a period of six months. Patients must have an AFP < 1000 at the time of listing, irrespective of tumor burden. The MELD upgrade is a calculation of the average MELD at the time of LT in each respective Organ Procurement Organization – 3 points.

Cholangiocarcinoma is the second most
common primary hepatic tumor. iCCA is the least common, followed by distal CCA and perihilar CCA (most common). Similar to HCC, the incidence of iCCA has increased and shares risk factors with HCC (cirrhosis, chronic viral hepatitis, alcohol excess, diabetes, and obesity). However, in contrast to HCC, iCCA can occur in patients with a normal architectural liver. The prognosis with iCCA is poor with 5-year overall survival rates under 5%. Currently patients with cirrhosis diagnosed with iCCA are not granted a MELD upgrade for LT due to poor outcomes. It is critical to distinguish a lesion as HCC versus iCCA. Generally these two entities can be distinguished on imaging however if not, then a biopsy of the lesion is warranted. The key radiographic findings in iCCA include progressive arterial enhancement and a lack of washout; ancillary features included capsular retraction and dilated peripheral bile ducts. Surgical resection has been the mainstay of therapy.

Other malignant lesions in the liver that are not related to the presence of cirrhosis include metastatic disease, angiosarcoma and hepatic epithelioid hemangioendothelioma (HEHE). Hepatic spread of other primary malignancies is rare in cirrhosis due to alterations in portal blood flow; the exception is colorectal adenocarcinoma, which has been reported in cirrhosis. Angiosarcoma carries a dismal prognosis with two-year survival of only 3%. Mortality is generally due to tumor rupture (high vascularity) or liver failure due to replacement of the liver with tumor. Risk factors include vinyl chloride, arsenic, cyclophosphamide, anabolic steroids, and OCP. Angiosarcoma is an absolute contraindication for LT. Treatment is resection, when possible, and chemotherapy. Lastly, HEHE is a very rare tumor of vascular origin, which is seen more commonly in middle age females. It has a more favorable prognosis compared to other hepatic malignancies, as it is generally slow growing. Treatment for HEHE includes resection, LT (>10 nodules or >4 involved hepatic segments) and anti-vascular endothelial growth factor (anti-VEGF) therapy.

CONCLUSION

Liver lesions require a careful approach to ensure correct diagnosis and therapy. It is vital to determine if a patient has cirrhosis or chronic liver disease, as this will alter the approach to a liver lesion. Fortunately, key radiographic features can help distinguish the most common benign lesion from each other and generally can be managed conservatively.

References

^{1. EASL Clinical Practice Guidelines on the management of benign liver tumours. European Association for the Study of the Liver (EASL) Journal of Hepatology 2016;65 :386–398}

^{2. Furlan A, Brancetelli G, Burgio MD et al. Focal Nodular Hyperplasia After Treatment With Oxaliplatin: A Multiinstitutional Series of Cases Diagnosed at MRI. AJR 2018;210:775-79.}

^{3. Nault JC, Couchy G, Balabaud C et al. Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation. Gastroenterology. 2017 Mar;152(4):880-894}

^{4. Heimback J, Kulik LM, Finn R et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67(1); 358-380.}

^{5. American College of Radiology Liver Imaging Reporting and Data System version 2018 core Available from: https://www.acr.org/Clinical-Resources/Reporting-andData-Systems/LI-RADS}

^{6. Marrero JA, Kulik LM, Sirlin CB et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Disease. Hepatology 2018;68,(2):723-750.}

FELLOWS’ CORNER

A Case of Sarcoidosis of Colon

Vijeta Pamudurthy,Daniel Errampalli

CASE PRESENTATION

The patient is a 61-year-old African American female with a history of diabetes mellitus type 2, hypertension, chronic kidney disease stage 4, obstructive sleep apnea, pulmonary sarcoidosis, hyperlipidemia and morbid obesity. She has been on chronic low-dose prednisone for management of pulmonary sarcoidosis. She presented for a screening colonoscopy and had no gastrointestinal symptoms. Colonoscopy revealed moderate diverticulosis of the colon, a 2 mm polyp in the ascending colon (Figure 1), two 2-4mm polyps in the transverse colon and external hemorrhoids.

QUESTIONS

1. What are some differential diagnoses of these polyps?

2. What would a pathology report of sarcoidosis show?

3. What are some possible gastrointestinal manifestations of this lesion?

4. What is the next step in the management of this patient?

DISCUSSION

Question 1.

The different types of colon polyps to consider include:

Polyps that arise from submucosa including: lipomas, carcinoids, or lymphoid tissue¹

Mucosal polyps including:

○ Inflammatory polyps

○ Hamartomatous polyps including juvenile polyps, Peutz-Jeghers polyps, phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome, and Cronkhite-Canada syndrome

○ Serrated polyps including hyperplastic polyps, sessile serrated polyps, traditional serrated adenomas, and serrated polyposis syndrome

○ Adenomatous polyps including tubular, villous, and tubulovillous

Further, there are very rare types of polyps including neurofibromal polyp of the colon and sarcoidosis of the colon. We present a patient with a history of pulmonary sarcoidosis who underwent a screening colonoscopy and was found to have a colon polyp with histology revealing sarcoidosis. Sarcoidosis is a granulomatous disease that causes noncaseating granulomas with multinucleated giant cells.²Gastrointestinal (GI) involvement is rare and usually occurs subclinically.³

Question 2.

Pathology of the ascending colon polyp revealed nonadenomatous colonic mucosa with nodules of non-necrotizing, “hard,” well formed, noncaseating granulomas and nonspecific chronic inflammation, suggestive of sarcoidosis (Figure 2). There was no histologic evidence of TB, fungal infection, colitis, or foreign body reaction. Remainder of polyps revealed tubular adenomas without highgrade dysplasia.

Question 3.

In a patient with a history of sarcoidosis, it is important to be aware of the various manifestations. Clinically evident GI system involvement occurs in less than 1% of patients with sarcoidosis. Sarcoidosis may present anywhere in the gastrointestinal tract with a multitude of symptoms including obstruction, dysmotility, ulcer, heartburn, nausea, vomiting, pain, and weight loss caused by granulomatous infiltration in the mucosa and muscular layer.⁴

Question 4.

The optimal treatment for GI involvement is unknown because of the rarity of cases of GI sarcoidosis. Some cases had spontaneous remission and while other cases required glucocorticoid therapy.⁴ Since our patient did not have any clinical manifestations of gastrointestinal sarcoidosis, she continued on the treatment same dose of glucocorticoid for pulmonary manifestations of the disease.

References

^{1. Meseeha M, Attia M. Colon Polyps. 2019 Dec 16. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/ NBK430761/ PubMed PMID: 28613512.}

^{2. Levine MS, Ekberg O, Rubesin SE, Gatenby RA. Gastrointestinal sarcoidosis: radiographic findings. AJR Am J Roentgenol. 1989 Aug;153(2):293-5.}

^{3. Friedman M, Ali MA, Borum ML. Gastric sarcoidosis: a case report and review of the literature. South Med J. 2007 Mar;100(3):301-3. Review. PubMed PMID: 17396736.}

^{4. Ungprasert P, Ryu JH, Matteson EL. Clinical Manifestations, Diagnosis, and Treatment of Sarcoidosis. Mayo Clin Proc Innov Qual Outcomes. 2019 Aug 2;3(3):358-375. doi: 10.1016/j. mayocpiqo.2019.04.006. eCollection 2019 Sep. Review. PubMed PMID: 31485575; PubMed Central PMCID: PMC6713839.}

MEDICAL BULLETIN BOARD

U.S. Food and Drug Administration Approves Epclusa for Children with Chronic Hepatitis C Infection

U.S. Food and Drug Administration Approves Epclusa® (Sofosbuvir/Velpatasvir) for Children Ages 6 And Older Or Weighing at Least 17 Kg with Chronic Hepatitis C Infection. Pediatric approval of protease inhibitor-free, pangenotypic, pan-fibrotic, once-daily regimen supports HCV elimination efforts by providing critical option for broad range of populations

Foster City, CA – Gilead Sciences, Inc. (NASDAQ: GILD) announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for Epclusa® (sofosbuvir 400mg/velpatasvir 100mg; sofosbuvir 200mg/velpatasvir 50 mg) for the treatment of people with chronic hepatitis C infection (HCV) as young as 6 years of age or weighing at least 17 kg, regardless of HCV genotype or liver disease severity. The recommended dosage of Epclusa in children ages 6 years and older is based on weight and liver function. Epclusa is the first pan-genotypic, protease inhibitor-free regimen approved in the United States for adults and children.

In the United States, there are approximately 23,000-46,000 children living with HCV. Children born to mothers with HCV are a growing concern, increasing in prevalence by 60 percent from 2011 to 2014. Additionally, engagement in high-risk practices, such as intravenous drug use, is an increasingly common route of HCV transmission in adolescents and young adults.

“While the treatment of HCV has been transformed in recent years, physicians caring for some children have still needed to take several factors into consideration, including genotype and liver disease severity, when selecting the appropriate treatment plan,” said Kathleen B. Schwarz, MD, Professor of Pediatrics, Johns Hopkins University School of Medicine. “The expanded approval of Epclusa can help eligible children living with HCV combat this life-threatening and debilitating disease.”

The approval of Epclusa is based on data from a Phase 2, open-label clinical trial (Study 1143) that enrolled 175 children who were treated with Epclusa for 12 weeks, of which 173 were included in the efficacy analysis. In children 12 to <18 years old, treatment with Epclusa resulted in a cure rate (SVR12) of 93 percent (71/76) in those with genotype 1 HCV infection and 100 percent in those with genotype 2 (6/6), genotype3 (12/12), genotype 4 (2/2) and genotype 6 (6/6) HCV infection. In children 6 to <12 years old, the SVR rate was 93 percent (50/54) in those with genotype 1 HCV infection, 91 percent (10/11) in those with genotype 3 HCV infection, and 100 percent in those with genotype 2 (2/2) and genotype 4 (4/4) HCV infection. The safety profile of Epclusa in children 6 years of age and older treated was generally consistent with that observed in clinical trials in adults. The most common adverse reactions (incidence greater than or equal to 10 percent, all grades) observed with treatment with Epclusa for 12 weeks in adults are headache and fatigue.

“Gilead’s continued commitment to HCV elimination includes bringing our medicines to the most difficult-to-cure populations and today’s decision by the FDA represents an important step toward that goal,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “With consistently high cure rates in clinical trials and in the real world, Epclusa has the potential to help many of the children living with HCV in the United States.”

For adults, Epclusa was first approved by the FDA and European Medicines Agency (EMA) in 2016. A line extension application for the use of Epclusa in children 6 to <18 years of age is currently under review with the EMA.

The U.S. product label for Epclusa contains a BOXED WARNING for the risk of hepatitis B reactivation in HCV/HBV co-infected patients. See below for U.S. Important Safety Information.

IMPORTANT U.S. SAFETY INFORMATION AND INDICATION FOR THE USE OF EPCLUSA

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment followup. Initiate appropriate patient management for HBV infection as clinically indicated.

Contraindications

If EPCLUSA is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.

Warnings and Precautions

Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.

Risk of Reduced Therapeutic Effect Due to Use with P-gp Inducers and/or Moderate to Potent Inducers of CYP2B6, CYP2C8 or CYP3A4: Rifampin, St. John’s wort and carbamazepine are not recommended for use with EPCLUSA as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations.

Adverse Reactions

The most common adverse reactions (≥10%, all grades) with EPCLUSA were headache and fatigue; and when used with RBV in decompensated cirrhotics were fatigue, anemia, nausea, headache, insomnia, and diarrhea.

Drug Interactions

Coadministration is not recommended with topotecan due to increased concentrations of topotecan; or with proton-pump inhibitors, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir.

Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments.

INDICATION

EPCLUSA is indicated for the treatment of adult and pediatric patients 6 years of age and older or weighing at least 17 kg with chronic hepatitis C virus genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis.

About Gilead Sciences

Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk that physicians may not see the benefits of prescribing Epclusa for the treatment of chronic HCV infection and the possibility of unfavorable results from ongoing and additional clinical studies involving Epclusa. Further, there is the possibility that the European Commision may not approve the line extension application for the use of Epclusa in the currently anticipated timelines or at all. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2019, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. Prescribing Information for Epclusa, including BOXED WARNING, is available at www.gilead.com.

Epclusa and Gilead are registered trademarks of Gilead Sciences, Inc., or its related companies.

For more information about Gilead, please visit the company’s website at gilead.com, follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Resources for Patients Fighting COVID-19 at Home

From ASPEN’s Website
As Chris Cuomo from CNN shares his battle with the coronavirus — reporting that he lost 13 pounds in 3 days — it’s never more apparent that nutrition and hydration are key weapons in the fight against COVID-19.

Mr. Cuomo’s struggle is the norm, as only around 12% of patients with COVID-19 are hospitalized.¹ Patients managing their illness at home have limited or no guidance on nutrition and hydration management, which are simple but essential weapons for fighting COVID-19.

With infections, the body must work intensely to mount an immune response; then, work overtime to heal and rebuild damaged tissues. Significant and quick weight loss is due to: a) large fluid losses from the fever, coughing, vomiting and/or diarrhea; and b) muscle breakdown due to the body using protein for energy. The body needs fluid and nutrition to enable it to fight the virus and prevent cannibalizing itself when providing the substrates needed for the fight.

The American Society for Parenteral and Enteral Nutrition (ASPEN) has created the resources below to help patients optimize their fight against COVID-19. We hope you will share them with your audience. You can find more resources for healthcare professionals at nutritioncare.org/COVID19.
Nutrition and Hydration: Key Weapons in the Fight Against COVID-19. This includes home recipes for a rehydration solution and a high protein shake.
Nutrition and Hydration: Quick Facts for COVID-19 Patients.

Please feel free to contact me if you have questions.  Sincerely,  Stephanie LeeASPENCommunications Director301-920-9124  1. Razzaghi H, The CDC COVID-19 Response Team. Severe outcomes among patients with coronavirus disease 2019 (COVID-19) — United States, February 12–March 16, 2020. 2020. MMWR Morb Mortal Wkly Rep. 2020;69:343-346.

About ASPEN The American Society for Parenteral and Enteral Nutrition (ASPEN) is dedicated to improving patient care by advancing the science and practice of nutrition support therapy and metabolism. Founded in 1976, ASPEN is an interdisciplinary organization whose members are involved in the provision of clinical nutrition therapies, including parenteral and enteral nutrition. With more than 6,000 members from around the world, ASPEN is a community of dietitians, nurses, nurse practitioners, pharmacists, physicians, scientists, students and other health professionals from every facet of nutrition support clinical practice, research and education. For more information about ASPEN, please visit nutritioncare.org.

How to Save the Back of Your Ears When Wearing a Mask

FROM THE PEDIATRIC LITERATURE

Esophageal Capsule Endoscopy in Children to Diagnose Portal Hypertension

It is recommended that adult patients with portal hypertension (PH) undergo screening for varices, especially in order to prevent the complication of variceal hemorrhage. There is variably in PH management in children, often due to complicating factors such as a child’s smaller size. Capsule endoscopy, specifically the esophageal capsule (EC) that captures images on both ends of the capsule at a rapid frequency, has been used to assess for esophageal varices in adults. Although EC has no therapeutic ability, it can screen for variceal formation in patients without the requirement of anesthesia. Minimal data on EC use in children with portal hypertension is available, and the authors performed a single-center, retrospective study to assess the capability of EC for variceal screening in a specific pediatric population with PH.

A 12-year chart review occurred to identify children with a diagnosis of PH who had underwent screening using EC. Patients had to be able to swallow an EC, and children with prior abdominal surgery or pacemaker placement were excluded. Three models of EC capsules (PillCam ESO, PillCam ESO2, and PillCam UGI Capsule made by Given Imaging Ltd, Yoqneam, Israel/Medtronic) were utilized. After a patient swallowed the EC by standard protocol, esophageal varices were described in regards to esophageal location (proximal, mid, or distal esophagus) and size (small, medium, or large). The electronic medical record was reviewed on each included patient to determine various aspects including testing indications for PH as well as medication use. The clinical status for each patient was defined as compensated cirrhosis, decompensated cirrhosis (cirrhosis with complications such as ascites, encephalopathy, variceal hemorrhage, or hepatopulmonary syndrome), noncirrhotic portal hypertension, cardiac cirrhosis (such as from congenital heart failure), and suspected PH.

A total of 98 patients were included in the study (57.1% male), and 146 completed EC studies were performed. The average age at the time of EC was 16 years with a median interquartile range of 13.7 – 18.5 years. Compensated cirrhosis was present in 57% of patients; noncirrhotic portal hypertension was present in 19.5% of patients. EC was used as a screening modality in 66.5% of studies and for surveillance for known varices in 33.5% of patients. No portal hypertension changes were seen in 74 EC studies, and 64 EC studies demonstrated variceal formation (59 esophageal, 17 gastric, 6 duodenal). Other findings included blood flecks (23% of studies), erosions (22.5%), portal gastropathy (18.1%), esophagitis (14.5%), heterotopic tissue (9.4%), scarring from prior ligation (12.3%), and ulcer formation (3.6%). Most identified varices were in the esophagus (59 studies), specifically in the distal esophagus (56 studies), and most varices were described as small (40 studies). The authors noted that 12 of the EC studies led to new medication use while 11 esophagogastroduodenoscopies were performed as a result of EC studies (mostly esophageal variceal band placement). Finally, a total of 4 patients had an episode of GI bleeding within 1 year of their EC study; however, none of these patients had a bleeding event due to missed findings on EC.

This study demonstrated that EC is an effective screening and surveillance tool for varices in children with portal hypertension. The safety of EC use makes it a potential quick tool for determining variceal formation, and it has the potential to be used for screening / surveillance in children who cannot tolerate anesthesia.

^{Pai A, Jonas M, Fox V. Esophageal capsule endoscopy in children and young adults with portal hypertension. Journal of Pediatric Gastroenterology and Nutrition. 2019; 69: 641-647}

^{John Pohl, M.D., Book Editor, is on the Editorial Board of Practical Gastroenterology}

NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #196

ORS: The Solutions to Optimize Hydration in Short Bowel Syndrome

Elizabeth Wall

Short bowel syndrome is a rare disorder characterized by malabsorption and dehydration. The degree of fluid and electrolyte losses will depend on the condition, length, and sites of remaining intestine. Recognition of the need for hydration in this population is imperative to prevent long term consequences of kidney injury. Home IV hydration therapy is possible, though expensive and laborious, and can result in undue burden to patients. Oral rehydration therapy is a non-invasive and relatively inexpensive alternative to maintain hydration in some patients. The question remains, who will benefit from oral rehydration (ORS)? This article will focus on assessment of hydration status in patients with short bowel syndrome, identification of patients who may benefit from ORS, and it will provide guidelines for the use of ORS.

INTRODUCTION

Short bowel syndrome (SBS) is a rare disorder characterized by malabsorption and dehydration after extensive surgical resection of the small bowel (SB); the resection may also include part or all of the colon.¹ The degree of malabsorption and fluid loss will depend on length, location, and condition of the remaining SB, and the presence or absence of not only the ileocecal valve, but more importantly, the colon as well. Small bowel length < 200 cm and/or ostomy effluent > 1.5L/d will result in malabsorption of nutrients, fluid, and electrolytes, and therefore defines SBS ^(2-4), although Medicare defines SBS as < 150 cm.⁵

Under normal conditions the intestinal tract secretes 6-7 L of fluid daily, reabsorbing virtually all, in addition to the 1-2 L of ingested fluid.⁶ After SB resection, patients have net losses of fluid and electrolytes; those without a colon will have an even greater net loss. Negative fluid balance can develop soon after surgery and progress rapidly to dehydration and acute kidney injury necessitating medical attention and fluid resuscitation.⁷ Some patients will “survive” in a state of chronic dehydration, without overt signs of kidney injury, but over time negative fluid balance can lead to nephrolithiasis and chronic kidney injury.^8,9 Long term parenteral support (PS) can replace electrolyte losses and prevent dehydration, but it is associated with serious risks such as infection and injury to central blood vessels, not to mention the impact on lifestyle and healthcare expenses.10 The long term goal for hydration management is to optimize enteral intake and reduce need for PS. Oral rehydration solutions (ORS) can help achieve this goal for many.

Intestinal resections disrupt neuroendocrine hormone signaling to the gastrointestinal tract and related organs.² The dysregulation of postprandial hormone responses affects motility and absorption. It is not uncommon for SBS patients to have rapid gastric emptying (dumping) of hypo- or hypertonic chyme into the SB. The proximal SB reacts to this by secreting sodium or water to adjust the luminal fluid concentration to isotonicity, thus increasing the total volume of fluid needing to be absorbed.² Water absorption across the SB epithelium is dependent on a sodium-glucose cotransport system; sodium and glucose molecules are transported together across the SB epithelium, dragging along water molecules.6,11 The ileum is more efficient than jejunum in reabsorbing water, but many with SBS have little or no ileum. Table 1 lists the expected daily volume of ostomy/stool output.^3,11

Oral rehydration solutions were developed to utilize the sodium-glucose co-transport system and are found to be effective in many patients with SBS.¹² The ideal solution contains 20-40 g (5-10 teaspoons) of sugar and 90-120 mEq sodium/L (1 teaspoon of salt = 104mEq of Na).¹³ The concentration of sodium makes these solutions unpalatable; therefore commercially available ORS products contain slightly less sodium to improve taste without loss of effectiveness. Pediatric ORS contain lower concentrations of both glucose and sodium. Table 2 lists ORS products commercially available in the United States.^14,15

Assessing Hydration Status in SBS

Accurate assessment of hydration status is imperative when considering ORS therapy, however the typical indicators of dehydration may not be accurate in SBS. The kidneys work to preserve blood volume despite total body water depletion from excessive gastrointestinal losses of sodium and water; serum sodium and blood urea nitrogen to creatinine ratio can remain normal until the patient is severely dehydrated.^12,16 Common signs of dehydration can be factitious in SBS including: deep yellow urine from multivitamin ingestion, muscle cramps from hypomagnesemia, and dry mouth from narcotic-based anti-motility or other medications. Physical exam with attention to clinical signs of dehydration (dry mucus membranes, skin tenting, dry or peeling skin) in conjunction with a downward spiral of serial weights, 24 hour volume of urine and ostomy/stool outputs, and spot urine sodium concentration are all helpful to assess true hydration status in this population.¹⁷ Table 3 lists physical signs of dehydration commonly experienced by SBS patients. Adequate hydration is indicated by urine volume > 1200mL/day and spot urine sodium > 20 mEq/L.¹⁷

Patient Selection

Many patients with SB ostomy, or those with only a small portion of colon in continuity, may benefit from ORS therapy; those with most of their colon usually do not need ORS to maintain hydration. Ideal candidates have insatiable thirst and drink large volumes of water (hypotonic fluids) without relief, have low urine volume and escalating ostomy/stool output. Patients who can accurately measure and track their weight, PS/enteral/oral intake, and output (urine and ostomy/stool) to determine efficacy of ORS are more likely to be successful with the therapy. If the patient has an ostomy, measurement of the pouch volume will help ease data collection by simply counting the number of times it is emptied in 24 hours; however actual measurement of the volume with a canister with ounces or mL marked on the outside is better, at least initially.

Using Oral Rehydration Solutions

In combination with anti-motility medications and strict adherence to recommended meal patterns, ORS can facilitate fluid absorption, but it will not necessarily decrease ostomy/stool output.17 Patients should start by sipping a low volume of ORS, 500-750mL/d, to gain acceptance to the taste, learn how to sip between meals throughout the day, all the while ensuring consumption of ORS does not worsen their hydration status (by driving their stool/ostomy volume too high to keep up). If ORS therapy leads to increased urine volume, irrespective of ostomy/stool output, then it can be considered effective. Patients can then gradually increase their consumption to 1-3 L/d while continuing to monitor their hydration. However, if stool/ostomy output increases without an increase in urine output, then ORS therapy is not effective and it should be discontinued, and the patient may require PS to maintain hydration and protect kidney function. Table 4 identifies keys factors for ORS success.

Some patients will try to consume ORS by gulping the daily volume, “just to get it down.” Rapid ingestion of ORS can cause dumping into the SB, exceeding its absorptive capacity, resulting in increased unabsorbed effluent into the ostomy appliance or colon. It is important to train patients to slowly sip ORS throughout the day for maximum absorption. In patients with enteral feeding access, slow infusion of ORS overnight via a pump has proven to be effective in maintaining hydration and weaning from PS.¹⁸

Long term adherence to ORS regimens is often poor due to unpalatable flavors and the expense of commercially prepared products.¹⁹ To overcome these barriers patients can mix their own solutions and reserve use of commercial ORS for times when self-preparation is not feasible (traveling). Recipes for homemade ORS are listed in Table 5.^14,15 It must be emphasized that these recipes are designed with specific balance between sugars and sodium for optimal absorption. Inaccurate measurement of ingredients or enhancing ORS with additional water, ice, juice or sugar-containing flavorings will alter the sodium to carbohydrate ratio making the beverage less effective. Non-nutritive flavorings and sweeteners (e.g., Crystal Light®, Zero Sugar Sunkist®, Kool-Aid Liquid Drops®, or Water Drops™) can be added without altering the sodiumcarbohydrate ratio; use of these products will help to prevent taste fatigue and maintain intake. Compliance improves when clinicians encourage creativity with ORS consistency and temperature such as freezing in ice cube trays, mixing with plain gelatin, and using a thermos to maintain warm or cool temperatures throughout the day.

Success of ORS therapy can be dependent on a patient’s access to proper tools for mixing of ORS ingredients and equipment to monitor their hydration status (Table 6). When trialing or adjusting daily volume of ORS the patient should record daily weight and 24 hour intake (including ORS) and output measurements (see Table 7). These data will help the patient and clinician ascertain whether or not ORS is an effective therapy for that patient.

Other Fluids

What about fluids other than ORS? Sugary or hypertonic fluids (soda, sweet tea, juice, fruit drinks, flavored coffees) will rapidly pass into the jejunum where water will be secreted into the SB lumen to dilute the chyme to isotonicity. Likewise, consumption of hypotonic fluids (plain water, diet soda, plain tea or coffee, dilute juices) leads to jejunal secretion of sodium (and water) to adjust the chyme to isotonicity. Both scenarios increase ostomy/stool output and result in net fluid and sodium losses. In the case of patients who are unable to tolerate, or refuse to drink ORS, the next “best” fluid options are hypotonic fluids that contain lower amounts of carbohydrate and sodium compared to ORS (e.g., G2 Gatorade® or Powerade® [not the “zero calorie” variety]). Electrolyte powders and waters such as Trioral Oral Rehydration Salts® and Propel Electrolyte Water® are sugar free and can be sipped while snacking on small portions of saltystarchy snack foods like pretzels, soda crackers, potato or corn chips. Small volumes (4-8 oz.) of these fluids or plain water are generally tolerated with meals. Caffeine and alcohol act as diuretics and can exacerbate dehydration in SBS. As discussed above, sports and electrolyte drinks contain the wrong proportions of carbohydrate and sodium and therefore are not considered ORS. Oral nutrition supplements (e.g., Boost® or Ensure® and store bought equivalents) are high in sugar and low in sodium, leading to water and sodium losses with increased stool/ostomy output. These supplements should not be offered to those with SBS or high volume ostomy output.

CONCLUSION

Maintaining hydration is a chronic issue for SBS patients. Although PS is available for most patients, it is associated with high costs, health risks and lifestyle burden. Oral rehydration therapy can be a viable option to reduce or eliminate the need for PS for many with SBS. To maximize benefits from ORS, it is essential that patients receive education and ongoing support from a knowledgeable provider. Patients must have proper tools to prepare the ORS and ability to self-monitor their response to sipping ORS throughout the day. Creativity and experimentation with flavors and consistency can improve acceptance and adherence to the therapy. Although ORS is not effective for all patients, in those with benefit, transition from PS to ORS will reduce risks of iatrogenic complications and overall healthcare expense, while permitting a more normal lifestyle

References

^{1. Jeppesen PB. Short bowel syndrome: Definition, classification, etiology, epidemiology, survival, and costs. In: DiBaise JK, Parrish CR, Thompson JS. Eds. Short Bowel Syndrome: Practical Approach to Management. CRC Press, Boca Raton, FL 2016;1-13.
2. Nightingale J. Short bowel syndrome: Anatomical and physiological considerations. In: DiBaise JK, Parrish CR, Thompson JS. Eds. Short Bowel Syndrome: Practical Approach to Management. CRC Press, Boca Raton, FL 2016;29-40.
3. Nightingale J, Woodward JM. Guidelines for management of patients with short bowel. Gut. 2006;55(suppl 4):iv1-iv12.
4. Buchman AL, Scolapio J, Fryer J, et al. AGA technical review on short bowel syndrome and intestinal transplantation. Gastroenterol. 2003;124(4):1111-1134.
5. Allen P. Medicare Coverage for Home Parenteral Nutrition – An Oxymoron? Part I. Prac Gastroenterol. 2016;Dec(12):34-50.
6. Barrett KE. Water and electrolyte absorption and secretion. In: Barrett KE. ed. Gastrointestinal Physiology, 2e New York, NY: McGraw-Hill; 2014. http://accessmedicine.mhmedical.com/content.aspx?bookid=691& sectionid=45431395. Accessed January 16, 2020.
7. Banerjee A, Warwicker P. Acute renal failure and metabolic disturbances in the short bowel syndrome. Q J Med. 2002;95:37-40.
8. Lauverjat M, Aissa AH, Vanhems P, et. al. Chronic dehydration may impair renal function in patients with chronic intestinal failure on long-term parenteral nutrition. Clin Nutr. 2006;25:75-81.
9. Bridges M, Nassar R, Parrish CR. High Output Ileostomies: The Stakes are Higher than the Output. Prac Gastroenterol. 2019;Sept (9):20-33.
10. Winkler MF, Hagan E, Wetle T, et al. An exploration of quality of life and experiences of living with home parenteral nutrition. JPEN J Parenter Enteral Nutr. 2010;34(10):395-407.
11. Parrish CR, DiBaise J. Part 3: Hydrating the adult patient with short bowel syndrome. Prac Gastroenterol. 2015;Feb(2):10-18.
12. Beaugerie L, Cosnes J, Verwaerde F, et al. Isotonic high-sodium oral rehydration solution for increasing sodium absorption in patients with short-bowel syndrome. Am J Clin Nutr. 1991;53:769-772.
13. Nightingale JMO, Lennard-Jones JE, Walker ER, et al. Jejunal efflux in short bowel syndrome. Lancet 1990;336:765-768.
14. Parrish CR, Ross V. Hydration and SBS in Adults Patient Handout. https://www.nmpgdpg.org/members/ page/digid-resources. Accessed January 19, 2020.
15. Parrish, CR. A Patient’s Guide to Managing a Short Bowel, 4th Edition. Intouch Solutions, Overland Park, KS; June 2016:1-66. Available at: no cost at: www.shortbowelsyndrome.com/sign-up
16. Blalock BE, Parrish CR. Maintaining hydration in the short bowel patient. In: DiBaise JK, Parrish CR, Thompson JS. Eds. Short Bowel Syndrome: Practical Approach to Management. CRC Press, Boca Raton, FL 2016:145-153.
17. O’Neil M, Teitelbaum DH, Harris MB. Total body sodium depletion and poor weight gain in children and young adults with an ileostomy: A case series. Nutr Clin Pract. 2014;29(3):397-401.
18. Nauth J, Chang CW, Mobarhan S, et. al. A therapeutic approach to wean total parenteral nutrition in the management of short bowel syndrome: Three cases using nocturnal enteral rehydration. Nutr Reviews. 2004;62(5):221-231.
19. Hurt RT, Vallusmsetta N, Varayil JE, et al. Piolet study comparing 2 oral rehydration solutions in patients with short bowel syndrome receiving home parenteral nutrition: A prospective double-blind randomized controlled trial. Nutr Clin Pract. 2017;32(6):814-819.}

FROM THE PEDIATRIC LITERATURE

Transnasal Endoscopy for Children with Eosinophilic Esophagitis

Currently, the best way to perform disease monitoring in eosinophilic esophagitis (EoE) is through direct visualization of the esophageal mucosa with biopsy via esophagogastroduodenoscopy (EGD). Repeat EGDs requiring sedation can be a potential risk in children, and the authors of this study evaluated the alternative use of transnasal endoscopy (TNE) to monitor disease in children with EoE. The authors of this study looked at a protocol of monitoring EoE in children in which the patients were given a web-based video to watch prior to the procedure. The patients did not eat or drink 2 hours before the procedure. During TNE the patients wore either movie goggles or virtual reality movie goggles. Topical lidocaine or aerosolized benzocaine was applied orally and intranasally. A small bronchoscope or endoscope (size range 2.8 mm to 4.9 mm outer diameter) was placed transnasally based on the patient’s nasal passage size, and esophageal biopsies were obtained via forceps placed through a 1.2 mm or 2 mm operating channel depending on the size of the bronchoscope or endoscope used. Patient demographics, procedure number, completion rate, type of endoscopy, and adverse events were recorded.

There were 300 TNE attempts recorded over a 3-year period, and 294 TNEs were performed successfully (98%). The study population consisted of 190 patients (age range 3 to 22 years). Both operating channel sizes were used throughout the age range. Throughout the 3-year study, the average number of TNE procedures increased every year (48 in 2015; 131 in 2017), and time from procedure check-in to discharge decreased by a small amount as well (maximum time 79 minutes which decreased to 71 minutes by the end of the study period). The total percentage of endoscopies for EoE that were performed via TNE increased as well (15.7% in 2015 to 31.8% in 2017). In 2018, the average cost for TNE with biopsy for EoE was $4393 while the average cost for EGD with biopsy for EoE was $9444.33 (a 53.4% reduction in cost using the transnasal approach). All biopsies obtained by TNE were adequate for examination by a pathologist. Adverse events were rare and only consisted of interventions that included telephone management, reassurance, and supportive care.

This study demonstrates that TNE with video goggles is a safe and effective diagnostic technique to perform in children with EoE. The ability to obtained esophageal tissue with no sedation and with an associated reduction in healthcare costs provides the possibility to expand the use of this procedure throughout pediatric healthcare systems.

^{Nguyen N, Lavery W, Capocelli K, Smith C, Deboer E, Deterding R, Prager J, Leinwand K, Kobak G, Kramer R, Menard-Katcher C, Furuta G, Atkins D, Fleischer D, Greenhawt M, Friedlander J. Transnasal endoscopy in unsedated children with eosinophilic esophagitis using virtual reality video goggles. Clinical Gastroenterology and Hepatology. 2019; 17: 2455-2462.}

^{John Pohl, M.D., Book Editor, is on the Editorial Board of Practical Gastroenterology}

A CASE REPORT

Colonic Adenocarcinoma Masquerading as a Pork Bone

Megan Willard

We present a patient with acute onset of abdominal pain and colonic obstruction occurring soon after eating a pork sandwich. Imaging was suggestive of a colonic obstruction related to a foreign body, likely a bone fragment. Ultimately, the patient was found to have a calcified colonic adenocarcinoma masquerading as a foreign body. Case reports have been written about foreign bodies masquerading as colonic tumors, but here we present a case of a colonic tumor masquerading as a foreign body.

INTRODUCTION

Intra-abdominal calcifications seen on imaging are usually benign, and do not portend significant pathology. Gastrointestinal tumors rarely have calcifications within the primary tumor, and occasionally calcification can be seen in a gastrointestinal tumor metastases. Calcifications within tumors of the gastrointestinal tract, when seen, are usually in association with a mucoid or mesenchymal tumor, but not in adenocarcinoma, as in this case. Herein, we report a case of a primary colonic adenocarcinoma with calcifications that resembled a bone fragment in a patient with an acute bowel obstruction.

Case Report

A 62-year-old male presented to the emergency department (ED) with diffuse abdominal pain, worst in the left lower quadrant, and constipation for the past 48 hours. The pain waxed and waned and was worsened by eating. He noted that his symptoms started soon after eating a BBQ pork sandwich. He was discharged from the ED with a diagnosis of constipation and a prescription for laxatives, but within 24 hours his pain worsened and he returned. At this time, he also complained of nausea and inability to tolerate oral intake. He noted that at baseline his stools were always normal in caliber and consistency, and that he had no new medications or dietary changes. On physical examination, his blood pressure was 167/101 mmHg, heart rate 88, and he was afebrile with normal oxygen saturation. He appeared uncomfortable but non-toxic. Abdominal exam revealed a distended and diffusely tender abdomen, with guarding but no rebound tenderness. On auscultation there were high-pitched, tinkling bowel sounds. Rectal exam revealed scant brown stool. Laboratory studies revealed a slightly elevated white blood cell count at 10.5 K/mcL, an otherwise normal complete blood count, and normal basic metabolic and liver enzyme panels. Computed tomography (CT) of the abdomen and pelvis with oral and intravenous contrast demonstrated focal colonic narrowing at the junction of the descending and sigmoid colon, with associated thickening and pericolonic stranding. A curvilinear 4 cm density presumed to be a foreign body, possibly a pork bone, was located at the proximal aspect of this narrowed segment (Arrow, Image 1). Surgery was performed. At laparotomy the proximal colon was severely dilated with no evidence of necrosis or perforation. No foreign body was noted; however, a sigmoid mass was palpated and a resection was performed. Pathology revealed a calcified invasive well-differentiated T3N1a colonic adenocarcinoma with tumor deposits in the mesenteric fat.

Discussion

Many case reports have been written about foreign bodies masquerading as colonic tumors, but here we present a case of a colonic tumor masquerading as a foreign body. This patient’s history of the acute onset of symptoms, so close in proximity to a meal which potentially contained a bone, and the CT scan which revealed a curvilinear density, which very much appeared to be a bone of some type, made foreign body ingestion and subsequent obstruction high on the differential. Ultimately, it was determined that the curvilinear density seen on CT scan represented calcification within the tumor. Intra-abdominal calcifications seen on imaging are usually benign.^1,2 Calcifications within tumors of the gastrointestinal tract are infrequent,^2,3 and when seen are usually in association with a mucoid or mesenchymal tumor, but not in adenocarcinomas, as in this case.^2,4 Calcifications associated with colonic adenocarcinomas are more frequently observed in the metastases of the colonic primary, especially in the liver, which occurs in 12-27% of cases.⁴ More frequently, calcifications are seen in more slow growing tumors. The pathophysiology of this process is unknown but is thought to be attributed, in part, to devitalized tissue or mucin within the tumor creating a more alkaline environment which allows for precipitation of phosphate and carbonate salts.^1,4 A few case reports exist in the literature of calcifications within colonic tumors, with the first case being reported in 1954.² These calcifications were described as small and punctate, or arranged in stippled fashion, and overwhelmingly, the histopathology revealed mucoid carcinoma, not adenocarcinoma.³ Our patient’s calcification more closely resembled a curvilinear foreign body. In summary, we present an unusual case of acute colonic obstruction with imaging suggestive of a foreign body, perhaps a bone, which ultimately was diagnosed as calcified colonic adenocarcinoma.

^{References
1. Chen YG, Kao WY, Tsai SH. Nonspecific but Significant. Am J Med. 2012 May;125(5):461-4.
2. Fletcher B, Morreels J, Christian W, Brogdon B. Calcified Adenocarcinoma of the Colon. Am J Roentgenol. 1967 Oct;101(2):301-5.
3. Engel S, Dockerty M. J Calcifications and Ossification in Rectal Malignant Processes. JAMA. 1962; 179(5): 347-350.
4. Chang SL, Lin CP, Lee RC. Calcification of Liver Metastases in a Colon Cancer Patient Following Chemotherapy with 5-fluorouracil: A Case Report. Chin J Radiol 2002; 27:73-77.}