Disease-a-Month ] (2014) ]]]–]]]

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Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth

Clinical pearls in gastroenterology (2013) John A. Schaffner, MD, Scott C. Litin, MD, John B. Bundrick, MD

Case 1 A 35-year-old woman with a BMI of 31 has a 3-year history of RUQ pain. The pain is characterized as 3/10 dull ache in the RUQ and is present most of the time but is aggravated by eating. It has not progressed. It is associated with occasional nausea but no vomiting. She has a tendency toward constipation. She is tender in the RUQ. Her AST, ALT, and alkaline phosphatase are normal. RUQ ultrasound is normal with no stones, and a HIDA scan shows an ejection fraction of 18% (normal 435%). During the HIDA she develops abdominal discomfort similar to her pain. Question You recommend: A. B. C. D. E.

Proton pump inhibitor (PPI) Cholecystectomy Colonoscopy Abdominal CT Symptomatic treatment with dicyclomine

Discussion RUQ pain in the absence of obvious gall bladder pathology such as gallstones or sonographic evidence of cholecystitis is common. Biliary dyskinesia is a functional motility disorder with characteristic symptoms that include episodic pain in the RUQ or epigastrium that lasts at least 30 min. The pain may be associated with nausea and vomiting and should interrupt normal daily activities. Biliary scintigraphy showing a low ejection fraction in response to CCK stimulation coupled with an appropriate history may or may not predict a good response to cholecystectomy. Symptoms related to CCK stimulation are not a reliable indicator of gall bladder dysfunction in the absence of a relevant history. Cholecystectomy in a patient without the above symptoms is far less likely to result in clinical improvement. In this case, a 3-year history of continuous RUQ pain is not likely to be associated with biliary dyskinesia. The low http://dx.doi.org/10.1016/j.disamonth.2014.04.011 0011-5029/& 2014 Mosby, Inc.. All rights reserved.

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ejection fraction is uninterpretable in this circumstance and is not a reliable predictor of response to surgery. Constant symptoms over 3 years are also highly unlikely to represent acid peptic disease. Colonoscopy is almost never helpful if the only symptom is pain and is not indicated for that purpose. Abdominal CT is an excellent test for abdominal evaluation; but with this pattern of symptoms, it is unlikely to find an answer. This is likely to be a functional syndrome and warrants a trial at symptomatic relief. Clinical pearl Decisions for cholecystectomy should not be based on HIDA alone. A clinical history is the best discriminator of biliary dyskinesia and can be confirmed by a HIDA scan. References 1. Hansel SL, DiBaise JK. Functional gallbladder disorder: gallbladder dyskinesia. Gastroenterol Clin N Am. 2010;39:369–379. 2. Francis G, Baillie J. Gallbladder dyskinesia: fact or fiction? Curr Gastroenterol Rep. 2011;13:188–192. Practice gap in gastroenterology Unwarranted cholecystectomies are being performed on patients whose symptoms are not suggestive of biliary disease just because of the results of HIDA scans showing low ejection fractions. Gap source 1. Bielefeldt K. The rising tide of cholecystectomy for biliary dyskinesia. Aliment Pharmacol Ther. 2013;37:98–106. Case 2 An otherwise healthy 55-year-old man has a history of kidney stones. On a CT urogram performed at a recent emergency room visit, a small cystic lesion measuring 7 mm is identified in the pancreas. Included in the differential of the radiologist is branch duct intraductal papillary mucinous neoplasm (IPMN). Question The next step would be: A. B. C. D. E.

An MRI of the pancreas A pancreatic protocol CT Endoscopic ultrasound Repeat imaging in 6–12 months Nothing

Discussion There is a highly significant increase in the rate of detection of cystic neoplasms of the pancreas likely related to the increased use of cross-sectional imaging and the advancements in techniques. The knowledge of what to do with these often incidental findings is still under scrutiny. The current state of knowledge and recommendations have recently been compiled and published. There are evolving recommendations based on the characteristics of the lesions.

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The classification of risk includes “high-risk stigmata” and “worrisome features,” which help guide therapy. The high-risk stigmata in any size lesion includes enhanced solid components, a main pancreatic duct 4 10 mm, or the presence of jaundice with a cystic lesion in the head of the pancreas. Worrisome features include cysts 43-cm, thickened cyst walls, non-enhanced mural nodules, main duct size of 5–9 mm, and an abrupt change in duct caliber with atrophy. All cysts with high-risk stigmata by cross-sectional imaging or EUS should be resected. All cysts with worrisome features should undergo EUS and recommendation should be made based on findings. If no worrisome features are present, no further workup is needed, but surveillance is still recommended. Resection is recommended in all MD-IPMN. Smaller lesions or lesions without worrisome features require at least one follow-up examination to determine stability of the lesion. Since the lesion in this case has no obvious worrisome features, repeat imaging would be recommended at an interval of 6–12 months and if stable the interval can be increased. Age and comorbidities will modify surveillance intervals in the future. Clinical pearl Cystic lesions of the pancreas have significant malignant potential, and growth characteristics may only be determined with time. References 1. Tanaka M, Castillo CF, Adsay V, et al. International Consensus Guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12:183–197. 2. LeeLS, Clancy T, Kadiyala V, et al. Interdisciplinary management of cystic neoplasms of the pancreas. Gastroenterol Res Pract. 2012;2012:513163. doi: 10.1155/2012/513163. Practice gap in gastroenterology The recognition and management of cystic neoplasms of the pancreas are changing rapidly and are not well known outside a small group of specialists. Lack of recognition of the importance of these lesions can result in either under or over testing. Gap source 1. Klibansky DA, Reid-Lombardo KM, Gordon SR, Gardner TB. The clinical relevance of the increasing incidence of intraductal papillary mucinous neoplasm. Clin Gastroenterol Hepatol. 2012;10:555–558. Case 3 A 58-year-old woman has right-sided upper abdominal pain for the last 2 years. The pain is present 24/7 at a level that fluctuates between 3–7/10. She cannot pinpoint a cause when it started, and it has not changed over the 2 years. It is aggravated by eating on occasion, by constipation, and by sitting for long periods. A CT scan, RUQ ultrasound, EGD, and colonoscopy are normal. On exam she can point to the location of a tender area with one finger in the MCL in the RUQ. Question Which of the following would you recommend: A. Repeat EGD B. Surgical consultation

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C. Trigger-point injection D. MRI of the abdomen E. Hydrocodone Discussion GI diseases are a major cause of morbidity, mortality, and cost in the U.S. Abdominal pain is the single most common GI symptom presenting for outpatient clinic visits, almost 4 times more frequent than the next presenting symptom. Abdominal wall pain represents a significant percent of those patients with pain, as many as 30%. Failure to recognize abdominal wall pain can result in unnecessary testing and surgery. Recognition of abdominal wall pain is important and primarily accomplished by history and physical examination. Focal 24/7 pain without a consistent relationship to GI function and exacerbation related to physical positions or activity often will indicate abdominal wall pain. A positive Carnett’s sign (increased tenderness at the symptomatic spot when the abdominal muscles are tensed either by raising the head or legs) can be confirmatory for abdominal wall pain. The best treatment for persistent abdominal wall pain is trigger-point injection. Clinical pearl Abdominal wall pain is often overlooked and the diagnosis is made by history and physical exam. References 1. Lindsetmo RO, Stulberg J. Chronic abdominal wall pain—a diagnostic challenge for the surgeon. Am J Surg. 2009;198:129–134. 2. Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012;143:1179–1187.

Practice gap in gastroenterology Failure to recognize abdominal wall pain leads to unnecessary testing and surgery. Gap source 1. Costanza CD, Longstreth GF, Liu AL. Chronic abdominal wall pain: clinical features, health care, costs, and long-term outcome. Clin Gastroenterol Hepatol. 2004;2:395–399. Case 4 A 65-year-old man has a family history of colon cancer with his father dying of the disease at age 75. He had a colonoscopy at 60 years of age that was normal. He had a colonoscopy recently that showed a 1.5-cm sessile serrated adenoma that was removed in piecemeal fashion. There is no comment in the report about completeness of the polypectomy and the endoscopist cannot remember. Question Your recommendation for the time of his next colonoscopy is A. 3–6 months B. 1 year

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C. 3 years D. 5 years E. 10 years

Discussion Surveillance guidelines for colorectal cancer have evolved as studies have produced more robust results. In 2012, the guidelines have again been revised. This recent revision has better defined the serrated adenoma, which has a different pathway to adenocarcinoma than the tubular or villous adenoma. Serrated polyps may be more difficult to detect because of their appearance and may account for patients who have developed adenocarcinoma despite adequate screening. The rapidity of cancer development in these lesions may be faster than in tubular adenomas as well. It is important to be aware of the significance of these lesions and insure appropriate follow-up. Aside from the pathology of the lesion, it is important to insure that the identified polyps are completely removed. If residual polyp remains, cancer development can still progress. In this circumstance, the patient has a serrated adenoma. If this was a tubular adenoma that had been completely resected, the next colonoscopy recommendation would be in 5 years. Because this is a serrated adenoma 4 1 cm, the normal recommendation would be a repeat exam in 3 years. One of the reasons for the shorter interval is that many patients may actually have additional lesions that were not detected. Since the lesion in this case may not have been completely removed, the recommendation is for follow-up in 3–6 months. Further information in the coming years may change these recommendations further. Clinical pearl Serrated polyps have significant malignant potential and different growth patterns from tubular adenomas and may be responsible for missed or interval colon cancers. References 1. Snover DC. Update on the serrated pathway to colorectal carcinoma. Hum Pathol. 2011;42:1–10. 2. Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138:2088–2100. 3. Arnold CA, Montgomery E, Iacobuzio-Donahue CA. The serrated pathway of neoplasia. Diagn Histopathol. 2011;17:367–375. Case 5 A 54-year-old man has long-standing heartburn that is well controlled by taking a PPI once a day. He is currently asymptomatic. You recommend an EGD, his first, which demonstrates 3 cm of Barrett’s esophagus with no dysplasia on biopsy. Question Which of the following would be the next step: A. B. C. D. E.

Repeat endoscopy in 3 years Endoscopic ablation of Barrett’s epithelium Increase his PPI dose Fundoplication No further surveillance

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Discussion Heartburn is a common symptom with as many as 40% of U.S. adults reporting some symptom of GERD. Up to half of these patients have weekly symptoms, and of that group, as many as 10% may have Barrett’s esophagus. The risk of developing adenocarcinoma in Barrett’s esophagus is related to dysplasia but the overall risk is low, with a recently reported risk in the absence of dysplasia of 0.27% a year. There are new recommendations for surveillance in patients with Barrett’s esophagus, with a 3-year interval in the absence of dysplasia—the answer in this case. There is no indication that higher-dose PPI therapy or fundoplication will alter the course of Barrett’s; therefore, modifications in therapy or surgery should be dictated by symptoms alone. There is considerable controversy in the GI literature about appropriate endoscopic therapy for Barrett’s esophagus without dysplasia so it should not be recommended at this time. Not everyone with GERD needs an endoscopy. The recommendations for endoscopy in GERD are well outlined in the ACP clinical guideline recently published in the Annals of Internal Medicine. Essentially, endoscopy should be performed (1) in anyone with alarm symptoms that include dysphagia, bleeding, anemia, weight loss, and recurrent vomiting; (2) in patients with typical symptoms who do not improve on twice daily PPI therapy; (3) in patients with severe or stricturing disease; (4) in men over the age of 50 years with more than a 5-year history of GERD and other risk factors that include nocturnal reflux, hiatal hernia, elevated BMI, and smoking. Clinical pearl In the absence of dysplasia in intestinal metaplasia, a surveillance interval of 3 years is recommended. There is growing controversy about treatment of Barrett’s esophagus. References 1. Wani S, Falk G, Hall M, et al. Patients with nondysplastic Barrett’s esophagus have low risks for developing dysplasia or esophageal adenocarcinoma. Clin Gastroenterol Hepatol. 2011;9: 220–227. 2. American Gastroenterological Association Medical Position Statement on the Management of Barrett’s Esophagus. Gastroenterology. 2011;140:1084–1091. 3. Shaheen NJ, Weinberg DS, Denberg TD, et al. Upper endoscopy for gastroesophageal reflux disese: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med. 2012;157:808–816. Case 6 A 61-year-old woman developed diarrhea after a course of antibiotics for a sinus infection. A stool specimen was positive for C. difficile and she was placed on metronidazole for 10 days with good results. Four days later her diarrhea recurred. She was given metronidazole for another 10 days and again responded, but she relapsed 5 days after stopping the antibiotic. Question Which of the following would you recommend: A. B. C. D. E.

Metronidazole for 3 weeks Prolonged course with taper of vancomycin Fecal transplant Oral vancomycin for 10 days Fidaxomycin

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Discussion C. difficile is a common cause of diarrhea that is not always associated with antibiotic usage. Recurrence after initial therapy with metronidazole or vancomycin in mild disease is approximately as high as 25%. Since this patient has already relapsed after standard therapy, the next step would be a prolonged course of vancomycin with a prolonged taper. Liquid vancomycin is generally a much cheaper alternative than tablet form. Because of the cost, new therapies using fidaxomycin or fecal transplant should be reserved for recurrence after prolonged therapy. Availability of fecal transplant and ultimate cost and insurance coverage may determine the next step in therapy. Several studies are now showing equivalent efficacy for transplant and fidaxomycin. A recent randomized trial indicated superiority of fecal transplant over vancomycin. There is no consensus yet on how fecal transplant should be performed. Probiotics after initial therapy have been shown to be helpful in reducing the recurrence rate. Clinical pearl While there are newer treatments available for C. difficile, standard therapies should be implemented first before more expensive therapies are utilized. Vancomycin with a prolonged taper would be the choice in second relapse. If that fails, fecal transplant would be the next step if available. References 1. Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2012;9:88–96. 2. McCollum DL, Rodriquez JM. Detection, treatment, and prevention of Clostridium difficile infection. Clin Gastroenterol Hepatol 2012;10:581–592. 3. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368:407–415. Case 7 A 27-year-old woman has a long history of bloating. She had not been able to identify any particular aggravating factor in the past. She has no weight loss and no diarrhea. She sometimes feels “constipated,” although she has a daily bowel movement. She has an unremarkable family history. After reading about the evils of gluten, she went on a gluten-free diet a month ago and feels much less bloated. Question Which of the following would you recommend: A. B. C. D. E.

Continuing the gluten-free diet Restarting gluten and performing a tTG A small bowel biopsy Genetic testing for celiac disease Performing a tTG now

Discussion There is an increasing interest in gluten- or wheat-free diets for the management of a host of symptoms, including many individuals with functional GI symptoms. While a small number of

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these patients may actually have celiac disease, a much larger group may actually feel better on a carbohydrate-reduced diet. Undigestible carbohydrates are a major contributor to gas in the GI tract. The important point of this case is that making the diagnosis of celiac disease in a patient on an established gluten-free diet can be difficult to impossible. Therefore, before individuals undertake a gluten-free diet, serological testing should always be performed. Abnormal serology will most often return to normal but it almost always takes several months. Therefore, performing a tTG now would still be a valid test. Genetic testing is not needed at this time and is only helpful if negative since 30% of the population carries the permissive genes. A better understanding of nonceliac gluten or wheat sensitivity is evolving. Clinical pearl Diagnosing celiac disease while on a gluten-free diet can be difficult, so gluten-free diets should not be instituted without testing first. References 1. Sapone A, Bai JC, Ciacci C, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012;7:10–13. 2. Gaesser GA, Angadi SS. Gluten-free diet: imprudent dietary advice for the general population? J Acad Nutr Diet. 2012;112:1330–1333. 3. Armstrong MJ, Hegade VS, Robins G. Advances in coeliac disease. Curr Opin Gastroenterol;28:104–112. Case 8 A 55-year-old obese woman with a BMI of 32 has a long-standing history of gastroesophageal reflux that is well controlled by daily PPI therapy. If she gets any symptoms, she knows it is because of something she did wrong. She has been reading about the harmful side effects of PPI therapy and is concerned about continuing. In the past, no other acid suppression helped as well. Question Which of the following would you recommend: A. B. C. D. E.

Gastric bypass surgery Discontinuing the PPI and trying high-dose H2 blockers Fundoplication Explaining the risks of ongoing therapy with PPIs Stopping all acid suppression and using gaviscon

Discussion GERD is the most common outpatient GI diagnosis in the U.S. PPIs are the third highest selling class of drugs in the U.S. In a survey published in 2009, 71% of patients with GERD took their PPI once a day, 22.2% took it twice a day, and 6.8% took it more than twice a day or as needed. Overall, 36% of individuals take additional OTC medications. Only 72% of patients are satisfied or very satisfied with their treatment. There are increasing reports of adverse effects of PPI therapy including fractures, pneumonia, C. difficile, bacterial overgrowth, malabsorption, fundic gland polyps, and drug interactions. While these are still safe medications to use, the awareness of inappropriate use is important and alternative treatment should be explored. This requires informing patients of the actual risks and benefits of the medications. In this case, since

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her symptoms are well controlled on PPI therapy, one could explore possible treatment that requires less acid suppression, which would include H2 blocker therapy. Lifestyle modifications are always recommended for patients with GERD. Surgery, either fundoplication or gastric bypass, is an option if indicated for other reasons. However, the long-term results of fundoplication have shown recurrent symptoms in as many as 40% of individuals at 10 years. It is possible that just explaining the actual risks may allay the patient’s concerns, but physicians should always try to manage patients with the least amount of acid suppression. Clinical pearl GERD symptoms should be controlled with the least possible amount of acid suppression. If unable to control the symptoms with anything other than PPI therapy, the risks should be explained to the patient. References 1. Johnson DA, Oldfield EC. Reported side effects and complications of long-term proton pump inhibitor use: dissecting the evidence. Clin Gastroenterol Hepatol. 2013 (in press). 2. Fass R. Alternative therapeutic approaches to chronic proton pump inhibitor treatment. Clin Gastroenterol Hepatol. 2012;10:338–345.

Answers: 1—E; 2—D; 3—C; 4—A; 5—A; 6—B; 7—E; 8—B

Clinical pearls in gastroenterology (2013).

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