Problem-based Approach to Gastroenterology and Hepatology E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 639

Veröffentlichungsjahr: 2012

Beschreibung

Taking the problem-based approach, this text helps clinicians improve their diagnostic and therapeutic skills in a focused and practical manner. The cases included demonstrate the diversity of clinical practice in the specialty worldwide, and are divided into five major sections: Upper GI, Pancreato-Biliary, Liver, Small and Large Bowel, and Miscellaneous.

Leseprobe

Table of Contents

Cover

Title page

Copyright page

Preface

Contributors

PART ONE: Gastroenterology

1  Dysphagia

Case 1: dysphagia for liquids and solids

Case 2: dysphagia with food impactions

Case 3 dysphagia for solids

Case presentation

2  The Problem of Heartburn, and Atypical Chest Pain

Case 1: patient with heartburn

Case 2: patient with atypical chest pain

3  The Clinical Approach to Dyspepsia

Case 1: intermittent epigastric pain

Case 2: intermittent abdominal discomfort

Commentary

4  Acute, Recurrent, and Chronic Abdominal Pain

Case 1: severe abdominal pain

Case 2: recurrent abdominal pain

Case 3: lower abdominal pain

Discussion

5  Hematemesis, Melena, and Occult Bleeding/Anemia

Case 1: hematemesis, melena

Case 2: occult bleeding/anemia

Conclusion

6  Acute Diarrhea and Vomiting

Case 1: patient with nausea, vomiting, and diarrhea

Case 2: patient with fever, vomiting and diarrhea post-chemotherapy

7  Chronic Diarrhea and Malabsorption

Case 1: diarrhea and anemia

Case 2: abdominal pain, diarrhea and weight loss

Case 3: diarrhea in a patient with type 1 diabetes

8  Rectal Bleeding

Case 1: intermittent small amounts of rectal bleeding

Case 2: acute severe lower GI bleeding

Case 3: recurrent rectal bleeding in an adolescent

9  Multisystem Disorders and Gastrointestinal Disease

Case 1: dysphagia, regurgitation, and vomiting

Case 2: history of breast cancer in family

PART TWO: Hepatology and Pancreatobiliary

10  Clinical Approach to Pancreatobiliary Disease

Case 1: right upper quadrant pain and jaundice

Case 2: epigastric and RUQ pain

Case 3: epigastric pain radiating to the back

Conclusion

11  The Problem of Right Upper Quadrant Pain

Case 1: right upper quadrant pain and jaundice

Case 2: right upper quadrant pain

Discussion

Conclusion

12  Abnormal Liver Function Tests: Diagnostic Approach

Case 1: high aminotransferase levels in an unconscious patient

Case 2: abnormal LFTs in an asymptomatic patient

Case 3: cholestatic LFTs in a young male patient

Case 4: pregnancy and abnormal LFTs

Conclusion

13  The Acute Liver Failure Patient

Case 1: paracetamol (acetaminophen) overdose

Case 2: jaundice in a young male patient

Case 3: nausea and jaundice in a young female patient

Conclusions

14  The Chronic Liver Disease Patient

Case 1: abnormal liver function tests in a diabetic patient

Case 2: jaundice and abdominal swelling

Case 3: abnormal liver function tests in a patient from Ghana

Discussion

15  Portal Hypertension: A Management Problem

Case 1: hematemesis in alcoholic liver disease

Case 2: abdominal distension in a diabetic patient

Case 3: confusion in a patient with chronic liver disease

Conclusion

16  Infections in the Liver

Case 1: infections in the post-transplantation immunocompromised patient

Case 2: chronic hepatitis B infection in the post-transplantation patient

Case 3: parasitic liver infections

Discussion

17  The Liver Transplant Recipient

Case 1: abnormal LFTs in the liver transplant recipient

Case 2: hepatopulmonary syndrome in alcoholic cirrhosis

Case 3: immunosuppression complications post-liver liver transplant

Case 4: Hepatitis C post-liver transplant

Unified discussion

18  Incidental Radiological Findings in the Asymptomatic Patient

Case 1: echogenic lesion in the right lobe of the liver

Case 2: incidental adrenal lesion

Case 3: pancreatic cystic mass

Conclusion

Index

This edition first published 2012 © 2012 by Blackwell Publishing Ltd

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Library of Congress Cataloging-in-Publication Data

Problem-based approach to gastroenterology and hepatology / edited by John N. Plevris, Colin W. Howden.

p. ; cm.

 Includes bibliographical references and index.

 ISBN-13: 978-1-4051-8227-0 (pbk. : alk. paper)

 ISBN-10: 1-4051-8227-X (pbk. : alk. paper)

 1. Gastrointestinal system–Diseases xDiagnosis–Case studies. 2. Liver–Diseases–Diagnosis–Case studies. I. Plevris, John N. II. Howden, Colin W.

 [DNLM: 1. Gastrointestinal Diseases–diagnosis–Case Reports. 2. Gastrointestinal Diseases–therapy–Case Reports. 3. Liver Diseases–diagnosis–Case Reports. 4. Liver Diseases–therapy–Case Reports. WI 140]

 RC808.P76 2012

 616.3'3–dc23

2011015322

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

ISBN-13: 978-1-4443-4635-0 (ePDF)

ISBN-13: 978-1-4443-4636-7 (epub)

ISBN-13: 978-1-4443-4637-4 (mobi)

Preface

Problem-based approaches are commonly used in Medicine as effective learning tools; the problem drives knowledge, thus promoting critical thinking and making the whole educational process interesting and relevant. We hope that this book, based on the above principles, will be of value to physicians who are training in Gastroenterology and Hepatology and who may be preparing to take a specialty postgraduate examination. Given its size, this book is clearly not intended to be a major treatise on digestive disorders. Furthermore, we do not claim that reading it will guarantee success in a relevant postgraduate examination in Gastroenterology/Hepatology. Rather, we hope that it will stimulate further reading, will supplement other preparations for those examinations and provide valuable insight into how some of the experts – from both sides of the Atlantic – approach common, important clinical issues in these specialties. Each chapter contains a number of case scenarios that raise questions of diagnosis and management. Our expert authors then present valuable discussion and important learning points about each case.

We have been fortunate to be able to draw on the expertise of friends and colleagues from both sides of the Atlantic (and beyond). We therefore expect that this book will be of value to a broad, multinational readership. It has been said that the UK and the USA are “two countries separated by a common language”. (The derivation of that is uncertain having been variously attributed to Winston Churchill, Oscar Wilde and George Bernard Shaw – any of whom could have prepared a more entertaining preface than this). We hope that this is not the perception of this book. Authors based in the USA have used American spelling and units of measurement; those based in the UK have used their own frames of reference. Hopefully, both are clear and readers will learn from both.

We would like to take this opportunity to thank all of our invited authors for their contributions to this book and their commitment to this project. We are also grateful to the editorial team at Wiley-Blackwell for all the support and effective co-ordination.

John N. Plevris

Colin W. Howden

January 2012

Contributors

Michael P. Angarone DO

Clinical Instructor

Northwestern University, Division of Infectious Disease

Northwestern University Feinberg School of Medicine

Chicago, IL, USA

Malcolm B. Barnes MBBS(Hons), FRACP

Consultant Gastroenterologist

Monash Medical Centre

Victoria, Australia

Andrew J. Bathgate MB.CHB, MD, FRCPE

Consultant Hepatologist

Scottish Liver Transplant Unit

The Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

Paul Beck PhD, MD, FRCPC

Associate Professor of Medicine

Division of Gastroenterology

University of Calgary

Calgary, Alberta, Canada

Tiffany J. Campbell BSC(Hons), MB ChB, MRCP, FRCR

Consultant Radiologist

Forth Valley Royal Hospital

Larbert, UK

Lotte Dinesen MD

Specialist Registrar

Gastroenterology Section, Division of Medicine

Imperial College London

Hammersmith Hospital

London, UK

Joanna K. Dowman MBChB(Hons), MRCP

Clinical Research Fellow and Specialist Registrar in Gastroenterology

Queen Elizabeth Hospital Birmingham, and NIHR Biomedical Research Unit and Centre for Liver Research

University of Birmingham, UK

Mary Farid MD

Fellow in Gastroentrology

UCLA Affiliated Training Program in Digestive Diseases

University of California

Los Angeles, USA

Ronnie Fass MD

Professor of Medicine

University of Arizona and Chief of Gastroenterology

Southern Arizona VA Health Care System

Tucson, AZ, USA

John P. Flaherty MD

Professor of Medicine

Division of Infectious Diseases

Northwestern University Feinberg School of Medicine

Chicago, IL, USA

O. James Garden BSc, MBChB, MD, FRCS(Glas), FRCS(Ed), FRCP(Ed), FRACS(Hon), FRCSC(Hon)

Regius Professor of Clinical Surgery

Clinical Surgery

The Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

Subrata Ghosh MBBS, MD(Edin.), FRCP, FRCPE, FRCPC

Professor of Medicine

Chairman of Department of Medicine

University of Calgary

Calgary, Alberta, Canada

Simon Glance MDBBS(Hons)

Consultant Gastroenterologist

The Northern Hospital

Melbourne, Australia

Nirmala Gonsalves MD

Assistant Professor of Medicine

Division of Gastroenterology

Northwestern University – The Feinberg School of Medicine

Chicago, IL, USA

Timothy T. Gordon-Walker MBChB, BSc

Specialist Registrar in Gastroenterology

The Royal Infirmary of Edinburgh

and

MRC Centre for Inflammation Research

Queen’s Medical Research Institute

Edinburgh, Scotland, UK

Peter C. Hayes MD, PhD, FRCPE

Professor of Hepatology

Centre for Liver and Digestive Disorders

The Royal Infirmary of Edinburgh

Edinburgh, Scotland UK

Neil C. Henderson BMSc(Hons), MBChB(Hons), MSc, PhD, MD, FRCP(Ed)

Senior Clinical Scientist and Consultant Hepatologist

Centre for Liver and Digestive Disorders

The Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

Tiberiu Hershcovici MD

Research Fellow

Southern Arizona VA Health Care System

Tucson, AZ, USA

Ikuo Hirano MD

Professor of Medicine

Division of Gastroenterology

Northwestern University Feinberg School of Medicine

Chicago, IL, USA

John P. Iredale DM, FRCP, FMedSci

Professor of Medicine

Tissue Injury and Regeneration Group

MRC Centre for Inflammation Research

Queen’s Medical Research Institute

Edinburgh, Scotland, UK

Brian E. Lacy MD, PhD

Associate Professor of Medicine

Dartmouth Medical School

and

Director

Gastrointestinal Motility Laboratory

Dartmouth-Hitchcock Medical Center

Lebanon, NH, USA

Anne-Marie Lennon MB, PhD, MRCP(UK)

Assistant Professor of Medicine

Department of Gastroenterology and Hepatology

Johns Hopkins Hospital

Baltimore, MA, USA

Grigorios I. Leontiadis MD, PhD

Assistant Professor

McMaster University Department of Medicine

Division of Gastroenterology

Health Sciences Centre

Hamilton, ON, Canada

Norma C. McAvoy MBChB, MRCP(UK)

Clinical Lecturer

Centre for Liver and Digestive Disorders

The Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

Lisa J. Massie MBChB

Specialist Surgical Registrar

Clinical Surgery

The Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

Lynne A. Meekison MBChB

Associate Specialist

Centre for Liver and Digestive Disorders

The Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

Phil N. Newsome PhD, FRCP

Senior Lecturer in Hepatology and Honorary Consultant Physician

Queen Elizabeth Hospital Birmingham, and NIHR Biomedical Research Unit and Centre for Liver Research

University of Birmingham, UK

Remo Panaccione MD, FRCPC

Associate Professor of Medicine

Division of Gastroenterology

University of Calgary

Calgary, Alberta, Canada

Dilip Patel BMedSci (Hons), MB BS, FRCP(Ed), FRCR

Consultant Radiologist and Honorary Clinical Senior Lecturer

The Royal Infirmary of Edinburgh

University of Edinburgh

Edinburgh, Scotland, UK

Prakash Ramachandran BSc, MBChB, PhD, MRCP(UK)

Specialist Registrar in Gastroenterology and Hepatology

Scottish Liver Transplant Unit

The Royal Infirmary of Edinburgh

Edinburgh, Scotland UK

Erica J. Revie BSc, MBChB, MRCS

Specialist Surgical Registrar

Clinical Surgery

The Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

Veerendra Sandur MBBS, MD, DNM, DM(Gastro)

Liver Transplantation Fellow

Multiorgan Transplant Program

Toronto General Hospital

Toronto, Ontario, Canada

Matthew Shale MRCP

Academic Clinical Fellow

Gastroenterology Section

Division of Medicine

Imperial College London, Hammersmith Hospital

London, UK

Virender K. Sharma FASGE, FACG, AGAF

Professor of Medicine and Director

Arizona Center for Digestive Health

Gilbert, AZ, USA

Kenneth J. Simpson MBChB, MD, PhD, FRCPE

Senior Lecturer in Hepatology

Centre for Liver and Digestive Disorders

The Royal Infirmary of Edinburgh

Edinburgh, Scotland, UK

Chad C. Spangler MD

Instructor in Medicine

Division of Gastroenterology and Hepatology

Dartmouth-Hitchcock Medical Center

Lebanon NH, USA

Brennan Spiegel MD, MSHS

Associate Professor of Medicine

VA Greater Los Angeles Healthcare System David Geffen School of Medicine at UCLA

and

Director

UCLA/VA Center for Outcomes Research and Education

Los Angeles, CA, USA

George Therapondos MBChB(Hons), PhD, MD, FRCP(Ed)

Assistant Professor of Medicine

Multiorgan Transplant Program

Toronto General Hospital

University Health Network

Toronto, Ontario, Canada

PART ONE: Gastroenterology

1

Dysphagia

Nirmala Gonsalves1, Ikuo Hirano1, and John N. Plevris2

1Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, USA

2Centre for Liver & Digestive Disorders, The Royal Infirmary, University of Edinburgh, Edinburgh, UK

Dysphagia refers to difficulty or inability in swallowing food or liquids. Most dysphagia patients are candidates for urgent upper digestive endoscopy, to exclude the presence of esophageal cancer. The annual incidence of upper gastrointestinal malignancy, particularly esophageal adenocarcinoma, is steadily increasing in the western world, being the 5th most common primary site in Scotland [1].

Traditionally, dysphagia has been classified as oropharyngeal or esophageal. Oropharyngeal dysphagia is due to impaired food bolus formation or propagation into hypopharynx. Causes include neuromuscular disorders, cerebrovascular events, mechanical obstruction in the oral cavity or hypophanynx, decreased salivation, Parkinson’s and Alzheimer’s disease or depression. Esophageal dysphagia can be due to mechanical obstruction, (benign or malignant stricture), dysmotility disorders or secondary to gastro-esophageal reflux. Significant dysphagia is often associated with aspiration pneumonia.

A detailed history is important to elicit a possible etiology. In younger patients dysmotility is more common. The presence of chest pain during swallowing strongly suggests esophageal spasm; dysphagia for both liquids and solids is common is achalasia. In young patients with food impaction eosinophilic esophagitis should always be considered. In the elderly, neurological causes should be considered if the dysphagia is high, while esophageal cancer usually presents with short duration progressive dysphagia for solids with regurgitation and weight loss. New onset hoarse voice and dysphagia, point towards malignant infiltration of the recurrent laryngeal nerve. High dysphagia associated with regurgitation of undigested food from previous days, is strongly suggestive of a pharyngeal pouch.

Despite the different presenting features associated with different causes of dysphagia, there is no reliable way to predict at presentation those patients likely to have a malignant cause. Recently, a scoring system based on 6 parameters (advanced age, male gender, weight loss of >3 kg, new onset dysphagia, localisation to the chest and absence of acid reflux at presentation) could strongly predict malignancy [2]. In this chapter, three selected cases will illustrate the different etiologies of this important alarm symptom.

Case 1: Dysphagia for Liquids and Solids

Case Presentation

A 52-year-old man reports a 9-month history of difficulty swallowing both liquids and solids with meals and localizes the problem to upper sternum. He gets frequent episodes of coughing and choking when lying flat at night after meals. More recently, he has noticed spontaneous regurgitation of clear, foamy liquid and undigested food into his mouth, especially when bending over after dinner. He has lost over 15 lb (6.8 kg) since his symptoms began. Heartburn, which had been a problem in the past, has notably improved since his dysphagia began. Additional complaints include episodes of squeezing pain lasting for several minutes to 1 hour without radiation that can occur at any time and are unrelated to physical activity or meals. Drinking cold water sometimes alleviates the pain.

Past medical history: hypertension

Medications: lisinopril

Social history: employed as a businessman. Moved to the USA from Bolivia 20 years ago. Smokes 20 cigarettes per day. Drinks 3–4 glasses of wine per week

Family history: no family history of cancer or swallowing disorders

Physical examination: unremarkable

In particular, oral cavity without mucosal abnormalities, intact dentition, with no neck masses, lymphadenopathy or goiter. No evidence of sclerodactyly or telangiectasia.

Upper endoscopy revealed a dilated esophagus with approximately 200 mL of retained, semisolid debris despite a 36-hour liquid diet (Figure 1.1a). The underlying mucosa appeared with scattered superficial erosions and mild, diffuse nodularity. Constriction of the esophagogastric junction was noted with minimal resistance to passage of the endoscope into the stomach (Figure 1.1b). Pylorus was patent and the duodenum was normal.

Figure 1.1 Endoscopic images of the esophagus: (a) a moderately dilated esophageal body with retained food and secretions in spite of a 12-hour fast; (b) a constriction at the level of the esophagogastric junction in the same patient.

Esophageal manometry was performed using a high-resolution, solid-state catheter assembly with contour pressure topography (Figure 1.2) showed panesophageal pressurization or common cavity phenomenon in response to a water swallow. Failed deglutitive relaxation of the lower esophageal sphincter was evident. The presence of an esophagogastric pressure gradient is seen in the esophagus before the swallow suggestive of achalasia.

Figure 1.2 High-resolution esophageal manometry pressure contour plot depicting a water swallow. Panesophageal pressurization above intragastric pressure is seen and failed lower esophageal sphincter relaxation is evident.

Questions

What are the diagnostic considerations in this patient?What are the clinical symptoms of achalasia?What diagnostic tests are useful in achalasia?What is the pathophysiology of achalasia?What are the benefits and risks of different treatment options that should be discussed with this patient?What are the complications of achalasia?

Differential Diagnosis

Esophageal dysmotility should be considered in any patient presenting with dysphagia for both liquids and solids. A few caveats to this rule exist:

First, patients with oropharyngeal dysphagia may present with liquid and solid dysphagia and, in fact, may have greater difficulty with liquids than solids. However, the fact that this patient localizes his dysphagia to the sternal area excludes an oropharyngeal etiology.Second, patients with esophageal food impaction typically have difficulty swallowing liquids and even their own saliva. However, the history was not consistent with repeated food impactions in this case.Third, the dysphagia that accompanies an advanced esophageal malignancy produces progressive obstruction. Although a consideration here, such patients present with a more rapid transition from solid to semisolid to liquid dysphagia over time.

The three major esophageal motor disorders are achalasia, scleroderma, and diffuse esophageal spasm (DES). Patients with scleroderma have typically mild dysphagia and in most cases is accompanied with cutaneous manifestations. Although both DES and achalasia are possible diagnoses in this patient, dysphagia in DES is generally less severe and more intermittent than in achalasia.

Clinical Presentation of Achalasia

Achalasia is an uncommon but important disease. The clinical manifestations as well as treatment center on the integrity of the lower esophageal sphincter (LES). Dysphagia and regurgitation are the most commonly reported symptoms. Nocturnal regurgitation can lead to night cough and aspiration. With progressive disease weight loss can occur. Chest pain is well recognized in achalasia and has been reported in 17–63% of patients but its mechanism is unclear although proposed etiologies include secondary or tertiary esophageal contractions, esophageal distension by retained food, gastro-esophageal reflux, esophageal irritation by retained medications, food, and bacterial or fungal overgrowth. Paroxysmal pain may be neuropathic in origin. Inflammation within the esophageal myenteric plexus could also be a contributory factor. More than one mechanism is likely operative in an individual patient.

A prospective study found no association between the occurrence of chest pain and either manometric or radiographic abnormalities [3]. Patients with chest pain were younger and had a shorter duration of symptoms compared with patients with no pain, but treatment of achalasia had little impact on the chest pain, in spite of adequate relief of dysphagia. Counter to this, a recent surgical series reported adequate relief of chest pain after a Heller myotomy [4]. Importantly, chest pain is not a universal feature in achalasia. In fact, many patients appear unaware of either esophageal distension or the prolonged the prolonged esophageal retention of food. Recent studies using esophageal barostat stimulation have demonstrated that some patients with achalasia have diminished mechanical and chemosensitivity of the esophagus [5]. Such differences may explain the heterogeneity of visceral sensitivity in the achalasia population.

Diagnostic Evaluation

Upper endoscopy is the first line investigation in suspected achalasia. Findings include esophageal dilation with retained saliva or food and annular constriction of the gastroesophageal junction. Intubation of the stomach is achieved with minor resistance due to raised LES pressure. Significant difficulty passing an endoscope through the gastroesophageal junction should raise the index of suspicion for pseudoachalasia due to neoplastic infiltration of the distal esophagus or gastric cardia. In spite of these recognized endoscopic features, upper endoscopy was reported as normal in 44% of a series of newly diagnosed achalasia patients [6]. A barium esophagogram (swallow) can be highly suggestive of achalasia, particularly when there is the combination of esophageal dilation with retained food and barium, and a smooth, tapered constriction of the gastroesophageal junction. However, the diagnosis of achalasia was suggested in only 64% of barium examinations in the previous study [6].

Esophageal manometry has the highest diagnostic sensitivity for achalasia and should be performed when the etiology of dysphagia is not evident by endoscopy alone. Findings include distal esophageal aperistalsis and incomplete or absent LES relaxation. Additional supportive features include a hypertensive LES and low-amplitude esophageal body contractions. by endoscopic or radiographic examination.

Although manometry is regarded as the “gold standard” for the diagnosis of achalasia, heterogeneity exists in the manometric presentation. The most commonly recognized variant is known as “vigorous achalasia,” variably defined by the presence of normal to high amplitude esophageal body contractions in the presence of a non-relaxing LES. Such contractions are generally simultaneous and can be difficult to distinguish from common cavity phenomena. Although vigorous achalasia may represent an early stage of achalasia, studies have failed to demonstrate differences in terms of clinical presentation, although botulinum toxin has been reported to be more effective in patients with vigorous achalasia. Additional manometric variants of achalasia include rare individuals with intact peristalsis through most of the esophageal body and with preservation of either deglutitive or transient LES relaxation [7]. The significance in defining these variants lies in the recognition that these sometimes confusing manometric findings are still consistent with achalasia when combined with clinical data supportive of the diagnosis.

High-resolution esophageal manometry (HRM) combined with contour plot topographic analyses can significantly improve the accuracy of esophageal manometry. HRM allows for automated analysis of more detailed quantitative data. An example of the utility of this methodology is the interpretation of impaired LES deglutitive relaxation in the setting of exaggerated respiratory contractions of the crural diaphragm. Intrabolus pressure elevations are more readily apparent and quantified using HRM. A recent retrospective study subclassified 99 achalasia patients into those with classic achalasia with minimal esophageal pressurization, achalasia with esophageal compression (panesophageal pressurization in excess of 30 mmHg), and achalasia with spasm [8]. Panesophageal pressurization was a positive predictor whereas esophageal spasm was a negative predictor of treatment response.

Secondary Forms of Achalasia

The most concerning secondary etiology is cancer, which can present as achalasia by one of three mechanisms. The first and most common occurs through direct mechanical obstruction of the gastroesophageal junction. This is referred to as pseudoachalasia, and has been most commonly described with distal esophageal and proximal gastric adenocarcinomas. Cancer can also infiltrate the submucosa and muscularis of the LES and disrupt the myenteric neurons, resulting in achalasia without an endoscopically visible mucosal abnormality. Finally, achalasia can be a manifestation of paraneoplastic syndrome with circulating autoantibodies that are directed at the myenteric neurons. This syndrome is a rare but important complication of small cell lung cancer.

Chagas’ disease, a parasitic infection caused by Trypanosoma cruzi, is endemic to areas of Central and South America. The esophagus is most commonly involved, and manifests itself as secondary achalasia in 7–10% of chronically infected individuals. Chagas’ disease should be a consideration in the evaluation of achalasia patients in the USA, given that the gastrointestinal sequelae can manifest years or decades after the acute infection. Our patient had positive serological testing for antibodies to T. cruzi, consistent with chronic infection. The management of his achalasia does not change but evaluation for other cardiac and visceral manifestations of the parasite are indicated.

Pathogenesis

While the etiology of primary achalasia remains unknown, several hypotheses have been proposed. Several studies have implicated viral agents. A study using DNA hybridization techniques found evidence of varicella-zoster virus in three of nine myotomy specimens from patients with achalasia [9]. The herpes virus family was specifically targeted in this study, given their neurotropic nature. The predilection of the herpesviruses for squamous epithelium as opposed to columnar epithelium makes this an attractive hypothesis and could explain why achalasia involves only the esophagus, while sparing the remainder of the gastrointestinal tract. More recent studies however, failed to detect the presence of measles, herpes, or human papillomaviruses in myotomy specimens of 13 patients with achalasia. This negative study does not exclude the possibility of either an alternate viral species or past viral infection with clearance of the inciting pathogen from the host tissue. Supporting the viral hypothesis is a recent study demonstrating immunoreactivity of lymphocytes from the LES of patients with achalasia in response to herpes simplex virus HSV-1 antigens. In this study, analysis of oligoclonal expansion of T cells provided evidence for immune activation thus resulting in autoimmune destruction of enteric neurons [10].

An autoimmune etiology of achalasia is supported by the presence of circulating autoantibodies against the myenteric plexus. These have been shown in a few studies to be more prevalent in achalasia patients than in controls. However, a recent study detected significantly higher immunostaining of the esophageal myenteric plexus neurons using serum from both achalasia and gastroesophageal reflux disease (GERD) patients than controls, suggesting that such antibodies represent an epiphenomenon rather than a causative factor [11]. The presence of a lymphocytic infiltrate consisting of CD3+ and CD8+ T cells in the myenteric plexus not found in controls, also supports an autoimmune etiology [11,12].

Treatment

Treatment options for idiopathic achalasia include medical therapy, endoscopic botulinum toxin injection, endoscopic pneumatic dilation, and surgical myotomy [13–15]. All forms of therapy seek to reduce the LES pressure to allow for improved esophageal clearance by gravity because the esophageal peristalsis is impaired.

Medical therapy with calcium channel antagonists or nitrates has demonstrated limited efficacy. Medical therapy is generally restricted to patients awaiting more definitive therapy or patients who are not candidates for more invasive therapies and who have not responded to treatment with botulinum toxin.

Botulinum toxin is both easy and safe to administer [16]. To date, there have been over 15 prospective studies involving over 450 patients from around the world that have examined its efficacy. Response rates at 1 month after administration average 78% (range 63–90%). By 6 months, the clinical response drops to 58% (range 25–78%), and to 49% (range 15–64%) at 12 months. Moreover, improvement in objective measures of esophageal function are significantly lower after botulinum toxin than other more definitive therapies for achalasia [17]. Given the limitations to the efficacy and durability of response, botulinum toxin is generally reserved for patients who are not candidates for pneumatic dilation or Heller myotomy.

Dilation of the esophagus is the oldest form of therapy for achalasia. Currently, the Rigiflex pneumatic dilator (Boston Scientific Corp, Boston, MA) is the most widely used dilating system. A non-compliant polythylene balloon that comes in three sizes designed to inflate to fixed diameters of 3, 3.5, or 4 cm is used. The overall success rates defined by good to excellent relief of symptoms averages 85% (range 70–92%) with a mean follow-up period of 20 months. Age, balloon diameter, post-dilation LES pressure, clearance of barium on an esophagogram, and prior dilation have been identified as predictors of success. Similar to the botulinum toxin experience, several studies have reported that older patients respond better. Eckardt found a 2-year remission rate of 29% in patients under 40 compared with 67% for those over 40 [18]. Long-term follow-up studies of the effectiveness of pneumatic dilation have reported a substantially lower response rate of 30–40% – approximately half that reported in the short-term studies. Thus, repeated dilations are to be expected when using pneumatic dilation as primary therapy. The main complication of pneumatic dilation is esophageal perforation. Published series have reported perforation rates of 0–8% with a mean rate of 2.6%.

Laparoscopic Heller myotomy has greatly advanced the surgical approach to achalasia. It allows for shorter hospital stays and less recovery time than open cardiomyotomy. Furthermore, the laparoscopic approach has substantially challenged the use of dilation as primary therapy since perforation from pneumatic dilation generally necessitates repair via open thoracotomy. Success rates reported in large series approximate 90%, with mean follow-up approaching 2 years. Perioperative complications of perforation, hemorrhage, or pneumothorax are uncommon and readily managed intraoperatively. Reflux is a not infrequent complication of both endoscopic and surgical therapies in the setting of an aperistaltic esophagus. In one of the larger surgical series, reflux was documented by pH testing in 17% of patients after laparoscopic myotomy with most of these patients not reporting heartburn [19]. Barrett’s esophagus and peptic stricture have been documented in several reported series after a Heller myotomy. Surgical approaches to the problem have included creation of a loose Nissen, partial posterior Toupet, or partial anterior Dor fundoplication. Similar to the experience with pneumatic dilation, the reported remission rates after Heller myotomy for achalasia reflect a gradual deterioration over time. Malthaner reported a 95% success rate at 1 year, 77% at 5 years, 68% at 10 years, and 67% at 20 years [20]. Thus, the effectiveness of what is considered the most definitive therapy for achalasia appears to wane with time.

Several studies have reported superior success rates for surgery compared with pneumatic dilation. A recent, retrospective, longitudinal study using an administrative database in Ontario, Canada compared outcomes of 1181 patients treated with pneumatic dilation with 280 patients treated with Heller myotomy as initial therapy [13]. Although the risk of subsequent therapeutic intervention at 10 years was significantly higher with dilation (64%) than with surgery (38%), this outcome is expected and attributed to repeated dilations that did not lead to a significantly higher risk of surgical intervention in the dilation group. On the other hand, the 38% risk of therapeutic intervention after surgery stresses that recurrent dysphagia occurs in a significant proportion of surgical patients. Currently, the choice of therapy remains an individualized decision that weighs factors including available expertise, patient’s acceptance of possible risks, and patient factors such as age and comorbidity.

Complications

The main complications of untreated achalasia include progressive malnutrition and aspiration; in particular postprandial and nocturnal coughing. Uncommon but important secondary complications include the formation of epiphrenic diverticula and esophageal cancer. Epiphrenic diverticula presumably form as a result of increased intraluminal pressures, and are most commonly detected in the distal esophagus immediately proximal to the LES. Squamous esophageal cancer is seen with an increased frequency in idiopathic achalasia although adenocarcinomas are also reported. A large cohort study from Sweden found a 16-fold increased risk of esophageal cancer during years 1 through 24 after initial diagnosis. Cancers detected in the first year after diagnosis of achalasia were excluded to eliminate primary cancers that may have presented as pseudoachalasia [21]. The overall prevalence of esophageal cancer in achalasia is approximately 3% with an incidence of approximately 197/100 000 per year [22]. The incidence significantly increases after 15 years of achalasia-related symptoms. However, routine endoscopic screening of patients with achalasia is not generally recommended due to low overall incidence of esophageal cancer. Nevertheless, some experts still advocate surveillance in long-standing achalasia patients who would be candidates for esophageal resection were a cancer to be detected [22]. Treatment of achalasia does not reduce cancer risk, and several cases of cancer have been reported after therapy with pneumatic dilation or surgical myotomy.

Case 2: Dysphagia with Food Impactions

Case Presentation

A 46-year-old white man has had difficulty swallowing for the past 20 years. He first noticed symptoms in high school with meat and bread. He has had multiple food impactions and has needed repeated dilations but has no problems with liquids. His symptoms are intermittent and localize to his lower chest. He denies any coughing with eating and does not have any difficulty initiating a swallow. His weight has been stable, he denies arthralgia or myalgia, fevers, chills, or sweats (or the american term swets is preferable?).

Past medical history: allergic rhinitis, which is exacerbated in the spring and fall.

Medications: loratidine, esomeprazole intermittently

Allergies: beer (wheezing and hives), seasonal allergies to pollen and grass. During high school he went through immunotherapy for seasonal allergies

Social history: he is married with two children, Works in finance. Denies any smoking or alcohol

Physical exam: normal

Questions

What is the differential diagnosis?What would be the next step in the workup of this patient?What treatment options are available?

Differential Diagnosis for Dysphagia

The differential diagnosis includes gastro-esophageal reflux, esophageal dysmotility, eosinophilic esophagitis, Schatzki’s ring or a peptic stricture.

Diagnostic Findings

The patient underwent an upper endoscopy; findings are presented in Figure 1.3. The concentric mucosal rings and linear furrows are typical endoscopic features of eosinophilic esophagitis (EoE). Diagnosis was confirmed on biopsy. Figure 1.4 shows the characteristic histological features of EoE, including intraepithelial eosinophils, superficial layering of eosinophils, and epithelial hyperplasia.

Figure 1.3 Endoscopic image of the esophagus in a patient with eosinophilic esophagitis. Findings present include concentric mucosal rings, linear furrows, and white exudates.

(Image courtesy of Dr Gonsalves and Dr Hirano.)

Figure 1.4 Histomicrograph of esophageal biopsy with H&E staining in a patient with eosinophilic esophagitis. Characteristic histopathological changes are present which include intramucosal eosinophils, superficial layering of eosinophils, eosinophilic microabcesses, epithelial hyperplasia, and spongiosis.

(Image courtesy of Dr Gonsalves and Dr Hirano.)

Epidemiology

Over the last few years, EoE has become a topic of increasing attention by gastroenterologists, pathologists, and allergists. EoE may occur in isolation or in conjunction with eosinophilic gastroenteritis. Previously considered a rare condition, there has been a dramatic increase in reports of EoE worldwide [23]. The cause for this rise is probably a combination of an increasing incidence of EoE and a growing awareness of the condition. The incidence of EoE has been rising in a population of children residing in Hamilton County in Ohio. In 2000, Noel et al. estimated the incidence to be 0.91 per 10 000 with a prevalence of 1 per 10 000, compared with 1.3 in 10 000 and a prevalence of 4.3 in 10 000 in 2003 [24]. Straumann and colleagues studied a population of adults in Olten County, Switzerland and found a similar trend [25]. These studies are likely to underestimate the true incidence and prevalence of EoE in the general population because these data are based on patients with symptoms sufficient to warrant endoscopy.

A population-based study in Sweden randomly surveyed 3000 adult members of the population and 1000 healthy adults underwent endoscopy with esophageal biopsies. Probable EoE was present in 1% of the population [26].

EoE tends to have a male predilection. Among 323 adult patients from 13 studies, 76% were male with a mean age of 38 (range 14–89). Among 754 children from 16 studies, 66% were boys with a mean age of 8.6 (range 0.5–21.1) [27]. One pediatric review suggested that there was a racial predilection, with 94.4% of the patients being white [28]. Wang and colleagues found a seasonal variation of EoE presentations in the children; fewer patients presented in winter, a season with low outdoor allergens, compared with spring, summer, or fall [29]. Eosinophilia was also decreased in winter. A familial pattern has been recognized among children with the condition. In a case series of 381 children with EoE, 5% of patients had siblings with EoE and 7% had a parent with either an esophageal stricture or a known diagnosis of EoE [30]. Eotaxin-3, a gene encoding an eosinophil-specific chemoattractant, was found to be the most highly induced gene in children with EoE, suggesting a potential genetic predisposition [31]. Therefore, workup of patients should include a thorough family history.

Clinical Features of EoE

Clinical presentation differs in adults from children. Adults usually present with dysphagia, food impaction, heartburn, and chest pain [27]. In one study, 50% of adults presenting with food impaction were ultimately diagnosed with EoE [32]. Younger children, tend to present with vomiting, heartburn, regurgitation, emesis, and abdominal pain [30], while dysphagia and food impaction, are more commonly seen in older children and adolescents [24]. In adults, this diagnosis has often been overlooked and many patients have had endoscopies with alternate diagnoses, including Schatzki’s rings or GERD before a diagnosis of EoE. Eosinophils are commonly seen in GERD and in the past many EoE cases were misdiagnosed as GERD. The presence ≥15 eosinophils per high power field is highly suggestive of EoE [27], so eosinophil counts on esophageal biopsies should be specifically requested if there is suspicion of such diagnosis.

Pathophysiology

Studies have shown that the esophageal infiltration of eosinophils may be related to an allergic response to both food and aeroallergens. Mishra et al. have induced eosinophilic esophagitis by exposing mice to an aeroallergen, Aspergillus fumigatus [33]. This group further investigated the roles of cytokines in the pathogenesis of this inflammatory response using interleukin-5 (IL5) and eotaxin knockout mice. They demonstrated that, in response to aeroallergen exposure, eotaxin knockout mice showed decreased esophageal eosinophilia whereas IL5 knockout mice did not demonstrate any esophageal eosinophilia. They thus concluded that both IL5 and eotaxin play important roles in eosinophil recruitment and may be potential therapeutic targets [33].

Certain environmental allergens contributing to esophageal eosinophilia has also been suggested in humans. A recent case report, of an adult with allergic rhinoconjunctivitis and asthma demonstrated an increase in symptoms as well as esophageal eosinophilia during the pollen season [34]. Interestingly, biopsies obtained during non-pollen months were normal, suggesting that tissue eosinophilia was triggered by pollen exposure. In addition, numerous clinical studies have shown an association between food allergies and EoE. The most commonly identified food allergens include milk, soy, egg, wheat, peanuts, and shellfish and after elimination of these agents or use of a elemental diet, esophageal eosinophilia resolves [35,36]. Future studies regarding the pathogenesis of this illness are critical to developing appropriate treatments.

Endoscopic Findings

Common endoscopic features in adults include linear furrows (80%), mucosal rings (64%), small-caliber esophagus (28%), white plaques/exudates (16%), and strictures (12%). In children, common endoscopic features include linear furrows (41%), normal appearance (32%), esophageal rings (12%), and white plaques (15%) [30]. However, the classic endoscopic features may be subtle or absent during endoscopy. therefore, biopsies should be taken in unexplained dysphagia, refractory heartburn, or chest pain despite such normal in appearances findings [27].

Pathology

EoE is ultimately diagnosed by the presence of increased intramucosal eosinophils in the esophagus, without concomitant eosinophilic infiltration in the stomach or duodenum [27]. Other features include superficial layering of the eosinophils, eosinophilic microabscesses, intercellular edema, and degranulation of eosinophils. Other inflammatory cells such as lymphocytes, polymorphonuclear leukocytes, and mast cells may also be present [37]. Epithelial hyperplasia, defined by papillary height elongation and basal zone proliferation is common [37] similarly to reflux esophagitis. Subepithelial fibrosis is sometimes seen in EoE, suggesting that deeper layers of the esophagus may be involved [38]. This has been confirmed by endoscopic ultrasonography [39]. It is speculated that this mucosal and submucosal fibrosis may lead to esophageal remodeling and decreased compliance of the esophagus, thus explaining the presence of dysphagia even in the absence of an identifiable stricture.

Although a single diagnostic threshold of eosinophil density has not been universally agreed, a recent consensus statement suggests using a threshold value of ≥15 eosinophils per high power field to diagnose EoE [27]. It is also recognized that the eosinophilic infiltration of the esophagus may not be evenly distributed [40]. Therefore, it is suggested that biopsies be obtained from both the proximal and the distal esophagus to obtain a higher diagnostic yield. A retrospective review suggested at least five biopsies to improve diagnostic yield in the adult population [40]. Prospective studies need to be performed to validate this recommendation.

Diagnostic Criteria

Recent consensus recommendations based on a systematic review of the literature and expert opinion have led to the following diagnostic criteria to diagnose EoE:

the presence of symptoms including, but not limited to, dysphagia and food impaction in adults and feeding intolerance, and GERD in children≥15 eosinophils per high power field in the esophageal biopsyexclusion of other disorders associated with similar clinical, histologic, or endoscopic features such as GERD, with either the use of high-dose acid suppression before biopsy procurement or normal pH monitoring [27].

Intraesophageal PH Testing

There have been 9 adult and 11 pediatric studies reporting data from pH monitoring. Of 228 adult patients, 40% had pH monitoring with normal results in 82% of patients. Of 223 children, 78% had pH monitoring with normal results in 90% of patients [27].

Radiography

Radiological studies such as barium esophagrams (swallow) are non-diagnostic although occasionally may identify esophageal strictures and esophageal rings thus alerting the endoscopist to use a smaller-caliber endoscope or to proceed more cautiously with passage of the endoscope [27].

Manometry

Esophageal manometry, studied in 77 adults in 7 studies and 14 children in 3 studies [27], was abnormal in 41 of 77 adult patients. In the adults, the LES was normal in 66, hypotensive in 10, and hypertensive in 1 patient. Peristaltic abnormalities were seen in 30 of 77 patients: 28 of 30 patients had non-specific peristaltic abnormalities and one each had DES and nutcracker esophagus. Compared with these abnormalities in adults, all 14 children had normal esophageal manometry. In a recent study by Chen and colleagues HRM was used in 24 adult patients with EoE [41]. The most common abnormality noted was elevation in peristaltic velocity. Some patients also had failed esophageal peristalsis and impaired relaxation of the LES.

Natural History

Straumann and colleagues followed a cohort of 30 adults with EoE for a mean of 7 years [42]. Although dysphagia persisted in almost every patient, eosinophil levels in the esophagus decreased in the absence of treatment. No patient had concomitant eosinophilic infiltration of the stomach or duodenum on either the index or follow-up endoscopy. Furthermore, none of the patients progressed to hypereosinophilic syndrome or developed a malignancy. Liacouras and colleagues followed 381 children with EoE over a period of 10 years [30] and found that, although medical treatment with either oral corticosteroids or topical fluticasone was effective in obtaining remission, all patients had recurrence of symptoms and esophageal eosinophilia upon discontinuation of treatment. Dietary treatment with either amino acid-based formula or dietary restriction was highly effective in inducing and maintaining remission. Assa’ad and colleagues studied another group of 89 children over a period of 8 years [29]. They found that the disease was chronic and relapsing in this population. For instance, of the 66% of patients who had initial resolution of their EoE, 79% later relapsed. An important question raised is whether children with EoE outgrow the condition or progress to long-term sequelae such as fibrosis and strictures. Additional long-term follow-up studies in both the pediatric and the adult populations are needed to address this concern.

Treatment

Treatment approaches for EoE vary between children and adult patients. In children treatment with an elemental diet for 1 month has been shown to improve both clinical symptoms and histological changes. Spergel et al. used skinprick and patch testing to identify food allergens in a cohort of children [35]. Once food allergens were identified, patients underwent either a food elimination diet or an elemental diet with an amino acid-based formula; 18 of 26 patients had complete resolution of symptoms and 6 of 26 had partial resolution. Overall, after dietary intervention, esophageal eosinophilia significantly improved. Recently Kagalwalla and colleagues showed that a targeted diet eliminating milk, soy, egg, wheat, nuts, and seafood has a remission rate of 74% [36]. This approach was recently tried in adults with a 52% response rate.

Systemic corticosteroids have shown to effectively treat children with EoE. In one study, 20 patients with EoE with symptoms of refractory reflux were treated with methylprednisolone (1.5 mg/kg per day, divided into twice daily dosing) for 4 weeks [43] 65% of patients became asymptomatic while the rest had significant improvement in symptoms within 4 weeks. The average time for clinical improvement was 8 ± 4 days. All patients in this group demonstrated decreased eosinophilia on biopsy, in addition to decreased peripheral eosinophilia and IgE levels. Topical corticosteroids have also demonstrated effectiveness. In a study by Remedios et al., 19 adults were studied after treatment with topical fluticasone (250 µg two puffs twice daily for 4 weeks) [44]. This therapy resulted in complete relief of dysphagia, significant decrease in esophageal eosinophilia and was well tolerated in all patients. Encouraging results have also been obtained in children with an approximate 50% response rate.

Attwood et al. treated with montelukast eight adult patients with EoE [45]. An initial dose of 10 mg daily was used and increased if needed to a total of 100 mg daily. Maintenance dosages for all patients were between 20 and 40 mg/day for 4 months. Therapy resulted in resolution of dysphagia while continuing the medication. However, 75% of patients had recurrence within 3 weeks of cessation or reduction in the medication. Also, treatment with montelukast for 4 months did not reduce the density of eosinophils on repeat biopsy. Another agent that has been shown to improve symptoms and histology of EoE is anti-IL5 (mepolizumab). This agent is currently being investigated in clinical trials for both EoE and eosinophilic gastroenteritis.

Esophageal dilation has been used to treat patients with strictures. Although dysphagia improves initially, symptoms recurred in all patients 3–8 months after dilation, with most patients requiring repeat dilation, on an average twice a year [23]. Such dilatations are associated with significant esophageal wall disruption with the potential for perforation. This risk might have been over-emphasized and for some patients dilatations are the only means for effective symptom relief if medical therapy fails [15].

Case 3 Dysphagia for Solids

Case presentation

A 68 year old man complains of a 6 month history of intermittent dysphagia at the lower sternum and nocturnal gastro-esophageal reflux with occasional regurgitation of food. He denies any weight loss and he has a good appetite. Past medical history has been unremarkable apart from progressive 10 kg weight gain since retirement as a hospital porter. He was diagnosed with celiac disease at the age of 35 and he has been on a gluten-free diet although he admits to erratic compliance. At the age of 58, and while at work, he suffered crush fractures of the vertebrae at the level of T12 and L1. A bone DEXA density scan confirmed osteoporosis of the spine and he was started on biphosphonates (alendronate sodium) and calcium/vitamin D supplements. He was also advised to adhere to a strict gluten free diet. He has been on omeprazole 20 mg for the last 3 years; recently increased to 40 mg because of worsening acid reflux.

Social history: Retired hospital porter; smokes 20 cigarettes per day and drinks approximately 24 units of alcohol per week, mainly spirits. Family history: No family history of cancer or swallowing disorders.

Physical examination was unremarkable apart from a BMI of 29.1 and a slightly distended abdomen with epigastric discomfort on palpation, but no organomegaly; bowel sounds were normal.

He had not been keen for an upper endoscopy but reluctantly agreed following the development of dysphagia. Endoscopy showed Barrett’s esophagus with the squamous-columnal junction at 36 cm with mild stricturing at 39 cm. Three tongues of Barrett’s esophagus were extending within the squamous epithelium. (C3M4 by the Prague classification criteria [46]). Four-quadrant biopsies every 2 cm from Barrett’s esophagus [47] confirmed the presence of specialised intestinal metaplasia and goblet cells. Fibrin and neutrophil infiltration were also present suggestive of active inflammation. In addition, focal glandular atypia in keeping with low-grade dysplasia was evident but no high-grade dysplasia.

Question

What are the main diagnostic considerations and the most appropriate management?

Diagnostic considerations:

This patient has long-standing acid reflux in a background history of celiac disease. Gaining weight, with alcohol intake above the upper limit exacerbated his acid reflux. He has an established inflamed Barrett’s esophagus with a mild benign esophageal stricture and low-grade dysplasia. It is well recognised that in the presence of chronic inflammation, it is difficult to differentiate between reactive changes and true dysplasia. In addition, this patient has been treated with a biphosphonates, which can cause esophageal ulceration and strictures. More recently, long term use of biphosphonates has been associated with higher risk of esophageal cancer. [48]

The principles of management are two fold: (a) to improve dysphagia and acid reflux and (b) to establish whether he has true low-grade dysplasia. If the patient suffers from mild intermittent dysphagia, one may treat him with high dose PPIs alone and observe whether his symptoms improve. If dysphagia persists, esophageal dilatation may be necessary to improve swallowing. This patient was prescribed add: dispersible lansoprazole (FasTab) 30 mg bd and he reluctantly undertook a second endoscopy 12 weeks later as he had symptomatically improved; the stricture was not present and repeat biopsies demonstrated less inflammation but persistent focal glandular atypia, suggestive of true low-grade dysplasia. The patient was advised to remain on high-dose PPIs and have a repeat endoscopy.

Questions

How often would you endoscope this patient?Would you advise the patient to stop taking the Biphosphonates for osteoporosis?

Answers:

A repeat endoscopy is advised 6 months later with four-quadrant biopsies every 2 cm. If low-grade dysplasia persists, yearly endoscopies thereafter are necessary to detect if there is progression to high-grade dysplasia.

The decision to continue with biphosphonate treatment would be based on the benefit/risk ratio. The patient would be advised to have a further bone DEXA scan and if there is a significant probability of further osteoporotic fractures, he should continue on osteoporosis therapy. Alternative medications, such as risedronate sodium or strontium ranelate, could be considered. Also the patient is now committed to long-term treatment with a PPI, which might further increase the risk of osteoporosis [49]. The importance of strict adherence to a gluten free diet should also be emphasised.

Patient Management

The patient declined further endoscopies as he became asymptomatic on PPIs. He agreed to a bone DEXA scan which showed significant osteoporosis of the spine (cumulative 10-year fracture risk in excess of 15%). Alendronate sodium was changed to risedronate sodium and the patient was advised to return for a follow up endoscopy, but he did not attend despite repeated calls.

Four years later he consulted his general practitioner because of a 3-month history of progressive dysphagia for solids with frequent choking and 4 kg weight loss. Clinical examination was normal.

Question

What is the differential diagnosis?

Answer:

The differential diagnosis includes development of esophageal adenocarcinoma on Barrett’s or development of further esophageal stricture due to acid reflux or due to treatment with biphosphonates. An upper GI endoscopy demonstrated an obstructed esophagus with an irregular exophytic lesion at 36 cm. He had a balloon dilatation of the stricture and biopsies confirmed esophageal adenocarcinoma developing on Barrett’s esophagus.

Questions

How would you investigate this patient further?What are the treatment options?

Answer:

This patient will require staging investigations and discussion at the upper GI cancer multidisciplinary case conference. A chest and abdomen CT followed by a PET scan and an endoscopic ultrasound (EUS) would be appropriate staging investigations. CT is mostly of value to exclude any distant metastases, particularly in the liver or lungs, and a PET scan is of value to further assess suspicious areas on CT in other organs or to establish whether some lymph nodes seen on CT are malignant or benign [50]. EUS remains the gold standard of tumour and nodal (TN) staging in esophageal cancer. The 3 tests should be considered complementary rather than being interpreted independently. A recent study highlighted the importance of case conference for those cases as the final staging following a multi disciplinary discussion approached 92% using pathology of surgical specimen as gold standard. [51]

Patient Management:

A chest and abdominal CT was clear of metastases but the tumour radiologically was a T3 (tumour invading into the adventitia) with regional lymphadenopathy (N1). A PET/CT has shown that the regional lymphadenopathy was 18FFDG avid suggestive of malignant lymph nodes. The patient had an endoscopic ultrasound, which confirmed a T3 tumour with 3 peri-tumour nodes. Final staging T3N1.

Therapeutic options for the treatment of a T3N1 esophageal tumour include surgery, preoperative chemotherapy followed by surgery, or chemoradiotherapy. Patient co-morbidity is important in deciding treatment options, as there is significant operative risk (5 to 10% mortality). This has to be balanced against the limited 5-year survival of T3N1 disease (approximately 10–15%), which could be increased to 25 to 30% with preoperative chemotherapy prior to surgery. Preoperative chemotherapy consisting of cisplatin and 5-FU (fluoroucil) can also help to achieve complete surgical clearance of cancer (60% of patients versus 54% if not receiving preoperative chemotherapy) and improvement in the 2-year survival from 34 to 43% [52].

This patient tolerated preoperative chemotherapy well with no side effects, such as leucopenia, cardiotoxicity, thromboembolic events or gastrointestinal upset and undertook surgery. Histology on the excised specimen confirmed a T3N1 tumour with 3 out of 20 nodes excised positive. The patient remains well 18 months later.

Discussion

Despite improvements in the management of esophageal cancer, prognosis remains poor because of the late presentation of the disease. At presentation over 60% of patients are inoperable. In general, patients who are fit for surgery with localised tumour and no nodal involvement will be candidates for surgery alone. The presence of lymph nodes significantly worsens prognosis and such patients will benefit from preoperative chemotherapy. In early T1N0 disease, endoscopic mucosal resection or endoscopic submucosal dissection can be considered, provided there is no satellite lymphadenopathy present. If in doubt, an EUS with sampling of suspicious nodes is recommended. For patients with advanced disease not fit for surgery, palliative measures such as esophageal stent insertion, argon plasma coagulation or Nd-YAG laser are appropriate to establish lumen patency and improve dysphagia, nutritional status and offer better quality of life. Esophageal stent technology has greatly advanced and a variety of covered and uncovered metal self-expandable stents are available depending on the length and the position of the malignant stricture. Such endoprostheses are placed under fluoroscopic control or direct endoscopic view under sedation. They are of value for sealing broncho-esophageal fistulas in advanced (T4) disease and are particularly suitable for elderly patients or those not keen to receive repeated endoscopic treatments. Complications of stenting are generally few with stent migration rate of approximately 5%. Perforations are rare. The most commonly encountered complications are pain following stent insertion, which is usually controlled by simple analgesia; in patients with advanced disease severe pain may herald very poor prognosis and may require use of opiate analgesia. Food bolus obstruction, cleared by endoscopy and tumour in-growth are common complications. Using covered stents reduces tumour in-growth. Patients with esophageal stents should be advised to drink warm or carbonated drinks before and after meals to clear food debris, to have a soft diet and regularly use PPIs particularly for the stents crossing the gastro-esophageal junction.

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