Christopher H. Blevins

Endoscopic therapy for Barrett's oesophagus

Barretts oesophagus (BO) is thought to progress through the development of dysplasia (low grade and high grade) to oesophageal adenocarcinoma, a lethal cancer with poor survival. The overall goal of endoscopic therapy of BO is to eliminate metaplastic and dysplastic epithelium, to prevent and/or reduce the risk of progression to OAC. Endoscopic therapy techniques can be divided into two broad complementary techniques: tissue acquiring (endoscopic mucosal resection and endoscopic submucosal dissection) and ablative. Endoscopic therapy has been established as safe and effective for the subjects with intra-mucosal cancer (IMC), high-grade dysplasia (HGD) and more recently in treating low-grade dysplasia (LGD). Challenges to endoscopic therapy are being recognized, such as incomplete response and recurrence. While eradication of intestinal metaplasia is the immediate goal of endoscopic therapy, surveillance must continue after complete elimination of intestinal metaplasia, to detect and treat recurrences.

Klinefelter’s syndrome

A 29 year old man presented to primary care with anxiety and depression that had worsened since childhood. Further questioning revealed a history of poor school performance, poor body image, and poor self esteem. On physical examination, the patient’s height was 189 cm and he had narrow shoulders, wide hips, sparse facial hair (which he shaved once every two months), and small, firm testicles. He was found to have elevated luteinising hormone and follicular stimulating hormone concentrations, low serum concentrations of testosterone, absent sperm on semen analysis, and a karyotype of 47,XXY. Klinefelter’s syndrome is the clinical result of an additional X chromosome in males (47,XXY), although other chromosome abnormalities (such as 46,XY/47,XXY mosaicism; 48,XXXY; 49,XXXXY) account for 10-20% of cases.1 2 Classic clinical findings include infertility, small testes, hypergonadotropic hypogonadism (elevated luteinising hormone and follicular stimulating hormone concentrations with low or low to normal testosterone concentrations), decreased facial and body hair, gynecomastia, tall stature with eunuchoid features, and psychosocial morbidity.1 3 #### How common is Klinefelter’s syndrome?

Putting it Through the Nose: The Ins and Outs of Transnasal Endoscopy

Sedated transoral endoscopy (sEGD) remains the conventional and most commonly utilized diagnostic tool to directly visualize the upper gastrointestinal tract for both diagnostic and therapeutic purposes. While this has become a relatively routine procedure with a favorable risk profi le, it is associated with complications (albeit at a low rate) that may be prohibitive in certain high-risk populations. In addition it is also expensive, making it a less suitable tool for large-scale applications such as screening for refl ux complications such as Barrett’s esophagus or complications of cirrhosis such as varices. Th e potential use of unsedated transnasal endoscopy (uTNE) for these conditions is attractive if proven to be acceptable, safe, and accurate. Recent data suggest that uTNE can be a safe and accurate alternative to sEGD for these indications ( Table 1 ). Commercially available transnasal endoscopes are listed in Table 2 . Transnasal endoscopes are slimmer than conventional diagnostic endoscopes with shaft diameters ranging from 5–6 mm ( Figure 1 ). Th eir working channel (if available) is smaller (2 mm in diameter) and hence cannot accommodate standard-sized biopsy forceps or other through-the-scope tools. Pediatric biopsy cables can be advanced through the therapeutic channel to obtain biopsies if needed. While some transnasal endoscopes have both rightleft and up-down controls, those slimmer than 5 mm only have an up-down control ( Figure 2 ). Most of these endoscopes are of adequate length to examine the stomach and proximal duodenum and need conventional light sources and disinfection aft er use. Recently an esophagoscope (65 cm in length) has been introduced which is covered with a disposable sheath (Endosheath, Cogentix Medical, Minnetonka, MN), and is available in two confi gurations: with or without a biopsy channel. Th is sheath protects the endoscope from coming into contact with body fl uids and can be discarded aft er use. Th e endoscope can then be disinfected with sopropyl alcohol wipes and reutilized with another sheath, without undergoing conventional disinfection. While the imaging in this endoscope, which is generated by a charge-coupled device, is not high defi nition, it appears to be adequate and comparable to conventional endoscopy from a diagnostic standpoint as shown in recent trials ( Figure 3 ). A disposable capsule attached to a shaft is also commercially available for visualization of the esophagus and stomach (E.G.Scan II, Intromedic, Seoul, Korea). It is connected to a controller and processor. Both these devices that do not require conventional disinfection make mobile or in offi ce examinations a possibility.

Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium

Background While central obesity increases gastroesophageal reflux (GER) by mechanically disrupting the anti-reflux barrier, limited data exist on pathways by which central obesity may potentiate esophageal injury by non-mechanical means. Obesity has been associated with an impaired epithelial intestinal barrier. Objective We aimed to assess the influence of central obesity and reflux on the squamous esophageal epithelial intercellular space diameter (ICSD). Methods The ICSD was measured using electron microscopy in esophageal biopsies from individuals who underwent ambulatory pH monitoring and endoscopy. Anthropometric measurements were obtained on all participants. Participants were classified into four groups: with and without central obesity and reflux. Results Sixteen individuals were studied with four in each study group. The mean ICSD was almost three-fold greater (p < 0.001) in the group with central obesity without reflux, compared to controls without central obesity and reflux. It was also comparable to the ICSD in groups with acid reflux only and those with both reflux and central obesity. Conclusions There is evidence of esophageal squamous ICSD increase in individuals with central obesity who do not have evidence of acid and nonacid reflux on ambulatory pH monitoring. This may reflect a mechanism by which central obesity potentiates reflux-induced esophageal injury and inflammation.

Who Deserves Endoscopic Screening for Esophageal Neoplasia

Despite the availability of safe and effective endoscopic treatment of Barretts esophagus (BE)-related dysplasia and neoplasia, the incidence and mortality from esophageal adenocarcinoma (EAC) have continued to increase. This likely stems from the large population of patients that develop EAC outside of a BE screening and surveillance program. Identification of BE with screening followed by enrollment in an appropriate surveillance/risk stratification program could be a strategy to address both the incidence of and mortality from EAC. This article summarizes the rationale and challenges for BE screening, the risk factors for BE, and the currently described BE risk assessment tools.

The Esophageal Epithelial Barrier in Health and Disease

&NA; Dysfunction in the esophageal epithelial barrier function is a major source for morbidity. To better understand the pathophysiologic pathways of the diseases associated with barrier dysfunction, including gastroesophageal reflux disease, eosinophilic esophagitis, Barrett’s esophagus, and obesity, it is important to understand the esophageal epithelial embryologic development, microscopic anatomy with a special focus on the barrier structure and function, extraepithelial defense mechanisms, and how these change in the diseased state. In recent years, significant progress has been made in elucidating the esophageal barrier structure and function both in vitro and in vivo. This has enhanced the understanding of mechanisms of disease, and may also allow identification of therapeutic targets that can help in the management of these diseases. This review provides a detailed discussion regarding the esophageal epithelial barrier structure and function, the current and historical techniques used to study the barrier, and how it is affected by common esophageal diseases.

52-Year-Old Woman With Hypotension, Hypothyroidism, and Hyponatremia

Resident in Internal Medicine (C.H.B.) and Fellow in Cardiovascular Diseases (A.M.K.), Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, MN; Advisor to resident and fellow and Consultant in Primary Care Internal Medicine, Mayo Clinic, Rochester, MN (A.C.G.). A 52-year-old woman with hypothyroidism presented to the emergency department with nausea, malaise, and hyponatremia. Her illness had begun 3 months previously with increasing generalized weakness, fatigue, insomnia, bilateral carpal tunnel syndrome requiring surgical release, and decreased appetite with a corresponding weight loss of 8 kg. At that time, her thyroid-stimulating hormone (TSH) level was 8.0 mIU/L (reference range, 0.3-5.0 mIU/L), so her physician increased her levothyroxine dosage from 75 mg/d to alternating daily doses of 75 mg and 88 mg. Her symptoms had accelerated during the past 2 weeks and now included constipation, worsening exercise tolerance, and vomiting. She noted that most women in her family have hypothyroidism and that her daughter had just been diagnosed as having granulomatosis with polyangiitis. The patient did not smoke tobacco, drink alcohol, or use illicit drugs, had never been incarcerated, had no sick contacts, and had not traveled outside her home state in the Midwest. Because her symptoms had not improved despite treatment during the past 3 months and now had worsened, she sought evaluation in the emergency department. On admission, her temperature was 37 C, and she had orthostatic vital signs. Her supine, sitting, and standing blood pressure and heart rate were 108/68 mm Hg and 79 beats/min, 88/71 mm Hg and 105 beats/min, and 64/39 mm Hg and 64 beats/min, respectively. She was alert and oriented and had a slender body habitus. Her mucous membranes were moist, but she appeared slightly volume depleted because jugular venous pulsations were not visible on examination despite manual pressure applied to her abdomen. Cardiothoracic, neurologic, thyroid, and abdominal examinations yielded normal findings. Her skin appeared slightly hyperpigmented, but there was no buccal or palmar crease hyperpigmentation.

Obesity and GERD impair esophageal epithelial permeability through 2 distinct mechanisms

The mechanism by which obesity leads to damage independent of reflux is unclear. We aimed to determine the influence of obesity on mean nocturnal baseline impedance (MNBI), a functional measure of the epithelial barrier, in the presence and absence of acid reflux, using ambulatory pH impedance measurements.