Klinisk institutt 1

Midtveisevaluering - Khanh Do-Cong Pham

Midtveisevaluering for ph.d.-graden ved Universitetet i Bergen for kandidat Khanh Do-Cong Pham

Khanh Do-Cong Pham er tilknyttet Klinisk institutt 1. Veiledere er Odd Helge Gilja og Roald Flesland.


The role of endoscopy for diagnosis and treatment of esophageal motility disorders


Paper 1: Outcome of Per Oral Endoscopic Myotomy for treatment of achalasia – Norwegian single center experience with median following-up of 24 months

Long term effects of Per Oral Endoscopic Myotomy (POEM) are still unknown. The aim of this study was to investigate and report the feasibility, safety, efficacy and complications of POEM from the introductory phase in a tertiary referral center in Norway.

Material and Method
Collected prospective data from the first 68 patients with achalasia who underwent POEM at Haukeland University Hospital from February 2014 until December 2017 were analyzed. The patients were followed up for 12 months with respect to acute and delayed complications, and efficiency of the treatment. The diagnosis was based on findings on high resolution manometry (HRM) and timed barium swallow X-ray (TBS). We repeated HRM, TBS, in addition to impedance and 24-hours pH measurement 12 months after POEM. Reflux was regarded as pathological if the acid exposure (pH<4) time was more than 6%. Eckardt score was used for symptom evaluation before, and at 6, 12 and up to 56 months after POEM.

41 males and 27 females with symptomatic achalasia and Eckardt score ≥6 were included. The mean age was 44,6y. Based on HRM, 15 patients had achalasia type I, 34 type II and 19 with type III. 36 patients (53%) were naïve to other treatment, while 11 (16%) had been previously treated with botulinum toxin injection, 14 (22%) with pneumatic balloon dilatation, and 10 (15%) with Heller´s myotomy. The average resting pressure over lower esophageal sphincter (LES) was median 25 mmHg (0-72) prior to POEM, and 6,5 mmHg (0-23.1) after. Dysphagia improved in all patients on follow up. The Eckardt score was significantly reduced from median 7 (4-12) before POEM to 1 (0-9) at 12 months after POEM (p < 0.0001).  The median myotomy length was 11 cm (4-20). 43 patients (63%) patients had posterior myotomy, while 25 (27%) anterior. The procedure time was mean 130 min, and admission time was mean 3 days. We did not experience any serious complications but observed capnoperitoneum and capnothorax in 10 patients (15%). 3 patients (4%) required peritoneal decompression during POEM (Grade 2 complication). At 12 months, 86.8% had Eckard score ≤3, and 75,5% Eckardt score ≤2. 24 -hours pH monitoring was recorded on 55 patients (80%). 12 months post-POEM pathological reflux was measured in 45%, but only 37% reported reflux symptoms, 22% needed proton pump inhibitors (PPI) daily while 9% needed PPI occasionally.

Results with 12-56 months following-up from our cohort of consecutive patients show that POEM is safe and relieves symptoms of achalasia significantly, but the risk of reflux is higher than what is previously reported in the literature. Further studies are needed to confirm the findings in a long-term follow-up.

Paper 2: Navigated retrograde endoscopic myotomy (REM) for the treatment of therapy-resistant achalasia

In achalasia, muscle spasm may involve the proximal esophagus. When the muscle spasm is located in the proximal esophagus, conventional per oral endo- scopic myotomy (POEM) may not be sufficient to relieve symptoms. In this paper, we describe retrograde endoscopic myotomy (REM) as a novel approach to perform my- otomy of the proximal esophagus, with the application of a navigation tool for ana- tomical guidance during REM. We aim to evaluate the feasibility and safety of REM and usefulness of the navigation during REM.

A 42-year-old male with type III achalasia who was treated with laparoscopic myotomy with fundoplication, multiple pneumatic balloon dilations, Botox injections and anterior POEM of the middle and distal esophagus without symptomatic effect. Repeated high-resolution- manometry (HRM) revealed occluding contractions of high amplitude around and above the aortic arch. A probe-based real-time electromagnetic navigation platform was used to facilitate real-time anatomical orientation and to evaluate myotomy position and length during REM.

The navigation system aided in identifying the major structures of the medi- astinum, and position and length of the myotomy. Twelve weeks after REM, the Eckardt score fell from seven at baseline seven to two. We also observed improve- ment with reduction of the pressure at the level of previous spasms in the proximal esophagus from 124 mmHg to 8 mmHg on HRM.

REM makes the proximal esophagus accessible for endoscopic myotomy. Potential indication for REM is motility disorders in the proximal esophagus and ther- apy failure after POEM.

Paper 3: Chromoendoscopy with iodine-potassium iodine solution in eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is an immune-mediated condition associated with chronic allergy. Endoscopic findings in EoE may include linear furrowing of the mucosa, white plaques or exudates, concentric rings, friable and diffuse luminal narrowing or strictures, but can often be normal. Biopsies are taken randomly and are often negative. The aim of the study was to evaluate whether chromoendoscopy with Iodine/Potassium iodine solution (IPIS) is useful for identification of EoE during endoscopy, target and reduce the numbers of needed biopsies.

Aims & Methods
We included 10 patients with known EoE and 10 patients with dyspepsia. All underwent gastroscopy with IPIS staining 0.5-1% of the whole esophagus. Selective biopsies were taken from the areas without uptake and areas with uptake of IPIS stain for histopathological comparison and diagnosis.

Normal squamous esophageal epithelium took up IPIS and colored it dark brown, while pathologic epithelium become light yellowish due to reduced iodine uptake. In all 10 patients with EoE we observed diminished uptake of IPIS in whole length of the esophagus. 4 patients with EoE had leopard skin pattern after installation IPIS. In these patients, all biopsies from areas with low uptake, showed histologically confirmed EoE (mean 88 eosinophils per high power field (HPF)), whereas areas with more normal uptake showed significantly lower number of eosinophils (mean 18 eosinophils/HPF). In the group with dyspepsia, the uptake of IPIS was found to be normal, with even dark brown colorization of the esophageal mucosa.

IPIS seems be useful for identification of patients with EoE during endoscopy. Areas with uptake deficit in otherwise normal looking squamous epithelium should be biopsied. The technique allows targeted biopsies for improved identification of EoE and reduce sampling errors. Further studies in an unselected patient population must be performed to further explore this finding.