TNMS

2019 Annual Meeting

臺北榮民總醫院 內視鏡診斷與治療中心

王彥博

Date: 2018/5/19

A man with chronic

dysphagia and recent

body weight loss

Patient profile

• Age: 67

• Gender: male

• Past history: – Colon cancer TisN0M0 s/p laparoscopic low anterior

resection in 2007– Gall bladder stone related cholecystitis in 2007– Asthma at youth

• Chief complaint:– Recent weight loss 10kg in recent two months with

dysphagia

• Drinking: 1-2 bottle liquor/ week over 20 years,

quitted 10 years

• Smoking(-)

• Betelnut(-)

• Herbal medication use (-)

• Allergy history (-)

• Animal Contact (-)

Personal history

• Dysphagia to both solid and liquid from 20 years ago

• Need water to help swallowing

• Frequent heartburn sensation

• Frequent retrosternal pain, especially in supine position

– Relieved after food vomiting

Present illness

2007 Chest X-ray

2007 UGI series

2007 Chest CT scan

• After coming back from Xinjiang, China where he took spicy food

• Retrosternal pain worsened in 2 months

– Food obstruction sensation at neck area

– Had no feeling of food intake into his stomach

• Symptom once improved after acupuncture

• Only taking liquid diet due to dysphagia

• Body weight loss from 58 to 48 kg in 2 months

Present illness

Eckardt score

Symptom Each meal Daily Weekly None

Dysphagia 3 2 1 0

Regurgitation 3 2 1 0

Chest pain 3 2 1 0

Weight loss>10 kg

3

5-10 kg

2

<5kg

1

No weight loss

0

Eckardt VF. Gastrointest Endosc Clin N Am. 2001;11(2):281–292. vi.

Eckardt VF. Gastroenterology 1992; 103, 1732-1738

Stage 0 1 2 3

Score 0-1 2-3 4-6 >6

Eckardt score=10

• Body height: 160cm Body weight:48kg

• T/P/R: 36.8/87/18, BP 108/54 mmHg

• HEENT: no icteric sclera, not anemic conjunctiva

no oral ulcer, not injected throat, supple thyroid

• Heart: regular rhythm, no murmur

• Chest: bilateral clear BS, no rales, no rhonchi

• Abdomen: soft, not distended, no tenderness, normoactive bowel sound

• Extremities: no rash, no limb edema

Physical examination

Laboratory tests result

Item Value Normal value

WBC 6400/cumm 4500-11000

Hgb 14.3 g/dl 12-16

Plt 247000/cumm 150000-350000

Seg 67.8% 45-75

Lym 20.7% 20-45

Mono 9.7% 0-9

Eos 1.5% 0-5

Na 143 mmol/L 135-147

K 4.1 mmol/L 3.4-4.7

Glu 82 mg/dl 65-115

BUN 12 mg/dl 7-20

Cr 0.88 mg/dl 0.5-1.2

ALT 11 U/L 0-40

AST 18 g/dl 0-45

T.Bil 0.50 mg/dl 0.2-1.5

2017 Chest X-ray

2017 Esophagogastroduodenoscopy

2017 UGI series

2017 Chest CT scan

1. Diagnose achalasia based on UGI series , EGD and CT scan and history

2. Only measure the esophageal peristalsis without LES pressure

3. Endoscopy guided manometry catheter insertion

Manometry catheter failed to pass through LESWhat to do next?

• In a series of 2000 HRM, 414(21%) imperfect

– 58% < 7 evaluable swallows

– 29% inability to transverse EGJ (50% large hiatal hernia, 24 % achalasia)

– 7% sensor malfunction

– 6% artifacts

• 33% imperfect study-achalasia

– 94% accuracy in unblindedreview

Imperfect high resolution manometry study

S Roman et al. CGH 2011;9:1050-1055

Gyawali, C. Prakash CGH 2011;9:1015–1016

Endoscopic guided manomery catheter insertion

IRP 4sec=33 mmHg

HRM

Type I achalasia

Achalasia, Type I, sigmoid type 2 , Eckardt score=10

1. Keep observation due to long history of dysphagia (over 20 years)

2. Endoscopic pneumatic dilation

3. Laparoscopic Heller’s myotomy or

peroral endoscopic myotomy (POEM)

4. Botulism injection

5. Esophagectomy

What to do next?

Courtesy from Dr Ping-Hsien Chen

Per-oral Endoscopic Myotomy (POEMS)

UGI series post-op day 2

EGD 2 months post-op

IRP 4sec=10 mmHg

HRM 2 months post-op

Weight gain 12 kg in 2 months; Eckardt score=0

What to do next?

1. Successful treatment, keep observation

2. Failed treatment, Re-do POEM

3. Failed treatment, Enodscopic pneumatic dilation

4. Failed treatment, botox injection

5. Failed treatment, esophagectomy

DiscussionAchalasia

• Achalasia is a rare motility disorder of the esophagus

characterized by impaired lower esophageal sphincter

(LES) relaxation with swallowing and aperistalsis in the

smooth muscle esophagus leading to impaired bolus

transport and stasis of food in the esophagus

• Annual incidence: 0.3-1.63/100,000 in US and Europe

– Incidence up to 1.07-2.92/100,000 since HRM use

• Prevalence about from 7/100,000 to 13.4/100,000

• Affects both genders equally

• Incidence increase with age

Sleisenger 9th edition

Gue E Boeckxstaens et al. Lancet 2014; 383: 83–93

Salih Samo et al. Clin Gastroenterol Hepatol. 2017 Mar; 15(3): 366–373.

Duffield JA et al. Clin Gastroenterol Hepatol. 2017 Mar;15(3):360-365

Achalasia - Definition and Epidemiology

• Esophageal dysphagia for both solid and liquids (90%)

• Chest pain

• Heartburn (bacterial fermentation, acidification of food

products)

• Regurgitation

• Weight loss

• Other symptoms

– Slow eating

– Stereotactic movements with eating

– Avoidance of social functions that involve meals

• Slow in progression, may take years to medical attention

• Reflux symptoms unresponsive to reflux therapy may

suggest achalasia

60%

Francis DL, Katzka DA. Achalasia: update on the disease and

its treatment. Gastroenterology. 2010;139(2):369-74.

Clinical Presentation

• Degeneration of ganglion cell in the myenteric plexus of the esophageal body and the LES

– Genetic factors? MHC class II HLA DQw1, myenteric antiplexusantibodies with specific HLA genotypes, abnormal VIP receptor 1 gene

– Molecullar mimicry with immune responses to HSV-1

– Autoimmune- Antineuronal antibodies (anti-hu)

• Leading to greatly loss of inhibitory enteric neurons, in particular nitric oxide–releasing neuron LES hypertonicity and incomplete relaxation with swallowing

• Ali-grove’s syndrome

• Amyloidosis

• Post-operation external compression

• Chagas disease

• Malignancy and paraneoplastic syndrome(Small cell lung cancer)

Francis DL, Katzka DA. Achalasia: update on the disease and its treatment. Gastroenterology. 2010;139(2):369-74.

Pathophysiology

• Require at least 2 and sometimes 3 modalities for diagnosis

• Endoscopy, Esophageal manometry, Barium esophagram

Vaesi MF et al. AJG 999 Dec;94(12):3406-12.

Francis DL, Katzka DA. Achalasia: update on the disease and its treatment. Gastroenterology. 2010;139(2):369-74.

Diagnosis

Timed Barium esophagogram

S. Kostic et al. Diseases of the Esophagus (2005) 18, 96–103

Zafar Neyaz et al. J Neurogastroenterol Motil 2013;19:251-256

Healthy individuals empty esophagus within 2 minutes

AJ Bredenoord& the HRM Working Group: Chicago Classification Criteria of EsoMotility Disorders Defined in HR

EPT; Neurogastroenterol Motil (2012) 24 (Suppl. 1), 57–65

2015 Chicago classification Version 3.0 for HRM

`

Median >15 mmHg

J.E. Pandolfino et al CGH 2013;11:887–897

Treatment success rate differ between types

Wout O. Rohof et al. Gastroenterology 2013;144:718–725

Mean follow-up 43 months (IQR, 29-62 months)

96%

81%

66%

24 months

Type I hazard ratio = 4.0

Type III hazard ratio = 6.8

N=44

N=114

N=18

• Sildenafil decrease LES tone, residual pressure and

amplitude within 60 min Luca Dughera et al, Clin Exp Gastroenterol. 2011; 4: 33–41.

Bortolotti M et al, Gastroenterology , 2000 Feb;118(2):253-7.

Pharmacologic Treatment

• 30 mm balloon catheter

was inserted through

guidewire and inflated for 1

min and repeatedly

• Perforation rate 2-6%

Francis DL, Katzka DA. Achalasia: update on the disease and its treatment. Gastroenterology. 2010;139(2):369-74.

Pneumatic dilation (PD)

From Mmorial Hermannhttp://www.memorialhermann.org/digestive/laparoscopic-heller-myotomy/

Francis DL, Katzka DA. Achalasia: update on the disease and its treatment. Gastroenterology. 2010;139(2):369-74.

• Complication rate 6%, mortality rate 0.1%

Heller’s Laparoscopic Myotomy & Dor Fundoplication (LHM)

Inoue H et al Endoscopy. 2010;42(04):265-71.

Per-oral Endoscopic Myotomy (POEM)

Japan POEM result- 10 year experiences

Item Number

Hospital 12

Cases 2271

Age 49.1 (3-95)

Gender (M/F) 47%/53%

Shape type (straight/sigmoid/advanced sigmoid/others)

80%/13%/6%/1%

Manometry type( I/II/III) 649/500/87(53%/40%/7%)

Primary procedures

Pneumatic dilation 26%

Heller-Dor operation 4%

POEM 2%

Botox injection 0.1%

Hironari Shiwaku Tokyo Live 2018/Apr

Beofre POEM 3 months later

LES pressure (mmHg) 37.3 16.8

IRP (mmHg) 27 11.7

Before poem 3 months later 1 year later

Eckardt score 6 1 1.2

3 months later 1 year later

Eckardt score<=3 97% 96%

Japan POEM result- 10 year experiences

Adverseevents

Mucosal injury

Submucosal hematoma

Bleeding(with transfusion)

Others Mortality

Cases(%) 108 (4.7%) 19 (0.8%) 1(0.04%) 53 (2.3%) 0 (0%)

Hironari Shiwaku Tokyo Live 2018/Apr

• 60-100U botulinum toxin in

divided dose into 4 quadrants

of the LES

http://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/esophagus_stomach/swallowing_disorders.pdf

Leyden JE et al, Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD005046.

Relative risk 2.67 (PD over BTX) in 12 months

Botulinum toxin injection

• 3-7 days of partially

covered self-

expandable metallic

stent(6x3cm)

• Migration rate 3-

27%

Jun-Gong Zhao et al, Eur Radiol (2009) 19: 1973–1980

Zhu YQ et al, J Gastroenterol Hepatol. 2010 Mar;25(3):499-505.

Cheng YS et al, World J Gastroenterol. 2010 October 28; 16(40): 5111-5117.

Stenting

PDp=00.212

Temporary tenting (SEMS)

Esophagectomy

For End-stage achalasia (<5%)

79% transthoracic ; 21% transhiatal

Morbidity 19-50%; mortality 0-5-4%

– 27.5% endoscopic dilation within 1 year

Unrestricted diet in 75-100% of patients

More technically difficult than resection of malignancy– Anatomy altered

– Richer bloody supply due to muscular hypertrophy

– Cervical esophagus mobilization difficult

– Previous treatment related stricture

Alberto Aiolfi et al. World J Surg (2018) 42:1469–1476

Julia M. Howard et al. International Journal of Surgery 9 (2011) 204e208

• European Achalasia Trial, 201 achalasia patients

prospectively randomized to receive PD or LHM and followed

up more than 2 years (mean follow-up period 43 mo)

Boeckxstaens GE et al, N Engl J Med. 2011;364(19):1807-16.

90%

90%

93%86%

Efficacy of PD v.s. LHM

POEM LHM P value

Improvement of dysphagia at 12 months

93.5% 91.0% 0.01

Improvement of dysphagia at 24 months

92.7% 90.0% 0.01

GERD symptoms 18.5% 17.5% P<0.01, OR 1.16

GERD-EGD 22.4% 11.5% P<0.01 OR 1.61

GERD-Ph 47.5% 11.1% P<0.01 OR 4.30

Francisco Schlottmann et al . Ann Surg 2018; 267(3): 451-460

• Meta-analysis

• 53 LHM studies (5834 patients)

• 21 POEM studies (1958 patients).

Efficacy of POEM vs. LHM

Ponds FA, Fockens P, Neuhaus H, et al. Peroral Endoscopic Myotomy (POEM) Versus Pneumatic Dilatation in

Therapy-Naive Patients with Achalasia: Results of a Randomized Controlled Trial. Gastroenterology;152:S139.

European Multicenter Randomized Trial POEM VS. PD

POEM (n=64) PD (n=66) P value

3 months F/U 98.4% 78.8% <0.01

1 year F/U 92.2% 70.0% <0.01

Type III 3 months 100% 50%

Type III 1 year 83.3% 33.3%

Adverse event 1 perforation1 chest pain needs admission

GERD- endoscopy 40% A/B8.3% C/D

13.1% A/B0% C/D

P=0.02

Pathologic acid exposure(EAT>6%) on 24 hours pH-metry

49.1% 38.6%

Efficacy of POEM vs. PD

Treatment considerations for achalasia and achalasia syndromes

Kahrilas PJ et al. Gastroenterology. 2017 Nov;153(5):1205-1211

Achalasia treatment algorithm

Vaezi MF et al. Am J Gastroenterol. 2013 Aug;108(8):1238-49

Thank you for your attention!!!

Thanks for efforts and help from:• Prof. Ching-Liang Lu• Prof. Ming-Chih Hou• Dr. Ping-Hsien Chen • Dr. I-Fan Hsin• Dr. Chih-Cheng Hiseh

• Dr. FU-Ming Chang• Dr. Ya-Chun Chu• MT. Yung-Hang Sun • Ms. Pei-Yi Liu• Mr. Shen-Kai Chang