Dies ist der Titel der Präsentation - Mucosal Immunology · Titel der Präsentation / Name Referent/-in 2 Gastroenterologie Impact? “Man should strive to have his intestines relaxed

Constipation

Titel der Präsentation / Name Referent/-in 2

Gastroenterologie

Impact?

“Man should strive to have his intestines relaxed

all the days of his life“

Moses Maimonides, AD 1135-1204

“If one’s bowels move, one is happy, and if they don’t move, one is unhappy. That is all there is to it.”

Lin Yutang (Chinese Philosopher), The Importance of Living, (1998)


Gastroenterologie

• Prevalence ~15 % USA and europe (2 – 87 %)

• > 60 y >30 % Suares Am J Gastroenterology 2011

Higgins Am J Gastroenterology 2004

• Economic impact!

Direct medical costs 230 million dollar/year (USA) +

additional indirect costs (off work,…) Doshi 2014

Gurkirpal 2007


Gastroenterologie

• < 3 bowel movements/w, hard stools, < 200g/d ?

• Abdominal discomfort / bloating / distention ?

• Subjective impression, despite 1/d frequency…

• Frequency often misestimated Sandler Dig Dis Sci 1987

Definition?


Gastroenterologie

ROME III constipation Longstreth Gastroenterology 2006

www.romecriteria.org

• Symptoms for ≥6 months and ≥2 of the following symptoms

for more 25 % of defecations during the past 3 months:

–Straining

–Lumpy or hard stools

–Sensation of incomplete evacuation

–Sensation of anorectal obstruction/blockade

–Manual maneuvers to facilitate defecations; <3

defecations/wk

–Loose stools are not present, and there are insufficient

criteria for IBS

What are the criteria for constipation in ROME III?


Gastroenterologie

ROME III constipation

What is needed for IBS-C?

• Discomfort, abdominal pain, meteorismus

• Change with/amelioration with defecation

• Possible intermittend diarrhoea (-25%)

Relevance?!?

IBS-C


Gastroenterologie

ROME = definition?


Gastroenterologie

• Normal Transit Constipation (NTC) (+/- IBS)

• Slow Transit Constipation (STC)

• Pelvic Floor Dysfunction/ Defecatory Disorders (DD)

• Combination of STC and DD

• Secondary Constipation and/or organic constipation

Clinical subgroups/Classification?


Gastroenterologie

• Metabolic/endocrine disturbances: diabetes,

hypothyreodism, pregnancy, hypokalemia, hypercalcemia …

• Neurologic: diabetic autonome neuropathy, M. Hirschsprung,

Chagas, M. Parkinson, MS, spinal cord injury

• Myopathy: Amyloidosis, Scleroderma

• Mechanical: IBD, obstruction, cancer, rectocele, diverticulitis, anal

fissure,

• Occasional: traveling, bed rest

Can be secondary to?


Gastroenterologie

Secondary Medications associated with

Constipation?

Medications associated with constipation?

Opioids

Anticholinergics

Antidepressivs (esp. tricyclic)

Gestagene

Chemotherapeutics eg Vincristine

Antihypertensives: Furosemid, Atenolol, Nifedipine

Parkinson medication

Antacids, Iron supplements

… many others


Gastroenterologie

• Duration of symptoms, objective frequence, Diet, work,

cofffee…breakfast, stool form (bristol stool chart)

what is most distressing symptom? (IBS)

• Straining? Need for manual maneuvers during

defecation?

• Which medication has been tried?

• Which medication is the patient on?

• Red flags?

Work up? First?


Gastroenterologie

• Physical examination + perianal and rectal examination

–Anal reflec, descent of perineum, anal fissure, tenderness of

puborectalis muscle, expel finger

–75 resp. 87 % sensitivity/specifity for dyssynergia Tantiphlachiva Clin Gastroenterol Hepatol 2010

• Blood tests

–BB (BSR, CRP, Electrolytes, Ca, Krea, Glu, TSH if clinical

suspicion)

• Ultrasound? - DGVS vs Francis et al 1996

• With red flags or > 50 years(Screening)…colonoscopy

Hamm 1999 2% Pathology

Work up? Second?


Gastroenterologie

Case 1

• 52 y, female, works in the post office

• Problems with defecation since years, bm 1/w

• Call during work never answered, since she is the only

worker in this post-office counter

• If asked admits straining, sense of anorectal blockage

• No red flags

• No improvement on fibre


Gastroenterologie

Case 1

• Colonoscopy normal since > 52 also without alarm

symptoms


Gastroenterologie

• Causative medication?!?

• Primary recomendations:

–Fibre rich diet 30-50g/d (15-20 g fibres/d in western europe

diet), esp. NTC

–Enough hydration

–Physical activity

–Pay attention to the gastrocolic reflex and call to stool (work)

and semisquated position on toilet

Therapy I? primary recomendations?


Gastroenterologie

Trial with fibres (cave STC) and laxtatives

BEFORE

other investigations

Therapy II?


Gastroenterologie

Trial with fibres

…How exactly? example?


Gastroenterologie


Gastroenterologie

IBS!

RECOMMENDATION IBS

• review the fibre intake in IBS, adjusting (usually reducing)

• discouraged from eating insoluble fibre

• increase soluble fibre such as oats

NTC

• Fibre rich diet 30-50g/d


Gastroenterologie

Which patients do not benefit from fibres?

• STC


Gastroenterologie


Gastroenterologie


Gastroenterologie


Gastroenterologie


Gastroenterologie Ruhedruck Klemmdruck Pressen (Valsalva)


Gastroenterologie

Pressen (Valsalva)


Gastroenterologie

Case 1

Diagnosis: Dyssynergia – Anismus

– 2/3 also STC


Gastroenterologie

Defecatory disorders

• Cave: possible wrong positive results because of

examination Vorderholzer Gut 1997


Gastroenterologie


therapy dyssynergia?

• Biofeedback and relaxation training

–More effective than laxatives

–Response rate 70 % Rao Clin Gastroenterol Hepatol 2007

Heymen Dis Colon Rectum 2007

• In refractory cases (all defecatory disorders) additional

effect with provocation of defecationreflex

Suppositories, enemas


Gastroenterologie

Examples for other Defecatory disorders

• Functional:

–Anismus, paradoxical Puborectalis contraction, pelvic floor

Dyssynergia

• Anatomical:

– rectocele (herniation of anterior rectal and posterior vaginal

wall into vaginal lumen), intussusception, prolaps,

Hirschsprung


Gastroenterologie


Gastroenterologie


• Defecography additional information about anatomic

lesions

–Rectocel, Intusception

–Pelvic floor dyssynergia/M. puborectalis

–MR-Defäkography, Barium


Gastroenterologie

External Perineal Endosonography Roche Eur Radiol 2001

At rest: anorectal angle 90 °

Contracted: anorectal angle 70 °

With defecation: anorectal angle130 °

• Dyssynergia if less than 15 °change of the angle


Gastroenterologie

Case 2

• 37 y housewive

• Since 20 years abdominal dyscomfort

• Consulted several physicians: „no possibility to help“

• She takes Prontolax everyday, and „one day without – no

bowel movement“

• What would you do?

• (No obstructive defacation)


Gastroenterologie


Gastroenterologie

Colonic transit time/Hintontest

• 6 days capsules with each containing 10 radiopaque

markers, Rx day 7 (144 hours)

• Colonic transit time = number of markers x 2.4 Metcalf et al, Gastroenterology 1987

Chaussade Gastroenterol. Clin. Biol. 1986

• Normal < 68 – 72 h


Gastroenterologie

Fall 2

57 marker of 60 = 136,8 h colonic transit time

STC


Gastroenterologie


Gastroenterologie

Case 1

Right hemiabdomen = about 19h

(norm max.19-38h)

Left hemiabdomen = about 24h

(norm. max. 17-37h)

Rectosigmoid = about 46h

(norm.11-18h, max. 25-44h)

Overall 37 markers colonic transit

time of 89h

slow-transit constipation, but highly

suspicious for defecatory disorder

STC does not exclude DD !


Gastroenterologie

case 1

Overall 29 markers colonic transit

time of 70h


Gastroenterologie


Gastroenterologie

Case 2 Therapy NTC and STC and IBS-C

• Our patient did try many things…

• Nonetheless start with algorithm


Gastroenterologie

What do you recommend as medical therapy

(examples of prescription/groups of laxatives)?


Gastroenterologie Laxative Dose Start of action Side effects

Fibres

Psyllium (Metamucil

N Mite®)

Up to 3x1 spoon

(=5.8g Ballaststoffe)

aim 25-30 g/d

12 - 72 h Meteorism * Start slow…

Osmotic Laxatives

Polypethylenglykol =

PEG (Movicol®)

1-2 Btl (up to 34 g) per

day

No absortion! No loss of

effect!

1 - 4 days nausea * Limitatio 1

Grosspackung

Saline

Magnesiumsulfat

0.5 -3 h Not longterm

Sugars (Lactulose) 15-30 ml 24 – 48 h flatulence

Stimulating

laxatives

(Sekretagoga)

habituation

Bisacodyl 10 mg Tbl. 6-10 h

Senna Bis 15 mg tgl. 6-12 h Melanosis coli

New

Lubiprostone/

Linaclotide

12-48 h diarrhoea

1. Macrogol + stimlant laxative as rescue

2. Sugars Combinations

3. Prucaloprid

4. …


Gastroenterologie

• Polyethylenglycol isoosmotic with the ability to bind

water, not absorbed

firstline treatment, better effect than e.g. lactulosis…

Belsey et al, Int J Clin Pract 2010

20 Studien (10 RCT)

• STC and NTC may be treated with longterm laxatives

(consensus and enough safety data)

Laxatives


Gastroenterologie

Newer drugs for constipation? Examples?


Gastroenterologie

Resolor® Prucalopride

• Serotonin (5-HT4) Receptor-Agonist

• I: Idiopathic chronic constipation in WOMAN

• 1x d, start with 1 mg, - 2 mg (4mg), stopp after 1 month if

no effect, independent of meals

• 1 month 99.65 CHF (28 Tbl)

• Since 11/14 not only for FMH gastroenterology

• Max 12 weeks, than „Kostengutsprache“

• Sideeffects: headache, diarrhoea, Cave NI,

• No data for older people


Gastroenterologie

Resolor® Prucalopride

Camilleri et al, A placebo-controlled trial of prucalopride for

severe chronic constipation, N Engl J Med. 2008 May

•12 doubleblinded

trials

•zw 4-12 Wochen

•4000 Patienten


Gastroenterologie

Amitizia ® Lubiproston

• Activates selective typ 2-Cloridionchanals in enterocyts

with increased fluidsecretion and faster intestinal transit

–Accelerates small bowel transit

• I:Chronic idiopathic constipation in male and female

patients, opiat associated constipation

• Only approved in USA/CH, recomendation 2 after Resolor

• Amitizia® Kaps 24 mcg bid, (IBS-C 8 mcg bid)

• 1 month 58.05 CHF

• Stop if without effect after 4 weeks

• Max. 52 weeks, afterwards „Kostengutsprache“ Chey et al, Aliment Pharmacol Ther 2012


Gastroenterologie

Constella® Linaclotid

• Guanylatcyclase C activator, low bioavailability

• I: IBS-C (USA 145 mcg Constipation)

• Kaps 290 mcg 1/d 30` bevor meal

• Stop if no effect after 1 month

• 1 month 94.35 CHF (28 Kps)

• Trials show positive economic effect/cost-effectiveness on

ability to work in IBS-C Buono et al, Am Health drug benefits 2014


Gastroenterologie

Lembo et al, Two randomized trials of linaclotide for chronic

constipation, N Engl J Med. 2011 Aug

Linaclotide


Gastroenterologie

• Hanning et al, Guanylate

cyclase-C/cGMP: an

emerging pathway in the

regulation of visceral pain

Front Mol Neurosci. 2014

• Castro et al, Linaclotide

inhibits colonic

nociceptors and relieves

abdominal pain via

guanylate cyclase-C and

extracellular cyclic

guanosine 3',5'-

monophosphate,

Gastroenterology 2013.

Linaclotide

http://www.ncbi.nlm.nih.gov/pubmed/23958540


Gastroenterologie

Kamm et al, Sacral nerve stimulation for intractable

constipation, Gut 2010

Therapie

62 %


Gastroenterologie

Halmos et al, A diet low in FODMAPs reduces symptoms of

irritable bowel syndrom, Gastroenterology 2014


Gastroenterologie

• Therapy resistant severe STC (transit time) and

– excluded defecatory disorder

– excludes upper GI-motility disorder (scintigraphy, …)

– (psychologic profil, not for IBS! does treat the constipation

not the pain or discomfort)

(venting ileostomy) Subtotale colektomie/ Ileorectal

anastomosis

• Overall data afer colectomy 39 - 100 % patient satisfaction,

mostly with ileorectal anastomosis eg 89 % satisfaction

Li, Int J Colorect Dis 2014

Appendiceal conduit/cecostomy catheserisable, antegrade

Lavage

Ileostomy

Surgical therapies in constipation?


Gastroenterologie

Obstructed defecation with anatomical causes

• Short segment Hirschsprung (aganglionotic segment of the

colonfail to relax, more pediatric patients)

resection, and where possible anal anastomosis

• Pouch of douglas protrusion sacrocolpopexy

• Cystoceles, rectocels, intussucseption, enteroceles,

vaginal vault prolaps together with gynecologic

procedures

but

Minority needs surgery!

Never Surgery? other reasons for surgery than STC?


Gastroenterologie

“An expert is a person who has made all the mistakes that can be made in a very narrow field.”

Niels Bohr

Documents

Dies ist der Titel der Präsentation - Mucosal Immunology · Titel der Präsentation / Name Referent/-in 2 Gastroenterologie Impact? “Man should strive to have his intestines relaxed