MASTERCLASS by liaoqinmei

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									THE MANAGEMENT OF
    DYSPEPSIA

   MASTERCLASS


    Friday 22nd July 2011



      Dr Derek Gillen
Consultant Gastroenterologist,
 Gartnavel General Hospital
Dyspepsia

 SIGN 68
• What is dyspepsia?
   DYSPEPSIA IS COMMON
• ~ 40% of UK adults c/o dyspepsia per 6/12
• ~ 1/2 self-medicate
• ~ 1/4 consult their GP per 6/12
    ( i.e.10% of UK adults )
   DYSPEPSIA IS COMMON

• ~30% of UK adults take “dyspepsia
  medicine”/year
             Endoscopy
• ~ 1% of UK population endoscoped p.a.
  (1992)
                 Cases
• 38 ♀; epigastric pain for 6/52
• 38 ♀; upper abdominal pain and nausea
  for 6/52; weight loss 3Kgs
• 49 ♂; epigastric pain for 6/52
• 64 ♂; central upper abdominal pain for
  6/52
   Non-invasive Hp testing as predictor of
 endoscopic diagnosis in dyspeptic patients
                                         Esophagitis
                                            12%
           DU 2%
                                              GU 13%
               GU 2%
      Esophagitis
         17%                    DU 40%

                                                Erosive
                                               duodenitis
                                                  2%
Hp Breath Test negative   Hp Breath Test positive
       (n=136)                   (n=182)

                                      McColl et al, Gut, 1997
     H. Pylori Test and Eradicate versus
   Prompt Endoscopy in Dyspeptic Patients
500 primary care patients (18 - 88 years)
- epigastric pain for > 2 weeks
- No sinister symptoms
                         Randomised

         HP Breath Test         Endoscopy
                 Outcome assessed at 1 year
Conclusion
- H. Pylori test and eradicate as efficient and safe as
  endoscopy
- 6% less patients very satisfied
- Saved ~ 60% of endoscopies            Lassen et al 2000
      Randomised Trial of H. Pylori Breath Test
        versus Endoscopy in Investigation of
          Dyspepsia (including heartburn)
704 patients < 55 years, No sinister symptoms, No NSAIDs
                                Randomised



             BT                                    Endoscopy



     +ve              -ve                    +ve               -ve

HP eradication    Symptomatic         HP eradication    Treatment based
                   treatment                             on endoscopy
                                                          + symptoms
                   Outcome assessed at one year
                                                               McColl et al
                                                               BMJ 2002
       Results of NHSME Trial
•   similar Dyspepsia score
•   similar in GP/OP attendance/prescription
•   similar subsequent Ix
•   similar Patient Oriented Outcomes
•   No difference in safety
     NHSME Dyspepsia Trial
• cost: £363 v £149
        Test and treat for > 55?
-Previous age limit based on increasing incidence of upper GI cancer
with age
- However: - (I) All cancers increase with age
       -
       - (II) no evidence that simple dyspepsia related to Ca
       - (III) patients with simple dyspepsia more likely to have
       underlying curable colorectal vs upper GI cancer
               (Meineche-Schmidt 2002)
-Two large H.pylori test and treat studies had no age cut-off

              (Lassen 2000,Chiba 2002)
-Systematic review found no evidence that an initial course of
empiric therapy adversely affected outcome of underlying cancer

              (Ofman 1999)
  Management of Uncomplicated
         Dyspepsia
• <55 “Test & Treat”
• >55 Probably the same
                                    “INDIGESTION”




Consider
                                                                     PREDOMINANT
 Heart                                                               HEARTBURN
 Liver
                                     DYSPEPSIA
 Gall bladder
 Pancreas             No                                            Yes
 Bowel
 NSAIDs etc                                                          MANAGE AS
                                    ALARM FEATURES
                                     Dysphagia
                                                                        GORD
                                
                      Yes           Evidence of GI blood
                                     loss
    REFER TO                        Persistent vomiting
    HOSPITAL                        Unexplained weight loss
   SPECIALIST                       Upper abdominal mass
                                                 No

                         UNCOMPLICATED DYSPEPSIA
                       Consider
                        Lifestyle
                        Antacids / H2RA


                            Persistent / recurrent symptoms



       Hp Test +ve                     Hp Test
                                                                  Hp Test -ve



                            Persistent / recurrent
       Eradicate Hp
                            symptoms despite
                            confirmed eradication

                                                                     Age
      Asymptomatic
                                                      <55
                                                                           >55


                              Manage as functional             Consider referral to
                                  dyspepsia                     hospital specialist
Upper GI cancer in uncomplicated dyspepsia vs
             sinister symptoms

                     Cancers     No spread       Survival
Simple dyspepsia       5            0%              20% ( 1 alive at
                                                 30 months)
Sinister symptoms      149         16%              16%
                                                 (24 alive at 3.3yrs)


                     Cancers     No spread       Survival
Simple dyspepsia       9            33%             11% ( 1 alive at
                                                 5 years)
Sinister symptoms      77           31%             16%
                                                 (13 alive at 5yrs)


    Curable cancers detected by investigating patients with
                    Simple dyspepsia = 3
                    Sinister symptoms = 37
                                             ( Gillen,Casburn-Jones, McColl )
Absence of alarm symptoms and site of
upper GI malignancy in patients under 55
yrs age (Phull et al, 2003)
                                   NO ALARM SYMPTOMS   ALARM SYMPTOMS

                        180
                        160
                        140
    NUMBER OF PATIENT




                        120
                        100
                         80
                         60
                         40
                         20
                          0
                              OESOPHAGEAL    OG JUNCTION        GASTRIC
Surgery in patients <55 yrs age without alarm symptoms


                              PALLIATIVE SURGERY (10)
NO SURGERY (8)




       NOT RECORDED (1)        CURATIVE SURGERY (2)
                               (1 patient <45 yrs age)
        Which HP test?

• Pre -treatment diagnosis
 –serology, C-UBT, faecal antigen
• Post eradication test
 –C-UBT (and faecal antigen)
        H.Pylori and Socio-Economic Status
                 in West of Scotland
           (Study of 1,428 random sample)
           100


            80
Prevalence
of H. Pylori 60


            40


            20


             0
                  I   II   IIIn    IIIm   IV   V

                           Social class
             H Pylori positive
• Eradicate:-First-line Rx:
  – One week course
  – PPI + 2 antibiotics give consistently high
    eradication rates:
     • Heliclear
     • Helimet
     • Lanso/MTZ/clarithro (penicillin-sensitive)
          2nd and 3rd line Rxs
• Pragmatic: if Heliclear → Helimet
• Quadruple Rx:
  – Bismuth, PPI, tetracycline and metronidazole
• Sequential therapies:
  – PPI and amoxycillin 1G 2x/day for 5/7→
    PPI/tinidazole 500/clarithro 500 2x/day for 5/7
    v triple Rx for 1/52
  – > 94% v 76% eradication
          2nd and 3rd line Rxs

• Other antibiotics: levofloxacin, rifabutine,
  furozolidone

• ? Cultures and sensitivities before 3rd line
  Who else to eradicate HP in?
• Maastricht III:
   –   DU
   –   GU
   –   Maltoma
   –   Following gastric Ca resection
   –   ITP
   –   Atrophic gastritis
   –   NUD
   –   FDRs of distal gastric ca patients
   –   Unexplained IDA
   –   Before NSAIDs
   –   Pts on long-term aspirin (who develop ulcers/bleeds)
   –   “At the patient`s request (after discussion of risks and benefits)”
  HP-ve/ Functional Dyspepsia

• as with other functional GI disorders (eg IBS),
  effective treatments are lacking:
  – PPIs benefit about 10% of patients (↑ in
    uninvestigated)
  – prokinetics are of uncertain benefit
  – ? visceral analgesia
                 Cases
• 38 ♀; epigastric pain for 6/52
• 38 ♀; upper abdominal pain and nausea
  for 6/52; weight loss 3Kgs
• 49 ♂; epigastric pain for 6/52
• 64 ♂; central upper abdominal pain for
  6/52
                                    “INDIGESTION”




Consider
                                                                     PREDOMINANT
 Heart                                                               HEARTBURN
 Liver
                                     DYSPEPSIA
 Gall bladder
 Pancreas             No                                            Yes
 Bowel
 NSAIDs etc                                                          MANAGE AS
                                    ALARM FEATURES
                                     Dysphagia
                                                                        GORD
                                
                      Yes           Evidence of GI blood
                                     loss
    REFER TO                        Persistent vomiting
    HOSPITAL                        Unexplained weight loss
   SPECIALIST                       Upper abdominal mass
                                                 No

                         UNCOMPLICATED DYSPEPSIA
                       Consider
                        Lifestyle
                        Antacids / H2RA


                            Persistent / recurrent symptoms



       Hp Test +ve                     Hp Test
                                                                  Hp Test -ve



                            Persistent / recurrent
       Eradicate Hp
                            symptoms despite
                            confirmed eradication

                                                                     Age
      Asymptomatic
                                                      <55
                                                                           >55


                              Manage as functional             Consider referral to
                                  dyspepsia                     hospital specialist
GORD
            GORD is common
• Prevalence:
  – UK
     • 4-9% daily
     • ~ 20% weekly
• GORD has increased fivefold since 1977
  Bardhan KD et al. Gut 2000
             GORD – Prevalence

                 Secondary
                care referrals
Presenters
                             Total population with GORD




                             Non-presenters



                                       Kinnear M et al. Pharmaceutical Journal 1999.
   Prevalence of GORD symptoms
           A systematic review of studies

Heartburn and/or
    regurgitation

       Heartburn

   Regurgitation
Upper abdominal
symptoms

                    0   10   20   30 40 50 60 70                      80       90 100
                                   Prevalence range (%)



                                          Heading RC. Scand J Gastroenterol 1999; (Suppl 231).
                    GORD
• Extra-Oesophageal Manifestations:
  – Middle ear/Eustachian tube: Glue ear, otalgia
  – Nasal/sinusal: Chronic sinusitis
  – Oral: Dental erosions, aphthous ulcers,
    halitosis
  – Pharynx/larynx: Pharyngitis, chronic laryngitis,
    laryngospasm, cancer, globus
  – Airways: Chronic cough, aspiration
    pneumonia, asthma
                     GORD and Quality of Life
                80

                70

                60     64%
% of patients




                50

                                              48%
                40

                30
                                                                                    29%
                20                                                   25%
                                   22%
                10                                     14%

                0
                     Symptoms     Interests   Sleep    Sex life      Sport +      Concentrating
                     unbearable                                      exercise        on job
                                                      Figures quoted from UK respondents (n=201).
      Erosive oesophagitis
    Grade A           Grade B




    Grade C           Grade D
A             B          D
Acid suppression v healing of
     reflux oesophagitis

                               Results of a meta-analysis
                      100
Patients healed (%)




                      80

                      60
                                                         Correlation coefficient=0.87
                                                                   (p<0.05)
                      40

                      20

                       0
                           2   4   6     8    10    12      14     16       18       20       22
                                       Duration intragastric pH>4 (hours)
                                                                  Bell NJ et al. Digestion 1992; 51 (suppl 1): 59-67.
• Are there differences between PPIs in
  their ability to keep intragastric pH >4?
               Acid suppression at day 5

                     esomeprazole, 40mg once daily                             n=36              p<0.001
Lind et al
                   omeprazole, 20 mg once daily


                     esomeprazole, 40mg once daily                             n=31              p<0.001
Wilder-Smith
et al               pantoprazole, 40 mg once daily


                     esomeprazole, 40mg once daily                             n=20              p<0.001
Thomson
et al               lansoprazole, 30 mg once daily


                    esomeprazole, 40mg once daily                              n=33              p<0.0001
Wilder-Smith
et al              rabeprazole, 20 mg once daily

               0          4            8              12                 16               20              24
                              time pH>4 (h)
                                                     Lindberg P et al. Aliment Pharmacol Ther 2003; 17: 481-488.
• Any differences in clinical efficacy?
                Healing of reflux oesophagitis
                      at 4 and 8 weeks
                                             p<0.001
                100                                                       esomeprazole
                                          94.1                            40mg od (n=654)
                              P<0.05
Patients healed (%)




                      80                           86.9
                                                                          omeprazole
                           75.9                                           20mg od (n=650)
                      60           64.7

                      40

                                                                         (Cumulative life table, ITT analysis)
                      20


                       0
                             4 weeks        8 weeks

                                            Kahrilas PJ et al. Aliment Pharmacol Ther 2000; 14: 1249-1258.
Healing of reflux oesophagitis at 8
               weeks                                         p=ns

                                          100                                     p<0.05
                                                                                                         p=0.0002
  % of patients in remission at 8 weeks




                                                                                                                                   p=0.0023
                                                    97.2%
                                          80                    97%
                                                                               92%
                                                                                                      88.3%
                                                                                                                                                            esomeprazole 40mg
                                                                                        91%                                   81.4%
                                          60                                                                   77.3%
                                                                                                                                                            lansoprazole 30mg
                                                                                                                                        64.4%
                                          40


                                          20                                                                                                       (Life table rates, ITT analysis)



                                           0
                                                esomeprazole lansoprazole esomeprazole lansoprazole esomeprazole lansoprazole esomeprazole lansoprazole
                                                40mg od      30mg od      40mg od      30mg od      40mg od      30mg od      40mg od      30mg od
                                                (n=962)      (n=916)      (n=1022)     (n=1054)     (n=482)      (n=477)      (n=158)      (n=169)
                                                     Mild disease             Mild disease         Moderate disease Severe disease
                                                       grade A                  grade B                grade C         grade D


                                                                                                                                   Castell DO et al. Am J Gastroenterol 2002
                       Maintenance of healed reflux
                           oesophagitis at 6/12
                             100            p=ns
                                                                                                                                                 esomeprazole 20mg
                                                                    p=0.0011
                                                                                                                             p=0.048
% of patients in remission




                                                                                                p=0.044
                              80       87%                                                                                                       lansoprazole 15mg
                                                 84%              83%
                                                                                             75%                         77%
                                                                           72%
                              60
                                                                                                       61%

                              40                                                                                                   50%



                              20


                               0
                                   esomeprazole lansoprazole esomeprazole lansoprazole   esomeprazole lansoprazole   esomeprazole lansoprazole
                                   20mg od      15mg od      20mg od      15mg od        20mg od      15mg od        20mg od      15mg od
                                   (n=232)      (n=229)      (n=269)      (n=278)        (n=95)       (n=82)         (n=19)       (n=20)

                                        Mild disease               Mild disease          Moderate disease               Severe disease
                                          grade A                    grade B                 grade C                       grade D

                                                                                                                Lauritsen K et al. Aliment Pharmacol Ther 2003.
Symptom relief at 6 months

                100
                           p<0.01             p<0.001              p<0.05
                 90
                 80
                         78%                 81%                80%
                 70
% of patients




                                                                        75%
                               71%                 72%
                 60
                 50
                 40
                 30
                 20
                 10
                  0
                      Heartburn         Acid regurgitation      Epigastric pain

                          esomeprazole 20mg (n=615 )         lansoprazole 15mg (n=609)




                                                                Lauritsen K et al. Aliment Pharmacol Ther 2003.
                 GORD
• Who to Investigate?
                 Epidemiology
• Prevalence:
  –   ~ 3% of the population
  –   ~ 8% of OGD patients
  –   ~ 12% of GORD patients
  –   ~ 36% of pts with oesophagitis
• Incidence:
  – ↑ 0.08% p.a
• Mean age at dx:
  – 62 (65% males)
  – Rare under 40 in studies
             Natural History
• Outcome for CLO patients:
  – NB Survival rates ~ identical for age and sex-
    matched controls
  – Dutch study: 166 pts with 1440 yrs of f/u:
    • 79 deaths (48%)
    • 2 deaths due to oesophageal ca (1%)
         Screening for CLO
• Who?
 – Heartburn patients?
   • “benefit is so unlikely that endoscopy … cannot be
     recommended”
 – Chronic Heartburn pts (> 50)?
   • “… cannot be recommended”
                 GORD
• How to Investigate?
  – Empirical Rx
  – OGD
  – Ba Meal
  – 24 hour pH and Manometry
              Management
• Lifestyle Factors:
  – Weight Loss
  – stop smoking
  – ↓ alcohol/fatty foods/ chocolate/ tea/coffee
• Domestic adjustments:
  – Avoid precipitating foods!
  – Elevate head end of bed
  – Eat small amounts regularly
         Medical Therapies
• Antacids and alginates
• H2 receptor antagonists (H2As)
• Proton pump inhibitors (PPIs)
         Proton pump inhibitors
• Accumulate selectively in
  the acid space (canaliculi)
  of the parietal cells
• Undergo an acid-catalysed
  rearrangement to the
  active drug
• This cationic sulfenamide
  binds irreversibly with
  sulphydryl groups on the
  proton pump causing
  inhibition
        PPIs – side-effects

• Diarrhoea
• Rash
• Headache
              Surgical Rx
• Fundoplication:
  – Open
  – Laparoscopic
• For whom?
                   PPIs
• What is gastric acid for?
• Other potential adverse reactions of
  profound acid inhibition?
        Possible Adverse
      Consequences of PPIs
• Hypergastrinaemia:
  – Rebound Hypersecretion
  – Tolerance
  – Carcinoid Tumours
• Hypochlorhydria:
  – Increased risk of enteric infection
  – Bacterial Overgrowth
  – Increased nitrite/ Decreased Vit C
Possible Adverse Consequences of
              PPIs
• Metabolic:
  – Hyponatraemia
  – Hypomagnesaemia
  – ?? Osteoporosis
  – ??? B12 deficiency
  – ??? Fe Deficiency
           GORD-Summary
•   Common!!!
•   Heartburn most common symptom
•   Ix: Empirical>OGD>BaM>pH/manometry
•   Rx: OTC>>PPI>>>Surgery
                    48 ♀
• Heartburn and regurgitation for 5 years;
  nocturnal choking
  – Self-medication with Rennie`s for 3 years
  – Omeprazole 20 mgs for 18 months
  – 40 mgs for 4/12
  – Metaclopramide 10mgs 3x/day added
  – > Referred
• At vetting key questions?
  – Alarm symptoms; NSAIDs
                    48 ♀
• Recommendation:
  – Increased PPI: Esomeprazole 40mgs 2x/day
  – Bedtime alginate
  – Review
• Improved, but still fortnightly LPR
• Way forward?:
  – pH and manometry and endoscopy
  – fundoplication
                   58 ♂
• Intermittent dyspepsia for 30 years,
  treated with H2As and antacids
• Daily vomiting for 6 weeks
• Options?
  – Targeted access endoscopy
  – DU found; CLO +ve
                        58 ♂
• Treatment?
  – Triple Rx (Heliclear)
• Symptom review
  – Still symptomatic
• What now?
  – UBT
  – > Still +ve
• What now?
                     58 ♂
• Options:
  – Further triple Rx: Helimet
  – Quadruple Rx
  – Alternative antibiotic: e.g. tetracycline 500mgs
    3x/day
• Helimet agreed: symptom resolution
                   45 ♀
• Epigastric pain and vomiting; weight loss 2
  stones in 5/12; ? Partial response to OME
  20
• OGD: Normal
• D2 Biopsies: Consistent with coeliac
                  45 ♀
• No response to higher dose PPI/GFD
• pH and manometry normal
• BaM and FT: Consistent with coeliac
  disease
• MRI Abdomen: consistent with coeliac
  disease
• Gastric Emptying study: Gastroparesis
                   45 ♀
• Repeat OGD: Consistent with partially
  treated coeliac
• Continuing weight loss, pain and sensori-
  motor neuropathy
• Weight gain with NJ feeding; sustained
  NG feeding, analgesia
                    45 ♀
•   Perforated TI
•   Histology non-specific
•   ? Ulcerative jejuno-ileitis
•   Rx: steroids and azathioprine; NG Feeding
•   Well for 3/12
                   45 ♀
• Further abdo pain
• Investigations?
• CT of abdomen: Coeliac and mesenteric
  stenosis
• No improvement with stenting
• Transferred to a National Intestinal Failure
  Centre
• Attempted revascularisation

								
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