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Thought of the day:
Once you start asking questions, the ignorance is gone.
- Mary Astor
1/7/2015 Dr SK Jain Prof Surgery MAMC
Peptic ulcer diseaseA journey through history
Prof. Dr. Sudhir. K. Jain
1/7/2015 Dr SK Jain Prof Surgery MAMC
Peptic Ulcer Disease:
Presented By:
Dr. Sudhir. K. Jain, M.S, MBA(HCA), FRCS, FICS, FIAS.
Professor of Surgery,
Maulana Azad Medical College and Associated Lok Nayak Hospital,
New Delhi.
With Credits to:
Dr. Vishnuraja, PG2, Dept of Surgery, MAMC.
Dr. Ronal Kori, PG2, Dept of Surgery, MAMC.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Peptic ulcer-What does it mean?
• Peptikos (Greek) - related to digestion
• Ulcer involving the upper digestive tract (Stomach and duodenum) is named as Peptic ulcer.
1/7/2015 Dr SK Jain Prof Surgery MAMC
How does it present? Usually,
• Abdominal pain, mainly in the epigastric region.
• Burning in nature, Non radiating or may be radiating to back.
• Showing periodicity- No pain for weeks to months.
• Gastric ulcer- Pain associated with meals hence anorexia and weight loss.
• Duodenal ulcer- Pain 2-3 hrs after the meal and at night which awakes the patient. No weight anorexia or weight loss.
• Nausea associated with bloating sensation
1/7/2015 Dr SK Jain Prof Surgery MAMC
Gastric Ulcer Duodenal Ulcer
Less common Most common
Common in lesser curvature and prepyloric region.
Common in the 1st part of duodenum.
Recurrent vomiting is common. Vomiting not common.
Weight Loss Weight gain
Increased chance of Malignancy Never become malignant
Tenderness in epigastrium. Tenderness in right hypochondrium.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Complications
• Perforation
• Bleeding
• Obstruction
• Penetration
• Malignant change (Gastric ulcer)
1/7/2015 Dr SK Jain Prof Surgery MAMC
He who sees things grow from the beginning will have the best view of them.
-Aristotle
1/7/2015 Dr SK Jain Prof Surgery MAMC
Search for the Cause of Pain:
• 1500- Autopsies were allowed to perform.
• 1586- Marcellus Donatus demonstrates Gastric ulcers in autopsy.
• 1688- Murault observes duodenal ulcers.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Henrietta, King Charles I daughter:
Ah! What a pain!! I must have been poisoned.
Autopsy done, which showed Duodenal perforation.
1st documented case of ulcer perforation.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Stress theory of Ulcer: Early 20th century
• Early part of the 20th century pathophysiology, ‘Psycho somatic stress’ as the cause of Ulcer.
• Don’t Worry OR you will get ulcer.
Logic:
• Increasing peptic ulcer case trend observed in the 20th century.
• Two World Wars in 20th century and the Great depression.
• Famous Freudian thoughts prevalent in the period.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Acid and Pepsin theory of Ulcer: Early 20th century
The cause of peptic ulcer- is the digestion by acid and pepsin of the oesophageal, gastric, duodenal or intestinal mucosa’.
‘No Acid, No Ulcer’- Schwartz 1910.
So simple, Isn’t it????
Solution: Reduce gastric acid !!………..How?
1/7/2015 Dr SK Jain Prof Surgery MAMC
How to reduce gastric acid? Before 1960s
1912-Prescription sheet
• Bed rest
• Bland diet
• Milk
• Alkali
• Bismuth
• Morphine
Continued for months……..
1/7/2015 Dr SK Jain Prof Surgery MAMC
Patient Cured Medically? No! Then, Go for Acid reducing surgery!!
1/7/2015 Dr SK Jain Prof Surgery MAMC
Surgical Anatomy: Stomach
Stomach is divided into: fundus, body, pyloric antrum and pylorus.
Fundus is dome shaped. It lies above a line drawn horizontally from the incisura cardiaca to the greater curvature.
Body extends from the fundus to the incisura angularis.
Pyloric antrum is the continuation of the body and it narrows to become the pyloric canal (1–2 cm long), which terminates at the pyloric orifice.1/7/2015 Dr SK Jain Prof Surgery MAMC
Surgical Anatomy: Duodenum
Pyloric orifice opens into the first part of the Duodenum.
Duodenum is divided into four parts.
Ist part is horizontal, deep to posterior wall lies Gastroduodenal artery.
IInd part is vertical, contains the major and minor duodenal papilla.
IIIrd part is horizontal, above which lies the superior mesenteric vessels.
IVth part continues as the jejunum at the duodenojejunal flexure.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Physiology of HCl secretion:Parietal cells in the Fundus and body of stomach secrete HCl.
Antrum of stomach secretes Gastrin,Gastrin stimulates ECL cells to secrete Histamine.
Histamine acts on H2 receptors on Parietal cell to stimulate HCl secretion.
HCl secretion is also stimulated by Acetyl choline from Vagal stimulation and partly directly by Gastrin.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Vagus Nerve and Acid
Ivan Pavlov and Classical conditioning
• Vagal Nerve stimulation cause Cephalic phase of gastric acid secretion.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Gastrin and Acid
• Antrum of the stomach secretes Gastrin
• Body of the stomach secretes HCland Pepsinogen
• Gastrin stimulates HCl secretion
1/7/2015 Dr SK Jain Prof Surgery MAMC
Billroth I gastroduodenal anastomosis
• Antrectomy (Removing antrum)
• Gastro duodenal anastomosis for bowel continuity.
• Achievement: Acid secretion reduced
• Problem: More mortality and morbidity with the surgery
1/7/2015 Dr SK Jain Prof Surgery MAMC
Billroth II gastrojejunal anastomosis
• Antrectomy (Removing antrum)
• Gastrojejunal anastomoses for bowel continuity
Achievement: No duodenal ulcer
(No acid pass through duodenum!)
Problem: Stoma ulcer (Oops! Jejunum is now acid exposed)
1/7/2015 Dr SK Jain Prof Surgery MAMC
Truncal vagotomy
• Anterior and posterior vagal trunks severed.
Achievement: No vagal acid stimulation
Problem: Gastric stasis
1/7/2015 Dr SK Jain Prof Surgery MAMC
Gastric stasis
• Crow’s Foot:
• Relaxes pyloric sphincter when stomach contracts.
• Loss of sphincter relaxation causes gastric stasis.
• Solution???
1/7/2015 Dr SK Jain Prof Surgery MAMC
Drainage procedure – Cut the sphincterHeineke Mikulicz Pyloroplasty
• Cut the Pylorus transversely
• Suture it longitudinally
• Sphincter action is lost!!
1/7/2015 Dr SK Jain Prof Surgery MAMC
Drainage procedure – Bypass the Sphincter
Gastro Jejunal anastomosis
• Sphincter bypassed!!
1/7/2015 Dr SK Jain Prof Surgery MAMC
Highly selective vagotomy
• Only the parietal cell mass of the stomach is denervated.
• Nerve of laterjet is spared.
Achievement:
• Acid secretion is reduced.
• Pylorus function preserved.
• No need for drainage procedure.
1/7/2015 Dr SK Jain Prof Surgery MAMC
What is Selective Vagotomy?
• Trunk of the vagal nerve is cut after sparing the Hepatic and Coeliac branches.
• Nerve of laterjet is not spared.
• Hence a drainage procedure is needed.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Completion of Vagotomy!!!
Intra Operative tests:
1. Controlled trial of Grassi
2. Burge test
Post Operative tests:
1. Hollander test
2. Congo red test
3. Modified sham feeding
1/7/2015 Dr SK Jain Prof Surgery MAMC
Completion of Vagotomy!!!
Hollander Test:
After the surgical procedure is done, insulin is administered to cause hypoglycemia.
If vagotomy is complete, the acid output from the stomach following administration of insulin is less than that before insulin administration.
If the reverse is true, vagotomy is incomplete is likely.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Modified Johnsons classification and Operative Options for Gastric Ulcer:
1/7/2015 Dr SK Jain Prof Surgery MAMC
Problems of surgery!
• Morbidity associated with surgery
• Dumping syndrome (Associated with rapid gastric emptying)
• Anemia (Poor Iron absorption due to lack of gastric acid)
• Malabsorption (Rapid gastric emptying and diarrhea)
• Stomal ulcers
• Diarrhoea (Post vagotomy)
1/7/2015 Dr SK Jain Prof Surgery MAMC
Question not explained!!! Number 1
• Hyperacidity is associated with duodenal ulcers and prepyloric ulcers.
• But, Gastric ulcer patients have relatively normal gastric acid levels.
Then what causes ulcer?
1/7/2015 Dr SK Jain Prof Surgery MAMC
Question not explained!! Number 2
• Peptic ulcer was there even before 2000 years. But……..
• Why Peptic ulcer incidence was increasing in 20th century?
Stress is the real reason???? Or May be others????
1/7/2015 Dr SK Jain Prof Surgery MAMC
Discovery of Pain Killers and Ulcer:
Discovery of NSAIDS in 20th century and rampant usage for pain.
No food during World War…but Cheap Cigarettes…YES you can get.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Loss of Balance = Ulceration
AcidPepsin
SmokingAlcoholNSAIDS
MucousHCO3 secretion
Blood flowRegeneration
Prostaglandins
1/7/2015 Dr SK Jain Prof Surgery MAMC
NSAIDS and Ulcer
PHOSPHOLIPID
ARACHDONIC ACID
PG E2
Steroids
NSAIDS
HCO3 excretion1/7/2015 Dr SK Jain Prof Surgery MAMC
Break through: The discovery of H2 Blockers:
1st
Advertisement in 1976
- Smith Kline
1/7/2015 Dr SK Jain Prof Surgery MAMC
Discovery of Cimetidine and Ranitidine: 1970
CimetidineRanitidine
1/7/2015 Dr SK Jain Prof Surgery MAMC
Every thing is understood!! That’s what the scientists at that time thought!!!
But!!
History repeats Itself!!!
1/7/2015 Dr SK Jain Prof Surgery MAMC
The Missed ‘Observation’!! 1924
‘Urease’ in gastric mucosa!
1924- Luck and Seth discover Urease in the human stomach, which they believe is naturally occuring.
No further questions asked…What a Pity!!
1/7/2015 Dr SK Jain Prof Surgery MAMC
One more question NOT ASKED!!
• Bismuth?!!
• Bismuth compounds were in use for treatment of Peptic ulcer since 1786.
• How does it work, even though it does not acts on gastric acidity!!?
1/7/2015 Dr SK Jain Prof Surgery MAMC
What is ‘Discovery’?
Discovery consists of
seeing what everybody has seen
and
thinking what nobody has thought.
-Albert Szent Györgyi, 1937 Nobel Laureate in Physiology and Medicine
1/7/2015 Dr SK Jain Prof Surgery MAMC
Infective Theory of Peptic Ulcer: 1982
In 1982, Robin Warren and Barry Marshall isolated a new bacterium and showed that it caused gastritis and stomach ulcers, diseases that affect millions of humans worldwide.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Infective Theory of Peptic Ulcer: 1982
At that time (1982/83) the conventional thinking was that no bacterium can live in the human stomach as the stomach produced extensive amounts of acid which was similar in strength to the acid found in a car-battery.Marshall & Warren literally “re-wrote” the text-books with reference to what causes gastritis & gastric ulcers.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Campylobacter pyloridis @Campylobacter pylori @Helicobacter pylori (Current name)
Produces Urease which splits Urea and creates Alkaline environment and survives in Acidic environment of the Stomach.
_ Basis of Urea Breath Test.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Investigation for Peptic Ulcer:UGI endoscopy.
Gastric Ulcer:
More common along the lesser curvature and pre pyloric region.
Biopsy should be taken in view of suspected malignancy.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Investigation for Peptic Ulcer:UGI endoscopy.
Duodenal Ulcer:
In the duodenum, care must be taken to view all of the first part as it is more common.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Tests for H.pylori:
• Urea breath test.
• Serological tests based on ELISA are available.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Treatment Goals:
• Gastric Ulcer: Complete ulcer healing, since non healing gastric ulcers may be associated with malignant changes.
• Duodenal Ulcer: Symptomatic relief is the minimum goal.
1/7/2015 Dr SK Jain Prof Surgery MAMC
Conventional First-Line Triple Therapies – (Twice-Daily PPI-Based Triple Therapies)
Cure rate 90%:with 2 weeks treatment in the U.S.; 1 week Treatment outside U.S.
• Omeprazole 20 mg bid or Lansoprazole 30 mg bid
• Clarithromycin 500 mg bid
• Amoxicillin 1 g bid
• or Metronidazole 500 mg bid if Amoxicillin intolerant
1/7/2015 Dr SK Jain Prof Surgery MAMC
Traditional Bismuth-Based Triple Therapy (also for Penicillin Allergic Patients)
Cure rate 80% with 2 weeks Treatment (USA) ;
Cure rate outside U.S.A.: 90% with 1-2 weeks Treatment
• De-Nol [Colloidal bismuth subcitrate ]* 120mg qid outside U.S.)• Tetracycline 500 mg qid
• Metronidazole 400 mg qid
• Proton Pump Inhibitor (20mg Omeprazole bid or 30 mg lansoprazole. bid
1/7/2015 Dr SK Jain Prof Surgery MAMC
Furazolidone & Bismuth Based (Second Line) Quadruple Therapies
Cure Rate >92% Duration of Treatment 14 days
• Furazolidone 200mg bid
• Colloidal Bismuth Subcitrate (De-Nol) 120mg qid
• Amoxicillin 1000mg bid
• 20mg Omeprazole bid OR 30 mg lansoprazole. bid
1/7/2015 Dr SK Jain Prof Surgery MAMC
Other US-FDA-Approved Dual Therapies
Cure rate 70% at 2 weeks
• Omeprazole 40 mg qid
• Clarithromycin 500 mg tid
Cure rate 80% at 2 weeks
• Ranitidine bismuth citrate 400 mg bid
• Clarithromycin 500 mg tid
1/7/2015 Dr SK Jain Prof Surgery MAMC
Current Indications for Surgery:
1. Ulcer perforation
2. Bleeding (Due to gastroduodenal artery erosion)
3. Obstruction (Chronic fibrotic changes due to peptic ulcer)
1/7/2015 Dr SK Jain Prof Surgery MAMC
• The End?????
• Any Unanswered Questions remaining?????
• Yes.
• What is it??
1/7/2015 Dr SK Jain Prof Surgery MAMC
The Question!!!
• Not all the H.pylori infected people develop Duodenal or Gastric ulcers!!
• Why??
•What is still Hiding????
1/7/2015 Dr SK Jain Prof Surgery MAMC