Gastroenterology Flashcards
Define Crohn’s disease
Crohn’s disease is a form of inflammatory bowel disease characterised by transmural (causes bowel wall to thicken) inflammation of the gastrointestinal tract (anywhere from mouth to anus), with the terminal ileum and colon most commonly affected.
Describe the epidemiology of Crohn’s disease
Epidemiology Jewish people, less common than UC, smoking increases risk 2-4x, more females than males, age 20-40
Describe the aetiology of Crohn’s disease
- Environmental factors e.g. smoking
- Genetic factors e.g. CARD15/NOD2 mutation
- Pathogens e.g. Mycobacterium paratuberculosis, Pseudomona and Listeria species
Describe the risk factors for Crohn’s disease
- Family history
- Smoking
- NSAIDs may exacerbate
- Stress and depression
Describe the pathophysiology of Crohn’s disease
Dysfunctional unregulated inflammatory response which causes tissue damage. Inflammation starts in the mucosa and progresses to involve deeper layers and forms granulomas (large masses of immune cells) and ulcers. The granulomas extend to involve all layers of the GI wall (transmural).
Describe the clinical manifestations of Crohn’s disease
Follows a relapsing and remitting course
- Signs
- Abdominal tenderness
- Fever
- Rectal examination: blood, skin tags, erythema, fissures, fistulas, ulceration
- Aphthous mouth ulcers
- Symptoms
- Diarrhoea
- Abdominal pain (most commonly in RLQ where the ileum is)
- Bloody stools: more common in ulcerative colitis
- Delayed puberty and failure to thrive: in children
- Weight loss
- Systemic symptoms:
- Anorexia
- Fever
- Malaise
- Lethargy
Describe some extra-intestinal manifestations of Crohn’s disease
More common in patients with colitis and peri-anal disease
- Cutaenous
- Erythema nodosum - inflammatory disorder affecting subcutaneous fat.
- Pyoderma gangrenosum - rapidly enlarging, very painful ulcer.
- Musculoskeletal
- Pauci-articular arthritis: asymmetrical
- Osteoporosis
- Axial arthritis
- Polyarticular arthritis: symmetrical
- Clubbing
- Sacroiliitis
- Ankylosing spondylitis
- Eyes
- Episcleritis - inflammation of your episclera
- Uveitis - eye inflammation
- Conjunctivitis
- Hepatobiliary
- Primary sclerosing cholangitis
- Autoimmune hepatitis
- Gallstones
- Other
- Calcium oxalaterenal stones
Describe the primary investigations for Crohn’s disease
1st line FBC: raised WCC, platelets, CRP&ESR, anaemia. Faecal calprotectin raised (indicates IBD). pANCA negative. Stool samples (rule out infection). LFTs: hypoalbuminemia. Low iron, vitamin B12 and folate (B9) levels.
What is the gold standard investigation for Crohn’s disease
Colonoscopy and biopsy (granulomatous transmural inflammation. Skip lesions, cobblestone appearance. Strictures “string sign”)
What are other investigations to consider for Crohn’s disease
Imaging: abdominal USS/x-ray/MRI (strictures and fistulae)
What are the differential diagnosis for Crohn’s disease
Ulcerative colitis, irritable bowel syndrome, diverticulitis, indeterminate/infectious/radiation colitis
Describe the general advice for Crohn’s disease
- General advice
- Advice regarding smoking cessation is extremely important
- There is some evidence to suggest that use of NSAIDs or the combined oral contraceptive pillmayincrease the risk of relapse. May consider ceasing use.
Describe the management for Crohn’s disease
For remission:
Mild to moderate disease: 1. oral corticosteroids (prednisolone).
Severe disease: IV hydrocortisone. If steroids don’t work add TNF-a inhibitor (infliximab) or immunosuppressants (azathioprine, methotrexate)
Maintaining remission: azathioprine, mercaptopurine
Surgery if no response to treatment: resection or worst affected bowel, temporary ileostomy (allows time for affected areas to rest). Surgery is not curative for Crohn’s as entire bowel is affected.
Also: stop smoking, replace iron/B12/folate deficiencies, antibiotics for perianal disease
Describe the management for maintaining remission for Crohn’s disease
Patients can either have no treatment, or pharmacological therapy depending on their risk of relapse. Glucocorticoids should not be offered
1st line:Azathioprine or Mercaptopurine
2nd line:Methotrexate, Infliximab, Adalimumab
Post-surgery: consider azathioprine, with or without methotrexate
Describe the complications for Crohn’s disease
Bowel: obstruction, malabsorption, toxic megacolon, perforation, fistula, colorectal cancer. Perianal disease. Extraintestinal: Oral aphthous ulcers, uveitis, episcleritis, erythema nodosum, pyoderma gangrenosum, arthritis, ankylosing spondylitis
Describe the prognosis for Crohn’s disease
This is a life-long condition, and most people will require medical management indefinitely.
There are multiple genetic and environmental factors that will determine the frequency of flare-ups and subsequent remission length.
Crohn’s NESTS
No blood or mucus
Entire GI tract
Skip lesions on endoscopy
Terminal ileum most affected and transmural inflammation
Smoking is a risk factor
Define ulcerative colitis
Type of inflammatory bowel disease. Inflammation of the walls of the colon and rectum, and ulcers, with periods of exacerbation and remission. CLOSE UP: Continuous inflammation (no skip lesions), Limited to colon and rectum, Only superficial mucosa affected, Smoking is protective, Excrete blood and mucus, Use aminosalicylates, Primary Sclerosing Cholangitis
Describe the epidemiology of ulcerative colitis
- Ulcerative colitis has a bimodal age distribution at approximately 15-25 and 55-70 years of age.
- Prevalence = 100-200/100,000
- Highest incidence and prevalence in Northern Europe, UK and North America
- Affects caucasians and eastern European Jews most
- Is 3 times more common in NON-SMOKERS
Describe the risk factors of ulcerative colitis
- Family history
- HLA-B27
- Caucasian
- Non-smoker
- NSAIDs- associated with flares
- Chronic stress and depression - associated with flares
Describe where ulcers tend to form in ulcerative colitis
UC is a type of inflammatory bowel disease that tends to form ulcers along the inner-surface or lumen of the large intestine, including both the colon and the rectum.
These ulcers are spots in the mucosa and submucosa where the tissue has eroded away and left behind open sores or breaks in the membrane.
Describe the origin of ulcerative colitis
Environmental factors like diet and stresswere once thought to be the culprit but now it’s thought that these are more secondary. UC is now thought to be autoimmune in origin.
Describe the pathophysiology of ulcerative colitis
Inappropriate autoimmune response against colonic flora in genetically susceptible individuals. T cells destroy cells lining the colon which leaves behind eroded areas called ulcers.
Describe the clinical manifestations of ulcerative colitis
- Signs
- Abdominal tenderness
- Fever - in acute UC
- Tachycardia - in acute severe UC
- Fresh blood on rectal examination
- Symptoms
- Diarrhoea
- Blood and mucus in stool
- Urgency and tenesmus (cramping rectal pain)
- Abdominal pain: particularly in left lower quadrant
- Weight loss and malnutrition
- Fever and malaise during attacks
Describe what extra-intestinal manifestations may occur with ulcerative collitis
- Cutaenous
- Erythema nodosum - inflammatory disorder affecting subcutaneous fat.
- Pyoderma gangrenosum - rapidly enlarging, very painful ulcer.
- Musculoskeletal
- Pauci-articular arthritis: asymmetrical
- Osteoporosis
- Axial arthritis
- Polyarticular arthritis: symmetrical
- Clubbing
- Sacroiliitis
- Ankylosing spondylitis
- Eyes
- Episcleritis - inflammation of your episclera
- Uveitis - eye inflammation
- Conjunctivitis
- Hepatobiliary
- Primary sclerosing cholangitis
- Autoimmune hepatitis
- Other
- Cholangiocarcinoma
- Aphthous oral ulcer
- Nutritional deficits
Define fulminant disease in relation to ulcerative colitis
- Fulminant refers to an abrupt and severe onset of a UC flare
- Suggested byoneof the following:
- > 10 bowel movements per day
- Continuous bleeding
- Abdominal tenderness and distention
- Toxicity
- Colonic dilation
- The need for blood transfusion
Describe the primary investigations for ulcerative colitis
- Faecal calprotectin: will be raised; a marker of inflammation in the gastrointestinal tract and helps differentiate from irritable bowel syndrome
- FBC:leukocytosis during a flare; may demonstrate anaemiafrom PR bleeding
- LFTs:should be checked every 6-12 months to screen for PSC; low albumin may suggest protein-losing enteropathy
- CRP/ESR: raised during acute inflammation of the bowel (flare)
-
Colonoscopy and biopsy: GOLD STANDARD and allows for biopsy
- Red and raw mucosa with widespreadshallow ulceration
- No inflammation beyond the submucosa, unless fulminant disease
- Lamina propria inflammatory cell infiltrates
- Pseudopolyps: mucosa adjacent to ulcers is preserved, which has the appearance of polyps
- Crypt abscessesdue to neutrophil migration through gland walls
- Goblet cell depletion, withinfrequentgranulomas
Describe the differential diagnosis of ulcerative colitis
Alternative causes of diarrhoea should be excluded e.g. Salmonella spp,
Giardia intestinalis and rotavirus
What is the management for ulcerative colitis dependent upon
Depends on the location and severity of disease.
Describe the general management for ulcerative colitis
- Mild = 1st line aminosalicylate and 2nd line corticosteroids
- Severe = 1st line IV corticosteroid and 2nd line IV ciclosporin
-
Colectomy may be required: leaves patient with J-pouch (can be reversed) or ileostomy.
- J- pouch: ileoanal anastomosis, colon removed and rectum fused to ileum
- Ileostomy: colon and rectum are removed and the ileum brought out on
to the abdominal wall as a stoma
- Maintenance = aminosalicylate, azathioprine, mercaptopurine
- Biologics = may be considered in patients who are intolerant/ not responding to immunomodulation e.g. infliximab, adalimumab, golimumab
Describe the complications of ulcerative colitis
- Toxic megacolon: this is an acute form of colonic distension and patients can become septic and perforate. Requires supportive care, bowel rest, NG decompression and antibiotics. Requires a colectomy if no improvement within 24-48 hours
- Perforation: associated with high mortality
- Colonic adenocarcinoma
- Strictures and obstruction:bowel loops can develop strictures following chronic inflammation and this can lead to bowel obstruction
- Extraintestinal manifestation (refer to signs^)
Describe the prognosis of ulcerative colitis
There does not appear to be an increased rate of mortality in patients with ulcerative colitis. However, the most common cause of death is toxic megacolon. Furthermore, colonic adenocarcinomas develop in 3-5% of patients
Describe the UC CLOSEUP pneumonic for UC
C–Continuous inflammation
L–Limited to colon and rectum
O–Only superficial mucosa affected
S–Smoking is protective
E–Excrete blood and mucus
U–Useaminosalicylates
P–Primary Sclerosing Cholangitis
Describe the symptomatic differences and similarities between UC and Crohn’s disease
UC and Crohn’s both have abdominal pain.
UC has bloody diarrhoea whereas Crohn’s disease is usually non-bloody diarrhoea
UC involves mucus and weight loss
Crohn’s disease involves significant weight loss and aphthous ulcers
Describe the impact smoking has on UC and Crohn’s disease
UC smoking reduces risk
Crohn’s disease smoking increases risk
Describe the differences in pathology between UC and Crohn’s disease
UC starts in the rectum and spreads proximally towards the ileocaecal valve. Never spreads into the small bowel or anus.
Crohn’s disease is any part of the GI tract and skip lesions may be seen. Tends not to involve the rectum
Where is the most common location for both UC and Crohn’s disease
UC rectal involvement is almost universal
Crohn’s disease is terminal ileum
Describe the differences in endoscopic findings between UC and Crohn’s disease
UC - shallow ulcers with pseudopolyps
Crohn’s disease - mucosal inflammation, deep ulcers, skip lesions and cobblestone mucosa
Describe the difference in histology between UC and Crohn’s disease
UC - mucosal and submucosal ulceration only. Crypt abscess with neutrophil infiltration
Crohn’s disease - transmural inflammation, granulomas and goblet cells
Describe the difference in specific extra-intestinal features between Crohn’s and UC
UC - primary sclerosing cholangitis and cholangiocarcinoma (can occur in Crohn’s disease but is much rarer)
Crohn’s disease - gallstones due to reduced bile reabsorption. Calcium oxalate renal stones
What are the shared extra-intestinal features between UC and Crohn’s disease
Arthritis, uveitis, episcleritis, erythema nodosum, pyoderma gangrenosum
Describe the different complications of UC and Crohn’s disease
UC - toxic megacolon and strictures
Crohn’s disease - fissures, fistulas and strictures
What are the risks of colorectal cancer for UC and Crohn’s disease
UC - marked increase
Crohn’s disease - slight increase
Describe the impact surgery has on UC and Crohn’s disease
UC- curative
Crohn’s disease - for complications such as strictures
Define irritable bowel syndrome
Irritable bowel syndrome (IBS) is a chronic condition characterised by abdominal pain associated with bowel dysfunction. It is a functional bowel disorder (there is no identifiable organic disease underlying the symptoms).
- IBS-C - with constipation
- IBS-D - with diarrhoea
- IBS-M - with constipation and diarrhoea
Describe the epidemiology of IBS
- It is very common and occurs in up to 20% of the population.
- Common, in western world around 1 in 5 report symptoms consistent with IBS
- It affects women more than men
- More common in younger adults <40 years
Describe the exacerbating factors for IBS
- Acute gastroenteritis
- Stress
- Menstruation
Describe the pathophysiology of IBS
Abdominal pain:
Patients have “visceral hypersensitivity,” which means that the sensory nerve endings in the intestinal wall have an abnormally strong response to stimuli like stretching during and after after a meal.
Abnormal bowel motility:
Eating FODMAPs (fermentable oligo-, di-, mono-saccharides and polyols) often trigger the symptoms. These unabsorbed short-chain carbohydrates act as solutes that draw water across the gastrointestinal wall and into the lumen.
In addition to triggering visceral hypersensitivity which causes pain, that excess water can also cause smooth muscle lining in the intestines to spasm, and create diarrhoea if the excess water is not reabsorbed back into the body.
In addition, the unabsorbed short-chain carbohydrates are often metabolised by gastrointestinal bacterial flora which produce gas that could trigger more bloating, spasm, or pain.
Describe the clinical manifestations of IBS
Symptoms are chronic: >6 months
- Signs
- General abdominal tenderness may be felt.
- Symptoms
- Fluctuating bowel habit
- Diarrhoea
- Constipation
- Incomplete evacuation
- Urgency
- Mucus PR
- Abdominal pain
- Pain worse after eating
- Improved by opening bowels
- Bloating
Describe the diagnostic criteria for IBS
- Diagnostic criteriaAbdominal pain / discomfort:
- Relieved on opening bowels, or
- Associated with a change in bowel habit
- Abnormal stool passage
- Bloating
- Worse symptoms after eating
- PR mucus
What investigations may be done for IBS
- Exclude other pathology
- Normal FBC, ESR and CRP blood tests
- Faecal calprotectinnegative, excludes inflammatory bowel disease
- Negative coeliac disease serology (anti-TTG antibodies)
- Cancer is not suspected or excluded if suspected: colonoscopy
What are the differential diagnosis for IBS
- Crohn’s disease
- Ulcerative colitis
- Coeliac disease
- Malignancies
What is the lifestyle advice for IBS
- Adequate fluid intake
- Regular small meals
- Reduced processed foods
- Limit caffeine and alcohol
- Low “FODMAP” diet (ideally with dietician guidance)
- Increase fibre if constipation, reduce fibre if diarrhoea
- Avoid sorbitol sweeteners, if diarrhoea
- Eat oats and linseeds if there is a problem with wind
- Trial ofprobioticsupplements for 4 weeks
- Reduce stress
- Increase activity
- Weight loss if obese or overweight
What is the pharmacological management for IBS
- First line
- Loperamidefor diarrhoea
-
Laxatives for constipation.
- Avoidlactuloseas it can cause bloating.
- Linaclotideis a specialist laxative for patients with IBS not responding to first-line laxatives
- Antispasmodics for cramps e.g.hyoscine butylbromide(Buscopan)
- Second line
- Tricyclic antidepressants (i.e. amitriptyline 5-10mg at night)
- Third line
- SSRIs antidepressants
What other options for management of IBS are there
- Peppermint oil can also be used as an antispasmodic
- Cognitive Behavioural Therapy (CBT) is also an option to help patients psychologically manage the condition and reduce distress associated with symptoms.
Describe the prognosis for IBS
Patients with IBS have a normal life expectancy, and there are no long-term complications of their disease.
When should other diagnoses be considered for IBS
- Age >60 years
- History <6 months
- Family history of cancer
- Anorexia
- Weight loss
- Waking at night with pain/ diarrhoea
- Mouth ulcers
- Abnormal CRP and ESR
- Malaena
- Rectal or abdominal mass
Define coeliac disease
Coeliac disease is a systemic autoimmune disorder that affects the small intestine and is triggered by the ingestion of gluten peptides found in wheat, barley, rye and other related grains. Malabsorption is the hallmark of coeliac disease.
Previously known as coeliac sprue.
Describe the epidemiology of Coeliac disease
- The estimated prevalence of coeliac disease in European populations is 1-2%, with a prevalence of 1% in the UK.
- Commoner if Irish
- Usually develops in early childhood but can start at any age. Another peak at 50-60 years.
What are triggers for coeliac disease
Prolamin’s: gliadin in wheat, hordeins in barley and secalins in rye
What are risk factors for coeliac disease
- Family historyof coeliac disease
- HLA-DQ2andHLA-DQ8:95% of patients have HLA-DQ2, and 80% have HLA-DQ8
- Autoimmunity:type 1 diabetes, autoimmune thyroid disease and autoimmune hepatitis
- IgA deficiency:allows increased gluten peptides to circulate in the submucosa
- Down’s syndrome
- Turner’s syndrome
Describe the pathophysiology of Coeliac disease
Type 4 hypersensitivity reaction mediated by T cells.
Gluten breaks down to gliadin which triggers the immune system to produce IgA autoantibodies such as anti-tissue transglutaminase (anti-tTG), and anti-endomysial (anti-EMA) which target the epithelial cells of the small bowel causing villous atrophy, crypt hyperplasia, intraepithelial lymphocytes.
Describe the clinical manifestations for coeliac disease
- Persistent abdominal symptoms:
- Indigestion
- Diarrhoea (watery) or steatorrhoea (pale, floating stools)
- Abdominal bloating or discomfort
- Constipation
- Prolonged fatigue
- Unexpected weight loss
- Failure to thrive in children
- Severe or persistent mouth ulcers
- Dermatitis herpetiformis: itchy vesicular skin eruption caused by IgA antibodies attacking tTG in the epidermis.
- Anaemia secondary to iron, B12 or folate deficiency
- Rarely coeliac disease can present withneurological symptoms:
- Peripheral neuropathy
- Cerebellar ataxia
- Epilepsy
Describe the gold standard investigations for coeliac disease
-
Small bowel histology: endoscopy and duodenal biopsy is thegold-standarddiagnostic test
- All patients with positive serology should be referred for biopsy
- Classic findings include 1) villous atrophy; 2) crypt hyperplasia; 3) an increase in intraepithelial lymphocytes; 4) lamina propria infiltration with lymphocytes
- The Marsh histological classification is used
Describe the first line investigations for coeliac disease
If possible, patients should beona gluten-containing diet for 6 weeks prior to investigations.
ALL new cases of type 1 diabetes are investigated, even if they don’t have symptoms as the conditions are often linked.
- **Tissue transglutaminase antibodies (tTG; IgA) and total IgA:**
- **First-line**serological test is for IgA antibodies against tTG
- Total IgA must also be measured as a small proportion of patients are IgA deficient, which would give a false negative anti-tTG measurement
- **Endomysial antibodies (IgA):**
- **Second-line**serological test and performed if anti-tTG is weakly positive
- **Anti-tTG, endomysial, or gliadin (IgG) antibodies:**
- If patients are**IgA deficient**, then IgG antibodies against tTG, gliadin or endomysium can be measured
- **Anti-casein antibodies**:
- Also found in some patients
What are other investigations to consider with coeliac disease
- FBC: typically a microcytic anaemia. Alternatively, folate or vitamin B12 deficiency can result in macrocytic anaemia
- Nutritional status:25-hydroxy vitamin D, calcium, iron studies, Vitamin B12, folate
- Skin biopsy:if there is evidence of possible dermatitis herpetiformis
- HLA testing:DQ2 or DQ8**testing is only performed in a specialist setting
Describe the management for coeliac disease
Gluten-free diet: this involves the avoidance of the following
- Wheat: bread, pastry and pasta
- Rye
- Barley: beer (whisky is made using malted barley but issafeto drink as gluten is removed in the distillation process)
- Oats: this remains controversial but may be required in some patients
Dietary supplements:
- Patients should receive calcium, vitamin D and iron supplementationifthe patient’s diet is insufficient
Dietician input:
- Patients may be offered input regarding their diet and risks associated with non-compliance with dietary measures
Refer to a specialist:
- If symptoms persist despite a gluten-free diet or significant extra-intestinal manifestations, the patient may require referral to a gastroenterologist
What other management steps may be taken for coeliac patients
Vaccinations:
- Due to functional hyposplenism, coeliac patients are at risk of pneumococcal infection so should all be offered vaccination, with a booster every 5 years;influenza vaccinationis offered on an individual basis
Describe the management for coeliac disease
- Check-ups to instruct and monitor their gluten-free diet adherence.
- DEXA scan to monitor osteoporotic risk
Describe the complications with coeliac disease
Osteopenia, anaemia, malignancy (T cell lymphoma, NHL), vitamin deficiency
Describe the prognosis for coeliac disease
Coeliac disease generally has a very good prognosis, with theresolution of symptoms in up to 90% of patients on a gluten-free diet. Rates of adherence have improved with the increased availability of gluten-free products.
The 10-30% of patients that remain symptomatic often have other intolerances such as lactose, fructose, sucrose, or sorbitol intolerance.
1-2% have refractory coeliac disease.
The importance of a gluten-free diet must be emphasised to patients, as the risk ofmalignancynormalises after a few years of gluten restriction. Villous atrophy and immunology usually reverse on a gluten-free diet.
Describe the layers of the GI tract
Normally, the wall of the entire gastrointestinal tract is made of 4 layers: the inner mucosa (innermost epithelial layer, a middle lamina propria, and outermost muscularis mucosa), the submucosa, a muscular layer, and an outer layer called the adventitia.
Describe the composition of the stomach mucosa
- The epithelial layer is made up of cylindrical cells, which dive into the lamina propria, forming pits (gastric glands).
- Among the cylindrical gland cells, there are different types of secretory cells:
- G cells: secrete gastrin
- Parietal cells: secrete HCl
- Chief cells: secrete pepsinogen
- There are also defence mechanisms:
- Foveolar cells: secrete mucus containing bicarbonate
- Rich in vessels: to get access to O2 and bicarbonate from the blood supply
Describe the composition of oesophageal mucosa
- Made up of stratified squamous epithelium, which is better equipped to resist abrasion from food going down.
- Epithelium doesn’t have defence mechanisms, like the stomach - so it’s more susceptible to acid damage.
- Defence mechanism of the oesophagus:
- Lower oesophageal sphincter: opens to pass food to stomach and closes to prevent acid reflux.
- Saliva also helps to neutralise the acidity
Define gastro-oesophageal reflux disease (GORD)
Reflux of stomach contents into the oesophagus.
Describe the epidemiology of GORD
In Western European and Northern American populations, the estimated prevalence is as high as 10-20%.
Describe the aetiology of GORD
- Lower oesophageal hypotension
- Oesophageal dysmotility
- Gastric acid hypersecretion
Describe the risk factors of GORD
- High BMI
- Genetic association
- Pregnancy
- Smoking
- NSAIDs, caffeine & alcohol
- Other medication (may lower LOS pressure) e.g. antihistamines, calcium channel blockers, antidepressants, benzodiazepines, and glucocorticoids.
- Hiatus hernia: part of the upper stomach pushes up through the diaphragm (lowering pressure of LOS)
- Scleroderma: muscle of the lower oesophageal sphincter is replaced by connective tissue, so it can’t contract properly.
- Zollinger-Ellison syndrome: increased gastrin causes increased HCl secretion
Describe the pathophysiology of GORD
Physiology:
Normally the oesophagus propels food into the stomach by peristalsis. At the gastro-oesophageal junction, a sphincter relaxes to allow food to enter the stomach. This is known as thelower oesophageal sphincter(LOS). After entry, the sphincter contracts to prevent reflux of stomach contents.
If the LOS relaxes inappropriately (becomes loose due to drop in pressure), stomach content willwash back into the oesophagus. This is a normal physiological response in most people. The episodes are brief and do not causes symptoms.
Pathology:
When the pressure of the LOS gets lower, reflux persists for longer, becoming pathological. Persistentacid reflux damages the oesophageal mucosa, causing local inflammation, or oesophagitis. This in turn, causes oedema and erosion of the mucosa, which leads to more complications.
As the epithelium is damaged, it is replaced by scar, making the walls thicker and the lumen narrower (oesophageal stenosis).
As it’s damaged, there may also be a change in the cells of the epithelium (Barret’s oesophagus), and may even eventually lead to adenocarcinoma.
Describe the clinical manifestations of GORD
-
Heartburn
- Usually worse when lying down and after meals
- Regurgitation
- Dyspepsia
- Chest pain/ retrosternal or epigastric pain
- Bloating
- Dysphagia(difficulty swallowing)
- Odynophagia(painful swallowing)
- Nausea and/or vomiting
- Water brash: mouth fills with saliva
- Cough: reflux goes into the respiratory tract
- Hoarse voice: reflux goes into the respiratory tract
Describe the investigations for GORD
- Can be diagnosed based on clinical presentation and based on whether PPI trial would resolve the symptoms
-
pH monitoring
- 24-hour pH monitoring: small tube inserted through the nose and positioned in lower oesophagus. Can be combined with high resolution manometry (assesses motor abnormalities of the oesophagus).
- Wireless pH capsules testing: insertion of pH capsule at gastro-oesophageal junction during endoscopy. Carry recording device to capture episodes. Will naturally fall off wall of oesophagus and pass through GI tract.
-
Endoscopy
- Able to diagnose the presence of oesophagitis, Barrett’s oesophagus or an alternative diagnosis (i.e. oesophageal/gastric malignancy).
- Usually reserved for patients with red flags symptoms, suspected complications, symptoms refractory to treatment or those being considered for surgery.
Describe the red flags for GORD
- New onset dyspepsia(>55 years)
- Weight loss
- Dysphagia
- Upper abdominal pain
- Nausea and vomiting
- Symptoms refractory to treatment
- Anaemia
- Raised platelet count
Describe the differential diagnosis of GORD
- Functional heartburn
- Achalasia(failed relaxation of LOS)
- Eosinophilic oesophagitis
- Peptic ulcer disease
- Non-ulcer dyspepsia
- Malignancy
- Pericarditis
- Ischaemic heart disease
Describe the lifestyle changes patients need to make with GORD
- Weight loss
- Smoking cessation
- Dietary modification: Smaller meals. Reduce tea, coffee, alcohol, spicy foods, fizzy drinks, chocolate
- Patients should avoid eating within two hours of sleep
- Patients should elevate the head of the bed
Describe the medical and surgical management for GORD patients
-
Medical
- PPI: prevent acid production within the stomach through inhibition of H+/K+ ATPases in parietal cells.
- H2 receptor antagonist e.g. ranitidine: reduces stomach acid
- Antacids e.g. gaviscon: neutralise stomach acid
-
Surgical
-
Nissen fundoplication: wrapping the fundus of the stomach around the lower oesophagus to tighten the sphincter
- SE: dysphagia, gas-bloat syndrome (inability to belch/vomit), new-onset diarrhoea
-
Nissen fundoplication: wrapping the fundus of the stomach around the lower oesophagus to tighten the sphincter
Describe the complications for GORD
Oesophageal:
- Typical reflux syndrome
- Reflux chest-pain syndrome
- Reflux oesophagitis(inflammation and damage of oesophageal mucosa, which can lead to ulcers, bleeding and peptic stricture formation.)
- Reflux stricture(narrowing of oesophagus, can cause dysphagia. May require dilatation or stenting.)
- Barrett’s oesophagus(premalignant condition in the oesophagus due to columnar metaplasia)
- Oesophageal adenocarcinoma
Extra-oesophageal:
- Reflux cough syndrome
- Reflux laryngitis syndrome: reflux goes all the way up to throat and down the larynx
- Reflux asthma syndrome
- Reflux dental erosion syndrome: acid refluxes far enough to erode the teeth enamel
- Proposed associations: idiopathic pulmonary fibrosis, sinusitis, etc
Describe the prognosis for GORD
Most patients respond to treatment with proton-pump inhibitors (PPIs). Maintenance PPI therapy is recommended for those who have symptoms when the PPI is discontinued, as well as for those with erosive oesophagitis and Barrett’s oesophagus.
Most patients relapse off PPI therapy but this has to be balanced with the risk of long-term drug use.
Oesophageal adenocarcinoma may be a serious though rare complication of GORD.
Define Barret’s oesophagus
Barrett’s oesophagus describes metaplasia (transformation of one differentiated cell type to another differentiated cell type) of the lower oesophageal lining from stratified squamous epithelium to mucous secreting columnar epithelium with goblet cells.
Barrett’s is classified as short segment (< 3 cm) and long segment (> 3 cm).
Describe the epidemiology of Barret’s oesophagus
- Around 1 in 10 patients who experience GORD have Barrett’s oesophagus on endoscopy
- Estimated to affect 0.9-10% of the general population
- M>F
- More common in Caucasians
Describe the risk factors for Barret’s oesophagus
- Gastro-oesophageal reflux disease:the single greatest risk factor for developing Barrett’s oesophagus
- Age
- Male sex
- Caucasian
- Smoking
- Obesity
- Family history
Describe the pathophysiology of Barret’s oesophagus
The lower oesophagus marks the junction between oesophagus and stomach. Tonic contractions of the lower oesophageal sphincter, coupled with extrinsic compression of the right crus of the diaphragm, are important toprevent acidic stomach content from entering the oesophageal lumen.
These mechanisms are not perfect and a small amount of reflux of stomach content (i.e. the refluxate) is common, but usually not associated with symptoms. Prolonged exposure to the refluxate can lead to symptomaticgastro-oesophageal reflux disease, oesophagitis and erosions.
In addition, chronic damagecan lead to transformation of normal squamous epithelium into metaplasticcolumnar epithelial cells (Barret’s oesophagus)
Metaplasia is an adaptive response to acid in order to protect the oesophageal wall, however, it also predisposes to subsequent dysplasia and oesophageal adenocarcinoma.
Adenocarcinoma may occur through further reflux-associated DNAdamage, genetic alterations and uncontrolled cellular proliferation.
Describe the clinical manifestations of Barret’s oesophagus
No specific symptoms or signs associated with Barrett’s oesophagus. It is typically diagnosed on endoscopy for upper gastrointestinal (GI) symptoms.
- Symptoms of GORD
- Heartburn:
- ‘Burning’ epigastric and retrosternal chest pain
- Worse with spicy meals and lying flat
- Wakes the patient up from sleep
- Indigestion (dyspepsia)
- Regurgitation: sour taste in mouth
- Chest discomfort
- Hoarseness of voice
- Cough: reflux-induced
- Dysphagia: suggestive of stricture or malignancy in context of BO
- Heartburn:
Describe the investigations for Barret’s oesophagus
Upper GI endoscopy (OGD) and biopsy:
- Typically performed in patients with chronic GORDandadditional risk factors such as age and obesity
- On endoscopy,normalstratified squamous epithelium is smooth and pale but, in Barrett’s, the squamocolumnar junction ispink-red
- Biopsy isdiagnosticand reveals metaplasia fromsquamous to glandular columnar epitheliumin the distal oesophagus, which resembles the cardia of the stomach or small intestine, withgoblet cellsand abrush border
- Biopsies should be quadrantic and at 2cm intervals (Seattle protocol): increases chance of detection
Describe the prague criteria classification for Barret’s oesophagus
The Prague criteria refers to the endoscopic description of BO, which is divided into two components:
- Circumferential (C) extent: maximal circumferential height of BO
- Maximal (M) length: refers to the longest segment of BO
and length:
- Short segment Barrett’s(< 3cm)
- Long segmentBarrett’s(> 3cm)
Describe the management for underlying reflux
- Management of underlying reflux
- Lifestyle changes:weight loss, smoking cessation, alcohol abstinence
- Proton pump inhibitor:omeprazole or lansoprazole; usually high dose
Describe the management for non-dysplastic Barrett’s oesophagus
Repeat surveillance endoscopy: at least every 5 years or sooner depending on the length of oesophagus affected (usually every 3-5 years)
Describe management for low-grade dysplasia
- Repeat endoscopy: every 6 months
- Endoscopic therapy:radiofrequency ablation (to destroy epithelium and replace with new cells) or mucosal resection may be considered if high-grade dysplasia develops. If there is no longer any dysplasia over 2 consistent endoscopies, the patient can be followed-up under the non-dysplastic pathway.
Describe the management for high-grade dysplasia
- Radiofrequency ablation:typically for flat lesions
- Endoscopic mucosal resection:typically for raised lesions
Describe the management for adenocarcinoma
Oesophagectomy: surgical intervention is indicated in non-metastatic disease
Describe the complications with Barrett’s oesophagus
- Associated with a50-100 foldincreased risk of oesophageal adenocarcinoma.
- Endoscopic complications: oesophageal rupture, or stricture development
Describe the prognosis for Barrett’s oesophagus
Oesophageal adenocarcinoma is unfortunately associated with a poor prognosis as it is often detected at an advanced stage. This explains the rationale behind surveillance of patients with Barrett’s oesophagus.
It is estimated that up to 13% of patients with Barrett’s oesophagus will develop oesophageal adenocarcinoma.
Describe the anatomy of the oesophagus
The oesophagus is a long tube going from the pharynx to the stomach, and it’s connected to the pharynx through the upper oesophageal sphincter, and to the stomach through the lower oesophageal sphincter.
Both relax during swallowing to allow the passage of food or liquids.
Additionally, the lower oesophageal sphincter is tightly closed between meals to prevent acid reflux.
The oesophageal wall has four layers - the adventitia; the muscular layer; the submucosa and the mucosa.
The mucosa comes into direct contact with food, and it protects the oesophageal wall from friction.
The mucosa also has three layers of its own: stratified squamous epithelium; the lamina propria; and the muscularis mucosae.
Finally, at the lower esophageal sphincter, the squamous epithelium joins the columnar gastric epithelium to form the gastroesophageal junction.
Define malignant oesophageal tumours
Oesophageal cancer is when malignant or cancerous cells arise in the oesophagus. It is divided into adenocarcinoma and squamous cell carcinoma.
Describe the epidemiology of malignant oesophageal tumours
- M>F
- Occurs mainly in those aged 60-70 years. Peak incidence around 80 years of age
- Adenocarcinoma is the commonest type in the Western world, whilst SCC is more common in countries such as Japan.
Describe the general risk factors for malignant oesophageal tumours
- Age > 60
- Smoking
- Achalasia
Describe the risk factors for adenocarcinoma
- Barret’s oesophagus:metaplasia from squamous epithelium to mucus-secreting columnar epithelium secondary toGORD
- Obesity
- Male sex
- Smoking
- Rare causes:coeliac disease and scleroderma
Describe the risk factors for squamous cell carcinoma
- Smoking:more associated with SCC
- Alcohol
- Achalasia
- Plummer-Vinson syndrome: rare disease characterised by difficulty swallowing, iron-deficiency anaemia, glossitis, cheilosis and oesophageal webs.
- Palmoplantar keratoderma: thick patches of skin develop on the hands and feet.
- Hot beverages
- Nitrosamines(dietary)
- Caustic strictures: strictures caused by caustic ingestions e.g. household bleach
Describe the pathophysiology of squamous cell carcinoma
Arises from squamous epithelium.
Most often in the upper two thirds.
When this epithelium is repeatedly exposed to risk factors like alcohol, cigarette smoke, or hot fluids, it gets damaged, so the squamous cells divide to replace the old damaged cells.
With each division, there is a risk that a mutation can occur. Mutations can occur in tumour suppressor genes or proto-oncogenes.
When this happens, squamous cells start dividing uncontrollably, and more mutations accumulate with each division.
Eventually, these mutations might make the cells malignant.
Describe the pathophysiology of oseophageal adenocarcinomas
Adenocarcinoma arises from columnar glandular epithelium.
Most often in the lower third of the oesophagus.
Most frequently, adenocarcinoma develops as a consequence of GORD
With GORD, the lower oesophageal sphincter is weaker than normal, and it allows acid from the stomach to go back up into the oesophagus after meals.
The presence of acid in the oesophagus can lead to Barrett’s oesophagus, which is when the squamous epithelium lining the oesophagus undergo metaplasia.
Over time, mutations might accumulate in either tumour suppressor genes or proto-oncogenesthat control the division of thesemetaplastic cells, ultimately resulting in a malignant tumour.
Describe the clinical manifestations of malignant oesophageal tumours
Patients often present late and have unresectable disease on presentation.
- Signs
- Lymphadenopathy
- Vocal cord paralysis
- Melaena on digital rectal examination: due to bleeding oesophageal cancer
- Symptoms
- Progressive dysphagia (solids then liquids): most common feature
- Regurgitation
- Pyrosis (heartburn)
- Pain in chest or back
- Odynophagia
- Weight loss and anorexia
- Hoarseness: with recurrent laryngeal nerve involvement
- Vomiting
Describe the investigations for malignant oesophageal tumours
- 1st line
- Upper GI endoscopy (OGD) and biopsy: first-line investigation and allows for visualisation of masses and biopsy
- Staging investigations
- Barium swallow: to see strictures
- CT chest, abdomen and pelvis (CAP): first-linestaginginvestigation in order to detect metastatic disease
- Endoscopic ultrasound (EUS):NICE suggests considering staging ultrasound to guide further management. It can aid detection of local invasion and lymphatic spread
- Staging laparoscopy: NICE suggests considering staging laparoscopy to guide further management. It may aid in detecting occult peritoneal disease
- PET CT: offered to all patients with oesophageal cancer who are suitable for curative surgery to rule out metastasis
- HER2 testing: patients with HER2-positive metastatic oesophageal cancer may be responsive to trastuzumab(Herceptin)
- StagingStaged using TNM
Describe the management for localised adenocarcinomas
- Endoscopic mucosal resection:only for very early lesions or for Barrett’s oesophagus
- Ivor Lewis oesophagectomy:the most common procedure and performed forlower thirdlesions. The stomach is mobilised into the thorax with the formation of an intrathoracic oesophagogastric anastomosis. Involves a lateral thoracotomy (incision to chest), and laparotomy (incision to abdomen)
- McKeown oesophagectomy:performed forproximaltumours. The stomach is mobilised into the thorax with the formation of a cervical oesophagogastric anastomosis. Involves an incision in the neck, lateral thoracotomy, and laparotomy
- Transhiatal oesophagectomy:carried out fordistaltumours. The stomach is mobilised into the thorax with the formation of a cervical oesophagogastric anastomosis. Involves an incision in the neck and laparotomy
- Chemotherapy:offered toallsurgical patients preoperatively (neoadjuvant) and may be given post-operatively (adjuvant)
Describe the management for squamous cell carcinoma
Radical chemoradiotherapy: localised SCC can be treated with curative chemoradiotherapy, although surgical resection may be offered
Describe the management for advanced or metastatic disease
- Palliation: stenting for dysphagia
- Chemotherapy or chemoradiotherapy: platinum-based agents
- Trastuzumab (Herceptin): for HER2 positive metastatic oesophageal cancer, in combination with chemotherapy
Describe the complications with malignant oesophageal tumours
Cancer-related:
- Tracheo-oesophageal or broncho-oesophageal fistula: when the cancer invades and perforates the entire oesophageal wall, it can invade the trachea in front of it, forming a fistula. This can cause pulmonary aspiration of oesophageal contents, which may cause symptoms like coughing and dyspnea.
- Aspiration pneumonia:oesophageal obstruction may result in aspiration
- Metastasis:lymph nodes, liver, lung, bones. If the cancer spreads to the diaphragm, it can cause hiccups.
Oesophagectomy-related:
-
Anastomotic leak: A leak may result in mediastinitis, which is associated with considerable morbidity and mortality and can result in profound sepsis
- Ivor-lewis oesophagectomy: potentially catastrophic if an anastomotic leak occurs, due to leakage of contents into the thorax (mediastinitis)
- McKeown oesophagectomy: the complications of a leak are less severe as the anastomosis is in the neck so it does not result in mediastinitis
- Recurrent laryngeal nerve injury: proximity of this nerve to the oesophagus places it at risk, either due to invasion of the tumour or iatrogenic injury
- Delayed gastric emptying:thought to be caused by bilateral vagotomy (one or more branches of the vagus nerve are cut) during the procedure which impairs gastric motility
Describe the prognosis of malignant oesophageal tumours
Unfortunately, the majority of oesophageal cancers are diagnosed at an advanced stage.
5-year survival is 15% but those who are diagnosed with early-stage disease have a survival rate of 55%
Describe the epidemiology of benign oesophageal tumours
- Account for 1% of all oesophageal tumours
- Leiomyomas are most common
- Papillomas
- Fibrovascular polyps
- Haemangiomas
- Lipomas
Describe the epidemiology of leiomyomas
Leiomyomas:
- Smooth muscle tumours arising from the oesophageal wall
- They are intact, well encapsulated and are within the overlying mucosa
- Slow growing
Describe the clinical manifestations of benign oesophageal tumours
- Usually asymptomatic, found incidentally on barium swallow
- Dysphagia
- Retrosternal pain
- Food regurgitation
- Recurrent chest infections
Describe the investigations for benign oesophageal tumours
- Endoscopy and biopsy: to rule out malignancy
- Barium swallow
Describe the management for oesophageal tumours
- Endoscopic removal
- Surgical removal of larger tumours
What is a barium swallow
Also called an esophagogram and is an imaging test that checks for problems in your upper GI tract
What are the 4 regions of the stomach
The stomach has four regions: the cardia, the fundus, the body, and the pyloric antrum.
There’s also a pyloric sphincter at the end of the stomach, which closes while eating, keeping food inside for the stomach to digest.
What are the 4 layers of the gastric wall
The gastric wall is made up of four layers:
The adventitia; the muscular layer; the submucosa; and the mucosa.
Describe the layers of the mucosa
The mucosa has three layers of its own.
- The innermost layer is the epithelial layer and it absorbs and secretes mucus and digestive enzymes.
- The middle layer is the lamina propria and it has blood, lymph vessels, and mucosa associated lymphoid tissue, which are nodules of immune cells called lymphocytes, in charge of eliminating pathogens that could pass through the epithelial layer.
- The outermost layer of the mucosa is the muscularis mucosa, and it’s a layer of smooth muscle that contracts and helps with the break down food.
Describe the epithelial layer of the stomach and the cells within it
The epithelial layer dips down below the surface of the stomach lining to form gastric pits. And these pits are contiguous with gastric glands below which contain various epithelial cell types, each secreting a variety of substances.
- Foveolar cells secrete mucus
- Parietal cells secrete hydrochloric acid
- Chief cells secrete pepsinogen
- G cells secrete gastrin
Describe the types of gastric cancer
Gastric cancer is when malignant or cancerous cells arise in the stomach.
This cancer can appear in any part of the stomach and it’s classified into adenocarcinoma (most common), lymphoma, carcinoid tumour, and leiomyosarcoma; depending on the type of cells it originates from.
Define gastric adenocarcinoma
Gastric adenocarcinomas arise from columnar glandular epithelium (adeno = gland)
Adenocarcinomas are divided into intestinal, or well-differentiated adenocarcinoma; and diffuse, or undifferentiated adenocarcinoma. Intestinal is the most common!
Describe the epidemiology of gastric adenocarcinoma
- Gastric cancer is most common in Japan and is the 5th most common cancer worldwide.
- Other countries with a high incidence include China, Finland and Colombia.
- Whilst the overall incidence is decreasing, the incidence of tumours affecting the cardia is increasing.
- Currently, cancers of the antrum remain the commonest.
- M>F
Describe the risk factors of gastric adenocarcinoma
Modifiable risk factors:
- H. pylori infection: commonest cause, accounting for 60% of cases
- Smoking
- Alcohol
- Diet: smoked and preserved foods (N-nitroso compounds), nitrosamines; salty and spicy foods
- Obesity
Non-modifiable risk factors:
- Male gender: gastric cancer is twice as common in males
- Increasing age: peak age of diagnosis is 70-80 years old
- Family history
- Pernicious anaemia: associated with a 2- to 3-fold increased risk of gastric cancer
- Blood type A
- Gastric adenomatous polyps: most common neoplastic polyp
- Lynch syndrome II: hereditary non-polyposis colorectal cancer
- Autoimmune gastritis: immune system attacks the parietal cells, causing inflammation
- Achlorhydria: decreased or lack of gastric acid production
Describe the pathophysiology of intestinal type gastric adenocarcinoma
Most commonly caused by H.pylori
H.pylori releases virulence factors, such as cagA, that go inside the epithelial cells and cause extensive damage.
The immune system detects this damage and cause an inflammatory response within the gastric lining, causinggastritis. The infection persists, leading to chronic gastritis.
The normal epithelium of the stomach gets continuously damaged and repaired. Over time, the stomach cells in the epithelium undergo metaplasia. These metaplastic cells might accumulate mutations in the genes that are in charge of thecell cycle and cell division.
Tumor suppressor genes and proto-oncogenes can experience mutations and the metaplastic cells divide uncontrollably and may become malignant.
Intestinal types are well differentiated - meaning they resemble normal intestinal cells.
This type typically appears on the lesser curvature of the antrum as a large, irregular ulcer, with heaped up edges.
Describe the pathophysiology of diffuse gastric adenocarcinoma
Appear in any part of the stomach
Mostly related to genetic mutations in the CDH1 gene, a tumor suppressor gene that codes for a membrane adhesion molecule called E-cadherin. Normally, E-cadherin helps epithelial cells stick to one another and it also transmits signals that control the progression of cell cycle.
When E-cadherin isn’t working properly, cells detach and starts dividing uncontrollably.
This type of adenocarcinoma has an increased ability to spread and invade adjacent structures, so it’s way more aggressive than the intestinal type.
This type can cause gastric linitis plastica, where the stomach wall grow thick and hard and look like a leather bottle, as the cancer invades the connective tissue of the submucosa.
Histologically, there’s ‘signet ring cells’: they look like a signet ring because the cytoplasm has giant vacuoles that push the nucleus to the edge of the cell.
Describe the clinical manifestations of gastric adenocarcinoma
Early stages may be asymptomatic so many patients present late!
- Signs
- Iron deficiency anaemia: koilonychia (spoon nails), pallor, angular cheilitis (swollen patches in corner of mouth)
- Palpable mass
- Melaena on digital rectal examination
- Acanthosis nigricans: darkening of the skin at the axilla and other skin folds.
- Troisier’s sign: an enlarged, hard Virchow’s node (left supraclavicular node)
- Leser-Trelat sign: sudden onset seborrhoeic keratosis (brown patches on skin)
- Polyarteritis nodosa: inflammation, weakening, and damage to small and medium-sized arteries.
- Trousseau syndrome: blood clotting disorder
- Symptoms
- Malaise
- Loss of appetite
- Anorexia and weight loss
- Dyspepsia
- Abdominal pain
- Difficulty swallowing
- Early satiety
- Nausea and vomiting
- May be malaena and haematamesis: if cancer ulcerates and bleeds
What are the investigations for gastric adenocarcinoma
- 1st line
- Upper GI endoscopy and biopsy: ulcer with heaped-up edges is a common presentation
- Staging investigations
- CT chest, abdomen and pelvis (CAP): if biopsy reveals malignancy, CT imaging is usually the first-line staging investigation to detect metastatic disease
- PET: offered after CT when metastatic disease is suspected and assists with staging
- Staging laparoscopy:allpatients with potentially curable disease should have a staging laparoscopy to exclude occult peritoneal metastasis
- Endoscopic ultrasound:assists with staging, particularly for patients where curative surgery is being considered; recent evidence suggests it may be superior to CT
- HER2 testing: patients with HER2-positive metastatic gastric cancer may be responsive to trastuzumab(Herceptin)
Describe the TNM classification of gastric adenocarcinoma
- TNM classification preferred for gastric tumoursT = tumour size and local extension, N = lymph node metastases, and M = distant metastases.Each of these categories have substages: T0 to T4, from N0 to N3, and M0 or M1, and the combinations of these substages determine the oesophageal cancerstage, from 0 to IV. The higher the number, the more the cancer has invaded and spread.e.g. T1N0M0 = invasion of submucosa but no spread to lymph nodes or distal organs
Describe the Siewert’s classification for gastro-oesophageal tumours
Type 1 - carcinoma of the distal oesophagus associated with Barrett’s oesophagus, which infiltrates the GOJ from above and located 1-5cm above the gastric cardia
Type 2 - junctional carcinoma of the cardia. Located 1cm above or 2cm below the gastric cardia; true GOJ tumour
Type 3 subcardial cancer, which indiltrates the GOJ from below and is located 2-5cm below the gastric cardia
Describe the differential diagnosis for gastric adenocarcinoma
- Peptic ulcer disease
- Oesophageal stricture
- Achalasia
Describe the management for localised gastric adenocarcinoma
- Oesophagogastrectomy: for type 2 GOJ tumours that extend into the oesophagus
- Total gastrectomy: for proximal tumours within 5cm from the GOJ
- Sub-total gastrectomy: if the tumour is >5cm from the GOJ
- Endoscopic submucosal resection: if the tumour is early and confined to the mucosa this may be appropriate but remains controversial
- D2 lymph node dissection: should be considered inallpatients undergoing a curative gastrectomy
- Chemotherapy: offer chemotherapy before and after surgery toallpatients with gastric cancer
Describe the management for advanced or metastatic gastric adenocarcinomas
- Chemotherapy or chemoradiotherapy: usually a combination of a platinum compound and fluorouracil
- Palliative gastrectomy
- Trastuzumab (Herceptin): for HER2 positive metastatic gastric cancer, in combination with chemotherapy
Describe the complications with gastric adenocarcinoma
Cancer-related:
- Bleeding: patients may present with melaena from a bleeding gastric tumour
- Gastric outlet obstruction: tumour blocks the gastric outlet causing non-bilious post-prandial (after a meal) vomiting
- Perforation: ulceration of a neoplastic lesion can weaken the stomach wall and if left untreated could lead to perforation
- Metastasis: Virchow’s node (left supraclavicular node), lung, liver, peritoneum, ovaries (Krukenberg tumour)
- Leser-Trélat sign: seborrheic keratosis, or brownish spots all over the skin. Results from the stimulation of keratinocytes by growth factors produced by the gastric cancer cells.
- Polyarteritis nodosa: inflammation and necrosis of multiple medium-sized arteries, including those that supply the kidneys and the heart
- Trousseau syndrome: cancer cells stimulate vascular and inflammatory cells to release tissue factor, which then activates the coagulation cascade; therefore, there’s an increase in blood coagulability that leads to thrombosis, or generation of blood clots.
- Pseudoachalasia syndrome: if gastric cancer grows near the gastro-oesophageal junction, it can cause a stricture that makes it difficult for food and liquids to pass through from the oesophagus into the stomach
Describe the complications of gastrectomy to treat gastric adenocarcinoma
-
Malabsorption:
- Vitamin B12 deficiency (reduced intrinsic factor)
- Iron deficiency due to reduced conversion of Fe2+to Fe3+in the stomach and hence reduced absorption
- Small bowel bacterial overgrowth:post gastrectomy, a blind-ending bowel loop is created to allow the gall bladder to drain into. Bacterial overgrowth within this portion of the bowel can lead to malabsorption
-
Dumping syndrome: occurs when sugar moves too quickly into the small bowel and associated with gastrectomy
- Early dumping syndrome:occurs 30 mins after a meal as fluid moves into the intestine due to the high osmotic load, resulting in dizziness and palpitations
- Late dumping syndrome: occurs 2 hours after a meal. As glucose is rapidly absorbed in the intestine, this causes reactive hyperinsulinaemia and subsequent hypoglycaemia
