5 - Upper GI Malignancy Flashcards
What is it important to remember about ascites and effusions?
They are ALWAYS pathological and should be investigated
20 L of fluid is filtered out of the circulation each day? How does it reenter the circulation?
90% reabsorbed via oncotic pressure
10% re-enters circulation from via the lymphatic system
What happens to fluid as it travels through the body?
Leaves the heart and travels to the capillaries - here a high hydrostatic pressure forces fluid into the interstitium. Pressure then decreases through the capillary and oncotic pressure in the capillary becomes greater than hydrostatic pressure - this draws water back into the capillary from the interstitial. 90% is reabsorbed.
What is the equation to determine filtration / reabsorption rate?
Qf = Peff x Kf
Qf = filtration / reabsorption rate
Peff = Effective filtration pressure
Kf = Filtration coefficient
Where are serous membranes found?
Peritoneum
Pericardium
Pleura
What are serous membranes comprised of?
Parietal and visceral layers - with space between the two layers which contains 50-75mls of fluid allowing the layers to slide over each other.
At what level of fluid can ascites be detected in each of the serous membranes?
Ascites in peritoneum - detectable >500mls
Pleural effusions - detectable >300mls
Pericardial effusion - detectable >50mls
Why do effusions form in the body?
Inc in hydrostatic pressure
Dec in oncotic pressure
Inc in permeability of a membrane
Inc to exchange area
What is an effusion?
An abnormal collection of fluid in hollow spaces or between tissues of the body
What is the difference between transudate and exudate?
Transudate = filtrate with LOW protein count - due to change in hydrostatic or oncotic pressure
Exudate = unfiltered plasma with HIGH protein content - due to change in vascular permeability or exchange areas
What is the most common mechanism for a hydrostatic cause of ascites?
Portal hypertension - most common cause overall
Due to cirrhosis, hepatitis, cardiac failure, pericarditis, PE or pulmonary embolism
What is the most common mechanism for an oncotic cause of ascites?
Hypoalbuminemia
Due to nephrotic syndrome, protein losing enteropathy, malnutrition
Which calculation can help determine the cause of ascites?
Serum-Ascites Albumin Gradient (SAAG)
Serum albumin - albumin level of ascitic fluid
High gradient (>1.1 g/DL) = portal hypertension
Low gradient (<1.1) = not due to portal hypertension
What is the most common mechanism for an inc permeability or exchange area cause of ascites?
Peritoneal disease
E.g. malignancy, infection, vasculitis, peritonitis, lymph malignancies
What disease is the biggest cause of ascites?
Liver cirrhosis = 80%
Liver cirrhosis = inc portal hypertension = ascites
What are the signs and symptoms of cirrhosis?
What blood abnormalities appear in liver failure?
Anaemia
Thrombocytopenia
High MCV
Hyponatremia
Low albumin, raised bilirubin, ALT can be normal or raised
Clotting = prolonged PTT due to reduced clotting factors
Ammonia can be raised
GGT - can be raised with ETOH excess
What tests can you do to see if a patient has liver problems?
How does ascitic fluid in portal hypertension present?
How does it present in bacterial peritonitis?
Pale yellow and watery
High SAAG gradient
Low WCC
Bacterial = turbid, cloudy, raised WCC
What is the presence of malignant cells in the peritoneum called?
Peritoneal carcinomatosis
Why does peritoneal carcinomatosis lead to ascites?
Causes ascites due to increased vascular permeability and lymphatic obstruction (this prevents reabsorption of fluid and protein - increasing oncotic pressure)
Why does malignant ascites alter vascular permeability?
Malignant cells attach to the peritoneal membrane and secrete hormones such as VEGF and IL2 - these inc new blood vessel formation - but the new vessels are more leaky
What are the signs and symptoms of peritoneal carcinomatosis?
What blood abnormalities can be detected with peritoneal carcinomatosis?
What are the following cancer markers for:
- CA125
- CEA
- Αlpha fetoprotein
- CA19-9
CA-125 = ovarian cancer
CEA = colon cancer
α fetoprotein = hepatocellular cancer
CA 19-9 = pancreatic or bile duct cancers
What is the first line investigation for ascites?
USS
What imaging can be done for ascites after USS?
How can it indicate what the underlying cause is?
CT
Can indicate cause due to the density of the fluid.
- Similar to water = transudate
- Higher than water = exudate
- Really high = blood (hemoperitoneum)
What can cause hypoalbuminemia?
Nephrotic syndrome
Protein losing enteropathy (not being absorbed by the gut)
Malnutrition
Reduced production (liver failure, poor health)
What are the functions of albumin?
Antioxidant and immunomodulation
Regulation of colloid oncotic pressure
Transporter of hormones, drugs etc
Endothelial stabilisation
How does hypoalbuminemia affect the kidneys?
Hypoalbuminemia = loss of intravascular oncotic pressure = oedema in legs, ascites and effusions in lungs and heart.
Less BV = activates RAAS - causes water and salt retention.
What colour is ascitic fluid due to hypoalbuminemia?
Clear or straw coloured
What is nephrotic syndrome?
Excessive renal protein loss –> hypoalbuminemia, hyperlipidaemia and oedema.
Glomeruli are affected by inflammation - allows protein to pass through and be excreted. Oedema then forms due to reduced vascular oncotic pressure.
What are the clinical features of nephrotic syndrome?
What investigations can be done for nephrotic syndrome?
What is the Tx for nephrotic syndrome?
Fluid and salt restriction, diuretics and ACEIs (reduce protein loss as reduce intraglomerular pressure and hyperfiltration)
What is the most common symptom of a pleural effusion?
Dyspnoea
What are the two types of pleural effusion?
How can you determine which it is?
Transudative
Exudative
Light’s criteria can determine which it is.
What can cause pleural effusions?
What is prehabilitation?
Prehabilitation (prehab) means getting ready for cancer treatment in whatever time you have before it starts. It is a programme of support and advice that some NHS hospitals are using. It covers three particular parts of your health:
what you’re eating and your weight
physical activity or exercise
mental wellbeing
Stopping smoking and cutting down on alcohol can also help. It helps while you’re having treatment, with your recovery, as well as improving your overall health
Why is depth of tumour penetration important?
Inc depth is linked to increased risk of lymph node spread (N) and distant organ spread (M).
This impacts prognosis and treatment options.
How has the incidence of oesophageal cancer changed over the past 4 decades?
Has gradually increased incidence - tumours at the GOJ have steadily increased.
What are the two types of oesophageal cancer?
Which is more prevalent in
- Asia
- The West
Squamous Cell Carcinoma - Asia
Adenocarcinoma - West
What are the RF for SCC of the oesophagus?
What are the RF for Adenocarcinoma of the oesophagus?
What is the difference between macroscopic and microscopic appearance?
Macroscopic = what it looks like with the naked eye
Microscopic = what it looks like under a microscope
Where is the highest incidence of Gastric Cancer?
Far East - Japan & Korea
What are the RF for gastric cancer?
How do most cancers spread?
Direct
Haematogenous to other viscera
Lymphatic
What types of cancer are there in gastric cancer?
Adenocarcinoma - most common and most aggressive
GIST (gastrointestinal stromal tumours)
Lymphoma
Neuroendocrine tumours
- less common and less aggressive, treated differently
What unusual spread can gastric cancer invade by?
Trans-peritoneal spread - mets to the peritoneum
What S&S of oesophageal and gastric cancer should you watch out for?
Dyspepsia complicated by dysphagia, weight loss and anorexia
What imaging should you do for suspected oesophageal or gastric cancer?
Gastroscopy (OGD) and biopsy first
Then you can do -
CT (for staging)
PET CT + Contrast (better for oesophageal as more radioisotope taken up, less taken up by gastric cancer)
EUS (endoscopic US)
Staging Laparoscopy - looking for peritoneal spread
What percentage of Ps will have potentially curable disease at presentation?
35-40%
What is the Tx for oesophageal and gastric cancer?
Early disease = endoscopic surgery or primary surgery
Locally advanced -
Adenocarcinioma = perioperatvie chemo / chemo radio + surgery
Oesophageal SCC = chemoradiotherapy
Metastatic disease - palliative (chemo, radio, immune), supportive (stents for dysphagia). Median survival = 8-10m
What is the 5 year survival rate of oesophageal and gastric cancer?
50%
What is the operative mortality and morbidity rates for oesophago-gastric surgery?
Operative mortality = 5%
Operative morbidity = 50% - cardio-respiratory complications, anastomic leak (causing sepsis abscess), mediastinitis
What are the post-op complications of oesophago-gastic surgery?
Anatomical reflux
Early satiety
Physiological - nutritional, weight loss, diarrhoea, vitamin deficiency, dumping
Psychological - major life impacts, esp surrounding food and social life
Why are liver, pancreas and biliary tract tumours (HPB tumours) grouped together?
Because they have similarities between them
- Uncommon
- Locally advanced a presentation
- Poor prognosis
How do HPB cancers present?
- Abdominal pain
- Nausea / anorexia
- Weight loss
Can get extra-hepatic obstructive jaundice
How does extra-hepatic obstructive jaundice present?
Deep jaundice
Pale stools
Dark urine
Pruritus
What imaging is done for HPB cancers?
1st line - USS - may show biliary duct dilatation
CT - extent of disease
MRCP - detailed images of biliary duct obstruction
ERCP +/- Stent
What are the causes of hepatocellular carcinoma?
Cirrhosis = biggest RF - 3-5% annual risk of developing HCC
- Alcohol excess
- Chronic viral hepatitis
- NAFLD (DM and metabolic syndrome)
- Haemochromatosis / Wilsons - rare
How do hepatocellular carcinomas present?
Liver mass on clinical exam
Incidental mass on CT / MRI / US
Which tumour marker is linked to hepatocellular carcinoma?
AFP - α fetoprotein
What investigations can be done to diagnose HCC?
What are the tx options for HCC?
What is the incidence of pancreatic cancer?
What are the RF for pancreatic cancer?
Where are the different locations in the pancreas that cancer can be found?
In the head - most common - turns Ps yellow because the tumour blocks the bile duct
Or in the body or tail - less common -doesn’t turn Ps yellow
What are the different types of pancreatic cancer?
Adenocarcinoma
Mucinous Cystic Tumour
Neuroendocrine Tumour
How does pancreatic cancer present?
Recent onset diabetes
Obstructive jaundice
Couvoisier’s sign
Pancreatitis
Abdominal mass
What is painless jaundice with a palpable gallbladder known as?
What usually causes this?
Courvoisier’s sign
Usually caused by malignant biliary obstruction
What is the tumour marker for pancreatic cancer?
CA 19-9
What are the imaging investigations for pancreatic cancer?
What is a Whipple procedure?
Removal of the head of the pancreas and the duodenum - used for Tx of cancer of the head of the pancreas
What surgery can be done for pancreatic tail lesions?
Distal pancreatectomy and splenectomy
What are the LT effects of pancreatic surgery?
How rare is gallbladder cancer?
Very rare - <1% of all cancer diagnoses.
F>M 6:1
What are the RF for gallbladder cancer?
Obesity
Age
FHx
Gallstone Hx
Gallbladder polyps
Porcelain GB
What are the S&S of gallbladder cancer?
Usually asymptomatic until late presentation
Usually incidental finding at surgery for gallstones
What are the tumour markers for gallbladder cancer?
CEA
CA19-9
What investigations can be done for gallbladder cancer?
What are the Tx options for gallbladder cancer?
What is cancer of the bile ducts call?
Cholangiocarcinoma
What are the RF for cholangiocarcinoma?
Liver flukes
Primary sclerosing cholangitis
Choledochal cysts (biliary cysts)
Bile duct stones
How does cholangiocarcinoma usually present?
As an incidental finding when imaging the biliary tree
Which tumour markers can indicate cholangiocarcinoma - but with low sensitivity / specificity?
CEA
CA19-9
What surgery can be done for cholangiocarcinoma?
Depends on site of cancer - whether intra or extra hepatic bile duct
Local resection (bile ducts)
Partial liver resection
Whipple
Liver transplantation
What biological treatment can be given than is a fibroblast growth factor receptor inhibitor?
Pemigatinib
What is the incidence of small bowel cancer?
Rare = only 3-5% of all GI malignancies in the West despite making up 90% of the GIT
What types of SBC are there?
Which SBC is associated with Crohn’s, FAP and Lynch syndrome?
Adenocarcinoma
How does SBC present?
What is carcinoid syndrome?
When P has a neuroendocrine tumour that secretes hormones such as serotonin which causes sx in Ps.
If carcinoid syndrome is suspected, what should you measure in the urine?
5-HIAA levels (primary metabolite of serotonin)
Helps detect serotonin secreting tumours
What is the treatment for SBC?
Complications following gastrectomy for cancer are:
overall 20%
respiratory infection in approximately 25%
due to poor wound healing in 40%
due to abdominal sepsis in 30%
the cause of mortality in 10%
The rate of complications after gastrectomy and oeophagectomy is 50% overall. Wound healing and abdominal sepsis do occur but are not as common as described. The commonest complication is respiratory infection. It is important to understand the need to undertake a careful assessment of any comorbidity preoperatively, particularly cardiovascular and respiratory. Students should recognise the need for a prehabilitation programme if necessary which includes physiotherapy exercises, weight loss and stopping smoking advice and psychological support.
Which is the preferred investigation for the diagnosis of extrahepatic bile duct obstruction?
Ultrasound
CT scan
PET-CT scan
MRCP
ERCP
All of these investigations could be considered for a patient presenting with obstructive jaundice. An US of the abdomen may show a dilated common bile duct with filling defects consistent with stones. US can be difficult to interpret because of overlying bowel gas. CT does show bile duct dilatation and can give a clue to diagnosis particularly if there is a tumour mass as in head of the pancreas cancers. PET-CT is not particularly used in HPB cancers for diagnosis but may have a role for assessment of metastatic disease. MRCP is the investigation of choice as it gives excellent detail of the anatomy of the biliary tree. ERCP can be used and has the advantage of allowing biopsy or cytology brushings from the bile duct lumen (targeted biopsy of pancreatic lesions can be undertaken with endoscopic ultrasound) and enabling stent placement but carries significant morbidity such as a risk of post ERCP pancreatitis.
Which of the following statements on oesophageal cancer is correct
In the UK the commonest histological type is squamous cell carcinoma
It occurs most frequently in women
It is usually affects obese men
It does not run in families
Vomiting blood is a common presenting symptom
In the UK the commonest histological type is adenocarcinoma which is increasing in incidence particularly of the oesophago-gastric junction. Men are more commonly affected and increasingly it affects middle aged obese men. There is a familial risk particularly with Barrett’s oesophagus which is columnar cell change associated with gastro-oesophageal reflux. Haematemesis can occur as presentation but it is not common – may be the presenting complaint for a gastric cancer.
Which of the following is recognised as a direct cause of gastric cancer
Smoking
Alcohol
Eating spicy foods
Helicobacter pylori
Family history
Although all of these are associated with the development of gastric cancer H pylori is the only WHO designated cause of gastric cancer. It is particularly responsible for distal gastric cancer. Because HP is commonly diagnosed in investigation for dyspepsia, eradication with antibiotics (clarithromycin, amoxicillin and metronidazole) and proton pump inhibitors is recommended. There are parts of the world particularly in lower socio-economic groups which have a very prevalence in young people with HP who have a high risk of getting gastric cancer.
A patient is diagnosed with pancreatic cancer. Which of the following are associated?
Acute pancreatitis
Recent onset diabetes mellitus
Gall stones
Gastric Ulcer
Irritable bowel syndrome
The commonest associated condition is diabetes. In an elderly patient with a recent diagnosis of diabetes investigations with cross sectional imaging are indicated to exclude a pancreatic cancer. Occasionally a patient may present with acute pancreatitis and have an underlying cancer. Such patients may have a chronic course and the acute becomes a chronic pancreatitis. They frequently develop a mass which can look very suspiciously like a cancer and the diagnosis is only confirmed once the lesion is resected. Gall stones are not associated but a patient may have a palpable gall bladder (Courvoisier’s sign) when they present with jaundice and pancreatic cancer. Gastric ulcer is not associated. Irritable bowel syndrome is not associated but many patients with pancreatic cancer have been treated for IBS because of the non-specific nature of their abdominal discomfort - this is why many patients present late with pancreatic cancer.
Which of the following is true of dumping syndrome?
It occurs after oesophagectomy
It can be categorised as early or late
It often requires surgical correction
It is caused by lack of satiety hormones produced by the stomach
It occurs within 10 minutes of eating
Dumping syndrome is caused by the rapid transition of hyperosmolar food into the small intestine caused by the lack of a stomach which usually would begin digestion and only allow small amounts of material at a time to enter the small bowel. Without this, undigested food rapidly enters the small bowel and leads to physiological disturbance which can be significant. It can be separated into two categories – early or late, the features of which are as follows:
Early dumping syndrome
* Rapid deposition of poorly digested food into small bowel
* Extracellular fluid shift from small bowel in response to hyperosmolar load
* Abdominal pain, nausea, vomiting, bloating, diarrhoea
Reactive hypoglycaemia (late dumping)
* Approx. 2 hours after food
* Flushing and hypoglycaemia symptoms
* High levels of insulin produced due to excessive carbohydrate in small bowel
Treatment of dumping usually requires diet/lifestyle advice only such as not drinking at the same time as eating or eating smaller meals at a time. Dumping is referred to in the lecture but not expanded upon, but is discussed in more detail in the associated reading material.
Which of the following is the most common presentation of small bowel tumours?
Chronic abdominal pain
Incidental finding on imaging
Emergency presentation
Iron deficiency anaemia
Carcinoid syndrome
Small bowel tumours are rare, making up only <5% of all GI tumours and most are asymptomatic. They are sometimes seen as incidental findings on imaging for other reasons and are very rare as a cause of iron deficiency anaemia. The most common presentation is, however, with an acute episode such as obstruction, perforation or acute bleeding and surgery is often required to deal with the problem. Carcinoid syndrome occurs from the systemic release of biologically active polypeptides, amines or prostaglandins from neuroendocrine tumours and can lead to symptoms such as flushing, wheezing, diarrhoea, fatigue and sometimes cardiac problems. This most often occurs when there are liver metastases from a GI NET as these substances are otherwise usually inactivated in the liver. This is a rare presentation (only approx. 10% patients with NETs).
Which of the following GI conditions can be associated with an increased risk of cholangiocarcinoma?
Ulcerative colitis
Crohns disease
Diverticular disease
Coeliac disease
Hirschsprung’s disease
The correct answer is ulcerative colitis. The incidence of cholangiocarcinoma increases with primary sclerosing cholangitis which is associated with UC (but this is not the only cause of PSC). Coeliac increases the risk of small bowel lymphoma and both Crohn’s and Ulcerative colitis can increase the risk of colorectal cancer. Hirschsprung’s disease is a congenital absence of nerves from part of the bowel, most often the colon, leading to constipation and narrowing. It occurs in around 5,000 live births but is not associated with cholangiocarcinoma.
